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Sample records for brain tumors targeting

  1. Brain tumor-targeted drug delivery strategies

    Directory of Open Access Journals (Sweden)

    Xiaoli Wei

    2014-06-01

    Full Text Available Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  2. Targeting Malignant Brain Tumors with Antibodies

    Directory of Open Access Journals (Sweden)

    Rok Razpotnik

    2017-09-01

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

  3. Targeting Nanomedicine to Brain Tumors: Latest Progress and Achievements.

    Science.gov (United States)

    Van't Root, Moniek; Lowik, Clemens; Mezzanotte, Laura

    2017-01-01

    Targeting nanomedicine to brain tumors is hampered by the heterogeneity of brain tumors and the blood brain barrier. These represent the main reasons of unsuccessful treatments. Nanomedicine based approaches hold promise for improved brain tissue distribution of drugs and delivery of combination therapies. In this review, we describe the recent advancements and latest achievements in the use of nanocarriers, virus and cell-derived nanoparticles for targeted therapy of brain tumors. We provide successful examples of nanomedicine based approaches for direct targeting of receptors expressed in brain tumor cells or modulation of pathways involved in cell survival as well as approaches for indirect targeting of cells in the tumor stroma and immunotherapies. Although the field is at its infancy, clinical trials involving nanomedicine based approaches for brain tumors are ongoing and many others will start in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    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.

  5. Brain Tumors

    Science.gov (United States)

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

  6. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

    Directory of Open Access Journals (Sweden)

    Daniel Y Joh

    Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

  7. hTe exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches

    Institute of Scientific and Technical Information of China (English)

    Vivek Agrahari

    2017-01-01

    Delivering therapeutics to the central nervous system (CNS) and brain-tumor has been a major challenge. hTe 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 provid-ing signiifcant beneifts 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). hTe BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nan-otherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer signiifcant ad vantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are brielfy discussed. hTe drug transport mechanisms at the BBB are outlined. hTe 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 ap-proaches for their enhanced clinical application in brain-tumor therapy are discussed.

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

    Directory of Open Access Journals (Sweden)

    Vivek Agrahari

    2017-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Wagner LM

    2017-04-01

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

  10. Addressing brain tumors with targeted gold nanoparticles: a new gold standard for hydrophobic drug delivery?

    Science.gov (United States)

    Cheng, Yu; Meyers, Joseph D; Agnes, Richard S; Doane, Tennyson L; Kenney, Malcolm E; Broome, Ann-Marie; Burda, Clemens; Basilion, James P

    2011-08-22

    EGF-modified Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide-targeted Au NPs. Compared to the untargeted conjugates, EGF-Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard-to-reach cancers. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    2015-07-01

    Full Text Available A relationship between cyclic adenosine 3’, 5’-monophosphate (cAMP levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor risk in individuals with Neurofibromatosis type 1 (NF1. Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.

  12. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

    Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

  13. Brain tumor - primary - adults

    Science.gov (United States)

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

  14. Understanding Brain Tumors

    Science.gov (United States)

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

  15. Brain tumor - children

    Science.gov (United States)

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

  16. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    Science.gov (United States)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  17. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Brain Tumors KidsHealth / For Parents / Brain Tumors What's in ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  18. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    International Nuclear Information System (INIS)

    Jain, Darshana S.; Bajaj, Amrita N.; Athawale, Rajani B.; Shikhande, Shruti S.; Pandey, Abhijeet; Goel, Peeyush N.; Gude, Rajiv P.; Patil, Satish; Raut, Preeti

    2016-01-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  19. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Darshana S., E-mail: darshanaj_cup@yahoo.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Bajaj, Amrita N. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Athawale, Rajani B., E-mail: rajani.athawale@gmail.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Shikhande, Shruti S. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Pandey, Abhijeet [H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra (India); Goel, Peeyush N.; Gude, Rajiv P. [Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210 (India); Patil, Satish; Raut, Preeti [Cipla Pvt. Ltd., Vikhroli (West), Mumbai (India)

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  20. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    OpenAIRE

    Nagendra Sanyasihally Ningaraj; Divya eKhaitan

    2013-01-01

    Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

  1. Pediatric Brain Tumor Foundation

    Science.gov (United States)

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

  2. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration

    OpenAIRE

    Chertok, Beata; David, Allan E.; Yang, Victor C.

    2010-01-01

    This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity – properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administra...

  3. Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.

    Science.gov (United States)

    Bianchi, Andrea; Moncelet, Damien; Lux, François; Plissonneau, Marie; Rizzitelli, Silvia; Ribot, Emeline Julie; Tassali, Nawal; Bouchaud, Véronique; Tillement, Olivier; Voisin, Pierre; Crémillieux, Yannick

    2015-06-01

    The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs. Copyright © 2015 John Wiley & Sons, Ltd.

  4. A tri-modality image fusion method for target delineation of brain tumors in radiotherapy.

    Directory of Open Access Journals (Sweden)

    Lu Guo

    Full Text Available To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors.A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT and tri-modality (MRI/CT/PET image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV, the average distance between surface and centroid (ADSC, and the local standard deviation (SDlocal. Analysis of COV was also performed to evaluate intra-observer volume variation.The inter-observer variation analysis showed that, the mean COV was 0.14(± 0.09 and 0.07(± 0.01 for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05 with tri-modality; SDlocal averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm and patient 3 (from 0.42 cm to 0.36 cm with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00 with the tri-modality method as compared with using the dual-modality method.With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.

  5. Childhood Brain Tumors

    Science.gov (United States)

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

  6. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  7. Children's Brain Tumor Foundation

    Science.gov (United States)

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

  8. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration.

    Science.gov (United States)

    Chertok, Beata; David, Allan E; Yang, Victor C

    2010-08-01

    This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 +/- 3 microg Fe/ml min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p=0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (zeta-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p=0.004) than that achieved with slightly anionic G100 (zeta-potential= -12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p=0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. 2010 Elsevier Ltd. All rights reserved.

  9. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  10. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors

    Directory of Open Access Journals (Sweden)

    Li Shengwen

    2008-05-01

    Full Text Available Abstract Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent stem cell population based on their capacity of targeting brain tumors. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors is proposed to fill the gap in the current work flow of stem cell-based therapy. The organotypic slice platform has advantages of being mimic in vivo model, easier to manipulate to optimize parameters than in vivo models such as rodents and primates. This model serves as a framework to address the discrepancy between anticipated in vivo results and actual in vivo results, a critical barrier to timely progress in the field of the use of stem cells for the treatment of neurological disorders.

  11. Epilepsy and Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhi-yi Sha

    2009-01-01

    @@ Epidemiology It is estimated 61,414 new cases of primary brain tumors are expected to be diagnosed in 2009 in the U.S. The incidence statistic of 61,414 persons diagnosed per year includes both malignant (22,738) and non-malignant (38,677) brain tumors. (Data from American Brain Tumor Association). During the years 2004-2005, approximately 359,000 people in the United States were living with the diagnosis of a primary brain or central nervous system tumor. Specifically, more than 81,000 persons were living with a malignant tumor, more than 267,000 persons with a benign tumor. For every 100,000 people in the United States, approximately 131 are living following the diagnosis of a brain tumor. This represents a prevalence rate of 130.8 per 100,000 person years[1].

  12. Synergistic tumor microenvironment targeting and blood-brain barrier penetration via a pH-responsive dual-ligand strategy for enhanced breast cancer and brain metastasis therapy.

    Science.gov (United States)

    Li, Man; Shi, Kairong; Tang, Xian; Wei, Jiaojie; Cun, Xingli; Long, Yang; Zhang, Zhirong; He, Qin

    2018-05-22

    Cancer associated fibroblasts (CAFs) which shape the tumor microenvironment (TME) and the presence of blood brain barrier (BBB) remain great challenges in targeting breast cancer and its brain metastasis. Herein, we reported a strategy using PTX-loaded liposome co-modified with acid-cleavable folic acid (FA) and BBB transmigrating cell penetrating peptide dNP2 peptide (cFd-Lip/PTX) for enhanced delivery to orthotopic breast cancer and its brain metastasis. Compared with single ligand or non-cleavable Fd modified liposomes, cFd-Lip exhibited synergistic TME targeting and BBB transmigration. Moreover, upon arrival at the TME, the acid-cleavable cFd-Lip/PTX showed sensitive cleavage of FA, which reduced the hindrance effect and maximized the function of both FA and dNP2 peptide. Consequently, efficient targeting of folate receptor (FR)-positive tumor cells and FR-negative CAFs was achieved, leading to enhanced anti-tumor activity. This strategy provides a feasible approach to the cascade targeting of TME and BBB transmigration in orthotopic and metastatic cancer treatment. Copyright © 2018. Published by Elsevier Inc.

  13. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  14. Epilepsy and brain tumors

    Science.gov (United States)

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

    2016-01-01

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

  15. Brain Tumor Targeting of Magnetic Nanoparticles for Potential Drug Delivery: Effect of Administration Route and Magnetic Field Topography

    Science.gov (United States)

    Chertok, Beata; David, Allan E.; Yang, Victor C.

    2011-01-01

    Our previous studies demonstrated feasibility of magnetically-mediated retention of iron-oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350 mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, Rd. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of Rd. PMID:21763736

  16. Targeting BRAF V600E and Autophagy in Pediatric Brain Tumors

    Science.gov (United States)

    2015-10-01

    tumors in vivo by using combination therapy with chloroquine (autophagy inhibition) and vemurafenib (Raf-inhibitor). The major goals of the project as...BRAFV600E Cell lines used : BRafCA/WTInk4alox/lox mouse neurospheres (Cell line provided by Dr. Claudia Petritsch, UCSF). We have been able to successfully...a dose dependent manner to chloroquine as shown by MTS and LDH. 0 1.25 2.5 5 10 20 40 0 50 100 150 CQ (µM) % S ur vi va l 0 1 2 3 LD H release

  17. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

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

  18. Subcellular targets of mercaptoborate (BSH), a carrier of 10B for neutron capture therapy (BNCT) of brain tumors

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Krajčí, D.; Lisá, Věra

    2003-01-01

    Roč. 52, č. 5 (2003), s. 629-635 ISSN 0862-8408 R&D Projects: GA MPO FD-K/048 Institutional research plan: CEZ:AV0Z5011922 Keywords : thermal neutrons * brain tumors * sodium borocaptate Subject RIV: FD - Oncology ; Hematology Impact factor: 0.939, year: 2003

  19. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    International Nuclear Information System (INIS)

    Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Dobrodumov, Anatolii V.; Marchenko, Yaroslav Y.; Margulis, Boris A.; Pitkin, Emil; Guzhova, Irina V.

    2015-01-01

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M 2 ). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T 2 -weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M 2 measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M 2 ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates effectively target the

  20. Epidemiological features of brain tumors

    OpenAIRE

    Živković Nenad; Mihailović Goran; Marković Marko; Berisavac Iva; Spaić Milan

    2013-01-01

    Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of b...

  1. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  3. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  4. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

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

  5. Mechanism of brain tumor headache.

    Science.gov (United States)

    Taylor, Lynne P

    2014-04-01

    Headaches occur commonly in all patients, including those who have brain tumors. Using the search terms "headache and brain tumors," "intracranial neoplasms and headache," "facial pain and brain tumors," "brain neoplasms/pathology," and "headache/etiology," we reviewed the literature from the past 78 years on the proposed mechanisms of brain tumor headache, beginning with the work of Penfield. Most of what we know about the mechanisms of brain tumor associated headache come from neurosurgical observations from intra-operative dural and blood vessel stimulation as well as intra-operative observations and anecdotal information about resolution of headache symptoms with various tumor-directed therapies. There is an increasing overlap between the primary and secondary headaches and they may actually share a similar biological mechanism. While there can be some criticism that the experimental work with dural and arterial stimulation produced head pain and not actual headache, when considered with the clinical observations about headache type, coupled with improvement after treatment of the primary tumor, we believe that traction on these structures, coupled with increased intracranial pressure, is clearly part of the genesis of brain tumor headache and may also involve peripheral sensitization with neurogenic inflammation as well as a component of central sensitization through trigeminovascular afferents on the meninges and cranial vessels. © 2014 American Headache Society.

  6. Intracerebral hemorrhage in brain tumors

    International Nuclear Information System (INIS)

    Fujita, Katsuzo; Matsumoto, Satoshi

    1980-01-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief. (author)

  7. Intracerebral hemorrhage in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, K; Matsumoto, S [Kobe Univ. (Japan). School of Medicine

    1980-10-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief.

  8. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    Energy Technology Data Exchange (ETDEWEB)

    Shevtsov, Maxim A., E-mail: shevtsov-max@mail.ru [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); A.L. Polenov Russian Research Scientific Institute of Neurosurgery, Mayakovsky str. 12, St. Petersburg 191014 (Russian Federation); Nikolaev, Boris P. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Ryzhov, Vyacheslav A. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, Gatchina 188300 (Russian Federation); Yakovleva, Ludmila Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Dobrodumov, Anatolii V. [Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), Bolshoi pr. 31, St. Petersburg 199004 (Russian Federation); Marchenko, Yaroslav Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Margulis, Boris A. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); Pitkin, Emil [The Wharton School, University of Pennsylvania, 3730 Walnut St., Philadelphia, PA 19104 (United States); Guzhova, Irina V. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation)

    2015-08-15

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M{sub 2}). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T{sub 2}-weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M{sub 2} measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M{sub 2} ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates

  9. Radiation therapy of brain tumor

    International Nuclear Information System (INIS)

    Sung, K. J.; Lee, D. H.; Park, C. Y.

    1980-01-01

    One hundred and six cases of brain tumors were treated at the Yonsei Cancer Center from January 1972 to August 1978 by Co-60 teletherapy unit. We analyses their clinical findings, histopathological findings, treatment and results. In those cases which computerized tomography had been used before and after radiation therapy, changes in tumor size and the presence of edema or necrosis following treatment was evaluated. 1. Among 106 cases, 90 cases were primary brain tumors and 16 cases were metastatic brain tumors. Pituitary tumors (38), glioma (34) and pinealoma (10) composed of most of primary brain tumors. 2. Post treatment follow-up was possible in 38 cases more than 1 years. Four among 11 cases of giloma expired and survivors had considerable neurological symptoms except 2 cases. Sixty five percent (12/20) of pituitary tumors showed improvement of visual symptoms and all cases (7) of pinealoma which post treatment follow-up was possible, showed remarkable good response. 3. Findings of CT scan after radiation treatment were compatible with results of clinical findings and post treatment follow-up. It showed complete regression of tumor mass in one case of pinealoma and medulloblastoma. One case of pituitary tumor showed almost complete regression of tumor mass. It also showed large residual lesion in cases of glioblastoma multiforme and cystic astrocytoma.

  10. Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

    International Nuclear Information System (INIS)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Lieberson, Robert E.; Soltys, Scott G.

    2012-01-01

    Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  11. Brain tumor and CT, 1

    International Nuclear Information System (INIS)

    Suzuki, Nobuyuki; Katada, Kazuhiro; Shinomiya, Youichi; Sano, Hirotoshi; Kanno, Tetsuo

    1981-01-01

    It is very important for a neurosurgeon to know the consistency of a brain tumor preoperatively, since the information which is of much use in indicating the likely difficulty of the operation, which operative tools should be selected, the amount of bleeding to be expected from the tumor, and so on. The authors, therefore, tried to evaluate the consistency of brain tumors preoperatively 27 cases in which the margin of the tumor was made clear with a homogeneous stain were studied concerning the relationship between the tumor consistency and the CT findings. The results are as follows: 1) A higher CT number on a plain CT indicated a harder consistency of the tumor. 2) A lesser contrast index (CT number on enhancement CT/CT number on plain CT) showed a harder consistency of the tumor. (author)

  12. Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.

    Science.gov (United States)

    Jones, Tania A; Jeyapalan, Jennie N; Forshew, Tim; Tatevossian, Ruth G; Lawson, Andrew R J; Patel, Sheena N; Doctor, Gabriel T; Mumin, Muhammad A; Picker, Simon R; Phipps, Kim P; Michalski, Antony; Jacques, Thomas S; Sheer, Denise

    2015-12-18

    Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.

  13. Assisted Care Options (Brain Tumors)

    Science.gov (United States)

    ... you with relief from the symptoms, pain, and stress of your brain tumor, while improving quality of life for both you and your family. Palliative care specialists work together as a team to provide an extra ...

  14. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  15. Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood-brain barrier and targeted fluorescence imaging of glioma and tumor vasculature.

    Science.gov (United States)

    Huang, Ning; Cheng, Si; Zhang, Xiang; Tian, Qi; Pi, Jiangli; Tang, Jun; Huang, Qing; Wang, Feng; Chen, Jin; Xie, Zongyi; Xu, Zhongye; Chen, Weifu; Zheng, Huzhi; Cheng, Yuan

    2017-01-01

    Delivery of imaging agents to brain glioma is challenging because the blood-brain barrier (BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots (QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides (NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH (4.0~8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo, contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Negative brain scintigrams in brain tumors

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    With 53 histologically verified and 2 histologically not identified brain tumors, that showed a negative scintigram, it was tried to find reasons for the wrong and negative dropout of these scintigrams. The electroencephalograms and angiograms, that were made simultaneously were taken into consideration with respect to their propositional capability and were compared with the scintigram findings. For the formation of the negative brain scintigrams there could be found no unique cause or causal constellation. The scintigraphic tumor representation is likely based on a complex process. Therefore the reasons for the negativity of the brain scintigrams can be a manifold of causes. An important role plays the vascularisation of the tumor, but not in a sole way. As well the tumor localisation gains some importance; especially in the temporal lobe or in the deeper structures situated tumors can be negative in the scintigram. To hold down the rate of wrong-negative quote in the case of intracranial tumor search, one is advised to continue with an further exposure after 2 to 4 hours besides the usual exposures, unless a sequential scintigraphy was made from the beginning. (orig./MG) [de

  17. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  18. Targeted Serum Metabolite Profiling Identifies Metabolic Signatures in Patients with Alzheimer's Disease, Normal Pressure Hydrocephalus and Brain Tumor

    Directory of Open Access Journals (Sweden)

    Matej Orešič

    2018-01-01

    Full Text Available Progression to AD is preceded by elevated levels of 2,4-dihydroxybutanoic acid (2,4-DHB, implicating hypoxia in early pathogenesis. Since hypoxia may play a role in multiple CNS disorders, we investigated serum metabolite profiles across three disorders, AD, Normal Pressure Hydrocephalus (NPH and brain tumors (BT. Blood samples were collected from 27 NPH and 20 BT patients. The profiles of 21 metabolites were examined. Additionally, data from 37 AD patients and 46 controls from a previous study were analyzed together with the newly acquired data. No differences in 2,4-DHB were found across AD, NPH and BT samples. In the BT group, the fatty acids were increased as compared to HC and NPH groups, while the ketone body 3-hydroxybutyrate was increased as compared to AD. Glutamic acid was increased in AD as compared to the HC group. In the AD group, 3-hydroxybutyrate tended to be decreased with respect to all other groups (mean values −30% or more, but the differences were not statistically significant. Serine was increased in NPH as compared to BT. In conclusion, AD, NPH and BT have different metabolic profiles. This preliminary study may help in identifying the blood based markers that are specific to these three CNS diseases.

  19. A comparison of perfusion computed tomography and contrast enhanced computed tomography on radiation target volume delineation using rabbit VX2 brain tumor model

    International Nuclear Information System (INIS)

    Sun Changjin; Luo Yunxiu; Yu Jinming; Lu Haibo; Li Chao; Zhang Dekang; Huang Jianming; Wang Jie; Lang Jinyi

    2010-01-01

    Objective: To compare the accuracy of blood volume perfusion imaging (perfusion CT)with contrast enhanced 64-slice spiral computed tomography (CECT) in the evaluation of gross tumor volume (GTV) and clinical target volume (CTV) using rabbits with VX2 brain tumor. Methods: Perfusion CT and CECT were performed in 20 rabbits with VX2 brain tumor. The GTV and CTV calculated with the maximal and minimal diameter of each tumor in the blood volume (BV) maps and CECT were measured and compared to those in pathological specimens. Results: The mean value of the maximal and minimal diameter of GTV was (8.19 ± 2.29) mm and (4.83 ± 1.31) mm in pathological specimens, (11.98 ±3.29) mm and (7.03±1.82) mm in BV maps, while (6.36±3.85) mm and (3.17±1.93) mm in CECT images, which were significantly different (pathological specimen vs. BV map, t = 7.17, P =0.000;pathological specimen vs. CECT, t = 8.37, P = 0.000, respectively). The mean value of the maximal and minimal diameter of CTV in pathologic specimens was (12.87 ± 3.74) mm and (7.71 ± 2.15) mm, which was significantly different from that of GTV and CTV in CECT (t = - 3. 18, P = 0. 005 and t = - 4.24, P =0.000; t= -11.59,P=0.000 and t= -9.39, P=0.000), while similar with that of GTV in BV maps (t = - 1.95,P = 0. 067; t = - 2. 06, P = 0. 054). For CECT, the margin from GTV to CTV was 81.83% ±40.33% for the maximal diameter and 276.73% ± 131.46% for the minimal. While for BV maps, the margin was 7.93% ± 17. 84% and 12.52% ± 27. 83%, which was significant different from that for CECT images (t=7.36, P=0. 000 and t= -8.78, P=0.000). Conclusions: Compared with CECT, the BV map from 64-slice spiral CT perfusion imaging might have higher accuracy in target volume delineation for brain tumor. (authors)

  20. Pediatric brain tumors; Kindliche Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-09-15

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

  1. Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors

    Science.gov (United States)

    2016-11-01

    tumors were monitored by bioluminescence. The quantification of bioluminescence based tumor growth. Figure 2-4. Immuno-staining of vascular ...marrow developed high-grade tumors, which had typical malignant features, including robust gadolinium enhancement on MRI, pseudopalisading necrosis , and...perfused with Rhodamine-Dextran. Upper scale bar, 50 µm. Lower panels are magnified views to highlight vascular permeability, scale bar, 20 µm

  2. Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors

    Science.gov (United States)

    2015-09-01

    described previously (21). Bioluminesence IVIS -100 (Xenogen) and MRI (Bruker Biospin) were performed to monitor the progression of tumor. Tumor margins in...Cancer Cell 2006;9:157–73. 16. Tang Z, Arjunan P, Lee C, Li Y, Kumar A, Hou X, et al. Survival effect of PDGF-CC rescues neurons from apoptosis in both

  3. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    Science.gov (United States)

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

    2013-01-01

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

  4. Brain tumors and syndromes in children

    NARCIS (Netherlands)

    Bleeker, Fonnet E.; Hopman, Saskia M. J.; Merks, Johannes H. M.; Aalfs, Cora M.; Hennekam, Raoul C. M.

    2014-01-01

    (Brain) tumors are usually a disorder of aged individuals. If a brain tumor occurs in a child, there is a possible genetic susceptibility for this. Such genetic susceptibilities often show other signs and symptoms. Therefore, every child with a brain tumor should be carefully evaluated for the

  5. Progress and perspectives on targeting nanoparticles for brain drug delivery

    Institute of Scientific and Technical Information of China (English)

    Huile Gao

    2016-01-01

    Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

  6. Progress and perspectives on targeting nanoparticles for brain drug delivery

    Directory of Open Access Journals (Sweden)

    Huile Gao

    2016-07-01

    Full Text Available Due to the ability of the blood–brain barrier (BBB to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier (BBTB, and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

  7. Fiber tracking for brain tumor

    International Nuclear Information System (INIS)

    Yamada, Kei; Nakamura, Hisao; Ito, Hirotoshi; Tanaka, Osamu; Kubota, Takao; Yuen, Sachiko; Kizu, Osamu; Nishimura, Tsunehiko

    2003-01-01

    The purpose of this study was to validate an innovative scanning method for patients diagnosed with brain tumors. Using a 1.5 Tesla whole body magnetic resonance (MR) imager, 23 patients with brain tumors were scanned. The recorded data points of the diffusion-tensor imaging (DTI) sequences were 128 x 37 with the parallel imaging technique. The parallel imaging technique was equivalent to a true resolution of 128 x 74. The scan parameters were repetition time (TR)=6000, echo time (TE)=88, 6 averaging with a b-value of 800 s/mm 2 . The total scan time for DTI was 4 minutes and 24 seconds. DTI scans and subsequent fiber tracking were successfully applied in all cases. All fiber tracts on the contralesional side were visualized in the expected locations. Fiber tracts on the lesional side had varying degrees of displacement, disruption, or a combination of displacement and disruption due to the tumor. Tract disruption resulted from direct tumor involvement, compression upon the tract, and vasogenic edema surrounding the tumor. This DTI method using a parallel imaging technique allows for clinically feasible fiber tracking that can be incorporated into a routine MR examination. (author)

  8. SU-E-T-01: (In)dependence of Plan Quality On Treatment Modalities and Target-To-Critical Structure Geometry for Brain Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, D; Shao, W; Low, D; Kupelian, P; Qi, S X [UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To evaluate and test the hypothesis that plan quality may be systematically affected by treatment delivery techniques and target-tocritical structure geometric relationship in radiotherapy for brain tumor. Methods: Thirty-four consecutive brain tumor patients treated between 2011–2014 were analyzed. Among this cohort, 10 were planned with 3DCRT, 11 with RadipArc, and 13 with helical IMRT on TomoTherapy. The selected dosimetric endpoints (i.e., PTV V100, maximum brainstem/chiasm/ optic nerve doses) were considered as a vector in a highdimensional space. A Pareto analysis was performed to identify the subset of Pareto-efficient plans.The geometric relationships, specifically the overlapping volume and centroid-of-mass distance between each critical structure to the PTV were extracted as potential geometric features. The classification-tree analyses were repeated using these geometric features with and without the treatment modality as an additional categorical predictor. In both scenarios, the dominant features to prognosticate the Pareto membership were identified and the tree structures to provide optimal inference were recorded. The classification performance was further analyzed to determine the role of treatment modality in affecting plan quality. Results: Seven Pareto-efficient plans were identified based on dosimetric endpoints (3 from 3DCRT, 3 from RapicArc, 1 from Tomo), which implies that the evaluated treatment modality may have a minor influence on plan quality. Classification trees with/without the treatment modality as a predictor both achieved accuracy of 88.2%: with 100% sensitivity and 87.1% specificity for the former, and 66.7% sensitivity and 96.0% specificity for the latter. The coincidence of accuracy from both analyses further indicates no-to-weak dependence of plan quality on treatment modality. Both analyses have identified the brainstem to PTV distance as the primary predictive feature for Pareto-efficiency. Conclusion: Pareto

  9. SU-E-T-01: (In)dependence of Plan Quality On Treatment Modalities and Target-To-Critical Structure Geometry for Brain Tumor

    International Nuclear Information System (INIS)

    Ruan, D; Shao, W; Low, D; Kupelian, P; Qi, S X

    2015-01-01

    Purpose: To evaluate and test the hypothesis that plan quality may be systematically affected by treatment delivery techniques and target-tocritical structure geometric relationship in radiotherapy for brain tumor. Methods: Thirty-four consecutive brain tumor patients treated between 2011–2014 were analyzed. Among this cohort, 10 were planned with 3DCRT, 11 with RadipArc, and 13 with helical IMRT on TomoTherapy. The selected dosimetric endpoints (i.e., PTV V100, maximum brainstem/chiasm/ optic nerve doses) were considered as a vector in a highdimensional space. A Pareto analysis was performed to identify the subset of Pareto-efficient plans.The geometric relationships, specifically the overlapping volume and centroid-of-mass distance between each critical structure to the PTV were extracted as potential geometric features. The classification-tree analyses were repeated using these geometric features with and without the treatment modality as an additional categorical predictor. In both scenarios, the dominant features to prognosticate the Pareto membership were identified and the tree structures to provide optimal inference were recorded. The classification performance was further analyzed to determine the role of treatment modality in affecting plan quality. Results: Seven Pareto-efficient plans were identified based on dosimetric endpoints (3 from 3DCRT, 3 from RapicArc, 1 from Tomo), which implies that the evaluated treatment modality may have a minor influence on plan quality. Classification trees with/without the treatment modality as a predictor both achieved accuracy of 88.2%: with 100% sensitivity and 87.1% specificity for the former, and 66.7% sensitivity and 96.0% specificity for the latter. The coincidence of accuracy from both analyses further indicates no-to-weak dependence of plan quality on treatment modality. Both analyses have identified the brainstem to PTV distance as the primary predictive feature for Pareto-efficiency. Conclusion: Pareto

  10. Therapy of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jellinger, K [ed.

    1987-01-01

    The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs.

  11. Therapy of malignant brain tumors

    International Nuclear Information System (INIS)

    Jellinger, K.

    1987-01-01

    The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs

  12. Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

    Directory of Open Access Journals (Sweden)

    Sarah E Mathis

    Full Text Available Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID, which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1 and a 5-month female (patient 2, affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity

  13. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

  14. Brain Tumor Image Segmentation in MRI Image

    Science.gov (United States)

    Peni Agustin Tjahyaningtijas, Hapsari

    2018-04-01

    Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

  15. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  16. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    , proliferate and differentiate in vitro and give rise to brain tumor spheres. This tumorigenic subset may provide both a platform for brain tumor research and a target for clinical treatment.

  17. Childhood brain tumors: epidemiology, current management and future directions.

    Science.gov (United States)

    Pollack, Ian F; Jakacki, Regina I

    2011-07-26

    Brain tumors are the most common solid tumors in children. With the increasingly widespread availability of MRI, the incidence of childhood brain tumors seemed to rise in the 1980s, but has subsequently remained relatively stable. However, management of brain tumors in children has evolved substantially during this time, reflecting refinements in classification of tumors, delineation of risk groups within histological subsets of tumors, and incorporation of molecular techniques to further define tumor subgroups. Although considerable progress has been made in the outcomes of certain tumors, prognosis in other childhood brain tumor types is poor. Among the tumor groups with more-favorable outcomes, attention has been focused on reducing long-term morbidity without sacrificing survival rates. Studies for high-risk groups have examined the use of intensive therapy or novel, molecularly targeted approaches to improve disease control rates. In addition to reviewing the literature and providing an overview of the complexities in diagnosing childhood brain tumors, we will discuss advances in the treatment and categorization of several tumor types in which progress has been most apparent, as well as those in which improvements have been lacking. The latest insights from molecular correlative studies that hold potential for future refinements in therapy will also be discussed.

  18. Application of PET in brain tumor

    International Nuclear Information System (INIS)

    Chung, June Key

    2002-01-01

    The annual incidence of primary brain tumors is 7-19 cases per 100,000 people. The unique capacity of visualizing biochemical processes allows PET to determine functional metabolic activities of the brain tumors. Like other malignant tumors, F-18 FDG has been used commonly in the imaging of brain tumors. FDG PET is valuable in grading malignancy, predicting prognosis, monitoring treatment, differentiating tumor recurrence from radiation nucrosis, and detecting primary lesion in metastatric brain tumors. Among amino acids labeled with positron emitters, C-11 methionine is used clinically.Tumor delineation is much better with methionine PET than with FDG PET. Low grade gliomas, in particular, are better evaluated with methionine than with FDG. PET opens another dimension in brain tumor imaging. PET imaging has clearly entered the clinical area with a profound impact on patient care in many indications

  19. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    Energy Technology Data Exchange (ETDEWEB)

    Aslian, Hossein [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Sadeghi, Mahdi [Agricultural, Medical and Industrial Research School, Karaj (Iran, Islamic Republic of); Mahdavi, Seied Rabie [Department of Medical Physics, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Babapour Mofrad, Farshid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Astarakee, Mahdi, E-mail: M-Astarakee@Engineer.com [Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khaledi, Navid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Fadavi, Pedram [Department of Radiation Oncology, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-09-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer.

  20. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    International Nuclear Information System (INIS)

    Aslian, Hossein; Sadeghi, Mahdi; Mahdavi, Seied Rabie; Babapour Mofrad, Farshid; Astarakee, Mahdi; Khaledi, Navid; Fadavi, Pedram

    2013-01-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer

  1. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith

    2013-01-01

    The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include inexpen...... was characterized in human colon carcinoma xenograft bearing nude mice. A tumor specific accumulation of HES 450 was observed, which proves it’s potential as carrier for passive tumor targeting....

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  3. Tumor-targeting peptides from combinatorial libraries*

    Science.gov (United States)

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

  4. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. METHODS: We treated...... mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis...... by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation -- as measured by MRI and by dry/wet weight measurement of water content -- but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage...

  5. Brain tumors in children; Hirntumoren beim Kind

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-15

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

  6. BNCT for malignant brain tumors in children

    International Nuclear Information System (INIS)

    Kageji, T.; Mizobuchi, Y.; Nagahiro, S.; Nakagawa, Y.; Kumada, Hiroaki

    2006-01-01

    BSH-based intra-operative BNCT as an initial treatment underwent in 4 children with malignant brain tumors since 1998. There were 2 glioblastomas, one primitive neuroectodermal tumor (PNET) and one anaplastic ependymoma patient. They included two children under 3-year-old. All GBM patients were died of CSF dissemination without tumor regrowth in the primary site. Another PNET and anaplastic ependymoma patients are still alive without tumor recurrence. We can consider BNCT is optimal treatment modality for malignant brain tumor in children. (author)

  7. Brain tumors in patients primarly treated psychiatrically

    Directory of Open Access Journals (Sweden)

    Ignjatović-Ristić Dragana

    2011-01-01

    Full Text Available Introduction. Psychiatric symptoms are not rare manifestations of brain tumors. Brain tumors presented by symptoms of raised intracranial pressure, focal neurological signs, or convulsions are usually first seen by the neurologist or less frequently by the neurosurgeon in routine diagnostic procedures. On the other hand, when psychiatric symptoms are the first manifestation in “neurologically silent” brain tumors, the patients are sent to the psychiatrist for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed for a long period of time. Case Report. We presented three patients with the diagnosed brain tumor where psychiatrist had been the first specialist to be consulted. In all three cases neurological examination was generally unremarkable with no focal signs or features of raised intracranial pressure. CT scan demonstrated right insular tumor in a female patient with obsessive-compulsive disorder (OCD; right parietal temporal tumor in a patient with delusions and depression and left frontal tumor in a patient with history of alcohol dependency. Conclusion. Psychiatric symptoms/disorders in patients with brain tumors are not specific enough and can have the same clinical presentation as the genuine psychiatric disorder. Therefore, we emphasize the consideration of neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those with a change in mental status, or when headaches suddenly appear or in cases of treatment resistant psychiatric disorders regardless the lack of neurological symptoms.

  8. Targeting the Brain with Nanomedicine.

    Science.gov (United States)

    Rueda, Felix; Cruz, Luis J

    2017-01-01

    Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Pediatric brain tumors of neuroepithelial tissue

    International Nuclear Information System (INIS)

    Papanagiotou, P.; Politi, M.; Bergmann, M.; Pekrun, A.; Juergens, K.U.

    2014-01-01

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [de

  10. Retrotransposon Targeting of Tumor Cells

    National Research Council Canada - National Science Library

    Wu, Dongdong; DeVaux, George

    2005-01-01

    .... Cancer gene therapy techniques include oncogene inactivation, tumor suppressor gene replacement, inhibition of angiogenesis, immunopotentiation, molecular chemotherapy, and transfer of drug resistance genes...

  11. BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells.

    Science.gov (United States)

    Thomaz, Amanda; Jaeger, Mariane; Buendia, Marienela; Bambini-Junior, Victorio; Gregianin, Lauro José; Brunetto, Algemir Lunardi; Brunetto, André T; de Farias, Caroline Brunetto; Roesler, Rafael

    2016-07-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

  12. Asymptomatic brain tumor detected at brain check-up

    International Nuclear Information System (INIS)

    Onizuka, Masanari; Suyama, Kazuhiko; Shibayama, Akira; Hiura, Tsuyoshi; Horie, Nobutaka; Miyazaki, Hisaya

    2001-01-01

    Brain check-up was performed in 4000 healthy subjects who underwent medical and radiological examinations for possible brain diseases in our hospital from April 1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one epidermoid cyst. The detection rate of incidental brain tumor in our hospital was 0.3%. Nine patients underwent surgery, with one case of morbidity due to postoperative transient oculomotor nerve paresis. The widespread use of brain check-up may increasingly detect asymptomatic brain tumors. Surgical indications for such lesions remain unclear, and the strategy for treatment should be determined with consideration of the patient's wishes. (author)

  13. Changing Epidemiology of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-07-01

    Full Text Available Neurosurgeons at the Hospital for Sick Children, Toronto, Canada, analyzed and classified 1, 866 surgical pathology cases of brain tumors in children under age 19 years, treated 1980-2008.

  14. Headache and Vascular Events with Brain Tumors

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-05-01

    Full Text Available Investigators at the Children's Hospital of Philadelphia, PA, performed a retrospective study of 265 children with brain tumors who received cranial irradiation and developed severe recurrent headache.

  15. Brain's tumor image processing using shearlet transform

    Science.gov (United States)

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

    2017-09-01

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

  16. Beyond Survival - Cognition after Pediatric Brain Tumor

    OpenAIRE

    Tonning Olsson, Ingrid

    2015-01-01

    Background: Pediatric Brain Tumor (PBT) survivors suffer from cognitive sequelae, especially within the areas of cognitive tempo, attention, executive function and memory. The cognitive difficulties are often accentuated over the years, but knowledge about the long term trajectory is still scarce. Aim: The aim of this thesis was to examine cognitive sequelae after Pediatric Brain Tumor (PBT); risk factors, common difficulties, development and neuroimaging correlates. Methods: In study...

  17. Radiotherapy for pediatric brain stem tumors

    International Nuclear Information System (INIS)

    Shcherbenko, O.I.; Parkhomenko, R.A.; Govorina, E.V.; Zelinskaya, N.I.; Ardatova, G.V.; Nechaeva, V.N.

    2000-01-01

    The immediate and short-term results of gamma therapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, magnetic resonance tomography showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was no clinical evidence of radiation injury [ru

  18. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

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

  19. Radionuclidr diagnosis of brain tumors, brain inflammatory and traumatic lesions

    International Nuclear Information System (INIS)

    Badmaev, K.N.; Mel'kishev, V.F.; Dement'ev, E.V.; Svetlova, N.L.

    1982-01-01

    A complex of problems of radionuclide diagnosis of central nervous system diseases including tumors, traumas, vascular lessons, inflammatory processes is considered. The principles, technique and results of radionuclide xintigraphy of a tumor, depending on its localization are given. Radioindication of brain tumours in the operation is given

  20. Multiparametric MR assessment of pediatric brain tumors

    International Nuclear Information System (INIS)

    Tzika, A.A.; Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T.; Goumnerova, L.; Black, P.McL.; Zurakowski, D.; Anthony, D.C.

    2003-01-01

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

  1. Proton MRS imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  2. Stereotaxic external irradiation for brain tumors

    International Nuclear Information System (INIS)

    Kim, Y.H.; Fayos, J.V.; Houdek, P.V.; Landy, H.; Van Buren, J.

    1987-01-01

    A system has been developed to deliver precision radiation therapy to a limited volume of brain tissue. A CT-compatible nonmetallic headband, or ''halo,'' is secured to the skull with screw pins. A metal frame attached to the CT couch and the patient's head is secured to the couch by temporarily affixing the halo to the frame. A CT scan is obtained to determine the x,y,z coordinates of the brain lesion. The same halo, frame, and coordinates are used in daily treatment with 10-MVX accelerator and a coplanar arc rotation technique. Field size is determined to cover the target volume with the 90% isodose line. Verification films are obtained twice a week. On completion of treatment, the halo is removed. From December 1982 to January 1986, 14 patients were treated with this system. Six had pituitary tumors, two had craniopharyngiomas, and six had astrocytomas. The dose delivered ranged from 3,600 rad in 12 fractions to 6,250 rad in 25 fractions at a rate of one fraction per day, 5 days a week. Judging from the verification films, daily administration of intended radiation was extremely good. Superficial infection of the screw-pin sites healed without sequelae. All patients were alive at the last follow-up. This system is relatively simple yet able to deliver precision irradiation without any remarkable complications

  3. Histopathological studies on the irradiated brain tumors

    International Nuclear Information System (INIS)

    Narita, Tadao

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy. (J.P.N.)

  4. Histopathological studies on the irradiated brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Narita, T [Gunma Univ., Maebashi (Japan).School of Medicine

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy.

  5. High efficiency diffusion molecular retention tumor targeting.

    Directory of Open Access Journals (Sweden)

    Yanyan Guo

    Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

  6. Study on intraoperative radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Uozumi, Akimasa

    1990-01-01

    Effects of a single large dose radiation on the brain of dogs were investigated for the purpose of determining the optimal dose and radiation field in intraoperative radiotherapy. The right parietal lobe of dogs (three groups, four dogs in each) were radiated at the dose of 30, 40 and 50 Gy respectively at the depth of 1.5 cm by 11 Nev electron beam with field size of 2 cm. CT and histopathological study were performed 2, 6, 12 and 24 months after radiation. L-hemiparesis developed 14 months after radiation in the 30 Gy group and 8 months in the 40 Gy group, 6 months in the 50 Gy group. All animals in the 40 Gy and 50 Gy groups died before 15 months of radiation. CT showed delayed radiation necrosis in all groups. Brain swelling and ventricular displacement in the radiated hemisphere and contralateral ventricular dilatation were depicted on plain CT. Diffuse heterogeneous contrast enhancement (CE) was observed on CE-CT. CT revealed disappearance of radiation necrosis in the 30 Gy group 24 months of radiation, suggesting that radiation necrosis may be dependent on the term after radiation. Histological findings of radiation necrosis were similar in all animals, and the vascular change preceding the parechymal necrosis was not observed. This supports the theory that the vascular alternation dose not play a major role in the production of radiation necrosis. The necrotic area grossly reflected the isodose curve and was observed in the radiation field with 15 to 20 Gy at the depth of 3 to 4.5 cm. Thus, the intraoperative radiotherapy should be planned on the basis of two such factors as electron beam energy and the field size, and the area out of the target should not be radiated at the dose of more than 15 Gy. The author believes that the information would contribute to safer and more effective application of intraoperative radiotherapy on malignant brain tumors. (J.P.N.) 63 refs

  7. Liquid biopsy for brain tumors

    Science.gov (United States)

    Shankar, Ganesh M.; Balaj, Leonora; Stott, Shannon L.; Nahed, Brian; Carter, Bob S.

    2018-01-01

    Introduction Minimally invasive methods will augment the clinical approach for establishing the diagnosis or monitoring treatment response of central nervous system tumors. Liquid biopsy by blood or cerebrospinal fluid sampling holds promise in this regard. Areas covered In this literature review, the authors highlight recent studies describing the analysis of circulating tumor cells, cell free nucleic acids, and extracellular vesicles as strategies to accomplish liquid biopsy in glioblastoma and metastatic tumors. The authors then discuss the continued efforts to improve signal detection, standardize the liquid biopsy handling and preparation, develop platforms for clinical application, and establish a role for liquid biopsies in personalized medicine. Expert commentary As the technologies used to analyze these biomarkers continue to evolve, we propose that there is a future potential to precisely diagnose and monitor treatment response with liquid biopsies. PMID:28875730

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

    African Journals Online (AJOL)

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

  9. MRI Brain Tumor Segmentation Methods- A Review

    OpenAIRE

    Gursangeet, Kaur; Jyoti, Rani

    2016-01-01

    Medical image processing and its segmentation is an active and interesting area for researchers. It has reached at the tremendous place in diagnosing tumors after the discovery of CT and MRI. MRI is an useful tool to detect the brain tumor and segmentation is performed to carry out the useful portion from an image. The purpose of this paper is to provide an overview of different image segmentation methods like watershed algorithm, morphological operations, neutrosophic sets, thresholding, K-...

  10. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference...... fever, headaches, nausea and vomiting, lethargy, and peritumoral edema. Out of 189 patients treated from 1973 to 2007, only five patients (3%) had severe and six patients (3%) had moderate adverse effects. One death was directly related to this treatment, where very high doses were used. Two patients...

  11. MR imaging of the brain: tumors

    International Nuclear Information System (INIS)

    Sartor, K.

    1999-01-01

    The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumor is MR imaging. A brain tumor can be reliably ruled out if the MR examination is performed properly and experts interpret the results as negative. If there is a tumor, however, its exact location and topography must be determined. Important for therapy and prognosis are also tumor properties such as histologic type and grade, as well as effects on adjacent brain structures. Although potentially a noninvasive method of in vivo neuropathology, MR is still far from being sufficiently specific, as dissimilar lesions may look the same despite the use of refined imaging protocols. The evolution of MR imaging continues, however, making further methodologic improvement likely. Presently, advanced methods, such as diffusion- and perfusion-weighted MR imaging, functional MR imaging, neuronavigation based on MR imaging data, and the use of MR imaging during surgery (intraoperative MR imaging), influence the way patients are treated. Likewise, follow-up imaging (monitoring) of tumor patients by MR has become more effective, and experience has shown how to distinguish reactive changes from recurrent tumor. In the future, MR imaging may gain importance in the development of novel therapeutic concepts. (orig.)

  12. Signs & Symptoms (of Brain Tumors)

    Science.gov (United States)

    ... memory are often more noticeable than effects on long-term memory. Memory terms to know Short-term memory : Short-term memory is where we ... process by which our brains move information from short-term to long-term memory. Retrieval: The process by which previously learned information ...

  13. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    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 pa-tients. 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.

  14. Peritumoral edema associated with metastatic brain tumor

    International Nuclear Information System (INIS)

    Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

    1992-01-01

    Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

  15. Radionecrosis after radiotherapy for brain tumor

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Tosa, Junichi; Tsuboi, Koji; Matsumura, Akira

    1984-01-01

    The neurological deterioration after radiotherapy of brain tumor may depend on radionecrosis or regrowth of the tumor. In the present study, five patients with brain tumor were irradiated with doses of 3,900 to 6,800 rads. The neurological deterioration appeared 3.5 to 46 months after radiotherapy in three patients, who received 5,000 to 5,680 rads, immediately after radiotherapy in one patient, who received 6,800 rads, and during radiotherapy in one patient, who received 3,900 rads. Ring enhancement was observed on sequential CT scans. This enhanced area was surgically removed and the correlation between histology and CT scans and superimposed dose distributions was studied in order to differentiate radionecrosis from regrowth of tumor. The radionecrosis was confirmed at the second operation in five patients, but regrowth of the tumor was also observed in the brain adjacent to radionecrosis in three out of five patients. Coagulation necrosis and fibrinoid necrosis were observed microscopically at the rim of the ring enhancement and necrotic and hyalinized debri were observed in the central low density area of the ring enhancement. Viable tumor cells were noted in the enhanced area adjacent to the ring enhancement on CT scans. Both radionecrosis and regrowth of tumor were observed in the dose distribution area of 3,500 to 6,120 rads on CT scans. This suggested that the superimposed dose distributions could not differentiate radionecrosis from tumor regrowth. Forty-eight cases of cerebral radionecrosis gathered from the literature were reviewed. (J.P.N.)

  16. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2016-04-01

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

  17. Computerized tomographic evaluation of primary brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Ok; Lee, Jong Soon; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song [Presbyterian Mediacal center, Cheonju (Korea, Republic of); Kim, Jong Deok [Inje Medical College, Paik Hospital, Pusan (Korea, Republic of)

    1985-10-15

    In a study of primary brain tumors 104 cases having satisfactory clinical, operative and histological proofs were analyzed by computerized tomography at Presbyterian Medical Center from May, 1982 to April 1985. The results were as follows: 1. The male to female ratio of primary brain tumor was 54 : 46. 2. The 2nd decade group (26%) was the most prevalent age group, followed by the 5th decade (16.3%), 1st decade (14.4%) , 3rd decade (12.5%), 4th decade (11.5%), 6th decade (10.6%), 7th decade (8.7%) in that order. 3. The incidence of primary brain tumors was found to be: glioma 64 cases (61.6%) among the GM, the most frequent 17 cases (16.3%), followed by meningioma 12 cases (11.5%), pituitary adenoma 10 cases (9.6%), craniopharyngioma 6 cases (5.8%), pinealoma and germinoma 3 cases (2.9%) respectively, and dermoid cyst 2 cases (1.9%) in that order. 4. The location of the primary brain tumors were as follows: cb. hemisphere (49%) of these 24.5% in parietal region, 11.9% in temporal region, 9.7% in frontal region, 3.0% in occipital region: juxtasella area (16.3%), cerebellar hemisphere (8.7%), parapineal and intraventricle (7.7%) respectively, cerebello-pontine angle area (5.8%), vermis and 4th ventricular region (4.8%). 5. There were no remarkable differences in the findings of pre- and post-contrast CT scanning of primary brain tumors computed with others.

  18. Gamma knife treatment of pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tatsuya; Kida, Yoshihisa; Tanaka, Takayuki; Oyama, Hirofumi (Komaki City Hospital, Hokkaido (Japan))

    1994-02-01

    Gamma knife radiosurgery was performed on 386 patients with intracranial lesions at Komaki City Hospital from May 1991 through December 1992. Forty three of the patients were under 15 years of age. Twenty six patients had arteriovenous malformations and 17 had brain tumors: 9 gliomas and 8 non-gliomatous tumors. The gliomas included 3 ependymomas, 2 benign astrocytomas, one ganglioglioma, one oligodendroglioma; one medulloblastoma and one glioblastoma multiforme. The non-gliomatous tumors included 3 pineal tumors, 2 craniopharyngiomas, 2 acoustic neurinomas, and one C-P angle epidermoid tumor. The male/female ratio was 12:5 and the mean diameter of the tumors was 19.3 mm. They were treated with a mean maximum dose of 32.5 Gy and a marginal dose of 17.1 Gy with a mean isocenter number of 4.9. The early results of single session treatment with Gamma knife of pediatric brain tumors were evaluated by repeated MRIs and changes of neurological signs during a mean follow-up period of 6.4 months. It was found that 5 of the 17 responded to treatment (29.5%), with partical response (PR) in 2 with craniopharyngioma and one with ganglioglioma. Central necrosis (CN) was present with optic glioma and one with neurinoma. In three patients (17.6%) the treatment was not effective. One with medulloblastoma and one with glioblastoma died at 4 and 6 months and the one with ependymoma was reoperated on after 3 months because of progression of the tumor (PG). The other nine patients (52.9%) were unchanged (NC). We must follow more patients to determine the effectiveness of gamma radiosurgery on these tumors. (author).

  19. Stereotactic gamma radiosurgery of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tatsuya; Kida, Yoshihisa; Tanaka, Takayuki; Oyama, Hirofumi; Yoshida, Kazuo; Maesawa, Satoshi; Kai, Osamu; Nakamura, Mototoshi; Arahata, Masashige [Komaki City Hospital, Aichi (Japan)

    1996-06-01

    One thousand cases with various head and neck diseases have been treated by gamma radiosurgery at Komaki City Hospital since May 1991. Five hundred and sixty-eight out of 1,000 cases were neoplastic lesions which consisted of 173 cases of neurinoma, 108 of metastatic tumors, 103 of meningioma, 69 of gliomas, 27 of pituitary adenoma, 26 of craniopharyngioma, 13 of pineal tumors, 11 of chordoma, 6 of malignant lymphoma, 5 of hemangioblastoma and so on. The most effective result has been shown in metastatic brain tumors. The complete response (disappearance of the lesion) was obtained in more than 50% of the treated lesions, and the control rate of 85% was maintained for more than 12 months. Next effective results were shown in craniopharyngioma, malignant pineal tumors and malignant lymphoma. There was a group which showed moderate response but no tumor disappearance. Those were pituitary adenoma, acoustic neurinoma, meningioma and chordoma. Gliomas showed less response and even progression of tumor at relatively higher rate. It has been found that malignant gliomas showed difficult control of the tumor and progression rate of 70%, while benign gliomas showed the control rate of more than 90%. Besides intracranial lesions, malignant skull base tumors such as chordoma, naso-pharyngeal cancer, adenoid cystic cancer showed better response to gamma radiosurgery and higher control rate for longer period of time with high QOL compaired to conventional irradiation. (author)

  20. Tumor-targeted nanomedicines for cancer theranostics

    Science.gov (United States)

    Lammers, Twan; Shi, Yang

    2017-01-01

    Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and the target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple different types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. PMID:27865762

  1. Delayed radiation necrosis of the brain simulating a brain tumor

    International Nuclear Information System (INIS)

    Ikeda, Hiroya; Kanai, Nobuhiro; Kamikawa, Kiyoo

    1976-01-01

    Two cases of delayed radiation necrosis of the brain are reported. Case 1 was a 50-year-old man who had right hemiparesis and disorientation 26 months after Linac irradiation (5,000 rad), preceded by an operation for right maxillar carcinoma. A left carotid angiogram demonstrated a left temporal mass lesion, extending to the frontal lobe. Case 2 was a 41-year-old man who had previously had an operation for right intraorbital plasmocytoma, followed by two Co irradiations (6,400 rad, and 5,000 rad). He had the signs and symptoms of intracranial hypertension 36 months after his last irradiation. A left carotid angiogram demonstrated a left temporal mass lesion. Both cases were treated by administration of steroid hormone (which alleviated the signs and symptoms) and by temporal lobectomy. Microscopic examinations showed necrosis of the brain tissues associated with hyaline degeneration of blood vessel walls and perivascular cell infiltration. The signs and symptoms of intracranial hypertension subsided postoperatively. Thirteen other cases the same as ours were collected from literature. They showed the signs and symptoms simulating a brain tumor (like a metastatic brain tumor) after irradiation to extracranial malignant tumors. Diagnosis of radiation necrosis was made by operation or autopsy. A follow-up for a long time is necessary, because the pathological changes in the brain may be progressive and extending in some cases, although decompressive operations for mass lesions give excellent results. (auth.)

  2. Stereotactic irradiation for metastatic brain tumor

    International Nuclear Information System (INIS)

    Nomura, Ryutaro

    2017-01-01

    First, this paper reviewed the latest findings of stereotactic irradiation (STI) for metastatic brain tumors. Then, it described the results of randomized controlled trials for single or a few (2-4) metastasis in the following comparison tests: (1) comparison between whole brain radiotherapy (WBRT) alone group and (WBRT + STI) group, (2) comparison between STI alone group and (STI + WBRT) group, (3) comparison between STI alone group and (tumorectomy + WBRT) group, (4) comparison between (STI + WBRT) group and (tumorectomy + WBRT) group, and (5) between (tumorectomy + WBRT) group and (tumorectomy + STI) group. Among these, STI alone without WBRT has obtained a certain consensus. Against multiple metastatic brain tumors of 5 or more, when considering cognitive impairment and QOL loss by adding WBRT, it is general consensus that STI alone may be sufficient. At the authors' institution, cyber knife (CK) was introduced in 2008 and nearly 300 stereotactic radiotherapy for metastatic brain tumors have been performed annually. By adopting a robot arm and development of a lesion tracking system, the positional correction against the deviation of the bone margin of the skull is guaranteed in real time to ensure accuracy during irradiation, and hypofractionated stereotactic irradiation becomes easier. (A.O.)

  3. Nanoparticle functionalization for brain targeting drug delivery and diagnostic

    DEFF Research Database (Denmark)

    Gomes, Maria João; Mendes, Bárbara; Martins, Susana

    2016-01-01

    carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery......Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have...... and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle...

  4. Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

    1987-01-01

    Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

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

    Science.gov (United States)

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

    2013-10-01

    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.

  6. A murine model of targeted infusion for intracranial tumors.

    Science.gov (United States)

    Kim, Minhyung; Barone, Tara A; Fedtsova, Natalia; Gleiberman, Anatoli; Wilfong, Chandler D; Alosi, Julie A; Plunkett, Robert J; Gudkov, Andrei; Skitzki, Joseph J

    2016-01-01

    Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

  7. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  8. Radiation treatment of brain tumors: Concepts and strategies

    International Nuclear Information System (INIS)

    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

  9. Spread of edema with brain tumors

    International Nuclear Information System (INIS)

    Hosoya, Takaaki

    1987-01-01

    Cerebral edema associated with brain tumors is visualized on CT as a hypodensity lesion involving mainly the white matter. The detailed features of its evolution were investigated in a review of CT examinations performed on 56 patients with brain tumors, with the following results. 1. The susceptibility to edema varied according to the types of fibers. Association fibers were more sensitive to edema than projection and commissural fibers. 2. The edema had a characteristic of spreading along not only the association fibers but also the projection and commissural fibers. 3. The spread of edema along the association fibers was interupted in sites of convergence of the fibers such as the external capsule and just beneath the central sulcus in the certrum semiovale. 4. In some cases with intra-axial tumors, the edema extended mainly in the projection and commissural fibers considered to be more resistant to it. For example, in cases with parietal and temporal intra-axial tumors, the posterior limb of the internal capsule was often more edematous than the external capsule. 5. The edema associated with meningioma had a characteristic of spreading mainly along the association fibers. When situated close to the corpus callosum, however, the commissural fibers were also involved. Edema extending mainly in the internal capsule, thus, was rarely observed in meningioma. 6. There was unique pattern of spread of edema in frontal tumors, which differentiated their CT pattern. Therefore, the location of the tumor could be correctly diagnosed by the pattern of the edema extension, even near the central sulcus or in the operculum region. (author)

  10. Cathepsin D and Its Prognostic Value in Neuroepithelial Brain Tumors

    OpenAIRE

    Pigac, Biserka; Dmitrović, Branko; Marić, Svjetlana; Mašić, Silvija

    2012-01-01

    Expression of Cathepsin D (Cath D) in some primary neuroepithelial brain tumors and its prognostic value were studied. The research included 65 samples of human primary neuroepithelial brain tumors. There were 50 glial tumors (10 diffuse astrocytomas (DA), 15 anaplastic astrocytomas (AA), 25 glioblastomas (GB), 15 embryonic tumors (15 medulloblastomas (MB) as well as 5 samples of normal brain tissue. Immunohistochemical method was applied to monitor diffuse positive reaction in the cytoplasm ...

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

    Science.gov (United States)

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

    2015-03-01

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

  12. Primary brain tumor presenting as intracranial hemorrhage

    International Nuclear Information System (INIS)

    Tsunoda, Shigeru; Sakaki, Toshisuke; Miyamoto, Seiji; Kyoi, Kikuo; Utsumi, Shozaburo; Kamada, Kitaro; Inui, Shoji; Masuda, Akio.

    1989-01-01

    Ten cases of primary brain tumor presenting as intracranial hemorrhage were studied in terms of the radiological and histological findings. The cases having hemorrhage in the tumor, as established through CT or histologically, were excluded if their onsets were not sudden due to intracranial hemorrhages. The results obtained may be summarized as follows: 1) From an anatomical point of view, cerebral subcortical hemorrhages account for 80%; hemorrhages in the cerebellopontine angle, 10%, and hemorrhages in the basal ganglia, 10%. 2) Plain CT findings showed perifocal low-density areas within 24 hours after onset in all 10 cases. 3) Enhanced CT findings showed enhanced areas in 4 or 6 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 5) From a histological point of view, glioblastomas account for 30%; malignant astrocytomas, 20%; astrocytomas, 20%; malignant ependymomas, 10%; hemangioblastoma, 10%, and transitional meningiomas, 10%. In conclusion, a perifocal low-density area on CT within 24 hours after onset is the most meaningful indication of intracranial hemorrhage originating from a brain tumor. A histological 'perinuclear halo' in an astrocytoma as an artifact due to hemorrhage may often be misleading in diagnosing mixed oligo-astrocytomas. (author)

  13. Non-FDG PET imaging of brain tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Zemin; GUAN Yihui; ZUO Chuantao; ZHANG Zhengwei; XUE Fangping; LIN Xiangtong

    2007-01-01

    Due to relatively high uptake of glucose in the brain cortex, the use of FDG PET imaging is greatly limited in brain tumor imaging, especially for low-grade gliomas and some metastatic tumours. More and more tracers with higher specificity were developed lately for brain tumor imaging. There are 3 main types of non-FDG PET tracers:amino acid tracers, choline tracers and nucleic acid tracers. These tracers are now widely applied in many aspects of brain tumor imaging. This article summarized the general use of non-FDG PET in different aspects of brain tumor imaging.

  14. Regional cerebral blood flow measurement in brain tumors

    International Nuclear Information System (INIS)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-01-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of 133 Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors. (author)

  15. Regional cerebral blood flow measurement in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-10-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of /sup 133/Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors.

  16. Intraoperative MRI in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  17. Intraoperative MRI in pediatric brain tumors

    International Nuclear Information System (INIS)

    Choudhri, Asim F.; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A.

    2015-01-01

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

  18. Photodynamic Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    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.

  19. Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

    Science.gov (United States)

    Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-05-01

    Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

  20. Target volumes in radiation therapy of childhood brain tumours

    International Nuclear Information System (INIS)

    Habrand, J.L.; Abdulkarim, B.; Beaudre, A.; El Khouri, M.; Kalifa, C.

    2001-01-01

    Pediatric tumors have enjoyed considerable improvements for the past 30 years. This is mainly due to the extensive use of combined therapeutical modalities in which chemotherapy plays a prominent role. In many children, local treatment including radiotherapy, can nowadays be adapted in terms of target volume and dose to the 'response' to an initial course of chemotherapy almost on a case by case basis. This makes precise recommendation on local therapy highly difficult in this age group. We will concentrate in this paper on brain tumors in which chemotherapy is of limited value and radiotherapy still plays a key-role. (authors)

  1. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

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

    2017-01-01

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

  2. Diagnosis and prognosis of brain tumors in clinical trials

    OpenAIRE

    Gorlia, Thierry

    2013-01-01

    textabstractAccording to the Central Brain Registry Of The United States (CBTRUS) statistical report (February 2012) the incidence rate of all primary non malignant and malignant brain and central nervous system tumors is 19.89 cases per 100.000 (11.58 for non-malignant tumors and 7.31 for malignant tumors). Malignant brain tumors account for only 1% to 2% of all adult cancers. As a comparison, in 2012, the incidence of women breast cancer was 121.2 (per 100.000). Tumors of neuroepithelial ti...

  3. Boron neutron capture therapy for malignant brain tumor in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yoshinobu [National Kagawa Children`s Hospital, Takamatsu, Kagawa (Japan)

    1998-03-01

    Since 1968, we have treated 149 patients and performed boron-neutron capture therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of tumor. The overall response rate in the glioma patients was 64%. Seven patients (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients (62%) of low grade astrocytoma lived more than 2 years Median survival time of glioblastoma was 640 days. Median survival times of patients with anaplastic astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT. Six patients lived more than 10 years. Histological grading, age of the patients, neutron fluence at the target point and target depth or size of the tumor were proved to be important factors. BNCT is an effective treatment for malignant brain tumors. We are now became able to radiate the tumor more correctly with a high enough dose of neutron beam even if we use thermal neutron beam. (author)

  4. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

    Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

  5. Obstacles to Brain Tumor Therapy: Key ABC Transporters

    Directory of Open Access Journals (Sweden)

    Juwina Wijaya

    2017-11-01

    Full Text Available The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in part, because of the inherent biological barrier, the blood–brain barrier. While its presence and role as a protector of the normal brain parenchyma has been acknowledged for decades, it is only recently that the important transporter components, expressed in the tightly knit capillary endothelial cells, have been deciphered. These transporters are ATP-binding cassette (ABC transporters and, so far, the major clinically important ones that functionally contribute to the blood–brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy of brain tumors or brain metastases is the blood–tumor barrier, where tumors erect a barrier of transporters that further impede drug entry. The expression and regulation of these two transporters at these barriers, as well as tumor derived alteration in expression and/or mutation, are likely obstacles to effective therapy.

  6. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  7. Magnetic resonance imaging in brain-stem tumors

    International Nuclear Information System (INIS)

    Nomura, Mikio; Saito, Hisazumi; Akino, Minoru; Abe, Hiroshi.

    1988-01-01

    Four patients with brain-stem tumors underwent magnetic resonance imaging (MRI) before and after radiotherapy. The brain-stem tumors were seen as a low signal intensity on T1-weighted images and as a high signal intensity on T2-weighted images. A tumor and its anatomic involvement were more clearly visualized on MRI than on cuncurrently performed CT. Changes in tumor before and after radiotherapy could be determined by measuring the diameter of tumor on sagittal and coronal images. This allowed quantitative evaluation of the reduction of tumor in association with improvement of symptoms. The mean T1 value in the central part of tumors was shortened in all patients after radiotherapy. The results indicate that MRI may assist in determining the effect of radiotherapy for brain-stem tumors. (Namekawa, K)

  8. Daily targeting of intrahepatic tumors for radiotherapy

    International Nuclear Information System (INIS)

    Balter, James M.; Brock, Kristy K.; Litzenberg, Dale W.; McShan, Daniel L.; Lawrence, Theodore S.; Haken, Randall Ten; McGinn, Cornelius J.; Lam, Kwok L.; Dawson, Laura A.

    2002-01-01

    Introduction: A system has been developed for daily targeting of intrahepatic tumors using a combination of ventilatory immobilization, in-room diagnostic imaging, and on-line setup adjustment. By reducing geometric position uncertainty, as well as organ movement, this system permits reduction of margins and thus potentially higher treatment doses. This paper reports our initial experience treating 8 patients with focal liver tumors using this system. Methods and Materials: The system includes diagnostic X-ray tubes mounted on the wall and ceiling of a treatment room, an active matrix flat panel imager, in-room control for image acquisition and setup adjustment, and a ventilatory immobilization system via active breathing control (ABC). Eight patients participated in the study, two using an early prototype ABC unit, and the remaining six with a commercial ABC system and improved setup measurement tools. Treatment margins were reduced, and dose consequently increased because of increased confidence in target position under this protocol. After daily setup via skin marks, orthogonal radiographs were acquired at suspended ventilation. The images were aligned to the CT model using the diaphragm for inferior-superior (IS) alignment, and the skeleton for left-right (LR) and anterior-posterior (AP) alignment. Adjustments were made for positioning errors greater than a threshold (3 or 5 mm). After treatment, retrospective analysis determined the final setup accuracy, as well as the error in initial setup measurement performed before setup adjustment. Results: Two hundred sixty-two treatment fractions were delivered on eight patients, with 171 treatments requiring repositioning. Typical treatment times were 25-30 min. Patients were able to tolerate ABC throughout the course of treatment. Breath holds up to 35 s long were used for treatment. The use of on-line imaging and setup adjustment reduced setup errors (σ) from 4.0 mm (LR), 6.7 mm (IS), and 3.8 mm (AP) to 2.1 mm (LR

  9. Anticonvulsant therapy in brain-tumor related epilepsy

    Directory of Open Access Journals (Sweden)

    Fröscher Walter

    2016-06-01

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

  10. Brain Tumor Trials Collaborative | Center for Cancer Research

    Science.gov (United States)

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

  11. Interphone study - on mobile phones and brain tumors

    International Nuclear Information System (INIS)

    2010-01-01

    Interphone study is the largest study on mobile phone use and risk of brain tumors that have been implemented. The study does not provide reliable answers to whether there is an increased risk of brain tumors using the mobile phone, but is an important contribution. (AG)

  12. Diagnosis and prognosis of brain tumors in clinical trials

    NARCIS (Netherlands)

    T.S. Gorlia (Thierry)

    2013-01-01

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

  13. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  14. Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

    Science.gov (United States)

    Wang, Denong; Wu, Lisa; Liu, Xiaohe

    2017-01-01

    We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

  15. Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy

    Institute of Scientific and Technical Information of China (English)

    Xiao Zhao; Rujing Chen; Mei Liu; Jianfang Feng; Jun Chen; Kaili Hu

    2017-01-01

    Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system(CNS) damage which endangers the patients’ lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier(BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix(ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.

  16. Imaging modalities in radiation treatment planning of brain tumors

    International Nuclear Information System (INIS)

    Georgiev, D.

    2009-01-01

    The radiation therapy is a standard treatment after surgery for most of malignant and some of benignant brain tumors. The restriction in acquiring local tumor control is an inability in realization of high dose without causing radiation necrosis in irradiated area and sparing normal tissues. The development of imaging modalities during the last years is responsible for better treatment results and lower early and late toxicity. Essential is the role of image methods not only in the diagnosis and also in the precise anatomical (during last years also functional) localisation, spreading of the tumor, treatment planning process and the effects of the treatment. Target delineation is one of the great geometrical uncertainties in the treatment planning process. Early studies on the use of CT in treatment planning documented that tumor coverage without CT was clearly inadequate in 20% of the patients and marginal in another 27 %. The image fusion of CT, MBI and PET and also the use of contrast materia helps to get over those restrictions. The use of contrast material enhances the signal in 10 % of the patients with glioblastoma multiform and in a higher percentage of the patients with low-grade gliomas

  17. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

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

  18. NMR relaxation times in human brain tumors (preliminary results)

    International Nuclear Information System (INIS)

    Benoist, L.; Certaines, J. de; Chatel, M.; Menault, F.

    1981-01-01

    Since the early work of Damadian in 1971, proton NMR studies of tumors has been well documented. Present study concerns the spin-lattice T 1 and spin-spin T 2 relaxation times of normal dog brain according to the histological differentiation and of 35 human benignant or malignant tumors. The results principally show T 2 important variations between white and gray substance in normal brain but no discrimination between malignant and benignant tumors [fr

  19. Preliminary study of MR elastography in brain tumors

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2008-01-01

    Objective: To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods: Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years) underwent brain MRE studies. Informed consent was obtained from all patients. A dedicated external force actuator for brain MRE study was developed. The actuator was fixed to the head coil. During scan, one side of the actuator was attached to the patients' head. Low frequency oscillation was produced by the actuator and caused shear waves propagating into brain tissue. The pulse sequence used in the study was phase-contrast gradient-echo sequence. Phase images of the brain were obtained and the shear waves within the brain were directly imaged. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity image. Consistency of brain tumors was evaluated at surgery and was classified as soft, intermediate, or hard with comparison to the white matter of the brain. Correspondence of MRE evaluation with operative results was studied. Results: The elastic modulus of the tumor was lower than that of white matter in 1 patient, higher in 11 patients, and similar in 2 patients. At surgery, the tumor manifested a soft consistency in 1 patient, hard consistency in 11 patients, intermediate consistency in 2 patients. The elasticity of tumors in 14 patients evaluated by MRE was correlated with the tumor consistency on the operation. Conclusion: MRE can noninvasively display the elasticity of brain tumors in vivo, and evaluate the brain tumor consistency before operation. (authors)

  20. Brain tumor radiosurgery. Current status and strategies to enhance the effect of radiosurgery

    International Nuclear Information System (INIS)

    Niranjan, A.; Lunsford, L.D.; Gobbel, G.T.; Kondziolka, D.; Maitz, A.; Flickinger, J.C.

    2000-01-01

    First, the current status of brain tumor radiosurgery is reviewed, and radiosurgery for brain tumors, including benign tumors, malignant tumors, primary glial tumors, and metastatic tumors, is described. Rapid developments in neuroimaging, stereotactic techniques, and robotic technology in the last decade have contributed to improved results and wider applications of radiosurgery. Radiosurgery has become the preferred management modality for many intracranial tumors, including schwannomas, meningiomas, and metastatic tumors. Although radiosurgery provides survival benefits in patients with diffuse malignant brain tumors, cure is still not possible. Microscopic tumor infiltration into surrounding normal tissue is the main cause of recurrence. Additional strategies are needed to specifically target tumor cells. Next, strategies to enhance the effect of radiosurgery are reviewed. Whereas the long-term clinical results of radiosurgery have established its role in the treatment of benign tumors, additional strategies are needed to improve cell killing in malignant brain tumors and to protect normal surrounding brain. The first strategy included the use of various agents to protect normal brain while delivering a high dose to the tumor cells, but finding an effective radioprotective agent has been problematic. Pentobarbital and 21-aminosteroid (21-AS) are presented as examples. The second strategy for radiation protection aimed at the repair of radiation-induced damage to the normal brain. The cause of radiation-induced breakdown of normal tissue is unclear. The white matter and the cerebral vasculature appear to be particularly susceptible to radiation. Oligodendrocytes and endothelial cells may be critical targets of radiation. The authors hypothesize that radiation-induced damage to these cell types can be repaired by neural stem cells. They also describe the use of tumor necrosis factor alpha (TNF-alpha) and neural stem cells as a means of enhancing the effect of

  1. [Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

    Science.gov (United States)

    Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

    2010-03-01

    Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  2. Detection of tumor recurrence using technetium99m-tetrofosmin brain SPECT in patients with previously irradiated brain tumors

    International Nuclear Information System (INIS)

    Llamas A; Reyes A; Uribe, L F; Martinez T

    2004-01-01

    Objective: to assess the clinical utility of brain SPECT with Tc-99m Tetrofosmin to differentiate between tumor recurrence and radionecrosis in patients with primary brain tumors previously treated with external beam radiotherapy. Materials and methods: thirteen patients with clinical or radiological suspicion of tumor recurrence were studied with brain SPECT using 20-mCi of Tc-99m Tetrofosmin. Obtained images were interpreted by consensus between two experienced observers and subsequently classified as positive or negative for tumor viability. Results were compared to those of conventional diagnostic imaging techniques. Diagnostic test values and 95% confidence intervals were quantified. Results: SPECT results included 7 true-positives, 5 true-negatives and 1 false negative result. Conclusions: Tc-99m Tetrofosmin brain SPECT night be a useful alternative to diagnose recurrent brain tumors, especially with non-conclusive clinical and radiological findings

  3. [The development of novel tumor targeting delivery strategy].

    Science.gov (United States)

    Gao, Hui-le; Jiang, Xin-guo

    2016-02-01

    Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

  4. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

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

    1991-01-01

    Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen...

  5. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    International Nuclear Information System (INIS)

    Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-01-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

  6. {sup 18}F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiaoyuan; Park, Ryan; Shahinian, Anthony H.; Tohme, Michel; Khankaldyyan, Vazgen; Bozorgzadeh, Mohammed H.; Bading, James R.; Moats, Rex; Laug, Walter E.; Conti, Peter S. E-mail: pconti@usc.edu

    2004-02-01

    Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin {alpha}{sub v}{beta}{sub 3} is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled {alpha}{sub v}{beta}{sub 3}-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate through the side-chain {epsilon}-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[{sup 18}F]fluorobenzoyl-RGD ([{sup 18}F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/{mu}mol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [{sup 18}F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[{sup 18}F]fluorobenzoyl labeled cyclic RGD peptide [{sup 18}F]FB-RGD is a potential tracer for imaging {alpha}{sub v}{beta}{sub 3}-integrin positive tumors in brain and other anatomic locations.

  7. Functional imaging for brain tumors (perfusion, DTI and MR spectroscopy)

    International Nuclear Information System (INIS)

    Essig, M.; Giesel, F.; Stieltjes, B.; Weber, M.A.

    2007-01-01

    This contribution considers the possibilities involved with using functional methods in magnetic resonance imaging (MRI) diagnostics for brain tumors. Of the functional methods available, we discuss perfusion MRI (PWI), diffusion MRI (DWI and DTI) and MR spectroscopy (H-MRS). In cases of brain tumor, PWI aids in grading and better differentiation in diagnostics as well as for pre-therapeutic planning. In addition, the course of treatment, both after chemo- as well as radiotherapy in combination with surgical treatment, can be optimized. PWI allows better estimates of biological activity and aggressiveness in low grade brain tumors, and in the case of WHO grade II astrocytoma showing anaplastically transformed tumor areas, allows more rapid visualization and a better prediction of the course of the disease than conventional MRI diagnostics. Diffusion MRI, due to the directional dependence of the diffusion, can illustrate the course and direction of the nerve fibers, as well as reconstructing the nerve tracts in the cerebrum, pons and cerebellum 3-dimensionally. Diffusion imaging can be used for describing brain tumors, for evaluating contralateral involvement and the course of the nerve fibers near the tumor. Due to its operator dependence, DTI based fiber tracking for defining risk structures is controversial. DWI can also not differentiate accurately between cystic and necrotic brain tumors, or between metastases and brain abscesses. H-MRS provides information on cell membrane metabolism, neuronal integrity and the function of neuronal structures, energy metabolism and the formation of tumors and brain tissue necroses. Diagnostic problems such as the differentiation between neoplastic and non-neoplastic lesions, grading cerebral glioma and distinguishing between primary brain tumors and metastases can be resolved. An additional contribution will discuss the control of the course of glial tumors after radiotherapy. (orig.)

  8. Differential diagnostic value of diffusion weighted imaging on brain abscess and necrotic or cystic brain tumors

    International Nuclear Information System (INIS)

    Zhang Xiaoya; Yin Jie; Wang Kunpeng; Zhang Jiandang; Liang Biling

    2009-01-01

    Objective: To investigate the value of diffusion weighted imaging (DWI)on brain abscess and necrotic or cystic brain tumors. Methods: 27 cases with brain abscesses and 33 cases with necrotic or cystic brain tumors (gliomas or metastases) were performed conventional MRI and DWI. Apparent diffusion coefficient (ADC) of region of interest (ROI) was measured and statistically tested. Sensitivity and specificity were calculated and compared with conventional MR and DWI. Results: Hyperintensity signal was seen on most brain abscesses. All necrotic or cystic brain tumors showed hypointensity signal on DWI. There was statistical significance on ADC of them. The sensitivity and specificity of conventional MRI was lower than that of DWI. Conclusion: DWI and ADC were useful in distinguishing brain abscessed from necrotic or cystic brain tumors, which was important in addition to conventional MRI. (authors)

  9. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

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

    OpenAIRE

    Bhowmik, Arijit; Khan, Rajni; 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 n...

  11. Uncertainces in tumor target definition using PET

    International Nuclear Information System (INIS)

    Kirov, A.

    2013-01-01

    Full text: Introduction: PET entered into the clinics for radiation therapy as a means of displaying the metabolically active part of the tumor. However this advantage, PET has a number of shortcomings that prevent its use for precise determination of the tumor boundaries. What you will learn: The aim of the lecture is to present: the requirements for the accuracy of the determination of tumor boundaries in radiation therapy; the main phenomena which bring uncertainty using PET and a brief overview of methods for segmentation of tumors and their problems

  12. Sequential computed tomographic imaging of a transplantable rabbit brain tumor

    International Nuclear Information System (INIS)

    Kumar, A.J.; Rosenbaum, A.E.; Beck, T.J.; Ahn, H.S.; Anderson, J.

    1986-01-01

    The accuracy of CT imaging in evaluating VX-2 tumor growth in the rabbit brain was assessed. CT scanning was performed in 5 outbred New Zealand white male rabbits before and at 4, 7, 9 and 13 (in 3 animals) days after surgical implantation of 3 x 10 5 viable VX-2 tumor cells in the frontoparietal lobes. The CT studies were correlated with gross pathology in each. The tumor was visualized with CT in all 5 rabbits by the 9th day post implantation when the tumor ranged in size from 4-6 x 3-4 x 2-3 mm. Between the 9th and 13th day, the tumor increased 6-fold in two rabbits and 12-fold in the third rabbit. CT is a useful technique to evaluate brain tumor growth in this model and should be valuable in documenting the efficacy of chemotherapy on tumor growth. (orig.)

  13. Local recurrence of metastatic brain tumor after surgery

    International Nuclear Information System (INIS)

    Shinoura, Nobusada; Yamada, Ryoji; Okamoto, Koichiro; Nakamura, Osamu; Shitara, Nobuyuki; Karasawa, Katsuyuki

    2006-01-01

    We analyzed factors associated with the local recurrence of brain metastases after surgery. Forty-seven patients with 67 metastatic brain tumors underwent surgery between 1994 and 2001. The survival time in the ''no recurrence'' group (34.7 months) was significantly longer than that in the recurrence group (21.9 months) (p=0.0008; log rank test). The factors affecting the local recurrence of brain metastases after surgery were as follows: cyst (p=0.0156), dural invasion (p=0.0029) of tumors, failure to totally remove tumors (p=0.0040), and lack of post-surgical irradiation (p<0.0001). Sex, age, tumor histology, tumor size, pre-surgical radiation, dose (≥45 vs <45, ≥50 vs <50 Gy) and the method (local vs whole brain) of post-surgical radiation did not affect the local recurrence rate of brain metastases after surgery. To avoid early recurrences of metastatic brain tumors, the factors associated with local recurrence should be considered in providing optimal treatment of tumors by surgery. (author)

  14. Usefulness of dynamic magnetic resonance imaging in brain tumors

    International Nuclear Information System (INIS)

    Joo, Yang Gu; Suh, Soo Jhi; Zeon, Seok Kil; Woo, Sung Ku; Kim, Hong; Kim, Jung Sik; Lee, Sung Moon; Lee, Hee Jung; Takahashi, Mutsumasa

    1994-01-01

    To investigate the usefulness of dynamic MR imaging in the differential diagnosis of brain tumors. Dynamic MR imaging was performed in 43 patients with histopathologically proved brain tumors. Serial images were sequentially obtained every 30 seconds for 3-5 minutes with use of spin-echo technique(TR 200msec/TE 15msec) after rapid injection of Gd-DTPA in a dose of 0.1mmol/kg body weight. Dynamics of contrast enhancement of the brain tumors were analyzed visually and by the sequential contrast enhancement ratio(CER). On the dynamic MR imaging, contrast enhancement pattern of the gliomas showed gradual increase in signal intensity(SI) till 180 seconds and usually had a longer time to peak of the CER. The SI of metastatic brain tumors increased steeply till 30 seconds and then rapidly or gradually decreased and the tumors had a shorter time to peak of the CER. Meningiomas showed a rapid ascent in SI till 30 to 60 seconds and then made a plateau or slight descent of the CER. Lymphomas and germinomas showed relatively rapid increase of SI till 30 seconds and usually had a longer time peak of the CER. Dynamic MR imaging with Gd-DTPA may lead to further information about the brain tumors as the sequential contrast enhancement pattern and CER parameters seem to be helpful in discriminating among the brain tumors

  15. Application of 31P MR spectroscopy to the brain tumors

    International Nuclear Information System (INIS)

    Ha, Dong Ho; Choi, Sun Seob; Oh, Jong Young; Yoon, Seong Kuk; Kang, Myong Jin; Kim, Ki Uk

    2013-01-01

    To evaluate the clinical feasibility and obtain useful parameters of 3 1P magnetic resonance spectroscopy (MRS) study for making the differential diagnosis of brain tumors. Twenty-eight patients with brain tumorous lesions (22 cases of brain tumor and 6 cases of abscess) and 11 normal volunteers were included. The patients were classified into the astrocytoma group, lymphoma group, metastasis group and the abscess group. We obtained the intracellular pH and the metabolite ratios of phosphomonoesters/phosophodiesters (PME/PDE), PME/inorganic phosphate (Pi), PDE/Pi, PME/adenosine triphosphate (ATP), PDE/ATP, PME/phosphocreatine (PCr), PDE/PCr, PCr/ATP, PCr/Pi, and ATP/Pi, and evaluated the statistical significances. The brain tumors had a tendency of alkalization (pH = 7.28 ± 0.27, p = 0.090), especially the pH of the lymphoma was significantly increased (pH = 7.45 ± 0.32, p = 0.013). The brain tumor group showed increased PME/PDE ratio compared with that in the normal control group (p 0.012). The ratios of PME/PDE, PDE/Pi, PME/PCr and PDE/PCr showed statistically significant differences between each brain lesion groups (p 1 'P MRS, and the pH, PME/PDE, PDE/Pi, PME/PCr, and PDE/PCr ratios are helpful for differentiating among the different types of brain tumors.

  16. Tumor and target delineation: current research and future challenges

    International Nuclear Information System (INIS)

    Austin-Seymour, Mary; Chen, George T.Y.; Rosenman, Julian; Michalski, Jeff; Lindsley, Karen; Goitein, Michael

    1995-01-01

    In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target. The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties

  17. Clinical results of BNCT for malignant brain tumors in children

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

    2009-01-01

    It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

  18. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, Antonios (ed.)

    2011-07-01

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

  20. Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors

    OpenAIRE

    Sun, Tao; Warrington, Nicole M; Rubin, Joshua B

    2012-01-01

    Abstract It is often reported that brain tumors occur more frequently in males, and that males suffer a worse outcome from brain tumors than females. If correct, these observations suggest that sex plays a fundamental role in brain tumor biology. The following review of the literature regarding primary and metastatic brain tumors, reveals that brain tumors do occur more frequently in males compared to females regardless of age, tumor histology, or region of the world. Sexually dimorphic mecha...

  1. Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model

    Science.gov (United States)

    On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.

    2013-01-01

    The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

  2. Brain tumor and CT, 1. Relationship between the consistency of a brain tumor and the CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, N.; Katada, K.; Shinomiya, Y.; Sano, H.; Kanno, T. (Fujita Gakuen Univ., School of Medicine, Toyoake, Aichi (Japan))

    1981-08-01

    It is very important for a neurosurgeon to know the consistency of a brain tumor preoperatively, since the information is of much use in indicating the likely difficulty of the operation, which operative tools should be selected, the amount of bleeding to be expected from the tumor, and so on. The authors, therefore, tried to evaluate the consistency of brain tumors preoperatively. Twenty-seven cases in which the margin of the tumor was made clear with a homogeneous stain were studied concerning the relationship between the tumor consistency and the CT findings. The results are as follows: 1) A higher CT number on a plain CT indicated a harder consistency of the tumor. 2) A lesser contrast index (CT number on enhancement CT/CT number on plain CT) showed a harder consistency of the tumor.

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

    Science.gov (United States)

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

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

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

    Directory of Open Access Journals (Sweden)

    Yacoob Sulafa M

    2012-08-01

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

  5. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    Directory of Open Access Journals (Sweden)

    Rossmeisl JH

    2017-04-01

    Full Text Available John H Rossmeisl,1–3 Kelli Hall-Manning,4 John L Robertson,1,3,5 Jamie N King,1,2 Rafael V Davalos,3,5 Waldemar Debinski,3 Subbiah Elankumaran6,† 1Veterinary and Comparative Neuro-Oncology Laboratory, 2Department of Small Animal Clinical Sciences, 3The Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC, 4Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, 5Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA†The authors regret to advise of the passing of Dr Subbiah Elankumaran prior to publicationBackground: The expression of the urokinase plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA, have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs.Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real

  6. Pet imaging of peripheral benzodiazepine binding sites in brain tumors

    International Nuclear Information System (INIS)

    Junck, L.; Jewett, D.M.; Olsen, J.M.; Kilbourn, M.R.; Koeppe, R.A.; Young, A.B.; Greenberg, H.S.; Kuhl, D.E.

    1991-01-01

    Studies in vitro have shown that the peripheral-type benzodiazepine binding site (PBBS) is present in moderate to high density on malignant gliomas as well as in areas of reactive gliosis, but in low density in normal brain. PK 11195 is an isoquinoline derivative that binds selectively to the PBBS but not to the central benzodiazepine receptor. We have used [ 11 C]PK 11195 with positron emission tomography (PET) to study brain tumors and cerebral infarcts. Preliminary results showed that, in 13 of 18 patients with astrocytomas, [ 11 C]PK 11195 radioactivity was increased in tumor compared to remote brain and that the concentration ratios of tumor-to-remote brain were higher for high grade astrocytomas than for low grade astrocytomas. Pharmacokinetic analysis suggests that the increased activity in tumor probably does not result from alterations in blood flow or vascular permeability. Patients with lymphoma, meningioma, medulloblastoma, brain metastasis, and neurosarcoidosis have also shown increased radioactivity in tumor. Among eight patients with acute and subacute cerebral infarcts, activity in the infarct was increased in seven and was often greatest at the periphery. We conclude that [ 11 C]PK 11195 is a promising radiopharmaceutical for further investigation of brain tumors as well as diseases characterized by reactive gliosis

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

    Science.gov (United States)

    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.

  8. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    Directory of Open Access Journals (Sweden)

    Liya Zhao

    2016-01-01

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

  9. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

    Science.gov (United States)

    Zhao, Liya; Jia, Kebin

    2016-01-01

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

  10. Preclinical models to study the impact of the blood-brain barrier in brain tumor chemotherapy

    NARCIS (Netherlands)

    Vries, N.A. de

    2009-01-01

    High-grade gliomas, in particular Glioblastoma Multiforme (GBM), are the most common primary brain tumors in adults and among the deadliest of human cancers. Their location and the extensively infiltrative character of tumor cells into surrounding normal brain structures is an impediment for all

  11. Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery.

    Science.gov (United States)

    Volak, Adrienn; LeRoy, Stanley G; Natasan, Jeya Shree; Park, David J; Cheah, Pike See; Maus, Andreas; Fitzpatrick, Zachary; Hudry, Eloise; Pinkham, Kelsey; Gandhi, Sheetal; Hyman, Bradley T; Mu, Dakai; GuhaSarkar, Dwijit; Stemmer-Rachamimov, Anat O; Sena-Esteves, Miguel; Badr, Christian E; Maguire, Casey A

    2018-05-16

    The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

  12. [Neuronavigator-guided microsurgery for resection of brain tumors].

    Science.gov (United States)

    Zhang, Xiang; Zhang, Jianning; Fei, Zhou; Wu, Jingwen; Fu, Luoan; Qu, Yan; Liu, Weiping; Wang, Zhanxiang; Yang, Lisun; He, Xiaosheng; Zhen, Haining; Gao, Dakuan; Cao, Weidong; Liang, Jingwen

    2002-02-25

    To study locating accuracy for the brain tumors and their peri-structures by the neuronavigator and elucidate the microsurgical effects. 65 patients with intracranial tumors were microsurgically treated by the application of Stealth Station and Vector Vision system. The treatment effects were summarized and the neuronavigational accuracy was discussed. After mean fiducial error (MFE) and sustained accuracy (SA) were satisfied. Total tumor removal was achieved in 63 cases (97.0%), subtotal removal in 2 cases (3.0%). The neurological functions were improved in 56 cases (86.2%), unchanged obviously in 9 cases (13.8%). No case deteriorated and died in the group. Navigation systems are reliable and accurate in making microneurosurgical plans for brain tumors. And they can provide tracing of the tumor in the operation and guide the operator's manipulation. The techniques, which help total removal of the tumors and reduce the postoperative complications, are very useful in guarantee operation effects.

  13. Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

    Science.gov (United States)

    Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

    2018-01-01

    Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

  14. PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

    Science.gov (United States)

    Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

    2016-11-01

    Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    Science.gov (United States)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  16. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Dittmann, Florian; Le, Matthieu; Shih, Helen A; Menze, Bjoern H; Ayache, Nicholas; Konukoglu, Ender

    2014-01-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher–Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

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

    Science.gov (United States)

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

    2017-10-17

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

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

    Science.gov (United States)

    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

  19. Clinical impact of anatomo-functional evaluation of brain function during brain tumor surgery

    International Nuclear Information System (INIS)

    Mikuni, Nobuhiro; Kikuchi, Takayuki; Matsumoto, Atsushi; Yokoyama, Yohei; Takahashi, Jun; Hashimoto, Nobuo

    2009-01-01

    To attempt to improve surgical outcome of brain surgery, clinical significance of anatomo-functional evaluation of brain function during resection of brain tumors was assessed. Seventy four patients with glioma located near eloquent areas underwent surgery while awake. Intraoperative tractography-integrated functional neuronavigation and cortical/subcortical electrical stimulation were correlated with clinical symptoms during and after resection of tumors. Cortical functional areas were safely removed with negative electric stimulation and eloquent cortices could be removed in some circumstances. Subcortical functional mapping was difficult except for motor function. Studying cortical functional compensation allows more extensive removal of brain tumors located in the eloquent areas. (author)

  20. Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells.

    Science.gov (United States)

    Schneider, Craig S; Perez, Jimena G; Cheng, Emily; Zhang, Clark; Mastorakos, Panagiotis; Hanes, Justin; Winkles, Jeffrey A; Woodworth, Graeme F; Kim, Anthony J

    2015-02-01

    A major limitation in the treatment of glioblastoma (GBM), the most common and deadly primary brain cancer, is delivery of therapeutics to invading tumor cells outside of the area that is safe for surgical removal. A promising way to target invading GBM cells is via drug-loaded nanoparticles that bind to fibroblast growth factor-inducible 14 (Fn14), thereby potentially improving efficacy and reducing toxicity. However, achieving broad particle distribution and nanoparticle targeting within the brain remains a significant challenge due to the adhesive extracellular matrix (ECM) and clearance mechanisms in the brain. In this work, we developed Fn14 monoclonal antibody-decorated nanoparticles that can efficiently penetrate brain tissue. We show these Fn14-targeted brain tissue penetrating nanoparticles are able to (i) selectively bind to recombinant Fn14 but not brain ECM proteins, (ii) associate with and be internalized by Fn14-positive GBM cells, and (iii) diffuse within brain tissue in a manner similar to non-targeted brain penetrating nanoparticles. In addition, when administered intracranially, Fn14-targeted nanoparticles showed improved tumor cell co-localization in mice bearing human GBM xenografts compared to non-targeted nanoparticles. Minimizing non-specific binding of targeted nanoparticles in the brain may greatly improve the access of particulate delivery systems to remote brain tumor cells and other brain targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Polymeric micelles as a drug carrier for tumor targeting

    Directory of Open Access Journals (Sweden)

    Neha M Dand

    2013-01-01

    Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

  2. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  3. Gamma knife radiosurgery for metastatic brain tumors from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

    2003-01-01

    The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

  4. Tumor target amplification: Implications for nano drug delivery systems.

    Science.gov (United States)

    Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

    2018-04-10

    Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Bridging from Brain to Tumor Imaging: (S-(−- and (R-(+-[18F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Mathias Kranz

    2018-03-01

    Full Text Available Sigma-1 receptors (Sig1R are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S-(−- and (R-(+-[18F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously implanted tumors. Therefore, a brain tumor model (U87-MG with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [18F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB.

  6. Evolution of Brain Tumor and Stability of Geometric Invariants

    Directory of Open Access Journals (Sweden)

    K. Tawbe

    2008-01-01

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

  7. Awake craniotomy for brain tumor: indications, technique and benefits.

    Science.gov (United States)

    Dziedzic, Tomasz; Bernstein, Mark

    2014-12-01

    Increasing interest in the quality of life of patients after treatment of brain tumors has led to the exploration of methods that can improve intraoperative assessment of neurological status to avoid neurological deficits. The only method that can provide assessment of all eloquent areas of cerebral cortex and white matter is brain mapping during awake craniotomy. This method helps ensure that the quality of life and the neuro-oncological result of treatment are not compromised. Apart from the medical aspects of awake surgery, its economic issues are also favorable. Here, we review the main aspects of awake brain tumor surgery. Neurosurgical, neuropsychological, neurophysiological and anesthetic issues are briefly discussed.

  8. Factors affecting intellectual outcome in pediatric brain tumor patients

    International Nuclear Information System (INIS)

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

    1987-01-01

    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

  9. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress

    NARCIS (Netherlands)

    Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.; Hennink, W.E.; Storm, Gerrit

    2012-01-01

    Abstract Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells,

  10. Neuroradiolological diagnosis and follow-up of brain tumors

    International Nuclear Information System (INIS)

    Kummer, R. von

    1997-01-01

    Primary tumors of the brain and cerebral metastases cause considerable morbidity and mortality. To assess the chance for cure and to develop a valid concept of treatment, the exact assessment of the tumor's location, of the tumor's borders and malignancy is essential. Today, neuroradiological examination mainly with magnetic resonance imaging (MRI) allows an almost histological diagnosis and description of the tumor's extent. MRI is as well useful for studying the patient's short- and long-term follow-up clinical course. This is illustrated by 3 case histories. (orig.)

  11. MR imaging assisted radiation therapy planning of brain tumors

    International Nuclear Information System (INIS)

    Just, M.; Roesler, H.P.; Higer, H.P.; Kutzner, J.; Thelen, M.

    1990-01-01

    This paper reports on the improvement of the accuracy of treatment portals in radiation therapy of brain tumors with use of MR imaging. After proper processing, the parasagittal MR image showing the largest tumor size and the midline sagittal image were superimposed. With common anatomic landmarks of midline tomogram and lateral simulation radiograph, commensurate reference grids were laid over both images in identical positions. Tumor coordinates were then transferred from the synthesized MR image to the lateral radiograph. Rectangular fields or individual shielding blocks encompassing the tumor could be drawn directly. This new method was used in 17 patients, and results were compared with CT-assisted results

  12. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  13. Brain and Spinal Tumors: Hope through Research

    Science.gov (United States)

    ... arm or leg. A sudden, marked change in handwriting may be a sign of a tumor. Balance ... coordination and balance, mental status, and changes in mood or behavior, among other abilities. Some tests require ...

  14. Targeting DNA Methyltranferases in Urological Tumors

    Directory of Open Access Journals (Sweden)

    Ângela Marques-Magalhães

    2018-04-01

    Full Text Available Urological cancers are a heterogeneous group of malignancies accounting for a considerable proportion of cancer-related morbidity and mortality worldwide. Aberrant epigenetic traits, especially altered DNA methylation patterns constitute a hallmark of these tumors. Nonetheless, these alterations are reversible, and several efforts have been carried out to design and test several epigenetic compounds that might reprogram tumor cell phenotype back to a normal state. Indeed, several DNMT inhibitors are currently under evaluation for therapeutic efficacy in clinical trials. This review highlights the critical role of DNA methylation in urological cancers and summarizes the available data on pre-clinical assays and clinical trials with DNMT inhibitors in bladder, kidney, prostate, and testicular germ cell cancers.

  15. Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

    International Nuclear Information System (INIS)

    Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

    1987-01-01

    In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

  16. Computational Modeling of Medical Images of Brain Tumor Patients for Optimized Radiation Therapy Planning

    DEFF Research Database (Denmark)

    Agn, Mikael

    In brain tumor radiation therapy, the aim is to maximize the delivered radiation dose to the targeted tumor and at the same time minimize the dose to sensitive healthy structures – so-called organs-at-risk (OARs). When planning a radiation therapy session, the tumor and the OARs therefore need...... to be delineated on medical images of the patient’s head, to be able to optimize a radiation dose plan. In clinical practice, the delineation is performed manually with limited assistance from automatic procedures, which is both time-consuming and typically suffers from poor reproducibility. There is, therefore...

  17. Groupwise registration of MR brain images with tumors

    Science.gov (United States)

    Tang, Zhenyu; Wu, Yihong; Fan, Yong

    2017-09-01

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

  18. Treatment of malignant brain tumor. Today and tomorrow. Image-guided neurosurgery for brain tumor. A current perspective

    International Nuclear Information System (INIS)

    Kajita, Yasukazu; Fujii, Masazumi; Yoshida, Jun; Maesawa, Satoshi

    2008-01-01

    Although usefulness of the image-guided neurosurgery is well documented, there are scarce facilities having the actually operating system in Japan. Since 2006, authors' Nagoya University Hospital has had an operating room named ''Brain THEATER'', where an open MRI system APERTO (Hitachi-Medical Co.) and a navigation system Vector Vision (BrainLAB) are connected to conduct the complete image-guided neurosurgery for brain tumor by using the intraoperative MRI for continuously updating the residual tumor tissue to be dissected out. The room is pre- and intra-operatively supported by Departments of image analysis and of radiation technology in the University, and as well, is connected by net-working with another image-guided surgical room ''Brain Suite'' (Siemens 1.5 T MRI system: BrainLAB) in the neighboring facility, Nagoya Central Hospital. This paper describes the circumstances of the introduction of these systems in the Hospital, details of the image-guided surgery in the operation rooms with illustration of actual photos of the rooms and of pre-, intra- and post-operative images, outcomes of image-guided neurosurgery for brain tumor reported hitherto, image-guided neurosurgery for brain tumor's future perspectives involving robotic surgery and operation on the virtual 3D image including the net-worked one. Efforts should be made to further spread the system for performing the more non-invasive and precise surgery, and for conducting the diagnosis united with treatment. (R.T.)

  19. Performance Analysis of Unsupervised Clustering Methods for Brain Tumor Segmentation

    Directory of Open Access Journals (Sweden)

    Tushar H Jaware

    2013-10-01

    Full Text Available Medical image processing is the most challenging and emerging field of neuroscience. The ultimate goal of medical image analysis in brain MRI is to extract important clinical features that would improve methods of diagnosis & treatment of disease. This paper focuses on methods to detect & extract brain tumour from brain MR images. MATLAB is used to design, software tool for locating brain tumor, based on unsupervised clustering methods. K-Means clustering algorithm is implemented & tested on data base of 30 images. Performance evolution of unsupervised clusteringmethods is presented.

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

    Directory of Open Access Journals (Sweden)

    Arijit Bhowmik

    2015-01-01

    Full Text Available 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.

  1. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

    Science.gov (United States)

    Lammers, Twan; Kiessling, Fabian; Hennink, Wim E; Storm, Gert

    2012-07-20

    Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Untapped Therapeutic Targets in the Tumor Microenvironment

    Science.gov (United States)

    2017-08-01

    that harbors the resistant cancer cells is simultaneously targeted. Since activated carcinoma-associated fibroblasts (CAFs) have a prominent role in...epithelial cells (IOSE) or HEYA8 epithelial ovarian cancer cells (EOC) using a Transwell membrane. Inverse -log2 values of the Robust Multi-array Average...barrier for drug transport. Thus, simultaneous targeting of CAFs and cancer cells may be necessary for chemotherapeutic accessibility. To identify

  3. A noninvasive multimodal technique to monitor brain tumor vascularization

    Science.gov (United States)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

    2007-09-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

  4. A noninvasive multimodal technique to monitor brain tumor vascularization

    International Nuclear Information System (INIS)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E

    2007-01-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present

  5. Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Hanneke Korsten

    Full Text Available Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m developed at older age (>10m into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC, adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK, and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1 and tumor class 2 (TC2. TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor

  6. Photon spectrum and absorbed dose in brain tumor

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  7. Photon spectrum and absorbed dose in brain tumor.

    Science.gov (United States)

    Vega-Carrillo, Hector Rene; Silva-Sanchez, Angeles; Rivera-Montalvo, Teodoro

    2016-11-01

    Using Monte Carlo methods a BOMAB phantom inside a treatment hall with a brain tumor nearby the pituitary gland was treated with photons produced by a Varian 6MV linac. The photon spectrum and the absorbed dose were calculated in the tumor, pituitary gland and the head. The treatment beam was collimated to illuminate only the tumor volume; however photons were noticed in the gland. Photon fluence reaching the tumor is and 15.7 times larger than the fluence in the pituitary gland, on the other hand the absorbed dose in the tumor is 37.1 times larger than the dose in the gland because photons that reach the pituitary gland are scattered, by the head and the tumor, through Compton effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Photon spectrum and absorbed dose in brain tumor

    International Nuclear Information System (INIS)

    Silva S, A.; Vega C, H. R.; Rivera M, T.

    2015-10-01

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

  9. Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

    1979-01-01

    C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

  10. Brain mapping in tumors: intraoperative or extraoperative?

    Science.gov (United States)

    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. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  11. Regional cerebral blood flow in the patient with brain tumor

    International Nuclear Information System (INIS)

    Tsuchida, Shohei

    1993-01-01

    Regional cerebral blood flow (rCBF) was measured with xenon-enhanced CT (Xe-CT) in 21 cases of intracranial tumors (13 meningiomas, 5 gliomas, 3 metastatic brain tumors). Peritumoral edema was graded as mild, moderate or severe based on the extent of edema on CT and MRI. According to intratumoral blood flow distribution patterns, three patterns were classified as central type with relatively high blood flow at the center of the tumor, homogeneous type with an almost homogeneous blood flow distribution, and marginal type with relatively high blood flow at the periphery of the tumor. High grade astrocytoma and metastatic brain tumor showed marginal type blood flow and moderate or severe edema except in one case. Five meningiomas with severe peritumoral edema revealed marginal type blood flow and four with mild peritumoral edema showed central type blood flow, except for one case. No correlation was found between the extent of peritumoral edema and histological subtype, tumor size, location, duration of clinical history, vascularization on angiogram, and mean blood flow in the tumor. These results suggest that blood flow distribution patterns within the tumor may affect the extension of peritumoral edema. Pre- and postoperative rCBFs were evaluated with Xe-CT and IMP-SPECT in 7 cases, mean rCBF of peritumoral edema was 6.2 ml/100 g/min preoperatively, and discrepancy between rCBF on Xe-CT and that on IMP-SPECT was shown in the remote cortical region ipsilateral to the tumor. Postoperative rCBF revealed an improved blood flow in both adjacent and remote areas, suggesting that the decreased blood flow associated with brain tumors might be relieved after surgery. (author) 53 refs

  12. Characterization of TEM1/endosialin in human and murine brain tumors

    International Nuclear Information System (INIS)

    Carson-Walter, Eleanor B; Walter, Kevin A; Winans, Bethany N; Whiteman, Melissa C; Liu, Yang; Jarvela, Sally; Haapasalo, Hannu; Tyler, Betty M; Huso, David L; Johnson, Mahlon D

    2009-01-01

    TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models. In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice. TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts. TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1

  13. Recent technological advances in pediatric brain tumor surgery.

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    V. S. Khalilov

    2015-01-01

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

  15. The impact of dietary isoflavonoids on malignant brain tumors

    International Nuclear Information System (INIS)

    Sehm, Tina; Fan, Zheng; Weiss, Ruth; Schwarz, Marc; Engelhorn, Tobias; Hore, Nirjhar; Doerfler, Arnd; Buchfelder, Michael; Eyüpoglu, IIker Y; Savaskan, Nic E

    2014-01-01

    Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose–response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach

  16. Active targeting of tumor cells using light emitting bacteria

    International Nuclear Information System (INIS)

    Moon, Sung Min; Min, Jung Joon; Hong, Yeong Jin; Kim, Hyun Ju; Le, Uuenchi N.; Rhee, Joon Haeng; Song, Ho Chun; Heo, Young Jun; Bom, Hee Seung; Choy, Hyon E

    2004-01-01

    The presence of bacteria and viruses in human tumors has been recognized for more than 50 years. Today, with the discovery of bacterial strains that specifically target tumors, and aided by genomic sequencing and genetic engineering, there is new interest in the use of bacteria as tumor vectors. Here, we show that bacteria injected intravenously into live animals entered and replicated in solid tumors and metastases using the novel imaging technology of biophotonics. Bioluminescence operon (LuxCDABE) or fluorescence protein, GFP) has been cloned into pUC19 plasmid to engineer pUC19lux or pUC19gfp. Engineered plasmid was transformed into different kinds of wild type (MG1655) or mutant E. coli (DH5, ppGpp, fnr, purE, crpA, flagella, etc.) strains to construct light emitting bacteria. Xenograft tumor model has been established using CT26 colon cancer cell line. Light emitting bacteria was injected via tail vein into tumor bearing mouse. In vivo bioluminescence imaging has been done after 20 min to 14 days of bacterial injection. We observed localization of tumors by light-emitting E. coli in tumor (CT-26) bearing mice. We confirmed the presence of light-emitting bacteria under the fluorescence microscope with E. coli expressing GFP. Althoug varying mutants strain with deficient invading function has been found in tumor tissues, mutant strains of movement (flagella) couldn't show any light signal from the tumor tissue under the cooled CCD camera, indicating bacteria may actively target the tumor cells. Based on their 'tumor-finding' nature, bacteria may be designed to carry multiple genes or drugs for detection and treatment of cancer, such as prodrug-converting enzymes, toxins, angiogenesis inhibitors and cytokines

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

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

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

  18. Targeting Killing of Breast Tumor Stem Cells

    National Research Council Canada - National Science Library

    Chen, Si-Yi

    2005-01-01

    .... Toward the goal, we have prepared HA molecules from human umbilical cord hyaluronic acid by hydrolysed by Bee venom. However, we have encountered the technical difficulty to produce CD44-targeted liposomes that are incorporated with HA molecules. Due to the technical problems, this proposed study has been extended for additional one year.

  19. Air pollution from traffic and risk for brain tumors

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  20. Gonadal status in male survivors following childhood brain tumors

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  1. Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

    International Nuclear Information System (INIS)

    Griebenow, M.L.; Dorn, R.V. III; Gavin, P.R.; Spickard, J.H.

    1988-01-01

    The United States (US) Department of Energy (DOE) recently initiated a focused, multidisciplined program to evaluate Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumors. The program, centered at the DOE/endash/Idaho National Engineering Laboratory (INEL), will develop the analytical, diagnostic and treatment tools, and the database required for BNCT technical assessment. The integrated technology will be evaluated in a spontaneously-occurring canine brain-tumor model. Successful animal studies are expected to lead to human clinical trials within four to five years. 2 refs., 3 figs

  2. Boron neutron capture therapy for children with malignant brain tumor

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

    1993-01-01

    Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

  3. Functional MRI procedures in the diagnosis of brain tumors. Perfusion- and diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Hartmann, M.; Heiland, S.; Sartor, K.

    2002-01-01

    Despite the increased diagnostic accuracy of contrast material enhanced MR imaging, specification and grading of brain tumors are still only approximate at best: neither morphology, nor relaxation times or contrast material enhancement reliably predict tumor histology or tumor grade. As histology and tumor grade strongly influence which therapy concept is chosen, a more precise diagnosis is mandatory. With diffusion- and perfusion-weighted MR imaging (DWI, PWI) it is now possible to obtain important information regarding the cellular matrix and the relative regional cerebral blood volume (rrCBV) of brain tumors, which cannot be obtained with standard MR techniques. These dynamic-functional imaging techniques are very useful in the preoperative diagnosis of gliomas, lymphomas, and metastases, as well as in the differentiation of these neoplastic lesions from abscesses, atypical ischemic infarctions, and tumor-like manifestations of demyelinating disease. Additionally, they appear suitable for determining glioma grade and regions of active tumor growth which should be the target of stereotactic biopsy and therapy. After therapy these techniques are helpful to better assess the tumor response to therapy, possible therapy failure and therapy complications such as radiation necrosis. (orig.) [de

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

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

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

  5. Brain tumor classification using Probabilistic Neural Network

    African Journals Online (AJOL)

    pc

    2018-03-05

    Mar 5, 2018 ... Baghdad, Iraq. 1sami.hasan@coie.nahrainuniv.edu.iq ... The Human brain is the most amazing and complex thing known in the world [1]. ... achieved using gray level co-occurrence matrix (GLCM). This work is aimed to ...

  6. Analysis of p53- immunoreactivity in astrocytic brain tumors

    Directory of Open Access Journals (Sweden)

    Shinkarenko T.V.

    2016-12-01

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

  7. Advanced age negatively impacts survival in an experimental brain tumor model.

    Science.gov (United States)

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-06

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Neuroradiologic work-up of brain tumors

    International Nuclear Information System (INIS)

    Fishbein, D.S.

    1988-01-01

    The presence of an intracranial tumor may be suspected or deduced from the clinical history and examination, or it may be discovered incidentally during investigation of another disorder. Once the suggestion is raised, a variety of neuroradiologic techniques are available to define the extent and nature of the lesion. The studies performed may allow a tissue diagnosis to be presumed, may serve as a guide to proposed surgical therapy, or may allow the course of a previously diagnosed lesion to be followed. This chapter discusses the utility of common neuroradiologic techniques and their specific indications in the work-up of intracranial tumors. Emphasis is placed upon tests that are most frequently utilized and have the greatest value

  9. Detecting brain tumor in pathological slides using hyperspectral imaging.

    Science.gov (United States)

    Ortega, Samuel; Fabelo, Himar; Camacho, Rafael; de la Luz Plaza, María; Callicó, Gustavo M; Sarmiento, Roberto

    2018-02-01

    Hyperspectral imaging (HSI) is an emerging technology for medical diagnosis. This research work presents a proof-of-concept on the use of HSI data to automatically detect human brain tumor tissue in pathological slides. The samples, consisting of hyperspectral cubes collected from 400 nm to 1000 nm, were acquired from ten different patients diagnosed with high-grade glioma. Based on the diagnosis provided by pathologists, a spectral library of normal and tumor tissues was created and processed using three different supervised classification algorithms. Results prove that HSI is a suitable technique to automatically detect high-grade tumors from pathological slides.

  10. Study on radiation necrosis following intraoperative radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Tanaka, Yoshiaki; Takeshita, Nagayuki; Niwa, Kohkichi; Kamata, Noriko; Matsuda, Tadayoshi; Matsutani, Masao

    1989-01-01

    Ninety-five patients with primary or metastatic brain tumors were treated with the intraoperative radiotherapy (IORT). In seven cases, surgery was performed a second time because of suspected of tumor recurrence, later found to be a radiation necrosis. Tumorous lesions were irradiated by IORT in the range of 15 Gy to 20 Gy together with external radiotherapy in the 30 Gy to 72 Gy range. In follow-up postcontrast CT studies, irregularly-shaped lesions appeared at the IORT site and increased in size with the perifocal low density area on subsequent scans. The images resembled those seen in tumor recurrence. Histopathologic changes seen during the follow-up surgery were thought to be mainly the result of radiation necrosis, though viable tumor cells at the marginal tumor site were one possible etiology. A coagulation necrosis with a fibrin exudate was observed in the IORT portal area and the vascular walls exhibited marked degeneration which is symptomatic of delayed radiation necrosis. Thus, post-IORT radiation necrosis is thought to be a direct reaction to this technique, and the delayed absorption of necrotic tissue to be a direct reaction to this technique, and the delayed absorption of necrotic tissue clearly indicates the possibility of adverse effects in its use for treatment of brain tumors. (author)

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

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

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

  12. American brain tumor patients treated with BNCT in Japan

    International Nuclear Information System (INIS)

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

    1995-01-01

    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

  13. Brain tumors and CT scans in infants and children, (3)

    International Nuclear Information System (INIS)

    Oi, Shizuo

    1983-01-01

    In clinical pictures of brain tumors in infants and children, many features are not identical to those in adults, including characteristics of the tumors in age population, the locations of the tumors, the clinical symptoms and signs, and various factors affecting prognosis. We have, therefore, clinically and extensively analyzed brain tumors in infants and children. This study was also performed in order to analyze the characteristic CT findings of astrocytoma, the tumor most frequently occurring among infants and children. The subjects were 24 cases of astrocytoma and 2 cases of glioblastoma in infants and children under 16 years. The locations and characteristics of the tumors were as follows. Most of the tumors occurred in the 4th ventricle, had a characteristic low density, and could almost entirely be clearly distinguished from medulloblastomas, but not from ependymomas, on CT. The features of the supratentorial tumors were similar to those of the astrocytomas and glioblastomas mostly appearing in adults, as previously reported, in the relatively close correlation with the location and malignancy of the tumor. There was also a case of diffuse astrocytoma, a ''non-enhanced low-density solid tumor,'' which raised clinical problems. Among low-grade astrocytomas in infants and children, only a few show a high density on plain CT, many have, at least macroscopically, a strong contrast enhancement, and peritumoral edema is not observed on CT or, if observed, is observed only slightly. As individual features, homogenous enhancement pattern, a mixed density, a central low density, and a rare absence of enhancement are listed. (author)

  14. Targeted drug delivery to the brain using magnetic nanoparticles.

    Science.gov (United States)

    Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Moos, Torben

    2015-01-01

    Brain capillary endothelial cells denote the blood-brain barrier (BBB), and conjugation of nanoparticles with antibodies that target molecules expressed by these endothelial cells may facilitate their uptake and transport into the brain. Magnetic nanoparticles can be encapsulated in liposomes and carry large molecules with therapeutic potential, for example, siRNA, cDNA and polypeptides. An additional approach to enhance the transport of magnetic nanoparticles across the BBB is the application of extracranially applied magnetic force. Stepwise targeting of magnetic nanoparticles to brain capillary endothelial cells followed by transport through the BBB using magnetic force may prove a novel mechanism for targeted therapy of macromolecules to the brain.

  15. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, Carla; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, Martine

    OBJECTIVE: Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

  16. Local anesthetics for brain tumor resection: Current perspectives

    NARCIS (Netherlands)

    J.W. Potters (Jan Willem); M. Klimek (Markus)

    2018-01-01

    textabstractThis review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local

  17. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, C.; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, M.J.E.

    Objective Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Radiotherapy combined with Tegafur (FT-207s) for brain tumors

    International Nuclear Information System (INIS)

    Aoki, Yoshiro

    1981-01-01

    5-Fluorouracil (5-FU) has anti-tumor effects as an anti-metabolite, but it cannot pass the Blood-Brain-Barrier (BBB). FT-207 a masked-compound of 5-FU, is easily lipid soluble and is able to pass the BBB. Twenty eight patients of primary brain tumor and 8 patients of metastatic brain tumor were treated with irradiation combined with 750 mg of FT-207 suppository. Twenty four patients of primary brain tumor were treated only with irradiation as control. The mean survival time was 20.4 +- 11.8 months for the combined therapy group and 17.6 +- 8.6 months for the control. The concentration of FT-207 and 5-FU in serum and in cerebrospinal fluid (CSF) was investigated after administration of 750 mg of FT-207 suppository per annum. The maximum concentration of FT-207 and of 5-FU in serum was 20.4 +- 11.8 mcg/ml and 0.06 +- 0.02 mcg/ml, respectively. There were observed several side effects, such as anorexia, nausea, exanthema and etc. These side effects were not so great as to interrupt the therapy at the dose level of 750 mg of FT-207. However, at the dose of 1500 mg, one case showed disturbance of consciousness, to which attention should be called. (author)

  20. Gadolinium neutron capture therapy for brain tumors. Biological aspects

    International Nuclear Information System (INIS)

    Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

    1994-01-01

    This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

  1. Computed tomography in the CSF seeding of brain tumors

    International Nuclear Information System (INIS)

    Nakagawa, Yoshio; Fujimoto, Masahito; Naruse, Shoji; Ueda, Satoshi; Hirakawa, Kimiyoshi

    1981-01-01

    In the past three years nine cases of brain tumors with CSF seeding have been revealed by computed tomography (CT). We have been analyzing the CT pattern of CSF seeding, CSF cytology, and spinal metastasis. The brain tumors were classified as follows: five medulloblastomas, two glioblastomas, one germinoma, and one meningeal carcinomatosis. Their CT patterns were divided into three groups: 1) diffuse seeding of the basal cisterns. 2) invasion of the ventricular wall. 3) solitary metastasis in the ventricle. The subarachnoid seeding included four medulloblastomas and one meningeal carcinomatosis. The second type of seeding included two glioblastomas and one germinoma. One medulloblastoma had a single metastasis in the lateral ventricle. In the medulloblastomas, the diffuse seeding of the basal cisterns was more common than the invasion of the ventricular wall or solitary metastasis in the ventricle. Medulloblastomas were also accompanied by spinal metastasis. Because there were many cases of spinal metastasis in the first type of seeding, we concluded that there was a definite correlation between the CSF seeding of the basal cisterns and spinal metastasis. Needless to say, CT was the most important method for the diagnosis of the CSF seeding of brain tumors. However, because there was a case of CSF seeding which had not been demonstrated by CT, we also emphasized the importance of neurological examination and CSF cytology in the diagnosis of the CSF seeding of brain tumors. (author)

  2. Brain Tumor Segmentation Based on Random Forest

    Directory of Open Access Journals (Sweden)

    László Lefkovits

    2016-09-01

    Full Text Available In this article we present a discriminative model for tumor detection from multimodal MR images. The main part of the model is built around the random forest (RF classifier. We created an optimization algorithm able to select the important features for reducing the dimensionality of data. This method is also used to find out the training parameters used in the learning phase. The algorithm is based on random feature properties for evaluating the importance of the variable, the evolution of learning errors and the proximities between instances. The detection performances obtained have been compared with the most recent systems, offering similar results.

  3. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Science.gov (United States)

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

  4. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Marc Baay

    2011-01-01

    Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

  5. Clinical study on brain tumors in the aged

    International Nuclear Information System (INIS)

    Teramoto, Akira; Manaka, Shinya; Takakura, Kintomo

    1981-01-01

    In order to investigate the clinical features and the prognosis of brain tumors in the aged, 132 cases over 60 years of age were studied from the consecutive series of 1,793 brain tumors in the University of Tokyo Hospital (1963 - 1979). The incidence of brain tumors in the aged was 7.4% on the whole, while it showed a significant increase from 4.8% (1960's) to 11.5% (the later half of 1970's). Histologically, meningiomas were the most common tumors (26%), followed by neurinomas (17%), pituitary adenomas (16%) and metastatic tumors (15%). Malignant gliomas were found more frequently than benign ones. There were more meningiomas as age advanced. The proportion and the number of meningioma cases has obviously increased in recent years when CT scanners became available. Symptoms of intracranial hypertention were found less frequently in aged patients although they were still common in cases of glioblastomas. The duration from onset to surgery was relatively long, especially in cases of neurinomas and pituitary adenomas. Two cases of astrocytomas belonged to the category of silent gliomas. Overall operative mortality rate was 10.6%, while it showed a marked decrease to 4.7% in the 1970's. Five-year survival rates were as follows: meningiomas (58%), pituitary adenomas (70%), neurinomas (80%), glioblastomas (20%) and astrocytomas (25%). As for functional prognoses, 30% of the patients showed poor states on ADL, mostly because of residual psychic disorders. (author)

  6. Targeted Delivery of siRNA Therapeutics to Malignant Tumors

    Directory of Open Access Journals (Sweden)

    Qixin Leng

    2017-01-01

    Full Text Available Over the past 20 years, a diverse group of ligands targeting surface biomarkers or receptors has been identified with several investigated to target siRNA to tumors. Many approaches to developing tumor-homing peptides, RNA and DNA aptamers, and single-chain variable fragment antibodies by using phage display, in vitro evolution, and recombinant antibody methods could not have been imagined by researchers in the 1980s. Despite these many scientific advances, there is no reason to expect that the ligand field will not continue to evolve. From development of ligands based on novel or existing biomarkers to linking ligands to drugs and gene and antisense delivery systems, several fields have coalesced to facilitate ligand-directed siRNA therapeutics. In this review, we discuss the major categories of ligand-targeted siRNA therapeutics for tumors, as well as the different strategies to identify new ligands.

  7. Targeting Autophagy in the Tumor Microenvironment: New Challenges and Opportunities for Regulating Tumor Immunity

    Directory of Open Access Journals (Sweden)

    Bassam Janji

    2018-04-01

    Full Text Available Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the “tumor ecosystem” and the diversity of the stromal cell types that constitute the tumor microenvironment. Emerging data indicate that several factors, such as hypoxic stress, activate a plethora of resistance mechanisms, including autophagy, in tumor cells. Hypoxia-induced autophagy in the tumor microenvironment also activates several tumor escape mechanisms, which effectively counteract anti-tumor immune responses mediated by natural killer and cytotoxic T lymphocytes. Therefore, strategies aiming at targeting autophagy in cancer cells in combination with other therapeutic strategies have inspired significant interest to overcome immunological tolerance and promote tumor regression. However, a number of obstacles still hamper the application of autophagy inhibitors in clinics. First, the lack of selectivity of the current pharmacological inhibitors of autophagy makes difficult to draw a clear statement about its effective contribution in cancer. Second, autophagy has been also described as an important mechanism in tumor cells involved in presentation of antigens to T cells. Third, there is a circumstantial evidence that autophagy activation in some innate immune cells may support the maturation of these cells, and it is required for their anti-tumor activity. In this review, we will address these aspects and discuss our current knowledge on the benefits and the drawbacks of targeting autophagy in the context of anti-tumor immunity. We believe that it is

  8. Combination radiotherapy in an orthotopic mouse brain tumor model.

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  9. Chemo-radiotherapy for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kochi, Masato; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    2002-05-01

    Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

  10. Chemo-radiotherapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Kochi, Masato; Ushio, Yukitaka

    2002-01-01

    Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

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

    Science.gov (United States)

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    In this paper, we present a fully automated generative method for brain tumor segmentation in multi-modal magnetic resonance images. The method is based on the type of generative model often used for segmenting healthy brain tissues, where tissues are modeled by Gaussian mixture models combined...... the use of the intensity information in the training images. Experiments on public benchmark data of patients suffering from low- and high-grade gliomas show that the method performs well compared to current state-of-the-art methods, while not being tied to any specific imaging protocol....... with a spatial atlas-based tissue prior. We extend this basic model with a tumor prior, which uses convolutional restricted Boltzmann machines (cRBMs) to model the shape of both tumor core and complete tumor, which includes edema and core. The cRBMs are trained on expert segmentations of training images, without...

  13. Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

    International Nuclear Information System (INIS)

    Badr El-Din, N.K.; Abdel-Hady, E.K.; Salem, F.K.; Settin, A.; ALI, N.

    2009-01-01

    Background: Cytokines are proposed to play important roles in brain tumor biology as well as neuro degeneration or impaired neuronal function. Objectives: This work aimed to check the association of polymorphisms of cytokine genes in Egyptian cases with brain tumors. Methods: This work included 45 cases affected by brain tumors diagnosed as 24 benign and 21 malignant. Their median age was 45 years, and they were 20 males and 25 females. These cases were taken randomly from the Neurosurgery Department of Mansoura University Hospital, Egypt. Case genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-a-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C) and IL-1Ra (VNTR) genes. Results: Cases affected with benign brain tumors showed a significant higher frequency of IL-10-1082 A/A [odds ratio (OR=8.0), p<0.001] and IL-6-174 C/C (OR=6.3, p=0.002) homozygous genotypes as compared to controls. Malignant cases, on the other hand, showed significantly higher frequency of IL-6-174 C/C (OR =4.8, p=0.002) homozygous genotype and TNF-a-308 A/A (OR=4.9, p<0.001) homozygous genotype when compared to controls. In the meantime, all cases showed no significant difference regarding the distribution of IL-1Ra VNTR genotype polymorphism compared to controls. Conclusions: Cytokine gene polymorphisms showed a pattern of association with brain tumors which may have potential impact on family counseling and disease management.

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

    Science.gov (United States)

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

    2011-02-01

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

  15. Non-tumor enhancement at the surgical margin on CT after the removal of brain tumors

    International Nuclear Information System (INIS)

    Adachi, Michito; Hosoya, Takaaki; Yamaguchi, Kohichi; Yamada, Kiyotada

    1992-01-01

    Marginal enhancement is occasionally seen at the surgical margin on CT after the total removal of brain tumors. This enhancement disappears in due time, and therefore we call it non-tumor enhancement. It is often difficult, however, to differentiate non-tumor enhancement from tumor recurrence. In this study, we attempted to determine the characteristics of non-tumor enhancement. The subjects of the study consisted of 15 patients with astrocytoma and one with metastatic tumor in whom sequential CT scans had been performed after total removal of the tumor. Based on the observation of these sequential CT scans, the characteristics of non-tumor enhancement were presumed to be as follows: (1) In four cases, enhancement at the surgical margin persisted more than four months after surgery and then disappeared. Therefore, these cases were considered non-tumor enhancement. Prolonged duration of enhancement such as that in these cases is not necessarily due to recurrence. Marginal enhancement within 3 mm in thickness and with a well-demarcated border like that of a flax is likely to be non-tumor enhancement. (author)

  16. The new WHO 2016 classification of brain tumors-what neurosurgeons need to know.

    Science.gov (United States)

    Banan, Rouzbeh; Hartmann, Christian

    2017-03-01

    The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification. Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the literature relevant for brain tumor classification from 2007 up to now. The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a "layered diagnosis" to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an "integrated diagnosis" at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only

  17. Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

    Science.gov (United States)

    Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

    2016-01-01

    Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

  18. "Facilitated" amino acid transport is upregulated in brain tumors.

    Science.gov (United States)

    Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

    1998-05-01

    The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary

  19. Investigating Contingency Risk Factors of Brain Tumor in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    A Nazemi

    2014-12-01

    Conclusion: According to research results, several preventable and predictable factors are linked to pediatric brain tumors. Therefore, children prone to brain tumors are recommended to be examined and screened for these risk factors.

  20. Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors.

    Science.gov (United States)

    Sun, Tao; Warrington, Nicole M; Rubin, Joshua B

    2012-01-25

    It is often reported that brain tumors occur more frequently in males, and that males suffer a worse outcome from brain tumors than females. If correct, these observations suggest that sex plays a fundamental role in brain tumor biology. The following review of the literature regarding primary and metastatic brain tumors, reveals that brain tumors do occur more frequently in males compared to females regardless of age, tumor histology, or region of the world. Sexually dimorphic mechanisms that might control tumor cell biology, as well as immune and brain microenvironmental responses to cancer, are explored as the basis for this sex disparity. Elucidating the mechanisms by which sex chromosomes and sex hormones impact on brain tumorigenesis and progression will advance our understanding of basic cancer biology and is likely to be essential for optimizing the care of brain tumor patients.

  1. Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors

    Directory of Open Access Journals (Sweden)

    Sun Tao

    2012-01-01

    Full Text Available Abstract It is often reported that brain tumors occur more frequently in males, and that males suffer a worse outcome from brain tumors than females. If correct, these observations suggest that sex plays a fundamental role in brain tumor biology. The following review of the literature regarding primary and metastatic brain tumors, reveals that brain tumors do occur more frequently in males compared to females regardless of age, tumor histology, or region of the world. Sexually dimorphic mechanisms that might control tumor cell biology, as well as immune and brain microenvironmental responses to cancer, are explored as the basis for this sex disparity. Elucidating the mechanisms by which sex chromosomes and sex hormones impact on brain tumorigenesis and progression will advance our understanding of basic cancer biology and is likely to be essential for optimizing the care of brain tumor patients.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

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

    DEFF Research Database (Denmark)

    Fahmideh, Maral Adel; Lavebratt, Catharina; Schüz, Joachim

    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...... 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....

  4. Measurement of P-31 MR relaxation times and concentrations in human brain and brain tumors

    International Nuclear Information System (INIS)

    Roth, K.; Naruse, S.; Hubesch, B.; Gober, I.; Lawry, T.; Boska, M.; Matson, G.B.; Weiner, M.W.

    1987-01-01

    Measurements of high-energy phosphates and pH were made in human brain and brain tumors using P-31 MR imaging. Using a Philips Gyroscan 1.5-T MRMRS, MR images were used to select a cuboidal volume of interest and P-31 MR spectra were obtained from that volume using the ISIS technique. An external quantitation standard was used. T 1 s were measured by inversion recovery. Quantitative values for metabolites were calculated using B 1 field plot of the head coil. The results for normal brain phosphates are as follows; adenosine triphosphate, 2.2 mM; phosphocreatin, 5.3 mM; inorganic phosphate, 1.6 mM. Preliminary studies with human brain tumors show a decrease of all phosphate compounds. These experiments are the first to quantitate metabolites in human brain

  5. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; Chen Yiru; He Wenjie; Hong Poda; Yu, Dah-Shyong; Domb, Abraham J.

    2013-01-01

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe 2+ solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  6. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

    2013-01-15

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  7. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.

    Directory of Open Access Journals (Sweden)

    A B Madhankumar

    Full Text Available Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs. Interleukin-13 receptor alpha 2 (IL13Rα2 is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR. This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.

  8. Selective tumor cell targeting by the disaccharide moiety of bleomycin.

    Science.gov (United States)

    Yu, Zhiqiang; Schmaltz, Ryan M; Bozeman, Trevor C; Paul, Rakesh; Rishel, Michael J; Tsosie, Krystal S; Hecht, Sidney M

    2013-02-27

    In a recent study, the well-documented tumor targeting properties of the antitumor agent bleomycin (BLM) were studied in cell culture using microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human breast carcinoma cells but not the "normal" breast cell line MCF-10A. Furthermore, it was found that the BLM analogue deglycobleomycin, which lacks the disaccharide moiety of BLM, did not target either cell line, indicating that the BLM disaccharide moiety is necessary for tumor selectivity. Not resolved in the earlier study were the issues of whether the BLM disaccharide moiety alone is sufficient for tumor cell targeting and the possible cellular uptake of the disaccharide. In the present study, we conjugated BLM, deglycoBLM, and BLM disaccharide to the cyanine dye Cy5**. It was found that the BLM and BLM disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells and were internalized. The same was also true for the prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the pancreatic cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells and comparable to that of BLM in BxPC-3 cells. These results establish that the BLM disaccharide is both necessary and sufficient for tumor cell targeting, a finding with obvious implications for the design of novel tumor imaging and therapeutic agents.

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

    Science.gov (United States)

    Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

    2014-02-01

    Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

  10. Improved apparatus for neutron capture therapy of rat brain tumors

    International Nuclear Information System (INIS)

    Liu, Hungyuan B.; Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1994-01-01

    The assembly for irradiating tumors in the rat brain at the thermal neutron beam port of the Brookhaven Medical Research Reactor was redesigned to lower the average whole-body dose from different components of concomitant radiation without changing the thermal neutron fluence at the brain tumor. At present, the tumor-bearing rat is positioned in a rat holder that functions as a whole-body radiation shield. A 2.54 cm-thick collimator with a centered conical aperture, 6 cm diameter tapering to 2 cm diameter, is used to restrict the size of the thermal neutron field. Using the present holder and collimator as a baseline design, Monte Carlo calculations and mixed-field dosimetry were used to assess new designs. The computations indicate that a 0.5 cm-thick plate, made of 6 Li 2 CO 3 dispersed in polyethylene (Li-poly), instead of the existing rat holder, will reduce the whole-body radiation dose. Other computations show that a 10.16 cm-thick (4 inches) Li-poly collimator, having a centered conical aperture of 12 cm diameter tapering to 2 cm diameter, would further reduce the whole-body dose. The proposed irradiation apparatus of tumors in the rat brain, although requiring a 2.3-fold longer irradiation time, would reduce the average whole-body dose to less than half of that from the existing irradiation assembly. 7 refs., 4 figs., 7 tabs

  11. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    International Nuclear Information System (INIS)

    Adam, Jean-Francois

    2005-01-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size 2 ) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal energy, for a

  12. Glucosylated polyethylenimine as a tumor-targeting gene carrier.

    Science.gov (United States)

    Park, In-Kyu; Cook, Seung-Eun; Kim, You-Kyoung; Kim, Hyun-Woo; Cho, Myung-Haing; Jeong, Hwan-Jeong; Kim, Eun-Mi; Nah, Jae-Woon; Bom, Hee-Seung; Cho, Chong-Su

    2005-11-01

    Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-%) had no cytotoxic effect on cells even at polymer concentrations higher than 200 microg/mL. Compared to unglucosylated PEI, glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEI. Gamma imaging technique revealed GPEI/DNA complex was distributed in liver, spleen, and tumors.

  13. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  14. Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties.

    Science.gov (United States)

    Schlageter, K E; Molnar, P; Lapin, G D; Groothuis, D R

    1999-11-01

    We studied microvessel organization in five brain tumor models (ENU, MSV, RG-2, S635cl15, and D-54MG) and normal brain, including microvessel diameter (LMVD), intermicrovessel distance (IMVD), microvessel density (MVD), surface area (S(v)), and orientation. LMVD and IMVD were larger and MVD was lower in tumors than normal brain. S(v) in tumors overlapped normal brain values and orientation was random in both tumors and brain. ENU and RG-2 tumors and brain were studied by electron microscopy. Tumor microvessel wall was thicker than that of brain. ENU and normal brain microvessels were continuous and nonfenestrated. RG-2 microvessels contained fenestrations and endothelial gaps; the latter had a maximum major axis of 3.0 microm. Based on anatomic measurements, the pore area of RG-2 tumors was estimated at 7.4 x 10(-6) cm(2) g(-1) from fenestrations and 3.5 x 10(-5) cm(2) g(-1) from endothelial gaps. Increased permeability of RG-2 microvessels to macromolecules is most likely attributable to endothelial gaps. Three microvessel populations may occur in brain tumors: (1) continuous nonfenestrated, (2) continuous fenestrated, and (3) discontinuous (with or without fenestrations). The first group may be unique to brain tumors; the latter two are similar to microvessels found in systemic tumors. Since structure-function properties of brain tumor microvessels will affect drug delivery, studies of microvessel function should be incorporated into clinical trials of brain tumor therapy, especially those using macromolecules. Copyright 1999 Academic Press.

  15. Specific targeting for the treatment of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    2003-01-01

    For the treatment of neuroendocrine tumors three ways of specific targeting of radionuclides prevail: by 131 I-meta-iodo-benzyl-guanidine (MIBG), which is taken up by an active uptake-1 mechanism and stored in neurosecretory granules of neural crest tumor cells, by radiolabeled peptides, in particular the somatostatin analogs octreotide and lanreotide, targeting the peptide receptors, and by radiolabeled antibodies, which target tumor cell surface antigens. The choice depends on the indication, the results of diagnostic imaging using tracer amounts of these agents, the availability and feasibility of radionuclide therapy and of other treatment modalities. The applications, clinical results and developments for the major indications are reviewed. 131 I-MIBG therapy has a cumulative response rate of 50%, associated with little toxicity, in metastatic pheochromocytoma, paraganglioma and neuroblastoma, whereas its role is primarily palliative in patients with medullary thyroid carcinoma and carcinoid tumors. Treatment using 90 Y- or 177 Lu-labeled octreotide/lanreotide is mostly used in neuroendocrine gastro-entero-pancreatic (GEP) tumors and paraganglioma, attaining stabilization of disease anti-palliation in the majority of patients. As this treatment is specific for the receptor rather than for the tumor type, it may also be applicable to other, non-neuroendocrine tumors. Radioimmunotherapy is applied in medullary thyroid carcinoma, in which a phase I/II study using bi-specific anti-DTPA/anti-CEA immuno-conjugates followed by 131 I-hapten has proven some degree of success, and may be used in neuroblastoma more effectively than before, once chimeric and humanized monoclonal antibodies become available for therapy. Integration of these specific and noninvasive therapies at an optimal moment into the treatment protocols of these diseases may enhance their effectiveness and acceptance. (author)

  16. BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

    Directory of Open Access Journals (Sweden)

    Françoise eREDINI

    2015-12-01

    Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  17. Chemotherapeutic drug delivery by tumoral extracellular matrix targeting

    NARCIS (Netherlands)

    Raavé , R.; Kuppevelt, T.H. van; Daamen, W.F.

    2018-01-01

    Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of chemotherapeutics to tumor cells have been designed and

  18. Radiation therapy of 9L rat brain tumors

    International Nuclear Information System (INIS)

    Henderson, S.D.; Kimler, B.F.; Morantz, R.A.

    1981-01-01

    The effects of radiation therapy on normal rats and on rats burdened with 9L brain tumors have been studied. The heads of normal rats were x-irradiated with single exposures ranging from 1000 R to 2700 R. Following acute exposures greater than 2100 R, all animals died in 8 to 12 days. Approximately 30% of the animals survived beyond 12 days over the range of 1850 to 1950 R; following exposures less than 1850 R, all animals survived the acute radiation effects, and median survival times increased with decreasing exposure. Three fractionated radiation schedules were also studied: 2100 R or 3000 R in 10 equal fractions, and 3000 R in 6 equal fractions, each schedule being administered over a 2 week period. The first schedule produced a MST of greater than 1 1/2 years; the other schedules produced MSTs that were lower. It was determined that by applying a factor of 1.9, similar survival responses of normal rats were obtained with single as with fractionated radiation exposures. Animals burdened with 9L gliosarcoma brain tumors normally died of the disease process within 18 to 28 days ater tumor inoculation. Both single and fractionated radiation therapy resulted in a prolongation of survival of tumor-burdened rats. This prolongation was found to be linearly dependent upon the dose; but only minimally dependent upon the time after inoculation at which therapy was initiated, or upon the fractionation schedule that was used. As with normal animals, similar responses were obtained with single as with fractionated exposures when a factor (1.9) was applied. All tumor-bearing animals died prior to the time that death was observed in normal, irradiated rats. Thus, the 9L gliosarcoma rat brain tumor model can be used for the pre-clinical experimental investigation of new therapeutic schedules involving radiation therapy and adjuvant therapies

  19. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

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

  20. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-02-18

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  1. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    International Nuclear Information System (INIS)

    Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

    2013-01-01

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  2. Adverse effect after external radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Takano, Shingo; Yanaka, Kiyoyuki

    1989-01-01

    This report discusses the effects on normal brain tissue of radiotherapy in relation to age and irradiation dose as determined from whole-brain sections of the autopsied brains with tumors. Twenty four patients (7 glioblastomas, 2 benign gliomas, 12 brain metastases, 2 malignant lymphomas, and 1 pituitary adenoma) older than 65 years (aged), and 17 younger than 65 years (non-aged) were treated by cobalt- or linear accelerator radiotherapy. Nine patients without brain disease (4 aged and 5 non-aged) were used as a control group. The histological findings were evaluated by grading the small and capillary vessels, fibrinoid necrosis, and myelination in the white matter in whole-brain sections. Those findings were compared to the irradiation doses within all radiation fields in whole-brain sections corresponding to CT scans. Hyalinization of the small vessels was observed within the postradiation 12 months in fields exposed to total doses of less than 800 neuret. Hyalinization of the capillary vessels was greater in the irradiated group than in the control group. Demyelination was observed within the postradiation 12 months in fields irradiated by more than 800 neuret in aged patients and in fields irradiated by less than 800 neuret in non-aged patients. Fibrinoid necrosis was observed after the post-radiation 12 months in fields irradiated by less than 800 neuret in aged patients and in fields irradiated by more than 800 neuret in non-aged patients. It is worth noting that in non-aged patients with brain tumors, adverse effects of radiotherapy on vessels and parenchyma were very high even in low-dose radiation areas; and in aged patients fibrinoid necrosis, which indicates irreversible damage of vessels, was observed in low-dose radiation areas. (author)

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

    Science.gov (United States)

    2017-12-11

    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

  4. Cellular phones and risk of brain tumors.

    Science.gov (United States)

    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.

  5. Clinical considerations for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

    1990-01-01

    The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

  6. Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

    Science.gov (United States)

    Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

    2010-09-01

    Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

  7. Brain tumor segmentation using holistically nested neural networks in MRI images.

    Science.gov (United States)

    Zhuge, Ying; Krauze, Andra V; Ning, Holly; Cheng, Jason Y; Arora, Barbara C; Camphausen, Kevin; Miller, Robert W

    2017-10-01

    Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of

  8. Transcranial Route of Brain Targeted Delivery of Methadone in Oil

    OpenAIRE

    Pathirana, W.; Abhayawardhana, P.; Kariyawasam, H.; Ratnasooriya, W. D.

    2009-01-01

    The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. The present study was to inv...

  9. Characterization of tumor vasculature in mouse brain by USPIO contrast-enhanced MRI.

    NARCIS (Netherlands)

    Gambarota, G.; Leenders, W.P.J.

    2011-01-01

    Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors

  10. Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors

    Directory of Open Access Journals (Sweden)

    Chong Jiang MD

    2017-01-01

    Full Text Available Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs, but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM, a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7, and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.

  11. Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

    Science.gov (United States)

    Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

    2017-01-01

    In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

  12. Intelligence Deficits in Chinese Patients with Brain Tumor: The Impact of Tumor Resection

    Directory of Open Access Journals (Sweden)

    Chao Shen

    2013-01-01

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

  13. Tumor Targeting and Drug Delivery by Anthrax Toxin

    Directory of Open Access Journals (Sweden)

    Christopher Bachran

    2016-07-01

    Full Text Available Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  14. Tumor Targeting and Drug Delivery by Anthrax Toxin.

    Science.gov (United States)

    Bachran, Christopher; Leppla, Stephen H

    2016-07-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  15. Targeted radionuclide therapy for solid tumors: An overview

    International Nuclear Information System (INIS)

    De Nardo, Sally J.; De Nardo, Gerald L.

    2006-01-01

    Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

  16. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Federica Ciregia

    2017-08-01

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

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

    International Nuclear Information System (INIS)

    Jereb, B.; Petric-Grabnar, G.; Zadravec-Zaletel, L.; Korenjak, R.; Krzisnik, C.; 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. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Jereb, B. (Institute of Oncology, Ljubljana (Slovenia)); Petric-Grabnar, G. (Institute of Oncology, Ljubljana (Slovenia)); Zadravec-Zaletel, L. (Institute of Oncology, Ljubljana (Slovenia)); Korenjak, R. (Clinical Center, Psychiatric Outpatient Dept., Ljubljana (Slovenia)); Krzisnik, C. (Clinical Center, Dept. of Pediatrics, Ljubljana (Slovenia)); Anzic, J. (Clinical Center, Dept. of Pediatrics, Ljubljana (Slovenia)); Stare, J. (Institute of Biomedical Informatics, Medical Faculty, Ljubljana (Slovenia))

    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. (orig.).

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

    Science.gov (United States)

    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.

  20. Natural killer activity of peripheral blood lymphocytes in patients with brain tumors

    International Nuclear Information System (INIS)

    Otsuka, Shin-ichi; Suda, Kinya; Yamashita, Junkoh; Takeuchi, Juji; Handa, Hajime

    1982-01-01

    Natural killer activity (NK activity) of peripheral blood ymphocytes in patients with brain tumors was examined by the method of 51 Cr release assay in order to study the effects of operation and radiotherapy on the immunological activity of the hosts. NK activity of peripheral blood lymphocytes in normal persons was about 50 to 70% and about 30 to 50% (% specific 51 Cr release) at a ratio of target to effector cells of 1 : 25 and 1 : 12.5 respectively. There were no significant differences in NK activity in regard to the histological types of brain tumors. As for the effects of operation on NK activity, NK activity decreased by the end of the 1st week after operation and then increased gradually and returned to the pre-operative level 2 to 3 weeks after operation. The causes of decrease of NK activity after operation are not clear but there are some factors to be considered, such as bleeding during operation, non-specific inflammation, use of steroid after operation and the decrease of the stimulation of tumor antigen. As regards the effects of radiotherapy on NK activity, NK activity increased within 3 weeks after the beginning of radiotherapy. The increase of NK activity may indicate that the immunological resistance to tumor was enhanced in hosts by local irradiation of the tumor. Some characteristics of the effector cells were examined. E rosette non-forming cells had a stronger cytoxicity against target cells than E rosette forming cells. Nylon wool non-adherent cells had slightly higher cytotoxicity than adherent cells but the cytotoxicity was recognized in both fractions. It is felt important to clarify further the clinical significance of changes of NK activity in relation to various treatments and prognosis in patients with brain tumors. (author)

  1. Specific features of epilepsy in children with brain tumors

    Directory of Open Access Journals (Sweden)

    G. V. Kalmykova

    2015-01-01

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

  2. MRI of neurosyphilis presenting as brain tumor: A case report

    Directory of Open Access Journals (Sweden)

    Yuling Xi

    2015-12-01

    Full Text Available Syphilis has a broad spectrum of clinical manifestations, among which cerebral gumma is a kind of neurosyphilis. However, it is rare and can be cured by penicillin. We report a case of syphilitic gumma of which the patient was first suspected of brain tumor, but confirmed by surgery to be cerebral gumma due to neurosyphilis. Magnetic resonance imaging, which is thought to be one of the potential and specific diagnostic methods for neurosyphilis, is discussed.

  3. Local anesthetics for brain tumor resection: current perspectives

    Directory of Open Access Journals (Sweden)

    Potters JW

    2018-02-01

    Full Text Available Jan-Willem Potters, Markus Klimek Department of Anesthesiology, Erasmus MC, Rotterdam, The Netherlands Abstract: This review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local anesthesia or under local anesthesia only. Literature shows a large variation in the postoperative pain intensity ranging from no postoperative analgesia requirement in two-thirds of the patients up to a rate of 96% of the patients suffering from severe postoperative pain. The only identified causative factor predicting higher postoperative pain scores is infratentorial surgery. Postoperative analgesia can be achieved with multimodal pain management where local anesthesia is associated with lower postoperative pain intensity, reduction in opioid requirement and prevention of development of chronic pain. In awake craniotomy patients, sufficient local anesthesia is a cornerstone of the procedure. An awake craniotomy and brain tumor resection can be carried out completely under local anesthesia only. However, the use of sedative drugs is common to improve patient comfort during craniotomy and closure. Local anesthesia for craniotomy can be performed by directly blocking the six different nerves that provide the sensory innervation of the scalp, or by local infiltration of the surgical site and the placement of the pins of the Mayfield clamp. Direct nerve block has potential complications and pitfalls and is technically more challenging, but mostly requires lower total doses of the local anesthetics than the doses required in surgical-site infiltration. Due to a lack of comparative studies, there is no evidence showing superiority of one technique versus the other. Besides the use of other local anesthetics for analgesia, intravenous lidocaine administration has

  4. Pediatric brain stem tumors: analysis of 25 cases

    International Nuclear Information System (INIS)

    Pinel, M.I.S.; Kalifa, C.; Sarrazin, D.; Lemerle, J.

    1985-01-01

    The charts of 25 pediatric patients with brain stem tumors have been reviewed. The use of computed tomography was found to have been valuable in diagnosis and follow-up, as well as in the design of radiation therapy portals. Radiotherapy and combination chemotherapy with VM-26 (4'-1 demethyl-epipodophyllo toxin B-D-thenylidene glucoside) and CCNU(1-2-chloroethyl-methyl-3-Cyclohexyl-1-nitrosourea) were the treatment employed. (M.A.C.) [pt

  5. Telomere length modulation in human astroglial brain tumors.

    Directory of Open Access Journals (Sweden)

    Domenico La Torre

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

  6. Immunotherapy targeting immune check-point(s) in brain metastases.

    Science.gov (United States)

    Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

    2017-08-01

    Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Holmium-166-chico intracavitary radiation therapy for cystic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, C. H.; Lee, S. H.; Jang, J. S.; Kim, E. H.; Choi, C. W.; Hong, S. W.; Lim, S. M. [Korea Cancer Center, Seoul (Korea, Republic of)

    1997-07-01

    Holmium-166-chitosan complex (Ho-166-chico) is injected into the unresectable seven cystic brain tumors (2 cases of metastatic brain tumors from lung cancer, 1 case of recurrent trigeminal neurinoma, 3 cases of recurrent low grade cystic astrocytomas, and 1 case of craniopharyngioma). The Ommaya reservoir was installed stereotactically. The cyst volume and wall thickness were measured by MRI before Ho-166-chico injection. The thickness of the cyst wall is up to 4 mm. Ho-166-chico (555-740 MBq) injected into the cyst to result in 25 Gy of dose to a cyst wall at a depth of 4 mm. Dose to the cyst wall was estimated by Monte Carlo simulation using the EGS4 code. All Ho-166-chico injected was assumed to be uniformly distributed in the spherical cyst. After Ho-166-chico injection, the distribution of isotopes was monitored by gamma camera. Two injections were administrated in two cases, and one injection in all the others. The response was evaluated with MRI. Four of 7 cases were shrunk in size with thinning of the cyst wall, 2 of 7 cases showed growth arrest, and one case showed progression. Estimated surface dose of cyst wall was between 78 and 2566 Gy. No one showed systemic absorption of Ho-166-chico, and specific complication associated with isotope injection. Ho-166-chico intracavitary radiation therapy for cystic brain tumor may be safe, and reliable method and deserves further evaluation.

  8. Sigma and opioid receptors in human brain tumors

    International Nuclear Information System (INIS)

    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 [ 3 H] 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: μ, [D-ala 2 , mePhe 4 , gly-ol 5 ] enkephalin (DAMGE); κ, ethylketocyclazocine (EKC) or U69,593; δ, [D-pen 2 , D-pen 5 ] enkephalin (DPDPE) or [D-ala 2 , D-leu 5 ] enkephalin (DADLE) with μ 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. κ 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

  9. Sigma and opioid receptors in human brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

    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.

  10. Epidemiology of brain tumors in childhood--a review

    International Nuclear Information System (INIS)

    Baldwin, Rachel Tobias; Preston-Martin, Susan

    2004-01-01

    Malignant brain tumors are the leading cause of cancer death among children and the second most common type of pediatric cancer. Despite several decades of epidemiologic investigation, the etiology of childhood brain tumors (CBT) is still largely unknown. A few genetic syndromes and ionizing radiation are established risk factors. Many environmental exposures and infectious agents have been suspected of playing a role in the development of CBT. This review, based on a search of the medical literature through August 2003, summarizes the epidemiologic evidence to date. The types of exposures discussed include ionizing radiation, N-nitroso compounds (NOC), pesticides, tobacco smoke, electromagnetic frequencies (EMF), infectious agents, medications, and parental occupational exposures. We have chosen to focus on perinatal exposures and review some of the recent evidence indicating that such exposures may play a significant role in the causation of CBT. The scientific community is rapidly learning more about the molecular mechanisms by which carcinogenesis occurs and how the brain develops. We believe that advances in genetic and molecular biologic technology, including improved histologic subtyping of tumors, will be of huge importance in the future of epidemiologic research and will lead to a more comprehensive understanding of CBT etiology. We discuss some of the early findings using these technologies

  11. Peritumoral hemorrhage immediately after radiosurgery for metastatic brain tumor

    International Nuclear Information System (INIS)

    Uchino, Masafumi; Kitajima, Satoru; Miyazaki, Chikao; Otsuka, Takashi; Seiki, Yoshikatsu; Shibata, Iekado

    2003-01-01

    We report a case of a 44-year-old woman with metastatic brain tumors who suffered peri-tumoral hemorrhage soon after stereotactic radiosurgery (SRS). She had been suffering from breast cancer with multiple systemic metastasis. She started to have headache, nausea, dizziness and speech disturbance 1 month before admission. There was no bleeding tendency in the hematological examination and the patient was normotensive. Neurological examination disclosed headache and slightly aphasia. Magnetic resonance imaging showed a large round mass lesion in the left temporal lobe. It was a well-demarcated, highly enhanced mass, 45 mm in diameter. SRS was performed on four lesions in a single session (Main mass: maximum dose was 30 Gy in the center and 20 Gy in the margin of the tumor. Others: maximum 25 Gy margin 20 Gy). After radiosurgery, she had severe headache, nausea and vomiting and showed progression of aphasia. CT scan revealed a peritumoral hemorrhage. Conservative therapy was undertaken and the patient's symptoms improved. After 7 days, she was discharged, able to walk. The patient died of extensive distant metastasis 5 months after SRS. Acute transient swelling following conventional radiotherapy is a well-documented phenomenon. However, the present case indicates that such an occurrence is also possible in SRS. We have hypothesized that acute reactions such as brain swelling occur due to breakdown of the fragile vessels of the tumor or surrounding tissue. (author)

  12. Prospective study of neuropsychological sequelae in children with brain tumors

    International Nuclear Information System (INIS)

    Bordeaux, J.D.; Dowell, R.E. Jr.; Copeland, D.R.; Fletcher, J.M.; Francis, D.J.; van Eys, J.

    1988-01-01

    Surgery and radiotherapy are the primary modalities of treatment for pediatric brain tumors. Despite the widespread use of these treatments, little is known of their acute effects (within one year posttreatment) on neuropsychological functions. An understanding of acute treatment effects may provide valuable feedback to neurosurgeons and a baseline against which delayed sequelae may be evaluated. This study compares pre- and posttherapy neuropsychological test performance of pediatric brain tumor patients categorized into two groups on the basis of treatment modalities: surgery (n = 7) and radiotherapy (n = 7). Treatment groups were composed of children aged 56 to 196 months at the time of evaluation with heterogeneous tumor diagnoses and locations. Comparisons of pretherapy findings with normative values using confidence intervals indicated that both groups performed within the average range on most measures. Outstanding deficits at baseline were observed on tests of fine-motor, psychomotor, and timed language skills, and are likely to be attributable to tumor-related effects. Comparisons of pre- versus posttherapy neuropsychological test findings indicated no significant interval changes for either group. Results suggest that surgery and radiotherapy are not associated with acute effects on neuropsychological functions

  13. mTHPC-mediated photodynamic diagnosis of malignant brain tumors

    International Nuclear Information System (INIS)

    Zimmermann, A.

    2001-03-01

    Radical tumor resection is the basis for prolonged survival of patients suffering from malignant brain tumors such as glioblastoma multiform. We have carried out a phase II study involving 22 patients with malignant brain tumors to assess the feasibility and the effectiveness of the combination of intraoperative photodynamic diagnosis (PDD) and fluorescence-guided resection (FGR) mediated by the second generation photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). In addition, intraoperative photodynamic therapy (PDT) was performed. Several commercially available fluorescence diagnostic systems were investigated for their applicability for clinical practice. We have adapted and optimized a diagnostic system which includes a surgical microscope, an excitation light source (filtered to 370-440 nm), a video camera detection system, and a spectrometer for clear identification of the mTHPC fluorescence emission at 652 nm. Especially in regions of faint fluorescence it turned out to be essential to maximize the spectral information by optimizing and matching the spectral properties of all components, such as excitation source, camera and color filters. In summary, based on 138 tissue samples derived from 22 tumor specimens we have been able to achieve a sensitivity of 87.9 % and a specificity of 95.7 %. This study demonstrates that mTHPC-mediated intraoperative fluorescence-guided resection followed by photodynamic therapy is a feasible concept. (author)

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

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

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

  15. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

    Directory of Open Access Journals (Sweden)

    Hangjun Ruan

    1999-11-01

    Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

  16. The role of stereotactic radiation therapy in the management of children with brain tumors.

    Science.gov (United States)

    Lew, C M; LaVally, B

    1995-10-01

    Conventional radiation therapy plays an important role in the management of intracranial tumors in children. For certain tumors radiation therapy serves as the primary mode of treatment, and for others it plays an adjuvant role with surgery and/or chemotherapy. Improvements in long-term survival rates have focused attention on the long-term sequelae of brain tumors and their treatment, and the sequelae, in turn, have become important targets for clinical investigation. Long-term side effects of particular concern in children include cranial nerve damage, memory and intellectual deficits, pituitary-hypothalamic dysfunction, demyelinization of brain tissue, and secondary malignancies. A new form of radiation therapy, stereotactic radiotherapy (SRT), merges the technologies of stereotactic surgery and conventional fractionated radiotherapy. The intent is to deliver maximum tumoricidal doses to the target while limiting the dose to normal surrounding brain tissue. The key feature of SRT is a noninvasive, relocatable immobilization system to assure accurate and reproducible positioning during planning and treatment. The headframes used for children have been modified to address their specific needs. The complexities of this process require careful preparation of patients and their families and the participation of many disciplines. Long-term follow-up will be essential to evaluate the effectiveness of this innovative treatment.

  17. Volumetric multimodality neural network for brain tumor segmentation

    Science.gov (United States)

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

    2017-11-01

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

  18. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  19. Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

    Science.gov (United States)

    Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

    2016-01-01

    Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  2. A fractional motion diffusion model for grading pediatric brain tumors.

    Science.gov (United States)

    Karaman, M Muge; Wang, He; Sui, Yi; Engelhard, Herbert H; Li, Yuhua; Zhou, Xiaohong Joe

    2016-01-01

    To demonstrate the feasibility of a novel fractional motion (FM) diffusion model for distinguishing low- versus high-grade pediatric brain tumors; and to investigate its possible advantage over apparent diffusion coefficient (ADC) and/or a previously reported continuous-time random-walk (CTRW) diffusion model. With approval from the institutional review board and written informed consents from the legal guardians of all participating patients, this study involved 70 children with histopathologically-proven brain tumors (30 low-grade and 40 high-grade). Multi- b -value diffusion images were acquired and analyzed using the FM, CTRW, and mono-exponential diffusion models. The FM parameters, D fm , φ , ψ (non-Gaussian diffusion statistical measures), and the CTRW parameters, D m , α , β (non-Gaussian temporal and spatial diffusion heterogeneity measures) were compared between the low- and high-grade tumor groups by using a Mann-Whitney-Wilcoxon U test. The performance of the FM model for differentiating between low- and high-grade tumors was evaluated and compared with that of the CTRW and the mono-exponential models using a receiver operating characteristic (ROC) analysis. The FM parameters were significantly lower ( p  < 0.0001) in the high-grade ( D fm : 0.81 ± 0.26, φ : 1.40 ± 0.10, ψ : 0.42 ± 0.11) than in the low-grade ( D fm : 1.52 ± 0.52, φ : 1.64 ± 0.13, ψ : 0.67 ± 0.13) tumor groups. The ROC analysis showed that the FM parameters offered better specificity (88% versus 73%), sensitivity (90% versus 82%), accuracy (88% versus 78%), and area under the curve (AUC, 93% versus 80%) in discriminating tumor malignancy compared to the conventional ADC. The performance of the FM model was similar to that of the CTRW model. Similar to the CTRW model, the FM model can improve differentiation between low- and high-grade pediatric brain tumors over ADC.

  3. Advancing theranostics with tumor-targeting peptides for precision otolaryngology

    Directory of Open Access Journals (Sweden)

    Chadwick L. Wright

    2016-06-01

    Full Text Available Worldwide, about 600,000 head and neck squamous cell carcinoma (HNSCC are detected annually, many of which involve high risk human papilloma virus (HPV. Surgery is the primary and desired first treatment option. Following surgery, the existence of cancer cells at the surgical margin is strongly associated with eventual recurrence of cancer and a poor outcome. Despite improved surgical methods (robotics, microsurgery, endoscopic/laparoscopic, and external imaging, surgeons rely only on their vision and touch to locate tumors during surgery. Diagnostic imaging systems like computed tomography (CT, magnetic resonance imaging (MRI, single-photon emission computed tomography (SPECT and positron-emission tomography (PET are too large, slow and costly to use efficiently during most surgeries and, ultrasound imaging, while fast and portable, is not cancer specific. This purpose of this article is to review the fundamental technologies that will radically advance Precision Otolaryngology practices to the benefit of patients with HNSCC. In particular, this article will address the potential for tumor-targeting peptides to enable more precise diagnostic imaging while simultaneously advancing new therapeutic paradigms for next generation image-guided surgery, tumor-specific chemotherapeutic delivery and tumor-selective targeted radiotherapy (i.e., theranostic. Keywords: Squamous cell carcinoma, Peptide, Optical surgical navigation, Diagnostic imaging, Theranostic

  4. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  5. Dosimetric Comparison Between 3DCRT and IMRT Using Different Multileaf Collimators in the Treatment of Brain Tumors

    International Nuclear Information System (INIS)

    Ding Meisong; Newman, Francis M.S.; Chen Changhu; Stuhr, Kelly; Gaspar, Laurie E.

    2009-01-01

    We investigated the differences between 3-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT), and the impact of collimator leaf-width on IMRT plans for the treatment of nonspherical brain tumors. Eight patients treated by 3DCRT with Novalis were selected. We developed 3 IMRT plans with different multileaf collimators (Novalis m3, Varian MLC-120, and Varian MLC-80) with the same treatment margins, number of beams, and gantry positions as in the 3DCRT treatment plans. Treatment planning utilized the BrainLAB treatment planning system. For each patient, the dose constraints and optimization parameters remained identical for all plans. The heterogeneity index, the percentage target coverage, critical structures, and normal tissue volumes receiving 50% of the prescription dose were calculated to compare the dosimetric difference. Equivalent uniform dose (EUD) and tumor control probability (TCP) were also introduced to evaluate the radiobiological effect for different plans. We found that IMRT significantly improved the target dose homogeneity compared to the 3DCRT. However, IMRT showed the same radiobiological effect as 3DCRT. For the brain tumors adjacent to (or partially overlapping with) critical structures, IMRT dramatically spared the volume of the critical structures to be irradiated. In IMRT plans, the smaller collimator leaf width could reduce the volume of critical structures irradiated to the 50% level for those partially overlapping with the brain tumors. For relatively large and spherical brain tumors, the smaller collimator leaf widths give no significant benefit

  6. Radiotherapy using bleomycin, ACNU, and vincristine for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Ryuichi; Murakami, Naoto; Suzuki, Yasuo; Takeda, Norio; Arai, Hiroyuki; Konno, Kimikazu; Tanimura, Ken-ichi

    1984-08-01

    Radiotherapy combined with bleomycin, ACNU, and vincristine was performed on 106 patients with malignant brain tumors. The treatment protocol was based on the concept of combination chemotherapy or chemoradiotherapy and synchronized chemoradiotherapy. For the purpose of synchronized chemoradiotherapy, bleomycin, ACNU, and vincristine were used as G/sub 2/M cell cycle phase accumulator, and radiation and bleomycin were used as agents to which G/sub 2/M or G/sub 2/ phase cells are sensitive. The short-term results of the chemoradiotherapy were evaluated by measuring tumor regression by computerized tomography (CT) in 80 patients with evaluable CT lesions. The response rate was 67% (6/9) for astrocytoma, 29% (7/24) for anaplastic glioma, 67% (4/6) for pontine glioma, 100%(5/5) for malignant lymphoma, 100% (8/8) for germ cell tumors and 65% (15/23) for metastatic tumors. A control study was performed using radiation alone on another 18 patients with metastatic tumors, and the response rate was 50% (9/18). Among the 106 patients treated with chemoradiotherapy, the major side effects observed were as follows: leukopenia in 33 patients (31%), thrombocytopenia in 14 (13%), paralytic ileus in 2 (2%), peripheral neuropathy in 2 (2%), and lung fibrosis in 1 (1%). Contrary to expectation, low-grade astrocytomas responded much better to the chemoradiotherapy than high-grade astrocytomas.

  7. Assessment of functional status in children with brain tumors

    International Nuclear Information System (INIS)

    Sugita, Yasuo; Kobayashi, Seiichi; Uegaki, Masami; Katayama, Masahiko; Miyagi, Jun; Iryo, Osamu; Shigemori, Minoru; Kuramoto, Shinken; Ootsubo, Masaaki

    1987-01-01

    Thirty children treated for brain tumors between 1978 - 1985 at Kurume university hospital were evaluated for alternation in intellectual, emotional, and social function. They were 15 males and 15 females, aged 3 to 16 years, on the averaged 1.7 years after treatment. Twenty-eight children had no neurological deficits and 2 children had slight neurological deficits. It was possible for twenty-eight children to be evaluated for intelligence quotient by Wechsler Intelligence Scale for Children-revised and Tanaka-Binet. The median score and standard deviation of intelligence quotient (IQ) test in children with brain tumors were as follows; verbal IQ: 84 ± 16, performance IQ: 77 ± 20, full scale IQ: 80 ± 20. There children with brain tumors obtained significant low IQ scores than children (t-test, P < 0.01). Twenty-one (72 %) children showed subnormal IQ scores (IQ < 90) and 7 children showed normal IQ scores (IQ ≥ 90). Concerning social and emotional function, twelve children (45.7 %) showed abnormal behaviour. The median scores and standard deviation of IQ scores in cranial irradiated patients were as follows; verbal IQ: 79 ± 13, performance IQ: 71 ± 15, full scale IQ: 71 ± 14. Especially, ten of twelve cranial irradiated patients showed subnormal IQ scores. Also, cranial irradiated patients obtained significant low IQ scores than non-cranial irradiated patients (t-test, P < 0.05). Serial evaluation of three cranial irradiated patients revealed further deterioration without recurrence of tumor and hydrocephalus. The results are discussed to: (1) the effects and mechanism of cranial irradiation on cognitive development: (2) the relationship between cognitive dysfunction and irradiation methods. The effects and mechanism of cranial irradiation on cognitive dysfunction is considered to be not only injury of cortex but also injury of fiber tracts. Also, cognitive dysfunction is apt to be related to age of irradiated patients. (J.P.N.)

  8. Assessment of functional status in children with brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Yasuo; Kobayashi, Seiichi; Uegaki, Masami; Katayama, Masahiko; Miyagi, Jun; Iryo, Osamu; Shigemori, Minoru; Kuramoto, Shinken; Ootsubo, Masaaki

    1987-06-01

    Thirty children treated for brain tumors between 1978 - 1985 at Kurume university hospital were evaluated for alternation in intellectual, emotional, and social function. They were 15 males and 15 females, aged 3 to 16 years, on the averaged 1.7 years after treatment. Twenty-eight children had no neurological deficits and 2 children had slight neurological deficits. It was possible for twenty-eight children to be evaluated for intelligence quotient by Wechsler Intelligence Scale for Children-revised and Tanaka-Binet. The median score and standard deviation of intelligence quotient (IQ) test in children with brain tumors were as follows; verbal IQ: 84 +- 16, performance IQ: 77 +- 20, full scale IQ: 80 +- 20. There children with brain tumors obtained significant low IQ scores than children (t-test, P < 0.01). Twenty-one (72 %) children showed subnormal IQ scores (IQ < 90) and 7 children showed normal IQ scores (IQ greater than or equal to 90). Concerning social and emotional function, twelve children (45.7 %) showed abnormal behaviour. The median scores and standard deviation of IQ scores in cranial irradiated patients were as follows; verbal IQ: 79 +- 13, performance IQ: 71 +- 15, full scale IQ: 71 +- 14. Especially, ten of twelve cranial irradiated patients showed subnormal IQ scores. Also, cranial irradiated patients obtained significant low IQ scores than non-cranial irradiated patients (t-test, P < 0.05). Serial evaluation of three cranial irradiated patients revealed further deterioration without recurrence of tumor and hydrocephalus. The results are discussed to: (1) the effects and mechanism of cranial irradiation on cognitive development: (2) the relationship between cognitive dysfunction and irradiation methods. The effects and mechanism of cranial irradiation on cognitive dysfunction is considered to be not only injury of cortex but also injury of fiber tracts. Also, cognitive dysfunction is apt to be related to age of irradiated patients. (J.P.N.).

  9. Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

    Science.gov (United States)

    Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

    2015-01-01

    The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

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

    Science.gov (United States)

    Gupta, Anjali; Pahuja, Gunjan

    2017-08-01

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

  11. Applications of polymeric micelles with tumor targeted in chemotherapy

    International Nuclear Information System (INIS)

    Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli

    2012-01-01

    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core–shell structure (with diameters of 10 ∼ 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles’ surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  12. Thermal dosimetry studies of ultrasonically induced hyperthermia in normal dog brain and in experimental brain tumors

    International Nuclear Information System (INIS)

    Britt, R.H.; Pounds, D.W.; Stuart, J.S.; Lyons, B.E.; Saxer, E.L.

    1984-01-01

    In a series of 16 acute experiments on pentobarbital anesthetized dogs, thermal distributions generated by ultrasonic heating using a 1 MHz PZT transducer were compared with intensity distributions mapped in a test tank. Relatively flat distributions from 1 to 3 cm have been mapped in normal dog brain using ''shaped'' intensity distributions generated from ultrasonic emission patterns which are formed by the interaction between compressional, transverse and flexural modes activated within the crystal. In contrast, these same intensity distributions generated marked temperature variations in 3 malignant brain tumors presumably due to variations in tumor blood flow. The results of this study suggest that a practical clinical system for uniform heating of large tumor volumes with varying volumes and geometries is not an achievable goal. The author's laboratory is developing a scanning ultrasonic rapid hyperthermia treatment system which will be able to sequentially heat small volume of tumor tissue either to temperatures which will sterilize tumor or to a more conventional thermal dose. Time-temperature studies of threshold for thermal damage in normal dog brain are currently in progress

  13. Detection of brain tumor margins using optical coherence tomography

    Science.gov (United States)

    Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

    2018-02-01

    In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, non-cancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancer-infiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End- Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

  14. Factors affecting radiation injury after interstitial brachytherapy for brain tumors

    International Nuclear Information System (INIS)

    Leibel, S.A.; Gutin, P.H.; Davis, R.L.

    1991-01-01

    The effects of brachytherapy on normal brain tissue are not easily delineated in the clinical setting because of the presence of concurrent radiation-induced changes in the coexistent brain tumor. Sequential morphologic studies performed after the implantation of radioactive sources into the brains of experimental animals have provided a better understanding of the character and magnitude of the structural changes produced by interstitial irradiation on normal brain tissue. Furthermore, the clinical experience accumulated thus far provides not only relevant information, but also some guidelines for future treatment policies. In this paper, the authors summarize the experimental findings and review the pathologic and clinical features of brain injury caused by interstitial brachytherapy. A number of studies in the older literature examined the effects of radioisotopes such as radium-226 (38--43), radon-22 (44--46), gold-198 (29,47--50), tantalum-182 (29,51,52) yttrium-9- (50,53,54), and cobalt-60 (29,50,55). This review is restricted to low- and high-activity encapsulated iodine-125 ( 125 I) and iridium-192 ( 192 Ir), the isotopes that are most commonly used in current clinical practice

  15. Exploratory case-control study of brain tumors in adults

    International Nuclear Information System (INIS)

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-01-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies

  16. Psychosocial profile of pediatric brain tumor survivors with neurocognitive complaints.

    Science.gov (United States)

    de Ruiter, Marieke Anna; Schouten-van Meeteren, Antoinette Yvonne Narda; van Vuurden, Dannis Gilbert; Maurice-Stam, Heleen; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Oosterlaan, Jaap; Grootenhuis, Martha Alexandra

    2016-02-01

    With more children surviving a brain tumor, neurocognitive consequences of the tumor and its treatment become apparent, which could affect psychosocial functioning. The present study therefore aimed to assess psychosocial functioning of pediatric brain tumor survivors (PBTS) in detail. Psychosocial functioning of PBTS (8-18 years) with parent-reported neurocognitive complaints was compared to normative data on health-related quality of life (HRQOL), self-esteem, psychosocial adjustment, and executive functioning (one-sample t tests) and to a sibling control group on fatigue (independent-samples t test). Self-, parent-, and teacher-report questionnaires were included, where appropriate, providing complementary information. Eighty-two PBTS (mean age 13.4 years, SD 3.2, 49 % males) and 43 healthy siblings (mean age 14.3, SD 2.4, 40 % males) were included. As compared to the normative population, PBTS themselves reported decreased physical, psychological, and generic HRQOL (d = 0.39-0.62, p psychosocial adjustment seemed not to be affected. Parents of PBTS reported more psychosocial (d = 0.81, p psychosocial adjustment problems for female PBTS aged 8-11 years than for the female normative population (d = 0.69, p psychosocial problems, as reported by PBTS, parents, and teachers. Systematic screening of psychosocial functioning is necessary so that tailored support from professionals can be offered to PBTS with neurocognitive complaints.

  17. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

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

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen; Haberer, Thomas; Jaekel, Oliver

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

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

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

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

  1. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

    Science.gov (United States)

    Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  2. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    International Nuclear Information System (INIS)

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  3. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  4. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

    Science.gov (United States)

    Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

    2007-12-01

    The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

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

    NARCIS (Netherlands)

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

    2014-01-01

    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

  6. SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Z [East Carolina University, Greenville, NC (United States); Feng, Y [East Carolina Univ, Rockville, MD (United States); Lo, S [Case Western Reserve University, Cleveland, OH (United States); Grecula, J [Ohio State University, Columbus, OH (United States); Mayr, N; Yuh, W [University of Washington, Seattle, WA (United States)

    2015-06-15

    Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) and lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as adaptive

  7. SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

    International Nuclear Information System (INIS)

    Huang, Z; Feng, Y; Lo, S; Grecula, J; Mayr, N; Yuh, W

    2015-01-01

    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

  8. Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death

  9. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies....

  10. Targeting sarcoma tumor-initiating cells through differentiation therapy

    Directory of Open Access Journals (Sweden)

    Dan Han

    2017-05-01

    Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

  11. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Peng

    2008-10-01

    Full Text Available Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI, which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therapy

  12. Automated delineation of brain structures in patients undergoing radiotherapy for primary brain tumors: From atlas to dose–volume histograms

    International Nuclear Information System (INIS)

    Conson, Manuel; Cella, Laura; Pacelli, Roberto; Comerci, Marco; Liuzzi, Raffaele; Salvatore, Marco; Quarantelli, Mario

    2014-01-01

    Purpose: To implement and evaluate a magnetic resonance imaging atlas-based automated segmentation (MRI-ABAS) procedure for cortical and sub-cortical grey matter areas definition, suitable for dose-distribution analyses in brain tumor patients undergoing radiotherapy (RT). Patients and methods: 3T-MRI scans performed before RT in ten brain tumor patients were used. The MRI-ABAS procedure consists of grey matter classification and atlas-based regions of interest definition. The Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm was applied to structures manually delineated by four experts to generate the standard reference. Performance was assessed comparing multiple geometrical metrics (including Dice Similarity Coefficient – DSC). Dosimetric parameters from dose–volume-histograms were also generated and compared. Results: Compared with manual delineation, MRI-ABAS showed excellent reproducibility [median DSC ABAS = 1 (95% CI, 0.97–1.0) vs. DSC MANUAL = 0.90 (0.73–0.98)], acceptable accuracy [DSC ABAS = 0.81 (0.68–0.94) vs. DSC MANUAL = 0.90 (0.76–0.98)], and an overall 90% reduction in delineation time. Dosimetric parameters obtained using MRI-ABAS were comparable with those obtained by manual contouring. Conclusions: The speed, reproducibility, and robustness of the process make MRI-ABAS a valuable tool for investigating radiation dose–volume effects in non-target brain structures providing additional standardized data without additional time-consuming procedures

  13. Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

    Directory of Open Access Journals (Sweden)

    Sabrina M Heisel

    Full Text Available BACKGROUND: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation. CONCLUSIONS/SIGNIFICANCE: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

  14. Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

    Science.gov (United States)

    Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

    2017-10-01

    Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

  15. Growth hormone deficiency in children with brain tumors

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; Morris-Jones, P.; Bamford, F.N.; Ribeiro, G.G.; Pearson, D.

    1976-01-01

    Nine children with brain tumors are described who have received various combinations of treatment, including surgery, radiotherapy, and chemotherapy. Many of the children were noted to be of short stature. Endocrine assessment was carried out from 2 to 10 years after treatment. The combined results of insulin tolerance and Bovril stimulation tests show an impaired growth hormone response in six of the nine children. Bone age is retarded in all cases, and the present height is below the 10th percentile in five of the six. The cause of this growth hormone deficiency is obscure, but further studies are in progress

  16. Analysis of mobile phone use among young patients with brain tumors in Japan.

    Science.gov (United States)

    Sato, Yasuto; Kojimahara, Noriko; Yamaguchi, Naohito

    2017-07-01

    The purpose of this study was to clarify ownership and usage of mobile phones among young patients with brain tumors in Japan. The subjects of this study were patients with brain tumors diagnosed between 2006 and 2010 who were between the ages of 6 and 18 years. The target population for the analysis was 82 patients. Patients were divided into two groups: 16 patients who were mobile phone owners 1 year before diagnosis, and 66 patients who did not own mobile phones (non-owners). Using data on the mobile phone ownership rate obtained from three general-population surveys, we calculated the expected number of mobile phone owners. The three age-adjusted standardized ownership ratios were 0.83 (95% confidence interval [CI]: 0.56-1.22), 0.51 (95% CI: 0.24-1.04), and 0.75 (95% CI: 0.42-1.32). The mobile phone ownership prevalence among the young Japanese patients with brain tumors in the current study does not differ from available estimates for the general population of corresponding age. However, since the use of mobile phones among children is increasing annually, investigations into the health effects of mobile phone use among children should continue. Bioelectromagnetics. 38:349-355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Utility and limitation of radiosurgery for metastatic brain tumors

    International Nuclear Information System (INIS)

    Kagawa, Kota; Kiya, Katsuzo; Satoh, Hideki; Mizoue, Tatsuya; Matsushige, Toshinori; Araki, Hayato; Akimitsu, Tomohide

    2003-01-01

    The purpose of this study was to evaluate the utility and limitations of radiosurgery for metastatic brain lesions, and to compare the clinical results of stereotactic radiosurgery (SRS) with those of whole-brain radiation therapy (WBRT) in 45 patients with metastatic brain tumors. The patients were divided into two groups: the SRS group (22 patients) and the WBRT group (23 patients). Mean survival was not significantly different between the two groups. However, in patients with 6 or more lesions, both survival time and recurrence-free time in the SRS group were inferior to those in the WBRT group. The main complication in the SRS group was perifocal edema, while dementia was seen in the WBRT group. The bedridden period was longer in the WBRT group than in the SRS group. Death caused by brain lesions was rare in both groups. From these results, SRS preserves high quality of life longer than WBRT, but SRS should be cautiously used in patients with 6 or more lesions. (author)

  18. FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

    Science.gov (United States)

    Briest, Franziska; Berg, Erika; Grass, Irina; Freitag, Helma; Kaemmerer, Daniel; Lewens, Florentine; Christen, Friederike; Arsenic, Ruza; Altendorf-Hofmann, Annelore; Kunze, Almut; Sänger, Jörg; Knösel, Thomas; Siegmund, Britta; Hummel, Michael; Grabowski, Patricia

    2015-01-01

    Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs. PMID:25797272

  19. Development of model plans in three dimensional conformal radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Pyo, Hongryull; Kim, Gwieon; Keum, Kichang; Chang, Sekyung; Suh, Changok; Lee, Sanghoon

    2002-01-01

    Three dimensional conformal radiotherapy planning is being used widely for the treatment of patients with brain tumor. However, it takes much time to develop an optimal treatment plan, therefore, it is difficult to apply this technique to all patients. To increase the efficiency of this technique, we need to develop standard radiotherapy plans for each site of the brain. Therefore we developed several 3 dimensional conformal radiotherapy plans (3D plans) for tumors at each site of brain, compared them with each other, and with 2 dimensional radiotherapy plans. Finally model plans for each site of the brain were decided. Imaginary tumors, with sizes commonly observed in the clinic, were designed for each site of the brain and drawn on CT images. The planning target volumes (PTVs) were as follows; temporal tumor-5.7 x 8.2 x 7.6 cm, suprasellar tumor-3 x 4 x 4.1 cm, thalamic tumor-3.1 x 5.9 x 3.7 cm, frontoparietal tumor-5.5 x 7 x 5.5 cm, and occipitoparietal tumor-5 x 5.5 x 5 cm. Plans using parallel opposed 2-portals and/or 3 portals including fronto-vertex and 2 lateral fields were developed manually as the conventional 2D plans, and 3D noncoplanar conformal plans were developed using beam's eye view and the automatic block drawing tool. Total tumor dose was 54 Gy for a suprasellar tumor, 59.4 Gy and 72 Gy for the other tumors. All dose plans (including 2D plans) were calculated using 3D plan software. Developed plans were compared with each other using dose-volume histograms (DVH), normal tissue complication probabilities (NTCP) and variable dose statistic values (minimum, maximum and mean dose, D5, V83, V85 and V95). Finally a best radiotherapy plan for each site of brain was selected. 1) Temporal tumor; NTCPs and DVHs of the normal tissue of all 3D plans were superior to 2D plans and this trend was more definite when total dose was escalated to 72 Gy (NTCPs of normal brain 2D plans: 27%, 8% → 3D plans: 1%, 1%). Various dose statistic values did not show any

  20. Aberrant paramagnetic signals outside the tumor volume on routine surveillance MRI of brain tumor patients.

    Science.gov (United States)

    Yust-Katz, Shlomit; Inbar, Edna; Michaeli, Natalia; Limon, Dror; Siegal, Tali

    2017-09-01

    Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only studies containing sequences of either susceptibility weighted images or gradient echo or blood oxygenation level dependent imaging were included. Lesions inside the tumor volume were not considered. 68 studies fulfilled the above criteria and included 48 patients with previous RT (35 followed for >2 years and 13 for 1 year) and 20 patients who were not treated with RT. The median age at time of irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%) patients followed for >2 years after RT and in only 1/13 (8%) patients followed for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ from the control group [2/20 (9%)]. Most lesions were within the radiation field and none of the patients had related symptomatology. The number and incidence of these lesions increased with time and amounted to 75% over 3 years post RT. MRI paramagnetic signal aberrations are common findings in adult brain tumor patients that evolve over time after RT. The clinical significance of these lesions needs further investigation.

  1. The folate receptor as a molecular target for tumor-selective radionuclide delivery

    International Nuclear Information System (INIS)

    Ke, C.-Y.; Mathias, Carla J.; Green, Mark A.

    2003-01-01

    The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We review here some background on the folate receptor as tumor-associated molecular target for drug delivery, and briefly survey the literature on tumor-targeting with radiolabeled folate-chelate conjugates

  2. SU-C-BRA-06: Automatic Brain Tumor Segmentation for Stereotactic Radiosurgery Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y; Stojadinovic, S; Jiang, S; Timmerman, R; Abdulrahman, R; Nedzi, L; Gu, X [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: Stereotactic radiosurgery (SRS), which delivers a potent dose of highly conformal radiation to the target in a single fraction, requires accurate tumor delineation for treatment planning. We present an automatic segmentation strategy, that synergizes intensity histogram thresholding, super-voxel clustering, and level-set based contour evolving methods to efficiently and accurately delineate SRS brain tumors on contrast-enhance T1-weighted (T1c) Magnetic Resonance Images (MRI). Methods: The developed auto-segmentation strategy consists of three major steps. Firstly, tumor sites are localized through 2D slice intensity histogram scanning. Then, super voxels are obtained through clustering the corresponding voxels in 3D with reference to the similarity metrics composited from spatial distance and intensity difference. The combination of the above two could generate the initial contour surface. Finally, a localized region active contour model is utilized to evolve the surface to achieve the accurate delineation of the tumors. The developed method was evaluated on numerical phantom data, synthetic BRATS (Multimodal Brain Tumor Image Segmentation challenge) data, and clinical patients’ data. The auto-segmentation results were quantitatively evaluated by comparing to ground truths with both volume and surface similarity metrics. Results: DICE coefficient (DC) was performed as a quantitative metric to evaluate the auto-segmentation in the numerical phantom with 8 tumors. DCs are 0.999±0.001 without noise, 0.969±0.065 with Rician noise and 0.976±0.038 with Gaussian noise. DC, NMI (Normalized Mutual Information), SSIM (Structural Similarity) and Hausdorff distance (HD) were calculated as the metrics for the BRATS and patients’ data. Assessment of BRATS data across 25 tumor segmentation yield DC 0.886±0.078, NMI 0.817±0.108, SSIM 0.997±0.002, and HD 6.483±4.079mm. Evaluation on 8 patients with total 14 tumor sites yield DC 0.872±0.070, NMI 0.824±0

  3. Prediction of tumor-brain adhesion in intracranial meningiomas by MR imaging and DSA

    International Nuclear Information System (INIS)

    Takeguchi, Takashi; Miki, Hitoshi; Shimizu, Teruhiko; Kikuchi, Keiichi; Mochizuki, Teruhito; Ohue, Shiro; Ohnishi, Takanori

    2003-01-01

    The purpose of this study was to evaluate the usefulness of MRI (magnetic resonance imaging) and DSA (digital subtraction angiography) by using preoperative MRI and DSA findings in the examination of meningiomas before excision. In particular, we focused on their usefulness in predicting tumor-brain adhesion during surgery. The subjects were 36 patients with intracranial meningioma who underwent tumor excision at which time neurosurgeons examined the tumor-brain adhesion. Two neurosurgeons evaluated the degree of tumor-brain adhesion from operation records and videotapes recorded during surgery. Two neuroradiologists retrospectively evaluated the preoperative MRI findings including tumor diameter, signal intensity of the tumor parenchyma obtained with T 2 -weighted imaging (T 2 WI), characteristics of the tumor-brain interface, and degree of peritumoral brain edema. The vascular supply was also evaluated from the preoperative DSA findings. The relationship between these MRI and DSA findings and the degree of tumor-brain adhesion during surgery as classified by the neurosurgeons was statistically analyzed. The degree of peritumoral brain edema and the shapes and characteristics of the tumor-brain interface, including the findings of FLAIR (fluid-attenuated inversion recovery) imaging and vascular supply observed by DSA, were significantly correlated with tumor-brain adhesion. In particular, the shapes and characteristics of the tumor-brain interface as observed by T 1 -weighted imaging (T 1 WI), T2WI, and FLAIR, respectively, as well as the vascular supply observed by DSA, were closely correlated with the degree of tumor-brain adhesion encountered during surgery. According to these results, we developed a method of predicting tumor-brain adhesion that considers the shape of the tumor-brain interface revealed by MRI and the vascular supply revealed by DSA. We retrospectively examined the findings of MRI and DSA performed before excision of meningioma and clarified

  4. Comparison of two brain tumor-localizing MRI agent. GD-BOPTA and GD-DTPA. MRI and ICP study of rat brain tumor model

    International Nuclear Information System (INIS)

    Zhang, T.; Matsumura, A.; Yamamoto, T.; Yoshida, F.; Nose, T.

    2000-01-01

    In this study, we compared the behavior of Gd-BOPTA as a brain tumor selective contrast agent with Gd-DTPA in a common dose of 0.1 mmol/kg. We performed a MRI study using those two agent as contrast material, and we measured tissue Gd-concentrations by ICP-AES. As a result, Gd-BOPTA showed a better MRI enhancement in brain tumor. ICP showed significantly greater uptake of Gd-BOPTA in tumor samples, at all time course peaked at 5 minutes after administration, Gd being retained for a longer time in brain tumor till 2 hours, without rapid elimination as Gd-DTPA. We conclude that Gd-BOPTA is a new useful contrast material for MR imaging in brain tumor and an effective absorption agent for neutron capture therapy for further research. (author)

  5. HER2-Targeted Polyinosine/Polycytosine Therapy Inhibits Tumor Growth and Modulates the Tumor Immune Microenvironment.

    Science.gov (United States)

    Zigler, Maya; Shir, Alexei; Joubran, Salim; Sagalov, Anna; Klein, Shoshana; Edinger, Nufar; Lau, Jeffrey; Yu, Shang-Fan; Mizraji, Gabriel; Globerson Levin, Anat; Sliwkowski, Mark X; Levitzki, Alexander

    2016-08-01

    The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits; however, patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study, we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vector induced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immunocompetent mice. The data presented here could open additional avenues in the treatment of HER2-positive breast cancer. Cancer Immunol Res; 4(8); 688-97. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. FDG-PET on Irradiated Brain Tumor: Ten Years' Summary

    International Nuclear Information System (INIS)

    Wang, S.X.; Boethius, J.; Ericson, K.

    2006-01-01

    Purpose: To evaluate FDG-PET in post-radiotherapy differentiation of tumor recurrence/malignant degeneration and radiation reaction, and to assess the role of PET in terms of survival. Material and Methods: 117 consecutive patients with a total of 156 FDG-PET examinations with positive but non-diagnostic MRI and/or CT were included. Final diagnosis was based on histopathology or correlated with radiologic and clinical follow-up. Brain metastases from lung carcinomas were further studied separately. Survival time was analysed using the Kaplan-Meier method. Results: There were 61 true-positive, 2 false-positive, 15 false-negative, and 51 true-negative PET examinations; 5 positive and 22 negative PET examinations were indeterminate. The positive predictive value of a PET examination was 96% in all and 100% in brain metastases from lung carcinoma. The negative predictive value based on the histopathologic results was 55.6%. Survival time was significantly longer in patients with negative PET. Conclusion: FDG-PET is a valuable tool in the detection of tumor recurrence, especially lung carcinoma metastasis. FDG uptake is a prognostic marker

  7. Is outpatient brain tumor surgery feasible in India?

    Science.gov (United States)

    Turel, Mazda K; Bernstein, Mark

    2016-01-01

    The current trend in all fields of surgery is towards less invasive procedures with shorter hospital stays. The reasons for this change include convenience to patients, optimal resource utilization, and cost saving. Technological advances in neurosurgery, aided by improvements in anesthesia, have resulted in surgery that is faster, simpler, and safer with excellent perioperative recovery. As a result of improved outcomes, some centers are performing brain tumor surgery on an outpatient basis, wherein patients arrive at the hospital the morning of their procedure and leave the hospital the same evening, thus avoiding an overnight stay in the hospital. In addition to the medical benefits of the outpatient procedure, its impact on patient satisfaction is substantial. The economic benefits are extremely favorable for the patient, physician, as well as the hospital. In high volume centers, a day surgery program can exist alongside those for elective and emergency surgeries, providing another pathway for patient care. However, due to skepticism surrounding the medicolegal aspects, and how radical the concept at first sounds, these procedures have not gained widespread popularity. We provide an overview of outpatient brain tumor surgery in the western world, discussing the socioeconomic, medicolegal, and ethical issues related to its adaptability in a developing nation.

  8. Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

    Science.gov (United States)

    Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2017-01-01

    The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

  10. Monte Carlo modeling and optimization of contrast-enhanced radiotherapy of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lopez, C E; Garnica-Garza, H M, E-mail: hgarnica@cinvestav.mx [Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Unidad Monterrey, Via del Conocimiento 201 Parque de Investigacion e Innovacion Tecnologica, Apodaca NL CP 66600 (Mexico)

    2011-07-07

    Contrast-enhanced radiotherapy involves the use of a kilovoltage x-ray beam to impart a tumoricidal dose to a target into which a radiological contrast agent has previously been loaded in order to increase the x-ray absorption efficiency. In this treatment modality the selection of the proper x-ray spectrum is important since at the energy range of interest the penetration ability of the x-ray beam is limited. For the treatment of brain tumors, the situation is further complicated by the presence of the skull, which also absorbs kilovoltage x-ray in a very efficient manner. In this work, using Monte Carlo simulation, a realistic patient model and the Cimmino algorithm, several irradiation techniques and x-ray spectra are evaluated for two possible clinical scenarios with respect to the location of the target, these being a tumor located at the center of the head and at a position close to the surface of the head. It will be shown that x-ray spectra, such as those produced by a conventional x-ray generator, are capable of producing absorbed dose distributions with excellent uniformity in the target as well as dose differential of at least 20% of the prescribed tumor dose between this and the surrounding brain tissue, when the tumor is located at the center of the head. However, for tumors with a lateral displacement from the center and close to the skull, while the absorbed dose distribution in the target is also quite uniform and the dose to the surrounding brain tissue is within an acceptable range, hot spots in the skull arise which are above what is considered a safe limit. A comparison with previously reported results using mono-energetic x-ray beams such as those produced by a radiation synchrotron is also presented and it is shown that the absorbed dose distributions rendered by this type of beam are very similar to those obtained with a conventional x-ray beam.

  11. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

    Directory of Open Access Journals (Sweden)

    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

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

    International Nuclear Information System (INIS)

    Mendes, Ana Carina; Ribeiro, Andre Santos; Oros-Peusquens, Ana Maria; Langen, Karl Josef; Shah, Jon; Ferreira, Hugo Alexandre

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-18

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

  14. CT-guided stereotaxic biopsy in 104 cases of brain tumors

    International Nuclear Information System (INIS)

    Niizuma, Hiroshi; Nakasato, Nobukazu; Jokura, Hidehumi; Otsuki, Taisuke; Katakura, Ryuichi; Suzuki, Jiro

    1988-01-01

    Biopsy of suspected brain tumor was performed on 104 cases using Leksell's CT-guided stereotaxic system. The entire operation was performed in the CT room. A Backlund's spiral biopsy needle was advanced to the target point in a stepwise fashion and two to nine tissue samples were obtained from one to three biopsy tracks. Tissue sampling was impossible in two cases because the tumors were too hard for biopsy needle to advance. Also, sampling was sometimes difficult in the case of soft and necrotic tumor, cystic tumor, already treated (irradiated) tumor and the lesion including old blood clot. After the biopsy, minimal bleeding occurred in nine cases, however, stopped within 10 minutes by controlling the blood pressure. A minimum sized hematoma was visible on the postoperative CT in four cases. Postoperative neurological deterioration was seen in two cases. One case was transient and the other seemed to be in his natural course. Anyway, there were neither cases of operative mortality nor severely complicated cases in these series. Useful pathological diagnosis was possible in 83 cases (80 %). Accurate diagnosis was not possible in the remaining 21 cases, however, their histological datum such as necrosis, blood clot, and so on were very useful to estimate the lesions. In summary, accurate diagnosis rate of CT-guided stereotaxic needle biopsy was 80 %. However, it appeared to be a safe and useful procedure in the diagnosis of intracranial mass lesions. (author)

  15. Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

    2012-01-01

    The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

  16. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

    Science.gov (United States)

    Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

    2010-01-01

    The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

  17. Utility of 99mTc-GHA Brain SPECT in the grading of brain tumors

    International Nuclear Information System (INIS)

    Bhattacharya, Anish; Mittal, B.R.; Kumar, Ashok

    2004-01-01

    Full text: Brain tumors are of diverse histological types, the most common being derived from glial tissue. The clinical management and prognosis of brain tumor patients is dependent on accurate neuro-pathologic diagnosis and grading. Radiological imaging is not always a good modality for assessing the exact nature and grade of a malignant tumor. Magnetic resonance imaging (MRI) has a very high soft tissue resolution and is helpful in classifying the grade of tumor. Radionuclide imaging techniques that can reveal metabolic activity within tumor cells are very helpful in predicting the degree of malignancy. Usefulness of Tl-201 SPECT and FDG PET studies have been widely reported to evaluate malignant lesions by measuring increased regional glucose metabolism and amino acid uptake. 99mTc-GHA (Glucoheptonate), more or less analogous to 18F-FDG, may show increased glucose metabolism and help in grading tumors. This study was carried out to determine the utility of 99mTc-GHA SPECT for grading cerebral gliomas. Nineteen patients (12M, 7F) aged 22 to 51 years (36.1 ± 8.3) diagnosed clinically and radiologically to have a brain tumor were evaluated with 99mTc-GHA brain SPECT. All the patients had undergone CT/ MRI examination prior to the brain SPECT study. No patient had undergone surgery, radiation therapy or chemotherapy before the imaging studies. Brain SPECT was performed twice, i.e 40 min and 3 hours after intravenous administration of 20 mCi of Tc99m-GHA under a dual head SPECT gamma camera (Ecam, Siemens), with a low energy high-resolution collimator. A total of 128 frames of 30 seconds each, 64 per detector, were acquired in 128 x 128 matrix, with 360-degree rotation in step and shoot mode. Reconstruction of the SPECT data was done using standard software. Abnormal concentration of tracer at the tumor site was compared to normal uptake on the contralateral side, and ratios obtained for early (40 min) and delayed (3 hours) uptake of tracer. Retention ratio (RR), a

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

    Science.gov (United States)

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

    2016-08-01

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

  19. Scintigraphy with In-111 labeled lymphokine-activated killer cells of malignant brain tumor

    International Nuclear Information System (INIS)

    Itoh, Kazuo; Sawamura, Yutaka; Hosokawa, Masuo; Kobayashi, Hiroshi

    1988-01-01

    This study was undertaken to assess the in vivo distribution and migration of lymphokine-activated killer (LAK) cells to the target malignant foci in four patients with advanced malignant brain tumor. All four patients had failed to respond to prior adoptive immunotherapy. After the intravenous administration of radiolabeled LAK cells, most of the radiolabeled cells were distributed in the liver and spleen, with lesser radioactivity in the lung and bone marrow. Scintigraphy revealed the target malignant foci in all four patients to be areas of increased radioactivity. The number of radiolabeled LAK cells that accumulated in the intracranial malignant lesions, however, seemed to be insufficient to mediate regression of the solid tumor mass by direct cell-to-cell interaction. We conclude that the failure of adoptive immunotherapy could be accounted for by the poor migration of infused LAK cells to the target malignant foci. We also conclude that radionuclide study with radiolabeled lymphokine-activated culture cells against tumors is likely to be helpful as a means to investigate effective possibilities for subsequent adoptive immunotherapy. (author)

  20. MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

    Directory of Open Access Journals (Sweden)

    Tarek Shalaby

    2014-11-01

    Full Text Available Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets.

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

    Science.gov (United States)

    2017-08-30

    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

  2. Irradiation of meningioma: a prototype circumscribed tumor for planning high-dose irradiation of the brain

    International Nuclear Information System (INIS)

    Friedman, M.

    1977-01-01

    The purpose of this report is to provide specific data concerning the radiation dose required to destroy meningioma, and to demonstrate that radiation doses much greater than the alleged tolerance dose, can be administered to the brain in some patients. Most meninglomas are not responsive to irradiation, but, some surgically incurable lesions benefit from irradiation with radically high doses to small volumes of tissue. The arrest of 7 of 12 consecutive meningiomas in adults for periods of 2 to 17 years following maximum tumor doses up to 8800 R in 40 days is reported in this paper. All patients, when irradiated, had active tumor in the form of inoperable primary tumor, recurrence, or known postoperative residual tumor. Three of the successful results were achieved with orthovoltage radiation. The incidence of brain damage may be acceptable to the patient when it is related to arrest of tumor growth but he must be forewarned of possible brain damage. The factors influencing the radioresponsiveness of meningioma are: the required tumor lethal dose, histology and vascularity of the tumor, anatomical site in the brain, treatment technique for each tumor site, small size of the treated volume, growth rate of the tumor, displacement of normal brain tissue by tumor, inherent individual variations of tumor and normal tissues, quality of the radiation, and tolerance of normal brain tissues. The role of these factors is discussed in the light of modern radiobiological concepts

  3. Geometric accuracy of field alignment in fractionated stereotactic conformal radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Kortmann, Rolf D.; Becker, Gerd; Perelmouter, Jury; Buchgeister, Markus; Meisner, Christoph; Bamberg, Michael

    1999-01-01

    Purpose: To assess the accuracy of field alignment in patients undergoing three-dimensional (3D) conformal radiotherapy of brain tumors, and to evaluate the impact on the definition of planning target volume and control procedures. Methods and Materials: Geometric accuracy was analyzed in 20 patients undergoing fractionated stereotactic conformal radiotherapy for brain tumors. Rigid head fixation was achieved by using cast material. Transfer of stereotactic coordinates was performed by an external positioning device. The accuracy during treatment planning was quantitatively assessed by using repeated computed tomography (CT) examinations in treatment position (reproducibility of isocenter). Linear discrepancies were measured between treatment plan and CT examination. In addition, for each patient, a series of 20 verifications were taken in orthogonal projections. Linear discrepancies were measured between first and all subsequent verifications (accuracy during treatment delivery). Results: For the total group of patients, the distribution of deviations during treatment setup showed mean values between -0.3-1.2 mm, with standard deviations (SD) of 1.3-2.0 mm. During treatment delivery, the distribution of deviations revealed mean values between 0.7-0.8 mm, with SDs of 0.5-0.6 mm, respectively. For all patients, deviations for the transition to the treatment machine were similar to deviations during subsequent treatment delivery, with 95% of all absolute deviations between less than 2.8 and 4.6 mm. Conclusion: Random fluctuations of field displacements during treatment planning and delivery prevail. Therefore, our quantitative data should be considered when prescribing the safety margins of the planning target volume. Repeated CT examination are useful to detect operator errors and large random or systematic deviations before start of treatment. Control procedures during treatment delivery appear to be of limited importance. In addition, our findings should help to

  4. Blocking Blood Flow to Solid Tumors by Destabilizing Tubulin: An Approach to Targeting Tumor Growth.

    Science.gov (United States)

    Pérez-Pérez, María-Jesús; Priego, Eva-María; Bueno, Oskía; Martins, Maria Solange; Canela, María-Dolores; Liekens, Sandra

    2016-10-13

    The unique characteristics of the tumor vasculature offer the possibility to selectively target tumor growth and vascularization using tubulin-destabilizing agents. Evidence accumulated with combretastatin A-4 (CA-4) and its prodrug CA-4P support the therapeutic value of compounds sharing this mechanism of action. However, the chemical instability and poor solubility of CA-4 demand alternative compounds that are able to surmount these limitations. This Perspective illustrates the different classes of compounds that behave similar to CA-4, analyzes their binding mode to αβ-tubulin according to recently available structural complexes, and includes described approaches to improve their delivery. In addition, dissecting the mechanism of action of CA-4 and analogues allows a closer insight into the advantages and drawbacks associated with these tubulin-destabilizing agents that behave as vascular disrupting agents (VDAs).

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

    NARCIS (Netherlands)

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

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

  6. Brain scintigraphy (SPECT) using 201thallium in patients with primary tumors of the brain

    International Nuclear Information System (INIS)

    Barzen, G.; Schubert, C.; Richter, W.; Calder, D.; Eichstaedt, H.; Felix, R.; Baerwald, M.

    1992-01-01

    We evaluated the role of thallium 201 Single-Photon-Emission-Computed-Tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201-SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningeomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changings proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up. (orig.) [de

  7. Games of lives in surviving childhood brain tumors.

    Science.gov (United States)

    Chen, Chin-Mi; Chen, Yueh-Chih; Haase, Joan E

    2008-06-01

    The purpose of this phenomenological study was to describe the commonality of the lived experience of adolescent and young adult survivors (AYAS) of brain tumors in Taiwan from a sociocultural perspective. Seven AYAS aged 13 to 22 years, who had survived 5 to 10 years from the time of diagnosis, participated in this study. In consideration of their emotional duress, each participant was interviewed only once. The data revealed an essential structure: the game of life. The essential structure included six themes as follows: (a) no longer playing well, (b) wandering on the outer edges of social life, (c) helplessly struggling with role obligations, (d) rationally regulating the meaning of surviving, (e) winning a new social face, and (f) mastering the game of life. The findings suggest how nurses might help AYAS to succeed in psychosocial adjustment.

  8. Brain tumor segmentation based on a hybrid clustering technique

    Directory of Open Access Journals (Sweden)

    Eman Abdel-Maksoud

    2015-03-01

    This paper presents an efficient image segmentation approach using K-means clustering technique integrated with Fuzzy C-means algorithm. It is followed by thresholding and level set segmentation stages to provide an accurate brain tumor detection. The proposed technique can get benefits of the K-means clustering for image segmentation in the aspects of minimal computation time. In addition, it can get advantages of the Fuzzy C-means in the aspects of accuracy. The performance of the proposed image segmentation approach was evaluated by comparing it with some state of the art segmentation algorithms in case of accuracy, processing time, and performance. The accuracy was evaluated by comparing the results with the ground truth of each processed image. The experimental results clarify the effectiveness of our proposed approach to deal with a higher number of segmentation problems via improving the segmentation quality and accuracy in minimal execution time.

  9. Effect of selenium on malignant tumor cells of brain.

    Science.gov (United States)

    Zhu, Z; Kimura, M; Itokawa, Y; Nakatsu, S; Oda, Y; Kikuchi, H

    1995-07-01

    Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

  10. Perfusion magnetic resonance imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

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

  11. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-01-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10 12 nvt for BMGP and 2x10 13 nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the α-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author)

  12. UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting therapy of brain glioma.

    Science.gov (United States)

    Zhang, Bo; Zhang, Yujie; Liao, Ziwei; Jiang, Ting; Zhao, Jingjing; Tuo, Yanyan; She, Xiaojian; Shen, Shun; Chen, Jun; Zhang, Qizhi; Jiang, Xinguo; Hu, Yu; Pang, Zhiqing

    2015-01-01

    Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy.

  13. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    Flament, J.

    2012-01-01

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin α v β 3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target α v β 3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author) [fr

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    African Journals Online (AJOL)

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Structural imaging with computed tomography (CT) and MR imaging is the mainstay in primary diagnosis of primary brain tumors, but these modalities depend on morphologic appearance and an intact blood-brain barrier, and important aspects of tumor biology are not addressed. Such issues may...

  18. Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    Astrocytic brain tumors are the most frequent primary brain tumors. Treatment with radio- and chemotherapy has increased survival making prognostic biomarkers increasingly important. The aim of the present study was to investigate the expression and prognostic value of transferrin receptor-1 (TfR...

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

    Czech Academy of Sciences Publication Activity Database

    Dvořák, Pavel; Kropatsch, W.G.; Bartušek, Karel

    2013-01-01

    Roč. 13, č. 5 (2013), s. 223-230 ISSN 1335-8871 R&D Projects: GA ČR GAP102/12/1104; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : Brain tumor * Brain tumor detection * Symmetry analysis Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.162, year: 2013

  20. Advances in Brain Tumor Surgery for Glioblastoma in Adults

    Directory of Open Access Journals (Sweden)

    Montserrat Lara-Velazquez

    2017-12-01

    Full Text Available Glioblastoma (GBM is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor’s margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain’s electrical activity have optimized glioma resection in eloquent areas such as the Broca’s, Wernike’s and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography.

  1. Study of Inter- and Intra-fraction Motion in Brain Tumor Patients Undergoing VMAT Treatment

    International Nuclear Information System (INIS)

    Ascencion Ybarra, Y.; Alfonso Laguardia, R.; Yartsev, S.

    2015-01-01

    Conforming dose to the tumor and sparing normal tissue can be challenging for brain tumors with complex shapes in close proximity to critical structures. The goal of this study was to evaluate the inter- and intra-fraction motion in brain tumor patients undergoing volumetric modulated arc therapy (VMAT). The image matching software was found to be very sensitive to the choice of the region of matching. It is recommended to use the same region of interest for comparing the image sets and perform the automatic matching based on bony landmarks in brain tumor cases. (Author)

  2. Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Ioannis N. Mavridis

    2017-12-01

    Full Text Available The concept of stereotactically standard areas (SSAs within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

  3. Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation.

    Science.gov (United States)

    Mavridis, Ioannis N

    2017-12-11

    The concept of stereotactically standard areas (SSAs) within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

  4. 99mTc-MIBI-SPECT-studies in the evaluation of brain tumors

    International Nuclear Information System (INIS)

    Ambrus, E.; Pavics, L.; Gruenwald, F.; Barath, B.; Tiszlavicz, L.; Bender, H.; Menzel, C.; Almasi, L.; Lang, J.; Bodosi, M.; Biersack, H.J.; Csernay, L.

    1994-01-01

    Brain SPECT studies were performed 5 and 60 minutes after 99m Tc-MIBI administration in 41 patients with brain tumors confirmed by CT and surgical removal (13 meningeomas, 8 astrocytomas grades I-III, 10 glioblastomas, 10 metastases). 99m Tc-MIBI uptake was found in 32 out of 41 brain tumors. According to the semiquantitative SPECT analysis, the tumor/non tumor radios revealed a statistically significant difference in the early tracer uptake between meningeomas and astrocytomas (+4.73±2.91 vs -1.75±0.75, p 99m Tc-MIBI uptake and its changes with time. We concluded that the combination of an early and late 99m Tc-MIBI brain SPECT may be helpful in the non invasive histological classification of brain tumors and the determination of the grade of theirs malignancy. (orig.) [de

  5. Viral infection of implanted meningeal tumors induces antitumor memory T-cells to travel to the brain and eliminate established tumors.

    Science.gov (United States)

    Gao, Yanhua; Whitaker-Dowling, Patricia; Barmada, Mamdouha A; Basse, Per H; Bergman, Ira

    2015-04-01

    Leptomeningeal metastases occur in 2%-5% of patients with breast cancer and have an exceptionally poor prognosis. The blood-brain and blood-meningeal barriers severely inhibit successful chemotherapy. We have developed a straightforward method to induce antitumor memory T-cells using a Her2/neu targeted vesicular stomatitis virus. We sought to determine whether viral infection of meningeal tumor could attract antitumor memory T-cells to eradicate the tumors. Meningeal implants in mice were studied using treatment trials and analyses of immune cells in the tumors. This paper demonstrates that there is a blood-meningeal barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier can be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cell transfer resulted in 89% cure of meningeal tumor in 2 different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Finally, this paper shows that successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the meninges of these same animals. These results support the hypothesis that a virally based immunization strategy can be used to both prevent and treat meningeal metastases. The meningeal barriers to cancer therapy may be much more permeable to treatment based on cells than treatment based on drugs or molecules. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

    Science.gov (United States)

    Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

    2017-05-30

    The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

  7. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  8. Six-color intravital two-photon imaging of brain tumors and their dynamic microenvironment

    Directory of Open Access Journals (Sweden)

    Clément eRicard

    2014-02-01

    Full Text Available The majority of intravital studies on brain tumor in living animal so far rely on dual color imaging. We describe here a multiphoton imaging protocol to dynamically characterize the interactions between six cellular components in a living mouse. We applied this methodology to a clinically relevant glioblastoma multiforme (GBM model designed in reporter mice with targeted cell populations labeled by fluorescent proteins of different colors. This model permitted us to make non-invasive longitudinal and multi-scale observations of cell-to-cell interactions. We provide examples of such 5D (x,y,z,t,color images acquired on a daily basis from volumes of interest, covering most of the mouse parietal cortex at subcellular resolution. Spectral deconvolution allowed us to accurately separate of each cell population as well as some components of the extracellular matrix. The technique represents a powerful tool for investigating how tumor progression is influenced by the interactions of tumor cells with host cells and the extracellular matrix micro-environment. It will be especially valuable for evaluating neuro-oncological drug efficacy and target specificity. The imaging protocol provided here can be easily translated to other mouse models of neuropathologies, and should also be of fundamental interest for investigations in other areas of systems biology.

  9. Six-color intravital two-photon imaging of brain tumors and their dynamic microenvironment.

    Science.gov (United States)

    Ricard, Clément; Debarbieux, Franck Christian

    2014-01-01

    The majority of intravital studies on brain tumor in living animal so far rely on dual color imaging. We describe here a multiphoton imaging protocol to dynamically characterize the interactions between six cellular components in a living mouse. We applied this methodology to a clinically relevant glioblastoma multiforme (GBM) model designed in reporter mice with targeted cell populations labeled by fluorescent proteins of different colors. This model permitted us to make non-invasive longitudinal and multi-scale observations of cell-to-cell interactions. We provide examples of such 5D (x,y,z,t,color) images acquired on a daily basis from volumes of interest, covering most of the mouse parietal cortex at subcellular resolution. Spectral deconvolution allowed us to accurately separate each cell population as well as some components of the extracellular matrix. The technique represents a powerful tool for investigating how tumor progression is influenced by the interactions of tumor cells with host cells and the extracellular matrix micro-environment. It will be especially valuable for evaluating neuro-oncological drug efficacy and target specificity. The imaging protocol provided here can be easily translated to other mouse models of neuropathologies, and should also be of fundamental interest for investigations in other areas of systems biology.

  10. 3D variational brain tumor segmentation using Dirichlet priors on a clustered feature set.

    Science.gov (United States)

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

    2012-07-01

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

  11. Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

    DEFF Research Database (Denmark)

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

    2016-01-01

    the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one......Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore...... with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic...

  12. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Directory of Open Access Journals (Sweden)

    Travis McMurphy

    Full Text Available Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  13. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Science.gov (United States)

    McMurphy, Travis; Xiao, Run; Magee, Daniel; Slater, Andrew; Zabeau, Lennart; Tavernier, Jan; Cao, Lei

    2014-01-01

    Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  14. Phosphaturic mesenchymal tumor of the brain without tumor-induced osteomalacia in an 8-year-old girl: case report.

    Science.gov (United States)

    Ellis, Mark B; Gridley, Daniel; Lal, Suresh; Nair, Geetha R; Feiz-Erfan, Iman

    2016-05-01

    Phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMT-MCT) are tumors that may cause tumor-induced osteomalacia and rarely appear intracranially. The authors describe the case of an 8-year-old girl who was found to have PMT-MCT with involvement of the cerebellar hemisphere and a small tumor pedicle breaching the dura mater and involving the skull. This was removed surgically in gross-total fashion without further complication. Histologically the tumor was confirmed to be a PMT-MCT. There was no evidence of tumor-induced osteomalacia. At the 42-month follow-up, the patient is doing well, has no abnormalities, and is free of recurrence. PMT-MCTs are rare tumors that may involve the brain parenchyma. A gross-total resection may be effective to cure these lesions.

  15. Brain tumors in children and teenagers up to 18 in CT

    International Nuclear Information System (INIS)

    Kabula, S.; Trzcinska, I.; Lasek, W.; Goszczynski, W.; Nawrot, M.; Boron, Z.

    1995-01-01

    The results of the CT investigation in children and teenagers up to 18, made in 1990-1994 were exposed to retrospective analysis: 2279 children were examined. The computer research proved the pathological changes in case 1205 people - 52%. In this group 58 children turned out to suffer from brain tumors. The most frequent tumor spatted was: astrocytoma (8), ependymoma (5), oligodendroglioma (3). The brain tumors happen to appear more often in case of boys (34) than in case of girls (22). (author)

  16. Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer.

    Science.gov (United States)

    Li, Yining; Xu, Shuxiong; Wang, Xiangwei; Shi, Hua; Sun, Zhaolin; Yang, Zhao

    2013-02-01

    To explore the exact mechanism of Pokemon in prostate cancer. Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry. The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth. Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed...

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

    NARCIS (Netherlands)

    Kuzmin, N.V.; Wesseling, P.; Hamer, P.C.; 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

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

    NARCIS (Netherlands)

    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.

    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

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

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

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

  1. The unique case-report of metachronous brain tumors of different histology

    Directory of Open Access Journals (Sweden)

    А. М. Zaitsev

    2013-01-01

    Full Text Available  The case of unusual course of brain tumor process – metachronous development of breast cancer brain metastasis and then development of malignant glioma is reported. The surgical treatment for both tumors were performed with intraoperative fluorescence diagnosis and photodynamic therapy. Due to multimodality treatment the patient was alive for 15 months from diagnosis of IV stage breast cancer (brain metastasis. 

  2. Activation analysis study on subcellular distribution of trace elements in human brain tumor

    International Nuclear Information System (INIS)

    Zheng Jian; Zhuan Guisun; Wang Yongji; Dong Mo; Zhang Fulin

    1992-01-01

    The concentrations of up to 11 elements in subcellular fractions of human brain (normal and malignant tumor) have been determined by a combination of gradient centrifugation and INAA methods. Samples of human brain were homogenized in a glass homogenizer tube, the homogenate was separated into nuclei, mitochondrial, myelin, synaptosome fractions, and these fractions were then analyzed using the INAA method. The discussions of elemental subcelleular distributions in human brain malignant tumor are presented in this paper. (author) 11 refs.; 2 figs.; 4 tabs

  3. A study of perifocal low-density area in metastatic brain tumor

    International Nuclear Information System (INIS)

    Suzuki, Ryuta; Okada, Kodai; Hiratsuka, Hideo; Inaba, Yutaka; Tsuyumu, Matsutaira.

    1980-01-01

    It is well known that vasogenic brain edema often develops in brain tumors, head injuries, and inflammatory brain lesions. In order to investigate the development and resolution of vasogenic brain edema, some CT findings of metastatic brain tumors were studied in detail. 20 cases of metastatic brain tumors of the past three years were examined by means of a CT scan. In almost all the cases there was a perifocal low-density area (PFL) in the CT findings. In the tumors which were cystic and/or located in the infratentorial space, PFL was not present or, if present, only slightly so. On the contrary, in the tumors which were nodular and/or in the supratentorial space, PFL was present extensively. In the supratentorial metastasis, PFL seemed to be restricted within the white matter and not to involve the gray matter nor such midline structures as basal ganglia and corpus callosum. Besides, PFL was always in contact with the lateral ventricular wall. These results show that PFL in the metastatic tumors resembles in shape the experimental cold-induced brain edema in cats. PFL is presumed to represent vasogenic brain edema; these findings support the hypothesis that the main mechanism of the resolution of vasogenic brain edema is the drainage of the edema fluid into the ventricular CSF. (author)

  4. Study of perifocal low-density area in metastatic brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, R; Okada, K; Hiratsuka, H; Inaba, Y [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Tsuyumu, M

    1980-04-01

    It is well known that vasogenic brain edema often develops in brain tumors, head injuries, and inflammatory brain lesions. In order to investigate the development and resolution of vasogenic brain edema, some CT findings of metastatic brain tumors were studied in detail. 20 cases of metastatic brain tumors of the past three years were examined by means of a CT scan. In almost all the cases there was a perifocal low-density area (PFL) in the CT findings. In the tumors which were cystic and/or located in the infratentorial space, PFL was not present or, if present, only slightly so. On the contrary, in the tumors which were nodular and/or in the supratentorial space, PFL was present extensively. In the supratentorial metastasis, PFL seemed to be restricted within the white matter and not to involve the gray matter nor such midline structures as basal ganglia and corpus callosum. Besides, PFL was always in contact with the lateral ventricular wall. These results show that PFL in the metastatic tumors resembles in shape the experimental cold-induced brain edema in cats. PFL is presumed to represent vasogenic brain edema; these findings support the hypothesis that the main mechanism of the resolution of vasogenic brain edema is the drainage of the edema fluid into the ventricular CSF.

  5. Magnetic resonance spectroscopy of brain tumors; MR-Spektroskopie bei Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

    Ditter, P.; Hattingen, E. [Universitaetsklinikum Bonn, FE Neuroradiologie, Radiologische Klinik, Bonn (Germany)

    2017-06-15

    Conventional magnetic resonance imaging (MRI) under consideration of clinical information enables the correct diagnosis and therapy for the majority of cerebral space-occupying lesions. Some important differential diagnoses, e. g. low vs. high-grade tumors, require additional MRI methods. This article critically discusses the importance of magnetic resonance spectroscopy ({sup 1}H-MRS) in brain tumors. The concentration of normal and pathological brain metabolites can be non-invasively measured by {sup 1}H-MRS. It is based on the principle that chemical proton compounds of certain brain metabolites focally attenuate the external magnetic field and change the proton resonance frequency according to typical patterns. In addition, parameter maps of MRS imaging (MRSI) can show the tumor heterogeneity as well as changes in the surrounding brain tissue. In this context, the patterns of N-acetylaspartate, total choline (tCho) and creatine are relatively robust, whereas the patterns of other metabolites, such as myoinositol, glutamate, lactate or lipids greatly depend on the external field strength and echo time. The signal intensity of tCho in vital tumor tissue increases with the WHO grade of the brain tumor, i.e. increases with the level of malignancy. The use of MRSI facilitates the WHO grading of gliomas by determining target points in biopsies. Different distribution patterns and specific metabolite signals enable a better differentiation between abscesses, metastases, central nervous system (CNS) lymphomas and gliomas. The use of {sup 1}H-MRS provides valuable information on the differential diagnosis and graduation of brain tumors; however, so far artefacts, signal strength, parameter selection and a lack of standardization impede the establishment of {sup 1}H-MRS for use in clinical routine diagnostics. (orig.) [German] Die konventionelle MRT ermoeglicht unter Beruecksichtigung klinischer Information bei einem Grossteil zerebraler Raumforderungen die richtige

  6. Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, A.; Sako, K.; Diksic, M.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using YF-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of YF. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

  7. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

    Science.gov (United States)

    Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

    2018-01-01

    Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Therapy of brain stem tumors - palliative conception with prospect of curative success

    International Nuclear Information System (INIS)

    Bamberg, M.; Budach, V.; Clar, H.E.; Schmitt, G.

    1984-01-01

    From 1969 to 1981, 23 patients with tumors in the pons region were irradiated at the Department of Radiotherapy of the West German Tumor Center in Essen. The age of the patients ranged from 18 months to 50 years. Fifteen patients (65%) were younger than 18 years, one was 25 years old, and seven were between 40 and 50 years old. In two cases the histologic diagnosis of an astrocytoma I and astrocytoma II could be confirmed by exploratory excision and cyst punction, respectively. Nineteen patients received a shunt system (ventriculoatrial shunt) prior to radiotherapy in order to achieve a pressure reduction. After a follow-up period of 1.5 to 12 years, eleven patients are alive, and twelve patients died from a local recurrence or from progressive tumor growth. The five-year survival rate is 47%. Five of the surviving patients show no or only slight adverse effects on their general condition and are able to attend school or carry out their profession (in Karnofsky: 90 to 100%). Four other patients suffering from marked remaining neurologic symptoms are able to take care of themselves (Karnofsky: 70 to 80%). Two patients need permanent nursing (Karnofsky: 50 to 60%). Because of the local propagation tendency of pons tumors, radiotherapy should be locally restricted to the brain stem and the adjacent brain structures, e.g. cerebellum and proximal neck marrow. The authors recommend target volumes of 55 to 60 Gy, which must be applied within 6 to 8 weeks, taking into account the age of patients. This palliative therapy conception should be applied routinely in the hope of bringing about a curative treatment to this group of patients. (orig.) [de

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hongsheng Miao

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

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

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

  13. Examination of human brain tumors in situ with image-localized H-1 MR spectroscopy

    International Nuclear Information System (INIS)

    Luyten, P.R.; Segebarth, C.; Baleriaux, D.; Den Hollander, J.A.

    1987-01-01

    Human brain tumors were examined in situ by combined imaging and H-1 MR spectroscopy at 1.5 T. Water-suppressed localized H-1 MR spectra obtained from the brains of normal volunteers show resonances from lactate, N-acetyl aspartate (NAA), creatine, and choline. Several patients suffering from different brain tumors were examined, showing spectral changes in the region of 0.5-1.5 ppm; spectral editing showed that these changes were not due to lactic acid, but to lipid signals. The NAA signal was decreased in the tumors as compared with normal brain. This study shows that H-1 MR spectroscopy can monitor submillimolar changes in chemical composition of human brain tumors in situ

  14. Treatment optimization of a brain tumor in BNCT by Monte Carlo method

    International Nuclear Information System (INIS)

    Nejat, S.; Binesh, A.; Karimian, A.

    2012-01-01

    Brain cancers are one of the most important diseases. BNCT (Boron Neutron Capture Therapy) is used to brain tumor treatment. In this method the 1 0B (n,α) 7 Li reaction is used. The purpose of this study is absorbed dose evaluation of tumoral and healthy parts of brain. To achieve this aim the brain was simulated by a cylindrical phantom with the dimensions of 20 cm in diameter and height. In BNCT treatment the BSH (Na 2 B 12 H 11 SH) is injected to the human body and absorbed in the healthy and tumoral parts by the ratios of 18 and 65 ppm respectively. So in this research the absorption of BSH in tumoral and healthy parts of brain was considered as the mentioned ratio. Then the neutron with the energy range of 50 eV - 10 keV was exposed to the brain and maximum absorbed dose in healthy and tumoral parts of brain were calculated for a cylindrical tumor with the thickness of about 1 cm which was considered in 5.5 cm depth of brain. This research showed the suitable energy to treat this tumor by BNCT is interval 4 keV- 6keV. The average of dose which is met with healthy and tumor tissue was gained for 6 keV energy of brain 1.18x10 -12 cGy/n and 5.98x10 -12 cGy/n respectively. Maximum of dose which is met with healthy tissue was 4.3 Gy which is much less than standard amount 12.6 Gy. Therefore BNCT method is known as an effective way in the therapy of this kind of tumor. (authors)

  15. Targeted Gene Transfer to the Brain via the Delivery of Brain-Penetrating DNA Nanoparticles with Focused Ultrasound

    Science.gov (United States)

    Mead, Brian P.; Mastorakos, Panagiotis; Suk, Jung Soo; Klibanov, Alexander L.; Hanes, Justin; Price, Richard J.

    2016-01-01

    Gene therapy holds promise for the treatment of many pathologies of the central nervous system (CNS), including brain tumors and neurodegenerative diseases. However, the delivery of systemically administered gene carriers to the CNS is hindered by both the blood-brain barrier (BBB) and the nanoporous and electrostatically charged brain extracelluar matrix (ECM), which acts as a steric and adhesive barrier. We have previously shown that these physiological barriers may be overcome by, respectively, opening the BBB with MR image-guided focused ultrasound (FUS) and microbubbles and using highly compact “brain penetrating” nanoparticles (BPN) coated with a dense polyethylene glycol corona that prevents adhesion to ECM components. Here, we tested whether this combined approach could be utilized to deliver systemically administered DNA-bearing BPN (DNA-BPN) across the BBB and mediate localized, robust, and sustained transgene expression in the rat brain. Systemically administered DNA-BPN delivered through the BBB with FUS led to dose-dependent transgene expression only in the FUS-treated region that was evident as early as 24 h post administration and lasted for at least 28 days. In the FUS-treated region ~42% of all cells, including neurons and astrocytes, were transfected, while less than 6% were transfected in the contralateral non-FUS treated hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. We conclude that the image-guided delivery of DNA-BPN with FUS and microbubbles constitutes a safe and non-invasive strategy for targeted gene therapy to the brain. PMID:26732553

  16. Radiotherapy for pediatric brain tumors: Standards of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Goldwein, Joel W.

    1995-01-01

    The objectives of the course are to evaluate the role of radiation therapy in the treatment of pediatric brain tumors. Areas where the role is evolving will be identified, and the results of clinical trials which been mounted to clarify radiotherapy's role will be reviewed. Brain tumors are the second most common malignancy of childhood after leukemias and lymphomas. However, they remain the most common group of childhood tumors to require radiation therapy. Therefore, a thorough understanding of these tumors, and the appropriate role of surgery, radiation and chemotherapy is critical. Issues surrounding the management of sequelae are no less important. The role of radiotherapy for the treatment of these tumors is far different from that for adults. These differences relate to the profound potential for sequelae from therapy, the higher overall cure rates, and the utility of multimodality therapies. In addition, the rarity of childhood brain tumors compared with adults' makes them more difficult to study. In this session, the following issues will be reviewed; 1. Incidence of pediatric brain tumors, 2. General issues regarding symptoms, diagnosis, diagnostic tests and evaluation, 3. Importance of a team approach, 4. General issues regarding treatment sequelae, 5. Specific tumor types/entities; a. Cerebellar Astrocytomas b. Benign and malignant Gliomas including brainstem and chiasmatic lesions c. Primitive Neuroectodermal Tumors (PNET) and Medulloblastoma d. Ependymomas e. Craniopharyngiomas f. Germ cell tumors g. Miscellaneous and rare pediatric brain tumors 6. Management of sequelae 7. New and future directions a. Treatment of infants b. The expanding role of chemotherapy c. Advances in radiotherapy. The attendees will complete the course with a better understanding of the role that radiation therapy plays in the treatment of pediatric brain tumors. They will be knowledgeable in the foundation for that role, and the changes which are likely to take place in the

  17. In vivo type 2 cannabinoid receptor-targeted tumor optical imaging using a near infrared fluorescent probe.

    Science.gov (United States)

    Zhang, Shaojuan; Shao, Pin; Bai, Mingfeng

    2013-11-20

    The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and progression and is emerging as a therapeutic target for cancers. However, the exact role of CB2R in cancer progression and therapy remains unclear. This has driven the increasing efforts to study CB2R and cancers using molecular imaging tools. In addition, many types of cancers overexpress CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such upregulation of the receptor in cancer cells provides opportunities for CB2R-targeted imaging with high contrast and for therapy with low side effects. In the present study, we report the first in vivo tumor-targeted optical imaging using a novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement at 72 h postinjection, whereas the fluorescence signal from the tumors of the mice treated with NIR760 free dye was nearly at the background level at the same time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears to be a promising molecular tool that may have great potential for use in diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as in elucidating the role of CB2R in cancer progression and therapy.

  18. An epidemiologic survey on brain tumors in Kerman from 1997 to 2001

    Directory of Open Access Journals (Sweden)

    Hamed Reihani kermani

    2004-09-01

    Full Text Available Central nervous system tumors contain neoplastic and nonneoplastic lesions. Incidence of brain tumors has increased in all age groups in recent 20 years. Developments of medical devices such as CT scan, MRI and varying of classification are important causes of this raising. The present study evaluates epidemiology of brain tumors from 1997 to 2001 in Kerman. In a cross sectional study all files of neurosurgery department, in Kerman Bahonar Hospital and from 1997 to 2001, were inquired. Variables such as age, sex and histological considerations were evaluated. A total of 338 tumors were studied. The most common tumor was glial (35%, and meningioma was the second common tumor (26.3%. The other tumors were anaplastic astrocytoma, astrocytoma, pituitary adenoma, aucostic neorinoma, medulloblastoma, ependymoma, choroid plexus carcinoma, craniopharyngioma, lymphoma, sarcoma and anaplastic ependymoma. There was statistical significant difference between tumors and sex and age (p<0.05. Age and sex distribution of brain tumors is compatible with other studies in many countries. These findings suggest that prevalence of brain tumors in Kerman has increased in recent years because of diagnostic methods have improved and other medical devices are available.

  19. EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice.

    Directory of Open Access Journals (Sweden)

    Alexei Shir

    2006-01-01

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most lethal form of brain cancer. With the available treatments, survival does not exceed 12-14 mo from the time of diagnosis. We describe a novel strategy to selectively induce the death of glioblastoma cells and other cancer cells that over-express the EGF receptor. Using a non-viral delivery vector that homes to the EGF receptor, we target synthetic anti-proliferative dsRNA (polyinosine-cytosine [poly IC], a strong activator of apoptosis, selectively to cancer cells. METHODS AND FINDINGS: Poly IC was delivered by means of a non-viral vector: 25kDa polyethylenimine-polyethyleneglycol-EGF (PEI25-PEG-EGF. EGFR-targeted poly IC induced rapid apoptosis in the target cells in vitro and in vivo. Expression of several cytokines and "bystander killing" of untransfected tumor cells was detected in vitro and in vivo. Intra-tumoral delivery of the EGFR-targeted poly IC induced the complete regression of pre-established intracranial tumors in nude mice, with no obvious adverse toxic effects on normal brain tissue. A year after treatment completion the treated mice remain cancer-free and healthy. Similarly, non-viral delivery of poly IC completely eliminated pre-established breast cancer and adenocarcinoma xenografts derived from EGFR over-expressing cancer cell lines, suggesting that the strategy is applicable to other EGFR-over-expressing tumors. CONCLUSION: The strategy described has yielded an effective treatment of EGFR over-expressing GBM in an animal model. If this strategy is translated successfully to the clinical setting, it may actually offer help to GBM patients. Moreover the elimination of two additional EGFR over-expressing cancers in vivo suggests that in principle this strategy can be applied to treat other tumors that over-express EGFR.

  20. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Science.gov (United States)

    Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

    2018-01-01

    Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

  1. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Kashif Riaz

    2018-01-01

    Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

  2. Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

    Science.gov (United States)

    Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

    2012-01-01

    Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

  3. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Tumor blood flow modifying effects of electrochemotherapy. A potential vascular targeted mechanism

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Miklavcic, D.

    2003-01-01

    Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut down of the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that, in addition to direct electroporation of