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  1. Brain Tumors

    MedlinePlus

    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 ...

  2. Brain tumor - primary - adults

    MedlinePlus

    ... 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, ...

  3. Understanding Brain Tumors

    MedlinePlus

    ... 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 ...

  4. Brain tumor - children

    MedlinePlus

    ... 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 ...

  5. Brain Tumor Diagnosis

    MedlinePlus

    ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ...

  6. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old 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 ...

  7. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Brain Tumors KidsHealth > For Parents > Brain Tumors A A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  8. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Pediatric Brain Tumor Foundation Board Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  9. Tumor Types: Understanding Brain Tumors

    MedlinePlus

    ... Resources Tools & Publications Tumor Types: Understanding Brain Tumors World Health Organization (WHO) Updates Official Classification of Tumors ... Central Nervous System On May 9, 2016, the World Health Organization (WHO) published an official reclassification of ...

  10. Childhood Brain Tumors

    MedlinePlus

    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 ...

  11. American Brain Tumor Association

    MedlinePlus

    ... Molecule Read More ABTA News April 6, 2017 Chicago-Based American Brain Tumor Association’s Breakthrough for Brain ... Association 8550 W. Bryn Mawr Ave. Ste 550 Chicago, IL 60631 © 2014 American Brain Tumor Association Phone: ...

  12. Epidemiology of Brain Tumors.

    PubMed

    McNeill, Katharine A

    2016-11-01

    Brain tumors are the commonest solid tumor in children, leading to significant cancer-related mortality. Several hereditary syndromes associated with brain tumors are nonfamilial. Ionizing radiation is a well-recognized risk factor for brain tumors. Several industrial exposures have been evaluated for a causal association with brain tumor formation but the results are inconclusive. A casual association between the common mutagens of tobacco, alcohol, or dietary factors has not yet been established. There is no clear evidence that the incidence of brain tumors has changed over time. This article presents the descriptive epidemiology of the commonest brain tumors of children and adults.

  13. Children's Brain Tumor Foundation

    MedlinePlus

    ... CBTF Justin's Hope Fund Grant Recipients Grants 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. Radioresistance of Brain Tumors

    PubMed Central

    Kelley, Kevin; Knisely, Jonathan; Symons, Marc; Ruggieri, Rosamaria

    2016-01-01

    Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation. PMID:27043632

  15. Immunology of brain tumors.

    PubMed

    Roth, Patrick; Eisele, Günter; Weller, Michael

    2012-01-01

    Brain tumors of different origin, but notably malignant gliomas, are characterized by their immunosuppressive properties which allow them to escape the host's immune surveillance. The activating immune cell ligands that are expressed by tumor cells, together with potentially immunogenic antigens, are overridden by numerous immune inhibitory signals, with TGF-3 as the master immunosuppressive molecule (Figure 4.1).The ongoing investigation of mechanisms of tumor-derived immunosuppression allows for an increasing understanding of brain tumor immunology. Targeting different mechanisms of tumor-derived immunosuppression, such as inhibition of TGF-[, may represent a promising strategy for future immunotherapeutic approaches.

  16. Familiality in brain tumors

    PubMed Central

    Blumenthal, Deborah T.; Cannon-Albright, Lisa A.

    2008-01-01

    Background: Familiality in brain tumors is not definitively substantiated. Methods: We used the Utah Population Data Base (UPDB), a genealogy representing the Utah pioneers and their descendants, record-linked to statewide cancer records, to describe the familial nature of primary brain cancer. We examined the familial clustering of primary brain tumors, including subgroups defined by histologic type and age at diagnosis. The UPDB includes 1,401 primary brain tumor cases defined as astrocytoma or glioblastoma, all with at least three generations of genealogy data. We tested the hypothesis of excess relatedness of brain tumor cases using the Genealogical Index of Familiality method. We estimated relative risks for brain tumors in relatives using rates of brain tumors estimated internally. Results: Significant excess relatedness was observed for astrocytomas and glioblastomas considered as a group (n = 1,401), for astrocytomas considered separately (n = 744), but not for glioblastomas considered separately (n = 658). Significantly increased risks to first- and second-degree relatives for astrocytomas were identified for relatives of astrocytomas considered separately. Significantly increased risks to first-degree relatives, but not second degree, were observed for astrocytoma and glioblastoma cases considered together, and for glioblastoma cases considered separately. Conclusions: This study provides strong evidence for a familial contribution to primary brain cancer risk. There is evidence that this familial aspect includes not only shared environment, but also a heritable component. Extended high-risk brain tumor pedigrees identified in the UPDB may provide the opportunity to identify predisposition genes responsible for familial brain tumors. GLOSSARY GBM = glioblastoma; GIF = Genealogical Index of Familiality; HGG = high-grade gliomas; ICD-O = International Classification of Disease–Oncology; LGG = low-grade gliomas; RR = relative risks; SEER = Surveillance

  17. Metastatic brain tumor

    MedlinePlus

    ... them create an advance directive and power of attorney for health care. Support Groups You can ease ... surgery Brain tumor - children Breast cancer Increased intracranial pressure Lung cancer - small cell Melanoma Renal cell carcinoma ...

  18. Brain Tumor Statistics

    MedlinePlus

    ... About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Press Releases Headlines Newsletter ... About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  19. Pediatric brain tumor cell lines.

    PubMed

    Xu, Jingying; Margol, Ashley; Asgharzadeh, Shahab; Erdreich-Epstein, Anat

    2015-02-01

    Pediatric brain tumors as a group, including medulloblastomas, gliomas, and atypical teratoid rhabdoid tumors (ATRT) are the most common solid tumors in children and the leading cause of death from childhood cancer. Brain tumor-derived cell lines are critical for studying the biology of pediatric brain tumors and can be useful for initial screening of new therapies. Use of appropriate brain tumor cell lines for experiments is important, as results may differ depending on tumor properties, and can thus affect the conclusions and applicability of the model. Despite reports in the literature of over 60 pediatric brain tumor cell lines, the majority of published papers utilize only a small number of these cell lines. Here we list the approximately 60 currently-published pediatric brain tumor cell lines and summarize some of their central features as a resource for scientists seeking pediatric brain tumor cell lines for their research.

  20. Aquaporins and Brain Tumors

    PubMed Central

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  1. Drugs Approved for Brain Tumors

    MedlinePlus

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

  2. Brain tumors in infants

    PubMed Central

    Ghodsi, Seyyed Mohammad; Habibi, Zohreh; Hanaei, Sara; Moradi, Ehsan; Nejat, Farideh

    2015-01-01

    Background: Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children. Materials and Methods: A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014. Results: Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy. Conclusion: Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary. PMID:26962338

  3. Adolescent and Pediatric Brain Tumors

    MedlinePlus

    ... a child you love is diagnosed with a brain tumor, it is difficult to think about anything else. There are often more questions than answers. Your life can feel as though it has been turned upside ... Brain Tumor Association for information, insight and support. Our ...

  4. Brain Tumor Epidemiology Consortium (BTEC)

    Cancer.gov

    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.

  5. Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

    PubMed Central

    Johnson, Kimberly J.; Cullen, Jennifer; Barnholtz-Sloan, Jill S.; Ostrom, Quinn T.; Langer, Chelsea E.; Turner, Michelle C.; McKean-Cowdin, Roberta; Fisher, James L.; Lupo, Philip J.; Partap, Sonia; Schwartzbaum, Judith A.; Scheurer, Michael E.

    2014-01-01

    Childhood brain tumors are the most common pediatric solid tumor and include several histological subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. PMID:25192704

  6. Precision radiotherapy for brain tumors

    PubMed Central

    Yan, Ying; Guo, Zhanwen; Zhang, Haibo; Wang, Ning; Xu, Ying

    2012-01-01

    OBJECTIVE: Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: 2002-2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) Corrected papers or book chapters. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) top cited publications; (5) distribution according to journals; and (6) comparison of study results on precision radiotherapy for brain tumors. RESULTS: The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven

  7. Spectroscopic-guided brain tumor resection

    NASA Astrophysics Data System (ADS)

    Lin, Wei-Chiang; Toms, Steven A.; Jansen, E. Duco; Mahadevan-Jansen, Anita

    2000-05-01

    A pilot in vivo study was conducted to investigate the feasibility of using optical spectroscopy for brain tumor margin detection. Fluorescence and diffuse reflectance spectra were acquired using a portable clinical spectroscopic system from normal brain tissues, tumors, and tumor margins in 21 brain tumor patients undergoing craniotomy. Results form this study show the potential of optical spectroscopy in detecting infiltrating tumor margins of primary brain tumors.

  8. Brain Tumor Symptoms

    MedlinePlus

    ... be associated with the type, size, and/or location of the tumor, as well as the treatments used to manage it. Surgery, radiation, chemotherapy, and other treatments all have the potential to ... American ...

  9. Cytogenetics of human brain tumors

    SciTech Connect

    Finkernagel, S.W.; Kletz, T.; Day-Salvatore, D.L.

    1994-09-01

    Chromosome studies of 55 brain tumors, including meningiomas, gliomas, astrocyomas and pituatary adenomas, were performed. Primary and first passage cultures were successfully obtained in 75% of these samples with an average of 18 G-banded metaphases analyzed per tumor. 44% of all the brain tumors showed numerical and or structural abnormalities. 46% of the primary and 38% of the first passage cultures showed similar numerical gains/losses and complex karyotypic changes. The most frequent numerical abnormalities (n {ge} 5) included loss of chromosomes 10, 22, and Y. The structural abnormalities most often seen involved 1p, 2, 5, 7, 17q and 19. This is an ongoing study which will attempt to correlate tumor type with specific karyotypic changes and to see if any of the observed chromosomal abnormalities provide prognostic indicators.

  10. Brain tumors in irradiated monkeys.

    NASA Technical Reports Server (NTRS)

    Haymaker, W.; Miquel, J.; Rubinstein, L. J.

    1972-01-01

    A study was made of 32 monkeys which survived one to seven years after total body exposure to protons or to high-energy X rays. Among these 32 monkeys there were 21 which survived two years or longer after exposure to 200 to 800 rad. Glioblastoma multiforme developed in 3 of the 10 monkeys surviving three to five years after receiving 600 or 800 rad 55-MeV protons. Thus, the incidence of tumor development in the present series was far higher than the incidence of spontaneously developing brain tumors in monkeys cited in the literature. This suggests that the tumors in the present series may have been radiation-induced.

  11. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... Search Search En Español Category Cancer A-Z Brain and Spinal Cord Tumors in Adults If you have a brain or spinal cord tumor or are close to ... cope. Here you can find out all about brain and spinal cord tumors in adults, including risk ...

  12. Survival Rates for Selected Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... Diagnosis, and Staging Survival Rates for Selected Childhood Brain and Spinal Cord Tumors Survival rates are often ... Childhood Brain and Spinal Cord Tumors More In Brain and Spinal Cord Tumors in Children About Brain ...

  13. Stereotaxic interstitial irradiation of malignant brain tumors

    SciTech Connect

    Gutin, P.H.; Leibel, S.A.

    1985-11-01

    The authors discuss the feasibility of treatment of malignant tumors with brachytherapy. The history of brain tumor brachytherapy, its present day use, and future directions are detailed. 24 references.

  14. Brain Tumor-Related Epilepsy

    PubMed Central

    Maschio, Marta

    2012-01-01

    In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures. In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient’s psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness. PMID:23204982

  15. Drug delivery systems for brain tumor therapy.

    PubMed

    Rautioa, Jarkko; Chikhale, Prashant J

    2004-01-01

    Brain tumors are one of the most lethal forms of cancer. They are extremely difficult to treat. Although, the rate of brain tumor incidence is relatively low, the field clearly lacks therapeutic strategies capable of overcoming barriers for effective delivery of drugs to brain tumors. Clinical failure of many potentially effective therapeutics for the treatment of brain tumors is usually not due to a lack of drug potency, but rather can be attributed to shortcomings in the methods by which a drug is delivered to the brain and into brain tumors. In response to the lack of efficacy of conventional drug delivery methods, extensive efforts have been made to develop novel strategies to overcome the obstacles for brain tumor drug delivery. The challenge is to design therapeutic strategies that deliver drugs to brain tumors in a safe and effective manner. This review provides some insight into several potential techniques that have been developed to improve drug delivery to brain tumors, and it should be helpful to clinicians and research scientists as well.

  16. The Microenvironmental Landscape of Brain Tumors.

    PubMed

    Quail, Daniela F; Joyce, Johanna A

    2017-03-13

    The brain tumor microenvironment (TME) is emerging as a critical regulator of cancer progression in primary and metastatic brain malignancies. The unique properties of this organ require a specific framework for designing TME-targeted interventions. Here, we discuss a number of these distinct features, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We also highlight recent advances in therapeutically targeting the brain TME in cancer. By developing a comprehensive understanding of the complex and interconnected microenvironmental landscape of brain malignancies we will greatly expand the range of therapeutic strategies available to target these deadly diseases.

  17. Brain tumor immunotherapy: an immunologist's perspective.

    PubMed

    Lampson, Lois A

    2003-01-01

    Key concepts in brain tumor immunotherapy are reviewed. "Immunotherapy" can refer to a fully-developed, tumor-specific immune response, or to its individual cellular or molecular mediators. The immune response is initiated most efficiently in organized lymphoid tissue. After initiation, antigen-specific T lymphocytes (T cells) survey the tissues--including the brain. If the T cells re-encounter their antigen at a tumor site, they can be triggered to carry out their effector functions. T cells can attack tumor in many ways, directly and indirectly, through cell-cell contact, secreted factors, and attraction and activation of other cells, endogenous or blood-borne. Recent work expands the list of candidate tumor antigens: they are not limited to cell surface proteins and need not be absolutely tumor-specific. Once identified, tumor antigens can be targeted immunologically, or in novel ways. The immune response is under complex regulatory control. Most current work aims to enhance initiation of the response (for example, with tumor vaccines), rather than enhancing the effector phase at the tumor site. The effector phase includes a rich, interactive set of cells and mediators; some that are not usually stressed are of particular interest against tumor in the brain. Within the brain, immune regulation varies from site to site, and local neurochemicals (such as substance P or glutamate) can contribute to local control. Given the complexity of a tumor, the brain, and the immune response, animal models are essential, but more emphasis should be given to their limitations and to step-by-step analysis, rather than animal "cures".

  18. Embryonal brain tumors and developmental control genes

    SciTech Connect

    Aguzzi, A.

    1995-12-31

    Cell proliferation in embryogenesis and neoplastic transformation is thought to be controlled by similar sets of regulatory genes. This is certainly true for tumors of embryonic origin, such as Ewing sarcoma, Wilms` tumor and retinoblastoma, in which developmental control genes are either activated as oncogenes to promote proliferation, or are inactivated to eliminate their growth suppressing function. However, to date little is known about the genetic events underlying the pathogenesis of medulloblastoma, the most common brain tumor in children, which still carries an unfavourable prognosis. None of the common genetic alterations identified in other neuroectodermal tumors, such as mutation of the p53 gene or amplification of tyrosine kinase receptor genes, could be uncovered as key events in the formation of medulloblastoma. The identification of regulatory genes which are expressed in this pediatric brain tumor may provide an alternative approach to gain insight into the molecular aspects of tumor formation.

  19. The proteomics of pediatric brain tumors.

    PubMed

    Anagnostopoulos, Athanasios K; Tsangaris, George T

    2014-10-01

    Pediatric tumors of the CNS are the leading cause of cancer-related mortality in children. In pediatric pathology, brain tumors constitute the most frequent solid malignancy. An unparalleled outburst of information in pediatric neuro-oncology research has been witnessed over the last few years, largely due to increased use of high-throughput technologies such as genomics, proteomics and meta-analysis tools. Input from these technologies gives scientists the advantage of early prognosis assessment, more accurate diagnosis and prospective curative intent in the pediatric brain tumor clinical setting. The present review aims to summarize current knowledge on research applying proteomics techniques or proteomics-based approaches performed on pediatric brain tumors. Proteins that can be used as potential disease markers or molecular targets, and their biological significance, are herein listed and discussed. Furthermore, future perspectives that proteomics technologies may offer regarding this devastating disorder are presented.

  20. How Are Brain and Spinal Cord Tumors in Children Diagnosed?

    MedlinePlus

    ... Children Early Detection, Diagnosis, and Staging How Are Brain and Spinal Cord Tumors Diagnosed in Children? Brain ... resonance angiography (MRA) or computerized tomographic angiography (CTA). Brain or spinal cord tumor biopsy Imaging tests such ...

  1. Metabolic brain imaging correlated with clinical features of brain tumors

    SciTech Connect

    Alavi, J.; Alavi, A.; Dann, R.; Kushner, M.; Chawluk, J.; Powlis, W.; Reivich, M.

    1985-05-01

    Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.

  2. Psychiatric aspects of brain tumors: A review

    PubMed Central

    Madhusoodanan, Subramoniam; Ting, Mark Bryan; Farah, Tara; Ugur, Umran

    2015-01-01

    Infrequently, psychiatric symptoms may be the only manifestation of brain tumors. They may present with mood symptoms, psychosis, memory problems, personality changes, anxiety, or anorexia. Symptoms may be misleading, complicating the clinical picture. A comprehensive review of the literature was conducted regarding reports of brain tumors and psychiatric symptoms from 1956-2014. Search engines used include PubMed, Ovid, Psych Info, MEDLINE, and MedScape. Search terms included psychiatric manifestations/symptoms, brain tumors/neoplasms. Our literature search yielded case reports, case studies, and case series. There are no double blind studies except for post-diagnosis/-surgery studies. Early diagnosis is critical for improved quality of life. Symptoms that suggest work-up with neuroimaging include: new-onset psychosis, mood/memory symptoms, occurrence of new or atypical symptoms, personality changes, and anorexia without body dysmorphic symptoms. This article reviews the existing literature regarding the diagnosis and management of this clinically complex condition. PMID:26425442

  3. Psychiatric aspects of brain tumors: A review.

    PubMed

    Madhusoodanan, Subramoniam; Ting, Mark Bryan; Farah, Tara; Ugur, Umran

    2015-09-22

    Infrequently, psychiatric symptoms may be the only manifestation of brain tumors. They may present with mood symptoms, psychosis, memory problems, personality changes, anxiety, or anorexia. Symptoms may be misleading, complicating the clinical picture. A comprehensive review of the literature was conducted regarding reports of brain tumors and psychiatric symptoms from 1956-2014. Search engines used include PubMed, Ovid, Psych Info, MEDLINE, and MedScape. Search terms included psychiatric manifestations/symptoms, brain tumors/neoplasms. Our literature search yielded case reports, case studies, and case series. There are no double blind studies except for post-diagnosis/-surgery studies. Early diagnosis is critical for improved quality of life. Symptoms that suggest work-up with neuroimaging include: new-onset psychosis, mood/memory symptoms, occurrence of new or atypical symptoms, personality changes, and anorexia without body dysmorphic symptoms. This article reviews the existing literature regarding the diagnosis and management of this clinically complex condition.

  4. Confronting pediatric brain tumors: parent stories.

    PubMed

    McMillan, Gigi

    2014-01-01

    This narrative symposium brings to light the extreme difficulties faced by parents of children diagnosed with brain tumors. NIB editorial staff and narrative symposium editors, Gigi McMillan and Christy A. Rentmeester, developed a call for stories that was distributed on several list serves and posted on Narrative Inquiry in Bioethics' website. The call asks parents to share their personal experience of diagnosis, treatment, long-term effects of treatment, social issues and the doctor-patient-parent dynamic that develops during this process. Thirteen stories are found in the print version of the journal and an additional six supplemental stories are published online only through Project MUSE. One change readers may notice is that the story authors are not listed in alphabetical order. The symposium editors had a vision for this issue that included leading readers through the timeline of this topic: diagnosis-treatment-acute recovery-recurrence-treatment (again)-acute recovery (again)-long-term quality of life-(possibly) end of life. Stories are arranged to help lead the reader through this timeline.Gigi McMillan is a patient and research subject advocate, co-founder of We Can, Pediatric Brain Tumor Network, as well as, the mother of a child who suffered from a pediatric brain tumor. She also authored the introduction for this symposium. Christy Rentmeester is an Associate Professor of Health Policy and Ethics in the Creighton University School of Medicine. She served as a commentator for this issue. Other commentators for this issue are Michael Barraza, a clinical psychologist and board member of We Can, Pediatric Brain Tumor Network; Lisa Stern, a pediatrician who has diagnosed six children with brain tumors in her 20 years of practice; and Katie Rose, a pediatric brain tumor patient who shares her special insights about this world.

  5. Neurologic sequelae of brain tumors in children.

    PubMed

    Ullrich, Nicole J

    2009-11-01

    Neurologic signs and symptoms are often the initial presenting features of a primary brain tumor and may also emerge during the course of therapy or as late effects of the tumor and its treatment. Variables that influence the development of such neurologic complications include the type, size, and location of the tumor, the patient's age at diagnosis, and the treatment modalities used. Heightened surveillance and improved neuroimaging modalities have been instrumental in detecting and addressing such complications, which are often not appreciated until many years after completion of therapy. As current brain tumor therapies are continually refined and newer targeted therapies are developed, it will be important for future cooperative group studies to include systematic assessments to determine the incidence of neurologic complications and to provide a framework for the development of novel strategies for prevention and intervention.

  6. Metabolism of steroids by human brain tumors.

    PubMed

    Weidenfeld, J; Schiller, H

    1984-01-01

    Hormonal steroids or their precursors can be metabolized in the CNS to products with altered hormonal activity. The importance of the intracerebral transformation of steroids has been demonstrated, particularly with regard to neuroendocrine regulation and sexual behavior. These studies were carried out on normal brain tissues, but the ability of neoplastic tissues of CNS origin to metabolize steroids is unknown. We investigated the in vitro metabolism of tritiated pregnenolone, testosterone, and estradiol-17 beta by homogenates of four brain tumors defined as astrocytomas. In three tumors of cortical origin, removed from adult patients, the only enzymic activity found was the conversion of estradiol to estrone. In one tumor of cerebellar origin removed from an 11-year-old boy, the following conversions were found: pregnenolone to progesterone, testosterone to either androstenedione or estradiol, and estradiol to estrone. These results demonstrate that human astrocytomas can transform steroids to compounds with modified hormonal activity. These compounds formed by the tumorous tissue can affect brain function, which may be of clinical significance. Furthermore, these results may add important parameters for biochemical characterization of neoplastic brain tissues.

  7. Ion transporters in brain tumors

    PubMed Central

    Cong, Damin; Zhu, Wen; Kuo, John S.; Hu, Shaoshan; Sun, Dandan

    2015-01-01

    Ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions. They have recently emerged as important players in cancer progression. In this review, we discussed two important ion transporter proteins, sodium-potassium-chloride cotransporter isoform 1 (NKCC-1) and sodium-hydrogen exchanger isoform 1 (NHE-1) in Glioblastoma multiforme (GBM) and other malignant tumors. NKCC-1 is a Na+-dependent Cl− transporter that mediates the movement of Na+, K+, and Cl− ions across the plasma membrane and maintains cell volume and intracellular K+ and Cl− homeostasis. NHE-1 is a ubiquitously expressed cell membrane protein which regulates intracellular pH (pHi) and extracellular microdomain pH (pHe) homeostasis and cell volume. Here, we summarized recent pre-clinical experimental studies on NKCC-1 and NHE-1 in GBM and other malignant tumors, such as breast cancer, hepatocellular carcinoma, and lung cancer. These studies illustrated that pharmacological inhibition or down-regulation of these ion transporter proteins reduces proliferation, increases apoptosis, and suppresses migration and invasion of cancer cells. These new findings reveal the potentials of these ion transporters as new targets for cancer diagnosis and/or treatment. PMID:25620102

  8. Brain tumors: Special characters for research and banking

    PubMed Central

    Kheirollahi, Majid; Dashti, Sepideh; Khalaj, Zahra; Nazemroaia, Fatemeh; Mahzouni, Parvin

    2015-01-01

    A brain tumor is an intracranial neoplasm within the brain or in the central spinal canal. Primary malignant brain tumors affect about 200,000 people worldwide every year. Brain cells have special characters. Due to the specific properties of brain tumors, including epidemiology, growth, and division, investigation of brain tumors and the interpretation of results is not simple. Research to identify the genetic alterations of human tumors improves our knowledge of tumor biology, genetic interactions, progression, and preclinical therapeutic assessment. Obtaining data for prevention, diagnosis, and therapy requires sufficient samples, and brain tumors have a wide range. As a result, establishing the bank of brain tumors is very important and essential. PMID:25625110

  9. Neurocutaneous Syndromes and Brain Tumors.

    PubMed

    Ullrich, Nicole J

    2016-10-01

    The etiology of most childhood cancer remains largely unknown, but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition involving a germline genetic mutation or chromosomal aberration. The term "neurocutaneous syndrome" encompasses a group of multisystem, hereditary disorders that are associated with skin manifestations as well as central and/or peripheral nervous system lesions of variable severity. This review outlines the central nervous system tumors associated with underlying neurocutaneous disorders, including neurofibromatosis type 1, neurofibromatosis type 2, schwannomatosis, tuberous sclerosis complex, Von Hippel Lindau, and nevoid basal cell carcinoma syndrome. Recognizing the presence of an underlying syndrome is critically important to both optimizing clinical care and treatment as well as genetic counseling and monitoring of these affected patients and their families.

  10. Brain Tumor Epidemiology: Consensus from the Brain Tumor Epidemiology Consortium (BTEC)

    PubMed Central

    Bondy, Melissa L.; Scheurer, Michael E.; Malmer, Beatrice; Barnholtz-Sloan, Jill S.; Davis, Faith G.; Il’yasova, Dora; Kruchko, Carol; McCarthy, Bridget J.; Rajaraman, Preetha; Schwartzbaum, Judith A.; Sadetzki, Siegal; Schlehofer, Brigitte; Tihan, Tarik; Wiemels, Joseph L.; Wrensch, Margaret; Buffler, Patricia A.

    2010-01-01

    Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings possibly due to small sample sizes in individual studies and differences between studies in subjects, tumor types, and methods of classification. Individual studies have generally lacked sufficient sample size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups such as pediatric brain tumors, the etiology of rare glioma subtypes, such as oligodendroglioma, and meningioma, which not uncommon, has only recently been systematically registered in the US. There is also a pressing need to bring more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. We review the group’s consensus on the current state of scientific findings and present a consensus on research priorities to identify the important areas the science should move to address. PMID:18798534

  11. Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors

    PubMed Central

    Sampson, John H.; Crotty, Laura E.; Lee, Samson; Archer, Gary E.; Ashley, David M.; Wikstrand, Carol J.; Hale, Laura P.; Small, Clayton; Dranoff, Glenn; Friedman, Allan H.; Friedman, Henry S.; Bigner, Darell D.

    2000-01-01

    The epidermal growth factor receptor (EGFR) is often amplified and rearranged structurally in tumors of the brain, breast, lung, and ovary. The most common mutation, EGFRvIII, is characterized by an in-frame deletion of 801 base pairs, resulting in the generation of a novel tumor-specific epitope at the fusion junction. A murine homologue of the human EGFRvIII mutation was created, and an IgG2a murine mAb, Y10, was generated that recognizes the human and murine equivalents of this tumor-specific antigen. In vitro, Y10 was found to inhibit DNA synthesis and cellular proliferation and to induce autonomous, complement-mediated, and antibodydependent cell-mediated cytotoxicity. Systemic treatment with i.p. Y10 of s.c. B16 melanomas transfected to express stably the murine EGFRvIII led to long-term survival in all mice treated (n = 20; P < 0.001). Similar therapy with i.p. Y10 failed to increase median survival of mice with EGFRvIII-expressing B16 melanomas in the brain; however, treatment with a single intratumoral injection of Y10 increased median survival by an average 286%, with 26% long-term survivors (n = 117; P < 0.001). The mechanism of action of Y10 in vivo was shown to be independent of complement, granulocytes, natural killer cells, and T lymphocytes through in vivo complement and cell subset depletions. Treatment with Y10 in Fc receptor knockout mice demonstrated the mechanism of Y10 to be Fc receptor-dependent. These data indicate that an unarmed, tumor-specific mAb may be an effective immunotherapy against human tumors and potentially other pathologic processes in the “immunologically privileged” central nervous system. PMID:10852962

  12. Perspectives on Dual Targeting Delivery Systems for Brain Tumors.

    PubMed

    Gao, Huile

    2017-03-01

    Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies.

  13. Brain Tumors - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Brain Tumors - Multiple Languages To use the sharing features on this page, please enable JavaScript. French (français) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (af Soomaali) Spanish (español) Ukrainian (Українська) ...

  14. [Chemotherapy of brain tumors in aduts].

    PubMed

    Roth, P; Weller, M

    2015-04-01

    The treatment of patients with brain tumors has long been the domain of neurosurgery and radiotherapy but chemotherapy is now well established as an additional treatment option for many tumor entities in neuro-oncology. This is particularly true for patients with newly diagnosed and relapsing glioblastoma and anaplastic glioma as well as the treatment of medulloblastoma and primary lymphoma of the central nervous system (CNS). In addition to purely histopathological features, treatment decisions including those for chemotherapy are now based increasingly more on molecular tumor profiling. Within the group of gliomas these markers include the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the 1p/19q status, which reflects the loss of genetic material on chromosome arms 1p and 19q. The presence of a 1p/19q codeletion is associated with a better prognosis and increased sensitivity to alkylating chemotherapy in patients with anaplastic gliomas.

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

    SciTech Connect

    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.

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

    PubMed

    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.

  17. Brain tumor segmentation with Deep Neural Networks.

    PubMed

    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.

  18. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  19. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

  20. Positron Scanner for Locating Brain Tumors

    DOE R&D Accomplishments Database

    Rankowitz, S.; Robertson, J. S.; Higinbotham, W. A.; Rosenblum, M. J.

    1962-03-01

    A system is described that makes use of positron emitting isotopes for locating brain tumors. This system inherently provides more information about the distribution of radioactivity in the head in less time than existing scanners which use one or two detectors. A stationary circular array of 32 scintillation detectors scans a horizontal layer of the head from many directions simultaneously. The data, consisting of the number of counts in all possible coincidence pairs, are coded and stored in the memory of a Two-Dimensional Pulse-Height Analyzer. A unique method of displaying and interpreting the data is described that enables rapid approximate analysis of complex source distribution patterns. (auth)

  1. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    PubMed Central

    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

  2. Brain tumor imaging: imaging brain metastasis using a brain-metastasizing breast adenocarcinoma.

    PubMed

    Madden, Kelley S; Zettel, Martha L; Majewska, Ania K; Brown, Edward B

    2013-03-01

    Brain metastases from primary or secondary breast tumors are difficult to model in the mouse. When metastatic breast cancer cell lines are injected directly into the arterial circulation, only a small fraction of cells enter the brain to form metastatic foci. To study the molecular and cellular mechanisms of brain metastasis, we have transfected MB-231BR, a brain-homing derivative of a human breast adenocarcinoma line MDA-MB-231, with the yellow fluorescent protein (YFP) variant Venus. MB-231BR selectively enters the brain after intracardiac injection into the arterial circulation, resulting in accumulation of fluorescent foci of cells in the brain that can be viewed by standard fluorescence imaging procedures. We describe how to perform the intracardiac injection and the parameters used to quantify brain metastasis in brain sections by standard one-photon fluorescence imaging. The disadvantage of this model is that the kinetics of growth over time cannot be determined in the same animal. In addition, the injection technique does not permit precise placement of tumor cells within the brain. This model is useful for determining the molecular determinants of brain tumor metastasis.

  3. Brain tumors in man and animals: report of a workshop.

    PubMed Central

    1986-01-01

    This report summarizes the results of a workshop on brain tumors in man and animals. Animals, especially rodents are often used as surrogates for man to detect chemicals that have the potential to induce brain tumors in man. Therefore, the workshop was focused mainly on brain tumors in the F344 rat and B6C3F1 mouse because of the frequent use of these strains in long-term carcinogenesis studies. Over 100 brain tumors in F344 rats and more than 50 brain tumors in B6C3F1 mice were reviewed and compared to tumors found in man and domestic or companion animals. In the F344 rat, spontaneous brain tumors are uncommon, most are of glial origin, and the highly undifferentiated glioblastoma multiforme, a frequent tumor of man was not found. In the B6C3F1 mouse, brain tumors are exceedingly rare. Lipomas of the choroid plexus and meningiomas together account for more than 50% of the tumors found. Both rodent strains examined have low background rates and very little variability between control groups. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. PMID:3536473

  4. Growth patterns of microscopic brain tumors

    NASA Astrophysics Data System (ADS)

    Sander, Leonard M.; Deisboeck, Thomas S.

    2002-11-01

    Highly malignant brain tumors such as glioblastoma multiforme form complex growth patterns in vitro in which invasive cells organize in tenuous branches. Here, we formulate a chemotaxis model for this sort of growth. A key element controlling the pattern is homotype attraction, i.e., the tendency for invasive cells to follow pathways previously explored. We investigate this in two ways: we show that there is an intrinsic instability in the model, which leads to branch formation. We also give a discrete description for the expansion of the invasive zone, and a continuum model for the nutrient supply. The results indicate that both strong heterotype chemotaxis and strong homotype chemoattraction are required for branch formation within the invasive zone. Our model thus can give a way to assess the importance of the various processes, and a way to explore and analyze transitions between different growth regimes.

  5. Fractal analysis of tumoral lesions in brain.

    PubMed

    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.

  6. Neural stem cell-based gene therapy for brain tumors.

    PubMed

    Kim, Seung U

    2011-03-01

    Advances in gene-based medicine since 1990s have ushered in new therapeutic strategy of gene therapy for inborn error genetic diseases and cancer. Malignant brain tumors such as glioblastoma multiforme and medulloblastoma remain virtually untreatable and lethal. Currently available treatment for brain tumors including radical surgical resection followed by radiation and chemotherapy, have substantially improved the survival rate in patients suffering from these brain tumors; however, it remains incurable in large proportion of patients. Therefore, there is substantial need for effective, low-toxicity therapies for patients with malignant brain tumors, and gene therapy targeting brain tumors should fulfill this requirement. Gene therapy for brain tumors includes many therapeutic strategies and these strategies can be grouped in two major categories: molecular and immunologic. The widely used molecular gene therapy approach is suicide gene therapy based on the conversion of non-toxic prodrugs into active anticancer agents via introduction of enzymes and genetic immunotherapy involves the gene transfer of immune-stimulating cytokines including IL-4, IL-12 and TRAIL. For both molecular and immune gene therapy, neural stem cells (NSCs) can be used as delivery vehicle of therapeutic genes. NSCs possess an inherent tumor tropism that supports their use as a reliable delivery vehicle to target therapeutic gene products to primary brain tumors and metastatic cancers throughout the brain. Significance of the NSC-based gene therapy for brain tumor is that it is possible to exploit the tumor-tropic property of NSCs to mediate effective, tumor-selective therapy for primary and metastatic cancers in the brain and outside, for which no tolerated curative treatments are currently available.

  7. Thermal imaging of brain tumors in a rat glioma model

    NASA Astrophysics Data System (ADS)

    Papaioannou, Thanassis; Thompson, Reid C.; Kateb, Babak; Sorokoumov, Oleg; Grundfest, Warren S.; Black, Keith L.

    2002-05-01

    We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P(greater than)0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

  8. Parallel optimization of tumor model parameters for fast registration of brain tumor images

    NASA Astrophysics Data System (ADS)

    Zacharaki, Evangelia I.; Hogea, Cosmina S.; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2008-03-01

    The motivation of this work is to register MR brain tumor images with a brain atlas. Such a registration method can make possible the pooling of data from different brain tumor patients into a common stereotaxic space, thereby enabling the construction of statistical brain tumor atlases. Moreover, it allows the mapping of neuroanatomical brain atlases into the patient's space, for segmenting brains and thus facilitating surgical or radiotherapy treatment planning. However, the methods developed for registration of normal brain images are not directly applicable to the registration of a normal atlas with a tumor-bearing image, due to substantial dissimilarity and lack of equivalent image content between the two images, as well as severe deformation or shift of anatomical structures around the tumor. Accordingly, a model that can simulate brain tissue death and deformation induced by the tumor is considered to facilitate the registration. Such tumor growth simulation models are usually initialized by placing a small seed in the normal atlas. The shape, size and location of the initial seed are critical for achieving topological equivalence between the atlas and patient's images. In this study, we focus on the automatic estimation of these parameters, pertaining to tumor simulation. In particular, we propose an objective function reflecting feature-based similarity and elastic stretching energy and optimize it with APPSPACK (Asynchronous Parallel Pattern Search), for achieving significant reduction of the computational cost. The results indicate that the registration accuracy is high in areas around the tumor, as well as in the healthy portion of the brain.

  9. Brain necrosis after radiotherapy for primary intracerebral tumor.

    PubMed

    Hohwieler, M L; Lo, T C; Silverman, M L; Freidberg, S R

    1986-01-01

    Radiotherapy is a standard postoperative treatment for cerebral glioma. We have observed the onset of symptoms related to brain necrosis, as opposed to recurrent tumor, in surviving patients. This has been manifest as dementia with a computed tomographic pattern of low density in the frontal lobe uninvolved with tumor, but within the field of radiotherapy. Two patients presented with mass lesions also unrelated to recurrent tumor. We question the necessity of full brain irradiation and suggest that radiotherapy techniques be altered to target the tumor and not encompass the entire brain.

  10. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2017-01-17

    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

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

    PubMed

    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.

  12. Brain tumors in children with neurofibromatosis: additional neuropsychological morbidity?

    PubMed Central

    De Winter, A. E.; Moore, B. D.; Slopis, J. M.; Ater, J. L.; Copeland, D. R.

    1999-01-01

    Neurofibromatosis type 1 is a common autosomal dominant genetic disorder associated with numerous physical anomalies and an increased incidence of neuropsychological impairment. Tumors of the CNS occur in approximately 15% of children with neurofibromatosis, presenting additional risk for cognitive impairment. This study examines the impact of an additional diagnosis of brain tumor on the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological tests was administered to 149 children with neurofibromatosis. Thirty-six of these children had a codiagnosis of brain tumor. A subset of 36 children with neurofibromatosis alone was matched with the group of children diagnosed with neurofibromatosis and brain tumor. Although mean scores of the neurofibromatosis plus brain tumor group were, in general, lower than those of the neurofibromatosis alone group, these differences were not statistically significant. Children in the neurofibromatosis plus brain tumor group who received cranial irradiation (n = 9) demonstrated weaker academic abilities than did children with brain tumor who had not received that treatment. These results suggest that neurofibromatosis is associated with impairments in cognitive functioning, but the severity of the problems is not significantly exacerbated by the codiagnosis of a brain tumor unless treatment includes cranial irradiation. PMID:11550319

  13. Lassa-Vesicular Stomatitis Chimeric Virus Safely Destroys Brain Tumors

    PubMed Central

    Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N.; Cepko, Connie

    2015-01-01

    ABSTRACT 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. IMPORTANCE 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

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

    PubMed

    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.

  15. High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea

    PubMed Central

    Jung, Bong-Kwang; Song, Hyemi; Kim, Min-Jae; Cho, Jaeeun; Shin, Eun-Hee; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID:27180580

  16. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Efficacy of cabazitaxel in mouse models of pediatric brain tumors

    PubMed Central

    Girard, Emily; Ditzler, Sally; Lee, Donghoon; Richards, Andrew; Yagle, Kevin; Park, Joshua; Eslamy, Hedieh; Bobilev, Dmitri; Vrignaud, Patricia; Olson, James

    2015-01-01

    Background There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. Methods The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. Results This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. Conclusion These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors. PMID:25140037

  19. Cytogenetics and molecular genetics of childhood brain tumors.

    PubMed Central

    Biegel, J. A.

    1999-01-01

    Considerable progress has been made toward improving survival for children with brain tumors, and yet there is still relatively little known regarding the molecular genetic events that contribute to tumor initiation or progression. Nonrandom patterns of chromosomal deletions in several types of childhood brain tumors suggest that the loss or inactivation of tumor suppressor genes are critical events in tumorigenesis. Deletions of chromosomal regions 10q, 11 and 17p, and example, are frequent events in medulloblastoma, whereas loss of a region within 22q11.2, which contains the INI1 gene, is involved in the development of atypical teratoid and rhabdoid tumors. A review of the cytogenetic and molecular genetic changes identified to date in childhood brain tumors will be presented. PMID:11550309

  20. Computational modeling of brain tumors: discrete, continuum or hybrid?

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

    In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

  1. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  2. Labeled Putrescine as a Probe in Brain Tumors

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  4. Fractal analysis of microvascular networks in malignant brain tumors.

    PubMed

    Di Ieva, Antonio

    2012-01-01

    Brain tumors are characterized by a microvascular network which differs from normal brain vascularity. Different tumors show individual angiogenic patterns. Microvascular heterogeneity can also be observed within a neoplastic histotype. It has been shown that quantification of neoplastic microvascular patterns could be used in combination with the histological grade for tumor characterization and to refine clinical prognoses, even if no objective parameters have yet been validated. To overcome the limits of the Euclidean approach, we employ fractal geometry to analyze the geometric complexity underlying the microangioarchitectural networks in brain tumors. We have developed a computer-aided fractal-based analysis for the quantification of the microvascular patterns in histological specimens and ultra-high-field (7-Tesla) magnetic resonance images. We demonstrate that the fractal parameters are valid estimators of microvascular geometrical complexity. Furthermore, our analysis allows us to demonstrate the high geometrical variability underlying the angioarchitecture of glioblastoma multiforme and to differentiate low-grade from malignant tumors in histological specimens and radiological images. Based on the results of this study, we speculate the existence of a gradient in the geometrical complexity of microvascular networks from those in the normal brain to those in malignant brain tumors. Here, we summarize a new methodology for the application of fractal analysis to the study of the microangioarchitecture of brain tumors; we further suggest this approach as a tool for quantifying and categorizing different neoplastic microvascular patterns and as a potential morphometric biomarker for use in clinical practice.

  5. Clinical applications of choline PET/CT in brain tumors.

    PubMed

    Giovannini, Elisabetta; Lazzeri, Patrizia; Milano, Amalia; Gaeta, Maria Chiara; Ciarmiello, Andrea

    2015-01-01

    Malignant gliomas and metastatic tumors are the most common forms of brain tumors. From a clinical perspective, neuroimaging plays a significant role, in diagnosis, treatment planning, and follow-up. To date MRI is considered the current clinical gold standard for imaging, however, despite providing superior structural detail it features poor specificity in identifying viable tumors in brain treated with surgery, radiation, or chemotherapy. In the last years functional neuroimaging has become largely widespread thanks to the use of molecular tracers employed in cellular metabolism which has significantly improved the management of patients with brain tumors, especially in the post-treatment phase. Despite the considerable progress of molecular imaging in oncology its use in the diagnosis of brain tumors is still limited by a few wellknown technical problems. Because 18F-FDG, the most common radiotracer used in oncology, is avidly accumulated by normal cortex, the low tumor/background signal ratio makes it difficult to distinguish the tumor from normal surrounding tissues. By contrast, radiotracers with higher specificity for the tumor are labeled with a short half-life isotopes which restricts their use to those centers equipped with a cyclotron and radiopharmacy facility. 11C-choline has been reported as a suitable tracer for neuroimaging application. The recent availability of choline labeled with a long half-life radioisotope as 18F increases the possibility of studying this tracer's potential role in the staging of brain tumors. The present review focuses on the possible clinical applications of PET/CT with choline tracers in malignant brain tumors and brain metastases, with a special focus on malignant gliomas.

  6. Sex steroids in human brain tumors and breast cancer.

    PubMed

    von Schoultz, E; Bixo, M; Bäckström, T; Silfvenius, H; Wilking, N; Henriksson, R

    1990-02-15

    The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor and breast cancer tissues. The concentrations in malignant gliomas and breast cancers showed interindividual variations, especially evident with regard to estradiol. High estradiol concentrations were recorded in two patients with malignant astrocytoma. The concentrations of 1.00 pg/mg and 3.32 pg/mg were 10 to 30 times as high as in normal female brain. In five of ten astrocytomas the estradiol concentration was higher than the lowest breast cancer value. The distribution of progesterone seemed more even, and the level was significantly lower in brain tumors and breast cancers as compared with female brain, perhaps indicating an increased metabolism. Testosterone levels were somewhat higher in brain tumors, as compared with breast cancers, but not different from values in brain tissue. There were no significant age or sex correlation or differences in the concentrations of steroids in the brain tumors. The results suggest that manipulation of sex steroid metabolism in malignant brain tumors can be of beneficial therapeutic value as has been shown for breast cancer and prostatic carcinoma.

  7. Glial brain tumor detection by using symmetry analysis

    NASA Astrophysics Data System (ADS)

    Pedoia, Valentina; Binaghi, Elisabetta; Balbi, Sergio; De Benedictis, Alessandro; Monti, Emanuele; Minotto, Renzo

    2012-02-01

    In this work a fully automatic algorithm to detect brain tumors by using symmetry analysis is proposed. In recent years a great effort of the research in field of medical imaging was focused on brain tumors segmentation. The quantitative analysis of MRI brain tumor allows to obtain useful key indicators of disease progression. The complex problem of segmenting tumor in MRI can be successfully addressed by considering modular and multi-step approaches mimicking the human visual inspection process. The tumor detection is often an essential preliminary phase to solvethe segmentation problem successfully. In visual analysis of the MRI, the first step of the experts cognitive process, is the detection of an anomaly respect the normal tissue, whatever its nature. An healthy brain has a strong sagittal symmetry, that is weakened by the presence of tumor. The comparison between the healthy and ill hemisphere, considering that tumors are generally not symmetrically placed in both hemispheres, was used to detect the anomaly. A clustering method based on energy minimization through Graph-Cut is applied on the volume computed as a difference between the left hemisphere and the right hemisphere mirrored across the symmetry plane. Differential analysis involves the loss the knowledge of the tumor side. Through an histogram analysis the ill hemisphere is recognized. Many experiments are performed to assess the performance of the detection strategy on MRI volumes in presence of tumors varied in terms of shapes positions and intensity levels. The experiments showed good results also in complex situations.

  8. Current state of our knowledge on brain tumor epidemiology.

    PubMed

    Ostrom, Quinn T; Barnholtz-Sloan, Jill S

    2011-06-01

    The overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 person-years; 11.52 per 100,000 person-years for benign tumors and 7.19 per 100,000 person-years for malignant tumors. Incidence, response to treatment, and survival after diagnosis vary greatly by age at diagnosis, histologic type of tumor, and degree of neurologic compromise. The only established environmental risk factor for brain tumors is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor for brain tumor development. However, studies have been inconsistent and inconclusive due to systematic differences in study designs and difficulty of accurately measuring cell phone use. Recently studies of genetic risk factors for brain tumors have expanded to genome-wide association studies. In addition, genome-wide studies of somatic genetic changes in tumors show correlation with clinical outcomes.

  9. Chemo Drug May Combat Serious Brain Tumor After All

    MedlinePlus

    ... Chemo Drug May Combat Serious Brain Tumor After All Certain glioblastomas respond to anti-angiogenic compounds, study ... Dec. 22, 2016 HealthDay Copyright (c) 2016 HealthDay . All rights reserved. News stories are written and provided ...

  10. Uranyl phthalocyanines show promise in the treatment of brain tumors

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.

    1967-01-01

    Processes synthesize sulfonated and nonsulfonated uranyl phthalocyanines for application in neutron therapy of brain tumors. Tests indicate that the compounds are advantageous over the previously used boron and lithium compounds.

  11. Childhood Brain and Spinal Cord Tumors Treatment Overview

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  12. General Information about Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

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

    PubMed Central

    2012-01-01

    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. PMID:22891953

  14. Emerging Insights into Barriers to Effective Brain Tumor Therapeutics

    PubMed Central

    Woodworth, Graeme F.; Dunn, Gavin P.; Nance, Elizabeth A.; Hanes, Justin; Brem, Henry

    2014-01-01

    There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM. PMID:25101239

  15. Challenges for the functional diffusion map in pediatric brain tumors

    PubMed Central

    Grech-Sollars, Matthew; Saunders, Dawn E.; Phipps, Kim P.; Kaur, Ramneek; Paine, Simon M.L.; Jacques, Thomas S.; Clayden, Jonathan D.; Clark, Chris A.

    2014-01-01

    Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size. PMID:24305721

  16. Characterization of distinct immunophenotypes across pediatric brain tumor types.

    PubMed

    Griesinger, Andrea M; Birks, Diane K; Donson, Andrew M; Amani, Vladimir; Hoffman, Lindsey M; Waziri, Allen; Wang, Michael; Handler, Michael H; Foreman, Nicholas K

    2013-11-01

    Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors' microenvironment has not been defined. To address this, the current study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common pediatric brain tumor types. The initial study cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5 glioblastoma (GBM), 6 medulloblastoma (MED), and 5 nontumor brain (NT) control samples obtained from epilepsy surgery. Immune cell types analyzed included both myeloid and T cell lineages and respective markers of activated or suppressed functional phenotypes. Immune parameters that distinguished each of the tumor types were identified. PA and EPN demonstrated significantly higher infiltrating myeloid and lymphoid cells compared with GBM, MED, or NT. Additionally, PA and EPN conveyed a comparatively activated/classically activated myeloid cell-skewed functional phenotype denoted in particular by HLA-DR and CD64 expression. In contrast, GBM and MED contained progressively fewer infiltrating leukocytes and more muted functional phenotypes similar to that of NT. These findings were recapitulated using whole tumor expression of corresponding immune marker genes in a large gene expression microarray cohort of pediatric brain tumors. The results of this cross-tumor comparative analysis demonstrate that different pediatric brain tumor types exhibit distinct immunophenotypes, implying that specific immunotherapeutic approaches may be most effective for each tumor type.

  17. Brain tumor locating in 3D MR volume using symmetry

    NASA Astrophysics Data System (ADS)

    Dvorak, Pavel; Bartusek, Karel

    2014-03-01

    This work deals with the automatic determination of a brain tumor location in 3D magnetic resonance volumes. The aim of this work is not the precise segmentation of the tumor and its parts but only the detection of its location. This work is the first step in the tumor segmentation process, an important topic in neuro-image processing. The algorithm expects 3D magnetic resonance volumes of brain containing a tumor. The detection is based on locating the area that breaks the left-right symmetry of the brain. This is done by multi-resolution comparing of corresponding regions in left and right hemisphere. The output of the computation is the probabilistic map of the tumor location. The created algorithm was tested on 80 volumes from publicly available BRATS databases containing 3D brain volumes afflicted by a brain tumor. These pathological structures had various sizes and shapes and were located in various parts of the brain. The locating performance of the algorithm was 85% for T1-weighted volumes, 91% for T1-weighted contrast enhanced volumes, 96% for FLAIR and T2-wieghted volumes and 95% for their combinations.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27456312

  20. Sports and childhood brain tumors: Can I play?

    PubMed Central

    Perreault, Sébastien; Lober, Robert M.; Davis, Carissa; Stave, Christopher; Partap, Sonia; Fisher, Paul G.

    2014-01-01

    Background It is unknown whether children with brain tumors have a higher risk of complications while participating in sports. We sought to estimate the prevalence of such events by conducting a systematic review of the literature, and we surveyed providers involved with pediatric central nervous system (CNS) tumor patients. Methods A systematic review of the literature in the PubMed, Scopus, and Cochrane databases was conducted for original articles addressing sport-related complications in the brain-tumor population. An online questionnaire was created to survey providers involved with pediatric CNS tumor patients about their current recommendations and experience regarding sports and brain tumors. Results We retrieved 32 subjects, including 19 pediatric cases from the literature. Most lesions associated with sport complications were arachnoid cysts (n = 21), followed by glioma (n = 5). The sports in which symptom onset most commonly occurred were soccer (n = 7), football (n = 5), and running (n = 5). We surveyed 111 pediatric neuro-oncology providers. Sport restriction varied greatly from none to 14 sports. Time to return to play in sports with contact also varied considerably between providers. Rationales for limiting sports activities were partly related to subspecialty. Responders reported 9 sport-related adverse events in patients with brain tumor. Conclusions Sport-related complications are uncommon in children with brain tumors. Patients might not be at a significantly higher risk and should not need to be excluded from most sports activities. PMID:26034627

  1. Multiscale modeling for image analysis of brain tumor studies.

    PubMed

    Bauer, Stefan; May, Christian; Dionysiou, Dimitra; Stamatakos, Georgios; Büchler, Philippe; Reyes, Mauricio

    2012-01-01

    Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.

  2. Current status of gene therapy for brain tumors.

    PubMed

    Murphy, Andrea M; Rabkin, Samuel D

    2013-04-01

    Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replication-competent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.

  3. Current status of gene therapy for brain tumors

    PubMed Central

    MURPHY, ANDREA M.; RABKIN, SAMUEL D.

    2013-01-01

    Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replication-competent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma. PMID:23246627

  4. An epigenetic gateway to brain tumor cell identity.

    PubMed

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

    2016-01-01

    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 microenvironmental factors on 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, as well as addressing the potential to exploit these alterations as new therapeutic strategies for the treatment of brain cancer.

  5. Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors

    ClinicalTrials.gov

    2010-03-15

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Poor Performance Status; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  6. Doublecortin is preferentially expressed in invasive human brain tumors.

    PubMed

    Daou, Marie-Claire; Smith, Thomas W; Litofsky, N Scott; Hsieh, Chung C; Ross, Alonzo H

    2005-11-01

    Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P<0.0001) and the low-grade invasive group (P<0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.

  7. Gene therapeutics: the future of brain tumor therapy?

    PubMed

    Cutter, Jennifer L; Kurozumi, Kazuhiko; Chiocca, E Antonio; Kaur, Balveen

    2006-07-01

    Primary glioblastoma multiforme is an aggressive brain tumor that has no cure. Current treatments include gross resection of the tumor, radiation and chemotherapy. Despite valiant efforts, prognosis remains dismal. A promising new technique involves the use of oncolytic viruses that can specifically replicate and lyse in cancers, without spreading to normal tissues. Currently, these are being tested in relevant preclinical models and clinical trials as a therapeutic modality for many types of cancer. Results from recent clinical trials with oncolytic viruses have revealed the safety of this approach, although evidence for efficacy remains elusive. Oncolytic viral strategies are summarized in this review, with a focus on therapies used in brain tumors.

  8. Medical management of brain tumors and the sequelae of treatment

    PubMed Central

    Schiff, David; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.

    2015-01-01

    Patients with malignant brain tumors are prone to complications that negatively impact their quality of life and sometimes their overall survival as well. Tumors may directly provoke seizures, hypercoagulable states with resultant venous thromboembolism, and mood and cognitive disorders. Antitumor treatments and supportive therapies also produce side effects. In this review, we discuss major aspects of supportive care for patients with malignant brain tumors, with particular attention to management of seizures, venous thromboembolism, corticosteroids and their complications, chemotherapy including bevacizumab, and fatigue, mood, and cognitive dysfunction. PMID:25358508

  9. The roles of viruses in brain tumor initiation and oncomodulation

    PubMed Central

    Kofman, Alexander; Marcinkiewicz, Lucasz; Dupart, Evan; Lyshchev, Anton; Martynov, Boris; Ryndin, Anatolii; Kotelevskaya, Elena; Brown, Jay; Schiff, David

    2012-01-01

    While some avian retroviruses have been shown to induce gliomas in animal models, human herpesviruses, specifically, the most extensively studied cytomegalovirus, and the much less studied roseolovirus HHV-6, and Herpes simplex viruses 1 and 2, currently attract more and more attention as possible contributing or initiating factors in the development of human brain tumors. The aim of this review is to summarize and highlight the most provoking findings indicating a potential causative link between brain tumors, specifically malignant gliomas, and viruses in the context of the concepts of viral oncomodulation and the tumor stem cell origin. PMID:21720806

  10. An evaluative tool for preoperative planning of brain tumor resection

    NASA Astrophysics Data System (ADS)

    Coffey, Aaron M.; Garg, Ishita; Miga, Michael I.; Thompson, Reid C.

    2010-02-01

    A patient specific finite element biphasic brain model has been utilized to codify a surgeon's experience by establishing quantifiable biomechanical measures to score orientations for optimal planning of brain tumor resection. When faced with evaluating several potential approaches to tumor removal during preoperative planning, the goal of this work is to facilitate the surgeon's selection of a patient head orientation such that tumor presentation and resection is assisted via favorable brain shift conditions rather than trying to allay confounding ones. Displacement-based measures consisting of area classification of the brain surface shifting in the craniotomy region and lateral displacement of the tumor center relative to an approach vector defined by the surgeon were calculated over a range of orientations and used to form an objective function. The objective function was used in conjunction with Levenberg-Marquardt optimization to find the ideal patient orientation. For a frontal lobe tumor presentation the model predicts an ideal orientation that indicates the patient should be placed in a lateral decubitus position on the side contralateral to the tumor in order to minimize unfavorable brain shift.

  11. [Surgery of metastatic brain tumors with new surgical instruments].

    PubMed

    Nomura, K; Shibui, S; Matsuoka, K; Watanabe, T; Nakamura, O

    1987-05-01

    The risk of damages of neurological function by the operation of metastatic brain tumors was reduced considerably after introduction of neurosurgical apparatuses, such as ultrasonograph, ultrasonic surgical aspirator and laser scalpel. Of these, ultrasonograph is useful to indicate the exact location of brain tumor at real time during the operation. Ultrasonic surgical aspirator reduced the risk of damage on important brain structures due to the selectivity of fragmentation and the safety of the dissection in the vicinity of important vessels and nerve tissues. Laser scalpel is also useful to extirpate the hemorrhagic tumor with hard consistency. Cases introduced in this paper were: case 1, brain metastasis from lung cancer located just under the left motor area in brain; case 2, metastasis with abundant neovascularization from renal cancer to orbital cavity which showed invasion to orbital roof and frontal bone; case 3, radiation induced sarcoma after the treatment of retinoblastoma; case 4, a large cerebellar metastatic tumor; case 5, neurogenic sarcoma which were successfully removed by using one of or combination of ultrasonograph, ultrasonic aspirator and laser scalpel. Advantage of these new instruments for the surgery on metastatic brain tumor was mentioned here. However, it is necessarily to get a custom before we use these apparatuses at operation efficiently.

  12. Brain tumor modeling: glioma growth and interaction with chemotherapy

    NASA Astrophysics Data System (ADS)

    Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

    2011-10-01

    In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

  13. Factors affecting intellectual outcome in pediatric brain tumor patients

    SciTech Connect

    Ellenberg, L.; McComb, J.G.; Siegel, S.E.; Stowe, S.

    1987-11-01

    A prospective study utilizing repeated intellectual testing was undertaken in 73 children with brain tumors consecutively admitted to Childrens Hospital of Los Angeles over a 3-year period to determine the effect of tumor location, extent of surgical resection, hydrocephalus, age of the child, radiation therapy, and chemotherapy on cognitive outcome. Forty-three patients were followed for at least two sequential intellectual assessments and provide the data for this study. Children with hemispheric tumors had the most general cognitive impairment. The degree of tumor resection, adequately treated hydrocephalus, and chemotherapy had no bearing on intellectual outcome. Age of the child affected outcome mainly as it related to radiation. Whole brain radiation therapy was associated with cognitive decline. This was especially true in children below 7 years of age, who experienced a very significant loss of function after whole brain radiation therapy.

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

    PubMed

    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.

  15. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I.; Lamothe-Molina, Paul J.; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A.

    2015-01-01

    Abstract. Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of 973±14, whereas oligodendrogliomas exhibit a mean of 942±21. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of 919±43, and the necrotic region presented a mean of 869±66. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  16. Research of the multimodal brain-tumor segmentation algorithm

    NASA Astrophysics Data System (ADS)

    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.

  17. The therapy of infantile malignant brain tumors: current status?

    PubMed

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

    Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors

  18. Blood Brain Barrier: A Challenge for Effectual Therapy of Brain Tumors

    PubMed Central

    Bhowmik, Arijit; Ghosh, Mrinal Kanti

    2015-01-01

    Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier. PMID:25866775

  19. Exosomes as Tools to Suppress Primary Brain Tumor.

    PubMed

    Katakowski, Mark; Chopp, Michael

    2016-04-01

    Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood-brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing. We previously demonstrated a novel treatment whereby mesenchymal stromal cells were employed to package tumor-suppressing miR-146b into exosomes, which were then used to reduce malignant glioma growth in rat. The use of exosomes to raise the immune system against tumor is also drawing interest. Exosomes from dendritic cells which are antigen-presenting, and have been used for treatment of brain tumor may be divided into three categories: (1) exosomes for immunomodulation-based therapy, (2) exosomes as delivery vehicles for anti-tumor nucleotides, and (3) exosomes as drug delivery vehicles. Here, we will provide an overview of these three applications of exosomes to treat brain tumor, and examine their prospects on the long road to clinical use.

  20. Telomerase activity in human brain tumors: astrocytoma and meningioma.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mohammadi-asl, Javad; Mehdipour, Parvin

    2013-05-01

    Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the standard protocols. In the brain tissues, telomerase activity was positive in 39 (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

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

    PubMed

    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.

  2. Brain mapping in tumors: intraoperative or extraoperative?

    PubMed

    Duffau, Hugues

    2013-12-01

    In nontumoral epilepsy surgery, the main goal for all preoperative investigation is to first determine the epileptogenic zone, and then to analyze its relation to eloquent cortex, in order to control seizures while avoiding adverse postoperative neurologic outcome. To this end, in addition to neuropsychological assessment, functional neuroimaging and scalp electroencephalography, extraoperative recording, and electrical mapping, especially using subdural strip- or grid-electrodes, has been reported extensively. Nonetheless, in tumoral epilepsy surgery, the rationale is different. Indeed, the first aim is rather to maximize the extent of tumor resection while minimizing postsurgical morbidity, in order to increase the median survival as well as to preserve quality of life. As a consequence, as frequently seen in infiltrating tumors such as gliomas, where these lesions not only grow but also migrate along white matter tracts, the resection should be performed according to functional boundaries both at cortical and subcortical levels. With this in mind, extraoperative mapping by strips/grids is often not sufficient in tumoral surgery, since in essence, it allows study of the cortex but cannot map subcortical pathways. Therefore, intraoperative electrostimulation mapping, especially in awake patients, is more appropriate in tumor surgery, because this technique allows real-time detection of areas crucial for cerebral functions--eloquent cortex and fibers--throughout the resection. In summary, rather than choosing one or the other of different mapping techniques, methodology should be adapted to each pathology, that is, extraoperative mapping in nontumoral epilepsy surgery and intraoperative mapping in tumoral surgery.

  3. Application of SLT contact laser in resection of brain tumors

    NASA Astrophysics Data System (ADS)

    Li, Han-Jie; Li, Zhi-Qiang; Li, Chan-Yuan

    1998-11-01

    28 cases of brain tumors were operated by SLT contact Nd:YAG laser from October 1995 to May 1997 in our hospital. Among these, 14 are menin-giomas, 5 are astrocytomas. Others are tumors such as acoustic neuromas, craniopharyngiomas, etc 21 cases underwent common craniotomy, 3, laser endoscopy operation; and 4, laser therapy under microscopy. Method of tumor resection: firstly, cutting and separating the tumor from brain tissues with GRP by 5-15w; secondly, vaporizing parenchyma of tumor with MTRL and sucking it, again, cutting and separating and so on, lastly removing the tumor entirely. The power of vaporization for glioma or tumors in ventricles is about 20-30w, but for meningiomas, 30-60w. MT was used on power of 15-20w to coagulate and homeostate the left cavity of tumor. According to our experience, laser operation can make bleeding reduced markedly, tumor resection become more thorough, and postoperative response and complications decrease obviously.

  4. Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate.

    PubMed

    Ram, Z; Samid, D; Walbridge, S; Oshiro, E M; Viola, J J; Tao-Cheng, J H; Shack, S; Thibault, A; Myers, C E; Oldfield, E H

    1994-06-01

    Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.

  5. Culture and Isolation of Brain Tumor Initiating Cells.

    PubMed

    Vora, Parvez; Venugopal, Chitra; McFarlane, Nicole; Singh, Sheila K

    2015-08-03

    Brain tumors are typically composed of heterogeneous cells that exhibit distinct phenotypic characteristics and proliferative potentials. Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), possess an ability to differentiate along multiple lineages, self-renew, and initiate tumors in vivo. This unit describes protocols for the culture and isolation BTICs. We applied culture conditions and assays originally used for normal neural stem cells (NSCs) in vitro to a variety of brain tumors. Using fluorescence-activated cell sorting for the neural precursor cell surface marker CD133/CD15, BTICs can be isolated and studied prospectively. Isolation of BTICs from GBM bulk tumor will enable examination of dissimilar morphologies, self-renewal capacities, tumorigenicity, and therapeutic sensitivities. As cancer is also considered a disease of unregulated self-renewal and differentiation, an understanding of BTICs is fundamental to understanding tumor growth. Ultimately, it will lead to novel drug discovery approaches that strategically target the functionally relevant BTIC population.

  6. Circulating biomarker panels for targeted therapy in brain tumors.

    PubMed

    Tanase, Cristiana; Albulescu, Radu; Codrici, Elena; Popescu, Ionela Daniela; Mihai, Simona; Enciu, Ana Maria; Cruceru, Maria Linda; Popa, Adrian Claudiu; Neagu, Ana Iulia; Necula, Laura Georgiana; Mambet, Cristina; Neagu, Monica

    2015-01-01

    An important goal of oncology is the development of cancer risk-identifier biomarkers that aid early detection and target therapy. High-throughput profiling represents a major concern for cancer research, including brain tumors. A promising approach for efficacious monitoring of disease progression and therapy could be circulating biomarker panels using molecular proteomic patterns. Tailoring treatment by targeting specific protein-protein interactions and signaling networks, microRNA and cancer stem cell signaling in accordance with tumor phenotype or patient clustering based on biomarker panels represents the future of personalized medicine for brain tumors. Gathering current data regarding biomarker candidates, we address the major challenges surrounding the biomarker field of this devastating tumor type, exploring potential perspectives for the development of more effective predictive biomarker panels.

  7. Delayed Contrast Extravasation MRI for Depicting Tumor and Non-Tumoral Tissues in Primary and Metastatic Brain Tumors

    PubMed Central

    Zach, Leor; Guez, David; Last, David; Daniels, Dianne; Grober, Yuval; Nissim, Ouzi; Hoffmann, Chen; Nass, Dvora; Talianski, Alisa; Spiegelmann, Roberto; Cohen, Zvi R.; Mardor, Yael

    2012-01-01

    The current standard of care for newly diagnosed glioblastoma multiforme (GBM) is resection followed by radiotherapy with concomitant and adjuvant temozolomide. Recent studies suggest that nearly half of the patients with early radiological deterioration post treatment do not suffer from tumor recurrence but from pseudoprogression. Similarly, a significant number of patients with brain metastases suffer from radiation necrosis following radiation treatments. Conventional MRI is currently unable to differentiate tumor progression from treatment-induced effects. The ability to clearly differentiate tumor from non-tumoral tissues is crucial for appropriate patient management. Ten patients with primary brain tumors and 10 patients with brain metastases were scanned by delayed contrast extravasation MRI prior to surgery. Enhancement subtraction maps calculated from high resolution MR images acquired up to 75 min after contrast administration were used for obtaining stereotactic biopsies. Histological assessment was then compared with the pre-surgical calculated maps. In addition, the application of our maps for prediction of progression was studied in a small cohort of 13 newly diagnosed GBM patients undergoing standard chemoradiation and followed up to 19.7 months post therapy. The maps showed two primary enhancement populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation. Comparison with histology confirmed the fast population to consist of morphologically active tumor and the slow population to consist of non-tumoral tissues. Our maps demonstrated significant correlation with perfusion-weighted MR data acquired simultaneously, although contradicting examples were shown. Preliminary results suggest that early changes in the fast volumes may serve as a predictor for time to progression. These preliminary results suggest that our high resolution

  8. Remote Postoperative Epidural Hematoma after Brain Tumor Surgery

    PubMed Central

    Chung, Ho-Jung; Park, Jae-Sung; Jeun, Sin-Soo

    2015-01-01

    A postoperative epidural hematoma (EDH) is a serious and embarrassing complication, which usually occurs at the site of operation after intracranial surgery. However, remote EDH is relatively rare. We report three cases of remote EDH after brain tumor surgery. All three cases seemed to have different causes of remote postoperative EDH; however, all patients were managed promptly and showed excellent outcomes. Although the exact mechanism of remote postoperative EDH is unknown, surgeons should be cautious of the speed of lowering intracranial pressure and implement basic procedures to prevent this hazardous complication of brain tumor surgery. PMID:26605271

  9. Interpreting WAIS-III performance after primary brain tumor surgery.

    PubMed

    Gonçalves, Marta de A; Simões, Mário R; Castro-Caldas, Alexandre

    2017-01-01

    The literature lacks information on the performance of patients with brain tumors on the Wechsler Intelligence Scales. This study aimed to explore the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) performance profile of 23 consecutive patients with brain tumors and 23 matched controls selected from the Portuguese WAIS-III standardization sample, using the technical manual steps recommended for score interpretation. The control group was demographically matched to the tumor group regarding gender, age, education, profession, and geographic region. The technical manual steps recommended for score interpretation were applied. Patients with brain tumors had significantly lower performances on the Performance IQ, Full-Scale IQ, Perceptual Organization Index, Working Memory Index, Processing Speed Index, Arithmetic, Object Assembly, and Picture Arrangement, though all scaled scores were within the normal range according to the manual tables. Only Vocabulary and Comprehension scatter scores were statistically different between groups. No strengths or weaknesses were found for either group. The mean discrepancy scores do not appear to have clinical value for this population. In conclusion, the study results did not reveal a specific profile for patients with brain tumors on the WAIS-III.

  10. Training stem cells for treatment of malignant brain tumors.

    PubMed

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-09-26

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  11. Diffusion in the extracellular space in brain and tumors

    NASA Astrophysics Data System (ADS)

    Verkman, A. S.

    2013-08-01

    Diffusion of solutes and macromolecules in the extracellular space (ECS) in brain is important for non-synaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. Diffusion in tumor ECS is important for delivery of anti-tumor drugs. The ECS in brain comprises ˜20% of brain parenchymal volume and contains cell-cell gaps down to ˜50 nm. We have developed fluorescence methods to quantify solute diffusion in the ECS, allowing measurements deep in solid tissues using microfiberoptics with micron tip size. Diffusion through the tortuous ECS in brain is generally slowed by ˜3-5-fold compared with that in water, with approximately half of the slowing due to tortuous ECS geometry and half due to the mildly viscous extracellular matrix (ECM). Mathematical modeling of slowed diffusion in an ECS with reasonable anatomical accuracy is in good agreement with experiment. In tumor tissue, diffusion of small macromolecules is only mildly slowed (<3-fold slower than in water) in superficial tumor, but is greatly slowed (>10-fold) at a depth of few millimeters as the tumor tissue becomes more compact. Slowing by ECM components such as collagen contribute to the slowed diffusion. Therefore, as found within cells, cellular crowding and highly tortuous transport can produce only minor slowing of diffusion in the ECS.

  12. Progress on the diagnosis and evaluation of brain tumors

    PubMed Central

    Gao, Huile

    2013-01-01

    Abstract Brain tumors are one of the most challenging disorders encountered, and early and accurate diagnosis is essential for the management and treatment of these tumors. In this article, diagnostic modalities including single-photon emission computed tomography, positron emission tomography, magnetic resonance imaging, and optical imaging are reviewed. We mainly focus on the newly emerging, specific imaging probes, and their potential use in animal models and clinical settings. PMID:24334439

  13. Agnosias: recognition disorders in patients with brain tumors.

    PubMed

    Gainotti, Guido

    2012-06-01

    Two main varieties of recognition disorders are distinguished in neuropsychology: agnosias and semantic disorders. The term agnosias is generally used to denote recognition defects limited to a single perceptual modality (which is itself apparently intact), whereas the term semantic disorders is used to denote recognition defects involving all the sensory modalities in a roughly similar manner. Brain tumors can be one of the aetiologies underlying agnosias and semantic disorders. However, due to the heterogeneity and the rarity of recognition disorders, their investigation can be useful only to suggest or exclude the oncological nature of a brain lesion, but not to systematically monitor the clinical outcome in tumor patients. Furthermore, the relevance of recognition disorders as a hint toward a diagnosis of brain tumor varies according to the type of agnosia and of semantic disorder and the localization of the underlying brain pathology. The hypothesis that a variety of agnosia (or of semantic disorder) may be due to a neoplastic lesion can, therefore, be advanced if it is consistent with our knowledge about the usual localization and the growing patterns of different types of brain tumors.

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

    PubMed

    Cheng, Jun; Huang, Wei; Cao, Shuangliang; Yang, Ru; Yang, Wei; Yun, Zhaoqiang; Wang, Zhijian; Feng, Qianjin

    2015-01-01

    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.

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

    PubMed Central

    Cheng, Jun; Huang, Wei; Cao, Shuangliang; Yang, Ru; Yang, Wei; Yun, Zhaoqiang; Wang, Zhijian; Feng, Qianjin

    2015-01-01

    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. PMID:26447861

  16. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies.

    PubMed

    Chadwick, Emily J; Yang, David P; Filbin, Mariella G; Mazzola, Emanuele; Sun, Yu; Behar, Oded; Pazyra-Murphy, Maria F; Goumnerova, Liliana; Ligon, Keith L; Stiles, Charles D; Segal, Rosalind A

    2015-11-07

    Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not easily grown in standard culture conditions. Neurosphere cultures under serum-free conditions and orthotopic xenografts have expanded the range of tumors that can be maintained. However, many types of brain tumors remain difficult to propagate or study. This is particularly true for pediatric brain tumors such as pilocytic astrocytomas and medulloblastomas. This protocol describes a system that allows primary human brain tumors to be grown in culture. This quantitative assay can be used to investigate the effect of microenvironment on tumor growth, and to test new drug therapies. This protocol describes a system where fluorescently labeled brain tumor cells are grown on an organotypic brain slice from a juvenile mouse. The response of tumor cells to drug treatments can be studied in this assay, by analyzing changes in the number of cells on the slice over time. In addition, this system can address the nature of the microenvironment that normally fosters growth of brain tumors. This brain tumor organotypic slice co-culture assay provides a propitious system for testing new drugs on human tumor cells within a brain microenvironment.

  17. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies

    PubMed Central

    Chadwick, Emily J.; Yang, David P.; Filbin, Mariella G.; Mazzola, Emanuele; Sun, Yu; Behar, Oded; Pazyra-Murphy, Maria F.; Goumnerova, Liliana; Ligon, Keith L.; Stiles, Charles D.; Segal, Rosalind A.

    2015-01-01

    Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not easily grown in standard culture conditions. Neurosphere cultures under serum-free conditions and orthotopic xenografts have expanded the range of tumors that can be maintained. However, many types of brain tumors remain difficult to propagate or study. This is particularly true for pediatric brain tumors such as pilocytic astrocytomas and medulloblastomas. This protocol describes a system that allows primary human brain tumors to be grown in culture. This quantitative assay can be used to investigate the effect of microenvironment on tumor growth, and to test new drug therapies. This protocol describes a system where fluorescently labeled brain tumor cells are grown on an organotypic brain slice from a juvenile mouse. The response of tumor cells to drug treatments can be studied in this assay, by analyzing changes in the number of cells on the slice over time. In addition, this system can address the nature of the microenvironment that normally fosters growth of brain tumors. This brain tumor organotypic slice co-culture assay provides a propitious system for testing new drugs on human tumor cells within a brain microenvironment. PMID:26575352

  18. Intracranial foreign body granuloma simulating brain tumor: a case report

    PubMed Central

    Saeidiborojeni, Hamid Reza; Fakheri, Taravat; Iizadi, Babak

    2011-01-01

    Intracranial foreign body granulomas are rarely reported. Clinical symptoms caused by foreign body granulomas can be noticed from months to many years after surgical procedure. The most common reported etiology is suture material. A 45-year-old woman was presented with grand mal epilepsy. She was operated for brain tumor 19 years ago. In CT scan, a round radio-dense mass resembling a tumor at anterior fossa was seen. She underwent craniotomy and resected a granuloma with cotton fibers surrounded by yellow capsule without residual or recurrent tumor. Granuloma can mimic intracranial meningioma and special attention should be paid not to leave cotton pledgets during operations. PMID:22091258

  19. Development of multifunctional nanoparticles for brain tumor diagnosis and therapy

    NASA Astrophysics Data System (ADS)

    Veiseh, Omid

    Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents developed for magnetic resonance (MR) imaging and drug delivery. MNPs have traditionally been developed for disease imaging via passive targeting, but recent advances in nanotechnology have enabled cellular-specific targeting, drug delivery and multi-modal imaging using these nanoparticles. Opportunities now exist to engineer MNP with designated features (e.g., size, coatings, and molecular functionalizations) for specific biomedical applications. The goal of this interdisciplinary research project is to develop targeting multifunctional nanoparticles, serving as both contrast agents and drug carriers that can effectively pass biological barriers, for diagnosis, staging and treatment of brain tumors. The developed nanoparticle system consists of a superparamagnetic iron oxide nanoparticle core (NP) and a shell comprised of biodegradable polymers such as polyethylene glycol (PEG) and chitosan. Additionally, near-infrared fluorescing (NIRF) molecules were integrated onto the NP shell to enable optical detection. Tumor targeting was achieved by the addition of chlorotoxin, a peptide with that has high affinity to 74 out of the 79 classifications of primary brain tumors and ability to illicit a therapeutic effect. This novel NP system was tested both in vitro and in vivo and was shown to specifically target gliomas in tissue culture and medulloblastomas in transgenic mice with an intact blood brain barriers (BBB), and delineate tumor boundaries in both MR and optical imaging. Additionally, the therapeutic potential of this NP system was explored in vitro, which revealed a unique nanoparticle-enabled pathway that enhances the therapeutic potential of bound peptides by promoting the internalization of membrane bound cell surface receptors. This NP system was further modified with siRNA and evaluated as a carrier for brain tumor targeted gene therapy. Most significantly, the evaluation of

  20. American brain tumor patients treated with BNCT in Japan

    SciTech Connect

    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.

  1. Dexamethasone alleviates tumor-associated brain damage and angiogenesis.

    PubMed

    Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael; Eyupoglu, Ilker Y; Savaskan, Nicolai E

    2014-01-01

    Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc-; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage.

  2. Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis

    PubMed Central

    Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael

    2014-01-01

    Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc−; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage. PMID:24714627

  3. MRI virtual biopsy and treatment of brain metastatic tumors with targeted nanobioconjugates: nanoclinic in the brain.

    PubMed

    Patil, Rameshwar; Ljubimov, Alexander V; Gangalum, Pallavi R; Ding, Hui; Portilla-Arias, Jose; Wagner, Shawn; Inoue, Satoshi; Konda, Bindu; Rekechenetskiy, Arthur; Chesnokova, Alexandra; Markman, Janet L; Ljubimov, Vladimir A; Li, Debiao; Prasad, Ravi S; Black, Keith L; Holler, Eggehard; Ljubimova, Julia Y

    2015-05-26

    Differential diagnosis of brain magnetic resonance imaging (MRI) enhancement(s) remains a significant problem, which may be difficult to resolve without biopsy, which can be often dangerous or even impossible. Such MRI enhancement(s) can result from metastasis of primary tumors such as lung or breast, radiation necrosis, infections, or a new primary brain tumor (glioma, meningioma). Neurological symptoms are often the same on initial presentation. To develop a more precise noninvasive MRI diagnostic method, we have engineered a new class of poly(β-l-malic acid) polymeric nanoimaging agents (NIAs). The NIAs carrying attached MRI tracer are able to pass through the blood-brain barrier (BBB) and specifically target cancer cells for efficient imaging. A qualitative/quantitative "MRI virtual biopsy" method is based on a nanoconjugate carrying MRI contrast agent gadolinium-DOTA and antibodies recognizing tumor-specific markers and extravasating through the BBB. In newly developed double tumor xenogeneic mouse models of brain metastasis this noninvasive method allowed differential diagnosis of HER2- and EGFR-expressing brain tumors. After MRI diagnosis, breast and lung cancer brain metastases were successfully treated with similar tumor-targeted nanoconjugates carrying molecular inhibitors of EGFR or HER2 instead of imaging contrast agent. The treatment resulted in a significant increase in animal survival and markedly reduced immunostaining for several cancer stem cell markers. Novel NIAs could be useful for brain diagnostic MRI in the clinic without currently performed brain biopsies. This technology shows promise for differential MRI diagnosis and treatment of brain metastases and other pathologies when biopsies are difficult to perform.

  4. Learning Profiles of Survivors of Pediatric Brain Tumors

    ERIC Educational Resources Information Center

    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…

  5. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    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, life-long 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 suggests 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 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. PMID:25027187

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

    PubMed

    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.

  7. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    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.

  8. Gene therapy for brain tumors: basic developments and clinical implementation.

    PubMed

    Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R; Castro, Maria G

    2012-10-11

    Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM.

  9. Gene Therapy for Brain Tumors: Basic Developments and Clinical Implementation

    PubMed Central

    Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R; Castro, Maria G

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. PMID:22906921

  10. Antiangiogenic (metronomic) chemotherapy for brain tumors: current and future perspectives.

    PubMed

    Samuel, David P; Wen, Patrick Y; Kieran, Mark W

    2009-07-01

    Significant advances in the diagnosis and treatment of brain tumors have been made through better imaging, surgical techniques and advances in radiation therapy. However, the cure rate for most adult and pediatric brain tumor patients has not mirrored this success. Angiogenesis, the development of neovascularization, provides the required nutrients and oxygen to an expanding tumor and is controlled by a complex balance of proangiogenic cytokines and antiangiogenic factors. A series of new inhibitors of angiogenesis are now in clinical trials. Most of these rely on inhibiting tumor cell-mediated cytokines or blocking the activation of their cognate receptors. Cytotoxic chemotherapy, by contrast, targets dividing cells but can be modulated to attack dividing endothelial cells. This review will focus on the use of low-dose antiangiogenic (also called metronomic) chemotherapy to inhibit endothelial cell function and resultant neovascularization in the treatment of adult and pediatric brain tumors. By examining the biology and preclinical findings that led to the development of antiangiogenic/metronomic chemotherapy, clinical studies have been undertaken that support the role of this approach in the clinic, and have led to the introduction of a number of markers being used to better predict active combinations and appropriate patient populations.

  11. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello Enrico; Schiariti, Marco P.; Grana, Chiara M.; Ferrari, Mahila; Cremonesi, Marta; Boschi, Federico

    2016-05-01

    We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.

  12. Unsupervised measurement of brain tumor volume on MR images.

    PubMed

    Velthuizen, R P; Clarke, L P; Phuphanich, S; Hall, L O; Bensaid, A M; Arrington, J A; Greenberg, H M; Silbiger, M L

    1995-01-01

    We examined unsupervised methods of segmentation of MR images of the brain for measuring tumor volume in response to treatment. Two clustering methods were used: fuzzy c-means and a nonfuzzy clustering algorithm. Results were compared with volume segmentations by two supervised methods, k-nearest neighbors and region growing, and all results were compared with manual labelings. Results of individual segmentations are presented as well as comparisons on the application of the different methods with 10 data sets of patients with brain tumors. Unsupervised segmentation is preferred for measuring tumor volumes in response to treatment, as it eliminates operator dependency and may be adequate for delineation of the target volume in radiation therapy. Some obstacles need to be overcome, in particular regarding the detection of anatomically relevant tissue classes. This study shows that these improvements are possible.

  13. Alterations of telomere length in human brain tumors.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mehdipour, Parvin

    2011-09-01

    Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100 bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

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

    PubMed Central

    Klinger, Neil V.

    2016-01-01

    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. PMID:27807473

  15. Simulation of brain tumor resection in image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Fontaine, Kathryn; Hartov, Alex; Roberts, David; Paulsen, Keith

    2011-03-01

    Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow

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

    PubMed

    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.

  17. What Are the Risk Factors for Brain and Spinal Cord Tumors in Children?

    MedlinePlus

    ... and Prevention What Are the Risk Factors for Brain and Spinal Cord Tumors in Children? A risk ... Factors with uncertain, controversial, or unproven effects on brain tumor risk Cell phone use Cell phones give ...

  18. Advanced MRI for Pediatric Brain Tumors with Emphasis on Clinical Benefits

    PubMed Central

    Ra, Young-Shin

    2017-01-01

    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. PMID:28096729

  19. Imaging of brain tumor proliferative activity with iodine-131-iododeoxyuridine

    SciTech Connect

    Tjuvajev, J.G.; Macapinlac, H.A.; Daghighian, F.

    1994-09-01

    Iodine-131-iododeoxyuridine (IUdR) uptake and retention was imaged with SPECT at 2 and 24 hr after administering a 10-mCi dose to six patients with primary brain tumors. The SPECT images were directly compared to gadolinium contrast-enhanced MR images as well as to ({sup 18}F) fluorodeoxyglucose (FDG) PET scans and {sup 201}Tl SPECT scans. Localized uptake and retention of IUdR-derived radioactivity was observed in five of six patients. The plasma half-life of ({sup 131}I) IUdR was short (1.5 min) in comparison to the half-life of total plasma radioactivity (6.4 hr). The pattern of ({sup 131}I)IUdR-derived radioactivity was markedly different in the 2-hr compared to 24-hr images. Radioactivity was localized along the periphery of the tumor and extended beyond the margin of tumor identified by contrast enhancement on MRI. The estimated levels of tumor radioactivity at 24 hr, based on semiquantitative phantom studies, ranged between <0.1 and 0.2 {mu}Ci/cc (<0.001% and 0.002% dose/cc); brain levels were not measurable. Iodine-131-IUdR SPECT imaging of brain tumor proliferation has low (marginal) sensitivity due to low count rates and can detect only the most active regions of tumor growth. Imaging at 24 hr represents a washout strategy to reduce {sup 131}I-labeled metabolites contributing to background activity in the tumors, and is more likely to show the pattern of ({sup 131}I)IUdR-DNA incorporation and thereby increase image specificity. Iodine-123-IUdR SPECT imaging at 12 hr and the use of ({sup 124}I)IUdR and PET will improve count acquisitions and image quality. 74 refs., 6 figs., 2 tabs.

  20. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references.

  1. Emerging techniques and technologies in brain tumor imaging

    PubMed Central

    Ellingson, Benjamin M.; Bendszus, Martin; Sorensen, A. Gregory; Pope, Whitney B.

    2014-01-01

    The purpose of this report is to describe the state of imaging techniques and technologies for detecting response of brain tumors to treatment in the setting of multicenter clinical trials. Within currently used technologies, implementation of standardized image acquisition and the use of volumetric estimates and subtraction maps are likely to help to improve tumor visualization, delineation, and quantification. Upon further development, refinement, and standardization, imaging technologies such as diffusion and perfusion MRI and amino acid PET may contribute to the detection of tumor response to treatment, particularly in specific treatment settings. Over the next few years, new technologies such as 23Na MRI and CEST imaging technologies will be explored for their use in expanding the ability to quantitatively image tumor response to therapies in a clinical trial setting. PMID:25313234

  2. Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series

    PubMed Central

    Dunn-Pirio, Anastasie M.; Billakota, Santoshi; Peters, Katherine B.

    2016-01-01

    Seizures are common among patients with brain tumors. Transient, postictal magnetic resonance imaging abnormalities are a long recognized phenomenon. However, these radiographic changes are not as well studied in the brain tumor population. Moreover, reversible neuroimaging abnormalities following seizure activity may be misinterpreted for tumor progression and could consequently result in unnecessary tumor-directed treatment. Here, we describe two cases of patients with brain tumors who developed peri-ictal pseudoprogression and review the relevant literature. PMID:27462237

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

    PubMed

    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.

  4. Brain Tumor Segmentation Using Convolutional Neural Networks in MRI Images.

    PubMed

    Pereira, Sergio; Pinto, Adriano; Alves, Victor; Silva, Carlos A

    2016-05-01

    Among brain tumors, gliomas are the most common and aggressive, leading to a very short life expectancy in their highest grade. Thus, treatment planning is a key stage to improve the quality of life of oncological patients. Magnetic resonance imaging (MRI) is a widely used imaging technique to assess these tumors, but the large amount of data produced by MRI prevents manual segmentation in a reasonable time, limiting the use of precise quantitative measurements in the clinical practice. So, automatic and reliable segmentation methods are required; however, the large spatial and structural variability among brain tumors make automatic segmentation a challenging problem. In this paper, we propose an automatic segmentation method based on Convolutional Neural Networks (CNN), exploring small 3 ×3 kernels. The use of small kernels allows designing a deeper architecture, besides having a positive effect against overfitting, given the fewer number of weights in the network. We also investigated the use of intensity normalization as a pre-processing step, which though not common in CNN-based segmentation methods, proved together with data augmentation to be very effective for brain tumor segmentation in MRI images. Our proposal was validated in the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013), obtaining simultaneously the first position for the complete, core, and enhancing regions in Dice Similarity Coefficient metric (0.88, 0.83, 0.77) for the Challenge data set. Also, it obtained the overall first position by the online evaluation platform. We also participated in the on-site BRATS 2015 Challenge using the same model, obtaining the second place, with Dice Similarity Coefficient metric of 0.78, 0.65, and 0.75 for the complete, core, and enhancing regions, respectively.

  5. Brain Tumor Segmentation using Convolutional Neural Networks in MRI Images.

    PubMed

    Pereira, Sergio; Pinto, Adriano; Alves, Victor; Silva, Carlos A

    2016-03-04

    Among brain tumors, gliomas are the most common and aggressive, leading to a very short life expectancy in their highest grade. Thus, treatment planning is a key stage to improve the quality of life of oncological patients. Magnetic Resonance Imaging (MRI) is a widely used imaging technique to assess these tumors, but the large amount of data produced by MRI prevents manual segmentation in a reasonable time, limiting the use of precise quantitative measurements in the clinical practice. So, automatic and reliable segmentation methods are required; however, the large spatial and structural variability among brain tumors make automatic segmentation a challenging problem. In this paper, we propose an automatic segmentation method based on Convolutional Neural Networks (CNN), exploring small 33 kernels. The use of small kernels allows designing a deeper architecture, besides having a positive effect against overfitting, given the fewer number of weights in the network. We also investigated the use of intensity normalization as a pre-processing step, which though not common in CNN-based segmentation methods, proved together with data augmentation to be very effective for brain tumor segmentation in MRI images. Our proposal was validated in the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013), obtaining simultaneously the first position for the complete, core, and enhancing regions in Dice Similarity Coefficient metric (0:88, 0:83, 0:77) for the Challenge data set. Also, it obtained the overall first position by the online evaluation platform. We also participated in the on-site BRATS 2015 Challenge using the same model, obtaining the second place, with Dice Similarity Coefficient metric of 0:78, 0:65, and 0:75 for the complete, core, and enhancing regions, respectively.

  6. Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

    PubMed

    Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

    2016-07-01

    This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.

  7. Neurodegeneration in the Brain Tumor Microenvironment: Glutamate in the Limelight

    PubMed Central

    Savaskan, Nicolai E.; Fan, Zheng; Broggini, Thomas; Buchfelder, Michael; Eyüpoglu, Ilker Y.

    2015-01-01

    Malignant brain tumors are characterized by destructive growth and neuronal cell death making them one of the most devastating diseases. Neurodegenerative actions of malignant gliomas resemble mechanisms also found in many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. Recent data demonstrate that gliomas seize neuronal glutamate signaling for their own growth advantage. Excessive glutamate release via the glutamate/cystine antiporter xCT (system xc-, SLC7a11) renders cancer cells resistant to chemotherapeutics and create the tumor microenvironment toxic for neurons. In particular the glutamate/cystine antiporter xCT takes center stage in neurodegenerative processes and sets this transporter a potential prime target for cancer therapy. Noteworthy is the finding, that reactive oxygen species (ROS) activate transient receptor potential (TRP) channels and thereby TRP channels can potentiate glutamate release. Yet another important biological feature of the xCT/glutamate system is its modulatory effect on the tumor microenvironment with impact on host cells and the cancer stem cell niche. The EMA and FDA-approved drug sulfasalazine (SAS) presents a lead compound for xCT inhibition, although so far clinical trials on glioblastomas with SAS were ambiguous. Here, we critically analyze the mechanisms of action of xCT antiporter on malignant gliomas and in the tumor microenvironment. Deciphering the impact of xCT and glutamate and its relation to TRP channels in brain tumors pave the way for developing important cancer microenvironmental modulators and drugable lead targets. PMID:26411769

  8. Numerical simulations of MREIT conductivity imaging for brain tumor detection.

    PubMed

    Meng, Zi Jun; Sajib, Saurav Z K; Chauhan, Munish; Sadleir, Rosalind J; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2013-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new modality capable of imaging the electrical properties of human body using MRI phase information in conjunction with external current injection. Recent in vivo animal and human MREIT studies have revealed unique conductivity contrasts related to different physiological and pathological conditions of tissues or organs. When performing in vivo brain imaging, small imaging currents must be injected so as not to stimulate peripheral nerves in the skin, while delivery of imaging currents to the brain is relatively small due to the skull's low conductivity. As a result, injected imaging currents may induce small phase signals and the overall low phase SNR in brain tissues. In this study, we present numerical simulation results of the use of head MREIT for brain tumor detection. We used a realistic three-dimensional head model to compute signal levels produced as a consequence of a predicted doubling of conductivity occurring within simulated tumorous brain tissues. We determined the feasibility of measuring these changes in a time acceptable to human subjects by adding realistic noise levels measured from a candidate 3 T system. We also reconstructed conductivity contrast images, showing that such conductivity differences can be both detected and imaged.

  9. Advanced MR Imaging in Pediatric Brain Tumors, Clinical Applications.

    PubMed

    Lequin, Maarten; Hendrikse, Jeroen

    2017-02-01

    Advanced MR imaging techniques, such as spectroscopy, perfusion, diffusion, and functional imaging, have improved the diagnosis of brain tumors in children and also play an important role in defining surgical as well as therapeutic responses in these patients. In addition to the anatomic or structural information gained with conventional MR imaging sequences, advanced MR imaging techniques also provide physiologic information about tumor morphology, metabolism, and hemodynamics. This article reviews the physiology, techniques, and clinical applications of diffusion-weighted and diffusion tensor imaging, MR spectroscopy, perfusion MR imaging, susceptibility-weighted imaging, and functional MR imaging in the setting of neuro-oncology.

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

    ClinicalTrials.gov

    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

  11. Cellular phones and risk of brain tumors.

    PubMed

    Frumkin, H; Jacobson, A; Gansler, T; Thun, M J

    2001-01-01

    As cellular telephones are a relatively new technology, we do not yet have long-term follow-up on their possible biological effects. However, the lack of ionizing radiation and the low energy level emitted from cell phones and absorbed by human tissues make it unlikely that these devices cause cancer. Moreover, several well-designed epidemiologic studies find no consistent association between cell phone use and brain cancer. It is impossible to prove that any product or exposure is absolutely safe, especially in the absence of very long-term follow-up. Accordingly, the following summary from the Food and Drug Administration Center for Devices and Radiological Health offers advice to people concerned about their risk: If there is a risk from these products--and at this point we do not know that there is--it is probably very small. But if people are concerned about avoiding even potential risks, there are simple steps they can take to do so. People who must conduct extended conversations in their cars every day could switch to a type of mobile phone that places more distance between their bodies and the source of the RF, since the exposure level drops off dramatically with distance. For example, they could switch to: a mobile phone in which the antenna is located outside the vehicle, a hand-held phone with a built-in antenna connected to a different antenna mounted on the outside of the car or built into a separate package, or a headset with a remote antenna to a mobile phone carried at the waist. Again the scientific data do not demonstrate that mobile phones are harmful. But if people are concerned about the radiofrequency energy from these products, taking the simple precautions outlined above can reduce any possible risk. In addition, people who are concerned might choose digital rather than analog telephones, since the former use lower RF levels.

  12. Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

    PubMed

    Corso, J J; Sharon, E; Dube, S; El-Saden, S; Sinha, U; Yuille, A

    2008-05-01

    We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor.

  13. Late sequelae in children treated for brain tumors and leukemia.

    PubMed

    Jereb, B; Korenjak, R; Krzisnik, C; Petric-Grabnar, G; Zadravec-Zaletel, L; Anzic, J; Stare, J

    1994-01-01

    Forty-two survivors treated at an age of 2-16 years for brain tumors or leukemia were, 4-21 years after treatment, subjected to an extensive follow-up investigation, including physical examination and interview; 35 of them also had endocrinological and 33 psychological evaluation. Hormonal deficiencies were found in about two-thirds of patients and were most common in those treated for brain tumors. The great majority had verbal intelligence quotient (VIQ) within normal range. Also, the performance intelligence quotients (PIQ) were normal in most patients. However, the results suggested that the primary intellectual capacity in children treated for cancer was not being fully utilized, their PIQ being on the average higher than their VIQ; this tendency was especially pronounced in the leukemia patients.

  14. Management of children with brain tumors in Paraguay

    PubMed Central

    Baskin, Jacquelyn L.; Lezcano, Eva; Kim, Bo Sung; Figueredo, Diego; Lassaletta, Alvaro; Perez-Martinez, Antonio; Madero, Luis; Caniza, Miguela A.; Howard, Scott C.; Samudio, Angelica; Finlay, Jonathan L.

    2013-01-01

    Background Cure rates among children with brain tumors differ between low-income and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country. Methods Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asunción and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death. Results All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities. Conclusions National and center-specific deficiencies in resources to manage pediatric brain tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain tumor programs in other low- and middle-income countries. PMID:23197688

  15. Automatic brain tumor detection in MRI: methodology and statistical validation

    NASA Astrophysics Data System (ADS)

    Iftekharuddin, Khan M.; Islam, Mohammad A.; Shaik, Jahangheer; Parra, Carlos; Ogg, Robert

    2005-04-01

    Automated brain tumor segmentation and detection are immensely important in medical diagnostics because it provides information associated to anatomical structures as well as potential abnormal tissue necessary to delineate appropriate surgical planning. In this work, we propose a novel automated brain tumor segmentation technique based on multiresolution texture information that combines fractal Brownian motion (fBm) and wavelet multiresolution analysis. Our wavelet-fractal technique combines the excellent multiresolution localization property of wavelets to texture extraction of fractal. We prove the efficacy of our technique by successfully segmenting pediatric brain MR images (MRIs) from St. Jude Children"s Research Hospital. We use self-organizing map (SOM) as our clustering tool wherein we exploit both pixel intensity and multiresolution texture features to obtain segmented tumor. Our test results show that our technique successfully segments abnormal brain tissues in a set of T1 images. In the next step, we design a classifier using Feed-Forward (FF) neural network to statistically validate the presence of tumor in MRI using both the multiresolution texture and the pixel intensity features. We estimate the corresponding receiver operating curve (ROC) based on the findings of true positive fractions and false positive fractions estimated from our classifier at different threshold values. An ROC, which can be considered as a gold standard to prove the competence of a classifier, is obtained to ascertain the sensitivity and specificity of our classifier. We observe that at threshold 0.4 we achieve true positive value of 1.0 (100%) sacrificing only 0.16 (16%) false positive value for the set of 50 T1 MRI analyzed in this experiment.

  16. Handling of solid brain tumor tissue for protein analysis.

    PubMed

    Ericsson, Christer; Nistér, Monica

    2011-01-01

    Optimal protein analysis requires unfixed tissue samples. We suggest handling the brain tumor tissue sterilely and coldly (on ice) for as short time as possible prior to processing, but for no more than 8 h. This simple protocol results in apparently intact morphology, immunoreactivity, protein integrity, and protein phosphorylation with the criteria we apply. Sample handling for Pathological Anatomical Diagnosis (PAD) and for protein analysis can be one and the same.

  17. Liposomally formulated phospholipid-conjugated indocyanine green for intra-operative brain tumor detection and resection.

    PubMed

    Suganami, Akiko; Iwadate, Yasuo; Shibata, Sayaka; Yamashita, Masamichi; Tanaka, Tsutomu; Shinozaki, Natsuki; Aoki, Ichio; Saeki, Naokatsu; Shirasawa, Hiroshi; Okamoto, Yoshiharu; Tamura, Yutaka

    2015-12-30

    Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor.

  18. Sigma and opioid receptors in human brain tumors

    SciTech Connect

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. )

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  19. Heavy Metals and Epigenetic Alterations in Brain Tumors

    PubMed Central

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-01-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

  20. Gene markers in brain tumors: what the epileptologist should know.

    PubMed

    Ostrom, Quinn; Cohen, Mark L; Ondracek, Annie; Sloan, Andrew; Barnholtz-Sloan, Jill

    2013-12-01

    Gene markers or biomarkers can be used for diagnostic or prognostic purposes for all different types of complex disease, including brain tumors. Prognostic markers can be useful to explain differences not only in overall survival but also in response to treatment and for development of targeted therapies. Multiple genes with specific types of alterations have now been identified that are associated with improved response to chemotherapy and radiotherapy, such as O(6)-methylguanine methyltranferase (MGMT) or loss of chromosomes 1p and/or 19q. Other alterations have been identified that are associated with improved overall survival, such as mutations in isocitrate dehydrogenase 1 (IDH1) and/or isocitrate dehydrogenase 2 (IDH2) or having the glioma CpG island DNA methylator phenotype (G-CIMP). There are many biomarkers that may have relevance in brain tumor-associated epilepsy that do not respond to treatment. Given the rapidly changing landscape of high throughput "omics" technologies, there is significant potential for gaining further knowledge via integration of multiple different types of high genome-wide data. This knowledge can be translated into improved therapies and clinical outcomes for patients with brain tumors.

  1. Childhood brain tumors and paternal occupation in the aerospace industry.

    PubMed

    Olshan, A F; Breslow, N E; Daling, J R; Weiss, N S; Leviton, A

    1986-07-01

    Data from a case-control study of childhood brain tumors were analyzed to examine the possibility that paternal occupation in the aerospace industry is related to the development of a brain tumor in offspring. Parents of 51 children with brain tumors diagnosed in western Washington State during 1978-81 were interviewed, and their responses were compared to those of parents of 142 children selected at random from this population. Among all children, proportions of case and control fathers who had ever been employed in the aerospace industry were nearly identical [relative risk (RR) = 0.94; 95% confidence interval (CI) = 0.40-2.19]. Employment in the aerospace industry during the period from 1 year prior to birth to the time of diagnosis and any employment in the manufacturing part of the industry were not associated with increased risk. However, stratification by age at diagnosis revealed an increased risk associated with father's ever-employment in the industry (RR = 2.10; 95% CI = 0.79-5.60) for children under 10 years old. A corresponding decreased risk (RR = 0.12; 95% CI = 0.01-1.08) was found for children over 10 years old. Because of the relatively small number of cases with a positive paternal occupational history, interpretations of the difference in the direction of the association according to age at diagnosis must remain tentative ones.

  2. The p53 gene and protein in human brain tumors

    SciTech Connect

    Louis, D.N. )

    1994-01-01

    Because p53 gene alterations are commonplace in human tumors and because p53 protein is involved in a number of important cellular pathways, p53 has become a topic of intensive investigation, both by basic scientists and clinicians. p53 was initially identified by two independent laboratories in 1979 as a 53 kilodalton (kD) protein that complexes with the large T antigen of SV40 virus. Shortly thereafter, it was shown that the E1B oncoprotein of adenovirus also binds p53. The binding of two different oncogenic viral tumor proteins to the same cellular protein suggested that p53 might be integral to tumorigenesis. The human p53 cDNA and gene were subsequently cloned in the mid-1980s, and analysis of p53 gene alterations in human tumors followed a few year later. During these 10 years, researchers grappling with the vagaries of p53 first characterized the gene as an oncogene, then as a tumor suppressor gene, and most recently as both a tumor suppressor gene and a so-called [open quotes]dominant negative[close quotes] oncogene. The last few years have seen an explosion in work on this single gene and its protein product. A review of a computerized medical database revealed approximately 650 articles on p53 in 1992 alone. p53 has assumed importance in neuro-oncology because p53 mutations and protein alterations are frequent in the common diffuse, fibrillary astrocytic tumors of adults. p53 mutations in astrocytomas were first described in 1989 and were followed by more extensive analyses of gene mutations and protein alterations in adult astrocytomas. The gene has also been studied in less common brain tumors. Elucidating the role of p53 in brain tumorigenesis will not only enhance understanding of brain tumor biology but may also contribute to improved diagnosis and therapy. This discussion reviews key aspects of the p53 gene and protein, and describe their emerging roles in central nervous system neoplasia. 102 refs., 6 figs., 1 tab.

  3. Monitoring brain tumor response to therapy using MRI segmentation.

    PubMed

    Vaidyanathan, M; Clarke, L P; Hall, L O; Heidtman, C; Velthuizen, R; Gosche, K; Phuphanich, S; Wagner, H; Greenberg, H; Silbiger, M L

    1997-01-01

    The performance evaluation of a semi-supervised fuzzy c-means (SFCM) clustering method for monitoring brain tumor volume changes during the course of routine clinical radiation-therapeutic and chemo-therapeutic regimens is presented. The tumor volume determined using the SFCM method was compared with the volume estimates obtained using three other methods: (a) a k nearest neighbor (kNN) classifier, b) a grey level thresholding and seed growing (ISG-SG) method and c) a manual pixel labeling (GT) method for ground truth estimation. The SFCM and kNN methods are applied to the multispectral, contrast enhanced T1, proton density, and T2 weighted, magnetic resonance images (MRI) whereas the ISG-SG and GT methods are applied only to the contrast enhanced T1 weighted image. Estimations of tumor volume were made on eight patient cases with follow-up MRI scans performed over a 32 week interval during treatment. The tumor cases studied include one meningioma, two brain metastases and five gliomas. Comparisons with manually labeled ground truth estimations showed that there is a limited agreement between the segmentation methods for absolute tumor volume measurements when using images of patients after treatment. The average intraobserver reproducibility for the SFCM, kNN and ISG-SG methods was found to be 5.8%, 6.6% and 8.9%, respectively. The average of the interobserver reproducibility of these methods was found to be 5.5%, 6.5% and 11.4%, respectively. For the measurement of relative change of tumor volume as required for the response assessment, the multi-spectral methods kNN and SFCM are therefore preferred over the seedgrowing method.

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

    PubMed Central

    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

  5. Radiomics in Brain Tumors: An Emerging Technique for Characterization of Tumor Environment.

    PubMed

    Kotrotsou, Aikaterini; Zinn, Pascal O; Colen, Rivka R

    2016-11-01

    The role of radiomics in the diagnosis, monitoring, and therapy planning of brain tumors is becoming increasingly clear. Incorporation of quantitative approaches in radiology, in combination with increased computer power, offers unique insights into macroscopic tumor characteristics and their direct association with the underlying pathophysiology. This article presents the most recent findings in radiomics and radiogenomics with respect to identifying potential imaging biomarkers with prognostic value that can lead to individualized therapy. In addition, a brief introduction to the concept of big data and its significance in medicine is presented.

  6. Multi-parametric analysis and registration of brain tumors: constructing statistical atlases and diagnostic tools of predictive value.

    PubMed

    Davatzikos, Christos; Zacharaki, Evangelia I; Gooya, Ali; Clark, Vanessa

    2011-01-01

    We discuss computer-based image analysis algorithms of multi-parametric MRI of brain tumors, aiming to assist in early diagnosis of infiltrating brain tumors, and to construct statistical atlases summarizing population-based characteristics of brain tumors. These methods combine machine learning, deformable registration, multi-parametric segmentation, and biophysical modeling of brain tumors.

  7. Image updating for brain deformation compensation in tumor resection

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Olson, Jonathan D.; Roberts, David W.; Hartov, Alex; Paulsen, Keith D.

    2016-03-01

    Preoperative magnetic resonance images (pMR) are typically used for intraoperative guidance in image-guided neurosurgery, the accuracy of which can be significantly compromised by brain deformation. Biomechanical finite element models (FEM) have been developed to estimate whole-brain deformation and produce model-updated MR (uMR) that compensates for brain deformation at different surgical stages. Early stages of surgery, such as after craniotomy and after dural opening, have been well studied, whereas later stages after tumor resection begins remain challenging. In this paper, we present a method to simulate tumor resection by incorporating data from intraoperative stereovision (iSV). The amount of tissue resection was estimated from iSV using a "trial-and-error" approach, and the cortical shift was measured from iSV through a surface registration method using projected images and an optical flow (OF) motion tracking algorithm. The measured displacements were employed to drive the biomechanical brain deformation model, and the estimated whole-brain deformation was subsequently used to deform pMR and produce uMR. We illustrate the method using one patient example. The results show that the uMR aligned well with iSV and the overall misfit between model estimates and measured displacements was 1.46 mm. The overall computational time was ~5 min, including iSV image acquisition after resection, surface registration, modeling, and image warping, with minimal interruption to the surgical flow. Furthermore, we compare uMR against intraoperative MR (iMR) that was acquired following iSV acquisition.

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

    PubMed

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

    2012-03-01

    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.

  9. The biology of radiosurgery and its clinical applications for brain tumors

    PubMed Central

    Kondziolka, Douglas; Shin, Samuel M.; Brunswick, Andrew; Kim, Irene; Silverman, Joshua S.

    2015-01-01

    Stereotactic radiosurgery (SRS) was developed decades ago but only began to impact brain tumor care when it was coupled with high-resolution brain imaging techniques such as computed tomography and magnetic resonance imaging. The technique has played a key role in the management of virtually all forms of brain tumor. We reviewed the radiobiological principles of SRS on tissue and how they pertain to different brain tumor disorders. We reviewed the clinical outcomes on the most common indications. This review found that outcomes are well documented for safety and efficacy and show increasing long-term outcomes for benign tumors. Brain metastases SRS is common, and its clinical utility remains in evolution. The role of SRS in brain tumor care is established. Together with surgical resection, conventional radiotherapy, and medical therapies, patients have an expanding list of options for their care. Clinicians should be familiar with radiosurgical principles and expected outcomes that may pertain to different brain tumor scenarios. PMID:25267803

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

    PubMed Central

    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

  11. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    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

  12. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    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.

  13. Radiopotentiation of human brain tumor cells by sodium phenylacetate.

    PubMed

    Ozawa, T; Lu, R M; Hu, L J; Lamborn, K R; Prados, M D; Deen, D F

    1999-08-03

    Phenylacetate (PA) inhibits the growth of tumor cells in vitro and in vivo and shows promise as a relatively nontoxic agent for cancer treatment. A recent report shows that prolonged exposure of cells to low concentrations of PA can enhance the radiation response of brain tumor cells in vitro, opening up the possibility of using this drug to improve the radiation therapy of brain tumor patients. We investigated the cytotoxicity produced by sodium phenylacetate (NaPA) alone and in combination with X-rays in SF-767 human glioblastoma cells and in two medulloblastoma cell lines, Masden and Daoy. Exposure of all three cell lines to relatively low concentrations of NaPA for up to 5 days did not enhance the subsequent cell killing produced by X-irradiation. However, enhanced cell killing was achieved by exposing either oxic or hypoxic cells to relatively high drug concentrations ( > 50-70 mM) for 1 h immediately before X-irradiation. Because central nervous system toxicity can occur in humans at serum concentrations of approximately 6 mM PA, translation of these results into clinical trials will likely require local drug-delivery strategies to achieve drug concentrations that can enhance the radiation response. The safety of such an approach with this drug has not been demonstrated.

  14. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images

    NASA Astrophysics Data System (ADS)

    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.

  15. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images

    PubMed Central

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

    2016-01-01

    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. PMID:27786240

  16. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    PubMed Central

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function. PMID:27516807

  17. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    NASA Astrophysics Data System (ADS)

    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.

  18. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    PubMed Central

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

    2016-01-01

    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. PMID:27883015

  19. MR Vascular Fingerprinting in Stroke and Brain Tumors Models.

    PubMed

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

    2016-11-24

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

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

    PubMed

    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.

  1. Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors

    PubMed Central

    Choi, Seung Ah; Choi, Jung Won; Wang, Kyu-Chang; Phi, Ji Hoon; Lee, Ji Yeoun; Park, Kyung Duk; Eum, Dayoung; Park, Sung-Hye; Kim, Il Han; Kim, Seung-Ki

    2015-01-01

    Background Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT. Methods Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo. Results AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH+ AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH+ AT/RT cells. Importantly, DSF reduced the metabolism of ALDH+ AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD+/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02). Conclusion Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application. PMID:25378634

  2. A neuropathology-based approach to epilepsy surgery in brain tumors and proposal for a new terminology use for long-term epilepsy-associated brain tumors.

    PubMed

    Blumcke, Ingmar; Aronica, Eleonora; Urbach, Horst; Alexopoulos, Andreas; Gonzalez-Martinez, Jorge A

    2014-07-01

    Every fourth patient submitted to epilepsy surgery suffers from a brain tumor. Microscopically, these neoplasms present with a wide-ranging spectrum of glial or glio-neuronal tumor subtypes. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNTs) are the most frequently recognized entities accounting for 65 % of 1,551 tumors collected at the European Epilepsy Brain Bank (n = 5,842 epilepsy surgery samples). These tumors often present with early seizure onset at a mean age of 16.5 years, with 77 % of neoplasms affecting the temporal lobe. Relapse and malignant progression are rare events in this particular group of brain tumors. Surgical resection should be regarded, therefore, also as important treatment strategy to prevent epilepsy progression as well as seizure- and medication-related comorbidities. The characteristic clinical presentation and broad histopathological spectrum of these highly epileptogenic brain tumors will herein be classified as "long-term epilepsy associated tumors-LEATs". LEATs differ from most other brain tumors by early onset of spontaneous seizures, and conceptually are regarded as developmental tumors to explain their pleomorphic microscopic appearance and frequent association with Focal Cortical Dysplasia Type IIIb. However, the broad neuropathologic spectrum and lack of reliable histopathological signatures make these tumors difficult to classify using the WHO system of brain tumors. As another consequence from poor agreement in published LEAT series, molecular diagnostic data remain ambiguous. Availability of surgical tissue specimens from patients which have been well characterized during their presurgical evaluation should open the possibility to systematically address the origin and epileptogenicity of LEATs, and will be further discussed herein. As a conclusion, the authors propose a novel A-B-C terminology of epileptogenic brain tumors ("epileptomas") which hopefully promote the discussion between neuropathologists

  3. Tumor treating fields: a novel treatment modality and its use in brain tumors

    PubMed Central

    Pacheco, Patricia

    2016-01-01

    Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient’s shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications. PMID:27664860

  4. Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Lau, Y.H.

    1994-05-01

    This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions of interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.

  5. Statistical feature selection for enhanced detection of brain tumor

    NASA Astrophysics Data System (ADS)

    Chaddad, Ahmad; Colen, Rivka R.

    2014-09-01

    Feature-based methods are widely used in the brain tumor recognition system. Robust of early cancer detection is one of the most powerful image processing tools. Specifically, statistical features, such as geometric mean, harmonic mean, mean excluding outliers, median, percentiles, skewness and kurtosis, have been extracted from brain tumor glioma to aid in discriminating two levels namely, Level I and Level II using fluid attenuated inversion recovery (FLAIR) sequence in the diagnosis of brain tumor. Statistical feature describes the major characteristics of each level from glioma which is an important step to evaluate heterogeneity of cancer area pixels. In this paper, we address the task of feature selection to identify the relevant subset of features in the statistical domain, while discarding those that are either redundant or confusing, thereby improving the performance of feature-based scheme to distinguish between Level I and Level II. We apply a Decision Structure algorithm to find the optimal combination of nonhomogeneity based statistical features for the problem at hand. We employ a Naïve Bayes classifier to evaluate the performance of the optimal statistical feature based scheme in terms of its glioma Level I and Level II discrimination capability and use real-data collected from 17 patients have a glioblastoma multiforme (GBM). Dataset provided from 3 Tesla MR imaging system by MD Anderson Cancer Center. For the specific data analyzed, it is shown that the identified dominant features yield higher classification accuracy, with lower number of false alarms and missed detections, compared to the full statistical based feature set. This work has been proposed and analyzed specific GBM types which Level I and Level II and the dominant features were considered as feature aid to prognostic indicators. These features were selected automatically to be better able to determine prognosis from classical imaging studies.

  6. Spatial organization and correlations of cell nuclei in brain tumors.

    PubMed

    Jiao, Yang; Berman, Hal; Kiehl, Tim-Rasmus; Torquato, Salvatore

    2011-01-01

    Accepting the hypothesis that cancers are self-organizing, opportunistic systems, it is crucial to understand the collective behavior of cancer cells in their tumorous heterogeneous environment. In the present paper, we ask the following basic question: Is this self-organization of tumor evolution reflected in the manner in which malignant cells are spatially distributed in their heterogeneous environment? We employ a variety of nontrivial statistical microstructural descriptors that arise in the theory of heterogeneous media to characterize the spatial distributions of the nuclei of both benign brain white matter cells and brain glioma cells as obtained from histological images. These descriptors, which include the pair correlation function, structure factor and various nearest neighbor functions, quantify how pairs of cell nuclei are correlated in space in various ways. We map the centroids of the cell nuclei into point distributions to show that while commonly used local spatial statistics (e.g., cell areas and number of neighboring cells) cannot clearly distinguish spatial correlations in distributions of normal and abnormal cell nuclei, their salient structural features are captured very well by the aforementioned microstructural descriptors. We show that the tumorous cells pack more densely than normal cells and exhibit stronger effective repulsions between any pair of cells. Moreover, we demonstrate that brain gliomas are organized in a collective way rather than randomly on intermediate and large length scales. The existence of nontrivial spatial correlations between the abnormal cells strongly supports the view that cancer is not an unorganized collection of malignant cells but rather a complex emergent integrated system.

  7. Confidence-based ensemble for GBM brain tumor segmentation

    NASA Astrophysics Data System (ADS)

    Huo, Jing; van Rikxoort, Eva M.; Okada, Kazunori; Kim, Hyun J.; Pope, Whitney; Goldin, Jonathan; Brown, Matthew

    2011-03-01

    It is a challenging task to automatically segment glioblastoma multiforme (GBM) brain tumors on T1w post-contrast isotropic MR images. A semi-automated system using fuzzy connectedness has recently been developed for computing the tumor volume that reduces the cost of manual annotation. In this study, we propose a an ensemble method that combines multiple segmentation results into a final ensemble one. The method is evaluated on a dataset of 20 cases from a multi-center pharmaceutical drug trial and compared to the fuzzy connectedness method. Three individual methods were used in the framework: fuzzy connectedness, GrowCut, and voxel classification. The combination method is a confidence map averaging (CMA) method. The CMA method shows an improved ROC curve compared to the fuzzy connectedness method (p < 0.001). The CMA ensemble result is more robust compared to the three individual methods.

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

    PubMed Central

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

    PubMed

    Menze, Bjoern H; 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 Antonió; 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

    2015-10-01

    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.

  10. Absence of human cytomegalovirus infection in childhood brain tumors

    PubMed Central

    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. PMID:26396923

  11. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model

    PubMed Central

    Wanjiku, Teresia; Rudek, Michelle A; Joshi, Avadhut; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Purpose Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different MBZ polymorphs (A, B and C) exist and a detailed assessment of the brain penetration, pharmacokinetics and anti-tumor properties of each individual MBZ polymorph is necessary to improve mebendazole-based brain cancer therapy. Experimental Design and Results In this study, various marketed and custom-formulated MBZ tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of MBZ polymorphs and two main metabolites were analyzed by LC-MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Both, polymorph B and C, reached concentrations in the brain that exceeded the IC50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusion Among MBZ polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with less side effects and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. PMID:25862759

  12. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    NASA Astrophysics Data System (ADS)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja; Majumdar, Subrata; Jain, Sanjay K.

    2013-11-01

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  13. Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

    SciTech Connect

    Higuchi, Yoshinori Serizawa, Toru; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Sato, Makoto; Iwadate, Yasuo; Saeki, Naokatsu

    2009-08-01

    Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm{sup 3} in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 {+-} 6.3 cm{sup 3} (mean {+-} SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 {+-} 6.5 (18.8% reduction) and 10.6 {+-} 6.1 cm{sup 3} (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed Central

    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.

    2016-01-01

    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 non-destructive, label-free optical method, to reveal glioma infiltration in animal models. Here 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. Importantly, 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. PMID:26468325

  17. Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0414 TITLE: Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors PRINCIPAL INVESTIGATOR: Jean Mulcahy...29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0414 Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors 5b. GRANT...ABSTRACT 200 words most significant findings 15. SUBJECT TERMS autophagy, BRAF, brain tumor. pediatric 16. SECURITY CLASSIFICATION OF: 17

  18. Consensus Conference on Brain Tumor Definition for registration. November 10, 2000.

    PubMed Central

    McCarthy, Bridget J.; Surawicz, Tanya; Bruner, Janet M.; Kruchko, Carol; Davis, Faith

    2002-01-01

    The Consensus Conference on Brain Tumor Definition was facilitated by the Central Brain Tumor Registry of the United States and held on November 10, 2000, in Chicago, Illinois, to reach multidisciplinary agreement on a standard definition of brain tumors for collecting and comparing data in the U.S. The Brain Tumor Working Group, convened in 1998 to determine the status of brain tumor collection in the U.S., outlined 4 recommendations of which the first 2 guided the discussion for the Consensus Conference: (1) standardization of a definition of primary brain tumors that is based on site alone, rather than on site and behavior, and that can be used by surveillance organizations in collecting these tumors; and (2) development of a reporting scheme that can be used for comparing estimates of primary brain tumors across registries. Consensus was reached on the collection of all primary brain tumor histologies found and reported in the brain or CNS ICD-O site codes (C70.0-C72.9 and C75.1-C75.3), including those coded benign and uncertain as well as those coded malignant. In addition, a comprehensive listing of histologies occurring in the brain and CNS, based on the CBTRUS grouping scheme, was formulated to provide a template for reporting in accordance with the second recommendation of the Brain Tumor Working Group. With consensus achieved on the first 2 recommendations, the stage is set to move forward in estimating additional resources necessary for the collection of these tumors, including funding, training for cancer registrars, identifying quality control measures, and developing computerized edit checks, as outlined in the last 2 recommendations of the Brain Tumor Working Group. PMID:11916506

  19. Validation of IR-spectroscopic brain tumor classification

    NASA Astrophysics Data System (ADS)

    Beleites, C.; Steiner, G.; Sobottka, S.; Schackert, G.; Salzer, R.

    2006-02-01

    As a molecular probe of tissue composition, infrared spectroscopic imaging serves as an adjunct to histopathology in detecting and diagnosing disease. In the past it was demonstrated that the IR spectra of brain tumors can be discriminated from one another according to their grade of malignancy. Although classification success rates up to 93% were observed one problem consists in the variation of the models depending on the number of samples used for the development of the classification model. In order to open the path for clinical trials the classification has to be validated. A series of classification models were built using a k-fold cross validation scheme and the classification predictions from the various models were combined to provide an aggregated prediction. The validation highlights instabilities in the models, error rates, sensitivity as well as specificity of the classification and allows the determination of confidence intervals. Better classification models could be achieved by an aggregated prediction. The validation shows that brain tumors can be classified by infrared spectroscopy and the grade of malignancy corresponds reasonably to the histopathological assignment.

  20. "Armed" oncolytic herpes simplex viruses for brain tumor therapy.

    PubMed

    Todo, Tomoki

    2008-01-01

    Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for brain tumors and other solid cancers. They can replicate in situ, spread and exhibit oncolytic activity via a direct cytocidal effect. One of the advantages of HSV-1 is the capacity to incorporate large and/or multiple transgenes within the viral genome. Oncolytic HSV-1 can therefore be "armed" to add certain functions. Recently, the field of armed oncolytic HSV-1 has drastically advanced, due to development of recombinant HSV-1 generation systems that utilize bacterial artificial chromosome and multiple DNA recombinases. Because antitumor immunity is induced in the course of oncolytic activities of HSV-1, transgenes encoding immunomodulatory molecules have been most frequently used for arming. Other armed oncolytic HSV-1 include those that express antiangiogenic factors, fusogenic membrane glycoproteins, suicide gene products, and proapoptotic proteins. Provided that the transgene product does not interfere with viral replication, such arming of oncolytic HSV-1 results in augmentation of antitumor efficacy. Immediate-early viral promoters are often used to control the arming transgenes, but strict-late viral promoters have been shown useful to restrict the expression in the late stage of viral replication when desirable. Some armed oncolytic HSV-1 have been created for the purpose of noninvasive in vivo imaging of viral infection and replication. Development of a wide variety of armed oncolytic HSV-1 will lead to an establishment of a new genre of therapy for brain tumors as well as other cancers.

  1. Cognitive Remediation Therapy for Brain Tumor Survivors with Cognitive Deficits

    PubMed Central

    Sacks-Zimmerman, Amanda; Liberta, Taylor

    2015-01-01

    Cognitive deficits have been widely observed in patients with primary brain tumors consequent to diagnosis and treatment. Given the early onset and the relatively long survival rate of patients, it seems pertinent to study and refine the techniques used to treat these deficits. The purpose of this article is to discuss cognitive deficits that follow neurosurgical treatment for low-grade gliomas as well as to outline a neuropsychological intervention to treat these deficits, specifically working memory and attention. Cognitive remediation therapy is a neuropsychological intervention that aims to enhance attention, working memory, and executive functioning, thereby diminishing the impact of these deficits on daily functioning. Computerized cognitive remediation training programs facilitate access to treatment through providing online participation. The authors include preliminary results of three participants who have completed the computerized training program as part of an ongoing study that is investigating the efficacy of this program in patients who have undergone treatment for low-grade gliomas. The results so far suggest some improvement in working memory and attention from baseline scores. It is the hope of the present authors to highlight the importance of this treatment in the continuity of care of brain tumor survivors. PMID:26623205

  2. What's New in Research and Treatment for Brain Tumors in Children?

    MedlinePlus

    ... Brain and Spinal Cord Tumors in Children What’s New in Research and Treatment for Brain and Spinal ... an investigational method, and studies are continuing. Other new treatment strategies Researchers are also testing some newer ...

  3. Analysis of plasma free amino acid profiles in canine brain tumors

    PubMed Central

    Utsugi, Shinichi; Azuma, Kazuo; Osaki, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu

    2017-01-01

    Canine brain tumors are best diagnosed using magnetic resonance imaging (MRI). However, opportunities of MRI examination are restricted due to its limited availability in veterinary facilities; thus, numerous canine brain tumors are diagnosed at an advanced stage. Therefore, development of a noninvasive diagnostic biomarker is required for the early detection of brain tumors. In the present study, plasma free amino acid (PFAA) profiles between dogs with and without brain tumors were compared. A total of 12 dogs with brain tumors, diagnosed based on clinical signs, and on the results of intracranial MRI and/or pathological examination were evaluated. In addition, eight dogs diagnosed with idiopathic epilepsy and 16 healthy dogs were also included. A liquid chromatography system with automated pre-column derivatization functionality was used to measure the levels of 20 amino acids. As a result, the levels of three amino acids (alanine, proline and isoleucine) were increased significantly (1.6-, 1.5- and 1.6-fold, respectively) in the plasma of dogs with brain tumors as compared with the levels in control dogs (all P<0.05). Thus, the PFAA levels of dogs with brain tumors differed from those of healthy dogs. The present study demonstrated that analysis of PFAA levels of dogs with brain tumors may serve as a useful biomarker for the early detection of canine brain tumors. PMID:28357072

  4. Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications

    NASA Astrophysics Data System (ADS)

    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

  5. Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications.

    PubMed

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

    2016-12-21

    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

  6. Long-term mobile phone use and brain tumor risk.

    PubMed

    Lönn, Stefan; Ahlbom, Anders; Hall, Per; Feychting, Maria

    2005-03-15

    Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified all cases aged 20-69 years who were diagnosed with glioma or meningioma during 2000-2002 in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.

  7. [Factors significant for cerebral circulacion in patients with supratentorial brain tumors].

    PubMed

    Sboev, A Yu; Dolgih, V T; Larkin, V I

    2013-01-01

    Using the Doppler ultrasonography method the condition of brain blood circulation of 90 patients with supratentorial brain tumors (gliomas--43, meningiomas--34, metastasis--9) during pre-surgical period was studied. The factors changing brain blood circulation at patients with with supratentorial brain tumors were brain displacement, increase of intracranial pressure, histologic structure and the first symptoms duration of illness. Localization (for an exception of an occipital lobe) and the size of a tumor directly didn't render influence on blood circulation parameters.

  8. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    PubMed

    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

    2013-10-01

    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) owing to preferential BTIC survival and to 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, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  9. Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

    ClinicalTrials.gov

    2017-02-21

    Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

  10. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  11. Isolated angiitis in the hypothalamus mimicking brain tumor.

    PubMed

    Tsutsumi, Satoshi; Ito, Masanori; Yasumoto, Yukimasa; Kaneda, Kazuhiko

    2008-01-01

    A 64-year-old female presented with exaggerating somnolence without contributory medical and lifestyle histories. She was not aware of any preceding infection or headache. Cerebral magnetic resonance imaging demonstrated an isolated enhanced mass in the hypothalamus without meningeal enhancement. Blood and cerebrospinal fluid examinations showed no significant findings except for hypernatremia and hyperprolactinemia. She underwent an open biopsy via the interhemispheric route. Histological examination revealed marked perivascular lymphocytic aggregation with polyclonal immunostaining both for B and T lymphocytes. No findings suggestive of underlying malignancy were recognized. Extensive work-up aiming at systemic vasculitis and lymphoma revealed no signs of extracranial lesion, so the most probable diagnosis was isolated angiitis in the hypothalamus. Angiitis may originate from the hypothalamus and should be considered in the differential diagnosis of hypothalamic lesion mimicking brain tumor on neuroimaging.

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

    PubMed

    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.

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

    PubMed

    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 < .01). However, patients' 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

  14. Household pesticides and risk of pediatric brain tumors.

    PubMed Central

    Pogoda, J M; Preston-Martin, S

    1997-01-01

    A follow-up to a population-based case-control study of pediatric brain tumors in Los Angeles County, California, involving mothers of 224 cases and 218 controls, investigated the risk of household pesticide use from pregnancy to diagnosis. Risk was significantly elevated for prenatal exposure to flea/tick pesticides -odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.1-2.6-, particularly among subjects less than 5 years old at diagnosis (OR = 2.5; CI, 1. 2-5.5). Prenatal risk was highest for mothers who prepared, applied, or cleaned up flea/tick products themselves (OR = 2.2; CI, 1.1-4.2; for subjects <5 years of age, OR = 5.4; CI, 1.3-22.3). A significant trend of increased risk with increased exposure was observed for number of pets treated (p = 0.04). Multivariate analysis of types of flea/tick products indicated that sprays/foggers were the only products significantly related to risk (OR =10.8; CI, 1.3-89.1). Elevated risks were not observed for termite or lice treatments, pesticides for nuisance pests, or yard and garden insecticides, herbicides, fungicides, or snail killer. Certain precautions,if ignored, were associated with significant increased risk: evacuating the house after spraying or dusting for pests (OR = 1.6; CI, 1.0-2.6), delaying the harvest of food after pesticide treatment (OR = 3.6; CI, 1.0-13.7), and following instructions on pesticide labels (OR = 3. 7;CI, 1.5-9.6). These findings indicate that chemicals used in flea/tick products may increase risk of pediatric brain tumors and suggest that further research be done to pinpoint specific chemicals involved. PMID:9370522

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

    PubMed

    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.

  16. The exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches

    PubMed Central

    Agrahari, Vivek

    2017-01-01

    Delivering therapeutics to the central nervous system (CNS) and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier (BBB). The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant advantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed.

  17. DNMTs as potential therapeutic targets in high-risk pediatric embryonal brain tumors.

    PubMed

    Sin-Chan, Patrick; Huang, Annie

    2014-10-01

    Malignant brain tumors, which are the leading cause of cancer-related morbidity and mortality in children, span a wide spectrum of diseases with distinct clinical phenotypes but may share remarkably similar morphologic features. Until recently, few molecular markers of childhood brain tumors have been identified, which has limited therapeutic advances. Recent global genomic studies have enabled robust molecular classification of childhood brain tumors and the identification and consolidation of rare, seemingly disparate clinical entities. It is now increasingly evident that deregulation of epigenetic processes contributes substantially to heterogeneity in tumor phenotypes and comprise significant drivers of cancer initiation and progression. Specifically, DNA hypermethylation and silencing of critical tumor suppressor genes by DNA methyltransferases (DNMT) has emerged as an important and fundamental mechanism in brain tumor pathogenesis. These observations have been underscored by the recent discovery of TTYH1-C19MC gene fusions in an aggressive pediatric embryonal brain tumor, which results in deregulation and increased expression of a neural-specific DNMT3B isoform in C19MC-associated brain tumors. Our observations that pharmacological inhibitors of DNMTs and histone deacetylases significantly inhibit growth of cells derived from C19MC-associated tumors indicate targeting of epigenomic modifiers as a novel therapeutic approach for these highly treatment-resistant tumors.

  18. The incidence of second brain tumors related to cranial irradiation.

    PubMed

    Marta, Gustavo Nader; Murphy, Erin; Chao, Samuel; Yu, Jennifer S; Suh, John H

    2015-03-01

    Secondary brain tumor (SBT) is a devastating complication of cranial irradiation (CI). We reviewed the literature to determine the incidence of SBT as related to specific radiation therapy (RT) treatment modalities. The relative risk of radiation-associated SBT after conventional and conformal RT is well established and ranges from 5.65 to 10.9; latent time to develop second tumor ranges from 5.8 to 22.4 years, depending on radiation dose and primary disease. Theories and dosimetric models suggest that intensity-modulated radiation therapy may result in an increased risk of SBT, but clinical evidence is limited. The incidence of stereotactic radiosurgery-related SBT is low. Initial data suggest that no increased risk from proton therapy and dosimetric models predict a lower incidence of SBT compared with photons. In conclusion, the incidence of SBT related to CI is low. Longer follow-up is needed to clarify the impact of intensity-modulated radiation therapy, proton therapy and other developing technologies.

  19. Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma.

    PubMed

    Delač, Mateja; Motaln, Helena; Ulrich, Henning; Lah, Tamara T

    2015-09-01

    Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients.

  20. A Mathematical Model to Elucidate Brain Tumor Abrogation by Immunotherapy with T11 Target Structure

    PubMed Central

    Chaudhuri, Swapna

    2015-01-01

    T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of glioma cells, macrophages, cytotoxic T-lymphocytes (CD8+ T-cells), TGF-β, IFN-γ and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy. PMID:25955428

  1. Occupational exposure to electromagnetic fields and the occurrence of brain tumors. An analysis of possible associations

    SciTech Connect

    Lin, R.S.; Dischinger, P.C.; Conde, J.; Farrell, K.P.

    1985-06-01

    To explore the association between occupation and the occurrence of brain tumor, an epidemiologic study was conducted using data from the death certificates of 951 adult white male Maryland residents who died of brain tumor during the period 1969 through 1982. Compared with the controls, men employed in electricity-related occupations, such as electrician, electric or electronic engineer, and utility company serviceman, were found to experience a significantly higher proportion of primary brain tumors. An increase in the odds ratio for brain tumor was found to be positively related to electromagnetic (EM) field exposure levels. Furthermore, the mean age at death was found to be significantly younger among cases in the presumed high EM-exposure group. These findings suggest that EM exposure may be associated with the pathogenesis of brain tumors, particularly in the promoting stage.

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

    ClinicalTrials.gov

    2016-07-26

    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

  3. Fotemustine in the treatment of brain primary tumors and metastases.

    PubMed

    Khayat, D; Giroux, B; Berille, J; Cour, V; Gerard, B; Sarkany, M; Bertrand, P; Bizzari, J P

    1994-01-01

    Fotemustine is a new chloroethylnitrosourea characterized by the grafting of a phosphonoalanine group onto a nitrosourea radical. Clinical studies using fotemustine have been conducted in malignant glioma, brain metastasis of non-small cell lung cancer, and disseminated malignant melanoma. In recurrent malignant glioma, fotemustine has been used as a single agent: assessed by computed tomography scan, after 8 weeks, the objective response rate was 26.3% among 38 evaluable patients. Median duration of response was 33 weeks. The main toxicity was hematological (thrombocytopenia and leucopenia). A trial with high-dose fotemustine and autologous bone marrow rescue in newly diagnosed glioma was conducted in 26 patients, and 6 showed a partial response. The median overall survival was approximately 11 months. Myelosuppression was noted in all patients except 1, and other toxicity reported was central nervous system toxicity and epigastric pain. Combined with radiotherapy in 55 patients, a 29% response rate was observed, and this combination was well tolerated and easily manageable on an outpatient basis. Finally, fotemustine has been used intraarterially, with 10 objective responses observed among 26 evaluable patients. In brain metastases of non-small cell lung cancer, fotemustine proved to be active with a response rate of 16.7%. Combined with cisplatinum, fotemustine is still under study, but preliminary results are promising. In cerebral metastases of disseminated malignant melanoma, fotemustine has been evaluated in a total of 140 patients in the various studies: median response rate is 24.3%, ranging from 8.3% to 60.0%. Fotemustine appears to be a good candidate in the treatment of primary brain tumors and metastases.

  4. Laser interstitial thermal therapy in treatment of brain tumors--the NeuroBlate System.

    PubMed

    Mohammadi, Alireza M; Schroeder, Jason L

    2014-03-01

    Treatment of brain tumors remains challenging. Cytoreductive surgery is used as the first line treatment for most brain tumors. However complete, curative, resection is not achievable in many tumors leading to the need for adjuvant chemotherapy and radiation therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment. A low voltage laser is used to induce hyperthermia and to kill tumor cells. The extent of thermal damage is controlled through use of real-time MR-thermography guidance. Initial results have shown the feasibility of LITT for a variety of brain pathologies. LITT can be considered as an alternative type of surgery for difficult to access brain tumors and also for tumors in patients who are deemed high risk for more traditional surgery. Randomized trials are currently planned to continue assessing the efficacy of LITT and long-term follow-up data are awaited.

  5. Apoptosis imaging for monitoring DR5 antibody accumulation and pharmacodynamics in brain tumors non-invasively

    PubMed Central

    Weber, Thomas G.; Osl, Franz; Renner, Anja; Pöschinger, Thomas; Galbán, Stefanie; Rehemtulla, Alnawaz; Scheuer, Werner

    2014-01-01

    High grade gliomas often possess an impaired blood-brain barrier (BBB) which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics and tumor retention kinetics, we studied an agonistic DR5 antibody in a brain tumor xenograft model to investigate a non-invasive imaging method for longitudinal monitoring of apoptosis induction by this antibody. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dose response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20–0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by 3D fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody crossing the BBB was facilitated its impairment in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of CNS targeting drugs. PMID:24509903

  6. Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study.

    PubMed

    Abramovitch, Rinat; Itzik, Anna; Harel, Hila; Nagler, Arnon; Vlodavsky, Israel; Siegal, Tali

    2004-01-01

    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 alpha1(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.

  7. Biphasic modeling of brain tumor biomechanics and response to radiation treatment.

    PubMed

    Angeli, Stelios; Stylianopoulos, Triantafyllos

    2016-06-14

    Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35% spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning.

  8. Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  9. [Interdisciplinary neuro-oncology: part 2: systemic therapy of primary brain tumors].

    PubMed

    Tabatabai, G; Hattingen, E; Schlegel, J; Stummer, W; Schlegel, U

    2014-08-01

    By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function has become dramatically more extensive. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

  10. [Interdisciplinary neuro-oncology: part 1: diagnostics and operative therapy of primary brain tumors].

    PubMed

    Tabatabai, G; Hattingen, E; Schlegel, J; Stummer, W; Schlegel, U

    2014-08-01

    By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function is increasingly feasible. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

  11. Invited review--neuroimaging response assessment criteria for brain tumors in veterinary patients.

    PubMed

    Rossmeisl, John H; Garcia, Paulo A; Daniel, Gregory B; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

    2014-01-01

    The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.

  12. INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

    PubMed Central

    Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

    2013-01-01

    The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

  13. What Are Brain and Spinal Cord Tumors in Children?

    MedlinePlus

    ... brain stem. Each area has a special function. Cerebrum: The cerebrum is the large, outer part of the brain. ... other senses Cerebellum: The cerebellum lies under the cerebrum at the back part of the brain. It ...

  14. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

    PubMed

    Rubin, Joshua B; Kung, Andrew L; Klein, Robyn S; Chan, Jennifer A; Sun, YanPing; Schmidt, Karl; Kieran, Mark W; Luster, Andrew D; Segal, Rosalind A

    2003-11-11

    The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Gi protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.

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

    PubMed

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

    2017-03-13

    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. Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

    SciTech Connect

    Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan; Brat, Daniel J.; Shu, Hui-Kuo; Olson, Jeffrey J.

    2011-11-15

    Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resection margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.

  17. Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis.

    PubMed

    Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Ding, Xiping; Huo, Lei; Wan, Xin; Liu, Jinfang; Xia, Zhenyun

    2016-04-01

    Hyperglycemia has been associated with poor outcomes of patients with various diseases. There were several studies published to assess the association between hyperglycemia and prognosis of patients with brain tumors, but no consistent conclusion was available. We therefore performed a meta-analysis of available studies to evaluate the prognostic role of hyperglycemia in brain tumors. Several common databases were searched for eligible studies on the association between hyperglycemia and survival of patients with brain tumors. Two investigators used a set of predefined inclusion criteria to assess eligible studies independently. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic role of hyperglycemia. Finally, seven studies with a total of 2168 patients with brain tumors were included into the meta-analysis. Meta-analysis of total seven studies showed that hyperglycemia was significantly associated with shorter overall survival of brain tumors (HR = 2.04, 95% CI 1.51-2.76, P < 0.001). Meta-analysis of studies focusing on hyperglycemia showed that hyperglycemia was still significantly associated with shorter overall survival of brain tumors (HR = 1.82, 95% CI 1.29-2.59, P = 0.001). Meta-analysis of three studies on diabetes showed that diabetes was significantly associated with shorter overall survival of brain tumors (HR = 2.09, 95% CI 1.22-3.57, P = 0.007). Meta-regression analysis showed that there was no obvious difference in the roles of between hyperglycemia caused by glucocorticoids and hyperglycemia from diabetes (P = 0.25). Thus, hyperglycemia has an obvious prognostic significance in patients with brain tumors, and hyperglycemia is significantly associated with shorter overall survival of brain tumors.

  18. Removal of a malignant cystic brain tumor utilizing pyoktanin blue and fibrin glue: Technical note

    PubMed Central

    Hayashi, Nobuhide; Sasaki, Takahiro; Tomura, Nagatsuki; Okada, Hideo; Kuwata, Toshikazu

    2017-01-01

    Background: The leakage of cystic fluid during metastatic cystic brain tumor resection may cause tumor dissemination. When the cyst wall is thin, excision without removing the wall is often difficult. Methods: We were able to perform an en bloc resection of a cystic malignant brain tumor after aspirating the cystic fluid, injecting pyoktanin blue into the cyst to stain the cyst walls, and solidifying the empty cyst cavity by filling it with fibrin glue. Results: Pyoktanin blue readily stained the thin cystic walls and enabled visualization of mural damage. Solidification of the tumor made it easier to grasp and facilitated the dissection of tumor margins. Conclusions: This method has the potential to become a useful technique for the resection of malignant cystic brain tumors. PMID:28303204

  19. The diagnostic accuracy of multiparametric MRI to determine pediatric brain tumor grades and types.

    PubMed

    Koob, Mériam; Girard, Nadine; Ghattas, Badih; Fellah, Slim; Confort-Gouny, Sylviane; Figarella-Branger, Dominique; Scavarda, Didier

    2016-04-01

    Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24%) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76%). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children.

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

    PubMed Central

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

    2016-01-01

    Introduction 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. Methods 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 Results 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). Conclusion 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. PMID:27757181

  1. Radiation Dose to the Brain and Subsequent Risk of Developing Brain Tumors in Pediatric Patients Undergoing Interventional Neuroradiology Procedures

    PubMed Central

    Thierry-Chef; Simon, S. L.; Land, C. E.; Miller, D. L.

    2014-01-01

    Radiation dose to the brain and subsequent lifetime risk of diagnosis of radiation-related brain tumors were estimated for pediatric patients undergoing intracranial embolization. Average dose to the whole brain was calculated using dosimetric data from the Radiation Doses in Interventional Radiology Study for 49 pediatric patients who underwent neuroradiological procedures, and lifetime risk of developing radiation-related brain tumors was estimated using published algorithms based on A-bomb survivor data. The distribution of absorbed dose within the brain can vary significantly depending on field size and movement during procedures. Depending on the exposure conditions and age of the patient, organ-averaged brain dose was estimated to vary from 6 to 1600 mGy. The lifetime risk of brain tumor diagnosis was estimated to be increased over the normal background rates (57 cases per 10,000) by 3 to 40% depending on the dose received, age at exposure, and gender. While significant uncertainties are associated with these estimates, we have quantified the range of possible dose and propagated the uncertainty to derive a credible range of estimated lifetime risk for each subject. Collimation and limiting fluoroscopy time and dose rate are the most effective means to minimize dose and risk of future induction of radiation-related tumors. PMID:18959462

  2. Systematic Review of Brain Tumor Treatment in Dogs.

    PubMed

    Hu, H; Barker, A; Harcourt-Brown, T; Jeffery, N

    2015-01-01

    Intracranial neoplasia is commonly diagnosed in dogs and can be treated by a variety of methods, but formal comparisons of treatment efficacy are currently unavailable. This review was undertaken to summarize the current state of knowledge regarding outcome after the treatment of intracranial masses in dogs, with the aim of defining optimal recommendations for owners. This review summarizes data from 794 cases in 22 previously published reports and follows PRISMA guidelines for systematic review. A Pubmed search was used to identify suitable articles. These then were analyzed for quality and interstudy variability of inclusion and exclusion criteria and the outcome data extracted for summary in graphs and tables. There was a high degree of heterogeneity among studies with respect to inclusion and exclusion criteria, definition of survival periods, and cases lost to follow-up making comparisons among modalities troublesome. There is a need for standardized design and reporting of outcomes of treatment for brain tumors in dogs. The available data do not support lomustine as an effective treatment, but also do not show a clear difference in outcome between radiotherapy and surgery for those cases in which the choice is available.

  3. Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells.

    PubMed

    Huang, Yu-Ja; Hoffmann, Gwendolyn; Wheeler, Benjamin; Schiapparelli, Paula; Quinones-Hinojosa, Alfredo; Searson, Peter

    2016-02-22

    Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments.

  4. Ex vivo brain tumor analysis using spectroscopic optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lenz, Marcel; Krug, Robin; Welp, Hubert; Schmieder, Kirsten; Hofmann, Martin R.

    2016-03-01

    A big challenge during neurosurgeries is to distinguish between healthy tissue and cancerous tissue, but currently a suitable non-invasive real time imaging modality is not available. Optical Coherence Tomography (OCT) is a potential technique for such a modality. OCT has a penetration depth of 1-2 mm and a resolution of 1-15 μm which is sufficient to illustrate structural differences between healthy tissue and brain tumor. Therefore, we investigated gray and white matter of healthy central nervous system and meningioma samples with a Spectral Domain OCT System (Thorlabs Callisto). Additional OCT images were generated after paraffin embedding and after the samples were cut into 10 μm thin slices for histological investigation with a bright field microscope. All samples were stained with Hematoxylin and Eosin. In all cases B-scans and 3D images were made. Furthermore, a camera image of the investigated area was made by the built-in video camera of our OCT system. For orientation, the backsides of all samples were marked with blue ink. The structural differences between healthy tissue and meningioma samples were most pronounced directly after removal. After paraffin embedding these differences diminished. A correlation between OCT en face images and microscopy images can be seen. In order to increase contrast, post processing algorithms were applied. Hence we employed Spectroscopic OCT, pattern recognition algorithms and machine learning algorithms such as k-means Clustering and Principal Component Analysis.

  5. Perceived social competency in children with brain tumors: comparison between children on and off therapy.

    PubMed

    Hardy, Kristina K; Willard, Victoria W; Watral, Melody Ann; Bonner, Melanie J

    2010-01-01

    Children with brain tumors are at risk for a number of cognitive, academic, and social difficulties as a consequence of their illness and its treatment. Of these, the least is known about social functioning, particularly over the course of the illness. Thirty children with brain tumors were evaluated using neurocognitive and psychological measures, including a measure of perceived competency. Results indicated that off-therapy brain tumor patients reported more concerns about their social competence than both a normative sample and children on treatment. Findings highlight the need for more research aimed at helping survivors cope with long-term stressors associated with their illness.

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

    PubMed Central

    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

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

    PubMed

    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.

  8. Third harmonic generation imaging for fast, label-free pathology of human brain tumors

    PubMed Central

    Kuzmin, N. V.; Wesseling, P.; Hamer, P. C. de Witt; Noske, D. P.; Galgano, G. D.; Mansvelder, H. D.; Baayen, J. C.; Groot, M. L.

    2016-01-01

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies. PMID:27231629

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

    PubMed

    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.

  10. Monitoring of /sup 57/Co-bleomycin delivery to brain metastases and their tumors of origin

    SciTech Connect

    Front, D.; Even-Sapir, E.; Iosilevsky, G.; Israel, O.; Frenkel, A.; Kolodny, G.M.; Feinsud, M.

    1987-10-01

    The concentration of cobalt-57 (/sup 57/Co)-labeled bleomycin delivered to three brain metastases and to their tumors of origin in the lungs was measured using a single-photon emission computerized tomography technique. In two brain metastases the /sup 57/Co-bleomycin concentration measured at different times after the intravenous injection was significantly lower than that in the originating lung tumors (p less than 0.01 and p less than 0.001). In these two patients, the tumor cumulative concentration (TCC) of drug in the brain neoplasm compared to the lung carcinoma was 12.92 versus 15.12 and 10.30 versus 19.74 micrograms/cc/min. In the third patient there was no significant difference in drug concentration between the tumor in the brain and in the lung (TCC 16.02 vs. 15.09 micrograms/cc/min). There was a significant difference in the drug TCC between the three brain metastases: the difference between the lowest and highest concentrations was more than 50% (10.3 vs. 16.02 micrograms/cc/min). When the concentration in the tumor over time (CT(t)) of the /sup 57/Co-bleomycin was compared in the brain and lung tumors, a good correlation was found in each of the three cases (r = 0.93, 0.99, and 0.97). This suggests that the difference in drug uptake between brain metastases and their originating lung tumor is a quantitative rather than a qualitative phenomenon. The results show that the amount of drug to which brain metastases are exposed varies and may be very low in some tumors; therefore, effectiveness of drug delivery may play a role in the nonresponsiveness of brain metastases to treatment.

  11. Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways

    PubMed Central

    Choy, Catherine T; Kim, Haseong; Lee, Ji-Young; Williams, David M; Palethorpe, David; Fellows, Greg; Wright, Alan J; Laing, Ken; Bridges, Leslie R; Howe, Franklyn A; Kim, Soo-Hyun

    2014-01-01

    Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active β1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors. PMID:24189182

  12. A survey of MRI-based medical image analysis for brain tumor studies.

    PubMed

    Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P; Reyes, Mauricio

    2013-07-07

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

  13. A survey of MRI-based medical image analysis for brain tumor studies

    NASA Astrophysics Data System (ADS)

    Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P.; Reyes, Mauricio

    2013-07-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

  14. Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens

    SciTech Connect

    Louis, D.N.; Rubio, M.P.; Correa, K.M.; Gusella, J.F.; Deimling, A. von )

    1993-09-01

    Brain stem gliomas are pediatric astrocytomas that histologically resemble adult supratentorial astrocytomas such as gliobastomas multiforme (GBM). The molecular genetic studies have suggested that adult GBM can be divided into two genetic subsets: Tumors with p53 tumor suppressor gene mutations and chromosome 17p loss that occur more commonly in younger patients; and tumors with epidermal growth factor receptor (EGFR) gene amplification that occur more commonly in older patients. Brain stem gliomas have not been studied since biopsies of these tumors are rare and extremely small. The authors investigated the molecular genetic composition of seven brain stem glioblastomas (two small biopsies, five autopsies) using polymerase chain reaction (PCR) assays for chromosomal loss, gene mutation and gene amplification. Four cases lost portions of chromosome 17p that included the 53p gene. These four cases and one additional case had mutations in the p53 gene. None of the cases showed amplification of the EGFR gene. Allelic losses of the long arm of chromosome 10 were noted in four cases. These results suggest similarities between pediatric brain stem glioblastomas and those GBM that occur in younger adult patients, and confirm the utility of PCR-based means of studying small and archival brain tumor specimens. 47 refs., 7 figs., 2 tabs.

  15. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    PubMed

    Lobos-Urbina, Diego; Kittsteiner-Manubens, Lucas; Peña, José

    2017-03-21

    Patients with brain tumors –primary or metastatic- have an increased risk of presenting seizures during the course of their disease. So, prophylactic antiepileptic drugs have been proposed. However, the effects of this intervention are not yet clear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 12 systematic reviews including 80 studies overall. Twelve corresponded to randomized trials, but only two answered the question of interest. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE method. We concluded primary prevention with antiepileptic drugs might not reduce the risk of seizures, and it is associated to frequent adverse effects.

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

    PubMed

    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.

  17. Magnetic resonance microscopy at 14 Tesla and correlative histopathology of human brain tumor tissue.

    PubMed

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples.

  18. Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

    PubMed Central

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples. PMID:22110653

  19. Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors.

    PubMed

    Morfouace, Marie; Nimmervoll, Birgit; Boulos, Nidal; Patel, Yogesh T; Shelat, Anang; Freeman, Burgess B; Robinson, Giles W; Wright, Karen; Gajjar, Amar; Stewart, Clinton F; Gilbertson, Richard J; Roussel, Martine F

    2016-01-01

    Chemotherapies active in preclinical studies frequently fail in the clinic due to lack of efficacy, which limits progress for rare cancers since only small numbers of patients are available for clinical trials. Thus, a preclinical drug development pipeline was developed to prioritize potentially active regimens for pediatric brain tumors spanning from in vitro drug screening, through intracranial and intra-tumoral pharmacokinetics to in vivo efficacy studies. Here, as an example of the pipeline, data are presented for the combination of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in three pediatric brain tumor models. The in vitro activity of nine novel therapies was tested against tumor spheres derived from faithful mouse models of Group 3 medulloblastoma, ependymoma, and choroid plexus carcinoma. Agents with the greatest in vitro potency were then subjected to a comprehensive series of in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies culminating in preclinical efficacy trials in mice harboring brain tumors. The nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) markedly reduced the proliferation in vitro of all three brain tumor cell types at nanomolar concentrations. Detailed intracranial PK studies confirmed that systemically administered FdCyd exceeded concentrations in brain tumors necessary to inhibit tumor cell proliferation, but no tumor displayed a significant in vivo therapeutic response. Despite promising in vitro activity and in vivo PK properties, FdCyd is unlikely to be an effective treatment of pediatric brain tumors, and therefore was deprioritized for the clinic. Our comprehensive and integrated preclinical drug development pipeline should reduce the attrition of drugs in clinical trials.

  20. In-vivo optical detection of brain tumor and tumor margin: a combined auto-fluorescence and diffuse reflectance spectroscopic study

    NASA Astrophysics Data System (ADS)

    Majumder, Shovan K.; Gebhart, Steven; Thompson, Reid; Weaver, Kyle D.; Johnson, Mahlon D.; Lin, Wei-Chiang; Mahadevan-Jansen, Anita

    2007-02-01

    Recently, optical spectroscopy has shown considerable promise to be used as a potential clinical tool for human brain tumor detection and therapeutic guidance. Our group showed for the first time the possibility of using combined autofluorescence and diffuse reflectance spectroscopy and established its applicability for human brain tumor demarcation in previous in vitro and in vivo studies. We report in this paper the results of a clinical study designed to further evaluate the efficacy of the approach for demarcation of brain tumors and tumor margins from normal brain tissues in intra-operative clinical setting. Using a portable system, optical spectra were collected from the brain of 110 patients undergoing craniotomy at the Vanderbilt University Medical Center. Spectral measurements were taken from multiple sites of tumor core, tumor margin and normal areas of brain tissues and the resulting spectra were correlated with the corresponding histopathologic diagnosis. Using histology as the gold standard, a probabilistic multi-class diagnostic algorithm was developed to simultaneously distinguish tumor core and tumor margin from normal brain tissue sites using independent training and validation sets of data. An unbiased estimate of the accuracy of the model indicates that combined autofluorescence and diffuse reflectance spectroscopy was able to distinguish tumor core and tumor margin from normal brain tissues with an average predictive accuracy of ~88%.

  1. Automatic Brain Tumor Detection in T2-weighted Magnetic Resonance Images

    NASA Astrophysics Data System (ADS)

    Dvořák, P.; Kropatsch, W. G.; Bartušek, K.

    2013-10-01

    This work focuses on fully automatic detection of brain tumors. The first aim is to determine, whether the image contains a brain with a tumor, and if it does, localize it. The goal of this work is not the exact segmentation of tumors, but the localization of their approximate position. The test database contains 203 T2-weighted images of which 131 are images of healthy brain and the remaining 72 images contain brain with pathological area. The estimation, whether the image shows an afflicted brain and where a pathological area is, is done by multi resolution symmetry analysis. The first goal was tested by five-fold cross-validation technique with 100 repetitions to avoid the result dependency on sample order. This part of the proposed method reaches the true positive rate of 87.52% and the true negative rate of 93.14% for an afflicted brain detection. The evaluation of the second part of the algorithm was carried out by comparing the estimated location to the true tumor location. The detection of the tumor location reaches the rate of 95.83% of correct anomaly detection and the rate 87.5% of correct tumor location.

  2. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    NASA Astrophysics Data System (ADS)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  3. Structural Brain Alterations in Children an Average of 5 Years after Surgery and Chemotherapy for Brain Tumors

    PubMed Central

    Nelson, Mary Baron; Macey, Paul M.; Harper, Ronald M.; Jacob, Eufemia; Patel, Sunita K.; Finlay, Jonathan L.; Nelson, Marvin D.; Compton, Peggy

    2014-01-01

    Background Young children with brain tumors are often treated with high-dose chemotherapy after surgery to avoid brain tissue injury associated with irradiation. The effects of systemic chemotherapy on healthy brain tissue in this population, however, are unclear. Our objective was to compare gray and white matter integrity using MRI procedures in children with brain tumors (n=7, mean age 8.3 years), treated with surgery and high-dose chemotherapy followed by autologous hematopoietic cell rescue (AuHCR) an average of 5.4 years earlier, to age- and gender-matched healthy controls (n=9, mean age 9.3 years). Methods Diffusion tensor imaging data were collected to evaluate tissue integrity throughout the brain, as measured by mean diffusivity (MD), a marker of glial, neuronal, and axonal status, and fractional anisotropy (FA), an index of axonal health. Individual MD and FA maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance, with age and sex as covariates. Results Higher mean diffusivity values, indicative of injury, emerged in patients compared with controls (p<0.05, corrected for multiple comparisons), and were especially apparent in the central thalamus, external capsule, putamen, globus pallidus and pons. Reduced FA values in some regions did not reach significance after correction for multiple comparisons. Conclusions Children treated with surgery and high-dose chemotherapy with AuHCR for brain tumors an average of 5.4 years earlier show alterations in white and gray matter in multiple brain areas distant from the tumor site, raising the possibility for long-term consequences of the tumor or treatment. PMID:24830985

  4. Non-invasive monitoring of hemodynamic changes in orthotropic brain tumor

    NASA Astrophysics Data System (ADS)

    Kashyap, Dheerendra; Sharma, Vikrant; Liu, Hanli

    2007-02-01

    Radio surgical interventions such as Gamma Knife and Cyberknife have become attractive as therapeutic interventions. However, one of the drawbacks of cyberknife is radionecrosis, which is caused by excessive radiation to surrounding normal tissues. Radionecrosis occurs in about 10-15% of cases and could have adverse effects leading to death. Currently available imaging techniques have failed to reliably distinguish radionecrosis from tumor growth. Development of imaging techniques that could provide distinction between tumor growth and radionecrosis would give us ability to monitor effects of radiation therapy non-invasively. This paper investigates the use of near infrared spectroscopy (NIRS) as a new technique to monitor the growth of brain tumors. Brain tumors (9L glioma cell line) were implanted in right caudate nucleus of rats (250-300 gms, Male Fisher C) through a guide screw. A new algorithm was developed, which used broadband steady-state reflectance measurements made using a single source-detector pair, to quantify absolute concentrations of hemoglobin derivatives and reduced scattering coefficients. Preliminary results from the brain tumors indicated decreases in oxygen saturation, oxygenated hemoglobin concentrations and increases in deoxygenated hemoglobin concentrations with tumor growth. The study demonstrates that NIRS technology could provide an efficient, noninvasive means of monitoring vascular oxygenation dynamics of brain tumors and further facilitate investigations of efficacy of tumor treatments.

  5. Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor.

    PubMed

    Yuan, Hsiangkuo; Wilson, Christy M; Xia, Jun; Doyle, Sarah L; Li, Shuqin; Fales, Andrew M; Liu, Yang; Ozaki, Ema; Mulfaul, Kelly; Hanna, Gabi; Palmer, Gregory M; Wang, Lihong V; Grant, Gerald A; Vo-Dinh, Tuan

    2014-04-21

    Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution.

  6. Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor

    PubMed Central

    Yuan, Hsiangkuo; Wilson, Christy M.; Xia, Jun; Doyle, Sarah L.; Li, Shuqin; Fales, Andrew M; Liu, Yang; Ozaki, Ema; Mulfaul, Kelly; Hanna, Gabi; Palmer, Gregory M.; Wang, Lihong V.; Grant, Gerald A.

    2014-01-01

    Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution. PMID:24619405

  7. Direct cortical stimulation but not transcranial electrical stimulation motor evoked potentials detect brain ischemia during brain tumor resection.

    PubMed

    Li, Fenghua; Deshaies, Eric M; Allott, Geoffrey; Canute, Gregory; Gorji, Reza

    2011-09-01

    Motor evoked potentials (MEPs) elicited by both direct cortical stimulation (DCS) and transcranial electrical stimulation are used during brain tumor resection. Parallel use of direct cortical stimulation motor evoked potentials (DCS-MEPs) and transcranial electrical stimulation motor evoked potentials (TCeMEPs) has been practiced during brain tumor resection. We report that DCS-MEPs elicited by direct subdural grid stimulation, but not TCeMEPs, detected brain ischemia during brain tumor resection. Following resection of a brainstem high-grade glioma in a 21-year-old, the threshold of cortical motor-evoked-potentials (cMEPs) increased from 13 mA to 20 mA while amplitudes decreased. No changes were noted in transcranial motor evoked potentials (TCMEPs), somatosensory evoked potentials (SSEPs), auditory evoked potentials (AEPs), anesthetics, or hemodynamic parameters. Our case showed the loss of cMEPs and SSEPs, but not TCeMEPs. Permanent loss of DCS-MEPs and SSEPs was correlated with permanent left hemiplegia in our patient even when appropriate action was taken. Parallel use of DCS- and TCeMEPs with SSEPs improves sensitivity of intraoperative detection of motor impairment. DCS may be superior to TCeMEPs during brain tumor resection.

  8. The Influence of Neuronal Activity on Breast Tumor Metastasis to the Brain

    DTIC Science & Technology

    2009-09-01

    drugs to alter brain activity: caffeine, methylphenidate and modafinil . While the smallest effect may be expected from caffeine which is not as potent...caffeine, we have initiated experiments to test the effects of modafinil on breast tumor metastasis to the brain in our model. Unfortunately, we have had

  9. Targeted delivery of nano-PTX to the brain tumor-associated macrophages

    PubMed Central

    Zou, Lei; Tao, Youhua; Payne, Gregory; Do, Linh; Thomas, Tima; Rodriguez, Juan; Dou, Huanyu

    2017-01-01

    Nanoparticles containing mixed lipid monolayer shell, biodegradable polymer core and rabies virus glycoprotein (RVG) peptide as brain targeting ligand, were developed for brain targeted delivery of paclitaxel (PTX) to treat malignant glioma. RVG conjugated PTX loaded NPs (RVG-PTX-NPs) had the desirable size (~140 nm), narrow size distribution and spherical shape. RVG-PTX-NPs showed poor uptake by neurons and selective targeting to the brain tumor associated macrophages (TAMs) with controlled release and tumor specific toxicity. In vivo studies revealed that RVG-PTX-NPs were significant to cross the blood-brain barrier (BBB) and had specific targeting to the brain. Most importantly, RVG-PTX-NPs showed effectiveness for anti-glioma therapy on human glioma of mice model. We concluded that RVG-PTX-NPs provided an effective approach for brain-TAMs targeted delivery for the treatment of glioma. PMID:28036254

  10. Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor

    PubMed Central

    Park, Jisoo; Lee, Hyunji; Tran, Quangdon; Mun, Kisun; Kim, Dohoon; Hong, Youngeun; Kwon, So Hee; Brazil, Derek; Park, Jongsun; Kim, Seon-Hwan

    2017-01-01

    Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers. PMID:28133515

  11. The Relationship between Parkinson Disease and Brain Tumor: A Meta-Analysis

    PubMed Central

    Ye, Rong; Shen, Ting; Jiang, Yasi; Xu, Lingjia; Si, Xiaoli; Zhang, Baorong

    2016-01-01

    Objective Epidemiological studies have investigated the association between Parkinson disease (PD) occurrence and the risk of brain tumors, while the results remain controversial. We performed a meta-analysis to clarify the exact relationship between PD and brain tumors. Methods A systematic literature search was conducted using PubMed, Embase, ScienceDirect and CBM (China Biology Medicine Disc) before February 2016. Eligible studies were those that reported risk estimates of brain tumors among patients with PD or vice versa. A random-effects model was used to calculate the pooled odds ratio (OR) of the outcomes. Subgroup analyses and sensitivity analysis were conducted to explore the potential sources of heterogeneity. Results In total, eight studies involving 329,276 participants met our inclusion criteria. The pooled OR was 1.51 (95%CI 1.21–1.89), indicating that PD carried a higher risk of brain tumor. Analyses by temporal relationship found that the occurrence of brain tumor was significantly higher after the diagnosis of PD (OR 1.55, 95% CI 1.18–2.05), but not statistically significant before PD diagnosis (OR 1.21, 95%CI 0.93–1.58). Subgroup analysis showed that gender differences, ethnicity differences and the characteristic of the tumor (benign or malignant) did not make much change in the association between brain tumor and PD. Conclusions Our meta-analysis collecting epidemiological studies suggested a positive association of PD with brain tumors, while the influence of anti-parkinson drugs and ascertainment bias could not be excluded. Further studies with larger sample size and more strict inclusion criteria should be conducted in the future. PMID:27764145

  12. Estimating the risk of brain tumors from cellphone use: Published case-control studies.

    PubMed

    Morgan, L Lloyd

    2009-08-01

    This paper reviews the results of early cellphone studies, where exposure duration was too short to expect tumorigenesis, as well as two sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Dr. Lennart Hardell. The recent studies reach very different conclusions. With four exceptions the industry-funded Interphone studies found no increased risk of brain tumors from cellphone use, while the Swedish studies, independent of industry funding, reported numerous findings of significant increased brain tumor risk from cellphone and cordless phone use. An analysis of the data from the Interphone studies suggests that either the use of a cellphone protects the user from a brain tumor, or the studies had serious design flaws. Eleven flaws are identified: (1) selection bias, (2) insufficient latency time, (3) definition of 'regular' cellphone user, (4) exclusion of young adults and children, (5) brain tumor risk from cellphones radiating higher power levels in rural areas were not investigated, (6) exposure to other transmitting sources are excluded, (7) exclusion of brain tumor types, (8) tumors outside the cellphone radiation plume are treated as exposed, (9) exclusion of brain tumor cases because of death or illness, (10) recall accuracy of cellphone use, and (11) funding bias. The Interphone studies have all 11 flaws, and the Swedish studies have 3 flaws (8, 9 and 10). The data from the Swedish studies are consistent with what would be expected if cellphone use were a risk for brain tumors, while the Interphone studies data are incredulous. If a risk does exist, the public health cost will be large. These are the circumstances where application of the Precautionary Principle is indicated, especially if low-cost options could reduce the absorbed cellphone radiation by several orders of magnitude.

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

    PubMed

    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.

  14. EARLY POSTOPERATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN FIVE DOGS WITH CONFIRMED AND SUSPECTED BRAIN TUMORS.

    PubMed

    Chow, Kathleen Ella; Tyrrell, Dayle; Long, Sam Nicholas

    2015-01-01

    Early postoperative neuroimaging has been performed in people for over 20 years to detect residual brain tumor tissue and surgical complications. The purpose of this retrospective study was to describe characteristics observed using early postoperative magnetic resonance imaging in a group of dogs undergoing craniotomy for brain tumor removal. Two independent observers came to a consensus opinion for presence/absence of the following MRI characteristics: residual tumor tissue; hemorrhage and ischemic lesions; abnormal enhancement (including the margins of the resection cavity, choroid plexus, meninges) and signal intensity changes on diffusion-weighted imaging. Five dogs were included in the study, having had preoperative and early postoperative MRI acquired within four days after surgery. The most commonly observed characteristics were abnormal meningeal enhancement, linear enhancement at margins of the resection cavity, hemorrhage, and a thin rim of hyperintensity surrounding the resection cavity on diffusion-weighted imaging. Residual tumor tissue was detected in one case of an enhancing tumor and in one case of a tumor containing areas of hemorrhage preoperatively. Residual tumor tissue was suspected but could not be confirmed when tumors were nonenhancing. Findings supported the use of early postoperative MRI as a method for detecting residual brain tumor tissue in dogs.

  15. Management of childhood brain tumors: consensus report by the Pediatric Hematology Oncology (PHO) Chapter of Indian Academy of Pediatrics (IAP).

    PubMed

    Bhat, Sunil; Yadav, Satya Prakash; Suri, Vaishali; Patir, Rana; Kurkure, Purna; Kellie, Stewart; Sachdeva, Anupam

    2011-12-01

    Brain tumors are the second most common childhood tumors and remain the leading cause of cancer related deaths in children. Appropriate diagnosis and management of these tumors are essential to improve survival. There are no clinical practical guidelines available for the management of brain tumors in India. This document is a consensus report prepared after a National Consultation on Pediatric Brain Tumors held in Delhi on 06 Nov 2008. The meeting was attended by eminent experts from all over the country, in the fields of Neurosurgery, Radiation Oncology, Pediatric Oncology, Neuropathology, Diagnostic Imaging, Pediatric Endocrinology and Allied Health Professionals. This article highlights that physicians looking after children with brain tumors should work as part of a multidisciplinary team to improve the survival, quality of life, neuro-cognitive outcomes and standards of care for children with brain tumors. Recommendations for when to suspect, diagnostic workup, initial management, long-term follow up and specific management of individual tumors are outlined.

  16. Improving the accuracy of brain tumor surgery via Raman-based technology.

    PubMed

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.

  17. Expression of the HOX genes and HOTAIR in atypical teratoid rhabdoid tumors and other pediatric brain tumors.

    PubMed

    Chakravadhanula, Madhavi; Ozols, Victor V; Hampton, Chris N; Zhou, Li; Catchpoole, Daniel; Bhardwaj, Ratan D

    2014-09-01

    Pediatric brain tumors such as atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive and predominantly occur in young children. A characteristic feature of ATRT is aberrations of the SMARCB1 (hSNF5/INI1) gene. Developmental gene defects may play an important role in the biology of pediatric brain tumors. HOX genes are transcription factors that play a pivotal role in anterior-posterior body axis patterning and are misexpressed in tumors such as lung carcinoma, neuroblastoma, and glioma. HOX genes are also known to be associated with long noncoding RNAs (lncRNAs) such as HOTAIR, which induces transcriptional silencing of the HOXD locus by recruiting polycomb repressive complex 2 to the HOXD locus. In this study, transcriptome analysis using the nanoString platform was performed, and expression of the HOX and HOTAIR genes was studied in pediatric tumors: 20 ATRTs, 10 ependymomas, 10 medulloblastomas, six glioblastoma multiforme, and nine juvenile pilocytic astrocytomas (JPAs). Results indicate that in ATRTs, medulloblastomas, and JPAs, the HOTAIR and HOXC genes are highly expressed; however, HOXD8-10 genes are not silenced. In ependymomas, there is low expression of the HOXC, HOTAIR, and HOXD8-10 genes. These interesting results need to be elucidated further so that the functions of these genes in pediatric tumors is understood.

  18. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

    PubMed Central

    Wang, Yuxuan; Springer, Simeon; Zhang, Ming; McMahon, K. Wyatt; Kinde, Isaac; Dobbyn, Lisa; Ptak, Janine; Brem, Henry; Chaichana, Kaisorn; Gallia, Gary L.; Gokaslan, Ziya L.; Groves, Mari L.; Jallo, George I.; Lim, Michael; Olivi, Alessandro; Quinones-Hinojosa, Alfredo; Rigamonti, Daniele; Riggins, Greg J.; Sciubba, Daniel M.; Weingart, Jon D.; Wolinsky, Jean-Paul; Ye, Xiaobu; Oba-Shinjo, Sueli Mieko; Marie, Suely K. N.; Holdhoff, Matthias; Agrawal, Nishant; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Bettegowda, Chetan

    2015-01-01

    Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57–88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88–100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord. PMID:26195750

  19. Childhood Brain Tumors, Residential Insecticide Exposure, and Pesticide Metabolism Genes

    PubMed Central

    Nielsen, Susan Searles; McKean-Cowdin, Roberta; Farin, Federico M.; Holly, Elizabeth A.; Preston-Martin, Susan; Mueller, Beth A.

    2010-01-01

    Background Insecticides that target the nervous system may play a role in the development of childhood brain tumors (CBTs). Constitutive genetic variation affects metabolism of these chemicals. Methods We analyzed population-based case–control data to examine whether CBT is associated with the functional genetic polymorphisms PON1C–108T, PON1Q192R, PON1L55M, BCHEA539T, FMO1C–9536A, FMO3E158K, ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls, ≤ 10 years of age, and born in California or Washington State between 1978 and 1990. Conception-to-diagnosis home insecticide treatment history was ascertained by interview. Results We observed no biologically plausible main effects for any of the metabolic polymorphisms with CBT risk. However, we observed strong interactions between genotype and insecticide exposure during childhood. Among exposed children, CBT risk increased per PON1–108T allele [odds ratio (OR) = 1.8; 95% confidence interval (CI), 1.1–3.0] and FMO1–9536A (*6) allele (OR = 2.7; 95% CI, 1.2–5.9), whereas among children never exposed, CBT risk was not increased (PON1: OR = 0.7; 95% CI, 0.5–1.0, interaction p = 0.005; FMO1: OR = 1.0; 95% CI, 0.6–1.6, interaction p = 0.009). We observed a similar but statistically nonsignificant interaction between childhood exposure and BCHEA539T (interaction p = 0.08). These interactions were present among both Hispanic and non-Hispanic white children. Conclusion Based on known effects of these variants, these results suggest that exposure in childhood to organophosphorus and perhaps to carbamate insecticides in combination with a reduced ability to detoxify them may be associated with CBT. Confirmation in other studies is required. PMID:20056567

  20. Blood flow in an experimental rat brain tumor by tissue equilibration and indicator fractionation.

    PubMed

    Graham, M M; Spence, A M; Abbott, G L; O'Gorman, L; Muzi, M

    1987-01-01

    The tissue equilibration technique (Kety) was compared with the indicator fractionation technique for the measurement of blood flow to normal brain and an experimental brain tumor in the rat. The tumor was a cloned astrocytic glioma implanted in the cerebral hemisphere of F-344 rats. I-125 Iodoantipyrine, using a rising infusion for one minute, was used for the tissue equilibration technique. C-14 butanol, injected as a bolus 8 seconds before sacrifice, was used for the indicator fractionation technique. Samples were assayed using liquid scintillation counting and the iodoantipyrine results were regressed against the butanol results. For normal tissue R = 0.832, SEE = 0.115 ml/g/min, and Slope = 0.626. For tumor R = 0.796, SEE = 0.070 ml/g/min, and Slope = 0.441. The iodoantipyrine tissue/blood partition coefficient for normal hemisphere (gray and white matter) was 0.861 +/-0.037 (SD) and for tumor was 0.876 +/-0.042. The indicator fractionation technique with C-14 butanol underestimated blood flow in a consistent manner, probably because of incomplete extraction, early washout of activity from tissue and from evaporation of butanol during processing. Our experiments revealed no differences between tumor and normal brain tissue that might invalidate the comparison of iodoantipyrine blood flow results in brain tumors and surrounding normal brain.

  1. Support after Brain Tumor Means Different Things: Family Caregivers’ Experiences of Support and Relationship Changes

    PubMed Central

    Ownsworth, Tamara; Goadby, Elizabeth; Chambers, Suzanne Kathleen

    2015-01-01

    Shorter hospital stays and greater emphasis on outpatient care means that family members have the primary responsibility for supporting a person with brain tumor to manage the physical, cognitive, behavioral, and emotional effects of the illness and its treatment. Given the integral role of family caregivers, it is essential to understand their experience of the impact of brain tumor and their own support needs. Accordingly, this qualitative study aimed to investigate family caregivers’ experiences of support and relationship changes in the context of brain tumor. In-depth interviews were conducted with 11 family caregivers (8 spouse/partner, 3 parents) of people with malignant or benign tumor. A thematic analysis of interview transcripts identified two major themes, namely, “Meanings of Support” and “Relationship Impacts.” The Meanings of Support theme was characterized by intertwined and distinct support needs, varied expectations of support and factors influencing support expectations. The Relationship Impacts theme depicted mixed experiences of strengthened, maintained, and strained relations with the person with brain tumor. Overall, the findings highlight that there is considerable variability in caregivers’ experiences and expectations of support and the impact of brain tumor on relationships. The implications of these findings for the provision of caregiver support are discussed. PMID:25729740

  2. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    PubMed

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

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

    SciTech Connect

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    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

  4. Distribution of anionic sites on the capillary endothelium in an experimental brain tumor model.

    PubMed

    Vincent, S; DePace, D; Finkelstein, S

    1988-02-01

    The distribution of anionic domains on the capillary endothelium of experimental brain tumors was determined using cationic ferritin (CF) in order to ascertain whether the pattern of these domains is different from that on normal cerebral capillaries. Tumors were induced by stereotaxic injection of cultured neoplastic glial cells, A15A5, into the caudate nucleus of Sprague-Dawley rats. Following a 14-21 day growth period tumors appeared as vascularized, sharply circumscribed masses which caused compression of the surrounding brain tissue. Anionic domains were distributed in a patchy and irregular pattern on the luminal plasma membrane of the endothelia of blood vessels in the tumors. Some variability in this pattern was observed infrequently in limited regions of the tumor where there was either a continuous layer of CF or an absence of CF binding. Plasmalemmal vesicles, coated vesicles, coated pits, multivesicular bodies, and some junctional complexes showed varying degrees of labeling with the probe. Capillaries in the tumor periphery and normal cerebral vessels showed a uniform distribution of anionic groups. These results indicate that there is an altered surface charge on the endothelial luminal plasma membrane of blood vessels in brain tumors. A correlation may exist between the altered surface charge and the degree to which the blood-brain barrier is impaired in these vessels.

  5. Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors

    PubMed Central

    Mulcahy Levy, Jean M; Zahedi, Shadi; Griesinger, Andrea M; Morin, Andrew; Davies, Kurtis D; Aisner, Dara L; Kleinschmidt-DeMasters, BK; Fitzwalter, Brent E; Goodall, Megan L; Thorburn, Jacqueline; Amani, Vladimir; Donson, Andrew M; Birks, Diane K; Mirsky, David M; Hankinson, Todd C; Handler, Michael H; Green, Adam L; Vibhakar, Rajeev; Foreman, Nicholas K; Thorburn, Andrew

    2017-01-01

    Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAFV600Emutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAFV600E inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance. We tested this hypothesis in vemurafenib-resistant brain tumors. Genetic and pharmacological autophagy inhibition overcame molecularly distinct resistance mechanisms, inhibited tumor cell growth, and increased cell death. Patients with resistance had favorable clinical responses when chloroquine was added to vemurafenib. This provides a fundamentally different strategy to circumvent multiple mechanisms of kinase inhibitor resistance that could be rapidly tested in clinical trials in patients with BRAFV600E brain tumors. DOI: http://dx.doi.org/10.7554/eLife.19671.001 PMID:28094001

  6. Differentiating histologic malignancy of primary brain tumors: Pentavalent Technetium-99m-DMSA

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

    This study assessed pentavalent {sup 99m}Tc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq {sup 99m}Tc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by {sup 99m}Tc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. 16 refs., 6 figs., 2 tabs.

  7. Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth.

    PubMed

    Orr, Brent A; Bai, Haibo; Odia, Yazmin; Jain, Deepali; Anders, Robert A; Eberhart, Charles G

    2011-07-01

    The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene in multiple human cancers. Currently, little is known about the expression of YAP1 either in normal human brain tissue or in central nervous system neoplasms. We used immunohistochemistry to evaluate nuclear YAP1 expression in the fetal and normal adult human brains and in 264 brain tumors. YAP1 was expressed in fetal and adult brain regions known to harbor neural progenitor cells, but there was little YAP1 immunoreactivity in the adult cerebral cortex. YAP1 protein was also readily detected in the nuclei of human brain tumors. In medulloblastoma, the expression varied between histologic subtypes and was most prominent in nodular/desmoplastic tumors. In gliomas, it was frequently expressed in infiltrating astrocytomas and oligodendrogliomas but rarely in pilocytic astrocytomas. Using a loss-of-function approach, we show that YAP1 promoted growth of glioblastoma cell lines in vitro. High levels of YAP1 messenger RNA expression were associated with aggressive molecular subsets of glioblastoma and with a nonsignificant trend toward reduced mean survival in human astrocytoma patients. These findings suggest that YAP1 may play an important role in normal human brain development and that it could represent a new target in human brain tumors.

  8. Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier.

    PubMed Central

    Zagzag, D.; Brem, S.; Robert, F.

    1988-01-01

    A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis. Images Figure 2 Figure 3 Figure 6 Figure 4 Figure 5 Figure 7 Figure 8 Figure 10 Figure 12 Figure 13 Figure 15 PMID:2451889

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27830712

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Effect of barrier opening on brain edema in human brain tumors.

    PubMed

    Sato, S; Suga, S; Yunoki, K; Mihara, B

    1994-01-01

    Blood-brain barrier (BBB) opening was carried out in 10 patients with cerebral lesions, and the MRI findings were evaluated following the barrier opening. An intra-arterial injection of 10% glycerol (4 ml/kg, 1 approximately 2 ml/s) was given as a hyperosmotic solution. T2-weighted MRI was undertaken using a TOSHIBA 22A at 30 minutes after BBB opening. Barrier-opening MRI was performed 10 times in 10 patients, including 5 cases of glioblastoma multiforme, 2 cases of astrocytoma, 1 case of malignant lymphoma, 1 case of cerebral contusion and 1 case of neurinoma. The high-intensity area (HIA) was compared with that in MRI without barrier opening. Three types of changes of HIA in MRI were observed after BBB opening as follows. Type 1: Expansion of the HIA was noted in 4 of 5 cases of glioblastoma multiforme, the 1 case of malignant lymphoma and the 1 case of cerebral contusion. Type 2: Almost no change was observed in the 1 case of neuronoma. Type 3: A decrease in HIA was noted in the 2 cases of astrocytoma and in 1 case of glioblastoma multiforme. The MRI following BBB opening evidently showed 3 types of changes according to the degree of BBB disruption. Glioblastoma multiforme or contusion with a severely disrupted BBB revealed an increase in HIA following barrier opening. Benign posterior fossa neurinoma showed no change in HIA after barrier opening. Moderate malignant tumors exhibited a decrease in HIA on barrier-opening MRI. It was concluded that malignant tumors have a severely damaged BBB, which is readily disrupted by osmotic barrier opening.

  12. Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

    PubMed

    Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

    2013-02-01

    Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response.

  13. Absorption edge subtraction imaging for volumetric measurement in an animal model of malignant brain tumor

    NASA Astrophysics Data System (ADS)

    Rigley, S.; Rigon, L.; Ataelmannan, K.; Chapman, D.; Doucette, R.; Griebel, R.; Juurlink, B.; Arfelli, F.; Menk, R.-H.; Tromba, G.; Barroso, R. C.; Beveridge, T.; Lewis, R.; Pavlov, K.; Siu, K.; Hall, C.; Schültke, E.

    2005-08-01

    The goal of this project is to determine the feasibility of utilizing colloidal gold as a marker for C6 glioblastoma cells implanted into rat brain as an appropriate model for volumetric measurements of tumors using absorption edge subtraction (AES). Phase sensitive X-ray imaging is combined with KES to give good soft tissue contrast. Current methods for volumetric measurements of implanted C6 glioblastoma tumors in rat brains using MRI technology are inadequate due to the small size of the tumor (2.5-4 mm in diameter) and the thickness of the MRI slice (1-1.5 mm). Previously, our group has shown that AES detection of colloidal gold labeled C6 glioblastoma cells implanted into a rat brains may be feasible. The long-term goal for this project is to establish a method, which would allow the researcher to monitor the development of a tumor over time. Most importantly, this technique should allow researchers to accurately determine the potency of a treatment on the size and growth rate for a C6 implanted tumors. In addition, we plan to challenge the hypothesis that tumors of the glioma type do not metastasize outside of the brain. A sensitive technique for the detection of C6 cells, such as that using colloidal gold and AES/DEI, should enable researchers to detect C6 cells, which have metastasized and migrated to different areas of the body. The ability to detect implanted C6 cells followed by the development of the tumor, the possible migration of the cells and the ability to accurately measure the effects of treatments on the volume of the tumor would be of the utmost importance to brain tumor research.

  14. Inflammatory infiltrates and natural killer cell presence in human brain tumors.

    PubMed

    Stevens, A; Klöter, I; Roggendorf, W

    1988-02-15

    Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T-helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.

  15. Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States.

    PubMed

    Dela Cruz, Florante N; Giannitti, Federico; Li, Linlin; Woods, Leslie W; Del Valle, Luis; Delwart, Eric; Pesavento, Patricia A

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.

  16. Notch1 and notch2 have opposite effects on embryonal brain tumor growth.

    PubMed

    Fan, Xing; Mikolaenko, Irina; Elhassan, Ihab; Ni, Xingzhi; Wang, Yunyue; Ball, Douglas; Brat, Daniel J; Perry, Arie; Eberhart, Charles G

    2004-11-01

    The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene in some neoplasms, and a tumor suppressor in others. Here, we show that different Notch receptors can have opposite effects in a single tumor type. Expression of truncated, constitutively active Notch1 or Notch2 in embryonal brain tumor cell lines caused antagonistic effects on tumor growth. Cell proliferation, soft agar colony formation, and xenograft growth were all promoted by Notch2 and inhibited by Notch1. We also found that Notch2 receptor transcripts are highly expressed in progenitor cell-derived brain tumors such as medulloblastomas, whereas Notch1 is scarce or undetectable. This parallels normal cerebellar development, during which Notch2 is predominantly expressed in proliferating progenitors and Notch1 in postmitotic differentiating cells. Given the oncogenic effects of Notch2, we analyzed its gene dosage in 40 embryonal brain tumors, detecting an increased copy number in 15% of cases. Notch2 gene amplification was confirmed by fluorescence in situ hybridization in one case with extremely high Notch2 mRNA levels. In addition, expression of the Notch pathway target gene Hes1 in medulloblastomas was associated with significantly shorter patient survival (P = 0.01). Finally, pharmacological inhibition of Notch signaling suppresses growth of medulloblastoma cells. Our data indicate that Notch1 and Notch2 can have opposite effects on the growth of a single tumor type, and show that Notch2 can be overexpressed after gene amplification in human tumors.

  17. Imaging diagnosis and fundamental knowledge of common brain tumors in adults.

    PubMed

    Tanaka, Akio

    2006-07-01

    The most common primary brain tumors in Japanese adults are meningiomas, gliomas, pituitary adenomas, and schwannomas, which together account for 84.0% of all primary brain tumors. The typical imaging findings of these tumors are well known by radiologists; therefore, the clinical and pathological issues, including terminology, genetics, and relation to hormones are discussed in this article. Other diseases important for the differential diagnoses are also mentioned. The molecular genetic analysis of brain tumors has recently become important. For instance, genetic analysis is important for differentiating oligodendroglial tumors from astrocytic tumors, and the gene mutation predicts response to chemotherapy for anaplastic oligodendrogliomas. Background factors such as hormones, history of cranial irradiation, and medications influence oncogenesis, tumor growth, and tumor appearances as seen by imaging modalities. A differential diagnosis with knowledge of the above may have some advantages over diagnoses based on imaging findings alone. Nonneoplastic diseases such as abscesses and demyelinating diseases may mimic gliomas. Pituitary adenomas may be confused with nonneoplastic conditions such as physiological hypertrophy and Rathke's cleft cyst. Such misdiagnoses would result in a treatment protocol very different from what would be suitable. Such conditions should be carefully distinguished from neoplasms.

  18. Immunotherapy of Malignant Tumors in the Brain: How Different from Other Sites?

    PubMed Central

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

    2016-01-01

    Immunotherapy is now advancing at remarkable pace for tumors located in various tissues, including the brain. Strategies launched decades ago, such as tumor antigen-specific therapeutic vaccines and adoptive transfer of tumor-infiltrating lymphocytes are being complemented by molecular engineering approaches allowing the development of tumor-specific TCR transgenic and chimeric antigen receptor T cells. In addition, the spectacular results obtained in the last years with immune checkpoint inhibitors are transfiguring immunotherapy, these agents being used both as single molecules, but also in combination with other immunotherapeutic modalities. Implementation of these various strategies is ongoing for more and more malignancies, including tumors located in the brain, raising the question of the immunological particularities of this site. This may necessitate cautious selection of tumor antigens, minimizing the immunosuppressive environment and promoting efficient T cell trafficking to the tumor. Once these aspects are taken into account, we might efficiently design immunotherapy for patients suffering from tumors located in the brain, with beneficial clinical outcome. PMID:28003994

  19. Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: Crossing the blood-brain-barrier divide

    PubMed Central

    Chacko, Ann-Marie; Li, Chunsheng; Pryma, Daniel A.; Brem, Steven; Coukos, George; Muzykantov, Vladimir R.

    2014-01-01

    Introduction Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBB) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large-molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications. Areas covered This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of CNS tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Non-invasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors. Expert Opinion Pre-clinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the blood-brain barrier divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly-targeted antibody delivery to CNS tumors to improve clinical outcomes. PMID:23751126

  20. Beauty product-related exposures and childhood brain tumors in seven countries: results from the SEARCH International Brain Tumor Study.

    PubMed

    Efird, J T; Holly, E A; Cordier, S; Mueller, B A; Lubin, F; Filippini, G; Peris-Bonet, R; McCredie, M; Arslan, A; Bracci, P; Preston-Martin, S

    2005-04-01

    Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0-2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child's birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child's birth was not associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1, CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR = 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR = 11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child's birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers' exposures to beauty products.

  1. Failed First Craniotomy and Tumor Removal of Parasagittal Meningioma with Severe Peritumoral Brain Edema

    PubMed Central

    Shim, Youngbo

    2016-01-01

    Parasagittal meningioma often presents as peritumoral brain edema (PTBE). The risk of edema increases when the tumor occludes the superior sagittal sinus (SSS). Although PTBE may be expected based on the patient’s symptoms or radiologic findings, extensive brain swelling and extracranial herniation during elective surgery are rare. Herniation during surgery could lead to irreversible neurological damage and even brain rupture. We report a case of a failed routine craniotomy for a parasagittal meningioma with complete occlusion of the posterior third of the SSS in a 30-year-old male patient. The patient developed extensive brain swelling and extracranial herniation during surgery. PMID:27867923

  2. Epidemiology of primary brain tumors: current concepts and review of the literature.

    PubMed Central

    Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

    2002-01-01

    The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

  3. Intraoperative Spectroscopy with Ultrahigh Sensitivity for Image-Guided Surgery of Malignant Brain Tumors.

    PubMed

    Kairdolf, Brad A; Bouras, Alexandros; Kaluzova, Milota; Sharma, Abhinav K; Wang, May Dongmei; Hadjipanayis, Constantinos G; Nie, Shuming

    2016-01-05

    Intraoperative cancer imaging and fluorescence-guided surgery have attracted considerable interest because fluorescence signals can provide real-time guidance to assist a surgeon in differentiating cancerous and normal tissues. Recent advances have led to the clinical use of a natural fluorophore called protoporphyrin IX (PpIX) for image-guided surgical resection of high-grade brain tumors (glioblastomas). However, traditional fluorescence imaging methods have only limited detection sensitivity and identification accuracy and are unable to detect low-grade or diffuse infiltrating gliomas (DIGs). Here we report a low-cost hand-held spectroscopic device that is capable of ultrasensitive detection of protoporphyrin IX fluorescence in vivo, together with intraoperative spectroscopic data obtained from both animal xenografts and human brain tumor specimens. The results indicate that intraoperative spectroscopy is at least 3 orders of magnitude more sensitive than the current surgical microscopes, allowing ultrasensitive detection of as few as 1000 tumor cells. For detection specificity, intraoperative spectroscopy allows the differentiation of brain tumor cells from normal brain cells with a contrast signal ratio over 100. In vivo animal studies reveal that protoporphyrin IX fluorescence is strongly correlated with both MRI and histological staining, confirming that the fluorescence signals are highly specific to tumor cells. Furthermore, ex vivo spectroscopic studies of excised brain tissues demonstrate that the hand-held spectroscopic device is capable of detecting diffuse tumor margins with low fluorescence contrast that are not detectable with current systems in the operating room. These results open new opportunities for intraoperative detection and fluorescence-guided resection of microscopic and low-grade glioma brain tumors with invasive or diffusive margins.

  4. Enhanced transfection of brain tumor suppressor genes by photochemical internalization

    NASA Astrophysics Data System (ADS)

    Chou, Chih H.; Sun, Chung-Ho; Zhou, Yi-Hong; Madsen, Steen J.; Hirschberg, Henry

    2011-03-01

    One of many limitations for cancer gene therapy is the inability of the therapeutic gene to transfect a sufficient number of tumor cells. Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. The utility of PCI for the delivery of a tumor suppressor gene (PAX-6) was investigated in monolayers and spheroids consisting of F98 rat glioma cells.

  5. 3D variational brain tumor segmentation on a clustered feature set

    NASA Astrophysics Data System (ADS)

    Popuri, Karteek; Cobzas, Dana; Jagersand, Martin; Shah, Sirish L.; Murtha, Albert

    2009-02-01

    Tumor segmentation from MRI data is a particularly challenging and time consuming 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. Our work addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multi-dimensional feature set. Further, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this paper is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to the previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned inside and outside region voxel probabilities 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 in the ventricles to be in the tumor and hence better disambiguate the tumor from brain tissue. We show the performance of our method on real MRI scans. The experimental dataset includes MRI scans, from patients with difficult instances, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Our method shows good results on these test cases.

  6. Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence.

    PubMed

    Shah, Ritu; Vattoth, Surjith; Jacob, Rojymon; Manzil, Fathima Fijula Palot; O'Malley, Janis P; Borghei, Peyman; Patel, Bhavik N; Curé, Joel K

    2012-01-01

    Radiation necrosis in the brain commonly occurs in three distinct clinical scenarios, namely, radiation therapy for head and neck malignancy or intracranial extraaxial tumor, stereotactic radiation therapy (including radiosurgery) for brain metastasis, and radiation therapy for primary brain tumors. Knowledge of the radiation treatment plan, amount of brain tissue included in the radiation port, type of radiation, location of the primary malignancy, and amount of time elapsed since radiation therapy is extremely important in determining whether the imaging abnormality represents radiation necrosis or recurrent tumor. Conventional magnetic resonance (MR) imaging findings of these two entities overlap considerably, and even at histopathologic analysis, tumor mixed with radiation necrosis is a common finding. Advanced imaging modalities such as diffusion tensor imaging and perfusion MR imaging (with calculation of certain specific parameters such as apparent diffusion coefficient ratios, relative peak height, and percentage of signal recovery), MR spectroscopy, and positron emission tomography can be useful in differentiating between recurrent tumor and radiation necrosis. In everyday practice, the visual assessment of diffusion-weighted and perfusion images may also be helpful by favoring one diagnosis over the other, with restricted diffusion and an elevated relative cerebral blood volume being seen much more frequently in recurrent tumor than in radiation necrosis.

  7. Numerical modelling and in vivo analysis of fluorescent and laser light backscattered from glial brain tumors

    NASA Astrophysics Data System (ADS)

    Savelieva, Tatiana A.; Kalyagina, Nina A.; Kholodtsova, Maria N.; Loschenov, Victor B.; Goryainov, Sergey A.; Potapov, Aleksander A.

    2012-03-01

    Brain glial tumors have peculiar features of the perifocal region extension, characterized by its indistinct area, which complicates determination of the borders for tissue resection. In the present study filter-reduced back-scattered laser light signals, compared to the data from mathematical modeling, were used for description of the brain white matter. The simulations of the scattered light distributions were performed in a Monte Carlo program using scattering and absorption parameters of the different grades of the brain glial tumors. The parameters were obtained by the Mie calculations for three main types of scatterers: myelinated axon fibers, cell nuclei and mitochondria. It was revealed that diffuse-reflected light, measured at the perifocal areas of the glial brain tumors, shows a significant difference relative to the signal, measured at the normal tissue, which signifies the possibility to provide diagnostically useful information on the tissue state, and to determine the borders of the tumor, thus to reduce the recurrence appearance. Differences in the values of ratios of diffuse reflectance from active growth parts of tumors and normal white matter can be useful for determination of the degree of tumor progress during the spectroscopic analysis.

  8. Metabolism of [U-13C]glucose in Human Brain Tumors In Vivo

    PubMed Central

    Maher, Elizabeth A.; Marin-Valencia, Isaac; Bachoo, Robert M.; Mashimo, Tomoyuki; Raisanen, Jack; Hatanpaa, Kimmo J.; Jindal, Ashish; Jeffrey, F. Mark; Choi, Changho; Madden, Christopher; Mathews, Dana; Pascual, Juan M.; Mickey, Bruce E.; Malloy, Craig R.; DeBerardinis, Ralph J.

    2012-01-01

    Glioblastomas (GBMs) and brain metastases demonstrate avid uptake of 18fluoro-2-deoxyglucose (FDG) by positron emission tomography (PET) and display perturbations of intracellular metabolite pools by 1H magnetic resonance spectroscopy (MRS). These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. FDG-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation compared to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain malignancies to oxidize glucose in the tricarboxylic acid cycle is unknown. Here we studied the metabolism of human brain tumors in situ. [U-13C]glucose was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. Analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the TCA cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-CoA pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse malignancies growing in their native microenvironment. PMID:22419606

  9. Pre- and postoperative neurocognitive deficits in brain tumor patients assessed by a computer based screening test.

    PubMed

    Hoffermann, Markus; Bruckmann, Lukas; Mahdy Ali, Kariem; Zaar, Karla; Avian, Alexander; von Campe, Gord

    2017-02-01

    Neurocognitive assessment becomes increasingly important in neuro-oncology. The presence and degree of neurocognitive deficits in patients with brain tumors appear to be important not only as outcome measures but also in treatment planning and as possible prognostic markers for tumor-progression. Common screening methods for neurocognitive deficits are often insufficient in uncovering subtle changes or harbor the risk of being observer-dependent and time-consuming. We present data of brain tumor patients screened by a computer-based neurocognitive assessment tool before and after surgery. 196 patients with tumor resections were tested at our institution using the NeuroCog Fx® software 2days before and 3-4months after surgery. Additionally to the test results, patient-related information, such as age, sex, handedness, level of education, pre- and postoperative neurological status, KPS, location and histopathological diagnosis were recorded. These prospectively collected results were correlated in the here presented retrospective study. The majority of patients with malignant gliomas, metastases and meningiomas showed significant deficits in various neurocognitive domains, most of them improved or did not decline in their postoperative neurocognitive performances. Interestingly, there was no significant correlation of neurocognitive deficits and brain tumor location. In future, standardized neuropsychological assessment should become an essential part of the management and care of patients with brain tumors to provide a more personalized and tailored treatment. Further studies will improve the understanding of the influence of various treatment modalities on neuro-cognition.

  10. Improving Care in Pediatric Neuro-oncology Patients:An Overview of the Unique Needs of Children with Brain Tumors

    PubMed Central

    Fischer, Cheryl; Petriccione, Mary; Donzelli, Maria; Pottenger, Elaine

    2016-01-01

    Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Childhood CNS tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from childhood CNS tumors is disproportionately high compared to other childhood malignancies. Management of children with CNS tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life. PMID:26245798

  11. Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors.

    PubMed

    Fischer, Cheryl; Petriccione, Mary; Donzelli, Maria; Pottenger, Elaine

    2016-03-01

    Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Pediatric central nervous system tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from pediatric central nervous system tumors is disproportionately high compared to other childhood malignancies. Management of children with central nervous system tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life.

  12. Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  13. Angiogenesis-targeting microbubbles combined with ultrasound-mediated gene therapy in brain tumors.

    PubMed

    Chang, En-Ling; Ting, Chien-Yu; Hsu, Po-Hong; Lin, Yu-Chun; Liao, En-Chi; Huang, Chiung-Yin; Chang, Yuan-Chih; Chan, Hong-Lin; Chiang, Chi-Shiun; Liu, Hao-Li; Wei, Kuo-Chen; Fan, Ching-Hsiang; Yeh, Chih-Kuang

    2017-04-10

    The major challenges in gene therapy for brain cancer are poor transgene expression due to the blood-brain barrier (BBB) and neurologic damage caused by conventional intracerebral injection. Non-viral gene delivery using ultrasound-targeted microbubble (MB) oscillation via the systematic transvascular route is attractive, but there is currently no high-yielding and targeted gene expression method. In this study, we developed a non-viral and angiogenesis-targeting gene delivery approach for efficient brain tumor gene therapy without brain damage. We developed a VEGFR2-targeted and cationic microbubble (VCMB) gene vector for use with transcranial focused ultrasound (FUS) exposure to allow transient gene delivery. The system was tested in a brain tumor model using the firefly luciferase gene and herpes simplex virus type 1 thymidine kinase/ganciclovir (pHSV-TK/GCV) with VCMBs under FUS exposure for transgene expression and anti-tumor effect. In vitro data showed that VCMBs have a high DNA-loading efficiency and high affinity for cancer cells. In vivo data confirmed that this technique enhanced gene delivery into tumor tissues without affecting normal brain tissues. The VCMB group resulted in higher luciferase expression (3.8 fold) relative to the CMB group (1.9 fold), and the direct injection group. The tumor volume on day 25 was significantly smaller in rats treated with the pHSV-TK/GCV system using VCMBs under FUS (9.7±5.2mm(3)) than in the direct injection group (40.1±4.3mm(3)). We demonstrated the successful use of DNA-loaded VCMBs and FUS for non-viral, non-invasive and targeted gene delivery to brain tumors.

  14. Brain tumor vessel response to synchrotron microbeam radiation therapy: a short-term in vivo study

    NASA Astrophysics Data System (ADS)

    Serduc, Raphaël; Christen, Thomas; Laissue, Jean; Farion, Régine; Bouchet, Audrey; van der Sanden, Boudewijn; Segebarth, Christoph; Bräuer-Krisch, Elke; LeDuc, Géraldine; Bravin, Alberto; Rémy, Chantal; Barbier, Emmanuel L.

    2008-07-01

    The aim of this work focuses on the description of the short-term response of a 9L brain tumor model and its vasculature to microbeam radiation therapy (MRT) using magnetic resonance imaging (MRI). Rat 9L gliosarcomas implanted in nude mice brains were irradiated by MRT 13 days after tumor inoculation using two orthogonal arrays of equally spaced 28 planar microbeams (25 µm width, 211 µm spacing and dose 500 Gy). At 1, 7 and 14 days after MRT, apparent diffusion coefficient, blood volume and vessel size index were mapped by MRI. Mean survival time after tumor inoculation increased significantly between MRT-treated and untreated groups (23 and 28 days respectively, log-rank test, p < 0.0001). A significant increase of apparent diffusion coefficient was observed 24 h after MRT in irradiated tumors versus non-irradiated ones. In the untreated group, both tumor size and vessel size index increased significantly (from 7.6 ± 2.2 to 19.2 ± 4.0 mm2 and +23%, respectively) between the 14th and the 21st day after tumor cell inoculation. During the same period, in the MRT-treated group, no difference in tumor size was observed. The vessel size index measured in the MRT-treated group increased significantly (+26%) between 14 and 28 days of tumor growth. We did not observe the significant difference in blood volume between the MRT-treated and untreated groups. MRT slows 9L tumor growth in a mouse brain but MRI results suggest that the increase in survival time after our MRT approach may be rather due to a cytoreduction than to early direct effects of ionizing radiation on tumor vessels. These results suggest that MRT parameters need to be optimized to further damage tumor vessels.

  15. Resting functional connectivity in patients with brain tumors in eloquent areas

    PubMed Central

    Martino, Juan; Honma, Susanne M.; Findlay, Anne M.; Guggisberg, Adrian G.; Kirsch, Heidi E.; Berger, Mitchel S.; Nagarajan, Srikantan S.

    2014-01-01

    Objective Resection of brain tumors adjacent to eloquent areas represents a challenge in neurosurgery. If maximal resection is desired without inducing postoperative neurological deficits, a detailed knowledge of the functional topography in and around the tumor is crucial. The aim of the present work is to evaluate the value of preoperative magnetoencephalography (MEG) imaging of functional connectivity to predict the results of intraoperative electrical stimulation (IES) mapping, the clinical gold standard for neurosurgical localization of functional areas. Methods Resting-state whole-cortex MEG recordings were obtained from 57 consecutive subjects with focal brain tumors near or within motor, sensory or language areas. Neural activity was estimated using adaptive spatial filtering algorithms, and the mean imaginary coherence between the rest of the brain and voxels in and around brain tumors were compared to the mean imaginary coherence between the rest of the brain and contralesional voxels as an index of functional connectivity. IES mapping was performed in all subjects. The cortical connectivity pattern near the tumor was compared to IES results. Results Maps with decreased resting-state functional connectivity in the entire tumor area had a negative predictive value of 100% for absence of eloquent cortex during IES. Maps showing increased resting-state functional connectivity within the tumor area had a positive predictive value of 64% for finding language, motor or sensory cortical sites during IES mapping. Interpretation Preoperative resting state MEG connectivity analysis is a useful noninvasive tool to evaluate the functionality of the tissue surrounding tumors within eloquent areas, and could potentially contribute to surgical planning and patient counseling. PMID:21400562

  16. A Correlative Optical Microscopy and Scanning Electron Microscopy Approach to Locating Nanoparticles in Brain Tumors

    PubMed Central

    Kempen, Paul J.; Kircher, Moritz F.; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V.; Mellinghoff, Ingo K.; Gambhir, Sanjiv S; Sinclair, Robert

    2014-01-01

    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. PMID:25464144

  17. A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

    PubMed

    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.

  18. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future

    PubMed Central

    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

  19. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future.

    PubMed

    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.

  20. Pharmacologic perturbation as a potential tool to increase the sensitivity of FDG-PET in the evaluation of brain tumors

    SciTech Connect

    Wong, F.C.L.; Kim, E.E.; Yung, W.K.A.

    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.

  1. Automatic brain tumor extraction from T1-weighted coronal MRI using fast bounding box and dynamic snake.

    PubMed

    Xu, Tao; Mandal, Mrinal

    2012-01-01

    Brain tumor segmentation from MRI data is an important but challenging task. This paper presents an efficient and fully automatic brain tumor segmentation technique. The proposed technique includes a fuzzy C-means (FCM) based preprocessing to enhance the quality of T1-weighted coronal MR images, a fast bounding box (FBB) detection algorithm to locate a rectangle around tumor, and a new dynamic snake using modified Hausdorff distance (MHD) for the final tumor extraction.

  2. Comparison of CT and MRI brain tumor imaging using a canine glioma model.

    PubMed

    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.

  3. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors.

    PubMed

    Aizer, Ayal A; Du, Rose; Wen, Patrick Y; Arvold, Nils D

    2015-09-01

    Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.

  4. Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

    PubMed Central

    Chandra, Subhash; Parker, Dylan J.; Barth, Rolf F.; Pannullo, Susan C.

    2016-01-01

    Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets. PMID:26703785

  5. Systems biology of human epilepsy applied to patients with brain tumors.

    PubMed

    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.

  6. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  7. Immunohistochemical characterization of spontaneous and acrylonitrile-induced brain tumors in the rat.

    PubMed

    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. Hybrid RGSA and Support Vector Machine Framework for Three-Dimensional Magnetic Resonance Brain Tumor Classification

    PubMed Central

    Rajesh Sharma, R.; Marikkannu, P.

    2015-01-01

    A novel hybrid approach for the identification of brain regions using magnetic resonance images accountable for brain tumor is presented in this paper. Classification of medical images is substantial in both clinical and research areas. Magnetic resonance imaging (MRI) modality outperforms towards diagnosing brain abnormalities like brain tumor, multiple sclerosis, hemorrhage, and many more. The primary objective of this work is to propose a three-dimensional (3D) novel brain tumor classification model using MRI images with both micro- and macroscale textures designed to differentiate the MRI of brain under two classes of lesion, benign and malignant. The design approach was initially preprocessed using 3D Gaussian filter. Based on VOI (volume of interest) of the image, features were extracted using 3D volumetric Square Centroid Lines Gray Level Distribution Method (SCLGM) along with 3D run length and cooccurrence matrix. The optimal features are selected using the proposed refined gravitational search algorithm (RGSA). Support vector machines, over backpropagation network, and k-nearest neighbor are used to evaluate the goodness of classifier approach. The preliminary evaluation of the system is performed using 320 real-time brain MRI images. The system is trained and tested by using a leave-one-case-out method. The performance of the classifier is tested using the receiver operating characteristic curve of 0.986 (±002). The experimental results demonstrate the systematic and efficient feature extraction and feature selection algorithm to the performance of state-of-the-art feature classification methods. PMID:26509188

  9. New Methods for Direct Delivery of Chemotherapy for Treating Brain Tumors

    PubMed Central

    Sawyer, Andrew J.; Piepmeier, Joseph M.; Saltzman, W. Mark

    2007-01-01

    Despite advances in diagnostic imaging and drug discovery, primary malignant brain tumors remain fatal. Median survival for patients with the most severe forms is rarely past eight months. The severity of the disease and the lack of substantial improvement in patient survival demand that new approaches be explored in drug delivery to brain tumors. Recently, local delivery of chemotherapy to brain tumors has provided a way to circumvent the blood-brain barrier, allowing delivery of chemotherapy drugs directly to malignant cells in the brain. Two methods of local delivery have been developed: polymeric-controlled release and convection-enhanced delivery. Controlled release utilizes degradable or non-degradable polymers as carriers of chemotherapy; polymer implants or microparticles are implanted locally to introduce a sustained source of drug for periods of days or months. Convection-enhanced delivery employs the bulk flow of drugs dissolved in fluid, which is introduced intracranially using a catheter and pump. The convective fluid flow is capable of delivering drugs great distances within the brain, potentially treating invasive cells at a distance from the catheter infusion site. These two new delivery strategies are capable of delivering both standard chemotherapeutic drugs and new methods of anti-cancer therapy. Taken individually, or used in tandem, they represent a potential revolution in brain cancer treatment. PMID:17940624

  10. Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

    PubMed Central

    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

  11. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    SciTech Connect

    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.

  12. Possible neuro-Sweet disease mimicking brain tumor in the medulla oblongata--case report.

    PubMed

    Akiba, Chihiro; Esaki, Takanori; Ando, Maya; Furuya, Tsuyoshi; Noda, Kazuyuki; Nakao, Yasuaki; Yamamoto, Takuji; Okuma, Yasuyuki; Mori, Kentaro

    2011-01-01

    A 62-year-old male presented with a rare case of possible neuro-Sweet Disease (NSD) mimicking brain tumor in the medulla oblongata, manifesting as numbness in the bilateral upper and lower extremities, gait disturbance, dysarthria, and swallowing disturbance which gradually deteriorated over 3 months. Magnetic resonance imaging showed a mass lesion in the medulla oblongata, extending to the upper cervical cord with rim enhancement by gadolinium. The preoperative diagnosis was brain tumor, such as glioma, or inflammatory disease. His neurological symptoms gradually deteriorated, so biopsy was performed through the midline suboccipital approach. Histological examination showed infiltration of inflammatory cells, mainly lymphocytes and macrophages. Human leukocyte antigen typing showed Cw1 and B54 which strongly suggested possible NSD. Steroid pulse therapy was started after surgery and the clinical symptoms improved. Neurosurgeons should be aware of inflammatory disorders such as NSD mimicking brain tumor.

  13. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  14. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    SciTech Connect

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  15. Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

    NASA Astrophysics Data System (ADS)

    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.

  16. [Cytology of the cerebrospinal fluid in dogs with brain tumors and spinal cord compression. Part 4].

    PubMed

    Grevel, V; Machus, B; Steeb, C

    1992-08-01

    The results of cerebrospinal fluid (CSF) cytology of 9 dogs with brain tumors and 50 dogs with spinal cord compression are discussed. Of the 50 dogs with spinal cord compression, disc protrusion was diagnosed in 31, myelomalacia in 7, discospondylitis in 3 and spinal cord tumors in 9 dogs. In 4 of 9 dogs with brain tumors, tumor cells could be found by the sedimentation apparatus of Kölmel. Pleocytosis existed in 6 patients. In about 70% (29 of 41) of cases with disc protrusion, more than 200 cells could be evaluated in the CSF sediment, consisting mostly of transformed lymphocytes and activated monocytes. As the neurologic deficits increased, the amount of cells and especially cell complexes increased. This was especially evident in cases with myelomalacia of the spinal cord. Only in cases with discospondylitis or spinal cord neoplasia was the CSF cytology unchanged.

  17. Assessing Region of Interest Schemes for the Corticospinal Tract in Patients With Brain Tumors

    PubMed Central

    Niu, Chen; Liu, Xin; Yang, Yong; Zhang, Kun; Min, Zhigang; Wang, Maode; Li, Wenfei; Guo, Liping; Lin, Pan; Zhang, Ming

    2016-01-01

    Abstract Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) techniques are widely used for identifying the corticospinal tract (CST) white matter pathways as part of presurgical planning. However, mass effects in patients with brain tumors tend to cause anatomical distortions and compensatory functional reorganization of the cortex, which may lead to inaccurate mapping of white matter tracts. To overcome these problems, we compared different region-of-interest (ROI) selection schemes to track CST fibers in patients with brain tumors. Our study investigated the CSTs of 16 patients with intracranial tumors. The patients were classified into 3 subgroups according to the spatial relationships of the lesion and the primary motor cortex (PMC)/internal capsule. Specifically, we investigated the key factors that cause distorted tractography in patients with tumors. We compared 3 CST tractography methods that used different ROI selection schemes. The results indicate that CST fiber tracking methods based only on anatomical ROIs could possibly lead to distortions near the PMC region and may be unable to effectively localize the PMC. In contrast, the dual ROI method, which uses ROIs that have been selected from both blood oxygen level-dependent functional MRI (BOLD-fMRI) activation and anatomical landmarks, enabled the tracking of fibers to the motor cortex. The results demonstrate that the dual ROI method can localize the entire CST fiber pathway and can accurately describe the spatial relationships of CST fibers relative to the tumor. These results illustrate the reliability of using fMRI-guided DTT in patients with tumors. The combination of fMRI and anatomical information enhances the identification of tracts of interest in brains with anatomical deformations, which provides neurosurgeons with a more accurate approach for visualizing and localizing white matter fiber tracts in patients with brain tumors. This approach enhances surgical performance and

  18. Pathology, treatment and management of posterior fossa brain tumors in childhood

    SciTech Connect

    Bonner, K.; Siegel, K.R.

    1988-04-01

    Brain tumors are the second most common childhood malignancy. Between 1975 and 1985, 462 newly diagnosed patients were treated at the Children's Hospital of Philadelphia; 207 (45%) tumors arose in the posterior fossa and 255 (55%) appeared supratentorially. A wide variety of histological subtypes were seen, each requiring tumor-specific treatment approaches. These included primitive neuroectodermal tumor (n = 86, 19%), astrocytoma (n = 135, 30%), brainstem glioma (n = 47, 10%), anaplastic astrocytoma (n = 32, 7%), and ependymoma (n = 30, 6%). Because of advances in diagnostic abilities, surgery, radiotherapy, and chemotherapy, between 60% and 70% of these patients are alive today. Diagnostic tools such as computed tomography and magnetic resonance imaging allow for better perioperative management and follow-up, while the operating microscope, CO/sub 2/ laser, cavitron ultrasonic aspirator and neurosurgical microinstrumentation allow for more extensive and safer surgery. Disease specific treatment protocols, utilizing radiotherapy and adjuvant chemotherapy, have made survival common in tumors such as medulloblastoma. As survival rates increase, cognitive, endocrinologic and psychologic sequelae become increasingly important. The optimal management of children with brain tumors demands a multidisciplinary approach, best facilitated by a neuro-oncology team composed of multiple subspecialists. This article addresses incidence, classification and histology, clinical presentation, diagnosis, pre-, intra- and postoperative management, long-term effects and the team approach in posterior fossa tumors in childhood. Management of specific tumor types is included as well. 57 references.

  19. Photo-acoustic imaging of blue nanoparticle targeted brain tumor for intra-operative glioma delineation

    NASA Astrophysics Data System (ADS)

    Ray, Aniruddha; Wang, Xueding; Koo Lee, Yong-Eun; Hah, HoeJin; Kim, Gwangseong; Chen, Thomas; Orrienger, Daniel; Sagher, Oren; Kopelman, Raoul

    2011-07-01

    Distinguishing the tumor from the background neo-plastic tissue is challenging for cancer surgery such as surgical resection of glioma. Attempts have been made to use visible or fluorescent markers to delineate the tumors during surgery. However, the systemic injection of the dyes requires high dose, resulting in negative side effects. A novel method to delineate rat brain tumors intra-operatively, as well as post-operatively, using a highly sensitive photoacoustic imaging technique enhanced by tumor targeting blue nanoparticle as contrast agent is demonstrated. The nanoparticles are made of polyacrylamide (PAA) matrix with covalently linked Coomassie-Blue dye. They contain 7.0% dye and the average size is 80nm. Their surface was conjugated with F3 peptide for active tumor targeting. These nanoparticles are nontoxic, chemically inert and have long plasma circulation lifetime, making them suitable as nanodevices for imaging using photoacoustics. Experiments on phantoms and rat brains tumors ex-vivo demonstrate the high sensitivity of photoacoustic imaging in delineating the tumor, containing contrast agent at concentrations too low to be visualized by eye. The control tumors without nanoparticles did not show any enhanced signal. This study shows that photoacoustic imaging facilitated with the nanoparticle contrast agent could contribute to future surgical procedures for glioma.

  20. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors.

    PubMed Central

    Hatva, E.; Kaipainen, A.; Mentula, P.; Jääskeläinen, J.; Paetau, A.; Haltia, M.; Alitalo, K.

    1995-01-01

    Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7856749

  1. Multi-fractal texture features for brain tumor and edema segmentation

    NASA Astrophysics Data System (ADS)

    Reza, S.; Iftekharuddin, K. M.

    2014-03-01

    In this work, we propose a fully automatic brain tumor and edema segmentation technique in brain magnetic resonance (MR) images. Different brain tissues are characterized using the novel texture features such as piece-wise triangular prism surface area (PTPSA), multi-fractional Brownian motion (mBm) and Gabor-like textons, along with regular intensity and intensity difference features. Classical Random Forest (RF) classifier is used to formulate the segmentation task as classification of these features in multi-modal MRIs. The segmentation performance is compared with other state-of-art works using a publicly available dataset known as Brain Tumor Segmentation (BRATS) 2012 [1]. Quantitative evaluation is done using the online evaluation tool from Kitware/MIDAS website [2]. The results show that our segmentation performance is more consistent and, on the average, outperforms other state-of-the art works in both training and challenge cases in the BRATS competition.

  2. Multilevel segmentation and integrated bayesian model classification with an application to brain tumor segmentation.

    PubMed

    Corso, Jason J; Sharon, Eitan; Yuille, Alan

    2006-01-01

    We present a new method for automatic segmentation of heterogeneous image data, which is very common in medical image analysis. The main contribution of the paper is a mathematical formulation for incorporating soft model assignments into the calculation of affinities, which are traditionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm. We apply the technique to the task of detecting and segmenting brain tumor and edema in multimodal MR volumes. Our results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of brain tumor.

  3. Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

    PubMed Central

    Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

    2014-01-01

    Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

  4. Raman spectroscopic imaging as complementary tool for histopathologic assessment of brain tumors

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Bergner, Norbert; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Geiger, Kathrin; Kirsch, Matthias; Schackert, Gabriele; Popp, Jürgen

    2012-02-01

    Raman spectroscopy enables label-free assessment of brain tissues and tumors based on their biochemical composition. Combination of the Raman spectra with the lateral information allows grading of tumors, determining the primary tumor of brain metastases and delineating tumor margins - even during surgery after coupling with fiber optic probes. This contribution presents exemplary Raman spectra and images collected from low grade and high grade regions of astrocytic gliomas and brain metastases. A region of interest in dried tissue sections encompassed slightly increased cell density. Spectral unmixing by vertex component analysis (VCA) and N-FINDR resolved cell nuclei in score plots and revealed the spectral contributions of nucleic acids, cholesterol, cholesterol ester and proteins in endmember signatures. The results correlated with the histopathological analysis after staining the specimens by hematoxylin and eosin. For a region of interest in non-dried, buffer immersed tissue sections image processing was not affected by drying artifacts such as denaturation of biomolecules and crystallization of cholesterol. Consequently, the results correspond better to in vivo situations. Raman spectroscopic imaging of a brain metastases from renal cell carcinoma showed an endmember with spectral contributions of glycogen which can be considered as a marker for this primary tumor.

  5. Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

    PubMed Central

    Fahmideh, Maral Adel; Lavebratt, Catharina; Schüz, Joachim; Röösli, Martin; Tynes, Tore; Grotzer, Michael A.; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Prochazka, Michaela; Schmidt, Lisbeth S; Feychting, Maria

    2016-01-01

    Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratified analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected. This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways. PMID:27613841

  6. Notching on Cancer’s Door: Notch Signaling in Brain Tumors

    PubMed Central

    Teodorczyk, Marcin; Schmidt, Mirko H. H.

    2015-01-01

    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 epidermal growth factor like protein 7 (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. PMID:25601901

  7. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  8. Preoperative Coiling of Coexisting Intracranial Aneurysm and Subsequent Brain Tumor Surgery

    PubMed Central

    Park, Keun Young; Kim, Dong Joon

    2016-01-01

    Objective 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. Materials and Methods 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. Results 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. Conclusion Preoperative coiling and subsequent tumor surgery was safe and effective, making it a reasonable treatment option for patients with brain tumor and cUIA. PMID:27833409

  9. Magnetic resonance imaging of pediatric brain tumors: state of the art.

    PubMed

    Poussaint, T Y

    2001-12-01

    Over the past 25 years, magnetic resonance imaging (MRI) has developed into the primary imaging tool for evaluation of the central nervous system. MRI is the essential imaging study in the twenty-first century for the evaluation of the child with a brain tumor for initial preoperative diagnosis, treatment planning and image-guided therapies. This article provides an overview of the locations and MRI features of common pediatric tumors of childhood.

  10. Signs and symptoms of pediatric brain tumors and diagnostic value of preoperative EEG.

    PubMed

    Preuß, Matthias; Preiss, Sophia; Syrbe, Steffen; Nestler, Ulf; Fischer, Lars; Merkenschlager, Andreas; Bertsche, Astrid; Christiansen, Holger; Bernhard, Matthias K

    2015-11-01

    In pediatric patients, brain tumors have been estimated to be the cause for seizures in only 0.2-0.3% of cases, whereas seizures occurred in about 13% of pediatric brain tumor patients at presentation. This survey was conducted to analyze EEG findings in pediatric tumor patients over the past 14 years to evaluate the diagnostic value of preoperative EEG for diagnosis of brain tumors. Surface EEG was obtained in awake patients using the international 10- to 20-electrode placement in all pediatric patients with intracranial neoplasms between 2000 and 2013 at the University Hospital of Leipzig except for those who needed emergency operative treatment. One hundred forty-two pediatric patients with 80 infratentorial and 62 supratentorial tumors (WHO grades I-II: 91 patients; WHO grades III-IV: 46 patients). Symptomatic hydrocephalus was found in 37. Sensitivity and specificity of ophthalmologic examination for predicting hydrocephalus was 0.39 and 0.72. Preoperative EEG has been conducted in 116 patients, showing normal activity in 54 patients (47%). Out of 62 pathologic EEGs, 40 indicated correctly to the site of the lesion, 15 were pathologic despite of infratentorial location of the tumor. Nineteen patients had a history of seizures of which six had normal EEGs. Sensitivity for and specificity of EEG examination for symptomatic epilepsy was 0.68 and 0.7. Conclusion Preoperative routine EEG provides no additional value in the diagnostic algorithm of pediatric train tumors. The low specificity and sensitivity of EEG (even in patients with clinical seizures as primary symptom of a brain tumor) underline that EEG does not contribute to diagnosis and a normal EEG might even delay correct diagnosis.

  11. Fluorescence microscopy studies of a peripheral-benzodiazepine-receptor-targeted molecular probe for brain tumor imaging

    NASA Astrophysics Data System (ADS)

    Marcu, Laura; Vernier, P. Thomas; Manning, H. Charles; Salemi, Sarah; Li, Aimin; Craft, Cheryl M.; Gundersen, Martin A.; Bornhop, Darryl J.

    2003-10-01

    This study investigates the potential of a new multi-modal lanthanide chelate complex for specifically targeting brain tumor cells. We report here results from ongoing studies of up-take, sub-cellular localization and binding specificity of this new molecular imaging probe. Fluorescence microscopy investigations in living rat C6 glioma tumor cells demonstrate that the new imaging agent has affinity for glioma cells and binds to mitochondria.

  12. Combining cytotoxic and immune-mediated gene therapy to treat brain tumors.

    PubMed

    Curtin, James F; King, Gwendalyn D; Candolfi, Marianela; Greeno, Remy B; Kroeger, Kurt M; Lowenstein, Pedro R; Castro, Maria G

    2005-01-01

    Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as 'immune privileged', brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important

  13. Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

    PubMed Central

    Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

    2006-01-01

    Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another

  14. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    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.

  15. Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors.

    PubMed

    Blanco, Víctor M; Chu, Zhengtao; Vallabhapurapu, Subrahmanya D; Sulaiman, Mahaboob K; Kendler, Ady; Rixe, Olivier; Warnick, Ronald E; Franco, Robert S; Qi, Xiaoyang

    2014-08-30

    Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors.

  16. Application of an enhanced fuzzy algorithm for MR brain tumor image segmentation

    NASA Astrophysics Data System (ADS)

    Hemanth, D. Jude; Vijila, C. Kezi Selva; Anitha, J.

    2010-02-01

    Image segmentation is one of the significant digital image processing techniques commonly used in the medical field. One of the specific applications is tumor detection in abnormal Magnetic Resonance (MR) brain images. Fuzzy approaches are widely preferred for tumor segmentation which generally yields superior results in terms of accuracy. But most of the fuzzy algorithms suffer from the drawback of slow convergence rate which makes the system practically non-feasible. In this work, the application of modified Fuzzy C-means (FCM) algorithm to tackle the convergence problem is explored in the context of brain image segmentation. This modified FCM algorithm employs the concept of quantization to improve the convergence rate besides yielding excellent segmentation efficiency. This algorithm is experimented on real time abnormal MR brain images collected from the radiologists. A comprehensive feature vector is extracted from these images and used for the segmentation technique. An extensive feature selection process is performed which reduces the convergence time period and improve the segmentation efficiency. After segmentation, the tumor portion is extracted from the segmented image. Comparative analysis in terms of segmentation efficiency and convergence rate is performed between the conventional FCM and the modified FCM. Experimental results show superior results for the modified FCM algorithm in terms of the performance measures. Thus, this work highlights the application of the modified algorithm for brain tumor detection in abnormal MR brain images.

  17. Evaluation of Vascular Supply with Angio-Computed Tomography During Intra-Arterial Chemotherapy for Brain Tumors

    SciTech Connect

    Hirai, Toshinori Korogi, Yukunori; Ono, Ken; Yamashita, Yasuyuki

    2005-04-15

    We report the utility of a combined angiography and computed tomography (angio-CT) system in assessing drug distribution to the tumor during intra-arterial chemotherapy for metastatic brain tumors in a 65-year-old man. Although digital subtraction angiography did not clearly show tumor perfusion in two cerebellar tumors, angio-CT provided definite tumor perfusion in the complicated vascular territory, and anticancer agents were infused based on its findings. To our knowledge, however, this application for intra-arterial chemotherapy of brain tumors has not been previously described.

  18. Intraventricular Delivery of Engineered Oncolytic Herpes Simplex Virotherapy to Treat Localized and Metastatic Pediatric Brain Tumors

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-15-1-0108 TITLE: Intraventricular Delivery of Engineered Oncolytic Herpes Simplex Virotherapy to Treat Localized and...children with brain tumors. Introduced mutations in the engineered virus prevent a productive infection in normal cells in the brain while...HSV-1 on day 2 indicating the engineered virus was able to enter the ependymal cells. By day 3, there was more diffuse disruption of the ependymal

  19. Enhancing the Efficacy of Drug-loaded Nanocarriers against Brain Tumors by Targeted Radiation Therapy

    PubMed Central

    Baumann, Brian C.; Kao, Gary D.; Mahmud, Abdullah; Harada, Takamasa; Swift, Joe; Chapman, Christina; Xu, Xiangsheng; Discher, Dennis E.; Dorsey, Jay F.

    2013-01-01

    Glioblastoma multiforme (GBM) is a common, usually lethal disease with a median survival of only ~15 months. It has proven resistant in clinical trials to chemotherapeutic agents such as paclitaxel that are highly effective in vitro, presumably because of impaired drug delivery across the tumor's blood-brain barrier (BBB). In an effort to increase paclitaxel delivery across the tumor BBB, we linked the drug to a novel filomicelle nanocarrier made with biodegradable poly(ethylene-glycol)-block-poly(ε-caprolactone-r-D,L-lactide) and used precisely collimated radiation therapy (RT) to disrupt the tumor BBB's permeability in an orthotopic mouse model of GBM. Using a non-invasive bioluminescent imaging technique to assess tumor burden and response to therapy in our model, we demonstrated that the drug-loaded nanocarrier (DLN) alone was ineffective against stereotactically implanted intracranial tumors yet was highly effective against GBM cells in culture and in tumors implanted into the flanks of mice. When targeted cranial RT was used to modulate the tumor BBB, the paclitaxel-loaded nanocarriers became effective against the intracranial tumors. Focused cranial RT improved DLN delivery into the intracranial tumors, significantly improving therapeutic outcomes. Tumor growth was delayed or halted, and survival was extended by >50% (p<0.05) compared to the results obtained with either RT or the DLN alone. Combinations of RT and chemotherapeutic agents linked to nanocarriers would appear to be an area for future investigations that could enhance outcomes in the treatment of human GBM. PMID:23296073

  20. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9-19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  1. Occurrence of brain tumors in rhesus monkeys exposed to 55-MeV protons

    NASA Astrophysics Data System (ADS)

    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.

  2. Radiosurgical treatment of previously irradiated primary brain tumors and brain metastiasis: Final report of Radiation Therapy Oncology Group (RTOG) protocol 90-05

    SciTech Connect

    Shaw, E.; Dinapoli, R.; Kline, R.

    1995-12-31

    The objective of this program was to determine the maximum single radiosurgical dose that can be given to patients (pts) with recurrent primary brain tumors (1{degree}BT) or brain metastasis (BM) who had received prior fractionated external beam radiation therapy (FEBRT). The treated tumor had to be {ge}40 mm in maximum diameter. Dose was prescribed to the periphery of the tumor (without margin) based on diameter, to the 50% to 90% isodose line.

  3. Brain tumor classification using the diffusion tensor image segmentation (D-SEG) technique

    PubMed Central

    Jones, Timothy L.; Byrnes, Tiernan J.; Yang, Guang; Howe, Franklyn A.; Bell, B. Anthony; Barrick, Thomas R.

    2015-01-01

    Background There is an increasing demand for noninvasive brain tumor biomarkers to guide surgery and subsequent oncotherapy. We present a novel whole-brain diffusion tensor imaging (DTI) segmentation (D-SEG) to delineate tumor volumes of interest (VOIs) for subsequent classification of tumor type. D-SEG uses isotropic (p) and anisotropic (q) components of the diffusion tensor to segment regions with similar diffusion characteristics. Methods DTI scans were acquired from 95 patients with low- and high-grade glioma, metastases, and meningioma and from 29 healthy subjects. D-SEG uses k-means clustering of the 2D (p,q) space to generate segments with different isotropic and anisotropic diffusion characteristics. Results Our results are visualized using a novel RGB color scheme incorporating p, q and T2-weighted information within each segment. The volumetric contribution of each segment to gray matter, white matter, and cerebrospinal fluid spaces was used to generate healthy tissue D-SEG spectra. Tumor VOIs were extracted using a semiautomated flood-filling technique and D-SEG spectra were computed within the VOI. Classification of tumor type using D-SEG spectra was performed using support vector machines. D-SEG was computationally fast and stable and delineated regions of healthy tissue from tumor and edema. D-SEG spectra were consistent for each tumor type, with constituent diffusion characteristics potentially reflecting regional differences in tissue microstructure. Support vector machines classified tumor type with an overall accuracy of 94.7%, providing better classification than previously reported. Conclusions D-SEG presents a user-friendly, semiautomated biomarker that may provide a valuable adjunct in noninvasive brain tumor diagnosis and treatment planning. PMID:25121771

  4. Expression and Prognostic Value of Oct-4 in Astrocytic Brain Tumors

    PubMed Central

    Dahl Sørensen, Mia; Winther Kristensen, Bjarne

    2016-01-01

    Background 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. 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 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. Conclusions 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. PMID:28030635

  5. Positron emission tomographic measurement of blood-to-brain and blood-to-tumor transport of 82Rb: the effect of dexamethasone and whole-brain radiation therapy

    SciTech Connect

    Jarden, J.O.; Dhawan, V.; Poltorak, A.; Posner, J.B.; Rottenberg, D.A.

    1985-12-01

    Unidirectional blood-to-brain and blood-to-tumor transport rate constants for rubidium 82 were determined using dynamic positron emission tomography in patients with primary or metastatic brain tumors. Regional influx rate constants (K1) and plasma water volume (Vp) were estimated from the time course of blood and brain radioactivity following a bolus injection of tracer. Eight patients were studied before and 24 to 72 hours after treatment using pharmacological doses of dexamethasone, and 6 additional patients with metastatic brain tumors were studied before and within 60 to 90 minutes after 200- to 600-rad whole-brain radiation therapy. Steroid treatment was associated with a 9 to 48% decrease in tumor K1 and a 21% mean decrease in tumor Vp. No consistent changes in K1 or Vp were observed in control brain regions. Tumor K1 and Vp did not increase in patients undergoing whole-brain radiation therapy, all of whom were taking dexamethasone at the time of study. These data suggest that corticosteroids decrease the permeability of tumor capillaries to small hydrophilic molecules (including those of some chemotherapeutic agents) and that steroid pretreatment prevents acute, and potentially dangerous, increases in tumor capillary permeability following cranial irradiation.

  6. Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  7. [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

    PubMed

    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.

  8. Molecular imaging of brain tumors personal experience and review of the literature.

    PubMed

    Schaller, Bernhard J; Cornelius, Jan F; Sandu, Nora; Buchfelder, Michael

    2008-12-01

    Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imaging of primary brain tumors therefore contain (i) primary brain tumor diagnosis, (ii) identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), and (iii) prediction of treatment response by measurement of tumor perfusion, or ischemia. The key-question remains whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival. Molecular imaging may identify early disease and differentiate benign from malignant lesions. Moreover, an early identification of treatment effectiveness could influence patient management by providing objective criteria for evaluation of therapeutic strategies for primary brain tumors. Specially, its novel potential to visualize metabolism and signal transduction to gene expression is used in reporter gene assays to trace the location and temporal level of expression of therapeutic and endogenous genes. The authors present here illustrative data of PET imaging: the thymidine kinase gene expression in experimentally transplanted F98 gliomas in cat brain indicates, that [(18)F]FHBG visualizes cells expressing TK-GFP gene in transduced gliomas as well as quantities and localizes transduced

  9. Single-photon emission computed tomography/computed tomography in brain tumors.

    PubMed

    Schillaci, Orazio; Filippi, Luca; Manni, Carlo; Santoni, Riccardo

    2007-01-01

    Anatomic imaging procedures (computed tomography [CT] and magnetic resonance imaging [MRI]) have become essential tools for brain tumor assessment. Functional images (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]) can provide additional information useful during the diagnostic workup to determine the degree of malignancy and as a substitute or guide for biopsy. After surgery and/or radiotherapy, nuclear medicine examinations are essential to assess persistence of tumor, to differentiate recurrence from radiation necrosis and gliosis, and to monitor the disease. The combination of functional images with anatomic ones is of the utmost importance for a full evaluation of these patients, which can be obtained by means of imaging fusion. Despite the fast-growing diffusion of PET, in most cases of brain tumors, SPECT studies are adequate and provide results that parallel those obtained with PET. The main limitation of SPECT imaging with brain tumor-seeking radiopharmaceuticals is the lack of precise anatomic details; this drawback is overcome by the fusion with morphological studies that provide an anatomic map to scintigraphic data. In the past, software-based fusion of independently performed SPECT and CT or MRI demonstrated usefulness for brain tumor assessment, but this process is often time consuming and not practical for everyday nuclear medicine studies. The recent development of dual-modality integrated imaging systems, which allow the acquisition of SPECT and CT images in the same scanning session, and their co-registration by means of the hardware, has facilitated this process. In SPECT studies of brain tumors with various radiopharmaceuticals, fused images are helpful in providing the precise localization of neoplastic lesions, and in excluding the disease in sites of physiologic tracer uptake. This information is useful for optimizing diagnosis, therapy monitoring, and radiotherapy treatment planning, with a

  10. Radiosurgery to the Postoperative Tumor Bed for Metastatic Carcinoma Versus Whole Brain Radiation After Surgery

    PubMed Central

    Scheitler-Ring, Kristen; Ge, Bin; Petroski, Greg; Biedermann, Gregory

    2016-01-01

    Background The treatment paradigm from postoperative whole brain radiation therapy (WBRT) to post-operative stereotactic radiosurgery (SRS) to the tumor bed has shifted with little data to evaluate whether each treatment modality confers equivalent tumor control and survival outcomes. Methods Patients with surgical resection of single brain metastases from January 2010 to December 2014 were treated postoperatively with either WBRT or SRS. Retrospective patient data was compared for local control, distant brain recurrence, overall survival, and radiation complications. Results Forty-six received WBRT, and 37 received tumor bed SRS. Twelve of 35 (34%) SRS patients experienced local recurrence compared to 17 of 31 (55%) WBRT patients (p = 0.09). The median survival was 440 days (14.7 months) for SRS and 202 days (6.7 months) for WBRT (p = 0.062, log-rank). SRS demonstrated improved survival benefit in the first six months (p = 0.0034; Wilcoxon). Radiation-related adverse changes after SRS (22%) were not statistically different from WBRT (8.7%) (p = 0.152). Age (p = 0.08), systemic cancer status (p = 0.30), Graded Prognostic Assessment (p = 0.28), number of brain metastases at diagnosis (p = 0.65), tumor volume at diagnosis (p = 0.13), new brain lesions (p = 0.74) and neurologic versus systemic cause of death (p = 0.11) did not differ between the groups. Conclusions Following surgical resection, tumor bed SRS can be used effectively in lieu of WBRT to treat brain metastases with comparable local control and distant control and without significantly more adverse events. PMID:28003949

  11. Convex Non-Negative Matrix Factorization for Brain Tumor Delimitation from MRSI Data

    PubMed Central

    Ortega-Martorell, Sandra; Lisboa, Paulo J. G.; Vellido, Alfredo; Simões, Rui V.; Pumarola, Martí; Julià-Sapé, Margarida; Arús, Carles

    2012-01-01

    Background Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation. Methodology/Principal Findings A pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered. Conclusions/Significance The unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the

  12. Transport processes in biological systems: Tumoral cells and human brain

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  13. Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry

    NASA Astrophysics Data System (ADS)

    Meier, Raphael; Knecht, Urspeter; Loosli, Tina; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

    2016-03-01

    Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83–0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments.

  14. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    PubMed Central

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    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. PMID:28203179

  15. Characterization of brain tumors by MRS, DWI and Ki-67 labeling index.

    PubMed

    Calvar, J A; Meli, F J; Romero, C; Calcagno, M L; Yánez, P; Martinez, A R; Lambre, H; Taratuto, A L; Sevlever, G

    2005-05-01

    With the advent of fast imaging hardware and specialized software, additional non-invasive magnetic resonance characterization of tumors has become available through proton magnetic resonance spectroscopy (MRS), hemodynamic imaging and diffusion-weighted imaging (DWI). Thus, patterns could be discerned to discriminate different types of tumors and even to infer their possible evolution in time. The purpose of this study was to investigate the correlation between MRS, DWI, histopathology and Ki-67 labeling index in a large number of brain tumors. Localized proton spectra were obtained in 47 patients with brain tumors who subsequently underwent surgery (biopsy or tumor removal). We performed MRS with short echo-time (30 ms) and metabolic values in spectra were measured using an external software with 25 peaks. In all patients who had DWI, we measured apparent diffusion coefficients (ADC) in the same region of interest (ROI) where the voxel in MRS was located. In most tumors the histological diagnosis and Ki-67 labeling index had been determined on our original surgical specimen. Cho/Cr, (Lip+Mm)/Cr, NAA/(Cho+Cr) and Glx/Cr indexes in MRS allowed discriminating between low- and high-grade gliomas and metastases (MTs). Likewise, absolute ADC values differentiated low- from high-grade gliomas expressed by Ki-67 labeling index. A novel finding was that high Glx/Cr in vivo MRS index (similar to other known indexes) was a good predictor of tumor grading.

  16. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts1

    PubMed Central

    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

  17. Chaperone proteins and brain tumors: Potential targets and possible therapeutics1

    PubMed Central

    Graner, Michael W.; Bigner, Darell D.

    2005-01-01

    Chaperone proteins are most notable for the proteo- and cyotoprotective capacities they afford during cellular stress. Under conditions of cellular normalcy, chaperones still play integral roles in the folding of nascent polypeptides into functional entities, in assisting in intracellular/intraorganellar transport, in assembly and maintenance of multi-subunit protein complexes, and in aiding and abetting the degradation of senescent proteins. Tumors frequently have relatively enhanced needs for chaperone number and activity because of the stresses of rapid proliferation, increased metabolism, and overall genetic instability. Thus, it may be possible to take advantage of this reliance that tumor cells have on chaperones by pharmacologic and biologic means. Certain chaperones are abundant in the brain, which implies important roles for them. While it is presumed that the requirements of brain tumors for chaperone proteins are similar to those of any other cell type, tumor or otherwise, very little inquiry has been directed at the possibility of using chaperone proteins as therapeutic targets or even as therapeutic agents against central nervous system malignancies. This review highlights some of the research on the functions of chaperone proteins, on what can be done to modify those functions, and on the physiological responses that tumors and organisms can have to chaperone-targeted or chaperone-based therapies. In particular, this review will also underscore areas of research where brain tumors have been part of the field, although in general those instances are few and far between. This relative dearth of research devoted to chaperone protein targets and therapeutics in brain tumors reveals much untrodden turf to explore for potential treatments of these dreadfully refractive diseases. PMID:16053701

  18. Use of preoperative FLAIR MRI and ependymal proximity of tumor enhancement as surrogate markers of brain tumor origin.

    PubMed

    Smith, Timothy R; Hulou, M Maher; Abecassis, Josh; Das, Sunit; Chandler, James P

    2015-09-01

    Neural stem cells proliferate in the subventricular zone and give rise to progeny that differentiate and migrate throughout the brain. We aimed to test the hypothesis that glioma behavior and grade may correlate with the identity of the tumor cell of origin. We evaluated three preoperative radiographic features (fluid attenuated inversion recovery [FLAIR] MRI characteristics, tumor proximity to ventricular ependyma, and subependymal representation) as surrogate markers of tumor origin using a retrospective cohort design. The medical records of 228 patients who underwent surgical resection of a glioma from January 2004 to August 2008 were reviewed. Average patient age was 54.5 years (standard deviation [SD] 15.3) with a male predominance (62.9%). World Health Organization glioma grades amongst the cohort were Grade IV (71.6%), Grade III (21.3%) and Grade II (7.1%). Mean survival was 11.2 months (SD 10.5) with a mean follow up of 12.8 months (SD 11.3). Glioma tumor grade was significantly correlated to FLAIR signal proximity to the ependymal surface (p<0.01) and inversely with proximity of tumor mass to the ependyma (p<0.01). The mean distance of tumor-associated FLAIR signal from the ependymal surface for glioblastoma multiforme (GBM) was 1.2mm (SD 3.3) compared to 4.8 (SD 6.5) for anaplastic astrocytomas and 6.6mm (SD 6.7; p<0.01) for low grade gliomas. Conversely, the mean distance of the enhancing tumor mass from the ependyma for GBM was 7.3mm (SD 9.4), Grade III glioma 2.3mm (SD 4.9), and Grade II glioma 3.8mm (SD 6.8; p<0.05). These findings suggest that higher grade gliomas might arise from less differentiated neuroepithelial cells in the subventricular zone that possess greater migratory potential.

  19. Proton-decoupled 31P MRS in untreated pediatric brain tumors.

    PubMed

    Albers, Mark J; Krieger, Mark D; Gonzalez-Gomez, Ignacio; Gilles, Floyd H; McComb, J Gordon; Nelson, Marvin D; Blüml, Stefan

    2005-01-01

    Proton-decoupled (31)P and (1)H MRS was used to quantify markers of membrane synthesis and breakdown in eight pediatric patients with untreated brain tumors and in six controls. Quantitation of these compounds in vivo in humans may provide important indicators for tumor growth and malignancy, tumor classification, and provide prognostic information. The ratios of phosphoethanolamine to glycerophosphoethanolamine (PE/GPE) and phosphocholine to glycerophosphocholine (PC/GPC) were significantly higher in primitive neuroectodermal tumors (PNET) (16.30 +/- 5.73 and 2.97 +/- 0.93) when compared with controls (3.42 +/- 1.62, P < 0.0001 and 0.45 +/- 0.13, P < 0.0001) and with other tumors (3.93 +/- 3.42, P < 0.001 and 0.65 +/- 0.30, P < 0.0001). Mean PC/PE was elevated in tumors relative to controls (0.48 +/- 0.11 versus 0.24 +/- 0.05, P < 0.001), but there was no difference between PNET and other tumors. Total choline concentration determined with quantitative (1)H MRS was significantly elevated (4.78 +/- 3.33 versus 1.73 +/- 0.56 mmol/kg, P < 0.05), whereas creatine was reduced in tumors (4.89 +/- 1.83 versus 8.28 +/- 1.50 mmol/kg, P < 0.05). A quantitative comparison of total phosphorylated cholines (PC+GPC)/ATP measured with (31)P MRS and total choline measured with (1)H MRS showed that in tumors a large fraction of the choline signal (>54 +/- 36%) was not accounted for by PC and GPC. The fraction of unaccounted choline was particularly large in PNET (>78 +/- 7%). The pH of tumor tissue was higher than the pH of normal brain tissue (7.06 +/- 0.03 versus. 6.98 +/- 0.03, P < 0.001).

  20. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

    NASA Astrophysics Data System (ADS)

    Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

    2015-01-01

    Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

  1. Retrieval of Brain Tumors by Adaptive Spatial Pooling and Fisher Vector Representation

    PubMed Central

    Huang, Meiyan; Huang, Wei; Jiang, Jun; Zhou, Yujia; Yang, Ru; Zhao, Jie; Feng, Yanqiu; Feng, Qianjin; Chen, Wufan

    2016-01-01

    Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast-enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset. PMID:27273091

  2. High-resolution whole-brain DCE-MRI using constrained reconstruction: Prospective clinical evaluation in brain tumor patients

    PubMed Central

    Guo, Yi; Lebel, R. Marc; Zhu, Yinghua; Lingala, Sajan Goud; Shiroishi, Mark S.; Law, Meng; Nayak, Krishna

    2016-01-01

    Purpose: To clinically evaluate a highly accelerated T1-weighted dynamic contrast-enhanced (DCE) MRI technique that provides high spatial resolution and whole-brain coverage via undersampling and constrained reconstruction with multiple sparsity constraints. Methods: Conventional (rate-2 SENSE) and experimental DCE-MRI (rate-30) scans were performed 20 minutes apart in 15 brain tumor patients. The conventional clinical DCE-MRI had voxel dimensions 0.9 × 1.3 × 7.0 mm3, FOV 22 × 22 × 4.2 cm3, and the experimental DCE-MRI had voxel dimensions 0.9 × 0.9 × 1.9 mm3, and broader coverage 22 × 22 × 19 cm3. Temporal resolution was 5 s for both protocols. Time-resolved images and blood–brain barrier permeability maps were qualitatively evaluated by two radiologists. Results: The experimental DCE-MRI scans showed no loss of qualitative information in any of the cases, while achieving substantially higher spatial resolution and whole-brain spatial coverage. Average qualitative scores (from 0 to 3) were 2.1 for the experimental scans and 1.1 for the conventional clinical scans. Conclusions: The proposed DCE-MRI approach provides clinically superior image quality with higher spatial resolution and coverage than currently available approaches. These advantages may allow comprehensive permeability mapping in the brain, which is especially valuable in the setting of large lesions or multiple lesions spread throughout the brain. PMID:27147313

  3. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  4. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    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

  5. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    PubMed Central

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. PMID:23502426

  6. Social Skills Training Interventions: A Promising Approach for Children Treated for Brain Tumors

    ERIC Educational Resources Information Center

    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…

  7. MIF Maintains the Tumorigenic Capacity of Brain Tumor-Initiating Cells by Directly Inhibiting p53.

    PubMed

    Fukaya, Raita; Ohta, Shigeki; Yaguchi, Tomonori; Matsuzaki, Yumi; Sugihara, Eiji; Okano, Hideyuki; Saya, Hideyuki; Kawakami, Yutaka; Kawase, Takeshi; Yoshida, Kazunari; Toda, Masahiro

    2016-05-01

    Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, brain tumor-initiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. ©2016 AACR.

  8. Systematic review of wireless phone use and brain cancer and other head tumors.

    PubMed

    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 < 0.05) for adult brain 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).

  9. Adolescent and young adult survivors of childhood brain tumors: Life after treatment in their own words

    PubMed Central

    Hobbie, Wendy L.; Ogle, Sue; Reilly, Maureen; Barakat, Lamia; Lucas, Matthew S.; Ginsberg, Jill P.; Fisher, Michael J.; Volpe, Ellen M.; Deatrick, Janet A.

    2015-01-01

    Background To date there are few studies that examine the perspectives of older survivors of childhood brain tumors who are living with their families in terms of their sense of self and their role in their families. Objective To describe how adolescent and young adult survivors (AYA) of childhood brain tumors describe their HRQOL, that is their physical, emotional, and social functioning. Methods This qualitative descriptive study included a purposive sample of 41 AYA survivors of a childhood brain tumor who live with their families. Home interviews were conducted using a semi-structured interview guide. Directed content analytic techniques were used to analyze data using HRQOL as a framework. Results This group of brain tumor survivors described their everyday lives in terms of their physical health, neurocognitive functioning, emotional health, social functioning, and self-care abilities. Overall, survivors struggle for normalcy in the face of changed functioning due to their cancer and the (late) effects of their treatment. Conclusions Neurocognitive issues seemed most compelling in the narratives. The importance of families went beyond the resources, structure, and support for functioning. Their families provided the recognition that they were important beings and their existence mattered to someone. Implications for Practice The value and complexity of care coordination was highlighted by the multifaceted needs of the survivors. Advocacy for appropriate and timely educational, vocational, and social support is critical as part of comprehensive cancer survivorship care. PMID:25950583

  10. Improving Brain Tumor Research in Resource-Limited Countries: A Review of the Literature Focusing on West Africa

    PubMed Central

    Fezeu, Francis; Ramesh, Arjun; Moosa, Shayan; Purow, Benjamin; Lopez, Beatrice; Schiff, David; Hussaini, Isa M; Sandabe, Umar K

    2015-01-01

    Neoplasms of the brain are often overlooked in resource-limited countries. Our literature search via AJOL and PubMed demonstrated that brain tumor research is still a rarity in these regions. We highlight the current status, importance, challenges, and methods of improving brain tumor research in West Africa. We suggest that more attention be given to basic, clinical, and epidemiological brain tumor research by national governments, private organizations, international organizations, non-governmental organizations (NGOs), and individuals in this region. PMID:26677422

  11. Finite element modeling of haptic thermography: A novel approach for brain tumor detection during minimally invasive neurosurgery.

    PubMed

    Sadeghi-Goughari, Moslem; Mojra, Afsaneh

    2015-10-01

    Intraoperative Thermal Imaging (ITI) is a novel neuroimaging method that can potentially locate tissue abnormalities and hence improves surgeon's diagnostic ability. In the present study, thermography technique coupled with artificial tactile sensing method called "haptic thermography" is utilized to investigate the presence of an abnormal object as a tumor with an elevated temperature relative to the normal tissue in the brain. The brain tissue is characterized as a hyper-viscoelastic material to be descriptive of mechanical behavior of the brain tissue during tactile palpation. Based on a finite element approach, Magnetic Resonance Imaging (MRI) data of a patient diagnosed to have a brain tumor is utilized to simulate and analyze the capability of haptic thermography in detection and localization of brain tumor. Steady-state thermal results prove that temperature distribution is an appropriate outcome of haptic thermography for the superficial tumors while heat flux distribution can be used as an extra thermal result for deeply located tumors.

  12. Nonlinear microscopy and infrared and Raman microspectroscopy for brain tumor analysis

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Dietzek, Benjamin; Meyer, Tobias; Bergner, Norbert; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Popp, Jürgen

    2011-03-01

    Scope of the neurosurgical management of brain tumors is to remove pathological tissue, preserve normal tissue and brain functions, and collect material for neuropathological diagnosis. A prerequisite is to recognize the tumor margins as precise as possible. Scope of neuropathology is to determine the type and grade of the tumor that is an important indicator for the treatment and prognosis of the patient. In this contribution we present vibrational spectroscopic approaches to complement existing neurosurgical and neuropathological tools. First, Fourier transform infrared (FTIR) imaging is applied to obtain molecular contrast from dried, thin tissue sections. Second, Raman spectroscopic images were collected from the same specimens. Finally, coherent anti-Stokes Raman scattering (CARS) microscopic images were obtained. To demonstrate the complementary nature of the techniques results from a brain metastasis of a lung cancer are discussed. Whereas CARS images could be collected within seconds, exposure times were minutes for FTIR images and hours for Raman images. However, the CARS microscope just probed a single band near 2850 cm-1. FTIR and Raman system probed the full spectral range involving the fingerprint region below 1800 cm-1 and the stretch vibrations between 2800 and 3600 cm-1. Morphological features were resolved in the images such as solid tumor, tumor islets, necrosis and cell nuclei.

  13. MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells.

    PubMed

    Modzelewska, Katarzyna; Boer, Elena F; Mosbruger, Timothy L; Picard, Daniel; Anderson, Daniela; Miles, Rodney R; Kroll, Mitchell; Oslund, William; Pysher, Theodore J; Schiffman, Joshua D; Jensen, Randy; Jette, Cicely A; Huang, Annie; Stewart, Rodney A

    2016-10-25

    Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway. Modeling NRAS activation in embryonic OPCs generated malignant brain tumors in zebrafish that closely mimic the human oligoneural/NB-FOXR2 CNS-PNET subgroup by histology and comparative oncogenomics. The zebrafish CNS-PNET model was used to show that MEK inhibitors selectively eliminate Olig2(+)/Sox10(+) CNS-PNET tumors in vivo without impacting normal brain development. Thus, MEK inhibitors represent a promising rationally designed therapy for children afflicted with oligoneural/NB-FOXR2 CNS-PNETs.

  14. In Vivo Follow-up of Brain Tumor Growth via Bioluminescence Imaging and Fluorescence Tomography

    PubMed Central

    Genevois, Coralie; Loiseau, Hugues; Couillaud, Franck

    2016-01-01

    Reporter gene-based strategies are widely used in experimental oncology. Bioluminescence imaging (BLI) using the firefly luciferase (Fluc) as a reporter gene and d-luciferin as a substrate is currently the most widely employed technique. The present paper compares the performances of BLI imaging with fluorescence imaging using the near infrared fluorescent protein (iRFP) to monitor brain tumor growth in mice. Fluorescence imaging includes fluorescence reflectance imaging (FRI), fluorescence diffuse optical tomography (fDOT), and fluorescence molecular Imaging (FMT®). A U87 cell line was genetically modified for constitutive expression of both the encoding Fluc and iRFP reporter genes and assayed for cell, subcutaneous tumor and brain tumor imaging. On cultured cells, BLI was more sensitive than FRI; in vivo, tumors were first detected by BLI. Fluorescence of iRFP provided convenient tools such as flux cytometry, direct detection of the fluorescent protein on histological slices, and fluorescent tomography that allowed for 3D localization and absolute quantification of the fluorescent signal in brain tumors. PMID:27809256

  15. Brain tumor segmentation in MR slices using improved GrowCut algorithm

    NASA Astrophysics Data System (ADS)

    Ji, Chunhong; Yu, Jinhua; Wang, Yuanyuan; Chen, Liang; Shi, Zhifeng; Mao, Ying

    2015-12-01

    The detection of brain tumor from MR images is very significant for medical diagnosis and treatment. However, the existing methods are mostly based on manual or semiautomatic segmentation which are awkward when dealing with a large amount of MR slices. In this paper, a new fully automatic method for the segmentation of brain tumors in MR slices is presented. Based on the hypothesis of the symmetric brain structure, the method improves the interactive GrowCut algorithm by further using the bounding box algorithm in the pre-processing step. More importantly, local reflectional symmetry is used to make up the deficiency of the bounding box method. After segmentation, 3D tumor image is reconstructed. We evaluate the accuracy of the proposed method on MR slices with synthetic tumors and actual clinical MR images. Result of the proposed method is compared with the actual position of simulated 3D tumor qualitatively and quantitatively. In addition, our automatic method produces equivalent performance as manual segmentation and the interactive GrowCut with manual interference while providing fully automatic segmentation.

  16. Heterogeneous Blood-Tumor Barrier Permeability Determines Drug Efficacy in Experimental Brain Metastases of Breast Cancer

    PubMed Central

    Lockman, Paul R.; Mittapalli, Rajendar K.; Taskar, Kunal S.; Rudraraju, Vinay; Gril, Brunilde; Bohn, Kaci A.; Adkins, Chris E.; Roberts, Amanda; Thorsheim, Helen R.; Gaasch, Julie A.; Huang, Suyun; Palmieri, Diane; Steeg, Patricia S.; Smith, Quentin R.

    2010-01-01

    Purpose Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases, however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain. Experimental Design Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy. Results Analysis of >2000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) demonstrated partial BTB permeability compromise in >89% lesions, varying in magnitude within and between metastases. Brain metastasis uptake of 14C- paclitaxel and 14C- doxorubicin was generally greater than normal brain but <15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (~10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with over expression of the pericyte protein, desmin. Conclusions This work demonstrates that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. PMID:20829328

  17. Immune factors and viral interactions in brain cancer etiology and outcomes, The 2016 Brain Tumor Epidemiology Consortium Meeting report

    PubMed Central

    Johnson, Kimberly J.; Hainfellner, Johannes A.; Lau, Ching C.; Scheurer, Michael E.; Woehrer, Adelheid; Wiemels, Joseph

    2016-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that aims to advance development of multicenter and interdisciplinary collaborations that focus on research related to the etiology, outcomes, and prevention of brain tumors. The 17th annual BTEC meeting was held in Barcelona, Spain on June 21 – 23, 2016. The meeting focused on immune and viral factors that influence brain tumor development. Fundamentals of innate and adaptive immunity were reviewed, the role of immune checkpoint inhibitors in primary and secondary brain tumors was addressed, vaccination strategies for glioma treatment were presented, and the potential contribution of immune dysfunction and viruses tropic for glial cells in gliomagenesis was discussed. Further contributions addressed the risk of non-ionizing radiation, molecular and birth characteristics on brain tumor induction/outcomes, and patterns of care and effects of different treatments on brain tumor survival in the real world setting. The next BTEC meeting will be held in June 2017 in Banff, Canada, and will focus on brain tumor epidemiology in the era of precision medicine. PMID:27546018

  18. Exploratory Evaluation of MR Permeability with 18F-FDG PET Mapping in Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

    PubMed Central

    Zukotynski, Katherine A.; Fahey, Frederic H.; Vajapeyam, Sridhar; Ng, Sarah S.; Kocak, Mehmet; Gururangan, Sridharan; Kun, Larry E.; Poussaint, Tina Y.

    2014-01-01

    The purpose of this study was to develop a method of registering 18F-FDG PET with MR permeability images for investigating the correlation of 18F-FDG uptake, permeability, and cerebral blood volume (CBV) in children with pediatric brain tumors and their relationship with outcome. Methods Twenty-four children with brain tumors in a phase II study of bevacizumab and irinotecan underwent brain MR and 18F-FDG PET within 2 wk. Tumor types included supratentorial high-grade astrocytoma (n = 7), low-grade glioma (n = 9), brain stem glioma (n = 4), medulloblastoma (n = 2), and ependymoma (n = 2). There were 33 cases (pretreatment only [n = 12], posttreatment only [n = 3], and both pretreatment [n = 9] and posttreatment [n = 9]). 18F-FDG PET images were registered to MR images from the last time point of the T1 perfusion time series using mutual information. Three-dimensional regions of interest (ROIs) drawn on permeability images were automatically transferred to registered PET images. The quality of ROI registration was graded (1, excellent; 2, very good; 3, good; 4, fair; and 5, poor) by 3 independent experts. Spearman rank correlations were used to assess correlation of maximum tumor permeability (Kpsmax), maximum CBV (CBVmax), and maximum 18F-FDG uptake normalized to white matter (T/Wmax). Cox proportional hazards models were used to investigate associations of these parameters with progression-free survival (PFS). Results The quality of ROI registration between PET and MR was good to excellent in 31 of 33 cases. There was no correlation of baseline Kpsmax with CBVmax (Spearman rank correlation =0.018 [P =0.94]) or T/Wmax (Spearman rank correlation = 0.07 [P = 0.76]). Baseline CBVmax was correlated with T/Wmax (Spearman rank correlation = 0.47 [P = 0.036]). Baseline Kpsmax, CBVmax, and T/Wmax were not significantly associated with PFS (P = 0.42, hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.90–1.045, and number of events [nevents] = 15 for Kpsmax; P = 0

  19. Neurocognitive functioning and genetic variation in patients with primary brain tumors

    PubMed Central

    Wefel, Jeffrey S.; Noll, Kyle R.; Scheurer, Michael E.

    2016-01-01

    Summary Impairment of neurocognitive functioning is a common consequence of cerebral neoplasms and treatment, though considerable heterogeneity exists in the pattern and severity of problems across individuals and tumor types. While the influence of numerous clinical and patient characteristics have been documented, relatively little research has been devoted to understanding the influence of genetic variation upon neurocognitive outcomes in patients with brain tumors. This review highlights preliminary evidence associating genes from diverse pathways with risk of adverse neurocognitive outcomes in brain tumor patients, including genes specific to neuronal function and those involved in more systemic cellular regulation. Related literature involving other disease populations is also briefly surveyed, pointing to additional candidate genes. Methodological considerations are also discussed and the need for future research integrating novel investigative techniques is emphasized. PMID:26972863

  20. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    NASA Astrophysics Data System (ADS)

    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.

  1. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    SciTech Connect

    Forte, Trudy

    2007-06-27

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  2. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    ScienceCinema

    Forte, Trudy

    2016-07-12

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  3. In vivo pink-beam imaging and fast alignment procedure for rat brain tumor radiation therapy.

    PubMed

    Nemoz, Christian; Kibleur, Astrid; Hyacinthe, Jean Noël; Berruyer, Gilles; Brochard, Thierry; Bräuer-Krisch, Elke; Le Duc, Géraldine; Brun, Emmanuel; Elleaume, Hélène; Serduc, Raphaël

    2016-01-01

    A fast positioning method for brain tumor microbeam irradiations for preclinical studies at third-generation X-ray sources is described. The three-dimensional alignment of the animals relative to the X-ray beam was based on the X-ray tomography multi-slices after iodine infusion. This method used pink-beam imaging produced by the ID17 wiggler. A graphical user interface has been developed in order to define the irradiation parameters: field width, height, number of angles and X-ray dose. This study is the first reporting an image guided method for soft tissue synchrotron radiotherapy. It allowed microbeam radiation therapy irradiation fields to be reduced by a factor of ∼20 compared with previous studies. It permitted more targeted, more efficient brain tumor microbeam treatments and reduces normal brain toxicity of the radiation treatment.

  4. Brain Tumor Cells in Circulation are Enriched for Mesenchymal Gene Expression

    PubMed Central

    Sullivan, James P.; Nahed, Brian V.; Madden, Marissa W.; Oliveira, Samantha M.; Springer, Simeon; Bhere, Deepak; Chi, Andrew S.; Wakimoto, Hiroaki; Rothenberg, S. Michael; Sequist, Lecia V.; Kapur, Ravi; Shah, Khalid; Iafrate, A. John; Curry, William T.; Loeffler, Jay S.; Batchelor, Tracy T.; Louis, David N.; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.

    2014-01-01

    Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination is extremely rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTCs). Staining and scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), and then applied clinically: CTCs were identified in at least one blood specimen from 13/33 patients (39%; 26/87 samples). Single GBM CTCs isolated from both patients and mouse PDX models demonstrated enrichment for mesenchymal over neural differentiation markers, compared with primary GBMs. Within primary GBMs, RNA-in-situ hybridization identifies a subpopulation of highly migratory mesenchymal tumor cells, and in a rare patient with disseminated GBM, systemic lesions were exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades into the vasculature, and may proliferate outside the brain. PMID:25139148

  5. Guiding Brain-Tumor Surgery via Blood-Brain-Barrier-Permeable Gold Nanoprobes with Acid-Triggered MRI/SERRS Signals.

    PubMed

    Gao, Xihui; Yue, Qi; Liu, Zining; Ke, Mengjing; Zhou, Xingyu; Li, Sihan; Zhang, Jianping; Zhang, Ren; Chen, Liang; Mao, Ying; Li, Cong

    2017-03-15

    Surgical resection is a mainstay in the treatment of malignant brain tumors. Surgeons, however, face great challenges in distinguishing tumor margins due to their infiltrated nature. Here, a pair of gold nanoprobes that enter a brain tumor by crossing the blood-brain barrier is developed. The acidic tumor environment triggers their assembly with the concomitant activation of both magnetic resonance (MR) and surface-enhanced resonance Raman spectroscopy (SERRS) signals. While the bulky aggregates continuously trap into the tumor interstitium, the intact nanoprobes in normal brain tissue can be transported back into the blood stream in a timely manner. Experimental results show that physiological acidity triggers nanoparticle assembly by forming 3D spherical nanoclusters with remarkable MR and SERRS signal enhancements. The nanoprobes not only preoperatively define orthotopic glioblastoma xenografts by magnetic resonance imaging (MRI) with high sensitivity and durability in vivo, but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner. Microscopy studies verify the precisely demarcated tumor margin marked by the assembled nanoprobes. Taking advantage of the nanoprobes' rapid excretion rate and the extracellular acidification as a hallmark of solid tumors, these nanoprobes are promising in improving brain-tumor surgical outcome with high specificity, safety, and universality.

  6. The transcriptional network for mesenchymal transformation of brain tumors

    PubMed Central

    Carro, Maria Stella; Lim, Wei Keat; Alvarez, Mariano Javier; Bollo, Robert J.; Zhao, Xudong; Snyder, Evan Y.; Sulman, Erik P.; Anne, Sandrine L.; Doetsch, Fiona; Colman, Howard; Lasorella, Anna; Aldape, Ken; Califano, Andrea; Iavarone, Antonio

    2013-01-01

    Inference of transcriptional networks that regulate transitions into physiologic or pathologic cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumor aggressiveness in human malignant glioma but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here, we show that reverse-engineering and unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPβ and Stat3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPβ and Stat3 reprograms neural stem cells along the aberrant mesenchymal lineage whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumor aggressiveness. In human glioma, expression of C/EBPβ and Stat3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results reveal that activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells. PMID:20032975

  7. Secondary tics or tourettism associated with a brain tumor.

    PubMed

    Luat, Aimee F; Behen, Michael E; Juhász, Csaba; Sood, Sandeep; Chugani, Harry T

    2009-12-01

    Tourette syndrome is generally considered to be a genetic disorder, but symptoms mimicking Tourette syndrome can be secondary to an underlying lesion disrupting the basal ganglia circuitry. Described here is a case of secondary tics, or tourettism, in a child with a large oligodendroglioma of the right temporal lobe extending to the basal ganglia. He presented with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and stimulant-induced tic disorder at the age of 11 years, and later also had also seizures. The family history was unremarkable. Cranial magnetic resonance imaging disclosed a right temporal lobe tumor extending to the basal ganglia. An alpha-[(11)C]methyl-l-tryptophan positron emission tomography scan showed asymmetric uptake in the basal ganglia and intense uptake in the tumor. He had a lesionectomy, and the histopathologic diagnosis was oligodendroglioma. Neuropsychologic testing after surgery revealed no attention-deficit hyperactivity disorder symptomatology, and only minimal features of obsessive-compulsive disorder. The present case provides additional evidence supporting the role of basal ganglia circuitry in the pathophysiology of tic disorder and its comorbid states. Children who present with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic disorder of late onset in the absence of family history should be further investigated with neuroimaging to exclude the presence of a secondary cause.

  8. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  9. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    PubMed Central

    Sarin, Hemant; Kanevsky, Ariel S; Wu, Haitao; Brimacombe, Kyle R; Fung, Steve H; Sousa, Alioscka A; Auh, Sungyoung; Wilson, Colin M; Sharma, Kamal; Aronova, Maria A; Leapman, Richard D; Griffiths, Gary L; Hall, Matthew D

    2008-01-01

    Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives. PMID:19094226

  10. Venous Thromboembolism in Patients Undergoing Craniotomy for Brain Tumors: A U.S. Nationwide Analysis.

    PubMed

    Cote, David J; Dubois, Heloise M; Karhade, Aditya V; Smith, Timothy R

    2016-11-01

    Background Patients who undergo craniotomy for brain tumor have an increased risk of developing venous thromboembolism (VTE). Using the National Surgical Quality Improvement Program (NSQIP) registry, patients undergoing craniotomy for brain tumor from 2006 and 2014 were analyzed to identify risk factors for postoperative VTE. Methods The study population, identified by Current Procedural Terminology codes, included all NSQIP-reported patients who underwent a craniotomy for brain tumor resection. Results There were 629 instances of VTE among 19,409 craniotomies for brain tumor (3.2%) recorded in NSQIP. Occurrence of VTE was associated with other postoperative complications on univariate analysis, including pneumonia, respiratory failure, stroke, and sepsis (all p < 0.001). On multivariate analysis, independent predictors of VTE included age 46 to 57 years (odds ratio [OR], 1.432; p = 0.006), 57 to 66 years (OR, 1.550; p = 0.001), or over 66 years (OR, 2.493; p < 0.001), body mass index (BMI) over 32.1 kg/m(2) (OR, 1.835; p < 0.001), functional dependence (OR, 1.657; p < 0.001), ventilator dependence (OR, 2.516; p < 0.001), steroid use (OR, 1.661; p < 0.001), prior sepsis (OR, 1.845; p < 0.001), and total operative time 183 to 271 minutes (OR, 1.462; p = 0.032) and longer than 271 minutes (OR, 1.945; p < 0.001). Conclusions VTE occurs in approximately 3% of patients undergoing craniotomy for brain tumor resection. Independent predictors for developing VTE include older age, higher BMI, recent steroid use, and total operative time.

  11. Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.

    PubMed

    Sneed, P K; Stauffer, P R; Gutin, P H; Phillips, T L; Suen, S; Weaver, K A; Lamb, S A; Ham, B; Prados, M D; Larson, D A

    1991-02-01

    Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

  12. Demographic and histopathologic profile of pediatric brain tumors: A hospital-based study

    PubMed Central

    Shah, Harshil C.; Ubhale, Bhushan P.; Shah, Jaimin K.

    2015-01-01

    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. PMID:26942148

  13. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    NASA Astrophysics Data System (ADS)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  14. MRI Brain Tumor Segmentation and Necrosis Detection Using Adaptive Sobolev Snakes

    PubMed Central

    Nakhmani, Arie; Kikinis, Ron; Tannenbaum, Allen

    2014-01-01

    Brain tumor segmentation in brain MRI volumes is used in neurosurgical planning and illness staging. It is important to explore the tumor shape and necrosis regions at different points of time to evaluate the disease progression. We propose an algorithm for semi-automatic tumor segmentation and necrosis detection. Our algorithm consists of three parts: conversion of MRI volume to a probability space based on the on-line learned model, tumor probability density estimation, and adaptive segmentation in the probability space. We use manually selected acceptance and rejection classes on a single MRI slice to learn the background and foreground statistical models. Then, we propagate this model to all MRI slices to compute the most probable regions of the tumor. Anisotropic 3D diffusion is used to estimate the probability density. Finally, the estimated density is segmented by the Sobolev active contour (snake) algorithm to select smoothed regions of the maximum tumor probability. The segmentation approach is robust to noise and not very sensitive to the manual initialization in the volumes tested. Also, it is appropriate for low contrast imagery. The irregular necrosis regions are detected by using the outliers of the probability distribution inside the segmented region. The necrosis regions of small width are removed due to a high probability of noisy measurements. The MRI volume segmentation results obtained by our algorithm are very similar to expert manual segmentation. PMID:25302005

  15. Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor

    PubMed Central

    Wu, Jason Boyang; Shi, Changhong; Chu, Gina Chia-Yi; Xu, Qijin; Zhang, Yi; Li, Qinlong; Yu, John S.; Zhau, Haiyen E.; Chung, Leland W.K.

    2016-01-01

    Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic aniontransporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors. PMID:26197410

  16. Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor.

    PubMed

    Wu, Jason Boyang; Shi, Changhong; Chu, Gina Chia-Yi; Xu, Qijin; Zhang, Yi; Li, Qinlong; Yu, John S; Zhau, Haiyen E; Chung, Leland W K

    2015-10-01

    Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic anion-transporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors.

  17. Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

    ClinicalTrials.gov

    2016-11-09

    Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

  18. SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

    SciTech Connect

    Huang, Z; Feng, Y; Lo, S; Grecula, J; Mayr, N; Yuh, W

    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

  19. Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas.

    PubMed

    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.

  20. No role of IFITM3 in brain tumor formation in vivo

    PubMed Central

    Kim, Ella L.; Bros, Matthias; Giese, Alf

    2016-01-01

    Glioblastoma multiforme (GBM) is one of the most lethal solid tumors in adults. Despite aggressive treatment approaches for patients, GBM recurrence is inevitable, in part due to the existence of stem-like brain tumor-propagating cells (BTPCs), which produce factors rendering them resistant to radio- and chemotherapy. Comparative transcriptome analysis of irradiated, patient-derived BTPCs revealed a significant upregulation of the interferon-inducible transmembrane protein 3 (IFITM3), suggesting the protein as a factor mediating radio resistance. Previously, IFITM3 has been described to affect glioma cells; therefore, the role of IFITM3 in the formation and progression of brain tumors has been investigated in vivo. Intracranial implantation studies using radio-selected BTPCs alongside non-irradiated parental BTPCs in immunodeficient mice displayed no influence of irradiation on animal survival. Furthermore, gain and loss of function studies using BTPCs ectopically expressing IFITM3 or having IFITM3 down-modulated by a shRNA approach, did affect neither tumor growth nor animal survival. Additionally, a syngeneic model based on the mouse glioma cell line GL261 was applied in order to consider the possibility that IFITM3 relies on an intact immune system to unfold its tumorigenic potential. GL261 cells ectopically expressing IFITM3 were implanted into the striatum of immunocompetent mice without influencing the survival of glioma-bearing animals. Lastly, the vasculature and the extent of microglia/macrophage invasion into the tumor were studied in BTPC and GL261 tumors but neither parameter was altered by IFITM3. This report presents for the first time that IFITM3 is upregulated in patient-derived BTPCs upon irradiation but does not affect brain tumor formation or progression in vivo. PMID:27835870

  1. Risk of brain tumors from wireless phone use.

    PubMed

    Dubey, Rash Bihari; Hanmandlu, Madasu; Gupta, Suresh Kumar

    2010-01-01

    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. Wireless communication has dramatically influenced our lifestyle; its impact on human health has not been completely assessed. Widespread concern continues in the community about the deleterious effects of radiofrequency radiations on human tissues and the subsequent potential threat of carcinogenesis. Exposure to low-frequency electromagnetic field has been linked to a variety of adverse health outcomes. This article surveys the results of early cell phone studies, where exposure duration was too short to expect tumor genesis, and 2 sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Hardell.

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

    PubMed Central

    Sergentanis, Theodoros N.; Tsivgoulis, Georgios; Perlepe, Christina; Ntanasis-Stathopoulos, Ioannis; Tzanninis, Ioannis-Georgios; Sergentanis, Ioannis N.; Psaltopoulou, Theodora

    2015-01-01

    Objective 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. Study Design 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. Results 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. Conclusion 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. PMID:26332834

  3. Brain Tumor Immunotherapy: What have We Learned so Far?

    PubMed Central

    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. PMID:26137448

  4. Radiosynthesis and Biological Evaluation of alpha-[F-18]Fluoromethyl Phenylalanine for Brain Tumor Imaging

    PubMed Central

    Huang, Chaofeng; Yuan, Liya; Rich, Keith; McConathy, Jonathan

    2013-01-01

    Objectives Radiolabeled amino acids have proven utility for imaging brain tumors in humans, particularly those that target system L amino acid transport. We have prepared the novel phenylalanine analogue, α-[18F]fluoromethyl phenylalanine (FMePhe, 9), as part of an effort to develop new system L tracers that can be prepared in high radiochemical yield through nucleophilic [18F]fluorination. The tumor imaging properties of both enantiomers this new tracer were evaluated through cell uptake, biodistribution and microPET studies in the mouse DBT model of high grade glioma. Methods The non-radioactive form of 9 and the cyclic sulfamidate labeling precursor were prepared from commercially available racemic α-benzylserine. Racemic [18F]9 was prepared from the labeling precursor in two steps using standard [18F]fluoride nucleophilic reaction conditions followed by acidic deprotection. The individual enantiomers [18F]9a and [18F]9b were isolated using preparative chiral HPLC. In vitro uptake inhibition assays were performed with each enantiomer using DBT cells. Biodistribution and microPET/CT studies were performed with each enantiomers in male BALB/c mice at approximately 2 weeks after implantation of DBT tumor cells. Results Radiolabeling of the cyclic sulfamidate precursor 5 provide racemic [18F]9 in high radiochemical yield (60–70%, n = 4) and high radiochemical purity (>96%, n = 4). In vitro uptake assays demonstrate that both [18F]9a and [18F]9b undergo tumor cell uptake through system L transport. The biodistribution studies using the single enantiomers [18F]9a and [18F]9b demonstrated good tumor uptake with lower uptake in most normal tissues, and [18F]9a had higher tumor uptake than [18F]9b. MicroPET imaging demonstrated good tumor visualization within 10 min of injection, rapid uptake of radioactivity, and tumor to brain ratios of approximately 6:1 at 60 min postinjection. Conclusions The novel PET tracer, [18F]FMePhe, is readily synthesized in good yield

  5. Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

    SciTech Connect

    Matsunaga, Shigeo; Shuto, Takashi; Takase, Hajime; Ohtake, Makoto; Tomura, Nagatsuki; Tanaka, Takahiro; Sonoda, Masaki

    2013-01-01

    Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most

  6. Tumors in murine brains studied by grating-based phase contrast microtomography

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Dominietto, Marco; Kovacs, Zsofia; Schmitz, Rüdiger; Hieber, Simone E.; Thalmann, Peter; Beckmann, Felix; Müller, Bert

    2014-09-01

    Angiogenesis, i.e. the formation of vessels, is one of the key processes during tumor development. The newly formed vessels transport oxygen and nutrients from the healthy tissue to the tumor and gives tumor cells the possibility to replicate. The principle of anti-angiogenic therapy is to block angiogenic process in order to stop tumor growth. The aim of the present study is the investigation of murine glioma vascular architecture at early (7 days), intermediate (10 and 15 days) and late (23 days) stage of growth by means of grating-based phase contrast microtomography. We demonstrate that this technique yields premium contrast between healthy and cancerous parts of murine brain tissues.

  7. Pharmacodynamic analysis of magnetic resonance imaging-monitored focused ultrasound-induced blood-brain barrier opening for drug delivery to brain tumors.

    PubMed

    Chu, Po-Chun; Chai, Wen-Yen; Hsieh, Han-Yi; Wang, Jiun-Jie; Wey, Shiaw-Pyng; Huang, Chiung-Yin; Wei, Kuo-Chen; Liu, Hao-Li

    2013-01-01

    Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors.

  8. Social self-perception among pediatric brain tumor survivors compared to peers

    PubMed Central

    Salley, Christina G.; Gerhardt, Cynthia A.; Fairclough, Diane L.; Patenaude, Andrea Farkas; Kupst, Mary Jo; Barrera, Maru; Vannatta, Kathryn

    2014-01-01

    Objective: To assess self-perceptions of social behavior among children treated for a brain tumor and comparison children. To investigate group differences in the accuracy of children’s self-perceptions as measured by discrepancies between self and peer reports of social behavior and to understand if these phenomena differ by gender. Method: Self and peer report of social behavior were obtained in the classrooms of 116 children who were treated for an intracranial tumor. Social behaviors were assessed utilizing the Revised Class Play (RCP) which generates indices for 5 behavioral subscales: Leadership-popularity, Prosocial, Aggressive-disruptive, Sensitive-isolated, and Victimization. A child matched for gender, race, and age, was selected from each survivor’s classroom to serve as a comparison. Abbreviated IQ scores were obtained in participants’ homes. Results: Relative to comparison children, those who had undergone treatment for a brain tumor overestimated their level of Leadership-popularity and underestimated levels of Sensitive-isolated behaviors and Victimization by peers. Female survivors were more likely to underestimate Sensitive-isolated behaviors and Victimization than male survivors. Conclusion: Following treatment for a brain tumor, children (particularly girls) may be more likely to underestimate peer relationship difficulties than healthy children. These discrepancies should be considered when obtaining self-report from survivors and developing interventions to improve social functioning. PMID:25127341

  9. CASP9 Germline Mutation in a Family with Multiple Brain Tumors.

    PubMed

    Ronellenfitsch, Michael W; Ji Eun, Oh; Satomi, Kaishi; Sumi, Koichiro; Harter, Patrick N; Steinbach, Joachim P; Felsberg, Jörg; Capper, David; Voegele, Catherine; Durand, Geoffroy; McKay, James; Le Calvez-Kelm, Florence; Schittenhelm, Jens; Klink, Barbara; Mittelbronn, Michel; Ohgaki, Hiroko

    2016-12-09

    We report a novel CASP9 germline mutation that may increase susceptibility to the development of brain tumors. We identified this mutation in a family in which three brain tumors had developed within three generations, including two anaplastic astrocytomas occurring in cousins. The cousins were diagnosed at similar ages (29 and 31 years), and their tumors showed similar histological features. Genetic analysis revealed somatic IDH1 and TP53 mutations in both tumors. However, no germline TP53 mutations were detected, despite the fact that this family fulfills the criteria of Li-Fraumeni-like syndrome. Whole exome sequencing revealed a germline stop-gain mutation (R65X) in the CASP9 gene, which encodes caspase-9, a key molecule for the p53-dependent mitochondrial death pathway. This mutation was also detected in DNA extracted from blood samples from the two siblings who were each a parent of one of the affected cousins. Caspase-9 immunohistochemistry showed the absence of caspase-9 immunoreactivity in the anaplastic astrocytomas and normal brain tissues of the cousins. These observations suggest that CASP9 germline mutations may have played a role at least in part to the susceptibility of development of gliomas in this Li-Fraumeni-like family lacking a TP53 germline mutation. This article is protected by copyright. All rights reserved.

  10. Quantitative analysis of topoisomerase II{alpha} to rapidly evaluate cell proliferation in brain tumors

    SciTech Connect

    Oda, Masashi; Arakawa, Yoshiki; Kano, Hideyuki; Kawabata, Yasuhiro; Katsuki, Takahisa; Shirahata, Mitsuaki; Ono, Makoto; Yamana, Norikazu; Hashimoto, Nobuo; Takahashi, Jun A. . E-mail: jat@kuhp.kyoto-u.ac.jp

    2005-06-17

    Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase II{alpha} (topo II{alpha}), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo II{alpha} mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo II{alpha} mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo II{alpha} mRNA was significantly correlated with its immuno-staining index (p < 0.0001, r = 0.9077). Furthermore, it sharply detected that topo II{alpha} mRNA decreased in growth-inhibited glioma cell. These results support that topo II{alpha} mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.

  11. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

    PubMed

    McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk.

  12. Epigenetics in clinical management of children and adolescents with brain tumors.

    PubMed

    Morales La Madrid, Andres; Kieran, Mark W

    2017-02-03

    Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the "classic boxes" heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically differently. Given that epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to "risk-group" stratification and better prognostication. Also, it will help unveil key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we will review the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.

  13. Functional Assays for Specific Targeting and Delivery of RNA Nanoparticles to Brain Tumor

    PubMed Central

    Lee, Tae Jin; Haque, Farzin; Vieweger, Mario; Yoo, Ji Young; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.

    2017-01-01

    Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy. Multifunctional RNA nanoparticles can be fabricated by bottom-up self-assembly of engineered RNA fragments harboring targeting (RNA aptamer or chemical ligand), therapeutic (siRNA, miRNA, ribozymes, and small molecule drugs), and imaging (fluorophore, radiolabels) modules. We have recently demonstrated that RNA nanoparticles can reach and target intracranial brain tumors in mice upon systemic injection with little or no accumulation in adjacent healthy brain tissues or in major healthy internal organs. Herein, we describe various functional imaging methods (fluorescence confocal microscopy, flow cytometry, fluorescence whole body imaging, and magnetic resonance imaging) to evaluate and monitor RNA nanoparticle targeting to intracranial brain tumors in mice. Such imaging techniques will allow in-depth evaluation of specifically delivered RNA therapeutics to brain tumors. PMID:25896001

  14. Circulating tumor cell is a common property of brain glioma and promotes the monitoring system

    PubMed Central

    Gao, Faliang; Cui, Yong; Jiang, Haihui; Sui, Dali; Wang, Yonggang; Jiang, Zhongli; Zhao, Jizong; Lin, Song

    2016-01-01

    Brain glioma is the most common primary intracranial tumor characterized by dismal prognosis and frequent recurrence, yet a real-time and reliable biological approach to monitor tumor response and progression is still lacking. Recently, few studies have reported that circulating tumor cells (CTCs) could be detected in glioblastoma multiform (GBM), providing the possibility of its application in brain glioma monitoring system. But its application limits still exist, because the detection rate of CTCs is still low and was exclusively limited to high- grade gliomas. Here, we adopted an advanced integrated cellular and molecular approach of SE-iFISH to detect CTCs in the peripheral blood (PB) of patients with 7 different subtypes of brain glioma, uncovering the direct evidences of glioma migration. We identified CTCs in the PB from 24 of 31 (77%) patients with glioma in all 7 subtypes. No statistical difference of CTC incidence and count was observed in different pathological subtypes or WHO grades of glioma. Clinical data revealed that CTCs, to some extent, was superior to MRI in monitoring the treatment response and differentiating radionecrosis from recurrence of glioma. Conclusively, CTCs is a common property of brain gliomas of various pathological subtypes, which has provided an ultimate paradox for the hypothesis “soil and seed”. It can be used to monitor the microenvironment of gliomas dynamically, which will be a meaningful complement to radiographic imaging. PMID:27517490

  15. Brain tumor demarcation with liquid-crystal tunable filter spectral imaging

    NASA Astrophysics Data System (ADS)

    Gebhart, Steven C.; Mahadevan-Jansen, Anita

    2006-02-01

    Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. This paper describes the design and testing of a combined fluorescence and diffuse reflectance imaging system which uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine its linearity, field of view, spatial and spectral resolution, and wavelength sensitivity. For functional testing, spectral images were acquired from tissue phantoms, mouse brain in vitro, and rat brain cortex in vivo. The spectral imaging system is characterized by measured intensities which are linear with sample emission intensity and integration time, a one-inch field of view for a seven-inch object distance, spectral resolution which is linear with wavelength, spatial resolution which is pixel-limited, and sensitivity functions which provide a guide for the distribution of total image integration time between wavelengths. Functional testing demonstrated good spatial and spectral constrast between brain tissue types, the capability to acquire adequate fluorescence and diffuse reflectance intensities within a one-minute imaging timeframe, and the importance of hemostasis to acquired signal strengths and imaging speed.

  16. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  17. Tl-201 and Tc-99m-Sestamibi SPECT for brain tumor detection: Comparison using MRI coregistration

    SciTech Connect

    Darcourt, J.; Itti, L.; Chang, L.

    1994-05-01

    Tl-201 (Tl) brain SPECT has been validated for the differential diagnosis of high versus low grade gliomas and recurrence versus radiation necrosis. We compared this technique to Tc-99m-Sestamibi (MIBI) SPECT in 9 patients (pts) with brain tumors using MRI coregistration. Pts were injected with 4 mCi of Tl and brain SPECT was performed using a dedicated brain system. This was immediately following by an injection of 20 mCi of MIBI and a brain SPECT using the same camera and with the pt in the same position. Four pts were studied for the diagnosis of radiation necrosis vs. tumor recurrence (2 had biopsy proven recurrence); 5 pts were studied for primary tumor evaluation: 2 meningiomas, 1 oligodendroglioma, 1 low-grade astrocytoma, 1 cysticercosis. Coregistration was performed for every pt by 3D surface fitting of the inner skull MIBI contour to the MRI brain surface extracted automatically. ROIs were drawn on the MRI and applied to the coregistered MIBI and Tl images for tumor to non-tumor ratios T/NT calculations. There was a tight correlation between MIBI and Tl T/NT (r-0.96) and a 1.5 threshold separated radiation necrosis from recurrence and low from high grade primary tumors. Therefore, the data already available on Tl brain tumor imaging can be used with MIBI SPECT with the advantage of a better image quality (2.5 to 4 times more counts).

  18. Integration of epidemiology, immunobiology, and translational research for brain tumors.

    PubMed

    Okada, Hideho; Scheurer, Michael E; Sarkar, Saumendra N; Bondy, Melissa L

    2013-05-01

    We recently identified a pivotal role for the host type I interferon (IFN) pathway in immunosurveillance against de novo mouse glioma development, especially through the regulation of immature myeloid cells (IMCs) in the glioma microenvironment. The present paper summarizes our published work in a number of areas. We have identified single-nucleotide polymorphisms (SNPs) in human IFN genes that dictate altered prognosis of patients with glioma. One of these SNPs (rs12553612) is located in the promoter of IFNA8 and influences its activity. Conversely, recent epidemiologic data show that chronic use of nonsteroidal anti-inflammatory drugs lowers the risk of glioma. We translated these findings back to our de novo glioma model and found that cyclooxygenase-2 inhibition enhances antiglioma immunosurveillance by reducing glioma-associated IMCs. Taken together, these findings suggest that alterations in myeloid cell function condition the brain for glioma development. Finally, in preliminary work, we have begun applying novel immunotherapeutic approaches to patients with low-grade glioma with the aim of preventing malignant transformation. Future research will hopefully better integrate epidemiological, immunobiological, and translational techniques to develop novel, preventive approaches for malignant gliomas.

  19. Alternating electric fields arrest cell proliferation in animal tumor models and human