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Sample records for brain tumor regression

  1. HMGB1 mediates endogenous TLR2 activation and brain tumor regression.

    Directory of Open Access Journals (Sweden)

    James F Curtin

    2009-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1, an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2 signaling on bone marrow-derived GBM-infiltrating DCs.Using a combined immunotherapy/conditional cytotoxic approach that utilizes adenoviral vectors (Ad expressing Fms-like tyrosine kinase 3 ligand (Flt3L and thymidine kinase (TK delivered into the tumor mass, we demonstrated that CD4(+ and CD8(+ T cells were required for tumor regression and immunological memory. Increased numbers of bone marrow-derived, tumor-infiltrating myeloid DCs (mDCs were observed in response to the therapy. Infiltration of mDCs into the GBM, clonal expansion of antitumor T cells, and induction of an effective anti-GBM immune response were TLR2 dependent. We then proceeded to identify the endogenous ligand responsible for TLR2 signaling on tumor-infiltrating mDCs. We demonstrated that HMGB1 was released from dying tumor cells, in response to Ad-TK (+ gancyclovir [GCV] treatment. Increased levels of HMGB1 were also detected in the serum of tumor-bearing Ad-Flt3L/Ad-TK (+GCV-treated mice. Specific activation of TLR2 signaling was induced by supernatants from Ad-TK (+GCV-treated GBM cells; this activation was blocked by glycyrrhizin (a specific HMGB1 inhibitor or with antibodies to HMGB1. HMGB1 was also released from melanoma, small cell lung carcinoma, and glioma cells treated with radiation or temozolomide. Administration of either glycyrrhizin or anti

  2. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  3. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  4. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  5. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  6. Brain tumor (image)

    Science.gov (United States)

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  7. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  8. Brain Tumor Diagnosis

    Science.gov (United States)

    ... Young Adult Guidelines For brain tumor information and support Call: 800-886-ABTA (2282) or Complete our contact form Brain Tumor Information Brain Anatomy Brain Tumor Symptoms Diagnosis Newly Diagnosed Neurological Exam ...

  9. Brain Tumor Symptoms

    Science.gov (United States)

    ... Young Adult Guidelines For brain tumor information and support Call: 800-886-ABTA (2282) or Complete our contact form Brain Tumor Information Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood ...

  10. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  11. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  12. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  13. Children's Brain Tumor Foundation

    Science.gov (United States)

    ... 2 Family Donate Volunteer Justin's Hope Fund Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  14. Metastatic brain tumor

    Science.gov (United States)

    ... JavaScript. A metastatic brain tumor is cancer that started in another part of the body ... of cancer rarely spread to the brain, such as colon cancer and prostate cancer. In other rare cases, a tumor can ...

  15. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... to reveal the vast diversity of genetic and epigenetic alterations that exist between brain tumors. This biological ... social workers, psychologists, and nurses. A supportive family environment is also helpful. Surgery GBM’s capacity to wildly ...

  16. Brain Tumor Surgery

    Science.gov (United States)

    ... tumor surgery include: Seizures Weakness Balance/coordination difficulties Memory or cognitive problems Spinal fluid leakage Meningitis Brain swelling Stroke Excess fluid in the brain Coma Death Recovery Time Recovery time depends on: The procedure performed. ...

  17. Craniotomy for supratentorial brain tumors

    DEFF Research Database (Denmark)

    Rasmussen, Mads; Bundgaard, Helle; Cold, Georg Emil

    2004-01-01

    physiological data) predictive of brain swelling through the dural opening. As a secondary aim the authors attempted to define subdural ICP thresholds associated with brain swelling. METHODS: The study population consisted of 692 patients (mean age 50+/-15 years) scheduled for elective craniotomy...... for supratentorial brain tumors. Brain swelling through the dural opening was estimated according to a four-point scale. The patients were dichotomized as those without cerebral swelling (that is, brain below the dura mater [59 patients] or brain at the level of the dura mater [386 patients]) and those with cerebral...... swelling (that is, moderate brain swelling [205 patients] or pronounced brain swelling [42 patients]). Logistic regression analysis was used to identify subdural ICP (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.72-2.1, p

  18. Brain Tumors and Fatigue

    Science.gov (United States)

    ... can help calm the mind. Meditation, guided imagery, music therapy, and yoga are just a few worth investigating. Home Donor and Privacy Policies Find Resources Disclaimer Donate Subscribe Login American Brain Tumor Association 8550 W. Bryn Mawr Ave. Ste ...

  19. Brain Tumors - Multiple Languages

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Brain Tumors URL of this page: https://medlineplus.gov/languages/braintumors.html Other topics A-Z Expand Section ...

  20. Epilepsy and brain tumors

    Science.gov (United States)

    ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  1. Drugs Approved for Brain Tumors

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Brain Tumors This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Brain Tumors Afinitor (Everolimus) Afinitor Disperz (Everolimus) Avastin (Bevacizumab) Becenum ( ...

  2. Metabolic Reprogramming in Brain Tumors.

    Science.gov (United States)

    Venneti, Sriram; Thompson, Craig B

    2017-01-24

    Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism. Furthermore, metabolic alterations directly impact epigenetics well beyond classical mechanisms of tumor pathogenesis. Metabolic reprogramming in brain tumors is also influenced by the tumor microenvironment contributing to drug resistance and tumor recurrence. Altered cancer metabolism can be leveraged to noninvasively image brain tumors, which facilitates improved diagnosis and the evaluation of treatment effectiveness. Many of these aspects of altered metabolism provide novel therapeutic opportunities to effectively treat primary brain tumors.

  3. [Markers of brain tumors].

    Science.gov (United States)

    Fumagalli, R; Pezzotta, S; Bernini, F; Racagni, G

    1984-05-19

    Biological markers of tumors are compounds or enzymatic activities measurable in body fluids. Their presence or concentration must be linked to tumoral growth. The markers of the central nervous system tumors are detected in CSF. Alpha-feto-protein, carcinoembryonic antigen, human chorionic gonadotropin, adenohypophyseal peptide hormones, enzymes, etc., have found some application in the early diagnosis of leptomeningeal metastasis. Other applications involve the early detection and recurrency of primary brain tumors, as well as the evaluation of efficacy of their therapy. The tests based on the CSF content of desmosterol and polyamines have been studied extensively. Their rationale is discussed and specificity, sensitivity, efficiency and predictive value are considered. Experimental results concerning a new possible biochemical marker, based on CSF concentration of cyclic adenosine monophosphate, are reported.

  4. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

    Full Text Available Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 persons/year. The most common benign brain tumor in adults is meningioma, which is most present in women, and the most common malignant tumor is glioblastoma, which is most present in adult men. Due to high mortality, especially in patients diagnosed with glioblastoma and significant brain tumor morbidity, there is a constant interest in understanding its etiology in order to possibly prevent tumor occurrence in future and enable more efficient treatment strategies for this fatal brain disease. Despite the continuously growing number of epidemiological studies on possible factors of tumor incidence, the etiology remains unclear. The only established environmental risk factor of gliomas is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor of brain tumor development. However, studies have been inconsistent and inconclusive, so more definite results are still expected.

  5. Epilepsy-related brain tumors.

    Science.gov (United States)

    Ertürk Çetin, Özdem; İşler, Cihan; Uzan, Mustafa; Özkara, Çiğdem

    2017-01-01

    Seizures are among the most common presentations of brain tumors. Several tumor types can cause seizures in varying rates; neuroglial tumors and the gliomas are the most common ones. Brain tumors are the second most common cause of focal intractable epilepsy in epilepsy surgery series, with the highest frequency being dysembryoplastic neuroepithelial tumors and gangliogliomas. Seizure management is an important part of the treatment of patients with brain tumors. This review discusses clinical features and management of seizures in patients with brain tumors, including, neuroglial tumors, gliomas, meningioma and metastases; with the help of recent literature data. Tumor-related seizures are focal seizures with or without secondary generalization. Seizures may occur either as initial symptom or during the course of the disease. Brain tumors related epilepsy tends to be resistant to antiepileptic drugs and treatment of tumor is main step also for the seizure treatment. Early surgery and extent of the tumor removal are important factors for achieving seizure freedom particularly in neuroglial tumors and low grade gliomas. During selection of the appropriate antiepileptic drug, the general approach to partial epilepsies can be followed. There are several factors influencing epileptogenesis in brain tumor-related epilepsy which also explains clinical heterogeneity of epilepsy among tumor types. Identification of molecular markers may guide future therapeutic approaches and further studies are needed to prove antitumor effects of different antiepileptic drugs. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch s...

  7. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors....

  8. Segmenting Brain Tumors with Symmetry

    OpenAIRE

    Zhang, Hejia; Zhu, Xia; Willke, Theodore L.

    2017-01-01

    We explore encoding brain symmetry into a neural network for a brain tumor segmentation task. A healthy human brain is symmetric at a high level of abstraction, and the high-level asymmetric parts are more likely to be tumor regions. Paying more attention to asymmetries has the potential to boost the performance in brain tumor segmentation. We propose a method to encode brain symmetry into existing neural networks and apply the method to a state-of-the-art neural network for medical imaging s...

  9. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

    The Brain Tumor Epidemiology Consortium is an open scientific forum organized to foster the development of multi-center, international and inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes, and prevention of brain tumors.

  10. Brain tumor survivors speak out.

    Science.gov (United States)

    Carlson-Green, Bonnie

    2009-01-01

    Although progress has been made in the treatment of childhood brain tumors,work remains to understand the complexities of disease, treatment, and contextual factors that underlie individual differences in outcome. A combination of both an idiographic approach (incorporating observations made by adult survivors of childhood brain tumors) and a nomothetic approach (reviewing the literature for brain tumor survivors as well as childhood cancer survivors) is presented. Six areas of concern are reviewed from both an idiographic and nomothetic perspective, including social/emotional adjustment, insurance, neurocognitive late effects, sexuality and relationships, employment, and where survivors accessed information about their disease and treatment and possible late effects. Guidelines to assist health care professionals working with childhood brain tumor survivors are offered with the goal of improving psychosocial and neurocognitive outcomes in this population.

  11. Multiparametric MR assessment of pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tzika, A.A. [Department of Radiology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); NMR Surgical Laboratory, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, 51 Blossom Street, Boston, MA 02114 (United States); Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T. [Department of Radiology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Goumnerova, L.; Black, P.McL. [Department of Neurosurgery, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Zurakowski, D. [Department of Biostatistics, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Anthony, D.C. [Department of Pathology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States)

    2003-01-01

    MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P<0.001). The relationship between rCBV and ADC was also inverse (P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P=0.51). A positive relationship was found between lipids and ADC (P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. (orig.)

  12. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated, and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma...... and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors....

  13. Monitoring Radiographic Brain Tumor Progression

    Directory of Open Access Journals (Sweden)

    John H. Sampson

    2011-03-01

    Full Text Available Determining radiographic progression in primary malignant brain tumors has posed a significant challenge to the neuroncology community. Glioblastoma multiforme (GBM, WHO Grade IV through its inherent heterogeneous enhancement, growth patterns, and irregular nature has been difficult to assess for progression. Our ability to detect tumor progression radiographically remains inadequate. Despite the advanced imaging techniques, detecting tumor progression continues to be a clinical challenge. Here we review the different criteria used to detect tumor progression, and highlight the inherent challenges with detection of progression.

  14. Brain Tumor Risk Factors

    Science.gov (United States)

    ... Professional Meetings Order Materials Clinical Trials Support Group Leader Training Adolescent and Young Adult Guidelines For brain ... nitrites), cigarette smoking, cell phone use, and residential power line exposure, for example—are true risk factors ...

  15. Brain tumors; Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

    Langen, K.J. [Forschungszentrum Juelich (Germany). Inst. fuer Neurowissenschaften und Biophysik; Stoffels, G. [Duesseldorf Univ. (Germany). C. und O. Vogt Inst. fuer Hirnforschung

    2007-09-15

    Magnetic Resonance Tomography (MRT) is the method of choice for the diagnostics of cerebral gliomas, but the differentiation of tumour tissue from unspecific tissue changes is limited. Positron emission tomography (PET) and Single-Photon-Emission-Computed Tomography (SPECT) may offer relevant additional information which allows for a more accurate diagnostics in unclear situations. Especially, radiolabeled amino acids offer a better delineation of cerebral gliomas which allows an improved guidance of biopsy, planning of surgery and radiation therapy. Furthermore, amino acid imaging appears to be useful to differentiate tumor recurrence from unspecific posttherapeutic tissue, to predict the prognosis especially in low grade gliomas and to monitor the metabolic response during tumor therapy. (orig.)

  16. Pediatric brain tumors; Kindliche Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W.; Bodea, S. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany); Muehl-Benninghaus, R.

    2017-09-15

    Brain tumors differ between children and adults both in histology and localization. Malignant gliomas and meningiomas predominate in adults while medulloblastomas and low-grade astrocytomas are the most frequent brain tumors in children. More than one half (50-70%) of pediatric brain tumors have an infratentorial location but only approximately 30% in adults. Brain tumors can be recognized in sonography, cranial computed tomography (CCT) and magnetic resonance imaging (MRI) by their space-consuming character and by their divergent density and intensity in comparison to normal brain parenchyma. They can grow extrusively, even infiltrate the parenchyma or originate from it. Besides clinical symptoms and diagnostics this article describes the most common pediatric brain tumors, i.e. astrocytoma, medulloblastoma, brainstem glioma, craniopharyngioma, neurofibromatosis and ganglioglioma. The most important imaging criteria are outlined. (orig.) [German] Sowohl Histologie als auch Lokalisation von Hirntumoren unterscheiden sich bei Kindern und Erwachsenen. Waehrend maligne Gliome und Meningeome bei Erwachsenen vorherrschen, kommen bei Kindern ueberwiegend Medulloblastome und niedriggradige Astrozytome vor. Mehr als die Haelfte (50-70 %) aller kindlichen Hirntumoren sind infratentoriell lokalisiert, dagegen sind es bei Erwachsenen nur etwa 30 %. Im Ultraschall, in der kranialen CT (CCT) oder MRT koennen Hirntumoren durch ihren raumfordernden Charakter und ihrer zum normalen Parenchym abweichenden Dichte oder Signalintensitaet erkannt werden. Sie koennen verdraengend wachsen, z. T. auch das Parenchym infiltrieren oder von diesem ausgehen. Neben der klinischen Symptomatik und Diagnostik werden im vorliegenden Artikel die haeufigsten kindlichen Hirntumoren, das Astrozytom, Medulloblastom, Hirnstammgliom, Kraniopharyngeom, die Neurofibromatose und das Gangliogliom beschrieben. Die wichtigsten bildgebende Kriterien werden dargestellt. (orig.)

  17. Pineal calcification is associated with pediatric primary brain tumor.

    Science.gov (United States)

    Tuntapakul, Supinya; Kitkhuandee, Amnat; Kanpittaya, Jaturat; Johns, Jeffrey; Johns, Nutjaree Pratheepawanit

    2016-12-01

    Melatonin has been associated with various tumors, including brain tumor, and shown to inhibit growth of neuroblastoma cells and gliomas in animal models. Likewise, patients with glioblastoma receiving melatonin reported better survival than controls. Pineal calcification may lead to a decreased production of melatonin by calcified glands. This study assessed association between pineal calcification and primary brain tumor in pediatric/adolescent patients. Medical chart review was conducted in 181 patients brain computed tomography (CT) during 2008-2012. Pineal calcification was identified using brain CT scan by an experienced neurosurgeon. Primary brain tumor was confirmed by CT scan and histology, and association with pineal calcification was estimated using multiple logistic regression, adjusted for age and gender. Primary brain tumor was detected in 51 patients (mean age 9.0, standard deviation 4.0 years), with medulloblastoma being the most common (11 patients). Pineal calcification was detected in 12 patients (23.5%) with primary brain tumor, while only 11 patients (8.5%) without tumor had pineal calcification. Adjusted for patients' ages and genders, pineal calcification was associated with an increase in primary brain tumor of 2.82-fold (odds ratio 2.82; 95% confidence interval 1.12-7.08, P = 0.027). Pineal calcification appears to be associated with primary brain tumor. Further studies to explore this link are discussed and warranted. © 2016 John Wiley & Sons Australia, Ltd.

  18. Pathological classification of brain tumors.

    Science.gov (United States)

    Pollo, B

    2012-04-01

    The tumors of the central nervous system are classified according to the last international classification published by World Health Organization. The Classification of Tumors of the Central Nervous System was done on 2007, based on morphological features, growth pattern and molecular profile of neoplastic cells, defining malignancy grade. The neuropathological diagnosis and the grading of each histotype are based on identification of histopathological criteria and immunohistochemical data. The histopathology, also consisting of findings with prognostic or predictive relevance, plays a critical role in the diagnosis and treatment of brain tumors. The recent progresses on radiological, pathological, immunohistochemical, molecular and genetic diagnosis improved the characterization of brain tumors. Molecular and genetic profiles may identify different tumor subtypes varying in biological and clinical behavior. To investigate new therapeutic approaches is important to study the molecular pathways that lead the processes of proliferation, invasion, angiogenesis, anaplastic transformation. Different molecular biomarkers were identified by genetic studies and some of these are used in neuro-oncology for the evaluation of glioma patients, in particular combined deletions of the chromosome arms 1p and 19q in oligodendroglial tumors, methylation status of the O-6 methylguanine- DNA methyltransferase gene promoter and alterations in the epidermal growth factor receptor pathway in adult malignant gliomas, isocitrate dehydrogenase 1 (IDH1) and IDH2 gene mutations in diffuse gliomas, as well as BRAF status in pilocytic astrocytomas. The prognostic evaluation and the therapeutic strategies for patients depend on synthesis of clinical, pathological and biological data: histological diagnosis, malignancy grade, gene-molecular profile, radiological pictures, surgical resection and clinical findings (age, tumor location, "performance status").

  19. What You Need to Know about Brain Tumors

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Brain Tumors This booklet is about tumors that begin in the brain. These tumors are called primary brain tumors. Cancer that spreads to the brain from another ...

  20. Targeting Malignant Brain Tumors with Antibodies

    OpenAIRE

    Rok Razpotnik; Neža Novak; Vladka Čurin Šerbec; Uros Rajcevic

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain deli...

  1. Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

    NARCIS (Netherlands)

    Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

    1993-01-01

    The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

  2. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference...... to the tolerability and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database search without date restriction was performed and over 500 articles were found. Twenty-five articles were used for this study based on relevance determined by: (i) clinical studies, (ii) use of bleomycin, and (iii......) direct injection into brain tissue or cysts. There were two main indications for the use of bleomycin directly into the brain: (i) cystic tumors in the form of craniopharyngiomas and (ii) solid brain tumors such as glioblastomas and astrocytomas. The most frequent adverse effects reported were transient...

  3. Brain tumors in children; Hirntumoren beim Kind

    Energy Technology Data Exchange (ETDEWEB)

    Harting, I.; Seitz, A. [Universitaetsklinikum Heidelberg (Germany). Abt. Neuroradiologie

    2009-06-15

    Brain tumors are common in children; in Germany approximately 400 children are diagnosed every year. In the posterior fossa, cerebellar neoplasms outnumber brainstem gliomas. In contrast to their rarity in adults, brainstem gliomas are not uncommon in children. Supratentorial tumors can be subdivided by location into neoplasms of the cerebral hemispheres, suprasellar and pineal tumors. Astrocytoma is the most common pediatric brain tumor followed by medulloblastoma, ependymoma and craniopharyngeoma. The combination of imaging morphology, tumor localisation and patient age at manifestation form the basis of the neuroradiological differential diagnosis. (orig.)

  4. CTLA-4 Limits Anti-CD20-Mediated Tumor Regression.

    Science.gov (United States)

    Ren, Zhenhua; Guo, Jingya; Liao, Jing; Luan, Yan; Liu, Zhida; Sun, Zhichen; Liu, Xiaojuan; Liang, Yong; Peng, Hua; Fu, Yang-Xin

    2017-01-01

    The inhibition of tumor growth by anti-CD20 antibody (Ab) treatment is mediated by Ab- and complement-dependent cytotoxicity in xenograft tumor models. In addition, anti-CD20 therapy for B-cell lymphoma can result in intrinsic and extrinsic tumor resistance to further Ab treatment. However, adaptive immune response-related resistance has not been well studied in anti-CD20-mediated tumor control, and adaptive immunity has long been underestimated. The purpose of this study was to explore whether T cells are involved in mediating the effects of anti-CD20 therapy and what factors contribute to adaptive immune response-related resistance. Using a syngeneic mouse B-cell lymphoma model, we investigated the role of CD8(+) T cells in anti-CD20-mediated tumor regression. Furthermore, we revealed how the tumor-specific T-cell response was initiated by anti-CD20. Finally, we studied adaptive immune response-related resistance in advanced B-cell lymphoma. CD8(+) T cells played an essential role in anti-CD20-mediated tumor regression. Mechanistically, anti-CD20 therapy promoted dendritic cell (DC)-mediated cross-presentation. Importantly, macrophages were also necessary for the increase in the tumor-specific CTL response after anti-CD20 treatment, via the production of type I IFN to activate DC function. Furthermore, adaptive resistance is gradually developed through the CTLA-4 pathway in Treg cells in larger lymphomas. Further blockade of CTLA-4 can synergize with anti-CD20 treatment in antitumor activities. The therapeutic function of anti-CD20 depends on tumor-specific CD8(+) T-cell responses initiated by anti-CD20 through macrophages and DCs. CTLA-4 blockade can synergize with anti-CD20 to overcome adaptive immune response-related resistance in advanced B-cell lymphoma. Clin Cancer Res; 23(1); 193-203. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Brain tumor stem cell dancing

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2014-09-01

    Full Text Available Background. Issues regarding cancer stem cell (CSC movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".

  6. Methylated DNA for monitoring tumor growth and regression

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Nielsen, Dorte; Söletormos, Georg

    2014-01-01

    Abstract A wide range of protein cancer biomarkers is currently recommended in international guidelines for monitoring the growth and regression of solid tumors. However, a number of these markers are also present in low concentrations in blood obtained from healthy individuals and from patients...... of evidence can partly be explained by incomplete collection of serial blood samples, by analytical challenges, and by lack of knowledge of how monitoring studies should be designed and how serial marker data obtained from individual patients should be interpreted. Here, we review the clinical validity...

  7. Regression of conjunctival tumor during dietary treatment of celiac disease

    Directory of Open Access Journals (Sweden)

    Tuncer Samuray

    2010-01-01

    Full Text Available A 3-year-old girl presented with a hemorrhagic conjunctival lesion in the right eye. The medical history revealed premature cessation of breast feeding, intolerance to the ingestion of baby foods, anorexia, and abdominal distention. Prior to her referral, endoscopic small intestinal biopsy had been carried out under general anesthesia with a possible diagnosis of Celiac Disease (CD. Her parents did not want their child to undergo general anesthesia for the second time for the excisional biopsy. We decided to follow the patient until all systemic investigations were concluded. In evaluation, the case was diagnosed with CD and the conjunctival tumor showed complete regression during gluten-free dietary treatment. The clinical fleshy appearance of the lesion with spider-like vascular extensions and subconjunctival hemorrhagic spots, possible association with an acquired immune system dysfunction due to CD, and spontaneous regression by a gluten-free diet led us to make a presumed diagnosis of conjunctival Kaposi sarcoma.

  8. Model-Based Evaluation of Spontaneous Tumor Regression in Pilocytic Astrocytoma.

    Directory of Open Access Journals (Sweden)

    Thomas Buder

    2015-12-01

    Full Text Available Pilocytic astrocytoma (PA is the most common brain tumor in children. This tumor is usually benign and has a good prognosis. Total resection is the treatment of choice and will cure the majority of patients. However, often only partial resection is possible due to the location of the tumor. In that case, spontaneous regression, regrowth, or progression to a more aggressive form have been observed. The dependency between the residual tumor size and spontaneous regression is not understood yet. Therefore, the prognosis is largely unpredictable and there is controversy regarding the management of patients for whom complete resection cannot be achieved. Strategies span from pure observation (wait and see to combinations of surgery, adjuvant chemotherapy, and radiotherapy. Here, we introduce a mathematical model to investigate the growth and progression behavior of PA. In particular, we propose a Markov chain model incorporating cell proliferation and death as well as mutations. Our model analysis shows that the tumor behavior after partial resection is essentially determined by a risk coefficient γ, which can be deduced from epidemiological data about PA. Our results quantitatively predict the regression probability of a partially resected benign PA given the residual tumor size and lead to the hypothesis that this dependency is linear, implying that removing any amount of tumor mass will improve prognosis. This finding stands in contrast to diffuse malignant glioma where an extent of resection threshold has been experimentally shown, below which no benefit for survival is expected. These results have important implications for future therapeutic studies in PA that should include residual tumor volume as a prognostic factor.

  9. Brain's tumor image processing using shearlet transform

    Science.gov (United States)

    Cadena, Luis; Espinosa, Nikolai; Cadena, Franklin; Korneeva, Anna; Kruglyakov, Alexey; Legalov, Alexander; Romanenko, Alexey; Zotin, Alexander

    2017-09-01

    Brain tumor detection is well known research area for medical and computer scientists. In last decades there has been much research done on tumor detection, segmentation, and classification. Medical imaging plays a central role in the diagnosis of brain tumors and nowadays uses methods non-invasive, high-resolution techniques, especially magnetic resonance imaging and computed tomography scans. Edge detection is a fundamental tool in image processing, particularly in the areas of feature detection and feature extraction, which aim at identifying points in a digital image at which the image has discontinuities. Shearlets is the most successful frameworks for the efficient representation of multidimensional data, capturing edges and other anisotropic features which frequently dominate multidimensional phenomena. The paper proposes an improved brain tumor detection method by automatically detecting tumor location in MR images, its features are extracted by new shearlet transform.

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

    OpenAIRE

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

    2013-01-01

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

  11. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

    Full Text Available Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon and primary (Gli36 glioma brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

  12. Air pollution from traffic and risk for brain tumors

    DEFF Research Database (Denmark)

    Poulsen, Aslak Harbo; Sørensen, Mette; Andersen, Zorana J.

    2016-01-01

    to replicate that finding in a large nationwide case-control study. METHODS: We identified all 4,183 adult brain tumor cases in Denmark in the years 2000-2009 and 8,018 risk set sampled population controls matched on gender and year of birth. We extracted residential address histories and estimated mean......PURPOSE: Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out...... residential nitrogen oxides (NOx) concentrations since 1971 with a validated dispersion model. Categorical and linear odds ratios (OR) and confidence intervals (CI) were calculated with conditional logistic regression models. RESULTS: The highest risk estimates for any brain cancer were observed among...

  13. Proton MRS imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zarifi, Maria [Aghia Sophia Children' s Hospital, Department of Radiology, Athens (Greece); Tzika, A.A. [Harvard Medical School, Department of Surgery, Massachusetts General Hospital, Boston, MA (United States); Shriners Burn Hospital, Boston, MA (United States)

    2016-06-15

    Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors. (orig.)

  14. [Brain tumor immunotherapy: Illusion or hope?

    Science.gov (United States)

    Migliorini, Denis; Dutoit, Valérie; Walker, Paul R; Dietrich, Pierre-Yves

    2017-05-01

    Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials. Indeed, the tumor bed is hostile to anti-tumor immune responses due to many escape mechanisms, and this is particularly true in the context of brain tumors, a master in eliciting immunosuppressive cells and molecules. The goal of this review is to describe the hopes and challenges of brain tumors immunotherapy and to propose an inventory of the current clinical research with specific focus on the therapies targeting the tumor microenvironment. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  15. Significant tumor regression induced by microencapsulation of recombinant tumor cells secreting fusion protein.

    Science.gov (United States)

    Shi, Meiqing; Hao, Siguo; Quereshi, Mabood; Guo, Xulin; Zheng, Changyu; Xiang, Jim

    2005-06-01

    Implantation of microencapsulated engineered cells secreting molecules with antineoplastic properties into tumors is a novel approach to cancer gene therapy. In this study, we constructed an engineered tumor cell line, VkCk/RM4-TNF-alpha, which secreted RM4/TNF-alpha fusion protein containing the chimeric antitumor antibody, F(ab')2 (RM4), recognizing the tumor antigen TAG72, as well as the TNF-alpha moiety. The engineered cells were encapsulated into microencapsules. The RM4/TNF-alpha fusion protein secreted by encapsulated VkCk/RM4-TNF-alpha cells could be diffused through the microencapsule membrane into the supernatant and exert a cytotoxic effect on L929 cells in vitro. The antigen-specific binding-reactivity of RM4/TNF-alpha for the TAG72 antigen was confirmed by immunohistochemical staining of rat LMCR tumor cells which expressed TAG72 antigen. Implantation of microencapsules containing VkCk/RM4-TNF-alpha cells into LMCR tumors in rats induced tumor regression as a result of tumor necrosis formation. Taken together, these data suggest that microencapsulation of recombinant tumor cells secreting antibody/cytokine fusion protein might be an alternative approach in the treatment of cancers.

  16. Unusual radiological characteristics of teratoid/rhabdoid brain tumor ...

    African Journals Online (AJOL)

    We report a case of atypical teratoid rhabdoid brain tumor for 4 months old male child, who presented with unusual radiological findings, that can be confused with other brain tumors ,so we high light these unusual imaging features to aid in making correct diagnosis. Keywords: atypical teratoid–rhabdoid tumor, brain tumor, ...

  17. Adenoviral virotherapy for malignant brain tumors

    OpenAIRE

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-01-01

    Glioblastoma multiforme (GBM) is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors (CAR) on surface of gliomas provides for inefficien...

  18. Within-brain classification for brain tumor segmentation.

    Science.gov (United States)

    Havaei, Mohammad; Larochelle, Hugo; Poulin, Philippe; Jodoin, Pierre-Marc

    2016-05-01

    In this paper, we investigate a framework for interactive brain tumor segmentation which, at its core, treats the problem of interactive brain tumor segmentation as a machine learning problem. This method has an advantage over typical machine learning methods for this task where generalization is made across brains. The problem with these methods is that they need to deal with intensity bias correction and other MRI-specific noise. In this paper, we avoid these issues by approaching the problem as one of within brain generalization. Specifically, we propose a semi-automatic method that segments a brain tumor by training and generalizing within that brain only, based on some minimum user interaction. We investigate how adding spatial feature coordinates (i.e., i, j, k) to the intensity features can significantly improve the performance of different classification methods such as SVM, kNN and random forests. This would only be possible within an interactive framework. We also investigate the use of a more appropriate kernel and the adaptation of hyper-parameters specifically for each brain. As a result of these experiments, we obtain an interactive method whose results reported on the MICCAI-BRATS 2013 dataset are the second most accurate compared to published methods, while using significantly less memory and processing power than most state-of-the-art methods.

  19. Life satisfaction in adult survivors of childhood brain tumors.

    Science.gov (United States)

    Crom, Deborah B; Li, Zhenghong; Brinkman, Tara M; Hudson, Melissa M; Armstrong, Gregory T; Neglia, Joseph; Ness, Kirsten K

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

  20. Carbonic anhydrase IX in oligodendroglial brain tumors

    Directory of Open Access Journals (Sweden)

    Pastorekova Silvia

    2008-01-01

    Full Text Available Abstract Background Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion. Methods This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas. Results 80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015. CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD and regulatory gammaglutamylcysteine synthetase (GLCL-R: CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008 and decreased in GLCL-R-positive tumors (p = 0.044. In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively, CA IX positivity predicting poorer outcome. Conclusion CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.

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

    Science.gov (United States)

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

    2017-03-01

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

  2. Fetal microchimerism in human brain tumors.

    Science.gov (United States)

    Broestl, Lauren; Rubin, Joshua B; Dahiya, Sonika

    2017-09-18

    Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively. © 2017 International Society of Neuropathology.

  3. Targeted toxins in brain tumor therapy.

    Science.gov (United States)

    Li, Yan Michael; Hall, Walter A

    2010-11-01

    Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

  4. Heterogeneous data fusion for brain tumor classification.

    Science.gov (United States)

    Metsis, Vangelis; Huang, Heng; Andronesi, Ovidiu C; Makedon, Fillia; Tzika, Aria

    2012-10-01

    Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset.

  5. Targeting Malignant Brain Tumors with Antibodies.

    Science.gov (United States)

    Razpotnik, Rok; Novak, Neža; Čurin Šerbec, Vladka; Rajcevic, Uros

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv) with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A "Trojan horse" method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT). Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs) are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts), are making their way into glioma treatment as another type of cell-based therapy using the

  6. Targeting Malignant Brain Tumors with Antibodies

    Directory of Open Access Journals (Sweden)

    Rok Razpotnik

    2017-09-01

    Full Text Available Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs, and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A “Trojan horse” method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT. Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs and neural stem cells (NSCs show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts, are making their way into glioma treatment as another type of cell

  7. Retinoblastoma regression patterns following chemoreduction and adjuvant therapy in 557 tumors.

    Science.gov (United States)

    Shields, Carol L; Palamar, Melis; Sharma, Pooja; Ramasubramanian, Aparna; Leahey, Ann; Meadows, Anna T; Shields, Jerry A

    2009-03-01

    To evaluate retinoblastoma regression patterns following chemoreduction and adjuvant therapy. A total of 557 retinoblastomas. A retrospective medical record review following 6 cycles of chemoreduction and tumor consolidation (thermotherapy or cryotherapy). Regression patterns included type 0 (no remnant), type 1 (calcified remnant), type 2 (noncalcified remnant), type 3 (partially calcified remnant), and type 4 (flat scar). Regression pattern. Retinoblastoma regressions were type 0 (n = 10), type 1 (n = 75), type 2 (n = 28), type 3 (n = 127), and type 4 (n = 317). Tumors with an initial thickness of 3 mm or less regressed most often to type 4 (92%), those 3 to 8 mm regressed to type 3 (34%) or type 4 (40%), and those thicker than 8 mm regressed to type 1 (40%) or type 3 (49%). Factors predictive of type 1 regression included larger tumor base and closer foveolar proximity. Factors predictive of type 3 included older age, larger tumor base, macular location, closer foveolar proximity, and lack of consolidation. Factors predictive of type 4 included familial hereditary pattern, smaller tumor base, greater foveolar distance, and tumor consolidation. Following chemoreduction, most small retinoblastomas result in a flat scar, intermediate tumors in a flat or partially calcified remnant, and large tumors in a more completely calcified remnant.

  8. Cognitive tasks challenging brain tumor survivors at work.

    Science.gov (United States)

    Collins, Courtney; Gehrke, Amanda; Feuerstein, Michael

    2013-12-01

    To identify problematic work tasks involving cognitive function in employed brain tumor survivors. Work tasks involving cognitive functions were compared between employed brain tumor survivors (n = 137) and a disease-free group (n = 96). Multivariable logistic regressions were conducted. In the brain tumor survivors, 44% (26/59) of work tasks were more likely to be problematic. Top five problematic work tasks included were as follows: following the flow of events (odds ratio [OR] = 11.72; 95% confidence interval [CI] = 3.19 to 43.07), remembering train of thought while speaking (OR = 11.70; 95% CI = 5.25 to 26.10), putting together materials for a task (OR = 10.90; 95% CI = 2.80 to 42.38), shifting between tasks (OR = 10.71; 95% CI = 3.62 to 31.74), and following written instructions (OR = 9.96; 95% CI = 2.65 to 37.41). Findings identified problematic work tasks involving major domains of cognitive function.

  9. Adenoviral virotherapy for malignant brain tumors.

    Science.gov (United States)

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-06-01

    Glioblastoma multiforme is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are overexpressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor-specific promoter elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review examines current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications.

  10. Subacute brain atrophy after radiation therapy for malignant brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  11. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

    Science.gov (United States)

    Bergamino, Maurizio; Hamilton, David J; Castelletti, Lara; Barletta, Laura; Castellan, Lucio

    2015-03-01

    In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org. © The Author(s) 2013.

  12. Brain tumor mutations detected in cerebral spinal fluid.

    Science.gov (United States)

    Pan, Wenying; Gu, Wei; Nagpal, Seema; Gephart, Melanie Hayden; Quake, Stephen R

    2015-03-01

    Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood-brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative "liquid biopsy" of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined. We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease. We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from tumor biopsy. Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care. © 2014 American Association for Clinical Chemistry.

  13. Deep learning for brain tumor classification

    Science.gov (United States)

    Paul, Justin S.; Plassard, Andrew J.; Landman, Bennett A.; Fabbri, Daniel

    2017-03-01

    Recent research has shown that deep learning methods have performed well on supervised machine learning, image classification tasks. The purpose of this study is to apply deep learning methods to classify brain images with different tumor types: meningioma, glioma, and pituitary. A dataset was publicly released containing 3,064 T1-weighted contrast enhanced MRI (CE-MRI) brain images from 233 patients with either meningioma, glioma, or pituitary tumors split across axial, coronal, or sagittal planes. This research focuses on the 989 axial images from 191 patients in order to avoid confusing the neural networks with three different planes containing the same diagnosis. Two types of neural networks were used in classification: fully connected and convolutional neural networks. Within these two categories, further tests were computed via the augmentation of the original 512×512 axial images. Training neural networks over the axial data has proven to be accurate in its classifications with an average five-fold cross validation of 91.43% on the best trained neural network. This result demonstrates that a more general method (i.e. deep learning) can outperform specialized methods that require image dilation and ring-forming subregions on tumors.

  14. Complete regression of transmissible venereal tumor (TVT)in ...

    African Journals Online (AJOL)

    Intravenous administration of 0.025mg/kg body weight vincristine sulphate, in normal saline, in four weekly doses led to complete regression of lesions, within 35 days, in 4 mongrel dogs and 6 bitches with histologically diagnosed transmissible venereal tumour (TVT). Early side effects observed in the dogs, such as ...

  15. Intraoperative MRI in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Choudhri, Asim F. [Le Bonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Neurosurgery, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Ophthalmology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Siddiqui, Adeel [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Klimo, Paul; Boop, Frederick A. [University of Tennessee Health Science Center, Department of Neurosurgery, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Semmes-Murphey Neurologic and Spine Institute, Memphis, TN (United States); St. Jude Children' s Hospital, Division of Neurosurgery, Department of Surgery, Memphis, TN (United States)

    2015-09-15

    Intraoperative magnetic resonance imaging (iMRI) has emerged as an important tool in guiding the surgical management of children with brain tumors. Recent advances have allowed utilization of high field strength systems, including 3-tesla MRI, resulting in diagnostic-quality scans that can be performed while the child is on the operating table. By providing information about the possible presence of residual tumor, it allows the neurosurgeon to both identify and resect any remaining tumor that is thought to be safely accessible. By fusing the newly obtained images with the surgical guidance software, the images have the added value of aiding in navigation to any residual tumor. This is important because parenchyma often shifts during surgery. It also gives the neurosurgeon insight into whether any immediate postoperative complications have occurred. If any complications have occurred, the child is already in the operating room and precious minutes lost in transport and communications are saved. In this article we review the three main approaches to an iMRI system design. We discuss the possible roles for iMRI during intraoperative planning and provide guidance to help radiologists and neurosurgeons alike in the collaborative management of these children. (orig.)

  16. Phosphorylethanolamine content of human brain tumors.

    Science.gov (United States)

    Kinoshita, Y; Yokota, A; Koga, Y

    1994-12-01

    Phosphorylethanolamine (PEA) is the major component of the phosphomonoester peak detected by phosphorus-31 magnetic resonance spectroscopy, but the absolute concentration has not been determined. This study measured the PEA concentration in biopsy specimens of brain tumors and lobectomized cerebral cortex using high-performance liquid chromatography. The concentration of PEA was 118.5 +/- 10.0 mumol/100 g wet wt in cortex, and was significantly higher in malignant gliomas, metastatic pulmonary adenocarcinoma, and neurinoma. The concentration of PEA was especially high in pituitary adenoma, malignant lymphoma, and medulloblastoma.

  17. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    Science.gov (United States)

    Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

    2013-01-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  18. Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFN gamma Signaling

    DEFF Research Database (Denmark)

    Donia, Marco; Harbst, Katja; van Buuren, Marit

    2017-01-01

    Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed...... disease recurrence following an initial, unequivocal radiologic complete regression after T-cell-based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune...... radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted....

  19. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

    Rasmussen, H Boje; Teisner, B; Schrøder, H D

    1991-01-01

    Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen...... in primary brain tumors except in gliosarcoma where FA2 was distributed diffusely in the sarcoma region and was absent in the glioma region. In metastatic carcinoma with tumor stroma a diffuse staining reaction was seen in the stroma and with a basement membrane (BM) like staining at the tumor cell....../stroma interface. Intracytoplasmic FA2 staining of the tumor cells was seen in areas without tumor stroma. In metastatic melanoma a BM like FA2 staining was seen around and between individual tumor cells. The staining patterns seen in the metastatic tumors were in accordance with that of the corresponding primary...

  20. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

    Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo

    2017-01-01

    In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    Science.gov (United States)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  2. Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand Inhibition

    Directory of Open Access Journals (Sweden)

    Martin F. Dietrich MD, PhD

    2014-11-01

    Full Text Available Lung metastases are a rare complication of giant cell tumors of bone. We herein describe an interesting case of histological regression and size reduction of lung metastases originating from a primary giant cell tumor of bone in response to the RANK ligand inhibitor denosumab.

  3. Fractal analysis of tumoral lesions in brain.

    Science.gov (United States)

    Martín-Landrove, Miguel; Pereira, Demian; Caldeira, María E; Itriago, Salvador; Juliac, María

    2007-01-01

    In this work, it is proposed a method for supervised characterization and classification of tumoral lesions in brain, based on the analysis of irregularities at the lesion contour on T2-weighted MR images. After the choice of a specific image, a segmentation procedure with a threshold selected from the histogram of intensity levels is applied to isolate the lesion, the contour is detected through the application of a gradient operator followed by a conversion to a "time series" using a chain code procedure. The correlation dimension is calculated and analyzed to discriminate between normal or malignant structures. The results found showed that it is possible to detect a differentiation between benign (cysts) and malignant (gliomas) lesions suggesting the potential of this method as a diagnostic tool.

  4. Brain Tumor Trials Collaborative | Center for Cancer Research

    Science.gov (United States)

    Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

  5. Diagnosis and prognosis of brain tumors in clinical trials

    NARCIS (Netherlands)

    T.S. Gorlia (Thierry)

    2013-01-01

    textabstractAccording to the Central Brain Registry Of The United States (CBTRUS) statistical report (February 2012) the incidence rate of all primary non malignant and malignant brain and central nervous system tumors is 19.89 cases per 100.000 (11.58 for non-malignant tumors and 7.31 for malignant

  6. Anticonvulsant therapy in brain-tumor related epilepsy

    Directory of Open Access Journals (Sweden)

    Fröscher Walter

    2016-06-01

    Full Text Available Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

  7. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. © 2013 AlphaMed Press.

  8. Stimulated Raman scattering microscopy for rapid brain tumor histology

    Directory of Open Access Journals (Sweden)

    Yifan Yang

    2017-09-01

    Full Text Available Rapid histology of brain tissues with sufficient diagnostic information has the great potential to aid neurosurgeons during operations. Stimulated Raman Scattering (SRS microscopy is an emerging label-free imaging technique, with the intrinsic chemical resolutions to delineate brain tumors from normal tissues without the need of time-consuming tissue processing. Growing number of studies have shown SRS as a “virtual histology” tool for rapid diagnosis of various types of brain tumors. In this review, we focus on the basic principles and current developments of SRS microscopy, as well as its applications for brain tumor imaging.

  9. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  10. Neuropsychiatric presentations of pediatrics brain tumors: cases series

    Directory of Open Access Journals (Sweden)

    Khairkar Praveen

    2016-12-01

    Full Text Available Brain tumors constitute the second most common tumors in the pediatric age group after the leukemias. Symptoms and signs depend on growth rate of tumor, its location in the central nervous system, the extent of peri-tumoral vasogenic edema and the age of the child. Most common neuropsychiatric problems reported in children with brain tumor(s include adjustment problems, anxiety disorder, neurocognitive deficits and depressive disorder as reported by very few case reports and isolated observational data. To the best of our knowledge no similar data or reports are as yet published from India on the similar lines. We wish to report case series of neuropsychiatric presentations in different types of brain tumors observed at our rural tertiary care multi-speciality hospital.

  11. CARS and non-linear microscopy imaging of brain tumors

    Science.gov (United States)

    Galli, Roberta; Uckermann, Ortrud; Tamosaityte, Sandra; Geiger, Kathrin; Schackert, Gabriele; Steiner, Gerald; Koch, Edmund; Kirsch, Matthias

    2013-06-01

    Nonlinear optical microscopy offers a series of techniques that have the potential to be applied in vivo, for intraoperative identification of tumor border and in situ pathology. By addressing the different content of lipids that characterize the tumors with respect to the normal brain tissue, CARS microscopy enables to discern primary and secondary brain tumors from healthy tissue. A study performed in mouse models shows that the reduction of the CARS signal is a reliable quantity to identify brain tumors, irrespective from the tumor type. Moreover it enables to identify tumor borders and infiltrations at a cellular resolution. Integration of CARS with autogenous TPEF and SHG adds morphological and compositional details about the tissue. Examples of multimodal CARS imaging of different human tumor biopsies demonstrate the ability of the technique to retrieve information useful for histopathological diagnosis.

  12. A case of metastatic brain tumor causing multifocal cerebral embolism.

    Science.gov (United States)

    Kawaguchi, Takuya; Yamanouchi, Yasuo; Numa, Yoshihiro; Sakurai, Yasuo; Yamahara, Takahiro; Seno, Toshitaka; Shikata, Nobuaki; Asai, Akio; Kawamoto, Keiji

    2012-01-01

    The patient was a 72-year-old woman who had previously undergone treatment for femoral chondrosarcoma (histologically rated as myxofibrosarcoma). She suddenly developed left homonymous hemianopsia and was diagnosed with cerebral embolism. Because she had atrial fibrillation, we treated her for cardiogenic cerebral embolism. About 3 months later, however, she developed left hemiplegia, and head magnetic resonance imaging revealed multiple tumorous lesions affecting the previously detected infracted area and several new areas. We assumed that a tumor embolus had caused cerebral embolism, which resulted in growth of the tumor from the embolus and formation of a metastatic brain tumor. The metastatic foci formed from the tumor embolus were visualized by diagnostic imaging, and histological examination of the resected tumor confirmed that the brain tumor had occluded the brain vessel (tumorigenic cerebral embolism). No such case has been reported to date, and this case seems to be important.

  13. Patients With Brain Tumors: Who Receives Postacute Occupational Therapy Services?

    Science.gov (United States)

    Chan, Vincy; Xiong, Chen; Colantonio, Angela

    2015-01-01

    Data on the utilization of occupational therapy among patients with brain tumors have been limited to those with malignant tumors and small samples of patients outside North America in specialized palliative care settings. We built on this research by examining the characteristics of patients with brain tumors who received postacute occupational therapy services in Ontario, Canada, using health care administrative data. Between fiscal years 2004-2005 and 2008-2009, 3,199 patients with brain tumors received occupational therapy services in the home care setting after hospital discharge; 12.4% had benign brain tumors, 78.2% had malignant brain tumors, and 9.4% had unspecified brain tumors. However, patients with benign brain tumors were older (mean age=63.3 yr), and a higher percentage were female (65.2%). More than 90% of patients received in-home occupational therapy services. Additional research is needed to examine the significance of these differences and to identify factors that influence access to occupational therapy services in the home care setting. Copyright © 2015 by the American Occupational Therapy Association, Inc.

  14. Lassa-vesicular stomatitis chimeric virus safely destroys brain tumors.

    Science.gov (United States)

    Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N; Cepko, Connie; van den Pol, Anthony N

    2015-07-01

    High-grade tumors in the brain are among the deadliest of cancers. Here, we took a promising oncolytic virus, vesicular stomatitis virus (VSV), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic VSV glycoprotein with the glycoprotein from one of five different viruses, including Ebola virus, Marburg virus, lymphocytic choriomeningitis virus (LCMV), rabies virus, and Lassa virus. Based on in vitro infections of normal and tumor cells, we selected two viruses to test in vivo. Wild-type VSV was lethal when injected directly into the brain. In contrast, a novel chimeric virus (VSV-LASV-GPC) containing genes from both the Lassa virus glycoprotein precursor (GPC) and VSV showed no adverse actions within or outside the brain and targeted and completely destroyed brain cancer, including high-grade glioblastoma and melanoma, even in metastatic cancer models. When mice had two brain tumors, intratumoral VSV-LASV-GPC injection in one tumor (glioma or melanoma) led to complete tumor destruction; importantly, the virus moved contralaterally within the brain to selectively infect the second noninjected tumor. A chimeric virus combining VSV genes with the gene coding for the Ebola virus glycoprotein was safe in the brain and also selectively targeted brain tumors but was substantially less effective in destroying brain tumors and prolonging survival of tumor-bearing mice. A tropism for multiple cancer types combined with an exquisite tumor specificity opens a new door to widespread application of VSV-LASV-GPC as a safe and efficacious oncolytic chimeric virus within the brain. Many viruses have been tested for their ability to target and kill cancer cells. Vesicular stomatitis virus (VSV) has shown substantial promise, but a key problem is that if it enters the brain, it can generate adverse neurologic consequences, including death. We tested a series of

  15. Multifractal texture estimation for detection and segmentation of brain tumors.

    Science.gov (United States)

    Islam, Atiq; Reza, Syed M S; Iftekharuddin, Khan M

    2013-11-01

    A stochastic model for characterizing tumor texture in brain magnetic resonance (MR) images is proposed. The efficacy of the model is demonstrated in patient-independent brain tumor texture feature extraction and tumor segmentation in magnetic resonance images (MRIs). Due to complex appearance in MRI, brain tumor texture is formulated using a multiresolution-fractal model known as multifractional Brownian motion (mBm). Detailed mathematical derivation for mBm model and corresponding novel algorithm to extract spatially varying multifractal features are proposed. A multifractal feature-based brain tumor segmentation method is developed next. To evaluate efficacy, tumor segmentation performance using proposed multifractal feature is compared with that using Gabor-like multiscale texton feature. Furthermore, novel patient-independent tumor segmentation scheme is proposed by extending the well-known AdaBoost algorithm. The modification of AdaBoost algorithm involves assigning weights to component classifiers based on their ability to classify difficult samples and confidence in such classification. Experimental results for 14 patients with over 300 MRIs show the efficacy of the proposed technique in automatic segmentation of tumors in brain MRIs. Finally, comparison with other state-of-the art brain tumor segmentation works with publicly available low-grade glioma BRATS2012 dataset show that our segmentation results are more consistent and on the average outperforms these methods for the patients where ground truth is made available.

  16. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  17. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    Science.gov (United States)

    Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli; Davitkov, Perica; Robbins, Sarah; Cherukuri, Rajesh; Patel, Ashokkumar; Gupta, Rajnish; Cohen, Mark; Barrios, Jaime Vengoechea; Brewer, Cathy; Schilero, Cathy; Smolenski, Kathy; McGraw, Mary; Denk, Barbara; Naska, Theresa; Laube, Frances; Steele, Ruth; Greene, Dale; Kastl, Alison; Bell, Susan; Aziz, Dina; Chiocca, E. A.; McPherson, Christopher; Warnick, Ronald; Barnett, Gene H.; Sloan, Andrew E.; Barnholtz-Sloan, Jill S.

    2012-01-01

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases. PMID:22649779

  18. Association rule mining based study for identification of clinical parameters akin to occurrence of brain tumor.

    Science.gov (United States)

    Sengupta, Dipankar; Sood, Meemansa; Vijayvargia, Poorvika; Hota, Sunil; Naik, Pradeep K

    2013-01-01

    Healthcare sector is generating a large amount of information corresponding to diagnosis, disease identification and treatment of an individual. Mining knowledge and providing scientific decision-making for the diagnosis & treatment of disease from the clinical dataset is therefore increasingly becoming necessary. Aim of this study was to assess the applicability of knowledge discovery in brain tumor data warehouse, applying data mining techniques for investigation of clinical parameters that can be associated with occurrence of brain tumor. In this study, a brain tumor warehouse was developed comprising of clinical data for 550 patients. Apriori association rule algorithm was applied to discover associative rules among the clinical parameters. The rules discovered in the study suggests - high values of Creatinine, Blood Urea Nitrogen (BUN), SGOT & SGPT to be directly associated with tumor occurrence for patients in the primary stage with atleast 85% confidence and more than 50% support. A normalized regression model is proposed based on these parameters along with Haemoglobin content, Alkaline Phosphatase and Serum Bilirubin for prediction of occurrence of STATE (brain tumor) as 0 (absent) or 1 (present). The results indicate that the methodology followed will be of good value for the diagnostic procedure of brain tumor, especially when large data volumes are involved and screening based on discovered parameters would allow clinicians to detect tumors at an early stage of development.

  19. Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

    Science.gov (United States)

    Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

    2016-05-01

    The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Distinctive responses of brain tumor cells to TLR2 ligands.

    Science.gov (United States)

    Yoon, Hee Jung; Jeon, Sae-Bom; Koh, Han Seok; Song, Jae-Young; Kim, Sang Soo; Kim, In-Hoo; Park, Eun Jung

    2015-05-01

    Malignant brain tumor mass contains significant numbers of infiltrating glial cells that may intimately interact with tumor cells and influence cancer treatments. Understanding of characteristic discrepancies between normal GLIA and tumor cells would, therefore, be valuable for improving anticancer therapeutics. Here, we report distinct differences in toll-like receptors (TLR)-2-mediated responses between normal glia and primary brain tumor cell lines. We found that tyrosine phosphorylation of STAT1 by TLR2 ligands and its downstream events did not occur in mouse, rat, or human brain tumor cell lines, but were markedly induced in normal primary microglia and astrocytes. Using TLR2-deficient, interferon (IFN)-γ-deficient, and IFNγ-receptor-1-deficient mice, we revealed that the impaired phosphorylation of STAT1 might be linked with defective TLR2 system in tumor cells, and that a TLR2-dependent pathway, not IFNγ-receptor machinery, might be critical for tyrosine STAT1 phosphorylation by TLR2 ligands. We also found that TLR2 and its heterodimeric partners, TLR1 and 6, on brain tumor cells failed to properly respond to TLR2 ligands, and representative TLR2-dependent cellular events, such as inflammatory responses and cell death, were not detected in brain tumor cells. Similar results were obtained in in vitro and in vivo experiments using orthotopic mouse and rat brain tumor models. Collectively, these results suggest that primary brain tumor cells may exhibit a distinctive dysfunction of TLR2-associated responses, resulting in abnormal signaling and cellular events. Careful targeting of this distinctive property could serve as the basis for effective therapeutic approaches against primary brain tumors. © 2015 Wiley Periodicals, Inc.

  1. Coffee and green tea consumption in relation to brain tumor risk in a Japanese population.

    Science.gov (United States)

    Ogawa, Takahiro; Sawada, Norie; Iwasaki, Motoki; Budhathoki, Sanjeev; Hidaka, Akihisa; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Narita, Yoshitaka; Tsugane, Shoichiro

    2016-12-15

    Few prospective studies have investigated the etiology of brain tumor, especially among Asian populations. Both coffee and green tea are popular beverages, but their relation with brain tumor risk, particularly with glioma, has been inconsistent in epidemiological studies. In this study, we evaluated the association between coffee and greed tea intake and brain tumor risk in a Japanese population. We evaluated a cohort of 106,324 subjects (50,438 men and 55,886 women) in the Japan Public Health Center-Based Prospective Study (JPHC Study). Subjects were followed from 1990 for Cohort I and 1993 for Cohort II until December 31, 2012. One hundred and fifty-seven (70 men and 87 women) newly diagnosed cases of brain tumor were identified during the study period. Hazard ratio (HR) and 95% confidence intervals (95%CIs) for the association between coffee or green tea consumption and brain tumor risk were assessed using a Cox proportional hazards regression model. We found a significant inverse association between coffee consumption and brain tumor risk in both total subjects (≥3 cups/day; HR = 0.47, 95%CI = 0.22-0.98) and in women (≥3 cups/day; HR = 0.24, 95%CI = 0.06-0.99), although the number of cases in the highest category was small. Furthermore, glioma risk tended to decrease with higher coffee consumption (≥3 cups/day; HR = 0.54, 95%CI = 0.16-1.80). No association was seen between green tea and brain tumor risk. In conclusion, our study suggested that coffee consumption might reduce the risk of brain tumor, including that of glioma, in the Japanese population. © 2016 UICC.

  2. The perivascular niche microenvironment in brain tumor progression

    Science.gov (United States)

    Charles, Nikki

    2010-01-01

    Glioblastoma, the most frequent and aggressive malignant brain tumor, has a very poor prognosis of approximately 1-year. The associated aggressive phenotype and therapeutic resistance of glioblastoma is postulated to be due to putative brain tumor stem-like cells (BTSC). The best hope for improved therapy lies in the ability to understand the molecular biology that controls BTSC behavior. The tumor vascular microenvironment of brain tumors has emerged as important regulators of BTSC behavior. Emerging data have identified the vascular microenvironment as home to a multitude of cell types engaged in various signaling that work collectively to foster a supportive environment for BTSCs. Characterization of the signaling pathways and intercellular communication between resident cell types in the microvascular niche of brain tumors is critical to the identification of potential BTSC-specific targets for therapy. PMID:20714216

  3. Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

    Science.gov (United States)

    Fontebasso, Adam M; Jabado, Nada

    2015-01-01

    Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

  4. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

    Science.gov (United States)

    MacDiarmid, Jennifer A.; Langova, Veronika; Bailey, Dale; Pattison, Scott T.; Pattison, Stacey L.; Christensen, Neil; Armstrong, Luke R.; Brahmbhatt, Vatsala N.; Smolarczyk, Katarzyna; Harrison, Matthew T.; Costa, Marylia; Mugridge, Nancy B.; Sedliarou, Ilya; Grimes, Nicholas A.; Kiss, Debra L.; Stillman, Bruce; Hann, Christine L.; Gallia, Gary L.; Graham, Robert M.; Brahmbhatt, Himanshu

    2016-01-01

    Background Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. Methodology/Principle Findings EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). Conclusions/Significance Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On

  5. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model.

    Directory of Open Access Journals (Sweden)

    Jennifer A MacDiarmid

    Full Text Available Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers.EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT and magnetic resonance imaging (MRI. Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973. No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs.Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of

  6. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

    Directory of Open Access Journals (Sweden)

    Katharina Galmbacher

    Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

  7. Brain tumor classification of microscopy images using deep residual learning

    Science.gov (United States)

    Ishikawa, Yota; Washiya, Kiyotada; Aoki, Kota; Nagahashi, Hiroshi

    2016-12-01

    The crisis rate of brain tumor is about one point four in ten thousands. In general, cytotechnologists take charge of cytologic diagnosis. However, the number of cytotechnologists who can diagnose brain tumors is not sufficient, because of the necessity of highly specialized skill. Computer-Aided Diagnosis by computational image analysis may dissolve the shortage of experts and support objective pathological examinations. Our purpose is to support a diagnosis from a microscopy image of brain cortex and to identify brain tumor by medical image processing. In this study, we analyze Astrocytes that is a type of glia cell of central nerve system. It is not easy for an expert to discriminate brain tumor correctly since the difference between astrocytes and low grade astrocytoma (tumors formed from Astrocyte) is very slight. In this study, we present a novel method to segment cell regions robustly using BING objectness estimation and to classify brain tumors using deep convolutional neural networks (CNNs) constructed by deep residual learning. BING is a fast object detection method and we use pretrained BING model to detect brain cells. After that, we apply a sequence of post-processing like Voronoi diagram, binarization, watershed transform to obtain fine segmentation. For classification using CNNs, a usual way of data argumentation is applied to brain cells database. Experimental results showed 98.5% accuracy of classification and 98.2% accuracy of segmentation.

  8. Adaptive radiotherapy based on the daily regression of a tumor in carbon-ion beam irradiation.

    Science.gov (United States)

    Nagano, Ai; Minohara, Shinichi; Kato, Shingo; Kiyohara, Hiroki; Ando, Ken

    2012-12-21

    We propose a new application of adaptive radiotherapy using a scanning beam, taking into account the daily regression of a tumor. No patient-specific hardware (such as collimators and compensating filters) is needed for the scanning technique; thus, it allows re-planning immediately before each fractional irradiation using the sophisticated conformations of dose distributions. We retrospectively modeled the tumor volume regression curves as a function of the dose from the CT images which were taken three times during the treatment course. The daily shape of the tumor was mathematically interpolated assuming constant continuity of the tumor deformation. We simulated the adaptive radiotherapy by optimizing the dose distribution on the estimated daily tumor volume for every fraction. The dose-volume histogram (DVH) for the organ at risk in the adaptive radiotherapy was compared with that of the current clinical protocol. We performed analysis using the CT images of cervical cancer patients who received carbon-ion radiotherapy in broad-beam irradiation. The DVH for the rectum and the sigmoid colon was improved by adaptive radiotherapy considering the inter-fractional tumor regression. The result shows that this approach has possible advantages.

  9. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

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    Leticia Corrales

    2015-05-01

    Full Text Available Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic.

  10. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity.

    Science.gov (United States)

    Corrales, Leticia; Glickman, Laura Hix; McWhirter, Sarah M; Kanne, David B; Sivick, Kelsey E; Katibah, George E; Woo, Seng-Ryong; Lemmens, Edward; Banda, Tamara; Leong, Justin J; Metchette, Ken; Dubensky, Thomas W; Gajewski, Thomas F

    2015-05-19

    Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT) administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN) derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Labeled Putrescine as a Probe in Brain Tumors

    Science.gov (United States)

    Volkow, Nora; Goldman, Stephen S.; Flamm, Eugene S.; Cravioto, Humberto; Wolf, Alfred P.; Brodie, Jonathan D.

    1983-08-01

    The polyamine metabolism of transplanted N-nitrosomethylurea-derived rat glioma was determined with radiolabeled putrescine used as a marker for malignancy. The uptake of putrescine in vivo was complete within 5 minutes and was specific for tumor tissue. The conversion of putrescine to spermine and other metabolites by the tumor was rapid, in contrast to the case for adjacent normal brain. These results suggest that putrescine labeled with carbon-11 may be used as a positron-emission tomographic tracer for the selective metabolic imaging of brain tumor and may be used in an appropriate model as a marker for tumor growth rate.

  12. Applications of nanotechnology to imaging and therapy of brain tumors.

    Science.gov (United States)

    Mohs, Aaron M; Provenzale, James M

    2010-08-01

    In the past decade, numerous advances in the understanding of brain tumor physiology, tumor imaging, and tumor therapy have been attained. In some cases, these advances have resulted from refinements of pre-existing technologies (eg, improvements of contrast-enhanced magnetic resonance imaging). In other instances, advances have resulted from development of novel technologies. The development of nanomedicine (ie, applications of nanotechnology to the field of medicine) is an example of the latter. In this review, the authors explain the principles that underlay nanoparticle design and function as well as the means by which nanoparticles can be used for imaging and therapy of brain tumors. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Gliomatosis cerebri: no evidence for a separate brain tumor entity.

    Science.gov (United States)

    Herrlinger, Ulrich; Jones, David T W; Glas, Martin; Hattingen, Elke; Gramatzki, Dorothee; Stuplich, Moritz; Felsberg, Jörg; Bähr, Oliver; Gielen, Gerrit H; Simon, Matthias; Wiewrodt, Dorothee; Schabet, Martin; Hovestadt, Volker; Capper, David; Steinbach, Joachim P; von Deimling, Andreas; Lichter, Peter; Pfister, Stefan M; Weller, Michael; Reifenberger, Guido

    2016-02-01

    Gliomatosis cerebri (GC) is presently considered a distinct astrocytic glioma entity according to the WHO classification for CNS tumors. It is characterized by widespread, typically bilateral infiltration of the brain involving three or more lobes. Genetic studies of GC have to date been restricted to the analysis of individual glioma-associated genes, which revealed mutations in the isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 (TP53) genes in subsets of patients. Here, we report on a genome-wide analysis of DNA methylation and copy number aberrations in 25 GC patients. Results were compared with those obtained for 105 patients with various types of conventional, i.e., non-GC gliomas including diffuse astrocytic gliomas, oligodendrogliomas and glioblastomas. In addition, we assessed the prognostic role of methylation profiles and recurrent DNA copy number aberrations in GC patients. Our data reveal that the methylation profiles in 23 of the 25 GC tumors corresponded to either IDH mutant astrocytoma (n = 6), IDH mutant and 1p/19q codeleted oligodendroglioma (n = 5), or IDH wild-type glioblastoma including various molecular subgroups, i.e., H3F3A-G34 mutant (n = 1), receptor tyrosine kinase 1 (RTK1, n = 4), receptor tyrosine kinase 2 (classic) (RTK2, n = 2) or mesenchymal (n = 5) glioblastoma groups. Two tumors showed methylation profiles of normal brain tissue due to low tumor cell content. While histological grading (WHO grade IV vs. WHO grade II and III) was not prognostic, the molecular classification as classic/RTK2 or mesenchymal glioblastoma was associated with worse overall survival. Multivariate Cox regression analysis revealed MGMT promoter methylation as a positive prognostic factor. Taken together, DNA-based large-scale molecular profiling indicates that GC comprises a genetically and epigenetically heterogeneous group of diffuse gliomas that carry DNA methylation and copy number profiles closely matching the common molecularly

  14. Predicting respiratory tumor motion with multi-dimensional adaptive filters and support vector regression

    Energy Technology Data Exchange (ETDEWEB)

    Riaz, Nadeem; Wiersma, Rodney; Mao Weihua; Xing Lei [Department of Radiation Oncology, Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305-5847 (United States); Shanker, Piyush; Gudmundsson, Olafur; Widrow, Bernard [Department of Electrical Engineering, Stanford University, Stanford, CA 94305 (United States)], E-mail: nriaz@stanford.edu

    2009-10-07

    Intra-fraction tumor tracking methods can improve radiation delivery during radiotherapy sessions. Image acquisition for tumor tracking and subsequent adjustment of the treatment beam with gating or beam tracking introduces time latency and necessitates predicting the future position of the tumor. This study evaluates the use of multi-dimensional linear adaptive filters and support vector regression to predict the motion of lung tumors tracked at 30 Hz. We expand on the prior work of other groups who have looked at adaptive filters by using a general framework of a multiple-input single-output (MISO) adaptive system that uses multiple correlated signals to predict the motion of a tumor. We compare the performance of these two novel methods to conventional methods like linear regression and single-input, single-output adaptive filters. At 400 ms latency the average root-mean-square-errors (RMSEs) for the 14 treatment sessions studied using no prediction, linear regression, single-output adaptive filter, MISO and support vector regression are 2.58, 1.60, 1.58, 1.71 and 1.26 mm, respectively. At 1 s, the RMSEs are 4.40, 2.61, 3.34, 2.66 and 1.93 mm, respectively. We find that support vector regression most accurately predicts the future tumor position of the methods studied and can provide a RMSE of less than 2 mm at 1 s latency. Also, a multi-dimensional adaptive filter framework provides improved performance over single-dimension adaptive filters. Work is underway to combine these two frameworks to improve performance.

  15. Local specific absorption rate in brain tumors at 7 tesla.

    Science.gov (United States)

    Restivo, Matthew C; van den Berg, Cornelis A T; van Lier, Astrid L H M W; Polders, Daniël L; Raaijmakers, Alexander J E; Luijten, Peter R; Hoogduin, Hans

    2016-01-01

    MR safety at 7 Tesla relies on accurate numerical simulations of transmit electromagnetic fields to fully assess local specific absorption rate (SAR) safety. Numerical simulations for SAR safety are currently performed using models of healthy patients. These simulations might not be useful for estimating SAR in patients who have large lesions with potentially abnormal dielectric properties, e.g., brain tumors. In this study, brain tumor patient models are constructed based on scans of four patients with high grade brain tumors. Dielectric properties for the modeled tumors are assigned based on electrical properties tomography data for the same patients. Simulations were performed to determine SAR. Local SAR increases in the tumors by as much as 30%. However, the location of the maximum 10-gram averaged SAR typically occurs outside of the tumor, and thus does not increase. In the worst case, if the tumor model is moved to the location of maximum electric field intensity, then we do observe an increase in the estimated peak 10-gram SAR directly related to the tumor. Peak local SAR estimation made on the results of a healthy patient model simulation may underestimate the true peak local SAR in a brain tumor patient. © 2015 Wiley Periodicals, Inc.

  16. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  17. Imaging of brain tumors with histological correlations. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, Antonios (ed.)

    2011-07-01

    This volume provides a deeper understanding of the diagnosis of brain tumors by correlating radiographic imaging features with the underlying pathological abnormalities. All modern imaging modalities are used to complete a diagnostic overview of brain tumors with emphasis on recent advances in diagnostic neuroradiology. High-quality illustrations depicting common and uncommon imaging characteristics of a wide range of brain tumors are presented and analysed, drawing attention to the ways in which these characteristics reflect different aspects of pathology. Important theoretical considerations are also discussed. Since the first edition, chapters have been revised and updated and new material has been added, including detailed information on the clinical application of functional MRI and diffusion tensor imaging. Radiologists and other clinicians interested in the current diagnostic approach to brain tumors will find this book to be an invaluable and enlightening clinical tool. (orig.)

  18. Blockade of Notch Signaling in Tumor-Bearing Mice May Lead to Tumor Regression, Progression, or Metastasis, Depending on Tumor Cell Types

    Directory of Open Access Journals (Sweden)

    Xing-Bin Hu

    2009-01-01

    Full Text Available It has been reported that blocking Notch signaling in tumor-bearing mice results in abortive angiogenesis and tumor regression. However, given that Notch signaling influences numerous cellular processes in vivo, a comprehensive evaluation of the effect of Notch inactivation on tumor growth would be favorable. In this study, we inoculated four cancer cell lines in mice with the conditional inactivation of recombination signal-binding protein-Jκ (RBP-J, which mediates signaling from all four mammalian Notch receptors. We found that whereas three tumors including hepatocarcinoma, lung cancer, and osteogenic sarcoma grew slower in the RBP-J-deficient mice, at least a melanoma, B16, grew significantly faster in the RBP-J-deficient mice than in the controls, suggesting that the RBP-J-deficient hosts could provide permissive cues for tumor growth. All these tumors showed increased microvessels and up-regulated hypoxia-inducible factor 1α, suggesting that whereas defective angiogenesis resulted in hypoxia, different tumors might grow differentially in the RBP-J-deleted mice. Similarly, increased infiltration of Gr1+/Mac1+ cells were noticed in tumors grown in the RBP-J-inactivated mice. Moreover, we found that when inoculated in the RBP-J knockout hosts, the H22 hepatoma cells had a high frequency of metastasis and lethality, suggesting that at least for H22, deficiency of environmental Notch signaling favored tumor metastasis. Our findings suggested that the general blockade of Notch signaling in tumor-bearing mice could lead to defective angiogenesis in tumors, but depending on tumor cell types, general inhibition of Notch signaling might result in tumor regression, progression, or metastasis.

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

    Science.gov (United States)

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

    2017-03-23

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

  20. Imaging cerebral tryptophan metabolism in brain tumor-associated depression.

    Science.gov (United States)

    Bosnyák, Edit; Kamson, David O; Behen, Michael E; Barger, Geoffrey R; Mittal, Sandeep; Juhász, Csaba

    2015-12-01

    Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[(11)C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD', an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. The mean BDI-II score was 12 ± 10 (range: 2-33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p Tumor size, grade, and tumor type were not related to depression scores. Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of

  1. FDTD analysis of a noninvasive hyperthermia system for brain tumors.

    Science.gov (United States)

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

    Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  2. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    Directory of Open Access Journals (Sweden)

    Yacoob Sulafa M

    2012-08-01

    Full Text Available Abstract Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  3. Long-term psychiatric outcomes in pediatric brain tumor survivors.

    Science.gov (United States)

    Shah, Sumedh Subodh; Dellarole, Anna; Peterson, Eric Cecala; Bregy, Amade; Komotar, Ricardo; Harvey, Philip D; Elhammady, Mohamed Samy

    2015-05-01

    The increased efficacy of cancer treatments has led to a greater survival rate of patients with pediatric brain cancers. Therefore, it is imperative to explore the long-term consequences of therapies employed to treat pediatric brain tumors. The goal of this study was to provide a review of literature regarding the downstream psychological and psychiatric consequences experienced by adult survivors of pediatric brain cancer as a result of treatment, tumor type, or tumor location. A PubMed MeSH search and additional online database searches were conducted to include pertinent studies that discussed psychological deficits in childhood brain cancer survivors. The studies included were subjected to data extraction to quantify relevant information for further analysis. A total of 17 papers with 5320 pediatric brain tumor patients were incorporated in our review. Mean age at diagnosis (8.13 ± 0.77 years), mean follow-up time (9.98 ± 3.05 years), and male-to-female ratios (1.08:1) were compiled from studies reporting this information. Incidences of depression (19 %), anxiety (20 %), suicidal ideation (10.9 %), schizophrenia and its related psychoses (9.8 %), and behavioral problem (28.7 %) were higher among pediatric brain cancer survivors than in the normal population. Craniospinal radiotherapy and/or surgery corresponded to an increased likelihood of developing adverse deficits. Astrocytomas or other glial tumors were linked to poorer outcomes. Physicians treating pediatric brain tumor patients should be aware of the possible consequences associated with treatment. Psychiatric monitoring is warranted in survivors of pediatric brain tumors, but further investigation is needed to elucidate late outcomes regarding tumor type and location.

  4. Tumor Cells and Micro-environment in Brain Metastases

    Directory of Open Access Journals (Sweden)

    Wen ZHONG

    2016-09-01

    Full Text Available Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis ”seed and soil”, that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases.

  5. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  6. Modeling the Interplay Between Tumor Volume Regression and Oxygenation in Uterine Cervical Cancer During Radiotherapy Treatment.

    Science.gov (United States)

    Belfatto, Antonella; Riboldi, Marco; Ciardo, Delia; Cattani, Federica; Cecconi, Agnese; Lazzari, Roberta; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto; Baroni, Guido; Cerveri, Pietro

    2016-03-01

    This paper describes a patient-specific mathematical model to predict the evolution of uterine cervical tumors at a macroscopic scale, during fractionated external radiotherapy. The model provides estimates of tumor regrowth and dead-cell reabsorption, incorporating the interplay between tumor regression rate and radiosensitivity, as a function of the tumor oxygenation level. Model parameters were estimated by minimizing the difference between predicted and measured tumor volumes, these latter being obtained from a set of 154 serial cone-beam computed tomography scans acquired on 16 patients along the course of the therapy. The model stratified patients according to two different estimated dynamics of dead-cell removal and to the predicted initial value of the tumor oxygenation. The comparison with a simpler model demonstrated an improvement in fitting properties of this approach (fitting error average value <5%, p < 0.01), especially in case of tumor late responses, which can hardly be handled by models entailing a constant radiosensitivity, failing to model changes from initial severe hypoxia to aerobic conditions during the treatment course. The model predictive capabilities suggest the need of clustering patients accounting for cancer cell line, tumor staging, as well as microenvironment conditions (e.g., oxygenation level).

  7. Regression of orthotopic neuroblastoma in mice by targeting the endothelial and tumor cell compartments

    Directory of Open Access Journals (Sweden)

    Stridsberg Mats

    2009-03-01

    Full Text Available Abstract Background High-risk neuroblastoma has an overall five-year survival of less than 40%, indicating a need for new treatment strategies such as angiogenesis inhibition. Recent studies have shown that chemotherapeutic drugs can inhibit angiogenesis if administered in a continuous schedule. The aim of this study was primarily to characterize tumor spread in an orthotopic, metastatic model for aggressive, MYCN-amplified neuroblastoma and secondarily to study the effects of daily administration of the chemotherapeutic agent CHS 828 on tumor angiogenesis, tumor growth, and spread. Methods MYCN-amplified human neuroblastoma cells (IMR-32, 2 × 106 were injected into the left adrenal gland in SCID mice through a flank incision. Nine weeks later, a new laparotomy was performed to confirm tumor establishment and to estimate tumor volume. Animals were randomized to either treatment with CHS 828 (20 mg/kg/day; p.o. or vehicle control. Differences between groups in tumor volume were analyzed by Mann-Whitney U test and in metastatic spread using Fisher's exact test. Differences with p Results The orthotopic model resembled clinical neuroblastoma in respect to tumor site, growth and spread. Treatment with CHS 828 resulted in tumor regression (p Conclusion The metastatic animal model in this study resembled clinical neuroblastoma and is therefore clinically relevant for examining new treatment strategies for this malignancy. Our results indicate that daily scheduling of CHS 828 may be beneficial in treating patients with high-risk neuroblastoma.

  8. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    Directory of Open Access Journals (Sweden)

    Liya Zhao

    2016-01-01

    Full Text Available Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs. Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness.

  9. Significant predictors of patients' uncertainty in primary brain tumors.

    Science.gov (United States)

    Lin, Lin; Chien, Lung-Chang; Acquaye, Alvina A; Vera-Bolanos, Elizabeth; Gilbert, Mark R; Armstrong, Terri S

    2015-05-01

    Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients is necessary throughout the

  10. Novel strategies of Raman imaging for brain tumor research.

    Science.gov (United States)

    Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

    2017-10-17

    Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that

  11. Toward real-time tumor margin identification in image-guided robotic brain tumor resection

    Science.gov (United States)

    Hu, Danying; Jiang, Yang; Belykh, Evgenii; Gong, Yuanzheng; Preul, Mark C.; Hannaford, Blake; Seibel, Eric J.

    2017-03-01

    For patients with malignant brain tumors (glioblastomas), a safe maximal resection of tumor is critical for an increased survival rate. However, complete resection of the cancer is hard to achieve due to the invasive nature of these tumors, where the margins of the tumors become blurred from frank tumor to more normal brain tissue, but in which single cells or clusters of malignant cells may have invaded. Recent developments in fluorescence imaging techniques have shown great potential for improved surgical outcomes by providing surgeons intraoperative contrast-enhanced visual information of tumor in neurosurgery. The current near-infrared (NIR) fluorophores, such as indocyanine green (ICG), cyanine5.5 (Cy5.5), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), are showing clinical potential to be useful in targeting and guiding resections of such tumors. Real-time tumor margin identification in NIR imaging could be helpful to both surgeons and patients by reducing the operation time and space required by other imaging modalities such as intraoperative MRI, and has the potential to integrate with robotically assisted surgery. In this paper, a segmentation method based on the Chan-Vese model was developed for identifying the tumor boundaries in an ex-vivo mouse brain from relatively noisy fluorescence images acquired by a multimodal scanning fiber endoscope (mmSFE). Tumor contours were achieved iteratively by minimizing an energy function formed by a level set function and the segmentation model. Quantitative segmentation metrics based on tumor-to-background (T/B) ratio were evaluated. Results demonstrated feasibility in detecting the brain tumor margins at quasi-real-time and has the potential to yield improved precision brain tumor resection techniques or even robotic interventions in the future.

  12. Brain Tumor Segmentation Using a Generative Model with an RBM Prior on Tumor Shape

    DEFF Research Database (Denmark)

    Agn, Mikael; Puonti, Oula; Rosenschöld, Per Munck af

    2016-01-01

    In this paper, we present a fully automated generative method for brain tumor segmentation in multi-modal magnetic resonance images. The method is based on the type of generative model often used for segmenting healthy brain tissues, where tissues are modeled by Gaussian mixture models combined...... with a spatial atlas-based tissue prior. We extend this basic model with a tumor prior, which uses convolutional restricted Boltzmann machines (cRBMs) to model the shape of both tumor core and complete tumor, which includes edema and core. The cRBMs are trained on expert segmentations of training images, without...

  13. An Epigenetic Gateway to Brain Tumor Cell Identity

    Science.gov (United States)

    Mack, Stephen C.; Hubert, Christopher G.; Miller, Tyler E.; Taylor, Michael D.; Rich, Jeremy N.

    2017-01-01

    Precise targeting of genetic lesions alone has been insufficient to extend brain tumor patient survival. Brain cancer cells are diverse in their genetic, metabolic, and microenvironmental compositions, accounting for their phenotypic heterogeneity and disparate responses to therapy. These factors converge at the level of the epigenome, representing a unified node that can be disrupted by pharmacologic inhibition. Aberrant epigenomes define many childhood and adult brain cancers, as demonstrated by widespread changes to DNA methylation patterns, redistribution of histone marks, and disruption of chromatin structure. In this review, we describe the convergence of genetic, metabolic, and micro-environmental factors upon mechanisms of epigenetic deregulation in brain cancer. We discuss how aberrant epigenetic pathways identified in brain tumors affect cell identity, cell state, and neoplastic transformation, in addition to the potential to exploit these alterations as novel therapeutic strategies for the treatment of brain cancer. PMID:26713744

  14. Evolution of Brain Tumor and Stability of Geometric Invariants

    Directory of Open Access Journals (Sweden)

    K. Tawbe

    2008-01-01

    Full Text Available This paper presents a method to reconstruct and to calculate geometric invariants on brain tumors. The geometric invariants considered in the paper are the volume, the area, the discrete Gauss curvature, and the discrete mean curvature. The volume of a tumor is an important aspect that helps doctors to make a medical diagnosis. And as doctors seek a stable calculation, we propose to prove the stability of some invariants. Finally, we study the evolution of brain tumor as a function of time in two or three years depending on patients with MR images every three or six months.

  15. Brain tumor symptoms as antecedents to uncertainty: an integrative review.

    Science.gov (United States)

    Cahill, Jennifer; LoBiondo-Wood, Geri; Bergstrom, Nancy; Armstrong, Terri

    2012-06-01

    Uncertainty is a common experience within human cancer. For brain tumor patients, irregular symptom pattern and presentation may promote uncertainties about treatment response, prognosis, and life quality. We sought to identify the somatic symptom experience associated with primary and secondary brain tumors and the potential impact on illness-related uncertainty. An integrative literature search of Medline and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed. Symptom data were excerpted into tables and reviewed critically against the broader uncertainty-focused oncology literature. Twenty-one studies investigated a diverse range of brain tumor symptoms that persist through the now-expanding, post-treatment survival. While symptoms such as fatigue were common, antecedents and patterns were poorly characterized and inconsistent between and within categories of tumor. Symptom investigation is an emerging and rapidly developing area of neuro-oncology. The extent to which symptoms are familiar, predictable, and understandable can mitigate uncertainty. The unstable nature of symptoms across the trajectory of a brain tumor may be a significant corollary to illness-related uncertainty. Because the majority of brain tumor patients cannot be cured of their cancer, understanding the symptom expanse and potential to promote uncertainty could inform alternative nursing strategies to reduce anxiety and distress, and to preserve life quality where cure is often unattainable. © 2012 Sigma Theta Tau International.

  16. Critical Care Management of Cerebral Edema in Brain Tumors.

    Science.gov (United States)

    Esquenazi, Yoshua; Lo, Victor P; Lee, Kiwon

    2017-01-01

    Cerebral edema associated with brain tumors is extremely common and can occur in both primary and metastatic tumors. The edema surrounding brain tumors results from leakage of plasma across the vessel wall into the parenchyma secondary to disruption of the blood-brain barrier. The clinical signs of brain tumor edema depend on the location of the tumor as well as the extent of the edema, which often exceeds the mass effect induced by the tumor itself. Uncontrolled cerebral edema may result in increased intracranial pressure and acute herniation syndromes that can result in permanent neurological dysfunction and potentially fatal herniation. Treatment strategies for elevated intracranial pressure consist of general measures, medical interventions, and surgery. Alhough the definitive treatment for the edema may ultimately be surgical resection of the tumor, the impact of the critical care management cannot be underestimated and thus patients must be vigilantly monitored in the intensive care unit. In this review, we discuss the pathology, pathophysiology, and clinical features of patients presenting with cerebral edema. Imaging findings and treatment modalities used in the intensive care unit are also discussed. © The Author(s) 2015.

  17. The social trajectory of brain tumor: a qualitative metasynthesis.

    Science.gov (United States)

    Cubis, Lee; Ownsworth, Tamara; Pinkham, Mark B; Chambers, Suzanne

    2017-04-19

    Research indicates that strong social ties can buffer the adverse effects of chronic illness on psychological well-being. Brain tumor typically leads to serious functional impairments that affect relationships and reduce social participation. This metasynthesis aimed to identify, appraise and integrate the findings of qualitative studies that reveal the impact of brain tumor on social networks. Four major databases (PubMed, CINAHL, Cochrane Library and PsycINFO) were systematically searched from inception to September 2016 for qualitative studies that reported findings on the impact of primary brain tumor on social networks during adulthood. Twenty-one eligible studies were identified and appraised according to the Consolidated Criteria for Reporting Qualitative Research. Key findings of these studies were integrated to form superordinate themes. The metasynthesis revealed the core themes of: 1) Life disrupted; 2) Navigating the new reality of life; and 3) Social survivorship versus separation. Multiple changes typically occur across the social trajectory of brain tumor, including a loss of pre-illness networks and the emergence of new ones. Understanding the barriers and facilitators for maintaining social connection may guide interventions for strengthening social networks and enhancing well-being in the context of brain tumor. Implications for rehabilitation Social networks and roles are disrupted throughout the entire trajectory of living with brain tumor Physical, cognitive and psychological factors represent barriers to social integration Barriers to social integration may be addressed by supportive care interventions Compensatory strategies, adjusting goals and expectations, educating friends and family and accepting support from others facilitate social reintegration throughout the trajectory of living with brain tumor.

  18. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    Energy Technology Data Exchange (ETDEWEB)

    Hartford, Alan C., E-mail: Alan.C.Hartford@Hitchcock.org [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Paravati, Anthony J. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Spire, William J. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Li, Zhongze [Biostatistics Shared Resource, Norris Cotton Cancer Center, Lebanon, New Hampshire (United States); Jarvis, Lesley A. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Fadul, Camilo E. [Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Rhodes, C. Harker [Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Erkmen, Kadir [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Friedman, Jonathan [Department of Surgery, Texas A and M College of Medicine, College Station, Texas (United States); Gladstone, David J. [Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States); Hug, Eugen B. [ProCure, New York, New York (United States); Roberts, David W.; Simmons, Nathan E. [Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States)

    2013-03-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

  19. Research of the multimodal brain-tumor segmentation algorithm

    Science.gov (United States)

    Lu, Yisu; Chen, Wufan

    2015-12-01

    It is well-known that the number of clusters is one of the most important parameters for automatic segmentation. However, it is difficult to define owing to the high diversity in appearance of tumor tissue among different patients and the ambiguous boundaries of lesions. In this study, a nonparametric mixture of Dirichlet process (MDP) model is applied to segment the tumor images, and the MDP segmentation can be performed without the initialization of the number of clusters. A new nonparametric segmentation algorithm combined with anisotropic diffusion and a Markov random field (MRF) smooth constraint is proposed in this study. Besides the segmentation of single modal brain tumor images, we developed the algorithm to segment multimodal brain tumor images by the magnetic resonance (MR) multimodal features and obtain the active tumor and edema in the same time. The proposed algorithm is evaluated and compared with other approaches. The accuracy and computation time of our algorithm demonstrates very impressive performance.

  20. CT-guided laser probe for ablation of brain tumors

    Directory of Open Access Journals (Sweden)

    Abdolhadi Daneshi

    2010-01-01

    Full Text Available   Abstract  In this study, 22 patients (15-75 years old were selected and transferred to CT scan for tumor ablation. For ablations, after prep and drep under the local anesthesia and mild sedation in proper position, small incision made and special needle inserted and guided by proper direction to the core of the tumor. Then, laser probe inserted through the needle and laser energy delivered. Although we have not a good prognosis in metastatic tumors but post-operative follow up and brain CT scan established the effect of laser on resection and evaporation and diminution of mass effect in tumor lesions.

  1. Neoadjuvant chemotherapy for brain tumors in infants and young children.

    Science.gov (United States)

    Iwama, Junya; Ogiwara, Hideki; Kiyotani, Chikako; Terashima, Keita; Matsuoka, Kentaro; Iwafuchi, Hideto; Morota, Nobuhito

    2015-05-01

    Because of their large size and high vascularity, complete removal of brain tumors in infants and young children is often difficult. In most cases the degree of resection is associated with prognosis. Neoadjuvant chemotherapy may facilitate resection by reducing the vascularity of the tumor. The authors evaluated the effectiveness of neoadjuvant chemotherapy in the management of these tumors. The authors performed a retrospective review of infants and young children who underwent tumor removal after neoadjuvant chemotherapy. Nine consecutive patients underwent resection after neoadjuvant chemotherapy during the period February 2004 to December 2012. The mean age at diagnosis was 18 months (range 2-50 months). The average largest tumor diameter was 71 mm (range 30-130 mm) at initial surgery. Five patients underwent partial resection, and 4 underwent biopsy as the initial surgery. The histopathological diagnoses were ependymoma in 2 patients, anaplastic ependymoma in 1, primitive neuroectodermal tumor (PNET) in 2, choroid plexus carcinoma in 1, atypical teratoid/rhabdoid tumor (AT/RT) in 1, glioblastoma in 1, and embryonal tumor with abundant neuropil and true rosettes in 1. After 2-4 courses of multiagent chemotherapy (mainly with vincristine, cyclophosphamide, etoposide, and cisplatin), the second-look surgery was performed. In 1 patient with a PNET, intratumoral hemorrhage was observed after 2 courses of chemotherapy. The mean interval between the initial and the second-look surgery was 3 months. The tumor volume was reduced to varying degrees in 5 patients (56%) after chemotherapy. Intraoperatively, the vascularity of the tumor was considerably reduced, and the tumor was more circumscribed in all cases. Gross-total resection was achieved in 8 patients (89%) and neartotal resection in 1 (11%). Histopathological examination demonstrated fibrotic tissue circumscribing the tumor in 6 of 9 cases (67%). The average blood loss was 20% of the estimated blood volume, and

  2. Brain and Spinal Tumors: Hope through Research

    Science.gov (United States)

    ... called lobes, which handle different neurological functions. The frontal lobes manage voluntary movement, such as writing, and let us set and prioritize goals. A frontal lobe tumor can cause changes in personality, intellect, reasoning, ...

  3. Convection-enhanced delivery for the treatment of brain tumors

    Science.gov (United States)

    Debinski, Waldemar; Tatter, Stephen B

    2013-01-01

    The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies. PMID:19831841

  4. Groupwise registration of MR brain images with tumors

    Science.gov (United States)

    Tang, Zhenyu; Wu, Yihong; Fan, Yong

    2017-09-01

    A novel groupwise image registration framework is developed for registering MR brain images with tumors. Our method iteratively estimates a normal-appearance counterpart for each tumor image to be registered and constructs a directed graph (digraph) of normal-appearance images to guide the groupwise image registration. Particularly, our method maps each tumor image to its normal appearance counterpart by identifying and inpainting brain tumor regions with intensity information estimated using a low-rank plus sparse matrix decomposition based image representation technique. The estimated normal-appearance images are groupwisely registered to a group center image guided by a digraph of images so that the total length of ‘image registration paths’ to be the minimum, and then the original tumor images are warped to the group center image using the resulting deformation fields. We have evaluated our method based on both simulated and real MR brain tumor images. The registration results were evaluated with overlap measures of corresponding brain regions and average entropy of image intensity information, and Wilcoxon signed rank tests were adopted to compare different methods with respect to their regional overlap measures. Compared with a groupwise image registration method that is applied to normal-appearance images estimated using the traditional low-rank plus sparse matrix decomposition based image inpainting, our method achieved higher image registration accuracy with statistical significance (p  =  7.02  ×  10-9).

  5. Factors affecting the cerebral network in brain tumor patients.

    Science.gov (United States)

    Heimans, Jan J; Reijneveld, Jaap C

    2012-06-01

    Brain functions, including cognitive functions, are frequently disturbed in brain tumor patients. These disturbances may result from the tumor itself, but also from the treatment directed against the tumor. Surgery, radiotherapy and chemotherapy all may affect cerebral functioning, both in a positive as well as in a negative way. Apart from the anti-tumor treatment, glioma patients often receive glucocorticoids and anti-epileptic drugs, which both also have influence on brain functioning. The effect of a brain tumor on cerebral functioning is often more global than should be expected on the basis of the local character of the disease, and this is thought to be a consequence of disturbance of the cerebral network as a whole. Any network, whether it be a neural, a social or an electronic network, can be described in parameters assessing the topological characteristics of that particular network. Repeated assessment of neural network characteristics in brain tumor patients during their disease course enables study of the dynamics of neural networks and provides more insight into the plasticity of the diseased brain. Functional MRI, electroencephalography and especially magnetoencephalography are used to measure brain function and the signals that are being registered with these techniques can be analyzed with respect to network characteristics such as "synchronization" and "clustering". Evidence accumulates that loss of optimal neural network architecture negatively impacts complex cerebral functioning and also decreases the threshold to develop epileptic seizures. Future research should be focused on both plasticity of neural networks and the factors that have impact on that plasticity as well as the possible role of assessment of neural network characteristics in the determination of cerebral function during the disease course.

  6. Chromogranin A is a sensitive marker of progression or regression in ileo-cecal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Jensen, Kenneth Højsgaard; Hilsted, Linda; Jensen, Claus Verner

    2013-01-01

    on the ROC curves a cutoff value of 25% change was selected to discriminate between increased, decreased, or unchanged CgA concentrations in plasma, using a sensitive radioimmunoassay with well-defined epitope specificity. Results. In the 97 events showing tumor progression diagnostic sensitivity...... and specificity of an increased CgA concentration were 86% and 86%, respectively. The positive and negative predictive values were 64% and 85%, respectively. In the 279 events with unchanged tumor size the diagnostic sensitivity and specificity of an unchanged CgA concentration were 73% and 86%, and the positive...... and negative predictive values were 91% and 63%, respectively. In the 50 events showing tumor regression, diagnostic sensitivity and specificity of a decrease in CgA concentration were 78% and 91%, the positive and negative predictive values being 55% and 97%. Conclusions. CgA concentrations in plasma have...

  7. Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor

    DEFF Research Database (Denmark)

    Andersen, Zorana J; Pedersen, Marie; Weinmayr, Gudrun

    2017-01-01

    Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent. Methods: In 12 cohorts from six European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated...... by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤ 2.5, ≤ 10, and 2.5-10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations...... of air pollutant concentrations and traffic intensity with total, malignant and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. Results: Of 282,194 subjects from 12 cohorts, 466 developed...

  8. Childhood brain tumors and residential electromagnetic fields (EMF).

    Science.gov (United States)

    Kheifets, L I; Sussman, S S; Preston-Martin, S

    1999-01-01

    There are many recent comprehensive reviews of the residential EMF epidemiologic literature, but they do not attempt to cover the issue of childhood brain tumors and EMF in depth. We present here background information on descriptive epidemiology of known or suspected causes of childhood brain tumors and a detailed review of studies that have examined the associations between EMF as represented by various surrogates, and childhood brain tumors. We evaluated nine studies of childhood brain tumors and residential exposure to EMF based on wire codes, distance, measurements, and modeling, and six studies that examined the use of appliances by children or their mothers during pregnancy. For each study we discussed analytical and methodological issues including choice of cutpoints, nonconcurrent control selection, random digit dialing, differential participation, and ability of a study to detect an association. On the basis of this comprehensive review of all available childhood brain cancer studies, we do not see support for an overall association between EMF and childhood brain cancer. This lack of support applied for all surrogates of past magnetic fields, including wire code, distance, measured or calculated fields, and use of appliances by either child or mother.

  9. Pathology Results at Autopsy in Brain-Dead Patients with Brain Tumors.

    Science.gov (United States)

    Sadegh Beigee, Farahnaz; Shahryari, Shagin; Mojtabaee, Meysam; Pourabdollah Toutkaboni, Mihan

    2017-02-01

    Brain tumors are the most challenging causes of brain deaths due to the lack of pathology results in many cases. It is not uncommon to find a brain tumor in a brain-dead patient with no pathology results or neuroradiology reports available; this would exclude the deceased from organ donation. The mortality that occurs while patients are on transplant wait lists motivated us to find a solution to prevent losing brain-dead patients as potential donors. We present our experiences in autopsy examinations of brain tumors and the results of frozen-section pathology. We performed autopsy examinations of 8 brain-dead patients who were suspected of having highly malignant brain tumors and in whom there were no pathology or radiology reports available. The autopsy process began at the conclusion of organ retrieval. First, we performed a complete brain dissection; the tumor was then removed with its adjacent brain tissue and sent for examination by an expert pathologist. Organ transplant was deferred until the pathology examination was completed. Organ transplant was cancelled if the frozen sections revealed a high-grade tumor. For all other results, the transplant was performed. If a medulloblastoma was confirmed, only the heart was transplanted. The duration of the delay for pathologic examination was 30 to 45 minutes. A total of 21 organs were donated that would otherwise have been rejected. It is worth performing an autopsy and frozen-section pathology examination to prevent losing potential organs from donors with brain tumors who are suspected of having a high-grade neoplasm but have no pathology or neuroradiology reports. This process is simple and has the potential to save lives.

  10. Assessment of serum L-fucose in brain tumor cases

    Directory of Open Access Journals (Sweden)

    Manjula S

    2010-01-01

    Full Text Available Background: Glycosylation of altered tumor cell in relation to cellular heterogeneity in human intracranial tumors remains relatively unexposed. Serum protein-bound carbohydrate, L-Fucose is reported to be overexpressed during tumor progression by many investigators. Therefore, there is a need to determine the diagnostic, prognostic, functional significance of glycoprotein elevations in various cases of tumors. Objective: The objective of the present study was to evaluate the clinical utility of serum L-fucose in patients with brain tumor. Materials and Methods: Serum glyco-conjugate levels were estimated in 99 patients with brain tumors. Estimation of L-fucose was carried out colorimetrically by the method of Winzler using cysteine hydrochloride. Results: There was a significant increase in L-fucose level in most of the patients. In the posttreatment cases, the L-fucose levels were apparently low compared to preoperative values. Conclusion: Our results showed that the rise in serum L-fucose may be used as a general marker for brain tumors in addition to other markers.

  11. Photon spectrum and absorbed dose in brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Silva S, A. [General Electric Healthcare, Antonio Dovali Jaime 70, Torre A 3er. piso, Col. Santa Fe, 01210 Mexico D. F. (Mexico); Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico); Rivera M, T. [IPN, Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada, Av. Legaria No. 694, 11500 Mexico D. F. (Mexico)

    2015-10-15

    Using Monte Carlo methods a BOMAB phantom inside a treatment hall with a brain tumor nearby the pituitary gland was treated with photons produced by a Varian 6 MV linac. The photon spectrum and the absorbed dose were calculated in the tumor, pituitary gland and the head. The treatment beam was collimated to illuminate only the tumor volume; however photons were noticed in the gland. Photon fluence reaching the tumor is 78.1 times larger than the fluence in the pituitary gland, on the other hand the absorbed dose in the tumor is 188 times larger than the dose in the gland because photons that reach the pituitary gland are scattered, by the head and the tumor, through Compton effect. (Author)

  12. Optimal factors of diffusion tensor imaging predicting cortico spinal tract injury in patients with brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Zhi Gang; Niu, Chen; Zhang, Qiu Li; Zhang, Ming [Dept. of Radiology, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an (China); Qian, Yu Cheng [Dept. of Medical Imaging, School of Medicine, Jiangsu University, Zhenjiang (China)

    2017-09-15

    To identify the optimal factors in diffusion tensor imaging for predicting corticospinal tract (CST) injury caused by brain tumors. This prospective study included 33 patients with motor weakness and 64 patients with normal motor function. The movement of the CST, minimum distance between the CST and the tumor, and relative fractional anisotropy (rFA) of the CST on diffusion tensor imaging, were compared between patients with motor weakness and normal function. Logistic regression analysis was used to obtain the optimal factor predicting motor weakness. In patients with motor weakness, the displacement (8.44 ± 6.64 mm) of the CST (p = 0.009), minimum distance (3.98 ± 7.49 mm) between the CST and tumor (p < 0.001), and rFA (0.83 ± 0.11) of the CST (p < 0.001) were significantly different from those of the normal group (4.64 ± 6.65 mm, 14.87 ± 12.04 mm, and 0.98 ± 0.05, respectively) (p = 0.009, p < 0.001, and p < 0.001). The frequencies of patients with the CST passing through the tumor (6%, p = 0.002), CST close to the tumor (23%, p < 0.001), CST close to a malignant tumor (high grade glioma, metastasis, or lymphoma) (19%, p < 0.001), and CST passing through infiltrating edema (19%, p < 0.001) in the motor weakness group, were significantly different from those of the patients with normal motor function (0, 8, 1, and 10%, respectively). Logistic regression analysis showed that decreased rFA and CST close to a malignant tumor were effective variables related to motor weakness. Decreased fractional anisotropy, combined with closeness of a malignant tumor to the CST, is the optimal factor in predicting CST injury caused by a brain tumor.

  13. Recent technological advances in pediatric brain tumor surgery.

    Science.gov (United States)

    Zebian, Bassel; Vergani, Francesco; Lavrador, José Pedro; Mukherjee, Soumya; Kitchen, William John; Stagno, Vita; Chamilos, Christos; Pettorini, Benedetta; Mallucci, Conor

    2017-01-01

    X-rays and ventriculograms were the first imaging modalities used to localize intracranial lesions including brain tumors as far back as the 1880s. Subsequent advances in preoperative radiological localization included computed tomography (CT; 1971) and MRI (1977). Since then, other imaging modalities have been developed for clinical application although none as pivotal as CT and MRI. Intraoperative technological advances include the microscope, which has allowed precise surgery under magnification and improved lighting, and the endoscope, which has improved the treatment of hydrocephalus and allowed biopsy and complete resection of intraventricular, pituitary and pineal region tumors through a minimally invasive approach. Neuronavigation, intraoperative MRI, CT and ultrasound have increased the ability of the neurosurgeon to perform safe and maximal tumor resection. This may be facilitated by the use of fluorescing agents, which help define the tumor margin, and intraoperative neurophysiological monitoring, which helps identify and protect eloquent brain.

  14. Multiresolution texture models for brain tumor segmentation in MRI.

    Science.gov (United States)

    Iftekharuddin, Khan M; Ahmed, Shaheen; Hossen, Jakir

    2011-01-01

    In this study we discuss different types of texture features such as Fractal Dimension (FD) and Multifractional Brownian Motion (mBm) for estimating random structures and varying appearance of brain tissues and tumors in magnetic resonance images (MRI). We use different selection techniques including KullBack - Leibler Divergence (KLD) for ranking different texture and intensity features. We then exploit graph cut, self organizing maps (SOM) and expectation maximization (EM) techniques to fuse selected features for brain tumors segmentation in multimodality T1, T2, and FLAIR MRI. We use different similarity metrics to evaluate quality and robustness of these selected features for tumor segmentation in MRI for real pediatric patients. We also demonstrate a non-patient-specific automated tumor prediction scheme by using improved AdaBoost classification based on these image features.

  15. Differential diagnosis of the epileptogenic supratentorial brain tumors in children

    Directory of Open Access Journals (Sweden)

    V. S. Khalilov

    2015-01-01

    Full Text Available Fifty-six out of 79 pediatric patients with supratentorial brain tumors were noted to have symptomatic epilepsy. Dysembryoplastic neuroepithelial tumors (DNET, diffuse astrocytomas (DA, and gangliogliomas (GG were the most epileptogenic tumors. Seizures were new-onset in all our noted cases of DNET and in 4 patients with GG and the only clinical tumor sign in 6 of 8 cases of DNET. The neuroimaging features of the MRI pattern of DNET, DA, and GG were an iso/hypointense signal on Tl-weighted magnetic resonance images and a signal, the intensity of which varied from heterogeneous to cerebrospinal fluid, on T2-weighted FLAIR images. Cases of DNET and GG displayed no mass effect or perifocal edema, a trend towards location in the temporoinsular regions, and a frequent concurrence with local gray-white matter differentiation disorders and atrophy. The FLAIR images clearly showed the so-called foam-like (multicystic structure with pericystic changes. No significant change in the dimensions of the identified DNET and GG was observed during the follow up period. In low-grade DA, tumor growth was reduced and it is difficult to differentiate minimal perifocal edema from tumor-like tissue. The sensitivity of these tumors to contrast enhancement is ambiguous. Along with DNET (that was epileptogenic in 100% of cases, DA (91,7% and GG (80% were the most common epileptogenic brain tumors.

  16. Enhanced Performance of Brain Tumor Classification via Tumor Region Augmentation and Partition.

    Directory of Open Access Journals (Sweden)

    Jun Cheng

    Full Text Available Automatic classification of tissue types of region of interest (ROI plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor in T1-weighted contrast-enhanced MRI (CE-MRI images. Spatial pyramid matching (SPM, which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM, and bag-of-words (BoW model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI.

  17. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  18. Neoadjuvant radiochemotherapy and surgery for advanced rectal cancer. Prognostic significance of tumor regression

    Energy Technology Data Exchange (ETDEWEB)

    Eich, Hans Theodor; Stepien, Anna; Zimmermann, Christian; Mueller, Rolf-Peter [Koeln Univ. (Germany). Dept. of Radiation Oncology; Hellmich, Martin [Koeln Univ. (Germany). Inst. of Medical Statistics, Informatics, and Epidemiology; Metzger, Ralf; Hoelscher, Arnulf [Koeln Univ. (Germany). Dept. of General, Visceral and Cancer Surgery

    2011-04-15

    Purpose: Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer. The predictive value of response to neoadjuvant treatment remains uncertain. We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery. Patients and Methods: A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis. All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later. Results: A sphincter-preserving procedure could be performed on 42 patients, and in all 72 patients complete resection (R0) was achieved. A pathological complete response (ypT0, ypN0) was achieved in 8 (11%) patients. None of the patients showing a complete pathological response relapsed or died during the follow-up period. At a median follow-up of 28 months, 65 patients were alive, none of these patients had local recurrence and 15 patients had metastatic disease. Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with {>=} 10% residual tumor cells (p = 0.024). Patients < 65 years showed a significantly better response rate, compared with those > 65 years of age (p = 0.036). Acute toxicity was moderate. Conclusion: Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer. Pathological parameters after preoperative radiochemotherapy, including tumor regression grading, could be correlated with disease-free survival. The impact of tumor regression grading needs to be further validated in prospective clinical trials. (orig.)

  19. Brain MRI tumor image fusion combined with Shearlet and wavelet

    Science.gov (United States)

    Zhang, Changjiang; Fang, Mingchao

    2017-11-01

    In order to extract the effective information in different modalities of the tumor region in brain Magnetic resonance imaging (MRI) images, we propose a brain MRI tumor image fusion method combined with Shearlet and wavelet transform. First, the source images are transformed into Shearlet domain and wavelet domain. Second, the low frequency component of Shearlet domain is fused by Laplace pyramid decomposition. Then the low-frequency fusion image is obtained through inverse Shearlet transform. Third, the high frequency subimages in wavelet domain are fused. Then the high-frequency fusion image is obtained through inverse wavelet transform. Finally, the low-frequency fusion image and high-frequency fusion image are summated to get the final fusion image. Through experiments conducted on 10 brain MRI tumor images, the result shown that the proposed fusion algorithm has the best fusion effect in the evaluation indexes of spatial frequency, edge strength and average gradient. The main spatial frequency of 10 images is 29.22, and the mean edge strength and average gradient is 103.77 and 10.42. Compared with different fusion methods, we find that the proposed method effectively fuses the information of multimodal brain MRI tumor images and improves the clarity of the tumor area well.

  20. Episodic Memory Impairments in Primary Brain Tumor Patients.

    Science.gov (United States)

    Durand, Thomas; Berzero, Giulia; Bompaire, Flavie; Hoffmann, Sabine; Léger, Isabelle; Jego, Virginie; Baruteau, Marie; Delgadillo, Daniel; Taillia, Hervé; Psimaras, Dimitri; Ricard, Damien

    2018-01-04

    Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors.

  1. Black hairy tongue after chemotherapy for malignant brain tumors.

    Science.gov (United States)

    Yamagishi, Yuki; Maruyama, Keisuke; Kobayashi, Keiichi; Kume, Satoshi; Sasaki, Nobuyoshi; Yokoya, Shigeomi; Saito, Kuniaki; Shiokawa, Yoshiaki; Nagane, Motoo

    2017-01-01

    Black hairy tongue (BHT) developed in five patients (2.6%) among 192 patients undergoing chemotherapy for malignant brain tumors. Three patients with a history of diabetes mellitus developed BHT within 10 days after the initiation of chemotherapy. The other two patients suffered more than 100 days after induction and lymphopenia of grade 3 or worse developed for more than 20 days, which was not observed in the three patients with diabetes. We found that BHT could develop after chemotherapy for malignant brain tumors. Patients with diabetes mellitus presented early after chemotherapy, while patients with longstanding severe lymphopenia presented in late phase.

  2. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  3. Analysis of p53- immunoreactivity in astrocytic brain tumors

    Directory of Open Access Journals (Sweden)

    Shinkarenko T.V.

    2016-12-01

    Full Text Available P53 is an antioncogene with the frequently occured mutations in human tumor cells, leading to corresponding protein overexpression which can be detected by immunohistochemistry. Researches dedicated to the investigation of possibilities of using this technique gave controversial results. The authors investigated features of p53 protein expression in astrocytic brain tumors with different degrees of malignancy. Analyzed the relationship of the expression level of p53 by tumor cells with clinical parameters and Ki-67 proliferation index (PI as well. Tissues were collected from 52 cases with diagnosed astrocytic brain tumors. The sections were immunohistochemically stained with p53 and Ki-67. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated using software package ImageJ 1,47v. In normal brain tissue p53- expression was not identified. p53-immunoreactive tumor cells were detected in 25% (1/4 pilocytic astrocytomas, 33.3% (2/6 of diffuse astrocytomas, 53.8% (7/13 anaplastic astrocytomas, 58.6% (17/29 glioblastomas. A high proportion of p53-immunoreactive cells (> 30% was observed only in glioblastomas. The level of p53-imunoreactivity was not related to the age, gender and Grade WHO (p> 0,05. Spearman correlation coefficient between the relative quantity of ki-67- and p53-immunoreactive nuclei showed weak direct correlation (0.023, but the one was not statistically significant (p> 0,05. The level of p53-imunoreactivity is not dependent from age and sex of patients, Grade (WHO and proliferative activity (p>0,05 but the high level of p53-immunoreactive cells (>30% is found in glioblastoma specimens only, that may be due to the accumulation of mutations in DNA of tumor cells. There is insignificant weak relationship between relative quantities of ki-67- and p53-immunoreactive tumor cells (p>0,05.

  4. Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Stock, Richard G

    2011-02-01

    Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation.

  5. Brain tumors and anorexia nervosa syndrome.

    Science.gov (United States)

    Chipkevitch, E

    1994-01-01

    This review presents 21 cases, found in the literature, of a CNS lesion (a tumor in 19 of them) associated with emaciation, anorexia and several psychic symptoms that had led to the diagnosis of anorexia nervosa (AN). Anorexia and psychic disturbances preceded the neurologic signs and/or the correct diagnosis in all patients (by a mean of 2.9 years, range = 0.2-17 years). Anorexia had begun before the age of 25 years in 18 patients of which two-thirds were females. Only a few cases fulfilled the DSM-III-R criteria for AN; the majority could be characterized as 'atypical AN'. Although AN is usually conceived as a primarily psychogenic disorder, structural lesions of the hypothalamus (or other sites involved in food regulation) in animal models and in these human cases mimic many features of AN, suggesting the possibility of an as yet unidentified structural hypothalamic disorder to be implicated in the etiopathogeny of AN. The unusually high incidence of germ-cell tumors in this review (33%) suggests that they are more likely than other tumors to influence the limbic system toward an anorectic syndrome.

  6. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2016-04-01

    Full Text Available Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents.

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

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

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

  8. Application of contact laser in microsurgery of brain stem tumors

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    Jian-wen GU

    2011-02-01

    Full Text Available Objective To explore the therapeutic efficacy of a new type sapphire contact laser using wavelength-shifting technique on microsurgery of brain stem tumors.Methods The clinical data were retrospectively analyzed of 23 patients(13 males and 10 females,aged 6 to 69 years with an average of 38 years,and the duration of disease was 14 to 36 months with average of 22 months with brain stem tumor admitted from Mar.2006 to May 2010.The major symptoms of the patients were cranial nerve impairment,cerebellum function impairment or paralysis.All patients received microsurgical resection of brain stem tumor using sapphire contact laser through median suboccipital incision and posterior brain stem approach,and the tumors were resected with precision operation and vaporization and ablation.Results Of the 23 patients,4 were with glioma,15 with cavernous angioma,2 with angioreticuloma and 2 with metastatic tumor.Total resection was achieved in 15 cases,while subtotal resection(more than 80% in 6 cases.Intraoperative hemorrhage was less and no intraoperative blood transfusion was required.A 6-months follow-up showed symptoms recovered in 15 patients,improved in 4,unchanged in 2,and worsen in 1.One patient died of recurrence of tumor.No postoperative intracranial infection was occurred,and 2 patients were undergone tracheotomy after operation.The average hospital stay was 15d.Conclusion The contact laser can precisely dissect and vaporize the tumors,increase the resection rate,reduce intraoperative hemorrhage and accessory injuries,and has a clear and definite effect.

  9. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

    Science.gov (United States)

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M

    2015-06-01

    Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (∼6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. American brain tumor patients treated with BNCT in Japan

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    Laramore, G.E.; Griffin, B.R.; Spence, A.

    1995-11-01

    The purpose of this work is to establish and maintain a database for patients from the United States who have received BNCT in Japan for malignant gliomas of the brain. This database will serve as a resource for the DOE to aid in decisions relating to BNCT research in the United States, as well as assisting the design and implementation of clinical trials of BNCT for brain cancer patients in this country. The database will also serve as an information resource for patients with brain tumors and their families who are considering this form of therapy.

  11. Gonadal status in male survivors following childhood brain tumors

    DEFF Research Database (Denmark)

    Schmiegelow, M; Lassen, S; Poulsen, H S

    2001-01-01

    The effect of radiotherapy (RT) and chemotherapy (CT) on gonadal function was assessed in males treated for a childhood brain tumor not directly involving the hypothalamus/pituitary (HP) axis in a population-based study with a long follow-up time. All males...

  12. Learning Profiles of Survivors of Pediatric Brain Tumors

    Science.gov (United States)

    Barkon, Beverly

    2009-01-01

    By 2010 it is predicted that one in 900 adults will be survivors of some form of pediatric cancer. The numbers are somewhat lower for survivors of brain tumors, though their numbers are increasing. Schools mistakenly believe that these children easily fit pre-existing categories of disability. Though these students share some of the…

  13. Imaging brain tumor proliferative activity with [I-124]iododeoxyuridine

    NARCIS (Netherlands)

    Blasberg, RG; Roelcke, U; Weinreich, R; Beattie, B; von Ammon, K; Yonekawa, Y; Landolt, H; Guenther, [No Value; Crompton, NEA; Vontobel, P; Missimer, J; Maguire, RP; Koziorowski, J; Knust, EJ; Finn, RD; Leenders, KL

    2000-01-01

    Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [I-124]IUdR in 20 patients with brain tumors, including meningiomas and gliomas, The PET images were directly compared with

  14. Genetic abnormality predicts benefit for a rare brain tumor

    Science.gov (United States)

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

  15. SU-E-J-269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

    Energy Technology Data Exchange (ETDEWEB)

    Kang, K [Case Western Reserve University, Cleveland, OH (United States); Biswas, T; Podder, T [Case Western Reserve University, Cleveland, OH (United States); University Hospitals Case Medical Center, Cleveland, OH (United States)

    2015-06-15

    Purpose: This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT. Methods: Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volume (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients. Results: A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week-1 and week-2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p-value > 0.05). Conclusion: Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co-relation between tumor volume reduction and treatment outcome.

  16. Multi-fractal detrended texture feature for brain tumor classification

    Science.gov (United States)

    Reza, Syed M. S.; Mays, Randall; Iftekharuddin, Khan M.

    2015-03-01

    We propose a novel non-invasive brain tumor type classification using Multi-fractal Detrended Fluctuation Analysis (MFDFA) [1] in structural magnetic resonance (MR) images. This preliminary work investigates the efficacy of the MFDFA features along with our novel texture feature known as multifractional Brownian motion (mBm) [2] in classifying (grading) brain tumors as High Grade (HG) and Low Grade (LG). Based on prior performance, Random Forest (RF) [3] is employed for tumor grading using two different datasets such as BRATS-2013 [4] and BRATS-2014 [5]. Quantitative scores such as precision, recall, accuracy are obtained using the confusion matrix. On an average 90% precision and 85% recall from the inter-dataset cross-validation confirm the efficacy of the proposed method.

  17. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Theodoros N Sergentanis

    Full Text Available This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS tumors.Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software.A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls. In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03-1.21, 10 study arms, meningiomas (pooled RR = 1.27, 95%CI: 1.13-1.43, 16 study arms and gliomas (pooled RR = 1.17, 95%CI: 1.03-1.32, six arms. Obese (BMI>30 kg/m2 females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05-1.36, six study arms and meningioma risk (pooled RR = 1.48, 95%CI: 1.28-1.71, seven arms. In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22-2.04, nine study arms, whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings.Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males.

  18. Rethinking Brain Cancer Therapy: Tumor Enzyme Activatable Theranostic Nanoparticles.

    Science.gov (United States)

    Daldrup-Link, Heike E

    2017-01-01

    This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain. In addition, the iron oxide nanoparticle backbone enabled in vivo drug tracking with magnetic resonance imaging (MRI). This commentary discusses previous efforts of MMP-targeted therapeutics as well as opportunities for further refinements of tumor enzyme-activatable TNPs. If successfully translated to clinical applications, the TNPs might hold substantial potential to improving cytotoxic indexes and long-term outcomes of patients with brain cancer compared to standard therapy.

  19. Development of stereotactic mass spectrometry for brain tumor surgery.

    Science.gov (United States)

    Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

    2011-02-01

    Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

  20. Banking Brain Tumor Specimens Using a University Core Facility.

    Science.gov (United States)

    Bregy, Amade; Papadimitriou, Kyriakos; Faber, David A; Shah, Ashish H; Gomez, Carmen R; Komotar, Ricardo J; Egea, Sophie C

    2015-08-01

    Within the past three decades, the significance of banking human cancer tissue for the advancement of cancer research has grown exponentially. The purpose of this article is to detail our experience in collecting brain tumor specimens in collaboration with the University of Miami/Sylvester Tissue Bank Core Facility (UM-TBCF), to ensure the availability of high-quality samples of central nervous system tumor tissue for research. Successful tissue collection begins with obtaining informed consent from patients following institutional IRB and federal HIPAA guidelines, and it needs a well-trained professional staff and continued maintenance of high ethical standards and record keeping. Since starting in 2011, we have successfully banked 225 brain tumor specimens for research. Thus far, the most common tumor histology identified among those specimens has been glioblastoma (22.1%), followed by meningioma (18.1%). The majority of patients were White, non-Hispanics accounting for 45.1% of the patient population; Hispanic/Latinos accounted for 23%, and Black/African Americans accounted for 14%, which represent the particular population of the State of Florida according to the 2010 census data. The most common tumors found in each subgroup were as follows: Black/African American, glioblastoma and meningioma; Hispanic, metastasis and glioblastoma; White, glioblastoma and meningioma. The UM-TBCF is a valuable repository, offering high-quality tumor samples from a unique patient population.

  1. Mitochondrial control by DRP1 in brain tumor initiating cells.

    Science.gov (United States)

    Xie, Qi; Wu, Qiulian; Horbinski, Craig M; Flavahan, William A; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N; Kashatus, David F; Bao, Shideng; Rich, Jeremy N

    2015-04-01

    Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs.

  2. Advance MRI for pediatric brain tumors with emphasis on clinical benefits

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo; Ra, Young Shin [Asan Medical Center, University of Ulsan College of Medicine, Seoul(Korea, Republic of)

    2017-01-15

    Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging. Because pediatric brain tumors differ from adult counterparts in various aspects, MRI protocols should be designed to achieve maximal clinical benefits in pediatric brain tumors. In this study, we review advanced MRI techniques and interpretation algorithms for pediatric brain tumors.

  3. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

    DEFF Research Database (Denmark)

    Menze, Bjoern H.; Jakab, Andras; Bauer, Stefan

    2015-01-01

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low......- and high-grade glioma patients – manually annotated by up to four raters – and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74...... a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing...

  4. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease.

    Directory of Open Access Journals (Sweden)

    Sandra L Dabora

    Full Text Available Tuberous sclerosis (TSC related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61; 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36, or were unevaluable (8.3%, 3/36. The mean decrease in kidney tumor size (sum of the longest diameters [sum LD] was 29.9% (95% CI, 22 to 37; n = 28 at week 52. Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia, proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs in 7/11 cases (26% mean decrease in diameter, regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter, subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15. A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline.Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children

  5. History and evolution of brain tumor imaging: insights through radiology.

    Science.gov (United States)

    Castillo, Mauricio

    2014-11-01

    This review recounts the history of brain tumor diagnosis from antiquity to the present and, indirectly, the history of neuroradiology. Imaging of the brain has from the beginning held an enormous interest because of the inherent difficulty of this endeavor due to the presence of the skull. Because of this, most techniques when newly developed have always been used in neuroradiology and, although some have proved to be inappropriate for this purpose, many were easily incorporated into the specialty. The first major advance in modern neuroimaging was contrast agent-enhanced computed tomography, which permitted accurate anatomic localization of brain tumors and, by virtue of contrast enhancement, malignant ones. The most important advances in neuroimaging occurred with the development of magnetic resonance imaging and diffusion-weighted sequences that allowed an indirect estimation of tumor cellularity; this was further refined by the development of perfusion and permeability mapping. From its beginnings with indirect and purely anatomic imaging techniques, neuroradiology now uses a combination of anatomic and physiologic techniques that will play a critical role in biologic tumor imaging and radiologic genomics.

  6. Optical spectroscopy for stereotactic biopsy of brain tumors

    Science.gov (United States)

    Markwardt, Niklas; von Berg, Anna; Fiedler, Sebastian; Goetz, Marcus; Haj-Hosseini, Neda; Polzer, Christoph; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

    2015-07-01

    Stereotactic biopsy procedure is performed to obtain a tissue sample for diagnosis purposes. Currently, a fiber-based mechano-optical device for stereotactic biopsies of brain tumors is developed. Two different fluorophores are employed to improve the safety and reliability of this procedure: The fluorescence of intravenously applied indocyanine green (ICG) facilitates the recognition of blood vessels and thus helps minimize the risk of cerebral hemorrhages. 5- aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence is used to localize vital tumor tissue. ICG fluorescence detection using a 2-fiber probe turned out to be an applicable method to recognize blood vessels about 1.5 mm ahead of the fiber tip during a brain tumor biopsy. Moreover, the suitability of two different PpIX excitation wavelengths regarding practical aspects was investigated: While PpIX excitation in the violet region (at 405 nm) allows for higher sensitivity, red excitation (at 633 nm) is noticeably superior with regard to blood layers obscuring the fluorescence signal. Contact measurements on brain simulating agar phantoms demonstrated that a typical blood coverage of the tumor reduces the PpIX signal to about 75% and nearly 0% for 633 nm and 405 nm excitation, respectively. As a result, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy.

  7. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

    To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

  8. Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

    Science.gov (United States)

    2016-11-21

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

  9. Intelligence deficits in Chinese patients with brain tumor: the impact of tumor resection.

    Science.gov (United States)

    Shen, Chao; Xie, Rong; Cao, Xiaoyun; Bao, Weimin; Yang, Bojie; Mao, Ying; Gao, Chao

    2013-01-01

    Intelligence is much important for brain tumor patients after their operation, while the reports about surgical related intelligence deficits are not frequent. It is not only theoretically important but also meaningful for clinical practice. Wechsler Adult Intelligence Scale was employed to evaluate the intelligence of 103 patients with intracranial tumor and to compare the intelligence quotient (IQ), verbal IQ (VIQ), and performance IQ (PIQ) between the intracerebral and extracerebral subgroups. Although preoperative intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found to have any significant difference between the intracerebral and extracerebral subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral subgroup, but an improvement of VIQ in the right intracerebral subgroup. Pituitary adenoma resection exerted no effect on intelligence. In addition, age, years of education, and tumor size were found to play important roles. Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor resection can deteriorate IQ and PIQ. However, right intracerebral tumor resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection performs no effect on intelligence.

  10. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Federica Ciregia

    2017-08-01

    Full Text Available Extracellular vesicles (EVs can be classified into apoptotic bodies, microvesicles (MVs, and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM, neuroblastoma (NB, medulloblastoma (MB, and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS, amyotrophic lateral sclerosis (ALS, Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis.

  11. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Science.gov (United States)

    Ciregia, Federica; Urbani, Andrea; Palmisano, Giuseppe

    2017-01-01

    Extracellular vesicles (EVs) can be classified into apoptotic bodies, microvesicles (MVs), and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM), neuroblastoma (NB), medulloblastoma (MB), and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis. PMID:28912682

  12. Specific features of epilepsy in children with brain tumors

    Directory of Open Access Journals (Sweden)

    G. V. Kalmykova

    2015-01-01

    Full Text Available Objective: to study the specific features of epilepsy in children and adolescents with brain tumors and to define the optimal tactics of management and antiepileptic therapy after surgical treatment. Patients and methods. Sixty-one patients aged 5 months to 15 years were examined. All the patients were diagnosed as having a brain tumor found in the presence of symptomatic epilepsy. They were all followed up for 5 years postsurgery or during their lifetime (in case of death. Comprehensive examination encompassing the assessment of history data and concomitant complaints, brain magnetic resonance imaging, video-EEC monitoring, and the neurological status (the presence of cognitive impairments and eye ground changes was done in all the cases. The probability of epileptic seizures in the clinical presentation of the disease, their semiology, and frequency were studied. Results and discussion. Epileptic seizures were the major complaint in all the patients at the first visit to their doctor. The disease occurred with status epilepticus in 9% of the patients. Different types of generalized seizures were more common (53%; p≥0.05. The tumor was located above the tentorium of the cerebellum in most examinees (77% and beneath it in the others (23%; p≤0.05. The significant clinical sign of a brain tumor in the epileptic children is focal neurological symptoms (72% of the cases. MRI was performed in children who had no focal neurological symptoms in the late periods. There was cerebrospinal fluid hypertension in 51% of the patients (p≥0.05 and cognitive impairments in 33% (p<0.05. The maximum number (74% of children with psycho-speech disorders and cognitive impairments were registered in the age group of 7–15 years. Eye ground changes characteristic of intracranial hypertension were identified in 19 epileptic children; they occurred in 27 patients more than 1 year after the onset of seizures. The late (few months-to-14 years diagnosis of a brain

  13. Telomere length modulation in human astroglial brain tumors.

    Directory of Open Access Journals (Sweden)

    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  14. Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients

    Directory of Open Access Journals (Sweden)

    Douw Linda

    2010-08-01

    Full Text Available Abstract Background Both epilepsy patients and brain tumor patients show altered functional connectivity and less optimal brain network topology when compared to healthy controls, particularly in the theta band. Furthermore, the duration and characteristics of epilepsy may also influence functional interactions in brain networks. However, the specific features of connectivity and networks in tumor-related epilepsy have not been investigated yet. We hypothesize that epilepsy characteristics are related to (theta band connectivity and network architecture in operated glioma patients suffering from epileptic seizures. Included patients participated in a clinical study investigating the effect of levetiracetam monotherapy on seizure frequency in glioma patients, and were assessed at two time points: directly after neurosurgery (t1, and six months later (t2. At these time points, magnetoencephalography (MEG was recorded and information regarding clinical status and epilepsy history was collected. Functional connectivity was calculated in six frequency bands, as were a number of network measures such as normalized clustering coefficient and path length. Results At the two time points, MEG registrations were performed in respectively 17 and 12 patients. No changes in connectivity or network topology occurred over time. Increased theta band connectivity at t1 and t2 was related to a higher total number of seizures. Furthermore, higher number of seizures was related to a less optimal, more random brain network topology. Other factors were not significantly related to functional connectivity or network topology. Conclusions These results indicate that (pathologically increased theta band connectivity is related to a higher number of epileptic seizures in brain tumor patients, suggesting that theta band connectivity changes are a hallmark of tumor-related epilepsy. Furthermore, a more random brain network topology is related to greater vulnerability to

  15. Computer-Aided Detection of Brain Tumors Using Morphological Reconstruction

    Directory of Open Access Journals (Sweden)

    Buket DOĞAN

    2016-11-01

    Full Text Available Computer aided detection (CAD systems helps the detection of abnormalities in medical images using advanced image processing and pattern recognition techniques. CAD has advantages in accelerating decision-making and reducing the human error in detection process. In this study, a CAD system is developed which is based on morphological reconstruction and classification methods with the use of morphological features of the regions of interest to detect brain tumors from brain magnetic resonance (MR images. The CAD system consists of four stages: the preprocessing, the segmentation, region of interest specification and tumor detection stages. The system is evaluated on REMBRANDT dataset with 497 MR image slices of 10 patients. In the classification stage the performance of CAD has achieved accuracy of 93.36% with Decision Tree Algorithm, 94.89% with Artificial Neural Network (Multilayer Perceptron, 96.93% with K-Nearest Neighbour Algorithm and 96.93% with  Meta-Learner (Decorate Algorithm. These results show that the proposed technique is effective and promising for detecting tumors in brain MR images and enhances the classification process to be more accurate. The using morphological reconstruction method is useful and adaptive than the methods used in other CAD applications.

  16. APOE polymorphisms and cognitive functions in patients with brain tumors.

    Science.gov (United States)

    Correa, Denise D; Satagopan, Jaya; Baser, Raymond E; Cheung, Kenneth; Richards, Elizabeth; Lin, Michael; Karimi, Sasan; Lyo, John; DeAngelis, Lisa M; Orlow, Irene

    2014-07-22

    The goal of this study was to assess whether the APOE ε4 allele and other APOE single nucleotide polymorphisms (SNPs) influence neuropsychological and neuroimaging outcomes in patients with brain tumors. Two hundred eleven patients with brain tumors participated in the study. All patients completed standardized neuropsychological tests and provided a blood sample for APOE genotyping. Ratings of white matter abnormalities were performed on MRI scans. Patients were classified into 2 groups based on the presence (n = 50) or absence (n = 161) of at least one APOE ε4 allele. Additional APOE SNPs were genotyped in a subset of 150 patients. Patients with at least one APOE ε4 allele had significantly lower scores in verbal learning and delayed recall, and marginally significant lower scores in executive function, in comparison to noncarriers of an ε4 allele. Patients with at least one ε4 allele and history of cigarette smoking had significantly higher scores in working memory and verbal learning than ε4 carriers who never smoked. Nine additional APOE SNPs were significantly associated with attention and executive and memory abilities. There were no significant differences between ε4 carriers and noncarriers on the extent of white matter abnormalities on MRI. The findings suggest that patients with brain tumors who are carriers of the APOE ε4 allele may have increased vulnerability to developing memory and executive dysfunction, and that additional SNPs in the APOE gene may be associated with cognitive outcome. © 2014 American Academy of Neurology.

  17. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.

    Science.gov (United States)

    Woolf, Eric C; Syed, Nelofer; Scheck, Adrienne C

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  18. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    Science.gov (United States)

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  19. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  20. Volumetric multimodality neural network for brain tumor segmentation

    Science.gov (United States)

    Silvana Castillo, Laura; Alexandra Daza, Laura; Carlos Rivera, Luis; Arbeláez, Pablo

    2017-11-01

    Brain lesion segmentation is one of the hardest tasks to be solved in computer vision with an emphasis on the medical field. We present a convolutional neural network that produces a semantic segmentation of brain tumors, capable of processing volumetric data along with information from multiple MRI modalities at the same time. This results in the ability to learn from small training datasets and highly imbalanced data. Our method is based on DeepMedic, the state of the art in brain lesion segmentation. We develop a new architecture with more convolutional layers, organized in three parallel pathways with different input resolution, and additional fully connected layers. We tested our method over the 2015 BraTS Challenge dataset, reaching an average dice coefficient of 84%, while the standard DeepMedic implementation reached 74%.

  1. Improved Brain Tumor Classification by Sodium MR Imaging: Prediction of IDH Mutation Status and Tumor Progression.

    Science.gov (United States)

    Biller, A; Badde, S; Nagel, A; Neumann, J-O; Wick, W; Hertenstein, A; Bendszus, M; Sahm, F; Benkhedah, N; Kleesiek, J

    2016-01-01

    MR imaging in neuro-oncology is challenging due to inherent ambiguities in proton signal behavior. Sodium-MR imaging may substantially contribute to the characterization of tumors because it reflects the functional status of the sodium-potassium pump and sodium channels. Sodium-MR imaging data of patients with treatment-naïve glioma WHO grades I-IV (n = 34; mean age, 51.29 ± 17.77 years) were acquired by using a 7T MR system. For acquisition of sodium-MR images, we applied density-adapted 3D radial projection reconstruction pulse sequences. Proton-MR imaging data were acquired by using a 3T whole-body system. We demonstrated that the initial sodium signal of a treatment-naïve brain tumor is a significant predictor of isocitrate dehydrogenase (IDH) mutation status (P model confirmed the sodium signal of treatment-naïve brain tumors as a predictor of progression (P = .003). Compared with the molecular signature of IDH mutation status, information criteria of model comparison revealed that the sodium signal is even superior to IDH in progression prediction. In addition, sodium-MR imaging provides a new approach to noninvasive tumor classification. The sodium signal of contrast-enhancing tumor portions facilitates differentiation among most glioma types (P sodium-MR imaging may help to classify neoplasias at an early stage, to reduce invasive tissue characterization such as stereotactic biopsy specimens, and overall to promote improved and individualized patient management in neuro-oncology by novel imaging signatures of brain tumors. © 2016 by American Journal of Neuroradiology.

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

    OpenAIRE

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

    2015-01-01

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

  3. Deep ensemble learning of sparse regression models for brain disease diagnosis.

    Science.gov (United States)

    Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2017-04-01

    Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer's disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call 'Deep Ensemble Sparse Regression Network.' To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  5. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  6. Quality of Life Among Parents of Adolescent and Young Adult Brain Tumor Survivors.

    Science.gov (United States)

    Buchbinder, David K; Fortier, Michelle A; Osann, Kathryn; Wilford, Justin; Shen, Violet; Torno, Lilibeth; Sender, Leonard S; Parsons, Susan K; Wenzel, Lari

    2017-11-01

    We aimed to describe the quality of life (QOL) among parents of adolescent and young adult brain tumor survivors as well as parent, survivor, and diagnosis/treatment-related factors associated with adverse QOL. A cross-sectional study of 28 parents of adolescent and young adult brain tumor survivors (who were on average 10 y postdiagnosis) was used to assess QOL. Parent QOL was measured using the Patient-Reported Outcomes Measurement Information System Global Health measure. Factors associated with adverse parent QOL were explored using logistic regression including: parent, survivor, and diagnosis/treatment-related factors. Parent QOL was within the normal range; however, 40% scored below the clinical threshold of 0.5 SD below the mean for physical and mental health. Parent perceptions of greater family impact, survivor emotional/behavioral health problems, improved cognitive function, and recurrence were associated with adverse parent physical health. Parent anger/sorrow, uncertainty, survivor emotional/behavioral health problems, speech/language problems, and recurrence were associated with adverse parent mental health. Parental emotional resources and perceptions of improved survivor peer relationships were associated with greater parent physical and mental health. The impact of a brain tumor diagnosis and treatment on the QOL of parents may be significant. Interventions are needed to ensure that the needs of parents are met.

  7. Hybrid Clustering And Boundary Value Refinement for Tumor Segmentation using Brain MRI

    Science.gov (United States)

    Gupta, Anjali; Pahuja, Gunjan

    2017-08-01

    The method of brain tumor segmentation is the separation of tumor area from Brain Magnetic Resonance (MR) images. There are number of methods already exist for segmentation of brain tumor efficiently. However it’s tedious task to identify the brain tumor from MR images. The segmentation process is extraction of different tumor tissues such as active, tumor, necrosis, and edema from the normal brain tissues such as gray matter (GM), white matter (WM), as well as cerebrospinal fluid (CSF). As per the survey study, most of time the brain tumors are detected easily from brain MR image using region based approach but required level of accuracy, abnormalities classification is not predictable. The segmentation of brain tumor consists of many stages. Manually segmenting the tumor from brain MR images is very time consuming hence there exist many challenges in manual segmentation. In this research paper, our main goal is to present the hybrid clustering which consists of Fuzzy C-Means Clustering (for accurate tumor detection) and level set method(for handling complex shapes) for the detection of exact shape of tumor in minimal computational time. using this approach we observe that for a certain set of images 0.9412 sec of time is taken to detect tumor which is very less in comparison to recent existing algorithm i.e. Hybrid clustering (Fuzzy C-Means and K Means clustering).

  8. Euler Elastica regularized Logistic Regression for whole-brain decoding of fMRI data.

    Science.gov (United States)

    Zhang, Chuncheng; Yao, Li; Song, Sutao; Wen, Xiaotong; Zhao, Xiaojie; Long, Zhiying

    2017-09-25

    Multivariate pattern analysis (MVPA) methods have been widely applied to functional magnetic resonance imaging (fMRI) data to decode brain states. Due to the "high features, low samples" in fMRI data, machine learning methods have been widely regularized using various regularizations to avoid overfitting. Both total variation (TV) using the gradients of images and Euler's elastica (EE) using the gradient and the curvature of images are the two popular regulations with spatial structures. In contrast to TV, EE regulation is able to overcome the disadvantage of TV regulation that favored piecewise constant images over piecewise smooth images. In this study, we introduced EE to fMRI-based decoding for the first time and proposed the EE regularized multinomial logistic regression (EELR) algorithm for multi-class classification. We performed experimental tests on both simulated and real fMRI data to investigate the feasibility and robustness of EELR. The performance of EELR was compared with sparse logistic regression (SLR) and TV regularized LR (TVLR). The results showed that EELR was more robustness to noises and showed significantly higher classification performance than TVLR and SLR. Moreover, the forward models and weights patterns revealed that EELR detected larger brain regions that were discriminative to each task and activated by each task than TVLR. The results suggest that EELR not only performs well in brain decoding but also reveals meaningful discriminative and activation patterns. This study demonstrated that EELR showed promising potential in brain decoding and discriminative/activation pattern detection.

  9. Recent advances in brain tumor-targeted nano-drug delivery systems.

    Science.gov (United States)

    Liu, Yu; Lu, Weiyue

    2012-06-01

    Brain tumors represent one of the most challenging and difficult areas in unmet medical needs. Fortunately, the past decade has seen momentous developments in brain tumor research in terms of brain tumor-targeted novel nano-drug delivery systems with significant important superiority over conventional formulations with respect to decreased toxicity and improved pharmacokinetics/pharmacodynamics. This review first introduces the characteristics of the two major obstacles in brain-tumor targeted delivery, blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), and then reviews recent advances in brain tumor-targeted novel nano-drug delivery systems according to their targeting strategies aimed at different stages of brain tumor development and growth. Based on continuously changing vascular characteristics of brain tumors at different development and growth stages, we propose the concept of 'whole-process targeting' for brain tumor for nano-drug delivery systems, referring to a series of overall targeted drug delivery strategies aimed at key points during the whole development of brain tumors.

  10. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell...

  11. Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

    Science.gov (United States)

    Ono, Tomohiro; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Ono, Yuka; Ishigaki, Takashi; Hiraoka, Masahiro

    2017-09-01

    To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  12. Parent reports of children's working memory, coping, and emotional/behavioral adjustment in pediatric brain tumor patients: A pilot study.

    Science.gov (United States)

    Desjardins, Leandra; Thigpen, Jennifer C; Kobritz, Molly; Bettis, Alexandra H; Gruhn, Meredith A; Ichinose, Megan; Hoskinson, Kristen; Fraley, Claire; Vreeland, Allison; McNally, Colleen; Compas, Bruce E

    2017-10-02

    Neurocognitive problems in childhood survivors of brain tumors are well documented. Further, research has shown that problems in cognitive functioning may be associated with impairment in the use of complex strategies needed to cope with stress, including secondary control coping strategies (e.g., acceptance and cognitive reappraisal) which have been associated with fewer adjustment problems. The present study measured cognitive function, coping strategies, and adjustment in children ages 6-16 years at the time of brain tumor diagnosis and at two follow-up time-points up to 1 year post-diagnosis. In a prospective design, working memory was assessed in a total of 29 pediatric brain tumor patients prior to undergoing surgery, child self-reported coping was assessed at 6 months post-diagnosis, and parent-reported child adjustment was assessed at 12 months post-diagnosis. Significant correlations were found between working memory difficulties and secondary control coping. Secondary control coping was also negatively correlated with child attention and total problems. Regression analyses did not support secondary control coping mediating the association between working memory difficulties and child attention or total problems. These findings represent the first longitudinal assessment of the association between working memory, coping, and adjustment across the first year of a child's brain tumor diagnosis and suggest a possible role for early interventions addressing both working memory difficulties and coping in children with brain tumors.

  13. Assessment of accessibility to the diagnosis and treatment of brain tumors in Argentina: Preliminary results.

    Science.gov (United States)

    Rabadán, Alejandra T; Hernandez, Diego; Vazquez, Néstor; Torino, Rafael; Marcelo, Blanco V

    2017-01-01

    As far as public health is concerned, brain tumors burden is significant despite their low incidence, because they comprise high direct costs (specific diagnostic resources, high complexity treatments, and rehabilitation) and high-unforeseen costs (labor leave, family, and social issues). Although the Argentine's Health System is supposed to provide healthcare to all the population, it would not guarantee equity of access for brain tumors treatment. In order to analyze this hypothesis we decided to carry out a survey to obtain data on access, availability and resources for tumor management in Argentina. An online questionnaire with eight dimensions and 29 queries was conducted addressing all professionals involved in tumor management. Two variables were generated: (1) type of medical center according to their financial support, and (2) the geographic region (GeoR). Analysis of association between these variables and the accessibility to different resources was performed with Chi-square and Fisher's exact test. Multivariate analyses through multiple logistic regression models were also tested. One hundred and fourteen surveys were collected from 56 state-managed centers and 55 private/trade-union managed centers. Responders came from 15 provinces grouped into integrated GeoR. Results and analysis of each dimension were reported. The data obtained provides information about the accessibility to brain tumors treatment, exposing the unequal distribution of human and technologic resources in Argentina. This problem exceeds the limits of public health to become a bioethical problem. We think these results could be essentially associated to our health system fragmented structure, and the large geographical extension of our country. Finally, we believe that collaboration of professional associations working together with public and private sector authorities responsible for financial resources and logistic should bring a principle of solution.

  14. Boron Neutron Capture Therapy for Malignant Brain Tumors

    Science.gov (United States)

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  15. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. (1)H magnetic resonance spectroscopy ((1)H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. (1)H-MRS showed significant reduction in taurine levels (Ptumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site

  16. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Haberer, Thomas [Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany); Jaekel, Oliver [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany)

    2013-10-15

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.

  17. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    Science.gov (United States)

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  18. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images.

    Science.gov (United States)

    Deng, He; Deng, Wankai; Sun, Xianping; Ye, Chaohui; Zhou, Xin

    2016-10-27

    Image enhancement techniques are able to improve the contrast and visual quality of magnetic resonance (MR) images. However, conventional methods cannot make up some deficiencies encountered by respective brain tumor MR imaging modes. In this paper, we propose an adaptive intuitionistic fuzzy sets-based scheme, called as AIFE, which takes information provided from different MR acquisitions and tries to enhance the normal and abnormal structural regions of the brain while displaying the enhanced results as a single image. The AIFE scheme firstly separates an input image into several sub images, then divides each sub image into object and background areas. After that, different novel fuzzification, hyperbolization and defuzzification operations are implemented on each object/background area, and finally an enhanced result is achieved via nonlinear fusion operators. The fuzzy implementations can be processed in parallel. Real data experiments demonstrate that the AIFE scheme is not only effectively useful to have information from images acquired with different MR sequences fused in a single image, but also has better enhancement performance when compared to conventional baseline algorithms. This indicates that the proposed AIFE scheme has potential for improving the detection and diagnosis of brain tumors.

  19. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

    Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  20. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    Science.gov (United States)

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

    2016-11-01

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

  1. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images

    Science.gov (United States)

    Deng, He; Deng, Wankai; Sun, Xianping; Ye, Chaohui; Zhou, Xin

    2016-10-01

    Image enhancement techniques are able to improve the contrast and visual quality of magnetic resonance (MR) images. However, conventional methods cannot make up some deficiencies encountered by respective brain tumor MR imaging modes. In this paper, we propose an adaptive intuitionistic fuzzy sets-based scheme, called as AIFE, which takes information provided from different MR acquisitions and tries to enhance the normal and abnormal structural regions of the brain while displaying the enhanced results as a single image. The AIFE scheme firstly separates an input image into several sub images, then divides each sub image into object and background areas. After that, different novel fuzzification, hyperbolization and defuzzification operations are implemented on each object/background area, and finally an enhanced result is achieved via nonlinear fusion operators. The fuzzy implementations can be processed in parallel. Real data experiments demonstrate that the AIFE scheme is not only effectively useful to have information from images acquired with different MR sequences fused in a single image, but also has better enhancement performance when compared to conventional baseline algorithms. This indicates that the proposed AIFE scheme has potential for improving the detection and diagnosis of brain tumors.

  2. Involvement of FLIP in 2-methoxyestradiol-induced tumor regression in transgenic adenocarcinoma of mouse prostate model.

    Science.gov (United States)

    Ganapathy, Manonmani; Ghosh, Rita; Jianping, Xie; Zhang, Xiaoping; Bedolla, Roble; Schoolfield, John; Yeh, I-Tien; Troyer, Dean A; Olumi, Aria F; Kumar, Addanki P

    2009-03-01

    The purpose of this study is to investigate whether Fas-associated death domain interleukin-1 converting enzyme like inhibitory protein (FLIP) inhibition is a therapeutic target associated with 2-methoxyestradiol (2-ME2)-mediated tumor regression. Expression and levels of FLIP were analyzed using (a) real-time PCR and immunoblot analysis in androgen-independent PC-3 cells treated with the newly formulated 2-ME2 and (b) immunohistochemistry in different Gleason pattern human prostate tumors. Transient transfections and chromatin immunoprecipitation (ChIP) assays were used to identify the transcription factors that regulate FLIP. Involvement of FLIP in 2-ME2-induced tumor regression was evaluated in transgenic adenocarcinoma mouse prostate (TRAMP) mice. High Gleason pattern (5+5) human prostate tumors exhibit significant increase in FLIP compared with low Gleason pattern 3+3 (P=ormanagement.

  3. Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors

    Science.gov (United States)

    2015-10-01

    for childhood central nervous system (CNS) tumors, they remain the leading cause of death in pediatric oncology . One potential therapeutic...clinical trial design for pediatric brain tumor patients harboring the mutation. Keywords: Autophagy BRAF Brain tumor Pediatric Resistance...I submitted an abstract of my most recent findings to the Society of Neuro- Oncology Pediatric Neuro- Oncology Basic and Translational Research

  4. Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor: the European Study of Cohorts for Air Pollution Effects (ESCAPE).

    Science.gov (United States)

    Andersen, Zorana J; Pedersen, Marie; Weinmayr, Gudrun; Stafoggia, Massimo; Galassi, Claudia; Jørgensen, Jeanette T; Sommar, Johan N; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Aasvang, Gunn Marit; Schwarze, Per; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Östenson, Claes-Göran; Fratiglioni, Laura; Eriksen, Kirsten T; Poulsen, Aslak H; Tjønneland, Anne; Vaclavik Bräuner, Elvira; Peeters, Petra H; Bueno-de-Mesquita, Bas; Jaensch, Andrea; Nagel, Gabriele; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Migliore, Enrica; Vermeulen, Roel; Sokhi, Ranjeet; Keuken, Menno; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Cesaroni, Giulia; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole

    2017-08-31

    Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent. In 12 cohorts from six European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤ 2.5, ≤ 10, and 2.5-10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. Of 282,194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts had also data on nonmalignant brain tumor, where among 106,786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically non-significant association between malignant brain tumor and PM2.5 absorbance (Hazard Ratio and 95% Confidence Interval: 1.67; 0.89-3.14 per 10 -5/m 3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38-2.71 per 10 -5/m 3) and all other pollutants were lower for nonmalignant than for malignant brain tumors. We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.

  5. Apoptosis in the transplanted canine transmissible venereal tumor during growth and regression phases Apoptose no tumor venéreo transmissível canino durante as fases de crescimento e regressão

    Directory of Open Access Journals (Sweden)

    F.G.A. Santos

    2008-06-01

    Full Text Available Twelve male, mongrel, adult dogs were subcutaneously transplanted with cells originated from two canine transmissible venereal tumors (TVT. The aim was to demonstrate and to quantify the occurrence of apoptosis in the TVT regression. After six months of transplantation, a tumor sample was obtained from each dog, being six dogs with TVT in the growing phase and six in the regression phase as verified by daily measurements. Samples were processed for histological and ultrastructural purposes as well as for DNA extraction. Sections of 4µm were stained by HE, Shorr, methyl green pyronine, Van Gieson, TUNEL reaction and immunostained for P53. The Shorr stained sections went through morphometry that demonstrated an increase of the apoptotic cells per field in the regressive tumors. It was also confirmed by transmission electron microscopy, which showed cells with typical morphology of apoptosis and by the TUNEL reaction that detected in situ the 3'OH nick end labeling mainly in the regressive tumors. The regressive TVTs also showed an intensified immunostaining for P53 besides a more intense genomic DNA fragmentation detected by the agarose gel electrophoresis. In conclusion, apoptosis has an important role in the regression of the experimental TVT in a way that is P53-dependent.Doze cães, adultos, machos e sem raça definida foram transplantados subcutaneamente, na região hipogástrica, com células originadas de dois tumores venéreos transmissíveis caninos (TVT. O objetivo do estudo foi demonstrar e quantificar a ocorrência de apoptose na regressão do TVT. Após seis meses, foi obtido um tumor de cada animal, totalizando seis em crescimento e seis em regressão. Fragmentos dos tumores foram processados para avaliação histológica, ultra-estrutural e também para extração de DNA. Cortes de 4µm foram corados em HE, Shorr, verde de metila pironina e Van Gieson e alguns foram submetidos à reação do TUNEL e à imunoistoquímica para P53

  6. Brain networks of temporal preparation: A multiple regression analysis of neuropsychological data.

    Science.gov (United States)

    Triviño, Mónica; Correa, Ángel; Lupiáñez, Juan; Funes, María Jesús; Catena, Andrés; He, Xun; Humphreys, Glyn W

    2016-11-15

    There are only a few studies on the brain networks involved in the ability to prepare in time, and most of them followed a correlational rather than a neuropsychological approach. The present neuropsychological study performed multiple regression analysis to address the relationship between both grey and white matter (measured by magnetic resonance imaging in patients with brain lesion) and different effects in temporal preparation (Temporal orienting, Foreperiod and Sequential effects). Two versions of a temporal preparation task were administered to a group of 23 patients with acquired brain injury. In one task, the cue presented (a red versus green square) to inform participants about the time of appearance (early versus late) of a target stimulus was blocked, while in the other task the cue was manipulated on a trial-by-trial basis. The duration of the cue-target time intervals (400 versus 1400ms) was always manipulated within blocks in both tasks. Regression analysis were conducted between either the grey matter lesion size or the white matter tracts disconnection and the three temporal preparation effects separately. The main finding was that each temporal preparation effect was predicted by a different network of structures, depending on cue expectancy. Specifically, the Temporal orienting effect was related to both prefrontal and temporal brain areas. The Foreperiod effect was related to right and left prefrontal structures. Sequential effects were predicted by both parietal cortex and left subcortical structures. These findings show a clear dissociation of brain circuits involved in the different ways to prepare in time, showing for the first time the involvement of temporal areas in the Temporal orienting effect, as well as the parietal cortex in the Sequential effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Absence of human cytomegalovirus infection in childhood brain tumors.

    Science.gov (United States)

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

  8. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

    Science.gov (United States)

    Jakab, Andras; Bauer, Stefan; Kalpathy-Cramer, Jayashree; Farahani, Keyvan; Kirby, Justin; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland; Lanczi, Levente; Gerstner, Elizabeth; Weber, Marc-André; Arbel, Tal; Avants, Brian B.; Ayache, Nicholas; Buendia, Patricia; Collins, D. Louis; Cordier, Nicolas; Corso, Jason J.; Criminisi, Antonio; Das, Tilak; Delingette, Hervé; Demiralp, Çağatay; Durst, Christopher R.; Dojat, Michel; Doyle, Senan; Festa, Joana; Forbes, Florence; Geremia, Ezequiel; Glocker, Ben; Golland, Polina; Guo, Xiaotao; Hamamci, Andac; Iftekharuddin, Khan M.; Jena, Raj; John, Nigel M.; Konukoglu, Ender; Lashkari, Danial; Mariz, José António; Meier, Raphael; Pereira, Sérgio; Precup, Doina; Price, Stephen J.; Raviv, Tammy Riklin; Reza, Syed M. S.; Ryan, Michael; Sarikaya, Duygu; Schwartz, Lawrence; Shin, Hoo-Chang; Shotton, Jamie; Silva, Carlos A.; Sousa, Nuno; Subbanna, Nagesh K.; Szekely, Gabor; Taylor, Thomas J.; Thomas, Owen M.; Tustison, Nicholas J.; Unal, Gozde; Vasseur, Flor; Wintermark, Max; Ye, Dong Hye; Zhao, Liang; Zhao, Binsheng; Zikic, Darko; Prastawa, Marcel; Reyes, Mauricio; Van Leemput, Koen

    2016-01-01

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients—manually annotated by up to four raters—and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%–85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource. PMID:25494501

  9. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression

    Directory of Open Access Journals (Sweden)

    Julien Fitamant

    2015-03-01

    Full Text Available Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC. Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte quiescence and differentiation. Importantly, treatment with small interfering RNA-lipid nanoparticles (siRNA-LNPs targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of the positional identity of hepatocytes, supports targeting of YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype that is potentially responsive to this approach.

  10. Trends in childhood brain tumor incidence, 1973-2009.

    Science.gov (United States)

    McKean-Cowdin, Roberta; Razavi, Pedram; Barrington-Trimis, Jessica; Baldwin, Rachel Tobias; Asgharzadeh, Shahab; Cockburn, Myles; Tihan, Tarik; Preston-Martin, Susan

    2013-11-01

    In the mid-1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990 s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due. We used Surveillance, Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site. The incidence of CBT remained stable from 1987 to 2009 [annual percent change (APC) = 0.10; 95 % confidence intervals (CI) -0.39 to 0.61] with an AAIR for all CBT of 3.32 (95 % CI 3.22-3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983-1986), when the incidence of CBT increased by 53 % (APC = 14.06; 95 % CI 4.05-25.0). From 1983 to 1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981 to 2009, suggesting a change from a more general to more specific classification. After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.

  11. Intratumoral injection of Ad-ISF35 (Chimeric CD154) breaks tolerance and induces lymphoma tumor regression.

    Science.gov (United States)

    Urquiza, Mauricio; Melo-Cardenas, Johanna; Aguillon, Robier; Kipps, Thomas J; Castro, Januario E

    2015-01-01

    Ad-ISF35, an adenovirus vector encoding a membrane-bound engineered CD154 chimeric protein (ISF35), induces complete A20 lymphoma tumor regression in mice after intratumoral direct injection (IDI). Ad-ISF35 induced durable local and systemic antitumor responses associated with a rapid tumor infiltration of macrophages and neutrophils as well as increased levels of proinflammatory cytokines in the tumor microenvironment. Ad-ISF35 IDI transduced preferentially fibroblasts and macrophages present in the tumor microenvironment, and ISF35 protein expression was observed in only 0.25% of cells present in the tumor. Moreover, Ad-ISF35 IDI induced upregulation of CD40 in tumor and immune regulatory cells, including those that did not express ISF35, suggesting the presence of a strong bystander effect. These responses resulted in the generation of IFN-γ-secreting cytotoxic lymphocytes and the production of specific cytotoxic antibodies against lymphoma cells. Overall, cellular immune therapy based on ISF35 induced phenotypic changes in the tumor cells and tumor microenvironment that were associated with a break in tumor immune tolerance and a curative antitumor effect in this lymphoma mouse model. Our data highlight the potential activity that modulation of costimulatory signaling has in cancer therapy.

  12. Tumor growth model for atlas based registration of pathological brain MR images

    Science.gov (United States)

    Moualhi, Wafa; Ezzeddine, Zagrouba

    2015-02-01

    The motivation of this work is to register a tumor brain magnetic resonance (MR) image with a normal brain atlas. A normal brain atlas is deformed in order to take account of the presence of a large space occupying tumor. The method use a priori model of tumor growth assuming that the tumor grows in a radial way from a starting point. First, an affine transformation is used in order to bring the patient image and the brain atlas in a global correspondence. Second, the seeding of a synthetic tumor into the brain atlas provides a template for the lesion. Finally, the seeded atlas is deformed combining a method derived from optical flow principles and a model for tumor growth (MTG). Results show that an automatic segmentation method of brain structures in the presence of large deformation can be provided.

  13. Profiles of Executive Function Across Children with Distinct Brain Disorders: Traumatic Brain Injury, Stroke, and Brain Tumor.

    Science.gov (United States)

    Araujo, Gabriel C; Antonini, Tanya N; Anderson, Vicki; Vannatta, Kathryn A; Salley, Christina G; Bigler, Erin D; Taylor, H Gerry; Gerhardt, Cynthia; Rubin, Kenneth; Dennis, Maureen; Lo, Warren; Mackay, Mark T; Gordon, Anne; Hajek Koterba, Christine; Gomes, Alison; Greenham, Mardee; Owen Yeates, Keith

    2017-08-01

    This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Participants were children with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch) subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).

  14. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

    Science.gov (United States)

    Ji, Minbiao; Lewis, Spencer; Camelo-Piragua, Sandra; Ramkissoon, Shakti H; Snuderl, Matija; Venneti, Sriram; Fisher-Hubbard, Amanda; Garrard, Mia; Fu, Dan; Wang, Anthony C; Heth, Jason A; Maher, Cormac O; Sanai, Nader; Johnson, Timothy D; Freudiger, Christian W; Sagher, Oren; Xie, Xiaoliang Sunney; Orringer, Daniel A

    2015-10-14

    Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery. Copyright © 2015, American Association for the Advancement of Science.

  15. Dental diagnostic X-ray exposure and risk of benign and malignant brain tumors.

    Science.gov (United States)

    Lin, M C; Lee, C F; Lin, C L; Wu, Y C; Wang, H E; Chen, C L; Sung, F C; Kao, C H

    2013-06-01

    This study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case-control study. We identified 4123 BBT cases and 16 492 controls without BBT (study 1) and 197 MBT cases and 788 controls without MBT (study 2) from Taiwan National Health Insurance claim data. The risks of both types of tumor were estimated in association with the frequency of received dental diagnostic X-ray. The mean ages were ~44.2 years in study 1 and 40.6 years in study 2. Multivariable unconditional logistic regression analysis showed that the risk of BBT increases as the frequency of received dental diagnostic X-ray increases. The BBT odds ratio increased from 1.33 [95% confidence interval (CI) 1.22-1.44] for those with annual mean X-ray examination of less than one to 1.65 (95% CI 1.37-1.98) for those with three or more X-ray examinations, after controlling for comorbidities. No significant association was found between MBTs and dental diagnostic X-ray exposure. Exposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.

  16. Relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma

    Directory of Open Access Journals (Sweden)

    Peng Y

    2015-07-01

    Full Text Available Yihua Peng,1,* Chunhong Shao,1,* Ye Gong,2 Xuehai Wu,2 Weijun Tang,3 Shenxun Shi1 1Psychiatry Department, 2Neurosurgery Department, 3Radiology Department, Huashan Hospital, Fudan University, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study is to assess the relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma. Methods: We enrolled 65 consecutive patients with meningioma and 31 normal controls matched for age, gender, and education. The patients were divided into frontal or non-frontal (NF meningioma groups based on magnetic resonance imaging; the frontal group was then subdivided to dorsolateral frontal (DLF, medial frontal (MF, and ventral frontal (VF groups. Tumor size and brain edema were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES. Assessments were carried out 1 week before and 3 months after surgery, respectively. Logistic regression analysis was performed to identify the predictive effect of tumor size, location, and brain edema on apathy. Analysis of variance and chi-square analysis were applied to compare apathy scores and apathy rates among the frontal, NF, and normal control groups, and all subgroups within the frontal group. Results: Compared with the NF and control groups, the mean AES score was much higher in the frontal group (34.0±8.3 versus 28.63±6.0, P=0.008, and 26.8±4.2, P<0.001. Subgroup analysis showed that AES scores in the MF group (42.1±6.6 and VF group (34.7±8.0 were higher than in the DLF group (28.5±4.36, NF group, and control group (P<0.05. The apathy rate was 63.6% in the MF group and 25% in the VF group, and significantly higher than in the DLF (5.6%, NF (5.3%, and control (0% groups (P<0.001. A moderate correlation was found between AES score and mean diameter of the meningioma in all patient groups. Further analysis demonstrated that the correlation existed in

  17. In vivo measurement of cell proliferation in canine brain tumor using C-11-labeled FMAU and PET

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Peter S. [PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, CA 90033 (United States)], E-mail: pconti@usc.edu; Bading, James R. [PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, CA 90033 (United States); Mouton, Peter P. [Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21218 (United States); Links, Jonathan M. [Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21218 (United States); Alauddin, Mian M.; Fissekis, John D. [PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, CA 90033 (United States); Ravert, Hayden T.; Hilton, John; Wong, Dean F.; Anderson, James H. [Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21218 (United States)

    2008-01-15

    Introduction: Noncatabolized thymidine analogs are being developed for use in imaging DNA synthesis. We sought to relate a labeling index measured by immunohistochemical staining bromodeoxyuridine (BUdR) technique to the uptake of {sup 11}C 2'-fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil (FMAU) measured with positron emission tomography (PET) in a brain tumor model. Methods: Adult beagles (n=8) with implanted brain tumors received [{sup 11}C]FMAU and dynamic imaging with arterial sampling. Six dogs were then infused with BUdR (200 mg/m{sup 2}) and sacrificed. Tumor time-activity curves (TACs) obtained from computed-tomography-defined regions of interest were corrected for partial volume effects and crosstalk from brain tissue. Tissue was analyzed for the percentage of tumor volume occupied by viable cells and by viable cells in S-phase as identified by BUdR staining. PET/[{sup 11}C]FMAU and BUdR were compared by linear regression analysis and analysis of variance, as well as by a nonparametric rank correlation test. Results: Tumor standardized uptake values (SUVs) and tumor-to-contralateral-brain uptake ratios at 50 min were 1.6{+-}0.4 and 5.5{+-}1.2 (n=8; mean{+-}S.E.M.), respectively. No {sup 11}C-labeled metabolites were observed in the blood through 60 min. Tumor TACs were well described with a three-compartment/four-parameter model (k{sub 4}=0) and by Patlak analysis. Parametric statistical analysis showed that FMAU clearance from plasma into tumor Compartment 3 (K{sub FMAU}) was significantly correlated with S-phase percent volume (P=.03), while tumor SUV was significantly correlated with both S-phase percent volume and cell percent volume (P=.02 and .03, respectively). Patlak slope, K{sub FMAU} and tumor SUV were equivalent with regard to rank correlation analysis, which showed that tumor uptake and trapping of FMAU were correlated with the volume density of dividing cells (P=.0003) rather than nondividing cells (P=.3). Conclusions: Trapping of

  18. Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications

    Science.gov (United States)

    Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lu, Weiguo; Yan, Yulong; Jiang, Steve B.; Timmerman, Robert; Abdulrahman, Ramzi; Nedzi, Lucien; Gu, Xuejun

    2016-12-01

    The objective of this study is to develop an automatic segmentation strategy for efficient and accurate metastatic brain tumor delineation on contrast-enhanced T1-weighted (T1c) magnetic resonance images (MRI) for stereotactic radiosurgery (SRS) applications. The proposed four-step automatic brain metastases segmentation strategy is comprised of pre-processing, initial contouring, contour evolution, and contour triage. First, T1c brain images are preprocessed to remove the skull. Second, an initial tumor contour is created using a multi-scaled adaptive threshold-based bounding box and a super-voxel clustering technique. Third, the initial contours are evolved to the tumor boundary using a regional active contour technique. Fourth, all detected false-positive contours are removed with geometric characterization. The segmentation process was validated on a realistic virtual phantom containing Gaussian or Rician noise. For each type of noise distribution, five different noise levels were tested. Twenty-one cases from the multimodal brain tumor image segmentation (BRATS) challenge dataset and fifteen clinical metastases cases were also included in validation. Segmentation performance was quantified by the Dice coefficient (DC), normalized mutual information (NMI), structural similarity (SSIM), Hausdorff distance (HD), mean value of surface-to-surface distance (MSSD) and standard deviation of surface-to-surface distance (SDSSD). In the numerical phantom study, the evaluation yielded a DC of 0.98  ±  0.01, an NMI of 0.97  ±  0.01, an SSIM of 0.999  ±  0.001, an HD of 2.2  ±  0.8 mm, an MSSD of 0.1  ±  0.1 mm, and an SDSSD of 0.3  ±  0.1 mm. The validation on the BRATS data resulted in a DC of 0.89  ±  0.08, which outperform the BRATS challenge algorithms. Evaluation on clinical datasets gave a DC of 0.86  ±  0.09, an NMI of 0.80  ±  0.11, an SSIM of 0.999  ±  0.001, an HD of 8

  19. Stereotactic interstitial brachytherapy for the treatment of oligodendroglial brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    El Majdoub, Faycal; Neudorfer, Clemens; Maarouf, Mohammad [University Hospital of Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne (Germany); University of Witten/Herdecke, Department of Stereotaxy and Functional Neurosurgery, Center of Neurosurgery, Cologne-Merheim Medical Center (CMMC), Cologne (Germany); Blau, Tobias; Deckert, Martina [University Hospital of Cologne, Department of Neuropathology, Cologne (Germany); Hellmich, Martin [University Hospital of Cologne, Institute of Statistics, Informatics and Epidemiology, Cologne (Germany); Buehrle, Christian [University Hospital of Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne (Germany); Sturm, Volker [University Hospital of Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne (Germany); University Hospital of Wurzburg, Department of Neurosurgery, Wuerzburg (Germany)

    2015-12-15

    We evaluated the treatment of oligodendroglial brain tumors with interstitial brachytherapy (IBT) using {sup 125}iodine seeds ({sup 125}I) and analyzed prognostic factors. Between January 1991 and December 2010, 63 patients (median age 43.3 years, range 20.8-63.4 years) suffering from oligodendroglial brain tumors were treated with {sup 125}I IBT either as primary, adjuvantly after incomplete resection, or as salvage therapy after tumor recurrence. Possible prognostic factors influencing disease progression and survival were retrospectively investigated. The actuarial 2-, 5-, and 10-year overall and progression-free survival rates after IBT for WHO II tumors were 96.9, 96.9, 89.8 % and 96.9, 93.8, 47.3 %; for WHO III tumors 90.3, 77, 54.9 % and 80.6, 58.4, 45.9 %, respectively. Magnetic resonance imaging demonstrated complete remission in 2 patients, partial remission in 13 patients, stable disease in 17 patients and tumor progression in 31 patients. Median time to progression for WHO II tumors was 87.6 months and for WHO III tumors 27.8 months. Neurological status improved in 10 patients and remained stable in 20 patients, while 9 patients deteriorated. There was no treatment-related mortality. Treatment-related morbidity was transient in 11 patients. WHO II, KPS ≥ 90 %, frontal location, and tumor surface dose > 50 Gy were associated with increased overall survival (p ≤ 0.05). Oligodendroglioma and frontal location were associated with a prolonged progression-free survival (p ≤ 0.05). Our study indicates that IBT achieves local control rates comparable to surgery and radio-/chemotherapy treatment, is minimally invasive, and safe. Due to the low rate of side effects, IBT may represent an attractive option as part of a multimodal treatment schedule, being supplementary to microsurgery or as a salvage therapy after chemotherapy and conventional irradiation. (orig.) [German] Die Behandlung oligodendroglialer Hirntumoren durch die interstitielle Brachytherapie

  20. Sleep complaints in survivors of pediatric brain tumors.

    Science.gov (United States)

    Brimeyer, Chasity; Adams, Leah; Zhu, Liang; Srivastava, Deo Kumar; Wise, Merrill; Hudson, Melissa M; Crabtree, Valerie McLaughlin

    2016-01-01

    Pediatric brain tumor survivors have increased risk of sleep problems, particularly excessive daytime sleepiness (EDS). Few studies have examined sleep disturbances in this population. 153 children and adolescents ages 8-18 and their parents completed questionnaires (Modified Epworth Sleepiness Scale, Kosair Children's Hospital Sleep Questionnaire, Children's Report of Sleep Patterns, Children's Sleep Hygiene Scale) during clinic visits. Participants were at least 5 years from diagnosis and 2 years post-treatment. Group differences in age at diagnosis, body mass index, type of treatment received, and tumor location were examined. One-third of adolescents and one-fifth of children reported EDS. Children and parents had fair concordance (kappa coefficient = .64) in their report of EDS, while adolescents and parents had poor concordance (kappa coefficient = .37). Per parents, most children slept 8 to 9 h per night. Poor bedtime routines were reported for children, while adolescents endorsed poor sleep stability. Extended weekend sleep was reported across age groups. A BMI in the obese range was related to higher parent-reported EDS in children. Sleep-disordered breathing was associated with elevated BMI in adolescents. While survivors reported achieving recommended amounts of sleep each night, 20 to 30% reported EDS. Poor concordance among parent and adolescent report highlights the importance of obtaining self-report when assessing sleep concerns. Obesity is a modifiable factor in reducing symptoms of EDS in this population. Finally, the lack of association between EDS and brain tumor location, BMI, or treatment received was unexpected and warrants further investigation.

  1. Genetic and modifying factors that determine the risk of brain tumors

    DEFF Research Database (Denmark)

    Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

    2011-01-01

    . Mutagen sensitivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms...... established that there is association between brain tumor risk and mutagen sensitivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immuno-suppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages...

  2. Preoperative functional mapping for rolandic brain tumor surgery.

    Science.gov (United States)

    Rizzo, Vincenzo; Terranova, Carmen; Conti, Alfredo; Germanò, Antonino; Alafaci, Concetta; Raffa, Giovanni; Girlanda, Paolo; Tomasello, Francesco; Quartarone, Angelo

    2014-11-07

    The resection of tumors within or close to eloquent motor areas is usually guided by the compromise between the maximal allowed resection and preservation of neurological functions. Navigated transcranial magnetic stimulation (nTMS) is an emerging technology that can be used for preoperative mapping of the motor cortex. We performed pre-surgical mapping by using nTMS in 17 patients with lesions in or close to the precentral gyrus. The study was conducted on consecutive patients scheduled for surgical treatment. nTMS allowed to exactly localize the motor cortex in 88.2% of cases. In 70.6% it provided the surgeon with new unexpected information about functional anatomy of the motor area, influencing the pre-operative planning. Moreover, in 29.4% these functional information had a clear impact on surgery, making necessary a change of surgical strategy to avoid damage to the motor cortex. Our results prove that nTMS has a large benefit in the treatment of rolandic brain tumors. It adds important information about spatial relationship between functional motor cortex and the tumor and reduces surgical-related post-operative motor deficits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Predictors of adaptive functioning and psychosocial adjustment in children with pediatric brain tumor: a report from the Brain Radiation Investigative Study Consortium.

    Science.gov (United States)

    Robinson, Kristen E; Wolfe, Kelly R; Yeates, Keith O; Mahone, E Mark; Cecil, Kim M; Ris, M Douglas

    2015-03-01

    Children are at risk for psychosocial and adaptive morbidities following diagnosis of and treatment for a pediatric brain tumor. This study examined whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict the acute psychosocial adjustment and adaptive functioning of children soon after an initial diagnosis. Participants included 56 children (mean age = 10.72, SD = 4.02) newly diagnosed with a pediatric brain tumor. Parents completed background/demographic forms and completed ratings of children's behavioral and emotional symptoms, and adaptive behavior. Diagnostic and treatment-related information was abstracted from medical records. Parent ratings of behavioral symptoms and adaptive functioning were within normative expectation, although rates of clinical impairment in adaptive functioning exceeded expected rates. A combination of familial/demographic and diagnostic variables were associated with acute functioning. In multiple regressions, tumor size best predicted adaptive functioning after initial diagnosis, whereas tumor location best predicted variance in behavioral symptoms. Children may be more vulnerable to acute impairment in adaptive functioning following diagnosis of a pediatric brain tumor, but rates of behavioral symptoms were within expectation. Familial, sociodemographic, and diagnostic variables may help to identify those most at risk of impairment. Screening of these factors within tertiary care settings will be useful to identify those most in need of psychosocial care during the initial phases of treatment. © 2014 Wiley Periodicals, Inc.

  4. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Yasojima, Hiroyuki; Iwasa, Tsutomu; Kanbayashi, Chizuko; Oshitanai, Risa; Tsuneizumi, Michiko; Watanabe, Ken-Ichi; Matsui, Akira; Fujisawa, Tomomi; Saji, Shigehira; Masuda, Norikazu; Tokuda, Yutaka; Iwata, Hiroji

    2017-11-28

    Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P L1, PD-L2, and HLA class I was also performed. There are significantly fewer TILs in brain metastases than in primary breast tumors.

  5. Brain connectivity study of brain tumor patients using MR-PET data: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Ana Carina [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal); Ribeiro, Andre Santos [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal); Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London (United Kingdom); Oros-Peusquens, Ana Maria; Langen, Karl Josef; Shah, Jon [Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich (Germany); Ferreira, Hugo Alexandre [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal)

    2015-05-18

    Brain activity results from anatomical and functional connections that can be disrupted or altered due to trauma or lesion. This work presents a first approach on the study of whole-brain connectivity of brain tumor patients using the Multimodal Imaging Brain Connectivity (MIBCA) toolbox. Two patients with glioblastoma lesions located in the left hemisphere (one in the motor cortex and the other in the temporal lobe) underwent simultaneous MRI and dynamic PET scans using a 3T MRI scanner with a BrainPET insert. The following data was acquired: T1-w MPRAGE (1x1x1mm{sup 3}), DTI (dir=30, b=0,800s/mm2, 2x2x2mm{sup 3}), and dynamic 18F-FET PET. The MIBCA toolbox was used to automatically pre-process MRI-PET data and to derive imaging and connectivity metrics from the multimodal data. Computed metrics included: cortical thickness from T1-w data; mean diffusivity (MD), fractional anisotropy (FA), node degree, clustering coefficient and pairwise ROI fibre tracking (structural connectivity) from DTI data; and standardized uptake value (SUV) from PET data. For all the metrics, the differences between left and right hemispherical structures were obtained, followed by a 25% threshold (except for SUV thresholded at 15%). Data was visualized in a connectogram, and both structural connectivity and metrics were studied in regions surrounding lesions. Preliminary results showed increased SUV values in regions surrounding the tumor for both patients. Patients also showed changes in structural connectivity involving these regions and also other more spatially distant regions such as the putamen and the pallidum, including decreased number of fibers between the subcortical structures themselves and with frontal regions. These findings suggest that the presence of a tumor may alter both local and more distant structural connections. Presently, a larger patient sample is being studied along with the inclusion of a control group to test the consistency of the findings.

  6. Vascular network remodeling via vessel cooption, regression and growth in tumors

    CERN Document Server

    Bartha, K

    2016-01-01

    The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts, that microvascular density (MVD, regarded as an important diagnostic tool in cancer treatment, does not necessarily determine the tempo of tumor progression. Instead it is suggested, that the MVD of the original tissue as well as the metabolic demand of the individual tumor cell plays the major role in the initial stages of tumor growth.

  7. Spectroscopic optical coherence tomography for ex vivo brain tumor analysis

    Science.gov (United States)

    Lenz, Marcel; Krug, Robin; Dillmann, Christopher; Gerling, Alexandra; Gerhardt, Nils C.; Welp, Hubert; Schmieder, Kirsten; Hofmann, Martin R.

    2017-02-01

    For neurosurgeries precise tumor resection is essential for the subsequent recovery of the patients since nearby healthy tissue that may be harmed has a huge impact on the life quality after the surgery. However, so far no satisfying methodology has been established to assist the surgeon during surgery to distinguish between healthy and tumor tissue. Optical Coherence Tomography (OCT) potentially enables non-contact in vivo image acquisition at penetration depths of 1-2 mm with a resolution of approximately 1-15 μm. To analyze the potential of OCT for distinction between brain tumors and healthy tissue, we used a commercially available Thorlabs Callisto system to measure healthy tissue and meningioma samples ex vivo. All samples were measured with the OCT system and three dimensional datasets were generated. Afterwards they were sent to the pathology for staining with hematoxylin and eosin and then investigated with a bright field microscope to verify the tissue type. This is the actual gold standard for ex vivo analysis. The images taken by the OCT system exhibit variations in the structure for different tissue types, but these variations may not be objectively evaluated from raw OCT images. Since an automated distinction between tumor and healthy tissue would be highly desirable to guide the surgeon, we applied Spectroscopic Optical Coherence Tomography to further enhance the differences between the tissue types. Pattern recognition and machine learning algorithms were applied to classify the derived spectroscopic information. Finally, the classification results are analyzed in comparison to the histological analysis of the samples.

  8. Determination of intra-axial brain tumors cellularity through the analysis of T2 Relaxation time of brain tumors before surgery using MATLAB software.

    Science.gov (United States)

    Abdolmohammadi, Jamil; Shafiee, Mohsen; Faeghi, Fariborz; Arefan, Douman; Zali, Alireza; Motiei-Langroudi, Rouzbeh; Farshidfar, Zahra; Nazarlou, Ali Kiani; Tavakkoli, Ali; Yarham, Mohammad

    2016-08-01

    Timely diagnosis of brain tumors could considerably affect the process of patient treatment. To do so, para-clinical methods, particularly MRI, cannot be ignored. MRI has so far answered significant questions regarding tumor characteristics, as well as helping neurosurgeons. In order to detect the tumor cellularity, neuro-surgeons currently have to sample specimens by biopsy and then send them to the pathology unit. The aim of this study is to determine the tumor cellularity in the brain. In this cross-sectional study, 32 patients (18 males and 14 females from 18-77 y/o) were admitted to the neurosurgery department of Shohada-E Tajrish Hospital in Tehran, Iran from April 2012 to February 2014. In addition to routine pulse sequences, T2W Multi echo pulse sequences were taken and the images were analyzed using the MATLAB software to determine the brain tumor cellularity, compared with the biopsy. These findings illustrate the need for more T2 relaxation time decreases, the higher classes of tumors will stand out in the designed table. In this study, the results show T2 relaxation time with a 85% diagnostic weight, compared with the biopsy, to determine the brain tumor cellularity (p<0.05). Our results indicate that the T2 relaxation time feature is the best method to distinguish and present the degree of intra-axial brain tumors cellularity (85% accuracy compared to biopsy). The use of more data is recommended in order to increase the percent accuracy of this techniques.

  9. Canine transmissible venereal tumor and seminoma: a cytohistopathology and chemotherapy study of tumors in the growth phase and during regression after chemotherapy.

    Science.gov (United States)

    Javanbakht, J; Pedram, B; Taheriyan, M R; Khadivar, F; Hosseini, S H; Abdi, F S; Hosseini, E; Moloudizargari, M; Aghajanshakeri, S H; Javaherypour, S; Shafiee, R; Emrani Bidi, R

    2014-06-01

    In this study, 12 dogs affected by canine transmissible venereal tumor (CTVT) and testicular seminoma tumor were studied retrospectively. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, and masses were surgically removed. The tumors were grossly examined, and sections of 4-μm thick were obtained from each sample and stained with H&E. For chemotherapy, vincristine sulfate was administered weekly as an infusion over 3 min via the cephalic vein at a dose of 0.025 mg/kg after diluting with physiological saline to a total amount of 10 ml. If no remission was observed after 8 weeks, chemotherapy was continued with weekly doxorubicin infusion at a dose of 1 mg/kg. All the tumor samples were divided into four cytohistopathologic groups, namely: multilobular (six cases), papillary (two cases), pedunculated (two cases), and tubular (two cases of seminoma). The most frequently represented tumor type was multilobular (6/10, 60 %) followed by pedunculated (2/10, 20 %), papillary (2/10, 20 %), and tubular (two cases of seminoma, 100 %). Cytological smears from eight tumors in regression after chemotherapy were poorly cellular, and many cells were fragmented. In two progressive tumors, there was an average of 1,406 ± 972 CTVT 200 cells/μl or 96.71 % of total cells counted. Thus, tumor cells represented 96.71 % of total cells within the biopsy specimens and the leukocytes 4.29 % (leukocyte, tumor cell ratio=0.062 ± 0.031). In eight regressive tumors, there was an average of 1,245 ± 1,032 CTVT 200 cells/μl or 97.31 % of total cells counted. Thus, tumor cells represented 97.31 % of total cells and leukocytes 2.69 % (leukocyte, tumor cell ratio=0.071 ± 0.174). Our data suggested that combination treatment with vincristine and doxorubicin in the future could be an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, and also, treatment success could easily be followed

  10. Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary tumors

    NARCIS (Netherlands)

    Burman, Pia; Van Beek, André P.; Biller, Beverly M.K.; Camacho-Hubner, Cecilia; Mattsson, Anders F.

    Background: Excess mortality due to de novo malignant brain tumors was recently found in a national study of patients with hypopituitarism following treatment of pituitary tumors. Here, we examined a larger multi-national cohort to corroborate and extend this observation. Objective: To investigate

  11. Role of magnetic resonance spectroscopy & diffusion weighted imaging in differentiation of supratentorial brain tumors

    Directory of Open Access Journals (Sweden)

    Abdel Monem Nooman Darwiesh

    2016-09-01

    Conclusion: Intra-lesional ADC values are not useful in the differentiation between primary and metastatic tumors. Perilesional ADC values can differentiate between primary & metastatic brain tumors. Intralesional MRS values (CHO/Cr ratio were able to grade the tumor and differentiate between high and low grade tumors, while Perilesional MRS values (CHO/Cr ratio could be able to differentiate primary tumors from metastasis.

  12. A murine model for virotherapy of malignant brain tumors

    Directory of Open Access Journals (Sweden)

    E. Gambini

    2011-01-01

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

  13. Perfusion magnetic resonance imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Dallery, F.; Michel, D.; Constans, J.M.; Gondry-Jouet, C. [University Hospital, Department of Radiology, Amiens (France); Bouzerar, R.; Promelle, V.; Baledent, O. [University Hospital, Department of Imaging and Biophysics, Amiens (France); Attencourt, C. [University Hospital, Departement of Pathology, Amiens (France); Peltier, J. [University Hospital, Departement of Neurosurgery, Amiens (France)

    2017-11-15

    The use of DSC-MR imaging in pediatric neuroradiology is gradually growing. However, the number of studies listed in the literature remains limited. We propose to assess the perfusion and permeability parameters in pediatric brain tumor grading. Thirty children with a brain tumor having benefited from a DSC-MR perfusion sequence have been retrospectively explored. Relative CBF and CBV were computed on the ROI with the largest lesion coverage. Assessment of the lesion's permeability was also performed through the semi-quantitative PSR parameter and the K2 model-based parameter on the whole-lesion ROI and a reduced ROI drawn on the permeability maps. A statistical comparison of high- and low-grade groups (HG, LG) as well as a ROC analysis was performed on the histogram-based parameters. Our results showed a statistically significant difference between LG and HG groups for mean rCBV (p < 10{sup -3}), rCBF (p < 10{sup -3}), and for PSR (p = 0.03) but not for the K2 factor (p = 0.5). However, the ratio K2/PSR was shown to be a strong discriminating factor between the two groups of lesions (p < 10{sup -3}). For rCBV and rCBF indicators, high values of ROC AUC were obtained (> 0.9) and mean value thresholds were observed at 1.07 and 1.03, respectively. For K2/PSR in the reduced area, AUC was also superior to 0.9. The implementation of a dynamic T2* perfusion sequence provided reliable results using an objective whole-lesion ROI. Perfusion parameters as well as a new permeability indicator could efficiently discriminate high-grade from low-grade lesions in the pediatric population. (orig.)

  14. Cerebral effect of acute normovolemic hemodilution during brain tumor resection.

    Science.gov (United States)

    Daif, Ahmed Attia Atwa; Hassan, Younis Mohamed Abd El Mageed; Ghareeb, Nawal Abd El-Galil; Othman, Mahmoud Mahmoud; Mohamed, Sherif Abdo Mousa

    2012-01-01

    Acute normovolemic hemodilution (ANH) is used in major surgery expected to be accompanied by excessive blood loss. Reducing the hemoglobin content may disturb cerebral oxygen balance. The aim of this study was to assess the effect of ANH on cerebral oxygen balance in patients subjected to brain tumor resection. Forty patients were randomly allocated into 2 groups (hemodilution and control). In the hemodilution group (HG), 1000 mL of blood was drawn and replaced with the same volume of HES 130/0.4 (6%, Voluven) colloid. In the control group (CG), no blood was drawn, and hemodynamics were stabilized using normal saline until allogenic blood was needed. Arterial and jugular bulb blood samples obtained after induction (basal, sample 1), 40 minutes after induction (or on completion of hemodilution, sample 2), after surgical hemostasis (sample 3), and just before extubation (sample 4) were used for the calculation of arterial-jugular oxygen content difference "Ca-jO(2)," cerebral oxygen extraction "CEO(2)," estimated cerebral metabolic rate for oxygen "eCMRO(2)," cerebral blood flow equivalent "CBFe," and jugular-arterial lactate difference "J-ALD" in both groups. Jugular oxygen saturation "SjvO(2)", CEO(2), and J-ALD showed no significant difference when the 2 groups were compared at the corresponding time points and when the values obtained at different time points were compared with the basal value in the same group. In CG, "Ca-jO(2)" significantly decreased at the end of surgery and before tracheal extubation (Pcerebral oxygenation parameters in patients subjected to brain tumor resection.

  15. Brain Tumor Epidemiology - A Hub within Multidisciplinary Neuro-oncology. Report on the 15th Brain Tumor Epidemiology Consortium (BTEC) Annual Meeting, Vienna, 2014.

    Science.gov (United States)

    Woehrer, Adelheid; Lau, Ching C; Prayer, Daniela; Bauchet, Luc; Rosenfeld, Myrna; Capper, David; Fisher, Paul G; Kool, Marcel; Müller, Martin; Kros, Johan M; Kruchko, Carol; Wiemels, Joseph; Wrensch, Margaret; Danysh, Heather E; Zouaoui, Sonia; Heck, Julia E; Johnson, Kimberly J; Qi, Xiaoyang; O'Neill, Brian P; Afzal, Samina; Scheurer, Michael E; Bainbridge, Matthew N; Nousome, Darryl; Bahassi, El Mustapha; Hainfellner, Johannes A; Barnholtz-Sloan, Jill S

    2015-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 - 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year's meeting, which will be held at the Mayo Clinic at Rochester, MN, USA.

  16. PET imaging in the surgical management of pediatric brain tumors.

    Science.gov (United States)

    Pirotte, Benoit; Acerbi, Francesco; Lubansu, Alphonse; Goldman, Serge; Brotchi, Jacques; Levivier, Marc

    2007-07-01

    The present article illustrates whether positron-emission tomography (PET) imaging may improve the surgical management of pediatric brain tumors (PBT) at different steps. Among 400 consecutive PBT treated between 1995 and 2005 at Erasme Hospital, Brussels, Belgium, we have studied with (18) F-2-fluoro-2-deoxy-D-glucose (FDG)-PET and/or L-(methyl-(11)C)methionine (MET)-PET and integrated PET images in the diagnostic workup of 126 selected cases. The selection criteria were mainly based on the lesion appearance on magnetic resonance (MR) sequences. Cases were selected when MR imaging showed limitations for (1) assessing the evolving nature of an incidental lesion (n = 54), (2) selecting targets for contributive and accurate biopsy (n = 32), and (3) delineating tumor tissue for maximal resection (n = 40). Whenever needed, PET images were integrated in the planning of image-guided surgical procedures (frame-based stereotactic biopsies (SB), frameless navigation-based resections, or leksell gamma knife radiosurgery). Like in adults, PET imaging really helped the surgical management of the 126 children explored, which represented about 30% of all PBT, especially when the newly diagnosed brain lesion was (1) an incidental finding so that the choice between surgery and conservative MR follow-up was debated, and (2) so infiltrative or ill-defined on MR that the choice between biopsy and resection was hardly discussed. Integrating PET into the diagnostic workup of these two selected groups helped to (1) take a more appropriate decision in incidental lesions by detecting tumor/evolving tissue; (2) better understand complex cases by differentiating indolent and active components of the lesion; (3) improve target selection and diagnostic yield of stereotactic biopsies in gliomas; (4) illustrate the intratumoral histological heterogeneity in gliomas; (5) provide additional prognostic information; (6) reduce the number of trajectories in biopsies performed in eloquent areas such

  17. The efficiency of adjusted-da-chai-ling-tang in radiation-induced brain edema in patients with brain tumors

    Directory of Open Access Journals (Sweden)

    Da-Tong Ju

    2015-01-01

    Full Text Available Background: Brain edema induced by radiotherapy is a common complication in patients with brain tumors, for which medical treatment is the treatment of choice. Adjusted-Da-Chai-Ling-Tang, a Chinese herbal formulation, has been confirmed to be protective against the radiation-induced edema. In this study, we investigated the efficiency of adjusted-Da-Chai-Ling-Tang in radiation-induced brain edema in patients with brain tumors. Materials and Methods: A total of 46 patients with brain tumors treated with radiotherapy alone or combined with surgery were enrolled. These patients were divided into two groups: The experimental group with adjusted-Da-Chai-Ling-Tang and the control group with conventional medical treatment. Clinical data including symptoms and serologic results were collected pretreatment and on the 4 th , 7 th and 10 th day posttreatment. Magnetic resonance imaging of the brain was performed to investigate changes in brain edema. Results: Clinical symptoms including headache, dizziness, nausea/vomiting and fatigue significantly improved in the experimental group (P < 0.05. No difference in serological results was observed. Brain edema was significantly reduced in the experimental group in magnetic resonance imaging (P < 0.05. Conclusion: Adjusted-Da-Chai-Ling-Tang is effective in the treatment of radiation-induced brain edema in patients with brain tumors. No obvious side effects were observed.

  18. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment

    NARCIS (Netherlands)

    Tellingen, O. van; Yetkin-Arik, B.; Gooijer, M.C. de; Wesseling, P.; Wurdinger, T.; Vries, H.E. de

    2015-01-01

    Gliomas are the most common primary brain tumors. Particularly in adult patients, the vast majority of gliomas belongs to the heterogeneous group of diffuse gliomas, i.e. glial tumors characterized by diffuse infiltrative growth in the preexistent brain tissue. Unfortunately, glioblastoma, the most

  19. Timed performance weaknesses on computerized tasks in pediatric brain tumor survivors: A comparison with sibling controls

    NARCIS (Netherlands)

    Ruiter, M.A. de; Grootenhuis, M.A.; Mourik, R. van; Maurice-Stam, H.; Breteler, M.H.M.; Gidding, C.E.M.; Beek, L.R.; Granzen, B.; Vuurden, D.G. van; Schouten-van Meeteren, A.Y.N.; Oosterlaan, J.

    2017-01-01

    With more children surviving a brain tumor, insight into the late effects of the disease and treatment is of high importance. This study focused on profiling the neurocognitive functions that might be affected after treatment for a pediatric brain tumor, using a broad battery of computerized tests.

  20. Drug-Resistant Brain Metastases: A Role for Pharmacology, Tumor Evolution, and Too-Late Therapy.

    Science.gov (United States)

    Stricker, Thomas; Arteaga, Carlos L

    2015-11-01

    Two recent studies report deep molecular profiling of matched brain metastases and primary tumors. In both studies, somatic alterations in the brain metastases were frequently discordant with those in the primary tumor, suggesting divergent evolution at metastatic sites and raising questions about the use of biomarkers in patients in clinical trials with targeted therapies. ©2015 American Association for Cancer Research.

  1. Health-related quality of life in long-term survivors of childhood brain tumors

    DEFF Research Database (Denmark)

    Reimers, Tonny Solveig; Mortensen, Erik Lykke; Nysom, Karsten

    2009-01-01

    BACKGROUND: To identify predictors for health-related quality of life (HRQOL) in survivors of childhood brain tumors and its relationship to cognitive function. PROCEDURE: One hundred twenty-six consecutive Danish childhood brain tumor patients treated 1970-1997 and being 7.9-40.4 years at follow...

  2. Brain tumors in children and adolescents and exposure to animals and farm life

    DEFF Research Database (Denmark)

    Christensen, Jeppe Schultz; Mortensen, Laust Hvas; Röösli, Martin

    2012-01-01

    The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs...

  3. Caring for patients with brain tumor: The patient and care giver ...

    African Journals Online (AJOL)

    Background: Patients with brain tumors form a heterogeneous group in terms of clinical presentation and pathology. However, the impact of the disease on patients' families is often more homogenous and frequently quite profound. A considerable body of literature is available on the management of brain tumors and ...

  4. Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors

    DEFF Research Database (Denmark)

    Reimers, Tonny Solveig; Ehrenfels, Susanne; Mortensen, Erik Lykke

    2003-01-01

    To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors.......To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors....

  5. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    National Research Council Canada - National Science Library

    Kılıçkaya, M. Mustafa; Aynali, Giray; Ceyhan, Ali Murat; Çiriş, Metin

    2016-01-01

    .... Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously...

  6. Targeting the PD-1 pathway in pediatric solid tumors and brain tumors

    Directory of Open Access Journals (Sweden)

    Wagner LM

    2017-04-01

    Full Text Available Lars M Wagner,1 Val R Adams2 1Division of Pediatric Hematology/Oncology, 2Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY, USA Abstract: While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1 pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such as sarcoma, neuroblastoma, and high-grade glioma. We summarize the completed and ongoing clinical trial data available, and suggest potential applications for further study. Keywords: PD-1, nivolumab, pembrolizumab, pediatric, sarcoma, neuroblastoma, glioma

  7. Histological and Demographic Characteristics of the Distribution of Brain and Central Nervous System Tumors' Sizes: Results from SEER Registries Using Statistical Methods.

    Science.gov (United States)

    Pokhrel, Keshav P; Vovoras, Dimitrios; Tsokos, Chris P

    2012-09-01

    The examination of brain tumor growth and its variability among cancer patients is an important aspect of epidemiologic and medical data. Several studies for tumors of brain interpreted descriptive data, in this study we perform inference in the extent possible, suggesting possible explanations for the differentiation in the survival rates apparent in the epidemiologic data. Population based information from nine registries in the USA are classified with respect to age, gender, race and tumor histology to study tumor size variation. The Weibull and Dagum distributions are fitted to the highly skewed tumor sizes distributions, the parametric analysis of the tumor sizes showed significant differentiation between sexes, increased skewness for both the male and female populations, as well as decreased kurtosis for the black female population. The effect of population characteristics on the distribution of tumor sizes is estimated by quantile regression model and then compared with the ordinary least squares results. The higher quantiles of the distribution of tumor sizes for whites are significantly higher than those of other races. Our model predicted that the effect of age in the lower quantiles of the tumor sizes distribution is negative given the variables race and sex. We apply probability and regression models to explore the effects of demographic and histology types and observe significant racial and gender differences in the form of the distributions. Efforts are made to link tumor size data with available survival rates in relation to other prognostic variables.

  8. [A case of cerebral syphilitic gumma mimicking a brain tumor].

    Science.gov (United States)

    Hamauchi, Akiko; Abe, Takenori; Nihira, Atsuko; Mizobuchi, Masahiro; Sako, Kazuya; Ito, Tamio

    2014-01-01

    We report a case of young immunocompetent woman who was presented with a left parieto-temporal mass as the first and single manifestation of syphilis. A 23 year-old woman with no significant past medical history was reffered to our hospital due to 3 month history of headache. She had a single unprotected sexual intercourse with a promiscuous man 6 month before the time of admission. Physical and neurological examinations revealed no obvious abnormalities. A brain tumor was firstly suggested according to the findings of brain magnetic resonance imaging (MRI). However, the serologic and cerebrospinal fluid test of syphilis proved to be positive, syphilitic gumma was most likely suspected. She responded dramatically to benzylpenicillin potassium. Cerebral syphilitic gumma is a rare manifestations of the neurosyphilis. Treponemal invasion of the cerebrospinal fluid occurs in approximately 25 to 60% of patients after the infection, but most cases spend asymptomatic. Cerebral gumma should be considered in differential diagnosis of any intracranial mass lesions, even in the early syphilitic stages.

  9. (18)F-Fluorodeoxyglucose PET/Computed Tomography for Primary Brain Tumors

    DEFF Research Database (Denmark)

    Antonsen Segtnan, Eivind; Hess, Søren; Grupe, Peter

    2015-01-01

    Structural imaging with computed tomography (CT) and MR imaging is the mainstay in primary diagnosis of primary brain tumors, but these modalities depend on morphologic appearance and an intact blood-brain barrier, and important aspects of tumor biology are not addressed. Such issues may...... be alleviated by (18)F-fluorodeoxyglucose (FDG)-PET and FDG-PET/CT imaging, which may provide clinically important information with regard to primary differentiation between tumor types, initial staging and risk stratification, therapy planning, response evaluation, and recurrence detection. This article...... describes some of the potential contemporary applications of FDG and PET in primary brain tumors....

  10. Separation of the tumor and brain surface by "water jet" in cases of meningiomas.

    Science.gov (United States)

    Toth, S; Vajda, J; Pasztor, E; Toth, Z

    1987-01-01

    In the surgery of meningiomas one of the most delicate problems is the separation of the tumor from the brain surface. The authors generally recommend microsurgery to preserve the brain surface anatomically and functionally. For this purpose we have developed a new surgical technique according to our concepts of tissue care. After excavating the tumor from inside the tumor brain surface was separated by repeated "water jets" into the tumor arachnoideal space. The "water jet" was produced by an ordinary bulb syringe. The front pressure of the jets was 300-1000 mm of water and the side pressure 100-300 mm of water. In the tumor-arachnoideal space the spreading water (phys. NaCl) separates the brain from the tumor with utmost care. We operated on 55 meningiomas of different types with the "water jet" technique. The immediate results were anatomically excellent. Intraoperative and postoperative acute and late edemas appeared only in a few cases. The functions of the nearby brain were generally preserved. The surgery was uneventful when the tumor surface was smooth and the tumor was spherical. When the tumor surface was uneven, one part of the tumor extended under the dura as a thin layer or the tumor was multilobulated with expanded vessels between the lobules, more microseparation was necessary. We compared the results of the "water jet" technique with the results of the "pre-water jet" series. The surgery with the "water jet" technique was much shorter and its results were better than those of microsurgery alone.

  11. Brain Tumor Initiating Cells Adapt to Restricted Nutrition through Preferential Glucose Uptake

    Science.gov (United States)

    Flavahan, William A.; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E.; Weil, Robert J.; Nakano, Ichiro; Sarkaria, Jann N.; Stringer, Brett W.; Day, Bryan W.; Li, Meizhang; Lathia, Justin D.; Rich, Jeremy N.; Hjelmeland, Anita B.

    2013-01-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) due to preferential BTIC survival and adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3 and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, TICs may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may instruct the tumor hierarchy and portend poor prognosis. PMID:23995067

  12. Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes.

    Science.gov (United States)

    Lim, Li Ying; Koh, Pei Yin; Somani, Sukrut; Al Robaian, Majed; Karim, Reatul; Yean, Yi Lyn; Mitchell, Jennifer; Tate, Rothwelle J; Edrada-Ebel, RuAngelie; Blatchford, David R; Mullin, Margaret; Dufès, Christine

    2015-08-01

    The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

    Science.gov (United States)

    Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E

    2012-11-15

    To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (pcapacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  15. Double-echo perfusion-weighted MR imaging: basic concepts and application in brain tumors for the assessment of tumor blood volume and vascular permeability.

    Science.gov (United States)

    Uematsu, Hidemasa; Maeda, Masayuki

    2006-01-01

    Perfusion-weighted magnetic resonance (MR) imaging using contrast agents plays a key role in characterizing tumors of the brain. We have shown that double-echo perfusion-weighted MR imaging (DEPWI) is potentially useful in assessing brain tumors. Quantitative indices, such as tumor blood volume, are obtained using DEPWI, which allows correction of underestimation of tumor blood volume due to leakage of contrast agents from tumor vessels, in addition to simultaneous acquisition of tumor vessel permeability. This article describes basic concepts of DEPWI and demonstrates clinical applications in brain tumors.

  16. Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

    Science.gov (United States)

    2017-07-31

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment; Radiation Toxicity

  17. 3D variational brain tumor segmentation using Dirichlet priors on a clustered feature set.

    Science.gov (United States)

    Popuri, Karteek; Cobzas, Dana; Murtha, Albert; Jägersand, Martin

    2012-07-01

    Brain tumor segmentation is a required step before any radiation treatment or surgery. When performed manually, segmentation is time consuming and prone to human errors. Therefore, there have been significant efforts to automate the process. But, automatic tumor segmentation from MRI data is a particularly challenging task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. In our work, we propose an automatic brain tumor segmentation method that addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multidimensional feature set. Then, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this work is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned region statistics in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters from the normal brain region to be in the tumor region. This leads to a better disambiguation of the tumor from brain tissue. We evaluated the performance of our automatic segmentation method on 15 real MRI scans of brain tumor patients, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Validation with the expert segmentation labels yielded encouraging results: Jaccard (58%), Precision (81%), Recall (67%), Hausdorff distance (24 mm). Using priors on the brain/tumor appearance, our proposed automatic 3D variational

  18. •Primary brain tumors: Proton magnetic resonance spectroscopic analysis and histopathological correlation

    Directory of Open Access Journals (Sweden)

    Abdurrahim Dusak

    2014-06-01

    Full Text Available Objective: Recent advances in treatment of primary brain tumors have increased the interest in radiological imaging in respect to both the diagnosis of tumor and the evaluation of the efficiency of therapy. Conventional Magnetic Resonance (MR imaging is commonly used for diagnosis and follows up of the primary brain tumors, but it fails in grading of the tumors. MR spectroscopy permits in-vivo biochemical evaluation of brain lesions. Methods: Twenty three patients with histopathologic diagnosis of primary brain tumor and control group consisting of 23 healthy volunteers were investigated. In addition to conventional MR imaging of all patients were underwent point resolved spectroscopy (PRESS sequence via single voxel MR spectroscopy. Using MR spectroscopy, metabolites [N-acetyl aspartate (NAA, choline (Cho, myo-inositol (mI, lipid, lactate and alanine] and their ratio to creatine (Cr were measured quantitatively. Results: MR spectroscopic imaging of neuroglial primary brain tumors revealed that the NAA/Cr and mI/Cr ratios were decreased. In extra axial primary brain tumors, which consist of meningioma, NAA wasn’t detected, Cho/Cr ratio was remarkably increased, mI/Cr, lipid/Cr and lactate/Cr ratios were mildly increased. Alanine peak was detected only in meningioma. In high grade neuroglial tumors in proportion to low grade ones NAA/Cr and mI/Cr ratios were decreased, Cho/Cr, lipid/Cr and lactate/Cr ratios were remarkably increased. Conclusion: MR spectroscopy provides extra information in classification of primary brain tumors as intra-axial and extra-axial, and in grading of neuroglial primary brain tumors as high grade or low grade. It was concluded that using conventional MR imaging in cooperation with MR spectroscopy is beneficial in differential diagnosis and in grading of primary brain tumors. J Clin Exp Invest 2014; 5 (2: 233-241

  19. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy

    DEFF Research Database (Denmark)

    Galldiks, Norbert; Law, Ian; Pope, Whitney B

    2017-01-01

    Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and......),O-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) and summarizes investigations regarding monitoring of brain tumor therapy....

  20. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  1. Hierarchical non-negative matrix factorization to characterize brain tumor heterogeneity using multi-parametric MRI

    NARCIS (Netherlands)

    Sauwen, Nicolas; Sima, Diana M.; Van Cauter, Sofie; Veraart, Jelle; Leemans, Alexander; Maes, Frederik; Himmelreich, Uwe; Van Huffel, Sabine

    2015-01-01

    Tissue characterization in brain tumors and, in particular, in high-grade gliomas is challenging as a result of the co-existence of several intra-tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor

  2. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Science.gov (United States)

    Miao, Hongsheng; Choi, Bryan D; Suryadevara, Carter M; Sanchez-Perez, Luis; Yang, Shicheng; De Leon, Gabriel; Sayour, Elias J; McLendon, Roger; Herndon, James E; Healy, Patrick; Archer, Gary E; Bigner, Darell D; Johnson, Laura A; Sampson, John H

    2014-01-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  3. Bacterial delivery of Staphylococcus aureus α-hemolysin causes regression and necrosis in murine tumors.

    Science.gov (United States)

    St Jean, Adam T; Swofford, Charles A; Panteli, Jan T; Brentzel, Zachary J; Forbes, Neil S

    2014-07-01

    Bacterial therapies, designed to manufacture therapeutic proteins directly within tumors, could eliminate cancers that are resistant to other therapies. To be effective, a payload protein must be secreted, diffuse through tissue, and efficiently kill cancer cells. To date, these properties have not been shown for a single protein. The gene for Staphylococcus aureus α-hemolysin (SAH), a pore-forming protein, was cloned into Escherichia coli. These bacteria were injected into tumor-bearing mice and volume was measured over time. The location of SAH relative to necrosis and bacterial colonies was determined by immunohistochemistry. In culture, SAH was released and killed 93% of cancer cells in 24 hours. Injection of SAH-producing bacteria reduced viable tissue to 9% of the original tumor volume. By inducing cell death, SAH moved the boundary of necrosis toward the tumor edge. SAH diffused 6.8 ± 0.3 µm into tissue, which increased the volume of affected tissue from 48.6 to 3,120 µm(3). A mathematical model of molecular transport predicted that SAH efficacy is primarily dependent on colony size and the rate of protein production. As a payload protein, SAH will enable effective bacterial therapy because of its ability to diffuse in tissue, kill cells, and expand tumor necrosis.

  4. Brain Metastasis from Gastrointestinal Stromal Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Hideaki Naoe

    2011-10-01

    Full Text Available Metastasis of gastrointestinal stromal tumor (GIST into the central nervous system is extremely rare. We report a patient with synchronous GIST and brain metastasis. At disease onset, there was left hemiplegia and ptosis of the right eyelids. Resection cytology of the brain tumor was reported as metastasis of GIST. After positron emission tomography examination, another tumor in the small bowel was discovered, which suggested a small bowel GIST associated with intracranial metastasis. Immunohistochemical analysis of the intestinal tumor specimen obtained by double balloon endoscopy showed a pattern similar to the brain tumor, with the tumors subsequently identified as intracranial metastases of jejunal GIST. After surgical resection of one brain tumor, the patient underwent whole brain radiation therapy followed by treatment with imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland. Mutational analysis of the original intestinal tumor revealed there were no gene alterations in KIT or PDGFRα. Since the results indicated the treatment had no apparent effect on either of the tumors, and because ileus developed due to an intestinal primary tumor, the patient underwent surgical resection of the intestinal lesion. However, the patient’s condition gradually worsen and she subsequently died 4 months after the initial treatment.

  5. Symptoms and management of pediatric patients with incurable brain tumors in palliative home care.

    Science.gov (United States)

    Kuhlen, Michaela; Hoell, Jessica; Balzer, Stefan; Borkhardt, Arndt; Janssen, Gisela

    2016-03-01

    Brain tumors have the highest disease-related mortality rate of all pediatric cancers. The goal of this study was to determine whether all children with incurable brain tumors cared for by a pediatric palliative care team in a home setting suffer from the same symptoms towards the end of their lives or whether there are differences between the tumor localizations with implications for palliative care. This study was conducted as a retrospective, single center chart review including all patients treated between January 1st 2000 and December 31st 2013. 70 children, adolescents and young adults were included in the analysis. Symptom burden was high with a mean number of symptoms of 7.2 per patient. 74% of the symptoms already existed one week before death. Within the last week of life, impaired consciousness (75.7%) most often occurred. Furthermore, symptoms considerably depended on tumor localization. Patients with supratentorial tumors presented more frequently with seizures (p paralysis (p brain stem tumors. 84.3% of the patients needed analgesics, only 64.4% WHO class III analgesics. Anticonvulsants were given more often in supratentorial tumors (p child suffering from a brain tumor needs increased awareness of the neurological deterioration. The symptom pattern strongly depends on the tumor localization and significantly differs between supratentorial, infratentorial and brain stem tumors. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    Directory of Open Access Journals (Sweden)

    M. Mustafa Kılıçkaya

    2016-01-01

    Full Text Available Malignant melanoma of the parotid gland is often metastatic and mainly originates from malignant melanomas in the head and neck. Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously. The investigation of a patient’s old photographs may help in the detection of preexisting and regressed pigmented lesions in the facial and neck regions.

  7. Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing.

    Science.gov (United States)

    van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank

    2016-02-16

    Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the 'sunburn group' but persisted and grew in the 'sub-sunburn group' (0.06 vs 2.50 SCCs and precursors ≥4 mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these 'usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide--with high mutagenic risk--gives rise to persisting (mainly 'in situ') skin carcinomas.

  8. Viral-mediated oncolysis is the most critical factor in the late-phase of the tumor regression process upon vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2011-02-01

    Full Text Available Abstract Background In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV. Methods Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient or upon cyclophosphamide-induced immunosuppression (MHCII+-cell depletion in nude mice. Results Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII+/CD31+ vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in

  9. Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches.

    Directory of Open Access Journals (Sweden)

    Iveta Selingerová

    Full Text Available We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time.In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed.There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months. The survival time of patients was significantly different for various diagnoses (p≪0.001, KI (p = 0.047 and stereotactic methods (p = 0.033. Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm3. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions.Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables.

  10. Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches.

    Science.gov (United States)

    Selingerová, Iveta; Doleželová, Hana; Horová, Ivanka; Katina, Stanislav; Zelinka, Jiří

    2016-01-01

    We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time. In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed. There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months). The survival time of patients was significantly different for various diagnoses (p≪0.001), KI (p = 0.047) and stereotactic methods (p = 0.033). Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm3. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions. Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables.

  11. Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches

    Science.gov (United States)

    Selingerová, Iveta; Doleželová, Hana; Horová, Ivanka; Katina, Stanislav; Zelinka, Jiří

    2016-01-01

    Purpose We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time. Methods In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed. Results There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months). The survival time of patients was significantly different for various diagnoses (p≪0.001), KI (p = 0.047) and stereotactic methods (p = 0.033). Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm3. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions. Conclusion Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables. PMID:26863415

  12. 18F-FDG PET and MR Imaging Associations Across a Spectrum of Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

    Science.gov (United States)

    Zukotynski, Katherine; Fahey, Frederic; Kocak, Mehmet; Kun, Larry; Boyett, James; Fouladi, Maryam; Vajapeyam, Sridhar; Treves, Ted; Poussaint, Tina Y.

    2014-01-01

    The purpose of this study was to describe 18F-FDG uptake across a spectrum of pediatric brain tumors and correlate 18F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS). Methods A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated. Results Baseline 18F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The 18F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of 18F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between 18F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had 18F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). Conclusion 18F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of 18F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had 18F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between 18F

  13. Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models.

    Science.gov (United States)

    Lu, Zhen; Zuo, Bingfeng; Jing, Renwei; Gao, Xianjun; Rao, Quan; Liu, Zhili; Qi, Han; Guo, Hongxing; Yin, HaiFang

    2017-10-01

    Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However, their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic that responds poorly to immunotherapy, remains to be investigated. Exosomes derived from α-fetoprotein (AFP)-expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically. Tumor growth and microenvironment were monitored. DEXAFP elicited strong antigen-specific immune responses and resulted in significant tumor growth retardation and prolonged survival rates in mice with ectopic, orthotopic and carcinogen-induced HCC tumors that displayed antigenic and pathological heterogeneity. The tumor microenvironment was improved in DEXAFP-treated HCC mice, demonstrated by significantly more γ-interferon (IFN-γ)-expressing CD8+ T lymphocytes, elevated levels of IFN-γ and interleukin-2, and fewer CD25+Foxp3+ regulatory T (Treg) cells and decreased levels of interleukin-10 and transforming growth factor-β in tumor sites. Lack of efficacy in athymic nude mice and CD8+ T cell-depleted mice showed that T cells contribute to DEXAFP-mediated antitumor function. Dynamic examination of the antitumor efficacy and the immune microenvironment in DEXAFP-treated orthotopic HCC mice at different time-points revealed a positive correlation between tumor suppression and immune microenvironment. Our findings provide evidence that AFP-enriched DEXs can trigger potent antigen-specific antitumor immune responses and reshape the tumor microenvironment in HCC mice and thus provide a cell-free vaccine option for HCC immunotherapy. Lay summary: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However, their potency in hepatocellular carcinoma (HCC) remains unknown. Here, we investigated exosomes from HCC antigen-expressing DCs in three different HCC mouse models and proved their feasibility

  14. A comparison of brain activity associated with language production in brain tumor patients with left and right sided language laterality

    NARCIS (Netherlands)

    Jansma, J. M.; Ramsey, N.; Rutten, G.J.M.

    2015-01-01

    Aim. Language dominance is an important factor for clinical decision making in brain tumor surgery. Functional MM can provide detailed information about the organization of language in the brain. One often used measure derived from fMRI data is the laterality index (LI). The LI is typically based on

  15. Quantitative assessment of Cerenkov luminescence for radioguided brain tumor resection surgery

    Science.gov (United States)

    Klein, Justin S.; Mitchell, Gregory S.; Cherry, Simon R.

    2017-05-01

    Cerenkov luminescence imaging (CLI) is a developing imaging modality that detects radiolabeled molecules via visible light emitted during the radioactive decay process. We used a Monte Carlo based computer simulation to quantitatively investigate CLI compared to direct detection of the ionizing radiation itself as an intraoperative imaging tool for assessment of brain tumor margins. Our brain tumor model consisted of a 1 mm spherical tumor remnant embedded up to 5 mm in depth below the surface of normal brain tissue. Tumor to background contrast ranging from 2:1 to 10:1 were considered. We quantified all decay signals (e±, gamma photon, Cerenkov photons) reaching the brain volume surface. CLI proved to be the most sensitive method for detecting the tumor volume in both imaging and non-imaging strategies as assessed by contrast-to-noise ratio and by receiver operating characteristic output of a channelized Hotelling observer.

  16. Implications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors.

    Science.gov (United States)

    Pak, Rebecca W; Hadjiabadi, Darian H; Senarathna, Janaka; Agarwal, Shruti; Thakor, Nitish V; Pillai, Jay J; Pathak, Arvind P

    2017-11-01

    Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data. Therefore, to avoid neurosurgical complications, it is crucial to understand the biophysical basis of NVU and its impact on fMRI. Here we review the physiology of the neurovascular unit, how it is remodeled, and functionally altered by brain cancer cells. We first discuss the latest findings about the components of the neurovascular unit. Next, we synthesize results from preclinical and clinical studies to illustrate how brain tumor induced NVU affects fMRI data interpretation. We examine advances in functional imaging methods that permit the clinical evaluation of brain tumors with NVU. Finally, we discuss how the suppression of anomalous tumor blood vessel formation with antiangiogenic therapies can "normalize" the brain tumor vasculature, and potentially restore neurovascular coupling.

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

    Science.gov (United States)

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

    2015-04-01

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

  18. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  19. Altered brain anatomical networks and disturbed connection density in brain tumor patients revealed by diffusion tensor tractography.

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    Yu, Zhou; Tao, Ling; Qian, Zhiyu; Wu, Jiangfen; Liu, Hongyi; Yu, Yun; Song, Jiantai; Wang, Shaobo; Sun, Jinyang

    2016-11-01

    Brain tumor patients are usually accompanied by impairments in cognitive functions, and these dysfunctions arise from the altered diffusion tensor of water molecules and disrupted neuronal conduction in white matter. Diffusion tensor imaging (DTI) is a powerful noninvasive imaging technique that can reflect diffusion anisotropy of water and brain white matter neural connectivity in vivo. This study was aimed to analyze the topological properties and connection densities of the brain anatomical networks in brain tumor patients based on DTI and provide new insights into the investigation of the structural plasticity and compensatory mechanism of tumor patient's brain. In this study, the brain anatomical networks of tumor patients and healthy controls were constructed using the tracking of white matter fiber bundles based on DTI and the topological properties of these networks were described quantitatively. The statistical comparisons were performed between two groups with six DTI parameters: degree, regional efficiency, local efficiency, clustering coefficient, vulnerability, and betweenness centrality. In order to localize changes in structural connectivity to specific brain regions, a network-based statistic approach was utilized. By comparing the edge connection density of brain network between two groups, the edges with greater difference in connection density were associated with three functional systems. Compared with controls, tumor patients show a significant increase in small-world feature of cerebral structural network. Two-sample two-tailed t test indicates that the regional properties are altered in 17 regions ([Formula: see text]). Study reveals that the positive and negative changes in vulnerability take place in the 14 brain areas. In addition, tumor patients lose 3 hub regions and add 2 new hubs when compared to normal controls. Eleven edges show much significantly greater connection density in the patients than in the controls. Most of the edges with

  20. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yuuki Takashima

    2012-10-01

    Full Text Available The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT in solution and in methoxy poly(ethylene glycol (MPEG/poly(e-caprolactone (PCL amphiphilic block copolymers (MPEG-PCL and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL. CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.

  1. 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know.

    Science.gov (United States)

    Johnson, Derek R; Guerin, Julie B; Giannini, Caterina; Morris, Jonathan M; Eckel, Lawrence J; Kaufmann, Timothy J

    2017-01-01

    Radiologists play a key role in brain tumor diagnosis and management and must stay abreast of developments in the field to advance patient care and communicate with other health care providers. In 2016, the World Health Organization (WHO) released an update to its brain tumor classification system that included numerous significant changes. Several previously recognized brain tumor diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and gliomatosis cerebri, were redefined or eliminated altogether. Conversely, multiple new entities were recognized, including diffuse leptomeningeal glioneuronal tumor and multinodular and vacuolating tumor of the cerebrum. The glioma category has been significantly reorganized, with several infiltrating gliomas in children and adults now defined by genetic features for the first time. These changes were driven by increased understanding of important genetic factors that directly impact tumorigenesis and influence patient care. The increased emphasis on genetic factors in brain tumor diagnosis has important implications for radiology, as we now have tools that allow us to evaluate some of these alterations directly, such as the identification of 2-hydroxyglutarate within infiltrating gliomas harboring mutations in the genes for the isocitrate dehydrogenases. For other tumors, such as medulloblastoma, imaging can demonstrate characteristic patterns that correlate with particular disease subtypes. The purpose of this article is to review the changes to the WHO brain tumor classification system that are most pertinent to radiologists. ©RSNA, 2017.

  2. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape.

    Science.gov (United States)

    Gajjar, Amar; Bowers, Daniel C; Karajannis, Matthias A; Leary, Sarah; Witt, Hendrik; Gottardo, Nicholas G

    2015-09-20

    Pediatric neuro-oncology has undergone an exciting and dramatic transformation during the past 5 years. This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors and survival of patients with these tumors. Advanced genomic analysis of the entire spectrum of pediatric brain tumors has heralded an era in which stakeholders in the pediatric neuro-oncology community are being challenged to reconsider their current research and diagnostic and treatment strategies. The incorporation of this new information into the next-generation treatment protocols will unleash new challenges. This review succinctly summarizes the key advances in our understanding of the common pediatric brain tumors (ie, medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma, and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid tumor and CNS primitive neuroectodermal tumor). The potential impact of this new information on future clinical protocols also is discussed. Cutting-edge genomics technologies and the information gained from such studies are facilitating the identification of molecularly defined subgroups within patients with particular pediatric brain tumors. The number of evaluable patients in each subgroup is small, particularly in the subgroups of rare diseases. Therefore, international collaboration will be crucial to draw meaningful conclusions about novel approaches to treating pediatric brain tumors. © 2015 by American Society of Clinical Oncology.

  3. Targeting c-Met receptor overcomes TRAIL-resistance in brain tumors.

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    Wanlu Du

    Full Text Available Tumor necrosis factor related apoptosis-inducing ligand (TRAIL induced apoptosis specifically in tumor cells. However, with approximately half of all known tumor lines being resistant to TRAIL, the identification of TRAIL sensitizers and their mechanism of action become critical to broadly use TRAIL as a therapeutic agent. In this study, we explored whether c-Met protein contributes to TRAIL sensitivity. We found a direct correlation between the c-Met expression level and TRAIL resistance. We show that the knock down c-Met protein, but not inhibition, sensitized brain tumor cells to TRAIL-mediated apoptosis by interrupting the interaction between c-Met and TRAIL cognate death receptor (DR 5. This interruption greatly induces the formation of death-inducing signaling complex (DISC and subsequent downstream apoptosis signaling. Using intracranially implanted brain tumor cells and stem cell (SC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that SC expressing a potent and secretable TRAIL (S-TRAIL have a significant anti-tumor effect in mice bearing c-Met knock down of TRAIL-resistant brain tumors. To our best knowledge, this is the first study that demonstrates c-Met contributes to TRAIL sensitivity of brain tumor cells and has implications for developing effective therapies for brain tumor patients.

  4. Robust brain ROI segmentation by deformation regression and deformable shape model.

    Science.gov (United States)

    Wu, Zhengwang; Guo, Yanrong; Park, Sang Hyun; Gao, Yaozong; Dong, Pei; Lee, Seong-Whan; Shen, Dinggang

    2018-01-01

    We propose a robust and efficient learning-based deformable model for segmenting regions of interest (ROIs) from structural MR brain images. Different from the conventional deformable-model-based methods that deform a shape model locally around the initialization location, we learn an image-based regressor to guide the deformable model to fit for the target ROI. Specifically, given any voxel in a new image, the image-based regressor can predict the displacement vector from this voxel towards the boundary of target ROI, which can be used to guide the deformable segmentation. By predicting the displacement vector maps for the whole image, our deformable model is able to use multiple non-boundary predictions to jointly determine and iteratively converge the initial shape model to the target ROI boundary, which is more robust to the local prediction error and initialization. In addition, by introducing the prior shape model, our segmentation avoids the isolated segmentations as often occurred in the previous multi-atlas-based methods. In order to learn an image-based regressor for displacement vector prediction, we adopt the following novel strategies in the learning procedure: (1) a joint classification and regression random forest is proposed to learn an image-based regressor together with an ROI classifier in a multi-task manner; (2) high-level context features are extracted from intermediate (estimated) displacement vector and classification maps to enforce the relationship between predicted displacement vectors at neighboring voxels. To validate our method, we compare it with the state-of-the-art multi-atlas-based methods and other learning-based methods on three public brain MR datasets. The results consistently show that our method is better in terms of both segmentation accuracy and computational efficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Science.gov (United States)

    Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  6. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Directory of Open Access Journals (Sweden)

    Daniel C Stewart

    Full Text Available While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  7. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

    Science.gov (United States)

    Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

  8. Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate.

    Science.gov (United States)

    Jiang, Z; Piao, D; Bartels, K E; Holyoak, G R; Ritchey, J W; Ownby, C L; Rock, K; Slobodov, G

    2011-12-01

    The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (StO2) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi-spectral detection at 705_nm, 785_nm and 808_nm rendered measurements of [HbT] and StO2. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63-day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day-63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra-lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate.

  9. [Cognitive functions and personality traits in patients with brain tumors: the role of lesion localization].

    Science.gov (United States)

    Razumnikova, O M; Perfil'ev, A M; Stupak, V V

    2014-01-01

    Personality traits and cognitive functions were studied depending on a tumor localization in the brain in 21 neurosurgical patients and the results were compared with a control group. In patients with brain damage, mostly affected were personality traits associated with emotion regulation and social interaction (neuroticism, psychoticism and social conformity). Increases in psychoticism and decreases in neuroticism were more expressed in patients with a left-hemisphere localization of tumors. The tumor-induced decrease in cognitive abilities was more presented in performing figurative tasks and less in verbal ones. Verbal functions were more decreased in the group with frontal localization of tumor compared to that with parietal localization.

  10. Endogenous expression of CD80 co-stimulatory molecule facilitates in vivo tumor regression of oral squamous carcinoma.

    Science.gov (United States)

    Thomas, Giovana R; Wen, Judy

    2006-01-01

    Most tumor tissues, especially those of non-hematopoietic origin, do not express CD80 co-stimulatory molecules, possibly as a mechanism to evade immune surveillance. The objective of this study was to determine whether abundant endogenous CD80 expression on oral squamous cell carcinoma (SCC) early during tumor progression can facilitate immune elimination and reverse immune tolerance. The growth of regressor and progressor oral SCC lines with differing endogenous CD80 expression were examined in immune-competent and -deficient mice. Immune effectors were determined by T-cell depletion experiments and immunohistochemistry. Our studies show regression of early tumor growth when immunocompetent animals are inoculated with oral SCC progressor cell lines expressing abundant endogenous CD80. The CD80-induced antitumor response was due largely to induced T-cell responses. Our findings suggest that inadequate CD80 expression during early oral SCC formation may contribute to the escape of tumors from immune elimination. This information can be useful in the design of new approaches to generate more effective immunotherapy against this disease.

  11. NC-03POLYMORPHISMS IN THE COMT, BDNF AND DTNBP1 GENES AND COGNITIVE FUNCTIONS IN PATIENTS WITH BRAIN TUMORS

    Science.gov (United States)

    Correa, Denise; Satagopan, Jaya; Baser, Raymond; Cheung, Kenneth; DeAngelis, Lisa; Orlow, Irene

    2014-01-01

    BACKGROUND: Cognitive dysfunction is prevalen among brain tumor patients treated with radiotherapy (RT) and chemotherapy (CT). However, little is known about genetic risk factors that may moderate their vulnerability for developing cognitive impairment. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in three genes, Catechol-O-Methyl-Transferase (COMT), Brain-Derived-Neurotrophic-Factor (BDNF), and dystrobrevin binding protein 1 (DTNBP1), and cognitive functions in brain tumor survivors. METHODS: One hundred and fifty brain tumor patients participated in the study: ninety had been treated with RT ± CT, fifty-seven had CT alone, and three had no therapy. All Patients completed a battery of neuropsychological tests of attention, executive functions and memory, and provided a blood sample. Genotyping of SNPs in the BDNF (n = 9), COMT (n = 17) and DTNBP1 (n = 7) genes was performed. RESULTS: Linear regressions with stepwise backward elimination of SNPs based on change in AIC criterion, adjusting for age, education, and treatment type indicated a significant (p< 0.05) association between the COMT SNP rs4680 (Val158Met) and cognitive function, with lower working memory scores in homozygotes (G/G) and higher executive function and delayed recall scores in heterozygotes (A/G). Five additional SNPs in the COMT gene were significantly associated with lower scores in attention and executive functions. There were significant associations among five SNPs in the BDNF gene and lower performance in executive function, learning and delayed recall. Four SNPs in the DTNBP1 gene were associated with attention and memory scores. CONCLUSION: The findings suggest that in brain tumor patients, cognitive outcome may be differentially affected by polymorphisms in genes previously associated with executive and memory functions in healthy individuals and other clinical populations. Further work is underway to quantify the variation in cognitive outcomes

  12. The role of Intravenous Levetiracetam in Treatment of Seizures in Brain Tumor Patients

    Directory of Open Access Journals (Sweden)

    Ekokobe eFonkem

    2013-10-01

    Full Text Available Levetiracetam, tradename Keppra, is a new second generation antiepileptic drug that is being used increasingly in brain tumor patients. In patients suffering with brain tumors, seizures are one of the leading neurologic complications seen in more than 30% of patients. Levetiracetam is a pyrollidine-derivative drug, which has a unique mechanism of action. Unlike other antiepileptic drugs, Levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting calcium release. Brain tumor patients are frequently on chemotherapy or other drugs that induce cytochrome P450, causing significant drug interactions. However, levetiracetam does not induce the P450 system and does not exhibit any relevant drug interactions. Intravenous delivery is as bioavailable as the oral medication allowing it to be used in emergency situations. Levetiracetam is an attractive option for brain tumor patients suffering from seizures, but also can be used prophylactically in patients with brain tumors or patients undergoing neurological surgery. Emerging studies have also demonstrated that levetiracetam can increase the sensitivity of Glioblastoma tumors to the chemotherapy drug Temozolomide. Levetiracetam is a safe alternative to conventional Antiepileptic drugs and an emerging tool for brain tumor patients combating seizures.

  13. Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy

    Science.gov (United States)

    Smith, Jenessa B; Lanitis, Evripidis; Dangaj, Denarda; Buza, Elizabeth; Poussin, Mathilde; Stashwick, Caitlin; Scholler, Nathalie; Powell, Daniel J

    2016-01-01

    B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6–8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo. PMID:27439899

  14. Magnetic resonance imaging tumor regression shrinkage patterns after neoadjuvant chemotherapy in patients with locally advanced breast cancer: Correlation with tumor biological subtypes and pathological response after therapy.

    Science.gov (United States)

    Ballesio, Laura; Gigli, Silvia; Di Pastena, Francesca; Giraldi, Guglielmo; Manganaro, Lucia; Anastasi, Emanuela; Catalano, Carlo

    2017-03-01

    The objective of this study is to analyze magnetic resonance imaging shrinkage pattern of tumor regression after neoadjuvant chemotherapy and to evaluate its relationship with biological subtypes and pathological response. We reviewed the magnetic resonance imaging studies of 51 patients with single mass-enhancing lesions (performed at time 0 and at the II and last cycles of neoadjuvant chemotherapy). Tumors were classified as Luminal A, Luminal B, HER2+, and Triple Negative based on biological and immunohistochemical analysis after core needle biopsy. We classified shrinkage pattern, based on tumor regression morphology on magnetic resonance imaging at the II cycle, as concentric, nodular, and mixed. We assigned a numeric score (0: none; 1: low; 2: medium; 3: high) to the enhancement intensity decrease. Pathological response on the surgical specimen was classified as complete (grade 5), partial (grades 4-3), and non-response (grades 1-2) according to Miller and Payne system. Fisher test was used to relate shrinkage pattern with biological subtypes and final pathological response. Seventeen patients achieved complete response, 25 partial response, and 9 non-response. A total of 13 lesions showed nodular pattern, 20 concentric, and 18 mixed. We found an association between concentric pattern and HER2+ (p < 0.001) and mixed pattern and Luminal A lesions (p < 0.001). We observed a statistical significant correlation between concentric pattern and complete response (p < 0.001) and between mixed pattern and non-response (p = 0.005). Enhancement intensity decrease 3 was associated with complete response (p < 0.001). Shrinkage pattern and enhancement intensity decrease may serve as early response indicators after neoadjuvant chemotherapy. Shrinkage pattern correlates with tumor biological subtypes.

  15. Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

    Science.gov (United States)

    Wrobel, Jagoda K; Wolff, Gretchen; Xiao, Rijin; Power, Ronan F; Toborek, Michal

    2016-08-01

    Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

  16. Boosted regression trees, multivariate adaptive regression splines and their two-step combinations with multiple linear regression or partial least squares to predict blood-brain barrier passage: a case study.

    Science.gov (United States)

    Deconinck, E; Zhang, M H; Petitet, F; Dubus, E; Ijjaali, I; Coomans, D; Vander Heyden, Y

    2008-02-18

    The use of some unconventional non-linear modeling techniques, i.e. classification and regression trees and multivariate adaptive regression splines-based methods, was explored to model the blood-brain barrier (BBB) passage of drugs and drug-like molecules. The data set contains BBB passage values for 299 structural and pharmacological diverse drugs, originating from a structured knowledge-based database. Models were built using boosted regression trees (BRT) and multivariate adaptive regression splines (MARS), as well as their respective combinations with stepwise multiple linear regression (MLR) and partial least squares (PLS) regression in two-step approaches. The best models were obtained using combinations of MARS with either stepwise MLR or PLS. It could be concluded that the use of combinations of a linear with a non-linear modeling technique results in some improved properties compared to the individual linear and non-linear models and that, when the use of such a combination is appropriate, combinations using MARS as non-linear technique should be preferred over those with BRT, due to some serious drawbacks of the BRT approaches.

  17. Tumor cell endocytosis imaging facilitates delineation of the glioma-brain interface.

    Science.gov (United States)

    Zimmer, C; Wright, S C; Engelhardt, R T; Johnson, G A; Kramm, C; Breakefield, X O; Weissleder, R

    1997-01-01

    We describe a method for measuring tumor cell endocytosis in vivo and provide the anatomic correlate of this tumor cell function using a superparamagnetic and histologically detectable marker for cell uptake (MION). Rats (n = 22) were intrahemispherically implanted with a thymidine kinase (TK)-positive 9L gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and underwent MR imaging ex vivo at near-microscopic resolution (isotropic voxel size of 86 microm, 9.4 T) prior to histologic processing. The imaging probe accumulated within tumor cells adjacent to the hyperpermeable tumor-brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has potential research and clinical implications for delineating the tumor-brain interface prior to therapy and/or for providing a rational basis for imaging nanocolloid drug delivery to solid tumors.

  18. Emerging Techniques in Brain Tumor Imaging: What Radiologists Need to Know

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Minjae; Kim, Ho Sung [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505 (Korea, Republic of)

    2016-11-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response.

  19. Analysis of Brain Tumors Due to the Usage of Mobile Phones

    Directory of Open Access Journals (Sweden)

    SOOBIA SAEED

    2017-07-01

    Full Text Available The impact of cellular phone radiation on human health is the subject of current mindfulness and is an outcome of the huge increase in phone usage throughout the world. Phones use electromagnetic radiation in the microwave range. The issue is associated with wireless use for 50 minutes and above. The excessive use of mobile phone may cause brain tumors. Nowadays the most commonly developed brain tumor type is GBM (Glioblastoma in multiform and Malignant Astrocytoma. In this paper, we focus on the causes of brain tumor (cancer due to the cell phone as this increase in glucose metabolism. The aim of the study is to address the aforementioned problems associated with the cell phone. MATLAB programming to detect a brain tumor has been used. We have conducted MRI (Magnetic Resonance Imaging study to get the best images and results.

  20. Surviving a brain tumor in childhood: impact on family functioning in adolescence

    NARCIS (Netherlands)

    Beek, Laura; Schappin, Renske; Gooskens, Rob; Huisman, Jaap; Jongmans, Marian

    2015-01-01

    OBJECTIVE: To investigate family functioning in families with an adolescent survivor of a pediatric brain tumor. We explored whether adolescent, parent, disease and treatment factors, and demographic characteristics predicted family functioning. METHODS: In this cross-sectional study, 45 adolescent

  1. Emerging techniques in brain tumor imaging: What radiologists need to know

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Jae; Kim, Ho Sung [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2016-09-15

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response.

  2. Targeting c-Met receptor overcomes TRAIL-resistance in brain tumors

    National Research Council Canada - National Science Library

    Du, Wanlu; Uslar, Liubov; Sevala, Sindhura; Shah, Khalid

    2014-01-01

    .... We show that the knock down c-Met protein, but not inhibition, sensitized brain tumor cells to TRAIL-mediated apoptosis by interrupting the interaction between c-Met and TRAIL cognate death receptor (DR) 5...

  3. Targeting c-Met Receptor Overcomes TRAIL-Resistance in Brain Tumors: e95490

    National Research Council Canada - National Science Library

    Wanlu Du; Liubov Uslar; Sindhura Sevala; Khalid Shah

    2014-01-01

    .... We show that the knock down c-Met protein, but not inhibition, sensitized brain tumor cells to TRAIL-mediated apoptosis by interrupting the interaction between c-Met and TRAIL cognate death receptor (DR) 5...

  4. Primary brain tumors and posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Kamiya-Matsuoka, Carlos; Cachia, David; Olar, Adriana; Armstrong, Terri S; Gilbert, Mark R

    2014-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBTs). The aim of this study was to analyze the clinicoradiological features and report the clinical outcomes of PRES in PBT patients. We identified 4 cases with PBT who developed PRES at MD Anderson Cancer Center (MDACC) between 2012 and 2014. Clinical and radiological data were abstracted from their records. In addition, we also solicited 8 cases from the literature. The median age at PRES onset was 19 years, male-to-female ratio was 1:1, and the syndrome occurred in patients with ependymoma (n = 4), glioblastoma (n = 3), diffuse intrinsic pontine glioma (DIPG; n = 3), juvenile pilocytic astrocytoma (n = 1), and atypical meningioma (n = 1). Two glioblastomas and 2 DIPG cases received bevacizumab and vandetanib before the onset of symptoms, respectively. The most common clinical presentation was seizures (n = 7). Three MDACC patients recovered completely in 3-4 weeks after the onset of symptoms. One patient died due to active cancer and several comorbidities including PRES. Hypertension seems to be the most important coexisting risk factor for development of PRES; however, the potential effects of chemotherapeutic agents in the pathogenesis of PRES should also be examined. The clinicoradiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. PRES must be considered as part of the differential diagnosis in patients with PBTs presenting with seizures or acute encephalopathy.

  5. Hierarchical design of a polymeric nanovehicle for efficient tumor regression and imaging

    Science.gov (United States)

    An, Jinxia; Guo, Qianqian; Zhang, Peng; Sinclair, Andrew; Zhao, Yu; Zhang, Xinge; Wu, Kan; Sun, Fang; Hung, Hsiang-Chieh; Li, Chaoxing; Jiang, Shaoyi

    2016-04-01

    Effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we designed a hierarchical polymeric nanoparticle structure for anti-cancer chemotherapy delivery by utilizing state-of-the-art polymer chemistry and co-assembly techniques. This novel structural design combines the most desired merits for drug delivery in a single particle, including a long in vivo circulation time, inhibited non-specific cell uptake, enhanced tumor cell internalization, pH-controlled drug release and simultaneous imaging. This co-assembled nanoparticle showed exceptional stability in complex biological media. Benefiting from the synergistic effects of zwitterionic and multivalent galactose polymers, drug-loaded nanoparticles were selectively internalized by cancer cells rather than normal tissue cells. In addition, the pH-responsive core retained their cargo within their polymeric coating through hydrophobic interaction and released it under slightly acidic conditions. In vivo pharmacokinetic studies in mice showed minimal uptake of nanoparticles by the mononuclear phagocyte system and excellent blood circulation half-lives of 14.4 h. As a result, tumor growth was completely inhibited and no damage was observed for normal organ tissues. This newly developed drug nanovehicle has great potential in cancer therapy, and the hierarchical design principle should provide valuable information for the development of the next generation of drug delivery systems.Effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we designed a hierarchical polymeric nanoparticle structure for anti-cancer chemotherapy delivery by utilizing state-of-the-art polymer chemistry and co-assembly techniques. This novel structural design combines the most desired merits for drug delivery in a single particle, including a long in vivo circulation time, inhibited non-specific cell uptake

  6. Analysis of Brain Tumors Due to the Usage of Mobile Phones

    OpenAIRE

    SOOBIA SAEED; ASADULLAH SHAIKH; SHABAZ AHMED NOOR

    2017-01-01

    The impact of cellular phone radiation on human health is the subject of current mindfulness and is an outcome of the huge increase in phone usage throughout the world. Phones use electromagnetic radiation in the microwave range. The issue is associated with wireless use for 50 minutes and above. The excessive use of mobile phone may cause brain tumors. Nowadays the most commonly developed brain tumor type is GBM (Glioblastoma) in multiform and Malignant Astrocytoma. In this paper, we focus ...

  7. Neurosurgical virtual reality simulation metrics to assess psychomotor skills during brain tumor resection.

    Science.gov (United States)

    Azarnoush, Hamed; Alzhrani, Gmaan; Winkler-Schwartz, Alexander; Alotaibi, Fahad; Gelinas-Phaneuf, Nicholas; Pazos, Valérie; Choudhury, Nusrat; Fares, Jawad; DiRaddo, Robert; Del Maestro, Rolando F

    2015-05-01

    Virtual reality simulator technology together with novel metrics could advance our understanding of expert neurosurgical performance and modify and improve resident training and assessment. This pilot study introduces innovative metrics that can be measured by the state-of-the-art simulator to assess performance. Such metrics cannot be measured in an operating room and have not been used previously to assess performance. Three sets of performance metrics were assessed utilizing the NeuroTouch platform in six scenarios with simulated brain tumors having different visual and tactile characteristics. Tier 1 metrics included percentage of brain tumor resected and volume of simulated "normal" brain tissue removed. Tier 2 metrics included instrument tip path length, time taken to resect the brain tumor, pedal activation frequency, and sum of applied forces. Tier 3 metrics included sum of forces applied to different tumor regions and the force bandwidth derived from the force histogram. The results outlined are from a novice resident in the second year of training and an expert neurosurgeon. The three tiers of metrics obtained from the NeuroTouch simulator do encompass the wide variability of technical performance observed during novice/expert resections of simulated brain tumors and can be employed to quantify the safety, quality, and efficiency of technical performance during simulated brain tumor resection. Tier 3 metrics derived from force pyramids and force histograms may be particularly useful in assessing simulated brain tumor resections. Our pilot study demonstrates that the safety, quality, and efficiency of novice and expert operators can be measured using metrics derived from the NeuroTouch platform, helping to understand how specific operator performance is dependent on both psychomotor ability and cognitive input during multiple virtual reality brain tumor resections.

  8. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model.

    Directory of Open Access Journals (Sweden)

    Weili Jiang

    Full Text Available Currently, effective and specific diagnostic imaging of brain glioma is a major challenge. Nanomedicine plays an essential role by delivering the contrast agent in a targeted manner to specific tumor cells, leading to improvement in accurate diagnosis by good visualization and specific demonstration of tumor cells. This study investigated the preparation and characterization of a targeted MR contrast agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf-SPIONs, for brain glioma detection. MR imaging showed the obvious contrast change of brain glioma before and after administration of Tf-SPIONs in C6 glioma rat model in vivo on T2 weighted imaging. Significant contrast enhancement of brain glioma could still be clearly seen even 48 h post injection, due to the retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian blue staining. Thus, these results suggest that Tf-SPIONs could be a potential targeting MR contrast agent for the brain glioma.

  9. Retrospective feasibility study of simultaneous integrated boost in cervical cancer using tomotherapy: the impact of organ motion and tumor regression

    Directory of Open Access Journals (Sweden)

    Herrera Fernanda G

    2013-01-01

    Full Text Available Abstract Background Whole pelvis intensity modulated radiotherapy (IMRT is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. Purpose To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB regression and motion during chemo-radiotherapy (CRT for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. Methods and materials Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM was used to evaluate the degree of motion. The Dice’s similarity coefficient (DSC was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. Results The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction

  10. Comparison of resilience in adolescent survivors of brain tumors and healthy adolescents.

    Science.gov (United States)

    Chen, Chin-Mi; Chen, Yueh-Chih; Wong, Tai-Tong

    2014-01-01

    Resilience is essential for the psychological adjustment of adolescents experiencing difficulty. Comparing differences in resilience between adolescent survivors of brain tumors and healthy adolescents may help identify factors related to resilience in adolescents. The purpose of this study was to clarify how illness impacts the normative development of adolescent survivors of brain tumors by comparing them to healthy adolescents in terms of resilience and how it is affected by various health problems. This cross-sectional, case-control study used convenience sampling to recruit 13- to 18-year-old adolescent survivors of brain tumors and healthy adolescents matched by school level, gender, and living area. Data were collected by structured questionnaires. The sample included 60 adolescent survivors and 120 healthy adolescents. Participants in both groups were predominantly male adolescents (63.3%) and junior high school students (55%). The 2 groups did not differ significantly in resilience, but survivors without emotional problems had a higher mean resilience score than did healthy adolescents and survivors with emotional problems (F = 8.65, P adolescent survivors of brain tumors and healthy adolescents. In addition, the impact of emotional problems on resilience was more severe in brain tumor survivors than in healthy adolescents. Our results suggest that pediatric oncology nurses design interdisciplinary school-based interventions to reduce the impact of emotional problems on resilience in both healthy adolescents and those who survived brain tumors.

  11. Model-based hypothesis of gut microbe populations and gut/brain barrier permeabilities in the development of regressive autism.

    Science.gov (United States)

    Downs, Ryan; Perna, Jonathon; Vitelli, Andrew; Cook, Daniel; Dhurjati, Prasad

    2014-12-01

    Regressive autism is a devastating disorder affecting children between the ages of 15-30 months. The disorder is characterized by the loss of social interaction and communication ability following otherwise healthy development. In spite of rising autism prevalence, current detection methods and treatment options for this disease are lacking. Therefore, this study introduces a systems-level model, which suggests that gut microbes and intestinal inflammation influence the onset of regressive autism through increasing gut permeability. This computational model provides a framework for quantitative understanding of how imbalances in populations of gut microbes alters the whole-body and brain distributions of neurotoxins produced by GI tract bacteria. Our results indicate that increased levels of the bacteria Bacteroides vulgatus lead to increased brain levels of propionic acid, a neurotoxin which has been known to cause symptoms characteristic of autism when injected into the brain of rats. Our results further indicate that immune response to virulence factors produced by bacteria in the gut leads to increased systemic levels of inflammatory cytokines, such as IL-1β, which significantly alter the permeability of the gut epithelial layer and the blood-brain barrier. Due to the large size of cytokines, however, we predict the time required for concentrations in the brain to stabilize to be on the order of years. This suggests that treatments preventing autism development could be administered after identifying microbial biomarkers of disease but before debilitating brain inflammation leads to regressive autism progression. Future research extending this work could provide new treatment options and diagnostic techniques to help combat regressive autism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Expression and prognostic value of Oct-4 in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Jensen, Per; Sørensen, M. D.

    2016-01-01

    suggested to have promising potentials as prognostic markers in gliomas. Methodology/Principal Findings: The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade. In total 114 grade II, III and IV...... astrocytic brain tumors were immunohistochemically stained for Oct-4, and the fraction and intensity of Oct-4 positive cells were determined by morphometric analysis of full tumor sections. Oct-4 was expressed in all tumors, and the Oct-4 positive cell fraction increased with tumor grade (p = 0.......045). There was no association between survival and Oct-4 positive cell fraction, neither when combining all tumor grades nor in analysis of individual grades. Oct-4 intensity was not associated with grade, but taking IDH1 status into account we found a tendency for high Oct-4 intensity to be associated with poor prognosis...

  13. Expression of CD44 splice variants in human primary brain tumors

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  14. Predictive value of clinical evaluation in the follow-up of children with a brain tumor

    NARCIS (Netherlands)

    Hew, JM; Fock, JM; Kamps, WA

    Background. During follow-up of children with a brain tumor, traditionally surveillance-imaging studies are done in addition to clinical evaluations, The purpose of this study was to determine the role of clinical evaluations by a multidisciplinary team for the detection of recurrent tumor.

  15. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  16. Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes.

    Science.gov (United States)

    Robinson, Kristen E; Pearson, Matthew M; Cannistraci, Christopher J; Anderson, Adam W; Kuttesch, John F; Wymer, Kevin; Smith, Samantha E; Park, Sohee; Compas, Bruce E

    2015-01-01

    Pediatric brain tumors are the second most common cancer diagnosis in individuals under age 20 and research has documented significant neurocognitive, psychosocial, and emotional late effects. Associations among these deficits have not been adequately considered and the role of survivors' coping with stress in relation to deficits is unknown. Further, research has yet to examine neurobiological processes related to neurocognitive, psychosocial, and emotional difficulties in survivors through the use of functional neuroimaging. Questionnaire measures and functional neuroimaging were used to examine the neurocognitive, psychosocial, and emotional functioning and coping responses of survivors of pediatric brain tumors (N = 17; age 8-16) and healthy children (N = 15). Survivors experienced elevated levels of psychosocial and behavioral/emotional difficulties relative to healthy controls and normative data. Increases in brain activation in prefrontal and other anterior regions in response to a working memory task were associated with better psychosocial functioning, use of engagement coping strategies, and less use of disengagement coping strategies. Regression analyses suggest coping accounts for a significant portion of the association between brain activation and behavioral/emotional functioning. This study extends late-effects research by examining neurobiological processes associated with psychosocial and emotional difficulties. These findings contribute to our understanding of difficulties in survivors and provide a foundation for research exploring these associations and mediators of deficits in future longitudinal studies.

  17. Steady-state properties of sodium channels from healthy and tumorous human brain

    NARCIS (Netherlands)

    Frenkel, C.; Wartenberg, H. C.; Duch, D. S.; Urban, B. W.

    1998-01-01

    This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and

  18. H-1 chemical shift imaging characterization of human brain tumor and edema

    NARCIS (Netherlands)

    Sijens, PE; Oudkerk, M

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) H-1 chemical shift imaging results at different repetition times (TR = 1500 and 5000 ms; T1: n = 19) and

  19. Quality of life and symptoms in pediatric brain tumor survivors: a systematic review.

    Science.gov (United States)

    Macartney, Gail; Harrison, Margaret B; VanDenKerkhof, Elizabeth; Stacey, Dawn; McCarthy, Patricia

    2014-01-01

    Little is known about the quality of life of children and youth under the age of 20 who have completed treatment for a pediatric brain tumor. This systematic review was conducted to (a) describe the health-related quality of life (HRQL) outcomes in pediatric brain tumor survivors, (b) identify instruments used to measure HRQL, and (c) determine the relationship between symptoms and HRQL. Using a systematic search and review methodology, databases searched included CINAHL, Medline, Embase, and PsycInfo. No date restrictions were used. Search results elicited 485 articles, of which16 met the inclusion criteria. Compared with their healthy peers, pediatric brain tumor survivors did worse on most measures of physical, psychosocial, social, and cognitive domains of HRQL. Compared with other cancer patients, survivors scored themselves significantly lower on the Pediatric Quality of Life Inventory (PedsQL) social functioning scale, and parents of brain tumor survivors reported lower PedsQL social and total functioning scores for their children. Other variables that were associated with decreased HRQL were degree of hypothalamic tumor involvement, osteopenia, need for special education, older age at diagnosis, greater than 1 year since treatment, and radiation treatment. In these studies, pediatric brain tumor survivors fared worse compared with other cancer survivors or healthy peers on several HRQL domains. Only 3 studies explored the relationship between symptoms, including pain or fatigue, and HRQL in pediatric brain tumor survivors. The relationship between symptoms and HRQL was not well elucidated. More research is needed to explore the multidimensional symptom experience and HRQL outcomes in pediatric brain tumor survivors.

  20. Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models.

    Directory of Open Access Journals (Sweden)

    Jinwei Hu

    2010-04-01

    Full Text Available Chemotherapeutic drugs and newly developed therapeutic monoclonal antibodies are adequately delivered to most solid and systemic tumors. However, drug delivery into primary brain tumors and metastases is impeded by the blood-brain tumor barrier (BTB, significantly limiting drug use in brain cancer treatment.We examined the effect of phosphodiesterase 5 (PDE5 inhibitors in nude mice on drug delivery to intracranially implanted human lung and breast tumors as the most common primary tumors forming brain metastases, and studied underlying mechanisms of drug transport. In vitro assays demonstrated that PDE5 inhibitors enhanced the uptake of [(14C]dextran and trastuzumab (Herceptin, a humanized monoclonal antibody against HER2/neu by cultured mouse brain endothelial cells (MBEC. The mechanism of drug delivery was examined using inhibitors for caveolae-mediated endocytosis, macropinocytosis and coated pit/clathrin endocytosis. Inhibitor analysis strongly implicated caveolae and macropinocytosis endocytic pathways involvement in the PDE5 inhibitor-enhanced Herceptin uptake by MBEC. Oral administration of PDE5 inhibitor, vardenafil, to mice with HER2-positive intracranial lung tumors led to an increased tumor permeability to high molecular weight [(14C]dextran (2.6-fold increase and to Herceptin (2-fold increase. Survival time of intracranial lung cancer-bearing mice treated with Herceptin in combination with vardenafil was significantly increased as compared to the untreated, vardenafil- or Herceptin-treated mice (p0.05.These findings suggest that PDE5 inhibitors may effectively modulate BTB permeability, and enhance delivery and therapeutic efficacy of monoclonal antibodies in hard-to-treat brain metastases from different primary tumors that had metastasized to the brain.

  1. Incidence and clinical course of radionecrosis in children with brain tumors. A 20-year longitudinal observational study

    Energy Technology Data Exchange (ETDEWEB)

    Strenger, V.; Lackner, H. [Graz Medical Univ. (Austria). Div. of Pediatric Hematology/Oncology; Mayer, R. [EBG MedAustron GmbH, Wiener Neustadt (Austria). Dept. of Radiotherapy] [and others

    2013-09-15

    Radionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29-20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7 %), 5-131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0-60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO

  2. Operator experience determines performance in a simulated computer-based brain tumor resection task.

    Science.gov (United States)

    Holloway, Terrell; Lorsch, Zachary S; Chary, Michael A; Sobotka, Stanislaw; Moore, Maximillian M; Costa, Anthony B; Del Maestro, Rolando F; Bederson, Joshua

    2015-11-01

    Develop measures to differentiate between experienced and inexperienced neurosurgeons in a virtual reality brain surgery simulator environment. Medical students (n = 71) and neurosurgery residents (n = 12) completed four simulated Glioblastoma multiforme resections. Simulated surgeries took place over four days with intermittent spacing in between (average time between surgeries of 4.77 ± 0.73 days). The volume of tumor removed (cc), volume of healthy brain removed (cc), and instrument path length (mm) were recorded. Additionally, surgical effectiveness (% tumor removed divided by % healthy brain removed) and efficiency (% tumor removed divided by instrument movement in mm) were calculated. Performance was compared (1) between groups, and (2) for each participant over time to assess the learning curve. In addition, the effect of real-time instruction ("coaching") was assessed with a randomly selected group of medical students. Neurosurgery residents removed less healthy brain, were more effective in removing tumor and sparing healthy brain tissue, required less instrument movement, and were more efficient in removing tumor tissue than medical students. Medical students approached the resident level of performance over serial sessions. Coached medical students showed more conservative surgical behavior, removing both less tumor and less healthy brain. In sum, neurosurgery residents removed more tumor, removed less healthy brain, and required less instrument movement than medical students. Coaching modified medical student performance. Virtual Reality brain surgery can differentiate operators based on both recent and long-term experience and may be useful in the acquisition and assessment of neurosurgical skills. Coaching alters the learning curve of naïve inexperienced individuals.

  3. Metronomic photodynamic therapy (mPDT): concepts and technical feasibility in brain tumor

    Science.gov (United States)

    Wilson, Brian C.; Bisland, Stuart K.; Bogaards, Arjen; Lin, Annie; Moriyama, Eduardo H.; Zhang, Kai; Lilge, Lothar D.

    2003-06-01

    The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates over extended periods in order to increase selective tumor cell kill through apoptosis. The focus of the present work is on mPDT treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. In order to produce enough tumor cell kill to be an effective therapy, multiple PDT treatments, such as hyperfractionation or metronomic delivery, are likely requried, based on the levels of apoptosis achieved and model calculations of tumor growth rates. mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery while allowing free movement. In rat models ALA administration via the drinking water has been accomplished at significant doses for up to 10 days, and ex vivo spectrofluorimetry of tumore, normal brain and other tissues post mortem demonstrates a 3-4 increase in the tumor-to-brain concentration of PpIX, without toxicity. Prototype light sources and delivery devices are also shown to be practical, either using a laser diode or light emitting diode (LED) coupled to an implanted optical fiber in the case of the rat model or a directly-implanted LED in rabbits. The combined delivery of both drug and light over an extended period, with survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.

  4. Neuro-Behçet disease mimicking brain tumor: A case report.

    Science.gov (United States)

    Tramontini, Pedro L; Finkelsztejn, Alessandro; Duarte, Juliana Á; Santos, Guilherme T; Roesler, Rafael; Isolan, Gustavo R

    2017-01-01

    Behçet's disease (BD) is an inflammatory multisystem disease with unknown etiology, and consists of a TRIAD comprising recurrent oral ulcers, genital ulcers, and uveitis. In some cases, the disease affects the central nervous system, called Neuro-Behçet Disease (NBD). Few cases of NBD simulating a brain tumor have been previously reported. Here, we describe the case of a 46-year-old male patient with a previous diagnosis of brain tumor who was later diagnosed for BD. This case highlights the importance of differential diagnosis of lesions with tumoral features. Checking for the possibility of NBD may help avoiding biopsy in these types of cases.

  5. Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.

    Science.gov (United States)

    Roddy, Erika; Sear, Katherine; Felton, Erin; Tamrazi, Benita; Gauvain, Karen; Torkildson, Joseph; Buono, Benedict Del; Samuel, David; Haas-Kogan, Daphne A; Chen, Josephine; Goldsby, Robert E; Banerjee, Anuradha; Lupo, Janine M; Molinaro, Annette M; Fullerton, Heather J; Mueller, Sabine

    2016-11-01

    A specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors. In a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age tumor survivors treated with radiation. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Pasteurella Pneumotropica causa la regresión de tumores humanos trasplantados en ratones inmunodeficientes Pasteurella pneumotropica produces regression of human tumors transplanted in immunodeficiency mice

    Directory of Open Access Journals (Sweden)

    Martín Carriquiriborde

    2006-06-01

    divided into 4 groups of 10 animals each was used to perform this study. Group 1: inoculated with the cell line; group 2, with the bacteria; group 3, with the cell line and the bacteria; group 4, as control with no inoculations. Significant differences were observed in tumor growth in groups 1 and 3, infected and not infected with P. pneumotropica. Although this microorganism is non lethal and only opportunistic, the infected animals are to be considered not suitable to be transplanted with the tumor cell line A549 for experimental studies since these bacteria interfere with tumor growth. However, the fact that a growing tumor regresses in the presence of the bacteria is an interesting observation which deserves further exploration in order to elucidate the mechanism involved.

  7. Detection of Hypoxia in Human Brain Tumor Xenografts Using a Modified Comet Assay

    Directory of Open Access Journals (Sweden)

    Jingli Wang

    2003-07-01

    Full Text Available We used the standard comet assay successfully to generate in vitro dose-response curves under oxic and hypoxic conditions. We then made mixtures of cells that had been irradiated with 3 and 9 Gy of X-rays to simulate two subpopulations in a tumor, but efforts to accurately detect and quantify the subpopulations using the standard comet assay were unsuccessful. Therefore, we investigated a modified comet assay to determine whether it could be used for measuring hypoxia in our model systems. U251 MG cells were grown as subcutaneous tumors in athymic mice; U251 MG and U87 MG cells were grown as intracerebral (i.c. tumors in athymic rats. Animals were injected with RSU 1069, irradiated, and euthanized. Tumors and normal brains were removed, and the cells were analyzed using a modified comet assay. Differences in comet tail moment distributions between tumor and contralateral normal brain, using tail moments at either the 25th or 50th percentile in each distribution, were taken as measures of the degree of tumor hypoxia. For U251 MG tumors, there was a positive relationship between tumor size and the degree of hypoxia, whereas preliminary data from U87 MG i.c. tumors showed less hypoxia and no apparent relationship between tumor size and hypoxia.

  8. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  9. Evaluation of health-related quality of life in Lithuanian brain tumor patients using the EORTC brain cancer module

    OpenAIRE

    Bunevičius, Adomas; Tamašauskas, Šarūnas; Tamašauskas, Arimantas; Deltuva, Vytenis Pranas

    2012-01-01

    Background and Objective. Health-related quality of life (HRQoL) is considered an important outcome measure in neuro-oncology. The aim of this study was to evaluate the psychometric properties of the brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) of the European Organization for Research and Treatment of Cancer (EORTC) in Lithuanian brain tumor patients. Material and Methods. One hundred consecutive patients (71% of women; mean age, 58±14 years) admitted for elective brain tum...

  10. Detection of an atypical teratoid rhabdoid brain tumor gene deletion in circulating blood using next-generation sequencing.

    Science.gov (United States)

    Chakravadhanula, Madhavi; Tembe, Waibhav; Legendre, Christophe; Carpentieri, David; Liang, Winnie S; Bussey, Kimberly J; Carpten, John; Berens, Michael E; Bhardwaj, Ratan D

    2014-09-01

    Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient. © The Author(s) 2013.

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

    Science.gov (United States)

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

    2016-11-01

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

  12. Association between resting-state brain network topological organization and creative ability: Evidence from a multiple linear regression model.

    Science.gov (United States)

    Jiao, Bingqing; Zhang, Delong; Liang, Aiying; Liang, Bishan; Wang, Zengjian; Li, Junchao; Cai, Yuxuan; Gao, Mengxia; Gao, Zhenni; Chang, Song; Huang, Ruiwang; Liu, Ming

    2017-10-01

    Previous studies have indicated a tight linkage between resting-state functional connectivity of the human brain and creative ability. This study aimed to further investigate the association between the topological organization of resting-state brain networks and creativity. Therefore, we acquired resting-state fMRI data from 22 high-creativity participants and 22 low-creativity participants (as determined by their Torrance Tests of Creative Thinking scores). We then constructed functional brain networks for each participant and assessed group differences in network topological properties before exploring the relationships between respective network topological properties and creative ability. We identified an optimized organization of intrinsic brain networks in both groups. However, compared with low-creativity participants, high-creativity participants exhibited increased global efficiency and substantially decreased path length, suggesting increased efficiency of information transmission across brain networks in creative individuals. Using a multiple linear regression model, we further demonstrated that regional functional integration properties (i.e., the betweenness centrality and global efficiency) of brain networks, particularly the default mode network (DMN) and sensorimotor network (SMN), significantly predicted the individual differences in creative ability. Furthermore, the associations between network regional properties and creative performance were creativity-level dependent, where the difference in the resource control component may be important in explaining individual difference in creative performance. These findings provide novel insights into the neural substrate of creativity and may facilitate objective identification of creative ability. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [NOVEL STRATEGY IN THE RADIOTHERAPY OF METASTATIC BRAIN TUMORS: SIMULTANEOUS WHOLE BRAIN RADIOTHERAPY AND INTEGRATED STEREOTACTIC RADIOSURGERY].

    Science.gov (United States)

    Kalincsák, Judit; László, Zoltán; Sebestyén, Zsolt; Kovács, Péter; Horváth, Zsolt; Dóczi, Tamás; Mangel László

    2015-11-30

    Treatment of central nervous system (CNS) tumors has always played an important role in development of radiotherapy techniques. Precise patient immobilisation, non-coplanar field arrangement, conformal treatment, arc therapy, radiosurgery, application of image fusion to radiation planning or re-irradiation were first introduced into clinical routine in the treatment of brain tumors. A modern multifunctional radiation instrument, Novalis TX has been installed at the University of Pécs two years ago. New methods, such as real time 3D image guided therapy, dynamic arc therapy and ultra-conformity offer further progress in treatment of CNS tumors. Whole brain irradiation and simultaneous fractionated stereotactic radiosurgery or integrated boost seem to be an optimal method in the treatment of not only soliter or oligo, but even a higher number (4-9) and not typically radiosensitive brain metastases. The new treatment strategy is illustrated by presentation of four case histories. Treatment protocol was completed in all cases. Treatment period of 1.5 to 3 weeks, and treatment time of only a few minutes were not stressful for the patients. A quite remarkable clinical improvement as to general condition of the patients was experienced in three cases. Follow-up images confirmed either remission or a stable disease. Simultaneous whole brain radiotherapy and integrated stereotactic radiosurgery is a reproducible, safe method that offers an effective irradiation with delivery of definitive dosage even in cases with radio-insensitive brain metastasis.

  14. Group independent component analysis and functional MRI examination of changes in language areas associated with brain tumors at different locations.

    Science.gov (United States)

    Wang, Liya; Chen, Dandan; Yang, Xiaofeng; Olson, Jeffrey J; Gopinath, Kaundinya; Fan, Tianning; Mao, Hui

    2013-01-01

    This study investigates the effect of tumor location on alterations of language network by brain tumors at different locations using blood oxygenation level dependent (BOLD) fMRI and group independent component analysis (ICA). BOLD fMRI data were obtained from 43 right handed brain tumor patients. Presurgical mapping of language areas was performed on all 43 patients with a picture naming task. All data were retrospectively analyzed using group ICA. Patents were divided into three groups based on tumor locations, i.e., left frontal region, left temporal region or right hemisphere. Laterality index (LI) was used to assess language lateralization in each group. The results from BOLD fMRI and ICA revealed the different language activation patterns in patients with brain tumors located in different brain regions. Language areas, such as Broca's and Wernicke's areas, were intact in patients with tumors in the right hemisphere. Significant functional changes were observed in patients with tumor in the left frontal and temporal areas. More specifically, the tumors in the left frontal region affect both Broca's and Wernicke's areas, while tumors in the left temporal lobe affect mainly Wernicke's area. The compensated activation increase was observed in the right frontal areas in patients with left hemisphere tumors. Group ICA provides a model free alternative approach for mapping functional networks in brain tumor patients. Altered language activation by different tumor locations suggested reorganization of language functions in brain tumor patients and may help better understanding of the language plasticity.

  15. Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Brink, Carsten, E-mail: carsten.brink@rsyd.dk [Institute of Clinical Research, University of Southern Denmark (Denmark); Laboratory of Radiation Physics, Odense University Hospital (Denmark); Bernchou, Uffe [Institute of Clinical Research, University of Southern Denmark (Denmark); Laboratory of Radiation Physics, Odense University Hospital (Denmark); Bertelsen, Anders [Laboratory of Radiation Physics, Odense University Hospital (Denmark); Hansen, Olfred [Institute of Clinical Research, University of Southern Denmark (Denmark); Department of Oncology, Odense University Hospital (Denmark); Schytte, Tine [Department of Oncology, Odense University Hospital (Denmark); Bentzen, Soren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (United States)

    2014-07-15

    Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.

  16. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  17. Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.

    Science.gov (United States)

    Mangraviti, Antonella; Gullotti, David; Tyler, Betty; Brem, Henry

    2016-10-28

    Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Mobile phones, brain tumors, and the interphone study: where are we now?

    Science.gov (United States)

    Swerdlow, Anthony J; Feychting, Maria; Green, Adele C; Leeka Kheifets, Leeka Kheifets; Savitz, David A

    2011-11-01

    In the past 15 years, mobile telephone use has evolved from an uncommon activity to one with > 4.6 billion subscriptions worldwide. However, there is public concern about the possibility that mobile phones might cause cancer, especially brain tumors. We reviewed the evidence on whether mobile phone use raises the risk of the main types of brain tumor—glioma and meningioma—with a particular focus on the recent publication of the largest epidemiologic study yet: the 13-country Interphone Study. Methodological defcits limit the conclusions that can be drawn from the Interphone study, but its results, along with those from other epidemiologic, biological, and animal studies and brain tumor incidence trends, suggest that within about 10–15 years after first use of mobile phones there is unlikely to be a material increase in the risk of brain tumors in adults. Data for childhood tumors and for periods beyond 15 years are currently lacking. Although there remains some uncertainty, the trend in the accumulating evidence is increasingly against the hypothesis that mobile phone use can cause brain tumors in adults.

  19. Investigation of the Association between Genetic Polymorphism of Microsomal Epoxide Hydrolase and Primary Brain Tumor Incidence

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    2013-01-01

    Full Text Available mEH is a critical biotransformation enzyme that catalyzes the conversion of xenobiotic epoxide substrates into more polar diol metabolites: it is also capable of inactivating a large number of structurally different molecules. Two polymorphisms affecting enzyme activity have been described in the exon 3 and 4 of the mEH gene. The hypothesis of this study is that inherent genetic susceptibility to a primary brain tumor is associated with mEH gene polymorphisms. The polymorphisms of the mEH gene were determined with PCR-RFLP techniques and 255 Turkish individuals. Our results indicate that the frequency of the mEH exon 4 polymorphism (in controls is significantly higher than that of primary brain tumor patients (OR = 1.8, 95% CI = 1.0–3.4. This report, however, failed to demonstrate a significant association between mEH exon 3 polymorphism and primary brain tumor susceptibility in this population. Analysis of patients by both histological types of primary brain tumor and gene variants showed no association, although analysis of family history of cancer between cases and controls showed a statistically significant association (χ2=7.0, P=0.01. Our results marginally support the hypothesis that genetic susceptibility to brain tumors may be associated with mEPHX gene polymorphisms.

  20. Intraoperative fluorescence imaging for personalized brain tumor resection: Current state and future directions

    Directory of Open Access Journals (Sweden)

    Evgenii Belykh

    2016-10-01

    Full Text Available Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical theranostics. In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients, as well as future applications of recent laboratory and translational studies.Methods: Review of the literature.Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-ALA and ICG, less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine can be used for rapid tumor detection and pathological tissue examination. Other emerging agents such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.Conclusion: We are standing on the doorstep of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

  1. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors.

    Science.gov (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D

    2003-02-01

    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  2. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007.

    Science.gov (United States)

    Leece, Rebecca; Xu, Jordan; Ostrom, Quinn T; Chen, Yanwen; Kruchko, Carol; Barnholtz-Sloan, Jill S

    2017-10-19

    Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age. Using data from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer's (IARC) Cancer Incidence in Five Continents X (including over 300 cancer registries), we calculated the age-adjusted incidence rates (AAIR) per 100000 person-years and 95% CIs for brain and other CNS tumors overall and by age groups and histology. There were significant differences in incidence by region. Overall incidence of malignant brain tumors per 100000 person-years in the US was 5.74 (95% CI = 5.71-5.78). Incidence was lowest in Southeast Asia (AAIR = 2.55, 95% CI = 2.44-2.66), India (AAIR = 2.85, 95% CI = 2.78-2.93), and East Asia (AAIR = 3.07, 95% CI = 3.02-3.12). Incidence was highest in Northern Europe (AAIR = 6.59, 95% CI = 6.52-6.66) and Canada (AAIR = 6.53, 95% CI = 6.41-6.66). Astrocytic tumors showed the broadest variation in incidence regionally across the globe. Brain and other CNS tumors are a significant source of cancer-related morbidity and mortality worldwide. Regional differences in incidence may provide clues toward genetic or environmental causes as well as a foundation for broadening knowledge of their epidemiology. Gaining a comprehensive understanding of the epidemiology of malignant brain tumors globally is critical to researchers, public health officials, disease interest groups, and clinicians and contributes to collaborative efforts in future research.

  3. A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

    Science.gov (United States)

    Kempen, Paul J; Kircher, Moritz F; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V; Mellinghoff, Ingo K; Gambhir, Sanjiv S; Sinclair, Robert

    2015-01-01

    The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    2015-07-01

    Full Text Available A relationship between cyclic adenosine 3’, 5’-monophosphate (cAMP levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor risk in individuals with Neurofibromatosis type 1 (NF1. Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.

  5. Comparison of CT and MRI brain tumor imaging using a canine glioma model.

    Science.gov (United States)

    Whelan, H T; Clanton, J A; Wilson, R E; Tulipan, N B

    1988-01-01

    A canine gliosarcoma model was used to study the effectiveness of magnetic resonance imaging (MRI) with gadolinium contrast enhancement in defining the histologic margins of brain tumors. The effectiveness of this technique was compared to conventional computed tomography (CT) using iodinated contrast enhancement. Cultured canine gliosarcoma cells were injected into the left hemisphere of adult mongrel dogs. The dogs developed brain tumors and progressive clinical signs. Serial MRI with and without gadolinium diethylene triamine penta-acetic acid was compared to serial CT with and without sodium iothalamate obtained on the same days. After the final scans, animals were sacrificed; the brains were removed and processed for routine histopathologic study. All tumors were visualized with contrast-enhanced MRI which proved most sensitive. Gadolinium di-ethylene triamine penta-acetic acid caused bright enhancement of tumors in a distribution that consistently corresponded to areas of pathologically proved tumor infiltration. Gross and microscopic autopsy findings correlated better with MRI than with CT which tended to produce poorer resolution and underrepresent the size of viable tumor. Gadolinium-enhanced MRI is more accurate than unenhanced MRI, unenhanced CT, or enhanced CT in defining the histologic margins of tumors.

  6. Pharmacologic perturbation as a potential tool to increase the sensitivity of FDG-PET in the evaluation of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Wong, F.C.L.; Kim, E.E.; Yung, W.K.A. [Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)] [and others

    1994-05-01

    The usefulness of F-18 FDG PET in the study of brain tumors is limited by the high baseline cortical uptake which decreases the contrast of the tumor. Two alternatives to increase the tumor/background contrast have been reported: barbiturate-induced coma and postprandial state. This project evaluates the effects of sedation with diazepam or of oral glucose intake on the brain tumor/background contrast during F-18 FDG PET studies.

  7. Immunohistochemical characterization of spontaneous and acrylonitrile-induced brain tumors in the rat.

    Science.gov (United States)

    Kolenda-Roberts, Holly Meredith; Harris, Nancy; Singletary, Emily; Hardisty, Jerry F

    2013-01-01

    Twenty-eight spontaneously occurring glial tumors (previously diagnosed as astrocytomas, oligodendrogliomas, and gliomas) and eleven granular cell tumors (GCTs) were selected for evaluation using a panel of immunohistochemistry (IHC) stains (Ricinus communis agglutinin type 1 [RCA-1], ionized calcium-binding adapter molecule 1 [Iba-1], OX-6/major immunohistocompatibility complex class II, oligodendrocytes transcription factor 2 [Olig2], glial fibrillary acidic protein [GFAP], S100 beta, glutamine synthetase, neurofilament, proliferating cell nuclear antigen). In addition, nine brain tumors from a 2-year drinking water study for acrylonitrile were obtained from the Acrylonitrile Group, Inc. Based on IHC staining characteristics, Olig2+ oligodendrogliomas were the most commonly diagnosed spontaneous tumor in these animals. Many of the spontaneous tumors previously diagnosed as astrocytomas were RCA-1+, Iba-1+ and negative for GFAP, S100beta, and glutamine synthetase; the diagnosis of malignant microglial tumor is proposed for these neoplasms. Three mixed tumors were identified with Olig2+ (oligodendrocytes) and Iba-1+ (macrophage/microglia) cell populations. The term mixed glioma is not recommended for these tumors, as it is generally used to refer to oligoastrocytomas, which were not observed in this study. GCT were positive for RCA-1 and Iba-1. All acrylonitrile tumors were identified as malignant microglial tumors. These results may indicate that oligodendrogliomas are more common as spontaneous tumors, while acrylonitrile-induced neoplasms are microglial/histiocytic in origin. No astrocytomas (GFAP, S100 beta, and/or glutamine synthetase-positive neoplasms) were observed.

  8. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

    Science.gov (United States)

    Mao, Xiao-Yuan; Dai, Jin-Xiang; Zhou, Hong-Hao; Liu, Zhao-Qian; Jin, Wei-Lin

    2016-01-01

    Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9-mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors. PMID:26993776

  9. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future.

    Science.gov (United States)

    Mao, Xiao-Yuan; Dai, Jin-Xiang; Zhou, Hong-Hao; Liu, Zhao-Qian; Jin, Wei-Lin

    2016-05-31

    Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9-mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors.

  10. Sparse Multi-Task Regression and Feature Selection to Identify Brain Imaging Predictors for Memory Performance

    OpenAIRE

    Wang, Hua; Nie, Feiping; Huang, Heng; Risacher, Shannon; Ding, Chris; Saykin, Andrew J.; Shen, Li

    2011-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive impairment of memory and other cognitive functions, which makes regression analysis a suitable model to study whether neuroimaging measures can help predict memory performance and track the progression of AD. Existing memory performance prediction methods via regression, however, do not take into account either the interconnected structures within imaging data or those among memory scores, which inevitably r...

  11. Systems biology of human epilepsy applied to patients with brain tumors.

    Science.gov (United States)

    Mittal, Sandeep; Shah, Aashit K; Barkmeier, Daniel T; Loeb, Jeffrey A

    2013-12-01

    Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many "systems" in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  12. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  13. Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kato, Y.; Holm, David Alberg; Okollie, B.

    2010-01-01

    detection of drug directly in the tumor can be critically important for accessing, predicting, and eventually improving effectiveness of therapy. In this study, in vivo magnetic resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide (TMZ), in vivo in murine xenotransplants of U87......MG human brain cancer. Dynamic magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent, gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate tumor vascular parameters. Carbon-13-labeled TMZ ([C-13]TMZ, 99%) was intraperitoneally administered at a dose...... experiments demonstrated slower recovery of MRI signal following an intravenous bolus injection of GdDTPA, higher vascular flow and volume obtained by T-2*-weighted MRI, as well as enhanced uptake of the contrast agent in the brain tumor compared with normal brain detected by T-1-weighted MRI. These data...

  14. Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

    Science.gov (United States)

    Hocking, Matthew C.; Hobbie, Wendy L.; Deatrick, Janet A.; Lucas, Matthew S.; Szabo, Margo M.; Volpe, Ellen M.; Barakat, Lamia P.

    2012-01-01

    Many childhood brain tumor survivors experience significant neurocognitive late effects across multiple domains that negatively affect quality of life. A theoretical model of survivorship suggests that family functioning and survivor neurocognitive functioning interact to affect survivor and family outcomes. This paper reviews the types of neurocognitive late effects experienced by survivors of pediatric brain tumors. Quantitative and qualitative data from three case reports of young adult survivors and their mothers are analyzed according to the theoretical model and presented in this paper to illustrate the importance of key factors presented in the model. The influence of age at brain tumor diagnosis, family functioning, and family adaptation to illness on survivor quality of life and family outcomes are highlighted. Future directions for research and clinical care for this vulnerable group of survivors are discussed. PMID:21722062

  15. Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    Aprile, Giuseppe; Casagrande, Mariaelena; De Maglio, Giovanna; Fontanella, Caterina; Rihawi, Karim; Bonotto, Marta; Pisa, Federica E; Tuniz, Francesco; Pizzolitto, Stefano; Fasola, Gianpiero

    2017-01-01

    Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.

  16. [Reconstruction method of language pathways in the preoperative planning of brain tumor surgery].

    Science.gov (United States)

    Yan, Jing; Lu, Junfeng; Cheng, Jingliang; Wu, Jinsong; Zhang, Jie; Wang, Chaoyan; Nie, Yunfei; Pang, Beibei; Liu, Xianzhi

    2015-05-01

    To propose a clinically practical and simple fiber tracking method for language pathways, and to explore its feasibility in preoperative planning for brain tumors adjacent to the language cortex. Diffusion tensor imaging was examined in 18 healthy subjects and 13 patients with brain tumors adjacent to the language cortex between December 2013 and June 2014. The associated fibers of language pathways were reconstructed using a commercial software (Syngo workstation). Firstly, the feasibility of fiber tracking method for language pathways in healthy subjects were studied, and then its application was assessed in patients with brain tumors. The anatomic relationship between tumors and the associated fibers was analyzed. By selecting appropriate regions of interest, the associated fibers in the dorsal pathways (superior longitudinal fasciculus/arcuate fasciculus, including both direct and indirect pathways) and ventral pathways (uncinate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus and inferiorfronto-occipital fasciculus) were reconstructed in all 18 healthy subjects. In patients with brain tumors, the relationship between the tumors and adjacent associated fibers were divided into two types: adjacent associated fibers could be displaced or separated, and involved the superior longitudinal fasciculus/arcuate fasciculus (n=6), middle longitudinal fasciculus (n=4), uncinate fasciculus (n=3), inferior longitudinal fasciculus (n=3) and inferiorfronto-occipital fasciculus (n=2); alternatively, the adjacent associated fibers were infiltrated or destroyed, and involved the inferiorfronto-occipital fasciculus (n=10), uncinate fasciculus (n=8), middle longitudinal fasciculus (n=5), inferior longitudinal fasciculus (n=4) and superior longitudinal fasciculus/arcuate fasciculus (n=3). The associated fibers of language pathways could be visualized rapidly and in real-time by fiber tracking technology based on diffusion tensor imaging. This is

  17. Cortical hemosiderin is associated with seizures in patients with newly diagnosed malignant brain tumors.

    Science.gov (United States)

    Roelcke, Ulrich; Boxheimer, Larissa; Fathi, Ali Reza; Schwyzer, Lucia; Ortega, Marcos; Berberat, Jatta; Remonda, Luca

    2013-12-01

    Hemorrhage is common in brain tumors. Due to characteristic magnetic field changes induced by hemosiderin it can be detected using susceptibility weighted MRI (SWI). Its relevance to clinical syndromes is unclear. Here we investigated the patterns of intra-tumoral SWI positivity (SWI(pos)) as a surrogate for hemosiderin with regard to the prevalence of epilepsy. We report on 105 patients with newly diagnosed supra-tentorial gliomas and brain metastasis. The following parameters were recorded from pre-operative MRI: (1) SWI(pos) defined as dot-like or fine linear signal changes; (2) allocation of SWI(pos) to tumor compartments (contrast enhancement, central hypointensity, non-enhancing area outside contrast-enhancement); (3) allocation of SWI(pos) to include the cortex, or SWI(pos) in subcortical tumor parts only; (4) tumor size on T2 weighted and gadolinium-enhanced T1 images. 80 tumors (76 %) showed SWI(pos) (4/14 diffuse astrocytoma WHO II, 5/9 anaplastic astrocytoma WHO III, 41/46 glioblastoma WHO IV, 30/36 metastasis). The presence of SWI(pos) depended on tumor size but not on patient's age, medication with antiplatelet drugs or anticoagulation. Seizures occurred in 60 % of patients. Cortical SWI(pos) significantly correlated with seizures in brain metastasis (p = 0.044), and as a trend in glioblastoma (p = 0.062). Cortical SWI(pos) may confer a risk for seizures in patients with newly diagnosed brain metastasis and glioblastoma. Whether development of cortical SWI(pos) induced by treatment or by the natural course of tumors also leads to the new onset of seizures has to be addressed in longitudinal studies in larger patient cohorts.

  18. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  19. 3D brain tumor localization and parameter estimation using thermographic approach on GPU.

    Science.gov (United States)

    Bousselham, Abdelmajid; Bouattane, Omar; Youssfi, Mohamed; Raihani, Abdelhadi

    2018-01-01

    The aim of this paper is to present a GPU parallel algorithm for brain tumor detection to estimate its size and location from surface temperature distribution obtained by thermography. The normal brain tissue is modeled as a rectangular cube including spherical tumor. The temperature distribution is calculated using forward three dimensional Pennes bioheat transfer equation, it's solved using massively parallel Finite Difference Method (FDM) and implemented on Graphics Processing Unit (GPU). Genetic Algorithm (GA) was used to solve the inverse problem and estimate the tumor size and location by minimizing an objective function involving measured temperature on the surface to those obtained by numerical simulation. The parallel implementation of Finite Difference Method reduces significantly the time of bioheat transfer and greatly accelerates the inverse identification of brain tumor thermophysical and geometrical properties. Experimental results show significant gains in the computational speed on GPU and achieve a speedup of around 41 compared to the CPU. The analysis performance of the estimation based on tumor size inside brain tissue also presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Preoperative coiling of coexisting intracranial aneurysm and subsequent brain tumor surgery

    Energy Technology Data Exchange (ETDEWEB)

    Park, Keun Young; Kim, Byung Moon; Kim, Dong Joon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-11-15

    Few studies have investigated treatment strategies for brain tumor with a coexisting unruptured intracranial aneurysm (cUIA). The purpose of this study was to evaluate the safety and efficacy of preoperative coiling for cUIA, and subsequent brain tumor surgery. A total of 19 patients (mean age, 55.2 years; M:F = 4:15) underwent preoperative coiling for 23 cUIAs and subsequent brain tumor surgery. Primary brain tumors were meningiomas (n = 7, 36.8%), pituitary adenomas (n = 7, 36.8%), gliomas (n = 3, 15.8%), vestibular schwannoma (n = 1, 5.3%), and Rathke's cleft cyst (n = 1, 5.3%). cUIAs were located at the distal internal carotid artery (n = 9, 39.1%), anterior cerebral artery (n = 8, 34.8%), middle cerebral artery (n = 4, 17.4%), basilar artery top (n = 1, 4.3%), and posterior cerebral artery, P1 segment (n = 1, 4.3%). The outcomes of preoperative coiling of cUIA and subsequent brain tumor surgery were retrospectively evaluated. Single-microcatheter technique was used in 13 cases (56.5%), balloon-assisted in 4 cases (17.4%), double-microcatheter in 4 cases (17.4%), and stent-assisted in 2 cases (8.7%). Complete cUIA occlusion was achieved in 18 cases (78.3%), while residual neck occurred in 5 cases (21.7%). The only coiling-related complication was 1 transient ischemic attack (5.3%). Neurological deterioration did not occur in any patient during the period between coiling and tumor surgery. At the latest clinical follow-up (mean, 29 months; range, 2-120 months), 15 patients (78.9%) had favorable outcomes (modified Rankin Scale, 0-2), while 4 patients (21.1%) had unfavorable outcomes due to consequences of brain tumor surgery. Preoperative coiling and subsequent tumor surgery was safe and effective, making it a reasonable treatment option for patients with brain tumor and cUIA.

  1. Functional characterization of brain tumors: An overview of the potential clinical value

    Energy Technology Data Exchange (ETDEWEB)

    Brunetti, Arturo; Alfano, Bruno; Soricelli, Andrea; Tedeschi, Enrico; Mainolfi, Ciro; Covelli, Eugenio M.; Aloj, Luigi; Panico, Maria Rosaria; Bazzicalupo, Lucio; Salvatore, Marco

    1996-08-01

    Early detection and characterization are still challenging issues in the diagnostic approach to brain tumors. Among functional imaging techniques, a clinical role for positron emission tomography studies with [{sup 18}F]-fluorodeoxyglucose and for single photon emission computed tomography studies with [{sup 201}Tl]-thallium-chloride has emerged. The clinical role of magnetic resonance spectroscopy is still being defined, whereas functional magnetic resonance imaging seems able to provide useful data for presurgical localization of critical cortical areas. Integration of morphostructural information provided by computed tomography and magnetic resonance imaging, with functional characterization and cyto-histologic evaluation of biologic markers, may assist in answering the open diagnostic questions concerning brain tumors.

  2. Occupational exposure to radio frequency/microwave radiation and the risk of brain tumors

    DEFF Research Database (Denmark)

    Berg, Gabriele; Spallek, Jacob; Schüz, Joachim

    2006-01-01

    It is still under debate whether occupational exposure to radio frequency/microwave electromagnetic fields (RF/MW-EMF) contributes to the development of brain tumors. This analysis examined the role of occupational RF/MW-EMF exposure in the risk of glioma and meningioma. A population-based, case....... No significant association between occupational exposure to RF/MW-EMF and brain tumors was found. For glioma, the adjusted odds ratio for highly exposed persons compared with persons not highly exposed was 1.21 (95% confidence interval: 0.69, 2.13); for meningioma, it was 1.34 (95% confidence interval: 0.64, 2...

  3. MR spectroscopy in children: protocols and pitfalls in non-tumorous brain pathology

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Jacques F. [University Children' s Hospital Basel (UKBB), Basel (Switzerland)

    2016-06-15

    Proton nuclear magnetic resonance spectroscopy (MRS) delivers information about cell content and metabolism in a noninvasive manner. The diagnostic strength of MRS lies in its evaluation of pathologies in combination with conventional magnetic resonance imaging (MRI). MRS in children has been most widely used to evaluate brain conditions like tumors, infections, metabolic diseases or learning disabilities and especially in neonates with hypoxic-ischemic encephalopathy. This article reviews some basic theoretical considerations, routine procedures, protocols and pitfalls and will illustrate the range of spectrum alterations occurring in some non-tumorous pediatric brain pathologies. (orig.)

  4. Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

    Science.gov (United States)

    Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

    2014-02-01

    Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

  5. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    Science.gov (United States)

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory.

  6. A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.

    Science.gov (United States)

    Zhao, Xiaomei; Wu, Yihong; Song, Guidong; Li, Zhenye; Zhang, Yazhuo; Fan, Yong

    2018-01-01

    Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning the FCNNs and the CRF-RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice-by-slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. FTIR, Raman, and CARS microscopic imaging for histopathologic assessment of brain tumors

    Science.gov (United States)

    Krafft, Christoph; Bergner, Norbert; Matthäus, Christian; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Dietzek, B.,; Popp, Jürgen

    2010-02-01

    The contribution demonstrates how the molecular contrast of Fourier transform infrared (FTIR), Raman and coherent anti-Stokes Raman scattering (CARS) microscopic imaging can be applied for the histopathological assessment of brain tumors. Human brain tissue specimens were obtained from patients undergoing neurosurgery. Thin sections of control brain tissue from an epilepsy patient and tumor tissue from a meningioma patient were prepared on calciumfluoride slides which were appropriate substrates for data acquisition in transmission and reflection mode. All CARS images correlate well with the FTIR and Raman images. Whereas CARS images were collected within seconds, exposure times were minutes for FTIR imaging and hours for Raman imaging. CARS images in the interval 2750-3000 cm-1 mainly probed spectral contributions of lipids which are important diagnostic markers of brain tumors. It was demonstrated that the CARS profile in the interval 2750-3000 cm-1 differed between the control sample and meningioma. Full spectral information could be extracted from Raman and FTIR images that enabled to distinguish different tissue types in brain tumors. Based on the current results we suggest a complementary application of FTIR, Raman and CARS imaging. FTIR and Raman imaging defines spectral regions and spectral markers that are essential for tissue classification. CARS images at different Stokes shifts or in the multiplex mode probe these spectral descriptors at video-time frame rates.

  8. [Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts].

    Science.gov (United States)

    Zuev, A A; Korotchenko, E N; Ivanova, D S; Pedyash, N V; Teplykh, B A

    aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.

  9. Occurrence of brain tumors in rhesus monkeys exposed to 55-MeV protons

    Science.gov (United States)

    Wood, D. H.; Yochmowitz, M. G.; Hardy, K. A.; Salmon, Y. L.

    Twenty-year observation of monkeys exposed to single doses of high energy protons simulating solar particles revealed that the most prevalent fatal cancers were brain tumors in the group of animals exposed to 55-MeV protons. Of 72 animals (50 males and 22 females) receiving 0.25 to 8.0 Gy total body surface dose, nine developed fatal tumors classified as grade IV astrocytoma or glioblastoma multiforme. The latent period for tumor development ranged from 14 months to 20 years, with a median of 5 years. Doses associated with the tumors were 4.0 to 8.0 Gy. Eight males and one female were affected. Depth-dose determinations suggest that the high incidence of cerebral neoplasia is associated with the Bragg Peak energy distribution of the 55-MeV protons. Comparison of the tumor incidence with that in humans with brain exposures incidental to radiotherapy indicates a high biological effectiveness compared with gamma radiation. Studies are in progress to attempt to replicate the results in rodents and establish a dose-response curve for proton-induced brain tumors.

  10. Anesthetic management for surgery of children with brain tumors: systematic review

    OpenAIRE

    NIKIFOROVA S.S.; A.I. Yakovlev

    2016-01-01

    Aim. Based on publications dedicated to anesthetic management for surgery of children with brain neoplasms we aimed to reveal and summarize the specific features of anesthesia of such patients. Materials and Methods. We performed a systematic review and processed the information from Russian and foreign literature published in 2001-2016. The analysis included patients younger than 18 who had undergone surgical procedures due to brain tumor. Results. The conducted analysis allowed us to classi...

  11. Invasion and Evasion: Investigations on Early Glioblastoma Growth Reveal Two Novel Mechanisms of Brain Tumor Progression

    OpenAIRE

    Baker, Gregory Joseph

    2014-01-01

    As glioma cells infiltrate the brain they associate with various microanatomic structures such as blood vessels and myelinated white matter tracts. How distinct invasion patterns coordinate tumor growth and influence clinical outcomes remains poorly understood. We have investigated how perivascular invasion affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to common...

  12. Fluorescence intensity and bright spot analyses using a confocal microscope for photodynamic diagnosis of brain tumors.

    Science.gov (United States)

    Yoneyama, Takeshi; Watanabe, Tetsuyo; Kagawa, Hiroyuki; Hayashi, Yutaka; Nakada, Mitsutoshi

    2017-03-01

    In photodynamic diagnosis using 5-aminolevulinic acid (5-ALA), discrimination between the tumor and normal tissue is very important for a precise resection. However, it is difficult to distinguish between infiltrating tumor and normal regions in the boundary area. In this study, fluorescent intensity and bright spot analyses using a confocal microscope is proposed for the precise discrimination between infiltrating tumor and normal regions. From the 5-ALA-resected brain tumor tissue, the red fluorescent and marginal regions were sliced for observation under a confocal microscope. Hematoxylin and eosin (H&E) staining were performed on serial slices of the same tissue. According to the pathological inspection of the H&E slides, the tumor and infiltrating and normal regions on confocal microscopy images were investigated. From the fluorescent intensity of the image pixels, a histogram of pixel number with the same fluorescent intensity was obtained. The fluorescent bright spot sizes and total number were compared between the marginal and normal regions. The fluorescence intensity distribution and average intensity in the tumor were different from those in the normal region. The probability of a difference from the dark enhanced the difference between the tumor and the normal region. The bright spot size and number in the infiltrating tumor were different from those in the normal region. Fluorescence intensity analysis is useful to distinguish a tumor region, and a bright spot analysis is useful to distinguish between infiltrating tumor and normal regions. These methods will be important for the precise resection or photodynamic therapy of brain tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Expression and Prognostic Value of Oct-4 in Astrocytic Brain Tumors.

    Science.gov (United States)

    Krogh Petersen, Jeanette; Jensen, Per; Dahl Sørensen, Mia; Winther Kristensen, Bjarne

    2016-01-01

    Glioblastomas are the most frequent type of malignant primary brain tumor with a median overall survival less than 15 months. Therapy resistance of glioblastomas has been attributed to the presence of tumor initiating stem-like cells (TSCs). TSC-related markers have therefore been suggested to have promising potentials as prognostic markers in gliomas. The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade. In total 114 grade II, III and IV astrocytic brain tumors were immunohistochemically stained for Oct-4, and the fraction and intensity of Oct-4 positive cells were determined by morphometric analysis of full tumor sections. Oct-4 was expressed in all tumors, and the Oct-4 positive cell fraction increased with tumor grade (p = 0.045). There was no association between survival and Oct-4 positive cell fraction, neither when combining all tumor grades nor in analysis of individual grades. Oct-4 intensity was not associated with grade, but taking IDH1 status into account we found a tendency for high Oct-4 intensity to be associated with poor prognosis in anaplastic astrocytomas. Double immunofluorescence stainings showed co-localization in the perivascular niches of Oct-4 and two other TSC markers CD133 and nestin in glioblastomas. In some areas Oct-4 was expressed independently of CD133 and nestin. In conclusion, high Oct-4 fraction was associated with tumor malignancy, but seemed to be without independent prognostic influence in glioblastomas. Identification of a potential prognostic value in anaplastic astrocytomas requires additional studies using larger patient cohorts.

  14. Optical guidance for stereotactic brain tumor biopsy procedures: preliminary clinical evaluation (Conference Presentation)

    Science.gov (United States)

    Haj-Hosseini, Neda; Richter, Johan; Milos, Peter; Hallbeck, Martin; Wârdell, Karin

    2017-02-01

    In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.

  15. Brain tumor segmentation using holistically nested neural networks in MRI images.

    Science.gov (United States)

    Zhuge, Ying; Krauze, Andra V; Ning, Holly; Cheng, Jason Y; Arora, Barbara C; Camphausen, Kevin; Miller, Robert W

    2017-10-01

    Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of

  16. Computational Modeling of Medical Images of Brain Tumor Patients for Optimized Radiation Therapy Planning

    DEFF Research Database (Denmark)

    Agn, Mikael

    In brain tumor radiation therapy, the aim is to maximize the delivered radiation dose to the targeted tumor and at the same time minimize the dose to sensitive healthy structures – so-called organs-at-risk (OARs). When planning a radiation therapy session, the tumor and the OARs therefore need...... to be delineated on medical images of the patient’s head, to be able to optimize a radiation dose plan. In clinical practice, the delineation is performed manually with limited assistance from automatic procedures, which is both time-consuming and typically suffers from poor reproducibility. There is, therefore...

  17. [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

    Science.gov (United States)

    Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

    2015-01-01

    Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

  18. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  19. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    Directory of Open Access Journals (Sweden)

    Haveman Jaap

    2007-09-01

    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  20. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts1

    Science.gov (United States)

    Herrmann, Kelsey; Erokwu, Bernadette O.; Johansen, Mette L.; Basilion, James P.; Gulani, Vikas; Griswold, Mark A.; Flask, Chris A.; Brady-Kalnay, Susann M.

    2016-01-01

    Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents. PMID:27084431

  1. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Eric D. Johnson

    2016-12-01

    Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

  2. Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors.

    Science.gov (United States)

    Thomas, Diana L; Doty, Rosalinda; Tosic, Vesna; Liu, Jia; Kranz, David M; McFadden, Grant; Macneill, Amy L; Roy, Edward J

    2011-10-01

    Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8(+) 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.

  3. Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model

    DEFF Research Database (Denmark)

    Sørensen, Maria Rathmann; Holst, Peter J; Steffensen, Maria Abildgaard

    2010-01-01

    Therapeutic vaccination with replication deficient adenovirus expressing a viral antigen linked to invariant chain was recently found to markedly delay the growth of B16.F10 melanomas expressing the same antigen; however, complete regression of the tumors was never observed. Here we show...... that the delay in tumor growth can be converted to complete regression and long-term survival in 30-40% of the mice by a booster vaccination plus combinational treatment with agonistic anti-CD40 monoclonal antibodies (mAb) and anti-CTLA-4 mAb. Regarding the mechanism underlying the improved clinical effect...

  4. Automated detection and quantification of residual brain tumor using an interactive computer-aided detection scheme

    Science.gov (United States)

    Gaffney, Kevin P.; Aghaei, Faranak; Battiste, James; Zheng, Bin

    2017-03-01

    Detection of residual brain tumor is important to evaluate efficacy of brain cancer surgery, determine optimal strategy of further radiation therapy if needed, and assess ultimate prognosis of the patients. Brain MR is a commonly used imaging modality for this task. In order to distinguish between residual tumor and surgery induced scar tissues, two sets of MRI scans are conducted pre- and post-gadolinium contrast injection. The residual tumors are only enhanced in the post-contrast injection images. However, subjective reading and quantifying this type of brain MR images faces difficulty in detecting real residual tumor regions and measuring total volume of the residual tumor. In order to help solve this clinical difficulty, we developed and tested a new interactive computer-aided detection scheme, which consists of three consecutive image processing steps namely, 1) segmentation of the intracranial region, 2) image registration and subtraction, 3) tumor segmentation and refinement. The scheme also includes a specially designed and implemented graphical user interface (GUI) platform. When using this scheme, two sets of pre- and post-contrast injection images are first automatically processed to detect and quantify residual tumor volume. Then, a user can visually examine segmentation results and conveniently guide the scheme to correct any detection or segmentation errors if needed. The scheme has been repeatedly tested using five cases. Due to the observed high performance and robustness of the testing results, the scheme is currently ready for conducting clinical studies and helping clinicians investigate the association between this quantitative image marker and outcome of patients.

  5. Tracking of Brain Tumors using Vision and Neurosonography

    Directory of Open Access Journals (Sweden)

    Rubén Machucho Cadena

    2010-01-01

    Full Text Available We have developed a method to render brain tumours from endoneurosonography. We propose to track an ultrasound probe in successive endoscopic images without relying on an external optic or magnetic tracking system. The probe is tracked using two different methods: one of them based on a generalised Hough transform and the other one based on particle filters. By estimating the pose of the ultrasound probe in several contiguous images, we use conformal geometric algebra to compute the geometric transformations that yield the 3D position of the tumour, which was segmented in the ultrasound image using morphological operators. We use images from brain phantoms to evaluate the performance of the proposed methods, and our results show that they are robust.

  6. Selective acceptance of MHC class I-deficient tumor grafts in the brain

    OpenAIRE

    1988-01-01

    H-2-deficient (H-2-) tumor variants were accepted equally well compared with H-2+ wild-type cells in the brain of syngeneic mice, while the H-2- cells were selectively eliminated when inoculated extracranially. This indicates a specific absence or suppression of the defense against MHC class I-deficient cells in the brain, suggested to be mediated by NK cells. In contrast, T cell-mediated immune reactions could clearly be detected in the brain under the same experimental conditions. This was ...

  7. The value of 11C-methionine PET in the differential diagnosis between brain tumor recurrence and radionecrosis

    NARCIS (Netherlands)

    Glaudemans, Andor W.J.M.; Enting, Roelien H.; Heesters, Martinus; van Rheenen, Ronald; Dierckx, Rudi; Slart, Riemer

    2014-01-01

    C-methionine (MET) positron emission tomography (PET) is one of the most used nuclear imaging modalities in brain tumors. Because of its characteristics, MET-PET should be able to provide us a high detection rate of brain tumors and good lesion delineation. This book chapter provides a clinical

  8. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...

  9. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  10. Intratumoral delivery of CD154 homolog (Ad-ISF35) induces tumor regression: analysis of vector biodistribution, persistence and gene expression.

    Science.gov (United States)

    Melo-Cardenas, J; Urquiza, M; Kipps, T J; Castro, J E

    2012-05-01

    Ad-ISF35 is an adenovirus (Ad) vector that encodes a mouse-human chimeric CD154. Ad-ISF35 induces activation of chronic lymphocytic leukemia (CLL) cells converting them into CLL cells capable of promoting immune recognition and anti-leukemia T-cell activation. Clinical trials in humans treated with Ad-ISF35-transduced leukemia cells or intranodal injection of Ad-ISF35 have shown objective clinical responses. To better understand the biology of Ad-ISF35 and to contribute to its clinical development, we preformed studies to evaluate biodistribution, persistence and toxicity of repeat dose intratumoral administration of Ad-ISF35 in a mouse model. Ad-ISF35 intratumoral administration induced tumor regression in more than 80% of mice bearing A20 tumors. There were no abnormalities in the serum chemistry. Mice receiving Ad-ISF35 presented severe extramedullary hematopoiesis and follicular hyperplasia in the spleen and extramedullary hematopoiesis with lymphoid hyperplasia in lymph nodes. After Ad-ISF35 injection, the vector was found primarily in the injected tumors with a biodistribution pattern that showed a rapid clearance with no evidence of Ad-ISF35 accumulation or persistence in the injected tumor or peripheral organs. Furthermore, pre-existing antibodies against Ad-5 did not abrogate Ad-ISF35 anti-tumor activity. In conclusion, intratumoral administration of Ad-ISF35 induced tumor regression in A20 tumor bearing mice without toxicities and with no evidence of vector accumulation or persistence.

  11. Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression

    NARCIS (Netherlands)

    Muhammad, A.K.M.G.; Candolfi, M.; King, G.D.; Yagiz, K.; Foulad, D.; Mineharu, Y.; Kroeger, K.M.; Treuer, K.A.; Nichols, W.S.; Sanderson, N.S.; Yang, J.; Khayznikov, M.; Rooijen, van N.; Lowenstein, P.R.; Castro, M.G.

    2009-01-01

    Purpose: Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design: We developed a combined treatment

  12. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors

    Science.gov (United States)

    Diaz, Roberto Jose; McVeigh, Patrick Z.; O’Reilly, Meaghan A.; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C.; Rutka, James T.

    2014-01-01

    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50 nm or 120 nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120 nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. PMID:24374363

  13. Significant tumor shift in patients treated with stereotactic radiosurgery for brain metastasis

    Directory of Open Access Journals (Sweden)

    Eline D. Hessen

    2017-02-01

    Conclusion: Our results show that large tumor shifts of brain metastases can occur over time. Because shifts may have a significant impact on the local dose coverage, we recommend minimizing the time between treatment preparation and delivery for Linac based SRS.

  14. Drug and cell encapsulation : Alternative delivery options for the treatment of malignant brain tumors

    NARCIS (Netherlands)

    Bhujbal, Swapnil V.; de Vos, Paul; Niclou, Simone P.

    2014-01-01

    Malignant brain tumors including glioblastoma are incurable cancers. Over the last years a number of promising novel treatment approaches have been investigated including the application of inhibitors of receptor tyrosine kinases and downstream targets, immune-based therapies and anti-angiogenic

  15. Leukemia and brain tumors in Norwegian railway workers, a nested case-control study.

    Science.gov (United States)

    Tynes, T; Jynge, H; Vistnes, A I

    1994-04-01

    In an attempt to assess whether exposure to electromagnetic fields on Norwegian railways induces brain tumors or leukemia, the authors conducted a nested case-control study of railway workers based on incident cases from the Cancer Registry of Norway in a cohort of 13,030 male Norwegian railway workers who had worked on either electric or non-electric railways. The cohort comprised railway line, outdoor station, and electricity workers. The case series comprised 39 men with brain tumors and 52 men with leukemia (follow-up, 1958-1990). Each case was matched on age with four or five controls selected from the same cohort. The exposure of each study subject to electric and magnetic fields was evaluated from cumulative exposure measures based on present measurements and historical data. Limited information on potential confounders such as creosote, solvents, and herbicides was also collected; information on whether the subject had smoked was obtained by interviews with the subjects or work colleagues. The case-control analysis showed that men employed on electric railways, compared with non-electric ones, had an odds ratio for leukemia of 0.70 (adjusted for smoking) and an odds ratio for brain tumor of 0.87. No significant trend was shown for exposure to either magnetic or electric fields. These results do not support an association between exposure to 16 2/3-Hertz electric or magnetic fields and the risk for leukemia or brain tumors.

  16. Brain tumor delineation based on CT and MR imaging. Implications for radiotherapy treatment planning

    NARCIS (Netherlands)

    Heesters, M A; Wijrdeman, H K; Struikmans, H; Witkamp, T; Moerland, M A

    1993-01-01

    This paper deals with the impact MRI may have on radiotherapy treatment planning of brain tumors. The authors analyzed differences in size and position of treatment fields as indicated by three observers (two radiotherapists and one neuroradiologist) using CT or MR based radiotherapy planning

  17. Surviving a brain tumor in childhood : impact on family functioning in adolescence

    NARCIS (Netherlands)

    Beek, Laura; Schappin, R; Gooskens, Rob; Huisman, Jaap; Jongmans, Marian

    ObjectiveTo investigate family functioning in families with an adolescent survivor of a pediatric brain tumor. We explored whether adolescent, parent, disease and treatment factors, and demographic characteristics predicted family functioning. MethodsIn this cross-sectional study, 45 adolescent

  18. Lack of Correlation between Benign Brain Tumors and Markers of Oral Health.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2015-04-01

    Case control studies implicating dental X-rays in the genesis of intracranial meningiomas have yielded conflicting results. To further evaluate what risk, if any, that intracranial meningioma might be associated with dental X-rays, we examined the association of benign brain tumor incidence with the number of dentists and other correlates of oral health in U.S. states and the District of Columbia. We compared these correlations to the association of the same markers of oral health with Alzheimer's death rates. Poor oral health, especially periodontal disease, is a well-established risk factor for dementia. Pearson correlations, number of cases (49, no data from Kansas or Maryland) and significance (2 tailed p values) of benign brain tumor incidence and parameters of oral health are presented. None of the correlations approached statistical significance. In contrast, Alzheimer's deaths by state were negatively correlated with number of dentists and other markers of oral health. Our finding of a total lack of correlation between benign brain tumors and markers of oral health and, by implication, dental X-rays, suggests there may be no relationship between dental X-rays and meningioma or other benign brain tumors. This conclusion is strengthened by our demonstration of the known negative correlation between Alzheimer's and dental care.

  19. Social Skills Training Interventions: A Promising Approach for Children Treated for Brain Tumors

    Science.gov (United States)

    Weinberger, Beverley Slome; Barakat, Lamia P.

    2007-01-01

    As a result of their disease, its treatment, and late effects, children treated for brain tumors are at risk for developing problems in social functioning in terms of social competence and peer acceptance, poor social skills, and social isolation. Despite research suggesting the effectiveness of social skills training interventions in improving…

  20. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Science.gov (United States)

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  1. Magnetic resonance imaging contrast enhancement of brain tumors at 3 tesla versus 1.5 tesla.

    Science.gov (United States)

    Nöbauer-Huhmann, Iris-Melanie; Ba-Ssalamah, Ahmed; Mlynarik, Vladimir; Barth, Markus; Schöggl, Alexander; Heimberger, Karl; Matula, Christian; Fog, Amura; Kaider, Alexandra; Trattnig, Siegfried

    2002-03-01

    To compare the diagnostic efficacy of a standard dose of MRI contrast agent in the evaluation of primary brain tumors and metastases using a high-field 3 tesla MR unit versus a 1.5 tesla MR unit. Sixteen patients with brain tumors were examined at both field strengths using identical axial T1-SE protocols pre- and postcontrast (0.1 mmol/kg gadolinium), and postcontrast coronal 3D GRE with magnetization preparation (MP-RAGE), which was adjusted separately for each field strength. Evaluation of the images was performed quantitatively and, in the case of T1-SE images, also by visual assessment. Tumor-to-brain-contrast after gadolinium administration using statistical evaluation of MP-RAGE scans was significantly higher at 3 tesla (97.5) than at 1.5 tesla (46.3). The same was true for T1-SE sequences (93.0 vs. 72.1). Signal enhancement of the lesions in T1-SE sequences was not significantly different between both field strengths. Administration of a gadolinium contrast agent produces higher contrast between tumor and normal brain at 3 tesla than at 1.5 tesla.

  2. Executive Functions and Social Skills in Survivors of Pediatric Brain Tumor

    Science.gov (United States)

    Wolfe, Kelly R.; Walsh, Karin S.; Reynolds, Nina C.; Mitchell, Frances; Reddy, Alyssa T.; Paltin, Iris; Madan-Swain, Avi

    2012-01-01

    Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper and pencil measures of social skills and real world executive skills. Social functioning was related to a specific aspect of executive functions, i.e., the survivors’ variability in response time, such that inconsistent responding was associated with better parent-report and survivor-report social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed. PMID:22420326

  3. Care for consequences in children treated for leukemia or brain tumor

    NARCIS (Netherlands)

    Aukema, E.J.

    2013-01-01

    This thesis demonstrates that long-term brain tumor survivors suffer from several late effects of their disease and their treatment many years after having been cured. Not only survivors who were treated with surgery and adjuvant therapy, but also survivors who were treated with surgery only can

  4. Molecular characterization of the porcine deleted in malignant brain tumors 1 gene (DMBT1)

    DEFF Research Database (Denmark)

    Haase, Bianca; Humphray, Sean J; Lyer, Stefan

    2006-01-01

    The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play a role in tumorigenesis and pathogen defense. It encodes a protein with multiple scavenger receptor cysteine-rich (SRCR) domains, which are involved in recognition and binding of a broad spectrum of bacterial pathogens...

  5. Kinome Profiling in Pediatric Brain Tumors as a New Approach for Target Discovery

    NARCIS (Netherlands)

    Sikkema, Arend H.; Diks, Sander H.; den Dunnen, Wilfred F. A.; ter Elst, Arja; Scherpen, Frank J. G.; Hoving, Eelco W.; Ruijtenbeek, Rob; Boender, Piet J.; de Wijn, Rik; Kamps, Willem A.; Peppelenbosch, Maikel P.; de Bont, Eveline S. J. M.

    2009-01-01

    Progression in pediatric brain tumor growth is thought to be the net result of signaling through various protein kinase-mediated networks driving cell proliferation. Defining new targets for treatment of human malignancies, without a priori knowledge on aberrant cell signaling activity, remains

  6. Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors

    Science.gov (United States)

    Kheirollahi, Majid; Moodi, Mahdiye; Ashouri, Saeideh; Nikpour, Parvaneh; Kazemi, Mohammad

    2017-01-01

    Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma. Materials and Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues. Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma. Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies. PMID:29142892

  7. SHOCK SYNDROME IN A PATIENT WITH HYPOPITUITARISM DUE TO BRAIN TUMOR

    Directory of Open Access Journals (Sweden)

    Andreja Sinkovič

    2004-04-01

    Full Text Available Background. Shock syndrome is an acute tissue hypoperfusion. Early diagnosis and adequate symptomatic and causal treatment are mandatory. In spite of different etiologies (dehidration, bleeding, heart failure, sepsis, clinical signs and symptomes are similar (hypotension, tachicardia, tachipnoe, pallor, cold and wet skin, oliguria and metabolic acidosis. Rarely, the shock syndrome is the consequence of the adrenal insufficiency due to hypopituitarism caused by brain tumor where early treatment with hydrocortisone is urgent.Methods. This article presents a patient with a shock syndrome and multiorgan failure. Endocrinological testing and brain CT demonstrated an endocrinologically inactive tumor of hypophysis. The tumor was growing into adjacent hypophyseal tissue and causing hypopituitarism with secondary hypothyroidism and adrenal insufficiency and deficit of both gonadotropins and growth hormone.Conclusions. Primary or secondary adrenal insufficiency are among rare causes of shock syndrome. Whenever it is suspected, estimation of serum levels of cortisol and ACTH is necessary and immediate treatment with hydrocortisone should be instituted.

  8. BRAIN TUMOR SEGMENTATION WITH SYMMETRIC TEXTURE AND SYMMETRIC INTENSITY-BASED DECISION FORESTS.

    Science.gov (United States)

    Bianchi, Anthony; Miller, James V; Tan, Ek Tsoon; Montillo, Albert

    2013-04-01

    Accurate automated segmentation of brain tumors in MR images is challenging due to overlapping tissue intensity distributions and amorphous tumor shape. However, a clinically viable solution providing precise quantification of tumor and edema volume would enable better pre-operative planning, treatment monitoring and drug development. Our contributions are threefold. First, we design efficient gradient and LBPTOP based texture features which improve classification accuracy over standard intensity features. Second, we extend our texture and intensity features to symmetric texture and symmetric intensity which further improve the accuracy for all tissue classes. Third, we demonstrate further accuracy enhancement by extending our long range features from 100mm to a full 200mm. We assess our brain segmentation technique on 20 patients in the BraTS 2012 dataset. Impact from each contribution is measured and the combination of all the features is shown to yield state-of-the-art accuracy and speed.

  9. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  10. [fMRI study of the dominant hemisphere for language in patients with brain tumor].

    Science.gov (United States)

    Buklina, S B; Podoprigora, A E; Pronin, I N; Shishkina, L V; Boldyreva, G N; Bondarenko, A A; Fadeeva, L M; Kornienko, V N; Zhukov, V Iu

    2013-01-01

    Paper describes a study of language lateralization of patients with brain tumors, measured by preoperative functional magnetic resonance imaging (fMRI) and comparison results with tumor histology and profile of functional asymmetry. During the study 21 patient underwent fMRI scan. 15 patients had a tumor in the left and 6 in the right hemisphere. Tumors were localized mainly in the frontal, temporal and fronto-temporal regions. Histological diagnosis in 8 cases was malignant Grade IV, in 13 cases--Grade I-III. fMRI study was perfomed on scanner "Signa Exite" with a field strength of 1.5 As speech test reciting the months of the year in reverse order was used. fMRI scan results were compared with the profile of functional asymmetry, which was received with the results of questionnaire Annette and dichotic listening test. Broca's area was found in 7 cases in the left hemisphere, 6 had a tumor Grade I-III. And one patient with glioblastoma had a tumor of the right hemisphere. Broca's area in the right hemisphere was found in 3 patients (2 patients with left sided tumor, and one with right-sided tumor). One patient with left-sided tumor had mild motor aphasia. Bilateral activation in both hemispheres of the brain was observed in 6 patients. All of them had tumor Grade II-III of the left hemisphere. Signs of left-handedness were revealed only in half of these patients. Broca's area was not found in 4 cases. All of them had large malignant tumors Grade IV. One patient couldn't handle program of the research. Results of fMRI scans, questionnaire Annette and dichotic listening test frequently were not the same, which is significant. Bilateral activation in speech-loads may be a reflection of brain plasticity in cases of long-growing tumors. Thus it's important to consider the full range of clinical data in studying the problem of the dominant hemisphere for language.

  11. A survival score for patients with brain metastases from less radiosensitive tumors treated with whole-brain radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Dziggel, L.; Rades, D. [University Hospital Schleswig-Holstein, Department of Radiation Oncology, Luebeck (Germany); Segedin, B.; Podvrsnik, N.H.; Oblak, I. [Institute of Oncology, Division of Radiation Oncology, Ljubljana (Slovenia); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, Arizona (United States)

    2014-01-15

    This study aimed to develop and validate a scoring system to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases from less radiosensitive tumors. The study included data from 176 patients with brain metastasis from renal cell carcinoma, malignant melanoma or colorectal cancer. Patients were divided into a test group (N=88) and a validation group (N=88). In the multivariate analysis of the test group, age, Karnofsky Performance Status and extracranial metastasis were significantly associated with survival. These three factors were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the three scores. According to the total scores - which ranged from 5 to14 points - three prognostic groups were created. The 6-month survival rates in the test group were 11% for 5-8 points (N=47, group A), 38% for 9-11 points (N=29, group B) and 83% for 12-14 points (N=12, group C). In the validation group the 6-month survival rates were 12, 31 and 75%, respectively. Comparisons between the prognostic groups A, B and C of the test group with those of the validation group did not reveal any significant differences. The new scoring system based on three independent prognostic factors can help to estimate the survival of patients with brain metastases from a less radiosensitive tumor. The score appears to be valid and reproducible. (orig.)

  12. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

    Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

  13. Efficacy and toxicity in brain tumor treatment - quantitative Measurements using advanced MRI

    DEFF Research Database (Denmark)

    Ravn, Søren

    2016-01-01

    From the clinical introduction in the 1980s, MRI has grown to become an indispensable brain imaging modality, mainly due to its excellent ability to visualize soft tissues. Morphologically, T1- and T2-weighted brain tumor MRI have been part of routine diagnostic radiology for more than two decades...... was to explore how different advanced MRI techniques could contribute to a higher degree of individualized treatment of brain tumor patients. The thesis is based on three studies in which advanced MRI is used to evaluate the possible role of fMRI in presurgical planning, Diffusion Tensor Imaging (DTI...... and are now being used for presurgical and radiation therapy (RT) planning. More advanced MRI sequences have gained attention. Sequences such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and functional magnetic resonance imaging (fMRI) have entered the clinical world concurrently...

  14. SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Z [East Carolina University, Greenville, NC (United States); Feng, Y [East Carolina Univ, Rockville, MD (United States); Lo, S [Case Western Reserve University, Cleveland, OH (United States); Grecula, J [Ohio State University, Columbus, OH (United States); Mayr, N; Yuh, W [University of Washington, Seattle, WA (United States)

    2015-06-15

    Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) and lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as adaptive

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

    OpenAIRE

    Sanjuán Tomás, Ana; Price, Cathy J.; Mancini, Laura; Josse, Goulven; Grogan, Alice; Yamamoto, Adam K.; Geva, Sharon; Leff, Alex P.; Yousry, Tarek A; Seghier, Mohamed L.

    2013-01-01

    Brain tumors can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI) procedure which enables brain tumor identification from single MR images. Our method rests on (A) a modified segmentation-normalization procedure with an explicit “extra prior” for the tumor and (B) an outlier d...

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

    OpenAIRE

    Sanjuán, A.; Price, C. J.; Mancini, L.; Josse, G.; Grogan, A.; Yamamoto, A. K.; Geva, S.; Leff, A.P.; Yousry, T. A.; Seghier, M.L.

    2013-01-01

    Brain tumors can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI) procedure which enables brain tumor identification from single MR images. Our method rests on (A) a modified segmentation-normalization procedure with an explicit "extra prior" for the tumor and (B) an outlier d...

  17. Cell phones and brain tumors: a review including the long-term epidemiologic data.

    Science.gov (United States)

    Khurana, Vini G; Teo, Charles; Kundi, Michael; Hardell, Lennart; Carlberg, Michael

    2009-09-01

    The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. In the present review, the authors attempt to address the following question: is there epidemiologic evidence for an association between long-term cell phone usage and the risk of developing a brain tumor? Included with this meta-analysis of the long-term epidemiologic data are a brief overview of cell phone technology and discussion of laboratory data, biological mechanisms, and brain tumor incidence. In order to be included in the present meta-analysis, studies were required to have met all of the following criteria: (i) publication in a peer-reviewed journal; (ii) inclusion of participants using cell phones for > or = 10 years (ie, minimum 10-year "latency"); and (iii) incorporation of a "laterality" analysis of long-term users (ie, analysis of the side of the brain tumor relative to the side of the head preferred for cell phone usage). This is a meta-analysis incorporating all 11 long-term epidemiologic studies in this field. The results indicate that using a cell phone for > or = 10 years approximately doubles the risk of being diagnosed with a brain tumor on the same ("ipsilateral") side of the head as that preferred for cell phone use. The data achieve statistical significance for glioma and acoustic neuroma but not for meningioma. The authors conclude that there is adequate epidemiologic evidence to suggest a link between prolonged cell phone usage and the development of an ipsilateral brain tumor.

  18. Demographic and histopathologic profile of pediatric brain tumors: A hospital-based study

    Directory of Open Access Journals (Sweden)

    Harshil C Shah

    2015-01-01

    Full Text Available Background: Very few hospital-based or population-based studies are published in the context to the epidemiologic profile of pediatric brain tumors (PBTs in India and Indian subcontinent. Aim: To study the demographic and histopathologic profile of PBTs according to World Health Organization 2007 classification in a single tertiary health care center in India. Materials and Methods: Data regarding age, gender, topography, and histopathology of 76 pediatric patients (0–19 years with brain tumors operated over a period of 24 months (January-2012 to December-2013 was collected retrospectively and analyzed using EpiInfo 7. Chi-square test and test of proportions (Z-test were used wherever necessary. Results: PBTs were more common in males (55.3% as compared to females (44.7% with male to female ratio of 1.23:1. Mean age was 10.69 years. Frequency of tumors was higher in childhood age group (65.8% when compared to adolescent age group (34.2%. The most common anatomical site was cerebellum (39.5%, followed by hemispheres (22.4%. Supratentorial tumors (52.6% were predominant than infratentorial tumors (47.4%. Astrocytomas (40.8% and embryonal tumors (29.0% were the most common histological types almost contributing more than 2/3rd of all tumors. Craniopharyngiomas (11.8% and ependymomas (6.6% were the third and fourth most common tumors, respectively. Conclusion: Astrocytomas and medulloblastomas are the most common tumors among children and adolescents in our region, which needs special attention from the neurosurgical department of our institute. Demographic and histopathologic profile of cohort in the present study do not differ substantially from that found in other hospital-based and population-based studies except for slight higher frequency of craniopharyngiomas.

  19. Brain tumor segmentation and characterization by pattern analysis of multispectral NMR images.

    Science.gov (United States)

    Soltanian-Zadeh, H; Peck, D J; Windham, J P; Mikkelsen, T

    1998-01-01

    A major problem in tumor treatment planning and evaluation is determination of the tumor extent. This paper presents a pattern analysis methodology for segmentation and characterization of brain tumors from multispectral NMR images. The proposed approach has been used in 15 clinical studies of cerebral tumor patients who have been scheduled for surgical biopsy and resection. The tissue biopsy results, obtained at specific spatial coordinates determined in the analysis, have been utilized to validate the methodology. It was found that in all cases the lesion had extended into normal tissue, at least to the location where the sample was taken. In most cases, the proposed method suggested that the lesion had extended several millimetres beyond the point from where the biopsy sample was taken. In some cases, the extent of the lesion into normal tissue was well beyond the boundary seen on T1- or T2-weighted images. It is concluded that the proposed approach indicates brain tumor infiltration more precisely than what is visualized in the original NMR images and therefore its utilization facilitates proper treatment planning for the cerebral tumor patients.

  20. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    Science.gov (United States)

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR

  1. Brain tumor presenting as somnambulism in an adolescent.

    Science.gov (United States)

    Prashad, Priya S; Marcus, Carole L; Brown, Lawrence W; Dlugos, Dennis J; Feygin, Tamara; Harding, Brian N; Heuer, Gregory G; Mason, Thornton B Alexander

    2013-09-01

    Sleepwalking is typically a benign and self-limited non-rapid eye movement parasomnia of childhood. We describe an unusual 15-year-old boy referred to our sleep center for new-onset sleepwalking. An overnight polysomnogram was normal from a respiratory standpoint, but a concurrent extended electroencephalogram montage showed frequent epileptiform discharges from the right parietal-temporal region and two electroclinical seizures arising from the right-frontal-central-temporal region during sleep. Magnetic resonance imaging scan revealed a right parasagittal parietal region lesion consistent with a low-grade neoplasm, and surgical resection of the lesion demonstrated a right parietal dysembryoplastic neuroepithelial tumor. Complex partial seizures and sleepwalking remitted completely with anticonvulsant therapy following surgery. This patient highlights the differential diagnosis of nocturnal events appearing to be typical parasomnias, especially when they arise abruptly at an older age. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas.

    Science.gov (United States)

    Rivera-Rivera, Paola A; Rios-Lago, Marcos; Sanchez-Casarrubios, Sandra; Salazar, Osman; Yus, Miguel; González-Hidalgo, Mercedes; Sanz, Ana; Avecillas-Chasin, Josué; Alvarez-Linera, Juan; Pascual-Leone, Alvaro; Oliviero, Antonio; Barcia, Juan A

    2017-04-01

    OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training ("prehabilitation"), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27-37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function.

  3. A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors.

    Science.gov (United States)

    Yomo, Shoji; Hayashi, Motohiro; Nicholson, Claire

    2012-08-01

    The purpose of this prospective study is to evaluate the efficacy and limitations of two-session Gamma Knife radiosurgery (GKS) alone for large metastatic brain tumors. Inclusion criteria were as follows: (i) patients with large metastatic brain tumors (volume >15 cm(3) in the supratentorial region or >10 cm(3) in the infratentorial region), and (ii) tumors not causing clinical signs of impending cerebral herniation. Twenty-eight lesions in 27 consecutive patients (18 men and 9 women, age range 32 to 88 years, median age 65 years) were included in this study. The radiosurgical protocol was as follows: 20-30 Gy given in two fractions 3-4 weeks apart. The local tumor control rate and the overall survival rate were calculated by using the Kaplan-Meier method. Median tumor volumes were 17.8 cm(3) at first GKS and 9.7 cm(3) at second GKS. Median follow-up time was 8.9 months. The local control rate was 85 % at 6 months and 61 % at 12 months. The overall survival rate after GKS was 63 % at 6 months and 45 % at 12 months. The 1-year rate of prevention of neurological death was maintained at 78 %. Mean Karnofsky performance status (KPS) improved from 61 [95 % confidence interval (CI), 57-71] at first GKS to 80 (95 % CI, 74-85) at second GKS; the best follow-up mean KPS was 85 (95 % CI, 78-91) (p session GKS for large brain metastases appears to be an effective treatment in terms of both local tumor control and neurological palliation with minimal treatment-related morbidity. These data suggest that two-session GKS could be used as an alternative to surgical resection of large tumors in patients with significant comorbidity and/or at an advanced age. The optimum regimen for dose and fraction schedule remains to be established.

  4. Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography

    DEFF Research Database (Denmark)

    Brink, Carsten; Bernchou, Uffe; Bertelsen, Anders

    2014-01-01

    for other clinical characteristics. RESULTS: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could...... potential use in response adapted personalized radiation therapy is evaluated empirically. METHODS AND MATERIALS: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment...... was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2...

  5. Development of the Japanese version of the Pediatric Quality of Life Inventory™ Brain Tumor Module

    Directory of Open Access Journals (Sweden)

    Terasaki Mizuhiko

    2010-04-01

    Full Text Available Abstract Background The Pediatric Quality of Life Inventory™ (PedsQL™ is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL™ Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL™ Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents. Methods Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children. Results Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70 except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95. Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents. Evaluation of known-groups validity confirmed

  6. Brain Tumor Immunotherapy: What have We Learned so Far?

    Science.gov (United States)

    Van Gool, Stefaan Willy

    2015-01-01

    High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients.

  7. Brain tumor immunotherapy. What have we learned so far ?

    Directory of Open Access Journals (Sweden)

    Stefaan Willy Van Gool

    2015-06-01

    Full Text Available High grade glioma (HGG is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme (GBM patients. The developmental program allows further improvements related to newest scientific insights. Finally we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients.

  8. Impacts of Blood-Brain Barrier in Drug Delivery and Targeting of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2012-02-01

    Full Text Available Introduction: Entry of blood circulating agents into the brain is highly selectively controlled by specific transport machineries at the blood brain barrier (BBB, whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. Methods: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. Results: Brain capillary endothelial cells (BCECs form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics. Conclusion: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.

  9. Conditional Expression of Oncogenic C-RAF in Mouse Pulmonary Epithelial Cells Reveals Differential Tumorigenesis and Induction of Autophagy Leading to Tumor Regression

    Directory of Open Access Journals (Sweden)

    Fatih Ceteci

    2011-11-01

    Full Text Available Here we describe a novel conditional mouse lung tumor model for investigation of the pathogenesis of human lung cancer. On the basis of the frequent involvement of the Ras-RAF-MEK-ERK signaling pathway in human non–small cell lung carcinoma (NSCLC, we have explored the target cell availability, reversibility, and cell type specificity of transformation by oncogenic C-RAF. Targeting expression to alveolar type II cells or to Clara cells, the two likely precursors of human NSCLC, revealed differential tumorigenicity between these cells. Whereas expression of oncogenic C-RAF in alveolar type II cells readily induced multifocal macroscopic lung tumors independent of the developmental state, few tumors with type II pneumocytes features and incomplete penetrance were found when targeted to Clara cells. Induced tumors did not progress and were strictly dependent on the initiating oncogene. Deinduction of mice resulted in tumor regression due to autophagy rather than apoptosis. Induction of autophagic cell death in regressing lung tumors suggests the use of autophagy enhancers as a treatment choice for patients with NSCLC.

  10. SU-F-J-64: Comparison of Dosimetric Robustness Between Proton Therapy and IMRT Plans Following Tumor Regression for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Teng, C; Ainsley, C; Teo, B; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-Neuve (Belgium)

    2016-06-15

    Purpose: In the light of tumor regression and normal tissue changes, dose distributions can deviate undesirably from what was planned. As a consequence, replanning is sometimes necessary during treatment to ensure continued tumor coverage or to avoid overdosing organs at risk (OARs). Proton plans are generally thought to be less robust than photon plans because of the proton beam’s higher sensitivity to changes in tissue composition, suggesting also a higher likely replanning rate due to tumor regression. The purpose of this study is to compare dosimetric deviations between forward-calculated double scattering (DS) proton plans with IMRT plans upon tumor regression, and assesses their impact on clinical replanning decisions. Methods: Ten consecutive locally advanced NSCLC patients whose tumors shrank > 50% in volume and who received four or more CT scans during radiotherapy were analyzed. All the patients received proton radiotherapy (6660 cGy, 180 cGy/fx). Dosimetric robustness during therapy was characterized by changes in the planning objective metrics as well as by point-by-point root-mean-squared differences for the entire PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs) DVHs. Results: Sixty-four pairs of DVHs were reviewed by three clinicians, who requested a replanning rate of 16.7% and 18.6% for DS and IMRT plans, respectively, with a high agreement between providers. Robustness of clinical indicators was found to depend on the beam orientation and dose level on the DVH curve. Proton dose increased most in OARs distal to the PTV along the beam path, but these changes were primarily in the mid to low dose levels. In contrast, the variation in IMRT plans occurred primarily in the high dose region. Conclusion: Robustness of clinical indicators depends where on the DVH curves comparisons are made. Similar replanning rates were observed for DS and IMRT plans upon large tumor regression.

  11. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  12. Plasticity of cognitive functions before and after awake brain tumor surgery

    Directory of Open Access Journals (Sweden)

    Djaina Satoer

    2015-04-01

    Results: P1 and P2 showed opposite preoperative cognitive profiles. P1 obtained normal cognitive results and P2 had clinically significant impairments in all cognitive domains, (language, memory, attentional and executive deficits (z-score ≥-1.50. P3 and P4 also demonstrate opposite preoperative profiles. P4 obtained intact cognitive results, whereas P3 was impaired in memory and executive functions (z-score ≥-1.50. Intraoperatively, in both P3 and P4 positive language sites were found (left inferior frontal gyrus and left parietal lobe. At 3 months postoperatively, P3 presented language deficits followed by recovery at 12 months, whereas P4 appeared to have recovered at 3 months postoperatively from the observed premorbid impairments in memory and executive functioning (z-score <-1.50. Pathological examination revealed a slow growing brain tumor (low-grade in P1 and P3 and a fast growing brain tumor (high-grade in P2 and P4. Conclusion: In patients with similar brain tumor localizations, we found distinct cognitive profiles, possibly affected by different neural plasticity processes. Preoperatively, a favorable plasticity effect on cognition was found in P1 (temporoparietal area, potentially affected by tumor grade. Preserved cognitive functions was possibly facilitated by the slow growth rate of a low-grade tumor allowing functional reorganization (Mandonnet et al., 2003. However, P2 with a brain tumor in the same area showed preoperative deficits in several domains (language, memory and attention/executive functions. A faster growth rate of a high-grade tumor could have more aggressively affected cognition. In P3 and P4 with the same localization (insula, we found a different effect on the cognitive recovery process; at short term (3 months, improvement of the preoperatively observed cognitive impairments in a low-grade tumor P3, whereas a more gradual functional reorganization was found in language (3-12 months in P4, a high-grade tumor, contrasting Habets

  13. Socioeconomic Disparities in the Quality of Life in Children with Cancer or Brain Tumors: The Mediating Role of Family Factors

    Science.gov (United States)

    Litzelman, Kristin; Barker, Emily; Catrine, Kristine; Puccetti, Diane; Possin, Peggy; Witt, Whitney P

    2012-01-01

    Objective This study aimed to determine if and to what extent: (1) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (2) family functioning and burden mediate the relationship between socioeconomic status and children’s QOL. Methods In this cross-sectional study, parents of children ages 2–18 with (n=71) and without (n=135) cancer or brain tumors completed in-person interviewer-assisted surveys assessing sociodemographics (including income and parental education), child QOL (measure: PedsQL), family functioning (measure: FACES IV) and burden (measure: Impact on the Family Scale). For children with cancer, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between income and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. Results In multivariate analyses, the effect of income differed by cancer status; lower income was associated with worse QOL in children with cancer, but not among healthy children. Among children with cancer, this relationship was significantly attenuated by family burden. Conclusions Significant socioeconomic disparities exist in the QOL of children with cancer. Family factors partially explain the relationship between low income and poor QOL outcomes among these children. Lower income families may have fewer resources to cope with their child’s cancer. Increased support, monitoring, and referrals to reduce burden for these families may lead to improved QOL in children with cancer. PMID:22645071

  14. Socioeconomic disparities in the quality of life in children with cancer or brain tumors: the mediating role of family factors.

    Science.gov (United States)

    Litzelman, Kristin; Barker, Emily; Catrine, Kristine; Puccetti, Diane; Possin, Peggy; Witt, Whitney P

    2013-05-01

    This study aimed to determine if and to what extent (i) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (ii) family functioning and burden mediate the relationship between socioeconomic status and children's QOL. In this cross-sectional study, parents of children ages 2-18 with (n = 71) and without (n = 135) cancer or brain tumors completed in-person interviewer-assisted surveys assessing sociodemographics (including income and parental education), child QOL (measure: PedsQL), family functioning (measure: Family Adaptability and Cohesion Evaluation Scale IV) and burden (measure: Impact on the Family Scale). For children with cancer, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between income and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. In multivariate analyses, the effect of income differed by cancer status; lower income was associated with worse QOL in children with cancer but not among healthy children. Among children with cancer, this relationship was significantly attenuated by family burden. Significant socioeconomic disparities exist in the QOL of children with cancer. Family factors partially explain the relationship between low income and poor QOL outcomes among these children. Lower-income families may have fewer resources to cope with their child's cancer. Increased support, monitoring, and referrals to reduce burden for these families may lead to improved QOL in children with cancer. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Cerebrospinal fluid and serum IL-8, CCL2, and ICAM-1 concentrations in astrocytic brain tumor patients.

    Science.gov (United States)

    Koper, O M; Kamińska, J; Sawicki, K; Reszeć, J; Rutkowski, R; Jadeszko, M; Mariak, Z; Dymicka-Piekarska, V; Kemona, H

    2017-10-30

    The aim of the study was the evaluation of serum and CSF concentrations of CCL2, IL-8, and sICAM-1 in patients with astrocytic tumors as compared to a group of non-tumoral patients. Chemokine concentrations were measured using the ELISA method. Regardless of the parameter tested and the patient group (brain tumor or non-tumoral patients), statistical differences (P < 0.05) were found between concentrations obtained in CSF compared to values obtained in serum for all proteins tested. CSF IL-8 concentrations were significantly elevated in CNS tumor patients as compared to non-tumoral individuals (P = 0.000); serum CCL2 and sICAM-1 concentrations were significantly decreased in CNS tumors in comparison with the comparative group (P = 0.002 and P = 0.026, respectively). Among proteins tested in the serum, a higher area under the ROC curve (AUC) revealed CCL2 compared to sICAM-1 in differentiating subjects with CNS brain tumors from non-tumoral subjects. AUC for CSF IL-8 was higher than for its index (CSF IL-8/serum IL-8). For individual biomarkers (IL-8 and CCL2, sICAM-1), measured in CNS brain tumor patients, the appropriate material, respectively CSF or serum, should be chosen and quantitatively tested. Increased cerebrospinal fluid IL-8 with decreased serum CCL2 create a pattern of biomarkers, which may be helpful in the management of CNS astrocytic brain tumors.

  16. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo.

    Science.gov (United States)

    Wennerberg, Erik; Kremer, Veronika; Childs, Richard; Lundqvist, Andreas

    2015-02-01

    Adoptive infusion of natural killer (NK) cells is being increasingly explored as a therapy in patients with cancer, although clinical responses are thus far limited to patients with hematological malignancies. Inadequate homing of infused NK cells to the tumor site represents a key factor that may explain the poor anti-tumor effect of NK cell therapy against solid tumors. One of the major players in the regulation of lymphocyte chemotaxis is the chemokine receptor chemokine (C-X-C motif) receptor 3 (CXCR3) which is expressed on activated NK cells and induces NK cell migration toward gradients of the chemokine (C-X-C motif) ligand (CXCL9, 10 and 11). Here, we show that ex vivo expansion of human NK cells results in a tenfold increased expression of the CXCR3 receptor compared with resting NK cells (p = 0.04). Consequently, these NK cells displayed an improved migratory capacity toward solid tumors, which was dependent on tumor-derived CXCL10. In xenograft models, adoptively transferred NK cells showed increased migration toward CXCL10-transfected melanoma tumors compared with CXCL10-negative wild-type tumors, resulting in significantly reduced tumor burden and increased survival (median survival 41 vs. 32 days, p = 0.03). Furthermore, administration of interferon-gamma locally in the tumor stimulated the production of CXCL10 in subcutaneous melanoma tumors resulting in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells. Our findings demonstrate the importance of CXCL10-induced chemoattraction in the anti-tumor response of adoptively transferred expanded NK cells against solid melanoma tumors.

  17. Multisession stereotactic radiosurgery for large benign brain tumors of >3cm- early clinical outcomes

    Science.gov (United States)

    Memon, Muhammad Ali; Ahmed, Usman; Saleem, Muhammad Abid; Bhatti, Amer Iqtidar; Ahmed, Naveed; Hashim, Abdul Sattar M.

    2012-01-01

    Objective To evaluate the clinical outcome of linear accelerator based multisession stereotactic radiosurgery (SRS) for large benign brain tumors of >3cm. Methods Between June 2009 and May 2011, 35 patients having large benign brain tumors of >3cm (≥15 cm3) were treated by multisession stereotactic radiosurgery. This retrospective study was carried out at Neurospinal & Medical Institute Karachi. There were 17 (48.6 %) males and 18(51.4 %) females. Median age was 36 years (range: 13-65 years). Median target volume was 49.4 cm3 (range: 15-184 cm3). The median marginal dose was 25 Gy (range: 20–27.5Gy) prescribed to a median 75% isodose line (range: 65-100 %). Median number of 5 fractions were used ranging 3-5 fractions. Results All the patients tolerated treatment very well. 21 (58.3%) patients had remarkable clinical improvement of neurological symptoms, 14 (38.9%) patients had stable symptoms, and only one patient had transient worsening of symptoms. No permanent neurological damage or radiation injury was seen. Radiologically, 9 (25.7%) patients achieved reduction in size of the tumor, 26(74.3 %) patients were having stable disease, and overall control rate was found to be 100 %. Median follow-up time from the end of SRS was 6.4 months (range: 1-22.5months). Conclusion Linear accelerator based multisession stereotactic radiosurgery for large benign brain tumors of >3cm is effective and well tolerated. PMID:29296340

  18. Systematic review of wireless phone use and brain cancer and other head tumors.

    Science.gov (United States)

    Repacholi, Michael H; Lerchl, Alexander; Röösli, Martin; Sienkiewicz, Zenon; Auvinen, Anssi; Breckenkamp, Jürgen; d'Inzeo, Guglielmo; Elliott, Paul; Frei, Patrizia; Heinrich, Sabine; Lagroye, Isabelle; Lahkola, Anna; McCormick, David L; Thomas, Silke; Vecchia, Paolo

    2012-04-01

    We conducted a systematic review of scientific studies to evaluate whether the use of wireless phones is linked to an increased incidence of the brain cancer glioma or other tumors of the head (meningioma, acoustic neuroma, and parotid gland), originating in the areas of the head that most absorb radiofrequency (RF) energy from wireless phones. Epidemiology and in vivo studies were evaluated according to an agreed protocol; quality criteria were used to evaluate the studies for narrative synthesis but not for meta-analyses or pooling of results. The epidemiology study results were heterogeneous, with sparse data on long-term use (≥ 10 years). Meta-analyses of the epidemiology studies showed no statistically significant increase in risk (defined as P cancer or other head tumors from wireless phone use. Analyses of the in vivo oncogenicity, tumor promotion, and genotoxicity studies also showed no statistically significant relationship between exposure to RF fields and genotoxic damage to brain cells, or the incidence of brain cancers or other tumors of the head. Assessment of the review results using the Hill criteria did not support a causal relationship between wireless phone use and the incidence of adult cancers in the areas of the head that most absorb RF energy from the use of wireless phones. There are insufficient data to make any determinations about longer-term use (≥ 10 years). © 2011 Wiley Periodicals, Inc.

  19. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

    Directory of Open Access Journals (Sweden)

    Hangjun Ruan

    1999-11-01

    Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

  20. Headache as a risk factor for neurovascular events in pediatric brain tumor patients.

    Science.gov (United States)

    Kranick, Sarah M; Campen, Cynthia J; Kasner, Scott E; Kessler, Sudha K; Zimmerman, Robert A; Lustig, Robert A; Phillips, Peter C; Beslow, Lauren A; Ichord, Rebecca; Fisher, Michael J

    2013-04-16

    To determine whether severe recurrent headache is a risk factor for neurovascular events in children who received radiation for brain tumors. This is a retrospective cohort study of children with brain tumors who received cranial irradiation at a large tertiary care center, aged 0-21 years at diagnosis, with initial treatment between January 1, 1993 and December 31, 2002, and 2 or more follow-up visits. Patients were considered to have severe recurrent headache if this appeared as a complaint on 2 or more visits. Headaches attributed to tumor progression, shunt malfunction, or infection, or appearing at the end of life, were excluded. Medical records were reviewed for events of stroke or TIA. Of 265 subjects followed for a median of 6.0 years (interquartile range 1.7-9.2 years), stroke or TIA occurred in 7/37 (19%) with severe headaches compared to 6/228 (3%) without these symptoms (hazard ratio 5.3, 95% confidence interval 1.8-15.9, p = 0.003). Adjusting for multiple variables did not remove the significance of this risk. Median time to first neurovascular event for the entire cohort was 4.9 years (interquartile range 1.7-5.5 years). Severe recurrent headache appears to be a risk factor or predictor for subsequent cerebral ischemia in pediatric brain tumor survivors treated with radiation. This finding has clinical implications for both monitoring survivors and targeting a specific population for primary stroke prevention.

  1. Correlation between MR imaging and histopathological findings of cystic metastatic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fukusumi, Akio [Nara Medical Univ., Kashihara (Japan); Iwasaki, Satoru; Ohkawa, Naosumi [and others

    1996-12-01

    To clarify the correlation between the histopathological findings and MR signal intensity of the cyst wall, fifteen cystic metastatic brain tumors of eleven patients were imaged using a 0.5T MR unit just before surgery, and the MRI findings were correlated with the histopathological findings of resected lesions. On T2-weighted images, all cyst walls showed hypointensity. On T1-weighted images, the intensity of the cyst wall could be classified into three groups, compared with the cerebral cortex. Walls with hyperintensity on T1WI (group H; n=6) consisted of ample tumor cells, blood vessels and connective tissues, suggesting viable tumor cells. Iso-intense walls on T1WI (group I; n=3) had abundant reactive glial tissues. Hypointense walls on T1WI (group L; n=5) revealed hemorrhage and/or hemosiderin in the wall, suggesting hemorrhagic necrosis. Thus a good correlation was demonstrated between the MR signal intensities and histopathological findings of cyst walls of cystic metastatic brain tumors. This may contribute not only to more precise diagnosis on MRI but also to more planning for treatment of cystic brain metastases. (author)

  2. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial.

    Science.gov (United States)

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Beissbarth, Tim; Hess, Clemens; Becker, Heinz; Ghadimi, Michael; Mrak, Karl; Merkel, Susanne; Raab, Hans-Rudolf; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2014-05-20

    We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting. © 2014 by American Society of Clinical Oncology.

  3. Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven

    OpenAIRE

    Dings, Ruud P. M.; Van Laar, Emily S.; Webber, Jeremy; Zhang, Yan; Griffin, Robert J.; Waters, Stephen J.; Macdonald, John R.; Mayo, Kevin H.

    2008-01-01

    Combination of chemotherapeutic agents and angiogenesis inhibitors is now commonly employed in the clinic to treat cancer. Here, we used angiostatic agents anginex and 0118, in combination with the chemotherapeutic irofulven, to treat human ovarian tumor xenografts in mice. General linear mixed models were used to statistically analyze tumor growth curves. Overall, combination of a low, non-toxic dose of irofulven with either angiogenesis inhibitor was more effective at inhibiting tumor growt...

  4. Covalent nano delivery systems for selective imaging and treatment of brain tumors.

    Science.gov (United States)

    Ljubimova, Julia Y; Sun, Tao; Mashouf, Leila; Ljubimov, Alexander V; Israel, Liron L; Ljubimov, Vladimir A; Falahatian, Vida; Holler, Eggehard

    2017-04-01

    Nanomedicine is a rapidly evolving form of therapy that holds a great promise for superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nano conjugates for imaging and drug delivery in the brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Increased frontal functional networks in adult survivors of childhood brain tumors

    Directory of Open Access Journals (Sweden)

    Hongbo Chen

    2016-01-01

    Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

  6. Resilience and Coping Strategies Influencing the Quality of Life in Patients With Brain Tumor.

    Science.gov (United States)

    Pan, Chiu-Ju; Liu, Hui-Chun; Liang, Shu-Yuan; Liu, Chieh-Yu; Wu, Wei-Wen; Cheng, Su-Fen

    2017-06-01

    The study purpose was to evaluate how much of the variance in quality of life (QOL) among Taiwanese patients with brain tumor could be accounted for by resilience and coping strategy. This cross-sectional study included 95 patients who had undergone a treatment of operations or chemotherapy or radiotherapy relevant to brain tumor after at least 1 month and completed the European Organization for Research and Treatment of Cancer QOL Questionnaire-Brain Cancer Module (EORTC QLQ-BN20), Resilience Scale (RS), and Ways of Coping Checklist-Revised (WCC-R). There was a significant negative correlation between resilience and future uncertainty QOL and motor dysfunction QOL. In addition, there was a significant positive correlation between the emotion-focused coping and future uncertainty QOL, as well as a significant negative correlation between problem-focused coping and motor dysfunction QOL. Resilience accounted for 4.8% and the emotion-focused coping accounted for 10.20% of the variance in separately predicting the future uncertainty QOL. This study highlights the potential importance of resilience and coping strategies in patients' QOL, which is relevant to brain tumor treatment.

  7. Mutation Screening of Her