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Sample records for primary brain tumor

  1. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  2. Brain Tumors

    MedlinePlus

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

  3. Rho GTPases in primary brain tumor malignancy and invasion.

    PubMed

    Khalil, Bassem D; El-Sibai, Mirvat

    2012-07-01

    Gliomas are the most common type of malignant primary brain tumor in humans, accounting for 80 % of malignant cases. Expression and activity of Rho GTPases, which coordinate several cellular processes including cell-cycle progression and cell migration, are commonly altered in many types of primary brain tumor. Here we review the suggested effects of deregulated Rho GTPase signaling on brain tumor malignancy, highlighting the controversy in the field. For instance, whereas expression of RhoA and RhoB has been found to be significantly reduced in astrocytic tumors, other studies have reported Rho-dependent LPA-induced migration in glioma cells. Moreover, whereas the Rac1 expression level has been found to be reduced in astrocytic tumor, it was overexpressed and induced invasion in medulloblastoma tumors. In addition to the Rho GTPases themselves, several of their downstream effectors (including ROCK, mDia, and N-WASP) and upstream regulators (including GEFs, GAPs, PI3K, and PTEN) have also been implicated in primary brain tumors.

  4. Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

    PubMed Central

    Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

    2010-01-01

    The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

  5. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

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

    2015-04-01

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

  6. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

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

    2015-01-01

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

  7. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

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

    2015-04-01

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

  8. The role of integrins in primary and secondary brain tumors.

    PubMed

    Schittenhelm, Jens; Tabatabai, Ghazaleh; Sipos, Bence

    2016-10-01

    The tumor environment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Integrins, a family of cell surface receptors, bridge the extracellular matrix to the intracellular cytoskeleton. Since their first characterization 25 years ago, a vast amount of work has been performed to understand the essential role of integrins in cell development, tissue organization, tumor growth, vessel development and their signaling mechanisms. Their potential as therapeutic targets in various types of cancer is intensively studied. In this review, we discuss the expression patterns and functional role of integrin in primary brain tumors and brain metastases, provide an overview of clinical data on integrin inhibition and their potential application in imaging and therapy of these tumors. PMID:27097828

  9. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  10. Brain tumor (image)

    MedlinePlus

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

  11. Use of chlorotoxin for targeting of primary brain tumors.

    PubMed

    Soroceanu, L; Gillespie, Y; Khazaeli, M B; Sontheimer, H

    1998-11-01

    Gliomas are primary brain tumors that arise from differentiated glial cells through a poorly understood malignant transformation. Although glioma cells retain some genetic and antigenic features common to glial cells, they show a remarkable degree of antigenic heterogeneity and variable mutations in their genome. Glioma cells have recently been shown to express a glioma-specific chloride ion channel (GCC) that is sensitive to chlorotoxin (CTX), a small peptide purified from Leiurus quinquestriatus scorpion venom [N. Ullrich et al, Neuroreport, 7: 1020-1024, 1996; and N. Ullrich and H. Sontheimer, Am. J. Physiol. (Cell Physiol.), 270: C1511-C1521, 1996]. Using native and recombinant 125I-labeled CTX, we show that toxin binding to glioma cells is specific and involves high affinity [dissociation constant (Kd)=4.2 nM] and low affinity (Kd=660 nml) binding sites. In radioreceptor assays, 125I-labeled CTX binds to a protein with Mr=72,000, presumably GCC or a receptor that modulates GCC activity. In vivo targeting and biodistribution experiments were obtained using 125I- and (131)I-labeled CTX injected into severe combined immunodeficient mice bearing xenografted gliomas. CTX selectively accumulated in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4% ID/g in control animals. In the tumor-bearing severe combined immunodeficient mice, the vast majority of the brain-associated radioactivity was localized within the tumor (tumor:muscle ratio, 39.13% ID/g; contralateral brain:muscle ratio, 6.68%ID/g). Moreover, (131)I-labeled CTX distribution, visualized through in vivo imaging by gamma ray camera scans, demonstrates specific and persistent intratumoral localization of the radioactive ligand. Immunohistochemical studies using biotinylated and fluorescently tagged CTX show highly selective staining of glioma cells in vitro, in situ, and in sections of patient biopsies. Comparison tissues including

  12. Primary brain tumors, delta 24 and tumor metabolism. Interview by Rona Williamson.

    PubMed

    Gilbert, Mark R

    2013-04-01

    Interview by Rona Williamson, Commissioning Editor Mark R Gilbert studied medicine at the Johns Hopkins School of Medicine in Baltimore (MD, USA). He completed residency training in internal medicine and neurology at the Johns Hopkins Hospital, then was named the first Keck Foundation Fellow in Neuro-Oncology at Johns Hopkins. After 2 years on the faculty at Johns Hopkins, he moved to the University of Pittsburgh to head the Brain Tumor Program. During his tenure at Pittsburgh (PA, USA), he was named Chair of the Brain Tumor Committee of the Eastern Cooperative Oncology Group. In 1996, Dr Gilbert moved to the Emory University in Atlanta (GA, USA) to lead the Medical Neuro-Oncology Program and successfully competed for the program's membership in the New Approaches to Brain Tumor Treatment consortium. Dr Gilbert moved to the MD Anderson Cancer Center in Houston (TX, USA) in 2000 as Deputy Chair of the Department of Neuro-Oncology. During his tenure at MD Anderson, he has created two brain tumor consortia. The Collaborative Ependymoma Research Network is an international effort that is focusing research efforts on patients, both adult and pediatric, with this uncommon central nervous system tumor. The Brain Tumor Trials Collaborative is a 23-institution consortium that focuses on innovative clinical trials for primary glial malignancies. In addition, Dr Gilbert holds a leadership position in the Radiation Therapy Oncology Group and has served as the principal investigator on several large randomized brain tumor clinical trials. His research focus has been in the area of clinical and translational research for primary brain tumors. This includes novel clinical trial designs and the integration of correlative tumor biology with these clinical studies.

  13. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

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

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

    PubMed

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

    2015-05-01

    Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P < .01). However, patients' uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients

  15. A multicenter study of primary brain tumor incidence in Australia (2000–2008)

    PubMed Central

    Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

    2011-01-01

    There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

  16. Brain Tumor Statistics

    MedlinePlus

    ... facts and statistics here include brain and central nervous system tumors (including spinal cord, pituitary and pineal gland ... U.S. living with a primary brain and central nervous system tumor. This year, nearly 17,000 people will ...

  17. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  18. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

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

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

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

  20. Brain tumor - children

    MedlinePlus

    ... symptoms, and improve brain function or the child's comfort. Surgery is needed for most primary brain tumors. ... Anticonvulsants to reduce or prevent seizures Pain medicines Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  1. Primary brain tumors associated with cerebral aneurysm: report of three cases.

    PubMed

    Suslu, Hikmet Turan; Bozbuga, Mustafa

    2011-01-01

    The primary brain tumors associated with cerebral aneurysms are rare in neurosurgical practice. The present article constitutes an evaluation of the management of coexistent primary brain tumor and cerebral aneurysm. A retrospective study of three cases of primary brain tumor with cerebral aneurysm was performed. We evaluated the complications and clinic outcomes by assessing the clinical and imaging findings. Case 1 presented with a subarachnoid hemorrhage from an aneurysm of the anterior communicating artery, with an incidental left frontal oligodendroglioma. Case 2 presented with chronic headache due to left frontal convexity meningioma, with proximal internal carotid artery aneurysm which was found incidentally during preoperative magnetic resonance angiography. Case 3 was admitted to our hospital complaining of headache, memory disturbance, and weakness in her left lower extremity. Magnetic resonance imaging revealed right frontal lymphoma and an unruptured aneurysm at the left middle cerebral artery. Preoperative magnetic resonance imaging revealed right frontal lymphoma and unruptured left middle cerebral artery. The frequency of primary brain tumor and cerebral aneurysm coexistence is increasing due to improvements in high-resolution imaging. In these complicated cases, the management will differ according to each pathology present, and this is an important problem for a neurosurgeon.

  2. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

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

    PubMed Central

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

    2002-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Use of complementary and alternative medical therapy by patients with primary brain tumors.

    PubMed

    Armstrong, Terri S; Gilbert, Mark R

    2008-05-01

    The use of complementary and alternative medicine (CAM) is increasing. CAM includes mind-body interventions, biologically based therapies, energy therapies, and body-based methods. Primary brain tumors arise within the brain and have a poor prognosis when malignant. Even patients with benign tumors suffer neurologic and systemic symptoms as a result of the tumor or its treatment. CAM is used by 30% of brain tumor patients, who often do not report its use to their physician. Herbal medicines may affect the metabolism of prescribed medications or produce adverse effects that may be attributed to other causes. In patients with systemic cancer, mind-body modalities such as meditation and relaxation therapy have been shown to be helpful in reducing anxiety and pain; acupuncture and hypnotherapy may also reduce both pain and nausea. Recent preclinical studies have reported that ginseng, Scutellaria baicalensis, and Angelica sinensis may promote apoptosis of tumor cells or exercise antiangiogenic effects. Further studies are needed to evaluate the impact of CAM on symptom control or tumor growth in this vulnerable patient population.

  7. [The first experience in interstitial brachytherapy for primary and metastatic tumors of the brain].

    PubMed

    Bentsion, D L; Gvozdev, P B; Sakovich, V P; Fialko, N V; Kolotvinov, V S; Baiankina, S N

    2006-01-01

    In 2001-2002, the authors performed a course of brachytherapy in 15 patients with inoperable primary, recurrent, and metastatic brain tumors. The histostructural distribution was as follows: low-grade astrocytoma (grade II according to the WHO classification) in 2 patients, anaplastic astrocytoma (AA) in 3, glioblastoma multiforme (GBM) in 5. Five patients had solid tumor deposits in the brain. Computer tomographic (CT) and magnetic resonance imaging (MRI) data were used to define a path for forthcoming biopsy and implantation at a "Stryker" navigation station, by taking into account the anatomy of the brain, vessels, and functionally significant areas. After having histological findings, plastic intrastats whose number had been determined by the volume of a target were implanted into a tumor by the predetermined path. Dosimetric planning was accomplished by using CT and MRI images on an "Abacus" system. The final stage involved irradiation on a "GammaMed plus" with a source of 192Ir. Irradiation was given, by hyperfractionating its dose (3-4 Gy twice daily at an interval of 4-5 hours) to the total focal dose (TFD) of 36-44 Gy. Patients with gliomas untreated with radiation also underwent external radiation in a TFD of 54-56 Gy and patients with brain metastases received total external irradiation of the brain in a TFD of 36-40 Gy. The tolerance of a course of irradiation was fair. In patients with AA and GBM, one-year survival was observed in 66 and 60%, respectively; in those having metastasis, it was in 20%. Six patients died from progressive disease. All patients with low-grade astrocytoma and one patient with anaplastic astrocytoma were alive at month 24 after treatment termination. The mean lifespan of patients with malignant gliomas and solid tumor metastasis was 11.5 and 5.8 months, respectively. Brachytherapy is a noninvasive and tolerable mode of radiotherapy that increases survival in some groups of patients with inoperable brain tumors.

  8. Trends in incidence of primary brain tumors in the United States, 1985-1994.

    PubMed Central

    Jukich, P. J.; McCarthy, B. J.; Surawicz, T. S.; Freels, S.; Davis, F. G.

    2001-01-01

    Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they

  9. Understanding Brain Tumors

    MedlinePlus

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

  10. Brain Tumor Diagnosis

    MedlinePlus

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

  11. Epidemiology of Primary Brain Tumors in the Middle Eastern Population in California, 2001–2005

    PubMed Central

    Nasseri, Kiumarss; Mills, John R.

    2009-01-01

    Background The fast growing Middle Eastern (ME) population has rarely been studied in the US. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. Methods ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8,352 benign, 6,812 malignant, 425 uncertain) in the NHNMW were available for this study. Results ME patients were significantly (p<0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p<0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. Conclusions This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies. PMID:19588542

  12. The role and clinical significance of DNA damage response and repair pathways in primary brain tumors

    PubMed Central

    2013-01-01

    Primary brain tumors, in particular, glioblastoma multiforme (GBM), continue to have dismal survivability despite advances in treating other neoplasms. The goal of new anti-glioma therapy development is to increase their therapeutic ratios by enhancing tumor control and/or decreasing the severity and incidence of side effects. Because radiotherapy and most chemotherapy agents rely on DNA damage, the cell’s DNA damage repair and response (DRR) pathways may hold the key to new therapeutic strategies. DNA double-strand breaks (DSBs) generated by ionizing radiation and chemotherapeutic agents are the most lethal form of damage, and are repaired via either homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Understanding and exploitation of the differences in the use of these repair pathways between tumor and normal brain cells will allow for an increase in tumor cell killing and decreased normal tissue damage. A literature review and discussion on new strategies which can improve the anti-glioma therapeutic ratio by differentially targeting HR and NHEJ function in tumor and normal neuronal tissues is the focus of this article. PMID:23388100

  13. Brain Tumors (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  14. Conditional Survival of All Primary Brain Tumor Patients by Age, Behavior, and Histology

    PubMed Central

    Porter, Kimberly R.; McCarthy, Bridget J.; Berbaum, Michael L.; Davis, Faith G.

    2011-01-01

    Background Survival statistics commonly reflect survival from the time of diagnosis but do not take into account survival already achieved after a diagnosis. The objective of this study was to provide conditional survival estimates for brain tumor patients as a more accurate measure of survival for those who have already survived for a specified amount of time after diagnosis. Methods Data on primary malignant and nonmalignant brain tumor cases diagnosed from 1985–2005 from selected SEER state cancer registries were obtained. Relative survival up to 15 years postdiagnosis and varying relative conditional survival rates were computed using the life-table method. Results The overall 1-year relative survival estimate derived from time of diagnosis was 67.8% compared to the 6-month relative conditional survival rate of 85.7% for 6-month survivors (the probability of surviving to 1 year given survival to 6 months). The 10-year overall relative survival rate was 49.5% from time of diagnosis compared to the 8-year relative conditional survival rate of 79.2% for 2-year survivors. Conditional survival estimates and standard survival estimates varied by histology, behavior, and age at diagnosis. The 5-year relative survival estimate derived from time of diagnosis for glioblastoma was 3.6% compared to the 3-year relative conditional survival rate of 36.4% for 2-year survivors. For most nonmalignant tumors, the difference between relative survival and the corresponding conditional survival estimates were minimal. Older age groups had greater numeric gains in survival but lower conditional survival estimates than other age groups. Similar findings were seen for other conditional survival intervals. Conclusions Conditional survival is a useful disease surveillance measure for clinicians and brain tumor survivors to provide them with better ‘real-time’ estimates and hope. PMID:21677447

  15. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

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

    ClinicalTrials.gov

    2016-07-26

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

  17. Existential Well-Being and Meaning Making in the Context of Primary Brain Tumor: Conceptualization and Implications for Intervention

    PubMed Central

    Ownsworth, Tamara; Nash, Kimberley

    2015-01-01

    When faced with a significant threat to life, people tend to reflect more intensely upon existential issues, such as the meaning and purpose of one’s life. Brain tumor poses a serious threat to a person’s life, functioning, and personhood. Although recognized as an important dimension of quality of life, existential well-being is not well understood and reflects an overlooked area of support for people with brain tumor. This perspective article reviews the historical underpinnings of the concept of existential well-being and integrates this discussion with theoretical perspectives and research on meaning making and psychological adjustment to primary brain tumor. We then provide an overview of psychosocial support interventions for people with brain tumor and describe the findings of a recently published psychotherapy trial targeting existential well-being. Overall, this article highlights the importance of assessing the existential support needs of people with primary brain tumor and their family members, and providing different avenues of support to facilitate the meaning-making process across the illness trajectory. PMID:25964883

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

    ClinicalTrials.gov

    2013-05-01

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

  19. Childhood Brain Tumors

    MedlinePlus

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

  20. Exploring Spirituality in Family Caregivers of Patients With Primary Malignant Brain Tumors Across the Disease Trajectory

    PubMed Central

    Newberry, Alyssa G.; Jean Choi, Chien-Wen; Donovan, Heidi S.; Schulz, Richard; Bender, Catherine; Given, Barbara; Sherwood, Paula

    2013-01-01

    Purpose/Objectives To determine whether the perceived level of spirituality in family caregivers of patients with primary malignant brain tumors (PMBTs) changes across the disease trajectory. Design Ongoing descriptive, longitudinal study. Setting Southwestern Pennsylvania. Sample 50 family caregivers of patients with PMBT. Methods Caregivers and care recipients were recruited at time of diagnosis. Participants were interviewed at two subse-quent time points, four and eight months following diagnosis. Main Research Variables Care recipients’ symptoms, neuro-psychologic status, and physical function, as well as caregiver social support. Findings Results showed no significant difference in spirituality scores reported at baseline and eight months (p = 0.8), suggesting that spirituality may be a stable trait across the disease trajectory. Conclusions Spirituality remains relatively stable along the course of the disease trajectory. Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality. Implications for Nursing Clinicians can better identify caregivers at risk for negative outcomes by identifying those who report lower levels of spirituality. Future interventions should focus on the development and implementation of interventions that provide protective buffers such as increased social support. Knowledge Translation Spirituality is a relatively stable trait. High levels of spirituality can serve as a protective buffer from negative mental health outcomes. Caregivers with low levels of spirituality may be at risk for greater levels of burden, anxiety, and stress. PMID:23615145

  1. Aquaporins and Brain Tumors

    PubMed Central

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

    2016-01-01

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

  2. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  3. Children's Brain Tumor Foundation

    MedlinePlus

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

  4. Pediatric Brain Tumor Foundation

    MedlinePlus

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

  5. American Brain Tumor Association

    MedlinePlus

    ... in the Ear Canals Read More ABTA News October 5, 2016 Largest American Brain Tumor Association Team Running in Bank of America Chicago Marathon Sunday, October 9 September 21, 2016 American Brain Tumor Association Awards 16 Grants to Support ...

  6. Brain and Spinal Tumors

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Brain and Spinal Tumors Information Page Synonym(s): Spinal Cord ... en Español Additional resources from MedlinePlus What are Brain and Spinal Tumors? Tumors of the brain and ...

  7. Intra-axial brain tumors.

    PubMed

    Rapalino, Otto; Batchelor, Tracy; González, R Gilberto

    2016-01-01

    There is a wide variety of intra-axial primary and secondary brain neoplasms. Many of them have characteristic imaging features while other tumors can present in a similar fashion. There are peculiar posttreatment imaging phenomena that can present as intra-axial mass-like lesions (such as pseudoprogression or radiation necrosis), further complicating the diagnosis and clinical follow-up of patients with intracerebral tumors. The purpose of this chapter is to present a general overview of the most common intra-axial brain tumors and peculiar posttreatment changes that are very important in the diagnosis and clinical follow-up of patients with brain tumors. PMID:27432670

  8. Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors

    PubMed Central

    Burger, Michael C.; Zeiner, Pia S.; Jahnke, Kolja; Wagner, Marlies; Mittelbronn, Michel; Steinbach, Joachim P.

    2016-01-01

    Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO°II, anaplastic astrocytoma WHO°III, anaplastic oligodendroglioma WHO°III, primitive neuroectodermal tumor and glioblastoma, both WHO°IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors. PMID:27253224

  9. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  10. Brain tumors in infants

    PubMed Central

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

    2015-01-01

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

  11. Centralized databases available for describing primary brain tumor incidence, survival, and treatment: Central Brain Tumor Registry of the United States; Surveillance, Epidemiology, and End Results; and National Cancer Data Base.

    PubMed Central

    Davis, F. G.; McCarthy, B. J.; Berger, M. S.

    1999-01-01

    Characteristics of three databases--the Central Brain Tumor Registry of the United States (CBTRUS) database; the Surveillance, Epidemiology and End Results (SEER) database; and the National Cancer Data Base (NCDB)--containing information on primary brain tumors are discussed. The recently developed population-based CBTRUS database comprises incidence data on all primary brain tumors from 11 collaborating state registries; however, follow-up data are not available. SEER, the population-based gold standard for cancer data, collects incidence and follow-up data on malignant brain tumors only. While not population-based, the NCDB identifies newly diagnosed cases and conducts follow-up on all primary brain tumors from hospitals accredited by the American College of Surgeons. The NCDB is the largest of the three databases and also contains more complete information regarding treatment of these tumors than either the SEER or CBTRUS databases. Additional strengths and limitations of each of these are described, and their judicious use for supporting research, education, and health care planning is encouraged. PMID:11554389

  12. Prospective assessment of quality of life in adult patients with primary brain tumors in routine neurooncology practice.

    PubMed

    Budrukkar, Ashwini; Jalali, Rakesh; Dutta, Debnarayan; Sarin, Rajiv; Devlekar, Rashmi; Parab, Sachin; Kakde, Anagha

    2009-12-01

    The aim of this article is to evaluate and assess the impact of various factors on quality of life (QOL) in adult patients with primary brain tumors seen consecutively in routine neurooncology practice. Two hundred and fifty-seven adult patients, after undergoing surgical intervention and histologically proven primary brain neoplasms were registered in the NeuroOncology Clinic at our centre during 1 full calendar year. The study included detailed neurological assessment, evaluation of QOL using EORTC questionnaire (QLQ-30) and specific Brain Cancer module (BN 20). In the present analysis, QOL scores before starting adjuvant treatment were measured and impact of patient and tumor related factors were analyzed. Baseline global QOL data of all patients (available in 243) was relatively low including in all histological tumor types. Physical function, role function, emotion function, cognitive and social function scores were 80, 78, 65.7, 70 and 70.5 (higher values better), respectively. Domains of future uncertainty, visual disorder, motor deficit, communication deficit, headache, seizures and drowsiness scores were 19.6, 18.2, 28.5, 30.7, 21, 31.8 and 16 (lower values better), respectively. Elderly patients had poorer global score (21 points difference; p = 0.161). Patients with lower performance status (KPS < 70) had a lower global QOL (KPS >or= 80 vs. tumors (p = <0.001). Illiterate patients had lower QOL score (p = 0.005). Tumor type is an important patient related factor that influences baseline global scores (LGG vs. HGG 62 and 52; p = 0.015). Economic status significantly influence QOL scores in HGG (p = 0.052). Type of surgery (biopsy/complete excision) (p = 0.284) and site of tumor (p = 0.309) did not show any impact on QOL score. Patients with primary brain tumours before starting adjuvant therapy have

  13. [Chemotherapy of brain tumors].

    PubMed

    Kuratsu, J; Ushio, Y

    1994-10-01

    Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted. PMID:7986118

  14. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship. PMID:26468140

  15. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

  16. Radiosurgery for Pediatric Brain Tumors.

    PubMed

    Murphy, Erin S; Chao, Samuel T; Angelov, Lilyana; Vogelbaum, Michael A; Barnett, Gene; Jung, Edward; Recinos, Violette R; Mohammadi, Alireza; Suh, John H

    2016-03-01

    The utility of radiosurgery for pediatric brain tumors is not well known. For children, radiosurgery may have an important role for treating unresectable tumors, residual disease, or tumors in the recurrent setting that have received prior radiotherapy. The available evidence demonstrates utility for some children with primary brain tumors resulting in good local control. Radiosurgery can be considered for limited residual disease or focal recurrences. However, the potential toxicities are unique and not insignificant. Therefore, prospective studies need to be performed to develop guidelines for indications and treatment for children and reduce toxicity in this population. PMID:26536284

  17. Radioresistance of Brain Tumors

    PubMed Central

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

    2016-01-01

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

  18. Modern Brain Tumor Imaging

    PubMed Central

    Barajas, Ramon F.; Cha, Soonmee

    2015-01-01

    The imaging and clinical management of patients with brain tumor continue to evolve over time and now heavily rely on physiologic imaging in addition to high-resolution structural imaging. Imaging remains a powerful noninvasive tool to positively impact the management of patients with brain tumor. This article provides an overview of the current state-of-the art clinical brain tumor imaging. In this review, we discuss general magnetic resonance (MR) imaging methods and their application to the diagnosis of, treatment planning and navigation, and disease monitoring in patients with brain tumor. We review the strengths, limitations, and pitfalls of structural imaging, diffusion-weighted imaging techniques, MR spectroscopy, perfusion imaging, positron emission tomography/MR, and functional imaging. Overall this review provides a basis for understudying the role of modern imaging in the care of brain tumor patients. PMID:25977902

  19. New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.

    PubMed

    Debinski, Waldemar; Dickinson, Peter; Rossmeisl, John H; Robertson, John; Gibo, Denise M

    2013-01-01

    appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts. PMID:24147065

  20. New Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumors

    PubMed Central

    Debinski, Waldemar; Dickinson, Peter; Rossmeisl, John H.; Robertson, John; Gibo, Denise M.

    2013-01-01

    appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts. PMID:24147065

  1. Cytogenetics of human brain tumors

    SciTech Connect

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

    1994-09-01

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

  2. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model.

    PubMed

    Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria

    2015-12-01

    Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.

  3. Sleep Loss and Its Effects on Health of Family Caregivers of Individuals with Primary Malignant Brain Tumors

    PubMed Central

    Lee, Shih-Yu; Clark, Patricia C.; Sherwood, Paula R.

    2013-01-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes. PMID:23633116

  4. Sleep loss and its effects on health of family caregivers of individuals with primary malignant brain tumors.

    PubMed

    Pawl, Jean D; Lee, Shih-Yu; Clark, Patricia C; Sherwood, Paula R

    2013-08-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes.

  5. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  6. [The frequency of seizures in patients with primary brain tumors or cerebral metastases. An evaluation from the Ludwig Boltzmann Institute of Neuro-Oncology and the Department of Neurology, Kaiser Franz Josef Hospital, Vienna].

    PubMed

    Oberndorfer, Stefan; Schmal, Thomas; Lahrmann, Heinz; Urbanits, Sabine; Lindner, Klaus; Grisold, Wolfgang

    2002-11-30

    Epileptic seizures are common in patients with cerebral metastases as well as in patients with primary brain tumors. In cancer patients without primary brain tumors or brain metastasis, epileptic seizures may occur due to metabolic or toxic causes, or due to infections. We performed a retrospective analysis from our neurooncological database concerning the occurrence of seizures in patients with primary brain tumors, patients with cerebral metastases and in cancer patients without brain tumors. Patients with low grade gliomas, such as astrocytoma WHO I + II (69%), oligodendroglioma WHO II (50%), and mixed glioma WHO II-III (56%) were more likely to have seizures than patients with anaplastic glioma WHO III (44%), glioblastoma WHO IV (48%) or meningeoma (45%). In patients with brain metastasis, melanoma (67%), cancer of the lung (29%), and gastrointestinal tumors (21%) were the primaries with the highest frequency of seizures. In cancer patients without brain metastases or primary brain tumors, seizures occurred in 4%. In conclusion, the occurrence of epileptic seizures in patients suffering from primary brain tumors, as well as in patients with cerebral metastases, varied within the tumor entity. Therefore, especially in brain tumors where a higher probability of epileptic seizures is expected, they should be taken into account in the care of cancer patients.

  7. Interstitial irradiation of brain tumors: a review

    SciTech Connect

    Bernstein, M.; Gutin, P.H.

    1981-12-01

    As an adjuvant to surgery, radiation therapy has consistently proven to be the most successful form of treatment for primary and secondary malignant brain tumors and possibly for inoperable benign tumors. Because the risk of radiation necrosis of normal brain limits the amount of radiation that can be given by external beam therapy at conventional dose rates, interstitial radiation of brain tumors is a logical alternative treatment approach. We discuss the radiobiological advantages of low dose rate irradiation and intratumoral placement of sources that make interstitial irradiation an attractive treatment for brain tumors and review the history of clinical brachytherapy for intracranial neoplasia.

  8. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

  9. Drugs Approved for Brain Tumors

    MedlinePlus

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

  10. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

    PubMed Central

    Mansfield, A. S.; Aubry, M. C.; Moser, J. C.; Harrington, S. M.; Dronca, R. S.; Park, S. S.; Dong, H.

    2016-01-01

    Background The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. Experimental design Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ2 or Fisher's exact test were used for analysis. Results We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). Conclusions We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment. PMID:27502709

  11. Acceptance and commitment therapy program for distressed adults with a primary brain tumor: a case series study.

    PubMed

    Kangas, Maria; McDonald, Skye; Williams, Janet R; Smee, Robert I

    2015-10-01

    Research has indicated that adults diagnosed with a primary brain tumor (BT) are susceptible to experiencing anxiety and depressive problems post-diagnosis. However, there is a notable paucity of psychological interventions which have been tested with adult BT patients. An acceptance and commitment therapy (ACT)-based manualized program was developed for anxious and/or depressed BT patients. The preliminary efficacy of this program was initially tested using a proof-of-concept study design based on a case series of four clinically distressed BT patients. Three of the four participants no longer met criteria for anxiety and/or depressive disorders at post-therapy, and these effects were maintained at 3 months of follow-up. The fourth participant, who had a premorbid psychiatric history, experienced a stabilization of anxiety and depressive symptoms. Given the current dearth of studies which have tested psychological interventions for distressed BT survivors, these preliminary findings have promising clinical utility. However, the efficacy of psychological interventions tailored for clinically distressed BT patients needs to be further tested using larger-scale controlled trial designs.

  12. Promising role of [18F] fluorocholine PET/CT vs [18F] fluorodeoxyglucose PET/CT in primary brain tumors-early experience.

    PubMed

    Lam, Winnie Wing-Chuen; Ng, David Chee-Eng; Wong, Wai Yin; Ong, Seng Chuan; Yu, Sidney Wing-Kwong; See, Siew Ju

    2011-02-01

    Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality.

  13. Brain tumors at a nuclear facility.

    PubMed

    Reyes, M; Wilkinson, G S; Tietjen, G; Voelz, G L; Acquavella, J F; Bistline, R

    1984-10-01

    In response to an observed excess risk of brain tumor deaths among workers at the Rocky Flats Nuclear Facility (Colorado), a case-control study of all (n = 16) primary brain tumor deaths occurring among white males employed during 1952 through 1977 was conducted to investigate their relationship with occupational radiation/nonradiation exposures. For each case, four controls were individually matched on year of birth and period of employment. Although limited by a small number of cases, our study showed no statistically significant association between brain tumor death and exposure to internally deposited plutonium, external radiation, or other occupational risk factors. PMID:6491777

  14. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  15. Brain Tumor Epidemiology Consortium (BTEC)

    Cancer.gov

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

  16. Pediatric brain tumors and epilepsy.

    PubMed

    Wells, Elizabeth M; Gaillard, William D; Packer, Roger J

    2012-03-01

    Seizures are a common complication of pediatric brain tumors and their treatment. This article reviews the epidemiology, evaluation, and treatment of seizures in children with brain tumors. Seizures in known brain tumor patients may signify tumor progression or recurrence, or treatment-related brain damage, as well as other causes, including low drug levels and metabolic disturbances. Careful selection of antiepileptic medications is needed in this population. There are advantages to nonenzyme-inducing antiepileptic drugs including valproic acid, which has potential antitumoral properties as a histone deacetylase inhibitor. Tumor surgery cures many cases of pediatric tumor-associated seizures, and some children are controlled with anti-epileptic medication, however additional epilepsy surgery may be needed for refractory cases.

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

    PubMed Central

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

    2014-01-01

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

  18. Oncogenic extracellular vesicles in brain tumor progression.

    PubMed

    D'Asti, Esterina; Garnier, Delphine; Lee, Tae H; Montermini, Laura; Meehan, Brian; Rak, Janusz

    2012-01-01

    The brain is a frequent site of neoplastic growth, including both primary and metastatic tumors. The clinical intractability of many brain tumors and their distinct biology are implicitly linked to the unique microenvironment of the central nervous system (CNS) and cellular interactions within. Among the most intriguing forms of cellular interactions is that mediated by membrane-derived extracellular vesicles (EVs). Their biogenesis (vesiculation) and uptake by recipient cells serves as a unique mechanism of intercellular trafficking of complex biological messages including the exchange of molecules that cannot be released through classical secretory pathways, or that are prone to extracellular degradation. Tumor cells produce EVs containing molecular effectors of several cancer-related processes such as growth, invasion, drug resistance, angiogenesis, and coagulopathy. Notably, tumor-derived EVs (oncosomes) also contain oncogenic proteins, transcripts, DNA, and microRNA (miR). Uptake of this material may change properties of the recipient cells and impact the tumor microenvironment. Examples of transformation-related molecules found in the cargo of tumor-derived EVs include the oncogenic epidermal growth factor receptor (EGFRvIII), tumor suppressors (PTEN), and oncomirs (miR-520g). It is postulated that EVs circulating in blood or cerebrospinal fluid (CSF) of brain tumor patients may be used to decipher molecular features (mutations) of the underlying malignancy, reflect responses to therapy, or molecular subtypes of primary brain tumors [e.g., glioma or medulloblastoma (MB)]. It is possible that metastases to the brain may also emit EVs with clinically relevant oncogenic signatures. Thus, EVs emerge as a novel and functionally important vehicle of intercellular communication that can mediate multiple biological effects. In addition, they provide a unique platform to develop molecular biomarkers in brain malignancies. PMID:22934045

  19. Primary tumors of the patella.

    PubMed

    Song, Mingzhi; Zhang, Zhen; Wu, Yuxuan; Ma, Kai; Lu, Ming

    2015-01-01

    The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant cell tumors and chondroblastoma. With the development of modern diagnostic technologies, there appear however many other histological types which raise challenges of diagnosis and treatment. In this article, we review the reported histological types of primary patellar tumors. Specifically, epidemiology, symptomatology, imageology, histopathology, and treatment options for these histological lesions will be discussed, respectively. As there is an increasing focus on the diagnosis and the treatment of these lesions, the availability of the integrated information about primary patellar tumors becomes more significant. PMID:25906772

  20. Primary Cardiac Solitary Fibrous Tumors

    PubMed Central

    2015-01-01

    Primary cardiac solitary fibrous tumors were reviewed. They are classified as pericardial tumors. Their incidences are very rare. Only 16 cases were reported in the literature. Basically, surgical treatments are performed. Their prognoses are generally good, although malignant cases are also reported. PMID:26156195

  1. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  2. Primary tracheobronchial tumors in children.

    PubMed

    Varela, Patricio; Pio, Luca; Torre, Michele

    2016-06-01

    Primary tracheobronchial tumors are rare lesions that can be benign or malignant, with different location along the airway tree. Symptoms may include wheezing, chronic pneumonia, asthma, chest pain, recurrent cough, atelectasis, haemoptysis, and weight loss. Due to the heterogeneity of symptoms, diagnosis can be difficult and the airway involvement can lead progressively to a bronchial or tracheal obstruction. Due to the rarity of primary tracheobronchial tumors in children, there are not any oncological guidelines on pre-operative work-up, treatment, and follow-up. Only few reports and multicentric studies are reported. In most cases, surgical resection seems to be the treatment of choice. Brachytherapy, endoscopic treatment, and chemotherapy are rarely described. In this article we present an overview on these rare tumors, including pathological aspects, clinical presentation, imaging assessment, and endoscopic or open surgical treatments. We discuss different surgical approaches, according with tumor location. PMID:27301601

  3. MRI and MRS of human brain tumors.

    PubMed

    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM).

  4. Metastatic brain tumor

    MedlinePlus

    ... be to relieve symptoms, improve functioning, or provide comfort. Radiation to the whole brain is often used ... symptoms. This is called palliative or supportive care. Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  5. Brain tumors in irradiated monkeys.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  6. Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

    ClinicalTrials.gov

    2014-04-21

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma

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

    PubMed

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

    2015-05-01

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

  8. Paracoccidioidomycosis simulating brain tumor

    PubMed Central

    Isolan, Gustavo R.; Vieira, Daniel M.; Hehn, Francine; Antunes, Ápio C. M.

    2014-01-01

    Background: Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis. Involvement of the central nervous system (CNS) occurs in about 10% of cases. Case Description: A 57-year-old white man presented with the complaint of headache and an episode of focal seizure 1 month earlier. Magnetic resonance imaging (MRI) revealed a ring-enhancing lesion in the right parietal lobe with peri-lesional vasogenic edema suggestive of a primary neoplasm. The patient underwent craniotomy and the intraoperative finding was a yellowish, hard lesion with thick content and yellow inside. Anatomo-pathological findings were pathognomonic of PCM: large, thick-walled, spherical yeast cells with multiple peripheral buds. The patient tested negative for human immunodeficiency virus (HIV). Encephalitis and meningitis were ruled out by cerebrospinal fluid analysis. Culture confirmed the diagnosis of PCM and the patient was treated with amphotericin B. The patient responded well to treatment with resolution of the headache and clinical improvement, despite a bitemporal hemianopia. He was clinically stable and then discharged in good general condition. Conclusions: Radiographic findings of PCM with CNS involvement may suggest neoplasia, making diagnosis difficult. In endemic areas, the diagnosis of PCM should be promptly considered when a ring-enhancing mass associated with peri-lesional edema is observed on MRI. PMID:25298916

  9. Deregulated proliferation and differentiation in brain tumors

    PubMed Central

    Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

    2014-01-01

    Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

  10. Development and evaluation of information resources for patients, families, and healthcare providers addressing behavioral and cognitive sequelae among adults with a primary brain tumor.

    PubMed

    Wright, Kylie M; Simpson, Grahame K; Koh, Eng-Siew; Whiting, Diane L; Gillett, Lauren; Simpson, Teresa; Firth, Rochelle

    2015-06-01

    Behavioral and cognitive changes in patients with primary brain tumor (PBT) are common and may be distressing to patients and their family members. Healthcare professionals report a strong need for information, practical strategies, and training to assist consumers and better address management issues. A literature review by the current project found that 53% of the information resources currently available to consumers and health professionals contained minimal or no information about cognitive/behavioral changes after PBT, and 71% of the resources contained minimal or no information on associated strategies to manage these changes. This project aimed to develop an information resource for patients, carers, and health professionals addressing the behavioral and cognitive sequelae of PBT, including strategies to minimize the disabling impact of such behaviors. In consultation with staff and patient groups, 16 key information topics were identified covering cognitive and communication changes and challenging behaviors including executive impairment, behavioral disturbance, and social/emotional dysfunction. Sixteen fact sheets and 11 additional resource sheets were developed and evaluated according to established consumer communication guidelines. Preliminary data show that these resources have been positively received and well utilized. These sheets are the first of their kind addressing challenging behaviors in the neuro-oncology patient group and are a practical and useful information resource for health professionals working with these patients and their families. The new resource assists in reinforcing interventions provided to individual patients and their relatives who are experiencing difficulties in managing challenging behaviors after PBT. PMID:25827649

  11. The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation

    PubMed Central

    Lauro, Christine; Macy, Margaret E.; Zeitler, Philip; Backus, Jennifer; Mettler, Pamela; Foreman, Nicholas; Liu, Arthur K.

    2014-01-01

    Purpose The aim of this work is to determine if a relationship exists between thyroid dose and incidence of primary hypothyroidism (PH) in children undergoing craniospinal irradiation (CSI). Methods A total of 22 patients received CSI with evaluable thyroid dose information. All patients received concurrent chemotherapy and 21 patients (95%) received adjuvant chemotherapy. Median follow-up was 42.9 months. Results The incidence of PH in our cohort was 59% at a median time after radiotherapy of 3.5 years (range: 8 months to 7.5 years). Mean thyroid dose appeared to best predict for PH, with a median of 2080 cGy for patients with PH versus 1736 cGy for children without PH (p=0.057). There was no association between the rate of PH and sex, age, CSI dose, minimum thyroid dose and maximum thyroid dose. Conclusions A relationship may exist between the mean thyroid dose and incidence of PH in patients undergoing CSI. Thus, new strategies to protect the thyroid gland may be warranted. PMID:24057590

  12. Gene therapy for brain tumors.

    PubMed

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  13. What underlies the diversity of brain tumors?

    PubMed Central

    Swartling, Fredrik J.; Hede, Sanna-Maria; Weiss, William A.

    2012-01-01

    Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children respectively. Recent genomic and transcriptional approaches present a complex group of diseases, and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development, and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development, and the potential for these animals to impact brain tumor research. PMID:23085857

  14. Brain angiogenesis: Mechanism and Therapeutic Intervention in Brain Tumors

    PubMed Central

    Kim, Woo-Young; Lee, Ho-Young

    2010-01-01

    Summary Formation of new blood vessels is required for growth and metastasis of all solid tumors. New blood vessels are established in tumors mainly through angiogenesis. Brain tumors in particular are highly angiogenic. Therefore, interventions designed to prevent angiogenesis may be effective at controlling brain tumors. Indeed, many recent findings from preclinical and clinical studies of antiangiogenic therapy for brain tumors showed that it is a promising approach to managing this deadly disease, especially when combined with other cytotoxic treatments. In this review, we summarize the basic characteristics of brain tumor angiogenesis and role of known angiogenic factors in regulating this angiogenesis, which can be targets of antiangiogenic therapy. We also discuss the current status of antiangiogenic therapy for brain tumors, the suggested mechanisms of this therapy, and the limitations of this strategy. PMID:19664069

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

    ClinicalTrials.gov

    2016-07-08

    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

  16. Molecular Culprits Generating Brain Tumor Stem Cells

    PubMed Central

    Oh, Se-Yeong

    2013-01-01

    Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes. PMID:24904883

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

    PubMed

    Fontebasso, Adam M; Jabado, Nada

    2015-01-01

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

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

    PubMed Central

    2012-01-01

    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. PMID:22277186

  19. MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors

    PubMed Central

    Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Park, Chul-Kee; Kim, Il Han; Choi, Seung Hong

    2015-01-01

    The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population. PMID:26322780

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

    MedlinePlus

    ... spinal cord tumors in children staged? How are brain and spinal cord tumors diagnosed in children? Brain ... resonance angiography (MRA) or computerized tomographic angiography (CTA). Brain or spinal cord tumor biopsy Imaging tests such ...

  1. Signaling the Unfolded Protein Response in primary brain cancers.

    PubMed

    Le Reste, Pierre-Jean; Avril, Tony; Quillien, Véronique; Morandi, Xavier; Chevet, Eric

    2016-07-01

    The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target. PMID:27016056

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

    PubMed

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

    2015-11-07

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

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

    PubMed

    Stricker, Thomas; Arteaga, Carlos L

    2015-11-01

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

  4. Staging Childhood Brain and Spinal Cord Tumors

    MedlinePlus

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

  5. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts. PMID:26917429

  6. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts.

  7. Three mutant genes cooperatively induce brain tumor formation in Drosophila malignant brain tumor.

    PubMed

    Riede, I

    1996-09-01

    The Drosophila melanogaster strain Malignant Brain Tumor reveals temperature-sensitive transformation of the larval brain tissue. Genetic analysis shows that three gene defects, spzMBT, yetiMBT, and tldMBT, cooperatively induce brain tumor formation. Whereas spz and tld belong to the genes inducing differentiation patterns in the embryo, yeti induces cell overgrowth. spzMBT-, yetiMBT-, and tldMBT-containing animals are larval lethal, whereas Malignant Brain Tumor is kept as a homozygous strain at a permissive temperature. This reveals that this tumor-forming strain is the result of a number of adaptive mutation events.

  8. Surgical Outcomes of Hemorrhagic Metastatic Brain Tumors

    PubMed Central

    Yoo, Heon; Jung, Eugene; Gwak, Ho Shin; Shin, Sang Hoon

    2011-01-01

    Purpose Hemorrhagic metastatic brain tumors are not rare, but little is known about the surgical outcome following treatment. We conducted this study to determine the result of the surgical outcome of hemorrhagic metastatic brain tumors. Materials and Methods From July 2001 to December 2008, 21 patients underwent surgery for hemorrhagic metastatic brain tumors at our institution. 15 patients had lung cancer, 3 had hepatocellular carcinoma, and the rest had rectal cancer, renal cell carcinoma, and sarcoma. 20 patients had macroscopic hemorrhage in the tumors, and one patient had intracerebral hemorrhage surrounding the tumor. A retrospective clinical review was conducted focusing on the patterns of presenting symptoms and signs, as well as local recurrence following surgery. Results Among 21 hemorrhagic brain metastases, local recurrence developed in two patients. The 12 month progression free survival rate was 86.1%. Mean time to progression was 20.8 months and median survival time after surgery was 11.7 months. Conclusion The results of our study showed that hemorrhagic metastatic brain tumors rarely recurred after surgery. Surgery should be considered as a good treatment option for hemorrhagic brain metastasis, especially in cases with increased intracranial pressure or severe neurologic deficits. PMID:21811426

  9. Primary mediastinal choriocarcinoma with brain metastasis in a female patient.

    PubMed

    Kuno, I; Matsumoto, Y; Kasai, M; Fukuda, T; Hashiguchi, Y; Ichimura, T; Yasui, T; Sumi, T

    2016-01-01

    Nongestational choriocarcinoma is very rare and carries a poor prognosis in female patients. In this report, the authors present a case of nongestational choriocarcinoma with brain metastasis in a female. A 58-year-old female with intermittent back pain was referred to a private hospital. On examination, a mediastinal tumor and a pancreatic tumor were detected. Endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor was performed for histological evaluation. Pathological diagnosis was difficult because only a small amount of tissue was collected. Head MRI showed multiple metastatic tumors in the brain. The patient was diagnosed with primary mediastinal choriocarcinoma with brain metastasis. She was treated with one course of an etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine regimen, but her general condition gradually deteriorated, and she died on day 41. Nongestational choriocarcinoma is drug resistant, whereas gestational choriocarcinoma has better chemotherapeutic sensitivity. PMID:27172760

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

    PubMed

    Lampson, Lois A

    2003-01-01

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

  11. Novel Magnetic Resonance Imaging Techniques in Brain Tumors.

    PubMed

    Nechifor, Ruben E; Harris, Robert J; Ellingson, Benjamin M

    2015-06-01

    Magnetic resonance imaging is a powerful, noninvasive imaging technique with exquisite sensitivity to soft tissue composition. Magnetic resonance imaging is primary tool for brain tumor diagnosis, evaluation of drug response assessment, and clinical monitoring of the patient during the course of their disease. The flexibility of magnetic resonance imaging pulse sequence design allows for a variety of image contrasts to be acquired, including information about magnetic resonance-specific tissue characteristics, molecular dynamics, microstructural organization, vascular composition, and biochemical status. The current review highlights recent advancements and novel approaches in MR characterization of brain tumors.

  12. New strategies to deliver anticancer drugs to brain tumors

    PubMed Central

    Laquintana, Valentino; Trapani, Adriana; Denora, Nunzio; Wang, Fan; Gallo, James M.; Trapani, Giuseppe

    2009-01-01

    BACKGROUND Malignant brain tumors are among the most challenging to treat and at present there are no uniformly successful treatment strategies. Standard treatment regimens consist of maximal surgical resection followed by radiotherapy and chemotherapy. The limited survival advantage attributed to chemotherapy is partially due to low CNS penetration of antineoplastic agents across the blood-brain barrier (BBB). OBJECTIVE The objective of this paper is to review recent approaches to deliver anticancer drugs into primary brain tumors. METHODS Both preclinical and clinical strategies to circumvent the BBB are considered that includes chemical modification and colloidal carriers. CONCLUSION Analysis of the available data indicates that novel approaches may be useful for CNS delivery, yet an appreciation of pharmacokinetic issues, and improved knowledge of tumor biology will be needed to significantly impact drug delivery to the target site. PMID:19732031

  13. General Information about Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

  14. Proton MRS imaging in pediatric brain tumors.

    PubMed

    Zarifi, Maria; Tzika, A Aria

    2016-06-01

    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. PMID:27233788

  15. [A unusual brain cortical tumor: angiocentric glioma].

    PubMed

    Tauziède-Espariat, Arnault; Fohlen, Martine; Ferrand-Sorbets, Sarah; Polivka, Marc

    2015-04-01

    We report the case of an 11-year-old girl, who was admitted for surgery of an epilepsy-associated brain tumor. The radiological and clinical hypothesis was dysembryoplasic neuroepithelial tumor. Histopathological examination revealed a tumoral proliferation composed of spindle-shaped cells with palisade arrangements around vessels. Tumor cells have small, round and regular nuclei without atypia or mitosis. On immunohistochemistry, the neoplastic cells strongly expressed GFAP and showed a characteristic cytoplasmic dot-like staining with EMA (epithelial membrane antigen). Ki-67 labeling index was low. Molecular analysis failed to reveal the V600E mutation of BRAF gene. The patient was free of seizures after surgery. Angiocentric glioma is a rare brain tumor occuring preferably in children and young adults and is associated with seizures. The precise histogenesis remains debated. The treatment of choice is total resection. The prognosis is favorable if totally resected.

  16. Epigenetics in Brain Tumors: HDACs Take Center Stage

    PubMed Central

    Eyüpoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Primary tumors of the brain account for 2 % of all cancers with malignant gliomas taking the lion’s share at 70 %. Malignant gliomas (high grade gliomas WHO° III and °IV) belong to one of the most threatening tumor entities known for their disappointingly short median survival time of just 14 months despite maximum therapy according to current gold standards. Malignant gliomas manifest various factors, through which they adapt and manipulate the tumor microenvironment to their advantage. Epigenetic mechanisms operate on the tumor microenvironment by de- and methylation processes and imbalances between the histone deacetylases (HDAC) and histone acetylases (HAT). Many compounds have been discovered modulating epigenetically controlled signals. Recent studies indicate that xCT (system xc-, SLC7a11) and CD44 (H-CAM, ECM-III, HUTCH-1) functions as a bridge between these epigenetic regulatory mechanisms and malignant glioma progression. The question that ensues is the extent to which therapeutic intervention on these signaling pathways would exert influence on the treatment of malignant gliomas as well as the extent to which manipulation of HDAC activity can sensitize tumor cells for chemotherapeutics through ‘epigenetic priming’. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of gliomas has never been so pressing. In this context the possibility of pharmacological intervention on tumor-associated genes by epigenetic priming opens a novel path in the treatment of primary brain tumors. PMID:26521944

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

    PubMed Central

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

    2002-01-01

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

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

    SciTech Connect

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

    1985-05-01

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

  19. Psychiatric aspects of brain tumors: A review

    PubMed Central

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

    2015-01-01

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

  20. Primary phospholipase C and brain disorders.

    PubMed

    Yang, Yong Ryoul; Kang, Du-Seock; Lee, Cheol; Seok, Heon; Follo, Matilde Y; Cocco, Lucio; Suh, Pann-Ghill

    2016-05-01

    In the brain, the primary phospholipase C (PLC) proteins, PLCβ, and PLCγ, are activated primarily by neurotransmitters, neurotrophic factors, and hormones through G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). Among the primary PLC isozymes, PLCβ1, PLCβ4, and PLCγ1 are highly expressed and differentially distributed, suggesting a specific role for each PLC subtype in different regions of the brain. Primary PLCs control neuronal activity, which is important for synapse function and development. In addition, dysregulation of primary PLC signaling is linked to several brain disorders including epilepsy, schizophrenia, bipolar disorder, Huntington's disease, depression and Alzheimer's disease. In this review, we included current knowledge regarding the roles of primary PLC isozymes in brain disorders. PMID:26639088

  1. Head, neck, and brain tumor embolization guidelines

    PubMed Central

    Duffis, E Jesus; Prestigiacomo, Charles Joseph; Abruzzo, Todd; Albuquerque, Felipe; Bulsara, Ketan R; Derdeyn, Colin P; Fraser, Justin F; Hirsch, Joshua A; Hussain, Muhammad Shazam; Do, Huy M; Jayaraman, Mahesh V; Meyers, Philip M; Narayanan, Sandra

    2012-01-01

    Background Management of vascular tumors of the head, neck, and brain is often complex and requires a multidisciplinary approach. Peri-operative embolization of vascular tumors may help to reduce intra-operative bleeding and operative times and have thus become an integral part of the management of these tumors. Advances in catheter and non-catheter based techniques in conjunction with the growing field of neurointerventional surgery is likely to expand the number of peri-operative embolizations performed. The goal of this article is to provide consensus reporting standards and guidelines for embolization treatment of vascular head, neck, and brain tumors. Summary This article was produced by a writing group comprised of members of the Society of Neurointerventional Surgery. A computerized literature search using the National Library of Medicine database (Pubmed) was conducted for relevant articles published between 1 January 1990 and 31 December 2010. The article summarizes the effectiveness and safety of peri-operative vascular tumor embolization. In addition, this document provides consensus definitions and reporting standards as well as guidelines not intended to represent the standard of care, but rather to provide uniformity in subsequent trials and studies involving embolization of vascular head and neck as well as brain tumors. Conclusions Peri-operative embolization of vascular head, neck, and brain tumors is an effective and safe adjuvant to surgical resection. Major complications reported in the literature are rare when these procedures are performed by operators with appropriate training and knowledge of the relevant vascular and surgical anatomy. These standards may help to standardize reporting and publication in future studies. PMID:22539531

  2. [Conformal radiotherapy of brain tumors].

    PubMed

    Haie-Meder, C; Beaudré, A; Breton, C; Biron, B; Cordova, A; Dubray, B; Mazeron, J J

    1999-01-01

    Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy. PMID:10572510

  3. The delivery of BCNU to brain tumors.

    PubMed

    Wang, C C; Li, J; Teo, C S; Lee, T

    1999-08-27

    This paper reports the development of three-dimensional simulations to study the effect of various factors on the delivery of 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to brain tumors. The study yields information on the efficacy of various delivery methods, and the optimal location of polymer implantation. Two types of drug deliveries, namely, systemic administration and controlled release from polymers, were simulated using fluid dynamics analysis package (FIDAP) to predict the temporal and spatial variation of drug distribution. Polymer-based delivery provides higher mean concentration, longer BCNU exposure time and reduced systemic toxicity than bolus injection. Polymer implanted in the core gives higher concentration of drug in both the core and viable zone than the polymer in the viable zone case. The penetration depth of BCNU is very short. This is because BCNU can get drained out of the system before diffusing to any appreciable distance. Since transvascular permeation is the dominant means of BCNU delivery, the interstitial convection has minor effect because of the extremely small transvascular Peclet number. The reaction of BCNU with brain tissues reduces the drug concentration in all regions and its effect increases with rate constant. The implantation of BCNU/ethylene-vinyl acetate copolymer (EVAc) matrix at the lumen of the viable zone immediately following the surgical removal of 80% of the tumor may be an effective treatment for the chemotherapy of brain tumors. The present study provides a quantitative examination on the working principle of Gliadel wafer for the treatment of brain tumors.

  4. [Differential infratentorial brain tumor diagnosis in children].

    PubMed

    Warmuth-Metz, M; Kühl, J; Rutkowski, S; Krauss, J; Solymosi, L

    2003-11-01

    With the exception of the first year of life, infratentorial brain tumors are more frequent in the first decade than tumors in the supratentorial compartment. In particular these are cerebellar low-grade astrocytomas, medulloblastomas, brainstem gliomas and ependymomas of the fourth ventricle. The morphology on MRI and CT and the mode of dissemination permit differential diagnosis in many cases. To allow correct stratification into different treatments in possibly disseminating malignant brain tumors, knowledge of the status of dissemination is essential, and therefore not only cranial but also spinal MRI is indispensable for staging. If the spinal MRI is performed in the immediate postoperative period, knowledge of the normal non-specific purely postoperative changes, often seen as enhancement in the subdural spinal spaces, is necessary in order to avoid misinterpretation as meningial seeding. The differential diagnosis of pediatric infratentorial brain tumors and the morphology of subdural enhancement are illustrated with typical images. The natural history of the most frequent tumors and its importance for treatment decisions is discussed in light of the literature.

  5. Primary hepatic neuroendocrine tumor: A case report

    PubMed Central

    MORISHITA, ASAHIRO; YONEYAMA, HIROHITO; NOMURA, TAKAKO; SAKAMOTO, TEPPEI; FUJITA, KOJI; TANI, JOJI; MIYOSHI, HISAAKI; HABA, REIJI; MASAKI, TSUTOMU

    2016-01-01

    We herein present a case of an 87-year-old patient with multiple liver tumors identified on abdominal ultrasound. The assessment performed on admission included physical examination, computed tomography (CT) during hepatic angiography and CT during arterial portography. The examination revealed contrast enhancement of a proportion of the liver tumors (20 mm maximum diameter) during the arterial phase and mild contrast washout of those tumors during the delayed phase. On contrast-enhanced magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, certain liver tumors exhibited contrast enhancement during the early phase and contrast washout during the hepatocyte phase in both lobes. By contrast, no lesions were identified during positron emission tomography imaging of the liver. A liver biopsy was performed and immunohistochemical staining revealed enhanced expression of cytokeratin AE1/AE3, synaptophysin, chromogranin A and CD56 and no expression of hepatocyte antigen or CΚ7. The mindbomb E3 ubiquitin protein ligase-1 index was ~2% in most of the tumor. The liver tumors were finally diagnosed as multiple intrahepatic metastases from a primary hepatic neuroendocrine tumor (PHNET). The patient underwent transarterial chemoembolisation with a combination of miriplatin (84 mg) mixed with gelatin sponge particles and lipiodol. To the best of our knowledge, this is the first report of PHNET in an patient aged >85 years. PMID:27284429

  6. A Rare Malignant Fetal Brain Tumor.

    PubMed

    Iruretagoyena, Jesus Igor; Heiser, Timothy; Iskandar, Bermans; Shah, Dinesh

    2016-01-01

    A gravida 4, para 3 female at 37 weeks' gestation presented for a routine ultrasound. She had an otherwise uncomplicated low-risk pregnancy. The sonographic evaluation of the fetus revealed a macrocephaly and a deviation of the brain midline structures with a mass effect as well as a massively dilated left cerebral ventricular system with ill-defined echogenic ventricular delineation. Multiple free intracavitary echogenicities and disruptions of the brain mantle were visible. Our images were suggestive of either an intracranial bleed with the presence of an underlying tumor or a spontaneous bleed. A postnatal MRI was consistent with our prenatal findings of a possible tumor. The postnatal biopsy revealed an anaplastic astroblastoma within a hemorrhagic background. The infant received multiple courses of chemotherapy and further tumor debulking. At present, the infant is 18 months old. This is only the 4th case of an astrocytoma identified in the fetal period, and our case has the longest known survival yet. PMID:26044034

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

    NASA Astrophysics Data System (ADS)

    Veiseh, Omid

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

  8. Primary renal carcinoid tumor: A radiologic review

    PubMed Central

    Lamb, Leslie; Shaban, Wael

    2015-01-01

    Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally) octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney. PMID:27186242

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  11. Clinical epidemiology for childhood primary central nervous system tumors.

    PubMed

    Bauchet, Luc; Rigau, Valérie; Mathieu-Daudé, Hélène; Fabbro-Peray, Pascale; Palenzuela, Gilles; Figarella-Branger, Dominique; Moritz, Jorge; Puget, Stéphanie; Bauchet, Fabienne; Pallusseau, Lorelei; Duffau, Hugues; Coubes, Philippe; Trétarre, Brigitte; Labrousse, François; Dhellemmes, Patrick

    2009-03-01

    This work was conducted by the French Brain Tumor Data Bank (FBTDB) and aims to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available. Results concerning children are presented. This study analyzes the childhood cases (0-19 years) of newly diagnosed and histologically confirmed PCNST (during the years 2004-2006) which have been recorded by the FBTDB. All French neuropathology and neurosurgery departments participated in this program. Neurosurgeons and neuropathologists completed a data file containing socio-demographic, clinical, radiologic and anatomopathologic information. The Tumor Registry from Herault was authorized to compile the data files with personal identifiers. About 1,017 cases (533 boys and 484 girls) of newly diagnosed childhood PCNST have been recorded (gliomas: 52%, all other neuroepithelial tumors: 31%, craniopharyngioma: 5%, germ cell tumors, meningioma and neurinoma: approximately 3% each, all histological subtypes have been detailed). Tumor resections were performed in 83.3%, and biopsies in 16.7%. The distributions by histology, cryopreservation of the samples, age, sex, tumor site and surgery have been detailed. To our knowledge, this work is the first databank in Europe dedicated to PCNST that includes the collection of clinical, radiological and histological data (including cryopreservation of the specimen). The long term goals of the FBTDB are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to evaluate and harmonize the healthcare of children and adult patients affected by PCNST. PMID:19020806

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

    SciTech Connect

    Adam, Jean-Francois

    2005-04-01

    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 <50x50 {mu}m{sup 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

  13. Gamma Knife Radiosurgery for Brain Metastases From Primary Breast Cancer

    SciTech Connect

    Kased, Norbert; Binder, Devin K.; McDermott, Michael W.; Nakamura, Jean L.; Huang, Kim; Berger, Mitchel S.; Wara, William M.; Sneed, Penny K.

    2009-11-15

    Purpose: The relative roles of stereotactic radiosurgery (SRS) vs. whole brain radiotherapy (WBRT) in the treatment of patients with brain metastases from breast cancer remain undefined. In this study, we reviewed our experience with these patients. Materials and Methods: We retrospectively reviewed all patients treated between 1991 and 2005 with Gamma Knife SRS for brain metastases from breast cancer. The actuarial survival and freedom from progression endpoints were calculated using the Kaplan-Meier method. Results: Between 1991 and 2005, 176 patients underwent SRS for brain metastases from breast cancer. The median survival time was 16.0 months for 95 newly diagnosed patients and 11.7 months for 81 patients with recurrent brain metastases. In the newly diagnosed patients, omission of upfront WBRT did not significantly affect the MST (p = .20), brain freedom from progression (p = .75), or freedom from new brain metastases (p = .83). Longer survival was associated with age <50 years, Karnofsky performance score >=70, primary tumor control, estrogen receptor positivity, and Her2/neu overexpression. No association was found between the number of treated brain metastases and the survival time. Conclusion: We have described prognostic factors for breast cancer patients treated with SRS for newly diagnosed or recurrent brain metastases. Most patient subsets had a median survival time of >=11 months. Unexpectedly, upfront WBRT did not appear to improve brain freedom from progression, and a larger number of brain metastases was not associated with a shorter survival time. Breast cancer might be distinct from other primary sites in terms of prognostic factors and the roles of WBRT and SRS for brain metastases.

  14. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice. PMID:26975959

  15. Primary Hepatic Carcinoid Tumor with Poor Outcome.

    PubMed

    Parkash, Om; Ayub, Adil; Naeem, Buria; Najam, Sehrish; Ahmed, Zubair; Jafri, Wasim; Hamid, Saeed

    2016-03-01

    Primary Hepatic Carcinoid Tumor (PHCT) represents an extremely rare clinical entity with only a few cases reported to date. These tumors are rarely associated with metastasis and surgical resection is usually curative. Herein, we report two cases of PHCT associated with poor outcomes due to late diagnosis. Both cases presented late with non-specific symptoms. One patient presented after a 2-week history of symptoms and the second case had a longstanding two years symptomatic interval during which he remained undiagnosed and not properly worked up. Both these cases were diagnosed with hepatic carcinoid tumor, which originates from neuroendocrine cells. Case 1 opted for palliative care and expired in one month’s time. Surgical resection was advised to the second case, but he left against medical advice.

  16. Radiosurgery for Brain Metastases From Unknown Primary Cancers

    SciTech Connect

    Niranjan, Ajay; Kano, Hideyuki; Khan, Aftab; Kim, In-Young; Kondziolka, Douglas; Flickinger, John C.; Lunsford, L. Dade

    2010-08-01

    Purpose: We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer. Methods and Materials: Twenty-nine patients who had solitary or multiple brain metastases without a detectable primary site underwent stereotactic radiosurgery between January 1990 and March 2007 at the University of Pittsburgh. The median patient age was 61.7 years (range, 37.9-78.7 years). The median target volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose was 16 Gy (range, 20-70 Gy). Results: After radiosurgery, the local tumor control rate was 88.5%. Twenty four patients died and 5 patients were living at the time of this analysis. The overall median survival was 12 months. Actuarial survival rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%, respectively. Factors associated with poor progression-free survival included large tumor volume (3 cc or more) and brainstem tumor location. Conclusions: Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases from an unknown primary site.

  17. Clinical considerations for neutron capture therapy of brain tumors

    SciTech Connect

    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 United States 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 now 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 causes gamma rays to be generated when it interacts with tissue, we 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. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues. 10 references.

  18. CT evaluation of primary benign retroperitoneal tumor.

    PubMed

    Hayasaka, K; Yamada, T; Saitoh, Y; Yoshikawa, D; Aburano, T; Hashimoto, H; Yachiku, S

    1994-01-01

    We studied CT patterns in 21 cases of primary benign retroperitoneal tumor including teratoma in nine cases, schwannoma in six, leiomyoma in three, lipoma in one, lymphangioma in one, and neurofibroma in one. The tumors were analyzed for size, internal homogeneity, CT density, calcification, border with neighboring organs, and contrast enhancement (CE). The mean diameter of the tumors was 10.2 (+/- 4.8) cm. Internal homogeneous distribution was observed in 33%, calcification in 43%, and well-defined border in 86%. The CT density and calcification were compared according to histology, and the results were as follows: teratoma showed fat density in 78%, water density in 100%, and calcification in 89%; schwannoma showed water density in 100% and septal CE in 33%; leiomyoma showed soft tissue density in 100%, CE in 100%, and water density in 33%; lipoma showed fat density and calcification; and lymphangioma and neurofibroma showed water density. Internal homogeneity, fat density, cyst formation, and calcification are considered to be important predictors of primary benign retroperitoneal tumor on CT.

  19. The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.

    PubMed

    Valvona, Cara J; Fillmore, Helen L; Nunn, Peter B; Pilkington, Geoffrey J

    2016-01-01

    There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non-neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.

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

    SciTech Connect

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

    1985-06-01

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

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

    SciTech Connect

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

    1989-05-15

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

  2. Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples

    PubMed Central

    Shahi, Mehdi H.; Zazpe, Idoya; Afzal, Mohammad; Sinha, Subrata; Rebhun, Robert B.; Meléndez, Bárbara; Rey, Juan A.

    2016-01-01

    Glioma constitutes one of the most common groups of brain tumors, and its prognosis is influenced by different genetic and epigenetic modulations. In this study, we demonstrated low or no expression of hedgehog interacting protein (HHIP) in most of the cell lines and primary glioma tumor samples. We further proceeded to promoter methylation study of this gene in the same cell lines and primary tumor samples and found 87 % (7/8) HHIP methylation in glioblastoma cell lines and 75 % (33/44) in primary tumor samples. These methylation pattern correlates with low or unexpressed HHIP in both cell lines and primary tumor samples. Our results suggest the possibility of epigenetic regulation of this gene in glioma, similarly to medulloblastoma, gastric, hepatic, and pancreatic cancers. Also, HHIP might be a diagnostic or prognostic marker in glioma and help to the detection of these tumors in early stages of disease. PMID:25416442

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

    PubMed

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

    2015-03-01

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

  4. Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT.

    PubMed

    Calabria, Ferdinando; Chiaravalloti, Agostino; Di Pietro, Barbara; Grasso, Cristina; Schillaci, Orazio

    2012-06-01

    The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.

  5. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

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

  6. Penetration of intra-arterially administered vincristine in experimental brain tumor1,2

    PubMed Central

    Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

    2004-01-01

    Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan’s blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors. PMID:15494097

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

    SciTech Connect

    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.

  8. Photodynamic Therapy for Malignant Brain Tumors

    PubMed Central

    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. PMID:26888042

  9. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  10. Multifocal brain radionecrosis masquerading as tumor dissemination

    SciTech Connect

    Safdari, H.; Boluix, B.; Gros, C.

    1984-01-01

    The authors report on an autopsy-proven case of multifocal widespread radionecrosis involving both cerebral hemispheres and masquerading as tumor dissemination on a CT scan done 13 months after complete resection of an oligodendroglioma followed by radiation therapy. This case demonstrates that radiation damage may be present in a CT scan as a multifocal, disseminated lesion. Since the survival of brain-tumor patients who have undergone radiation therapy is prolonged by aggressive therapy, the incidence and variability of radiation-induced complications in such cases is likely to increase. For similar reasons, the radionecrosis in such cases should be taken into consideration. A short review of the CT scan findings and diagnostic and therapeutic considerations in a case of widespread radionecrosis is presented. The need for appropriate diagnosis and subsequent life-saving management is emphasized.

  11. Positron Scanner for Locating Brain Tumors

    DOE R&D Accomplishments Database

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

    1962-03-01

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

  12. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    PubMed Central

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

    2013-01-01

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

  13. NI-78LABEL-FREE MULTIPHOTON MICROSCOPY: A NOVEL TOOL FOR THE IMAGING OF BRAIN TUMORS

    PubMed Central

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

    2014-01-01

    Changes in tissue composition caused by brain tumor growth involve a series of complex biochemical alterations which can be imaged on unstained native tissue using multiphoton microscopy: We used coherent anti-Stokes Raman scattering (CARS) imaging that resonantly excites the symmetric stretching vibration of CH2 groups at 2850 cm−1 and visualizes lipid content in combination with imaging of endogenous two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) to discern different types of tumors from normal tissue in unstained, native brain samples. Experimental brain tumors were induced in nude mice NMRI nu/nu (n = 25) by stereotactic implantation of glioblastoma (U87), melanoma (A375) and breast cancer (MCF-7) cell lines. Label-free multiphoton microscopy of brain cryosections provided exhaustive information of the tumor morphochemistry. The tumor border was defined with cellular resolution by a strong reduction of CARS signal intensity to 61% (glioblastoma), 71% (melanoma) and 68% (breast cancer). This reduction of lipid content within the tumor was confirmed by Raman spectroscopy. Micrometastases infiltrating normal tissue (size 50 - 200 µm) were identified in glioblastoma and melanoma. Additionally, multiphoton microscopy proved a reduction of CARS signal intensity in all human glioblastoma samples analyzed (to 72%, n = 6). Additionally, relevant SHG and TPEF signals were detected in human primary and secondary brain tumor samples and enabled to image variations in tumor associated vasculature, fibrosis, necrosis and nuclear size and density. All primary or secondary brain tumors investigated were characterized by a lower intensity of the CARS signal, therefore offering a simple tool for objective tumor detection and delineation. The combination of techniques allows retrieving a quantity of information on native unstained tissue which is comparable to H&E staining. Therefore, label-free multiphoton microscopy has the potential to become a

  14. Treatment of primary brain tumours in adults.

    PubMed

    McNamara, Shanne

    This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse's contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

  15. Comparative Membranome expression analysis in primary tumors and derived cell lines.

    PubMed

    Uva, Paolo; Lahm, Armin; Sbardellati, Andrea; Grigoriadis, Anita; Tutt, Andrew; de Rinaldis, Emanuele

    2010-01-01

    Despite the wide use of cell lines in cancer research, the extent to which their surface properties correspond to those of primary tumors is poorly characterized. The present study addresses this problem from a transcriptional standpoint, analyzing the expression of membrane protein genes--the Membranome--in primary tumors and immortalized in-vitro cultured tumor cells. 409 human samples, deriving from ten independent studies, were analyzed. These comprise normal tissues, primary tumors and tumor derived cell lines deriving from eight different tissues: brain, breast, colon, kidney, leukemia, lung, melanoma, and ovary. We demonstrated that the Membranome has greater power than the remainder of the transcriptome when used as input for the automatic classification of tumor samples. This feature is maintained in tumor derived cell lines. In most cases primary tumors show maximal similarity in Membranome expression with cell lines of same tissue origin. Differences in Membranome expression between tumors and cell lines were analyzed also at the pathway level and biological themes were identified that were differentially regulated in the two settings. Moreover, by including normal samples in the analysis, we quantified the degree to which cell lines retain the Membranome up- and down-regulations observed in primary tumors with respect to their normal counterparts. We showed that most of the Membranome up-regulations observed in primary tumors are lost in the in-vitro cultured cells. Conversely, the majority of Membranome genes down-regulated upon tumor transformation maintain lower expression levels also in the cell lines. This study points towards a central role of Membranome genes in the definition of the tumor phenotype. The comparative analysis of primary tumors and cell lines identifies the limits of cell lines as a model for the study of cancer-related processes mediated by the cell surface. Results presented allow for a more rational use of the cell lines as a

  16. Bioluminescence imaging of invasive intracranial xenografts: implications for translational research and targeted therapeutics of brain tumors.

    PubMed

    Dinca, Eduard B; Voicu, Ramona V; Ciurea, Alexandru V

    2010-10-01

    Despite decades of study, the etiology of brain cancer remains elusive. However, extensive molecular characterization of primary brain tumors has been accomplished, outlining recurrent features that are proving useful for devising targeted therapies. There are far too few patients available for comparing the efficacy of therapeutic combinations, especially when variations in dosing, frequency, and sequencing are taken into account. Consequently, there is a substantial need for increasing preclinical testing throughput using clinically relevant models. We review luminescent optical imaging for its potential in facilitating in vivo assessment of intracranial tumor growth and response to therapy in rodent orthotopic xenograft models of primary brain malignancies. We review the rationale behind the need of an in vivo model, why orthotopic tumor models displaying an invasive phenotype may be a superior choice when compared to flank-implanted tumors, and what advantages may be drawn from the use of modified cells, suitable for sequential monitoring by in vivo optical imaging. Studies show that luminescent signal correlates highly both with tumor burden and Kaplan-Meier survival curves of rodents bearing intracranial xenografts. We conclude that bioluminescent imaging is a highly sensitive technique for assessment of tumor burden, response to therapy, tumor recurrence, and behavior to salvage therapy, making it a superior option for longitudinal monitoring in intracranial rodent models of primary brain tumors.

  17. The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.

    PubMed Central

    Criscuolo, G. R.

    1993-01-01

    Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention. Images Figure 1 Figure 2 Figure 3 PMID:7516104

  18. A versatile ex vivo technique for assaying tumor angiogenesis and microglia in the brain

    PubMed Central

    Ghoochani, Ali; Yakubov, Eduard; Sehm, Tina; Fan, Zheng; Hock, Stefan; Buchfelder, Michael

    2016-01-01

    Primary brain tumors are hallmarked for their destructive activity on the microenvironment and vasculature. However, solely few experimental techniques exist to access the tumor microenvironment under anatomical intact conditions with remaining cellular and extracellular composition. Here, we detail an ex vivo vascular glioma impact method (VOGIM) to investigate the influence of gliomas and chemotherapeutics on the tumor microenvironment and angiogenesis under conditions that closely resemble the in vivo situation. We generated organotypic brain slice cultures from rats and transgenic mice and implanted glioma cells expressing fluorescent reporter proteins. In the VOGIM, tumor-induced vessels presented the whole range of vascular pathologies and tumor zones as found in human primary brain tumor specimens. In contrast, non-transformed cells such as primary astrocytes do not alter the vessel architecture. Vascular characteristics with vessel branching, junctions and vessel length are quantitatively assessable as well as the peritumoral zone. In particular, the VOGIM resembles the brain tumor microenvironment with alterations of neurons, microglia and cell survival. Hence, this method allows live cell monitoring of virtually any fluorescence-reporter expressing cell. We further analyzed the vasculature and microglia under the influence of tumor cells and chemotherapeutics such as Temozolamide (Temodal/Temcad®). Noteworthy, temozolomide normalized vasculare junctions and branches as well as microglial distribution in tumor-implanted brains. Moreover, VOGIM can be facilitated for implementing the 3Rs in experimentations. In summary, the VOGIM represents a versatile and robust technique which allows the assessment of the brain tumor microenvironment with parameters such as angiogenesis, neuronal cell death and microglial activity at the morphological and quantitative level. PMID:26673818

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

    PubMed

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

    2015-04-01

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

  20. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    NASA Astrophysics Data System (ADS)

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

    2005-07-01

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

  1. Awake brain tumor resection during pregnancy: Decision making and technical nuances.

    PubMed

    Meng, Lingzhong; Han, Seunggu J; Rollins, Mark D; Gelb, Adrian W; Chang, Edward F

    2016-02-01

    The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial.

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

    SciTech Connect

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

    2011-11-15

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

  3. Awake brain tumor resection during pregnancy: Decision making and technical nuances.

    PubMed

    Meng, Lingzhong; Han, Seunggu J; Rollins, Mark D; Gelb, Adrian W; Chang, Edward F

    2016-02-01

    The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial. PMID:26498092

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

    SciTech Connect

    Not Available

    1986-09-01

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

  5. Cervical lymph node metastases from remote primary tumor sites

    PubMed Central

    López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

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

    SciTech Connect

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

    2009-08-01

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

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

    SciTech Connect

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

    1994-05-01

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

  8. Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors.

    PubMed

    Kovar, Joy L; Curtis, Evan; Othman, Shadi F; Simpson, Melanie A; Olive, D Michael

    2013-09-15

    Primary brain tumors present significant challenges for surgical resection because of their location and the frequent occurrence of malignant projections extending beyond the primary tumor. Visualization of the tumor margins during surgery is critical for a favorable outcome. We report the use of IRDye 800CW chlorotoxin (CLTX) as a targeted imaging agent for brain tumors in a spontaneous mouse model of medulloblastoma, ND2:SmoA1. Specificity and functionality of the targeted agent were confirmed in cell-based assays. Tumors were detected by magnetic resonance imaging and IRDye 800CW CLTX administered to individual animals for optical imaging at 1-month increments. The integrity of the blood-brain barrier (BBB) was measured by Evan's Blue perfusion prior to sacrifice. Results show that IRDye 800CW CLTX specifically targeted tumor tissue. The extravasation of Evan's Blue was observed in all tumors, suggesting that the presence of the tumors can introduce alterations in the permeability of the BBB. Because increased vascular permeability was observed early in the disease model, larger dye-labeled imaging agents that exceed current BBB size restrictions may warrant renewed consideration as candidates for tumor detection and surgical resection. Our study provides data characterizing in vitro and in vivo use of IRDye 800CW CLTX as a broadly applicable tumor imaging agent. PMID:23711726

  9. Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors.

    PubMed

    Kovar, Joy L; Curtis, Evan; Othman, Shadi F; Simpson, Melanie A; Olive, D Michael

    2013-09-15

    Primary brain tumors present significant challenges for surgical resection because of their location and the frequent occurrence of malignant projections extending beyond the primary tumor. Visualization of the tumor margins during surgery is critical for a favorable outcome. We report the use of IRDye 800CW chlorotoxin (CLTX) as a targeted imaging agent for brain tumors in a spontaneous mouse model of medulloblastoma, ND2:SmoA1. Specificity and functionality of the targeted agent were confirmed in cell-based assays. Tumors were detected by magnetic resonance imaging and IRDye 800CW CLTX administered to individual animals for optical imaging at 1-month increments. The integrity of the blood-brain barrier (BBB) was measured by Evan's Blue perfusion prior to sacrifice. Results show that IRDye 800CW CLTX specifically targeted tumor tissue. The extravasation of Evan's Blue was observed in all tumors, suggesting that the presence of the tumors can introduce alterations in the permeability of the BBB. Because increased vascular permeability was observed early in the disease model, larger dye-labeled imaging agents that exceed current BBB size restrictions may warrant renewed consideration as candidates for tumor detection and surgical resection. Our study provides data characterizing in vitro and in vivo use of IRDye 800CW CLTX as a broadly applicable tumor imaging agent.

  10. Brain tumor resection guided by fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Leblond, Frederic; Fontaine, Kathryn M.; Valdes, Pablo; Ji, Songbai; Pogue, Brian W.; Hartov, Alex; Roberts, David W.; Paulsen, Keith D.

    2009-02-01

    We present the methods that are being used in the scope of an on-going clinical trial designed to assess the usefulness of ALA-PpIX fluorescence imaging when used in conjunction with pre-operative MRI. The overall objective is to develop imaging-based neuronavigation approaches to aid in maximizing the completeness of brain tumor resection, thereby improving patient survival rate. In this paper we present the imaging methods that are used, emphasizing technical aspects relating to the fluorescence optical microscope, including initial validation approaches based on phantom and small-animal experiments. The surgical workflow is then described in detail based on a high-grade glioma resection we performed.

  11. Increasing brain tumor rates: is there a link to aspartame?

    PubMed

    Olney, J W; Farber, N B; Spitznagel, E; Robins, L N

    1996-11-01

    In the past two decades brain tumor rates have risen in several industrialized countries, including the United States. During this time, brain tumor data have been gathered by the National Cancer Institute from catchment areas representing 10% of the United States population. In the present study, we analyzed these data from 1975 to 1992 and found that the brain tumor increases in the United States occurred in two distinct phases, an early modest increase that may primarily reflect improved diagnostic technology, and a more recent sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s). Compared to other environmental factors putatively linked to brain tumors, the artificial sweetener aspartame is a promising candidate to explain the recent increase in incidence and degree of malignancy of brain tumors. Evidence potentially implicating aspartame includes an early animal study revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared to no brain tumors in concurrent controls, the recent finding that the aspartame molecule has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). We conclude that there is need for reassessing the carcinogenic potential of aspartame.

  12. Multimodality Brain Tumor Imaging: MR Imaging, PET, and PET/MR Imaging.

    PubMed

    Fink, James R; Muzi, Mark; Peck, Melinda; Krohn, Kenneth A

    2015-10-01

    Standard MR imaging and CT are routinely used for anatomic diagnosis in brain tumors. Pretherapy planning and posttreatment response assessments rely heavily on gadolinium-enhanced MR imaging. Advanced MR imaging techniques and PET imaging offer physiologic, metabolic, or functional information about tumor biology that goes beyond the diagnostic yield of standard anatomic imaging. With the advent of combined PET/MR imaging scanners, we are entering an era wherein the relationships among different elements of tumor metabolism can be simultaneously explored through multimodality MR imaging and PET imaging. The purpose of this review is to provide a practical and clinically relevant overview of current anatomic and physiologic imaging of brain tumors as a foundation for further investigations, with a primary focus on MR imaging and PET techniques that have demonstrated utility in the current care of brain tumor patients.

  13. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis.

    PubMed

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M; Zhao, Ming

    2015-02-20

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). ND-GFP mice express GFP in nascent blood vessels. In the orthotopically-injected mice, the primary tumor was surgically-resected in order to allow brain metastasis to develop. At various time points, the tumors and vasculature in the brain were imaged by confocal and stereo fluorescence microscopy. Some of the breast cancer cells that reached the brain extravasated and grew perivascularly and some of the cells proliferated within the vasculature. S. typhimurium A1-R significantly inhibited brain metastasis in both metastatic models and increased survival of the orthotopically-transplanted, primary-tumor-resected mice (p<0.05). The results of the present study suggest the clinical potential of bacterial therapy of breast cancer brain metastasis.

  14. Primary brain targets of nerve agents

    PubMed Central

    Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Apland, James P.; Qashu, Felicia; Braga, Maria F.M.

    2009-01-01

    Exposure to nerve agents and other organophosphorus acetylcholinesterases used in industry and agriculture can cause death, or brain damage, producing long-term cognitive and behavioral deficits. Brain damage is primarily caused by the intense seizure activity induced by these agents. Identifying the brain regions that respond most intensely to nerve agents, in terms of generating and spreading seizure activity, along with knowledge of the physiology and biochemistry of these regions, can facilitate the development of pharmacological treatments that will effectively control seizures even if administered when seizures are well underway. Here, we contrast the pathological (neuronal damage) and pathophysiological (neuronal activity) findings of responses to nerve agents in the amygdala and the hippocampus, the two brain structures that play a central role in the generation and spread of seizures. The evidence so far suggests that the amygdala suffers the most extensive damage by nerve agent exposure, which appears consistent with the tendency of the amygdala to generate prolonged, seizure-like neuronal discharges in vitro in response to the nerve agent soman, at a time when the hippocampus generates only interictal-like activity. In vivo experiments are now required to confirm the primary role that the amygdala seems to play in nerve agent-induced seizure generation. PMID:19591865

  15. New treatment modalities for brain tumors in dogs and cats.

    PubMed

    Rossmeisl, John H

    2014-11-01

    Despite advancements in standard therapies, intracranial tumors remain a significant source of morbidity and mortality in veterinary and human medicine. Several newer approaches are gaining more widespread acceptance or are currently being prepared for translation from experimental to routine therapeutic use. Clinical trials in dogs with spontaneous brain tumors have contributed to the development and human translation of several novel therapeutic brain tumor approaches. PMID:25441624

  16. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Chan, Vincy; Xiong, Chen; Colantonio, Angela

    2015-01-01

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

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

    PubMed

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

    2013-11-01

    A stochastic model for characterizing tumor texture in brain magnetic resonance (MR) images is proposed. The efficacy of the model is demonstrated in patient-independent brain tumor texture feature extraction and tumor segmentation in magnetic resonance images (MRIs). Due to complex appearance in MRI, brain tumor texture is formulated using a multiresolution-fractal model known as multifractional Brownian motion (mBm). Detailed mathematical derivation for mBm model and corresponding novel algorithm to extract spatially varying multifractal features are proposed. A multifractal feature-based brain tumor segmentation method is developed next. To evaluate efficacy, tumor segmentation performance using proposed multifractal feature is compared with that using Gabor-like multiscale texton feature. Furthermore, novel patient-independent tumor segmentation scheme is proposed by extending the well-known AdaBoost algorithm. The modification of AdaBoost algorithm involves assigning weights to component classifiers based on their ability to classify difficult samples and confidence in such classification. Experimental results for 14 patients with over 300 MRIs show the efficacy of the proposed technique in automatic segmentation of tumors in brain MRIs. Finally, comparison with other state-of-the art brain tumor segmentation works with publicly available low-grade glioma BRATS2012 dataset show that our segmentation results are more consistent and on the average outperforms these methods for the patients where ground truth is made available. PMID:23807424

  20. Gene Therapy and Virotherapy: Novel Therapeutic Approaches for Brain Tumors

    PubMed Central

    Kroeger, Kurt M.; Ghulam Muhammad, A.K.M.; Baker, Gregory J.; Assi, Hikmat; Wibowo, Mia K.; Xiong, Weidong; Yagiz, Kader; Candolfi, Marianela; Lowenstein, Pedro R.; Castro, Maria G.

    2010-01-01

    Glioblastoma multiforme (GBM) is a deadly primary brain tumor in adults, with a median survival of ~12–18 months post-diagnosis. Despite recent advances in conventional therapeutic approaches, only modest improvements in median survival have been achieved; GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are desperately needed. Our group and others are pursuing virotherapy and gene therapy strategies for the treatment of GBM. In this review, we will discuss various virotherapy and gene therapy approaches for GBM currently under preclinical and clinical evaluation including direct or conditional cytotoxic, and/or immunostimulatory approaches. We also discuss cutting-edge technologies for drug/gene delivery and targeting brain tumors, including the use of stem cells as delivery platforms, the use of targeted immunotoxins, and the therapeutic potential of using GBM microvesicles to deliver therapeutic siRNAs or virotherapies. Finally, various animal models available to test novel GBM therapies are discussed. PMID:21034670

  1. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    SciTech Connect

    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.

    2008-10-01

    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 {alpha}/{beta} 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 {alpha}/{beta} 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.

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

    PubMed Central

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

    2016-01-01

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

  3. Novel treatment strategies for brain tumors and metastases

    PubMed Central

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

    2015-01-01

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

  4. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    PubMed Central

    Johnson, Theodore S.; Munn, David H.; Maria, Bernard L.

    2012-01-01

    Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance. PMID:22312408

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

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

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

  6. Radiosurgery-induced brain tumor. Case report.

    PubMed

    Kaido, T; Hoshida, T; Uranishi, R; Akita, N; Kotani, A; Nishi, N; Sakaki, T

    2001-10-01

    The authors describe a case of glioblastoma multiforme (GBM) associated with previous gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was performed using a 201-source 60Co gamma knife system at another institution. The maximum and margin radiation doses used in the procedure were 40 and 20 Gy, respectively. One year after radiosurgery, the patient noticed onset of mild left hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery, at the age of 20 years, the patient experienced an attack of generalized tonic-clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain tumor in the right parietal lobe. The patient underwent an operation and the histological diagnosis of the lesion was GBM. Ten months following the operation, that is, 99 months postradiosurgery, this patient died. To the best of the authors' knowledge, this is the first reported case of a neoplasm induced by radiosurgery for an AVM and the second case in which it occurred following radiosurgery for intracranial disease.

  7. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  8. Location of brain tumor intersecting white matter tracts predicts patient prognosis.

    PubMed

    Mickevicius, Nikolai J; Carle, Alexander B; Bluemel, Trevor; Santarriaga, Stephanie; Schloemer, Fallon; Shumate, Derrick; Connelly, Jennifer; Schmainda, Kathleen M; LaViolette, Peter S

    2015-11-01

    Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design.

  9. Location of brain tumor intersecting white matter tracts predicts patient prognosis.

    PubMed

    Mickevicius, Nikolai J; Carle, Alexander B; Bluemel, Trevor; Santarriaga, Stephanie; Schloemer, Fallon; Shumate, Derrick; Connelly, Jennifer; Schmainda, Kathleen M; LaViolette, Peter S

    2015-11-01

    Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design. PMID:26376654

  10. Enucleation and the appearance of second primary tumors in cats bearing virally induced intraocular tumors.

    PubMed

    Niederkorn, J Y; Shadduck, J A; Albert, D

    1982-12-01

    The effect of enucleation of an eye containing a malignant intraocular neoplasm on the occurrence of secondary tumors was studied in cats with tumors, mainly melanomas, induced by Gardner feline fibrosarcoma virus. Enucleation of eyes containing progressively growing tumors was followed by a sharp increase in the frequency of secondary tumors. Secondary tumors were detected in 13 of 14 (92.8%) cats subjected to enucleation but in only seven of 21 (33.3%) untreated cats. The data suggest that the secondary tumors were not metastases but rather second primary tumors induced by local transformation of fibrosarcoma virus shed from the intraocular neoplasms. The increased incidence of these second primary tumors in cats subjected to enucleation was associated with depressed antibody titers to a tumor-specific transplantation antigen, the feline oncornavirus-associated cell membrane antigen.

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

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.

    1967-01-01

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

  12. Childhood Brain and Spinal Cord Tumors Treatment Overview

    MedlinePlus

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

  13. Treatment of Newly Diagnosed and Recurrent Childhood Brain Tumors

    MedlinePlus

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

  14. Primary solitary fibrous tumor of the retroperitoneum.

    PubMed

    Charhi, Hind; Bernoussi, Zakiya; Haddan, Azzouz; Mesmoudi, Siham; Elktaibi, Abderrahim; Mansouri, Fatima; Elktaibi, Rachid; Lahlou, Khalid; Jahid, Ahmed; Mahassini, Najat

    2011-09-28

    Solitary fibrous tumor is an uncommon neoplasm affecting adults and typically located in the pleura and can also occur in a large number of other extra thoracic sites. We present the case of a solitary fibrous tumor (SFT) of the retroperitoneum and describe their histopathological and immunohistochemical features. The identification of SFT in the retroperitoneum is of importance because its clinico-pathological behaviour is still unclear. The pathologist plays a fundamental role in establishing both the positive and differential diagnosis.

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

    PubMed Central

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

    2015-01-01

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

  16. [Tumor Cells and Micro-environment in Brain Metastases].

    PubMed

    Zhong, Wen; Hu, Chengping

    2016-09-20

    Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis "seed and soil", that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases. PMID:27666556

  17. Metastatic brain tumor from urothelial carcinoma of the prostatic urethra

    PubMed Central

    Morita, Kohei; Oda, Masashi; Koyanagi, Masaomi; Saiki, Masaaki

    2016-01-01

    Background: Urothelial carcinoma occurs in the bladder, upper urinary tract, and lower urinary tract, including prostatic urethra. A majority of the reported cases of intracranial metastasis from urothelial carcinoma originates from the bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. Case Description: A 72-year-old male presented with a metastatic brain tumor and a 3-year history of urothelial carcinoma of the prostatic urethra treated with cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological diagnosis for tumor removal was compatible with metastatic brain tumor from urothelial carcinoma. Conclusion: Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. It is an extremely rare case, however, we should be careful of brain metastasis during follow-up for urothelial carcinoma in the lower urinary tract. PMID:27512612

  18. Automated segmentation of MR images of brain tumors.

    PubMed

    Kaus, M R; Warfield, S K; Nabavi, A; Black, P M; Jolesz, F A; Kikinis, R

    2001-02-01

    An automated brain tumor segmentation method was developed and validated against manual segmentation with three-dimensional magnetic resonance images in 20 patients with meningiomas and low-grade gliomas. The automated method (operator time, 5-10 minutes) allowed rapid identification of brain and tumor tissue with an accuracy and reproducibility comparable to those of manual segmentation (operator time, 3-5 hours), making automated segmentation practical for low-grade gliomas and meningiomas. PMID:11161183

  19. Radiation therapy options for management of the brain tumor patient.

    PubMed

    Lamb, S A

    1995-03-01

    Radiation therapy rarely cures malignant brain tumors; however, it is the best treatment available at present. Refinement of radiation delivery systems must continue in order to minimize normal tissue injury and to maximize the quality of life. Multimodal therapy designed to attack cancer at its genetic makeup holds great promise. Radiation therapy will always remain one of the forms of therapy used to treat malignant brain tumors.

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

    PubMed Central

    2012-01-01

    Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors. PMID:22891953

  1. Emerging insights into barriers to effective brain tumor therapeutics.

    PubMed

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

    2014-01-01

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

  2. Emerging Insights into Barriers to Effective Brain Tumor Therapeutics

    PubMed Central

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

    2014-01-01

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

  3. Brain and Spinal Tumors: Hope through Research

    MedlinePlus

    ... of the CNS. Some tools used in the operating room include a surgical microscope, the endoscope (a ... cells, which support other brain function. central nervous system (CNS)—the brain and spinal cord. cerebrospinal fluid ( ...

  4. Infant brain tumors: a neuropathologic population-based institutional reappraisal.

    PubMed

    Dunham, Christopher; Pillai, Shibu; Steinbok, Paul

    2012-10-01

    The factors that impact the long-term functional outcome for infants with brain tumor are unclear. The clinicopathologic features of all infant brain tumors occurring at our institution (1982-2005) were reexamined to explore the factors influencing prognosis. The details of the neuropathologic review are reported herein. Thirty-five cases were identified and included 7 astrocytomas (6 low grade and 1 glioblastoma), 6 atypical teratoid rhabdoid tumors, 5 choroid plexus papillomas, 4 ependymomas (3 anaplastic), 4 teratomas (3 immature), 2 supratentorial primitive neuroectodermal tumors, 2 gangliogliomas, 2 desmoplastic tumors of infancy, and 1 each of "medulloblastoma with extensive nodularity," adamantinomatous craniopharyngioma, and 1 "malignancy not otherwise specified." The original diagnosis was changed in 8 cases (23%), and atypical teratoid rhabdoid tumors was the most common revision (n = 5). Case 9 was unusual in that both the patient and her 2-year-old sister displayed INI-1 immunonegative posterior fossa tumors and extended survival. Tumor grade was altered in 6 cases (17%), the most significant instance being the downgrading from the World Health Organization grade IV to I (case 18: supratentorial primitive neuroectodermal tumors to desmoplastic tumors of infancy). As opposed to other reports in the literature, our cohort contained a substantially higher frequency of atypical teratoid rhabdoid tumors and a lower frequency of medulloblastoma. Changes in the histologic diagnosis/grade in a significant subset of cases most likely reflect the continual evolution of brain tumor classification schemes. INI-1 immunohistochemistry was instrumental in the pathologic assessment of select cases and raised the possibility that atypical teratoid rhabdoid tumors may be the most common infant brain malignancy.

  5. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

    PubMed

    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. PMID:27069501

  6. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    PubMed Central

    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. PMID:27069501

  7. Imaging of Brain Tumors With Paramagnetic Vesicles Targeted to Phosphatidylserine

    PubMed Central

    Winter, Patrick M.; Pearce, John; Chu, Zhengtao; McPherson, Christopher M.; Takigiku, Ray; Lee, Jing-Huei; Qi, Xiaoyang

    2014-01-01

    Purpose To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. Materials and Methods Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/ SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. Results The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)−1 relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). Conclusion These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS. PMID:24797437

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

    PubMed Central

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

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  10. Measles may be a Risk Factor for Malignant Brain Tumors

    PubMed Central

    Green, Sheryl; Rendo, Angela; Rosenzweig, Kenneth E.

    2015-01-01

    Background A possible risk factor for brain tumor might be measles, since late neurologic sequelae are part of measles pathology. Subacute sclerosing panencephalitis, a devastating neurologic illness, is prone to develop years after measles infection. Methods Because measles damage to the brain might increase the risk of brain tumor, we examined the relationship of measles incidence in 1960 and brain tumor incidence in 50 US States and the District of Columbia, 2004-2007. Data on number of cases of measles by state in 1960 are from the Morbidity and Mortality Weekly Report. In 1960 measles was a childhood illness. We calculated measles incidence by obtaining the population of each state from the 1960 US Census and then age adjusting our results to the cumulative percent of the state population under age 21, since this would have been the measles-infected group. Data on the percentage white population by state are from the US Census (www.census.gov). Age-adjusted incidence (to the 2000 US standard population) of brain tumors is from the Central Brain Tumor Registry of the United States 2011 report. Results There was a significant correlation between 1960 measles incidence and incidence of malignant brain tumors in persons 20 and older in 2004-2007 (r=0.321, p=0.026). Because glioblastoma is more frequent in whites and males, multivariate linear regression was performed with tumor incidence as the dependent variable, measles incidence, percent white population, and sex ratio by state as independent variables. Measles incidence was significantly correlated with malignant brain tumor incidence (β=0.361, p<0.001) and independent of the effect of race (β=0.734, p<0.001) and sex ratio m/f (β=-0.478, p<0.001). There was no correlation of measles incidence with brain tumor incidence in persons younger than 20. Conclusion Inflammation is a critical component of tumor development. The inflammation of measles-induced subacute sclerosing panencephalitis, even subclinical

  11. Sox2: regulation of expression and contribution to brain tumors.

    PubMed

    Mansouri, Sheila; Nejad, Romina; Karabork, Merve; Ekinci, Can; Solaroglu, Ihsan; Aldape, Kenneth D; Zadeh, Gelareh

    2016-07-01

    Tumors of the CNS are composed of a complex mixture of neoplastic cells, in addition to vascular, inflammatory and stromal components. Similar to most other tumors, brain tumors contain a heterogeneous population of cells that are found at different stages of differentiation. The cancer stem cell hypothesis suggests that all tumors are composed of subpopulation of cells with stem-like properties, which are capable of self-renewal, display resistance to therapy and lead to tumor recurrence. One of the most important transcription factors that regulate cancer stem cell properties is SOX2. In this review, we focus on SOX2 and the complex network of signaling molecules and transcription factors that regulate its expression and function in brain tumor initiating cells. We also highlight important findings in the literature about the role of SOX2 in glioblastoma and medulloblastoma, where it has been more extensively studied. PMID:27230973

  12. Multiclass feature selection for improved pediatric brain tumor segmentation

    NASA Astrophysics Data System (ADS)

    Ahmed, Shaheen; Iftekharuddin, Khan M.

    2012-03-01

    In our previous work, we showed that fractal-based texture features are effective in detection, segmentation and classification of posterior-fossa (PF) pediatric brain tumor in multimodality MRI. We exploited an information theoretic approach such as Kullback-Leibler Divergence (KLD) for feature selection and ranking different texture features. We further incorporated the feature selection technique with segmentation method such as Expectation Maximization (EM) for segmentation of tumor T and non tumor (NT) tissues. In this work, we extend the two class KLD technique to multiclass for effectively selecting the best features for brain tumor (T), cyst (C) and non tumor (NT). We further obtain segmentation robustness for each tissue types by computing Bay's posterior probabilities and corresponding number of pixels for each tissue segments in MRI patient images. We evaluate improved tumor segmentation robustness using different similarity metric for 5 patients in T1, T2 and FLAIR modalities.

  13. Critical role of ABCG2 in ALA-photodynamic diagnosis and therapy of human brain tumor.

    PubMed

    Ishikawa, Toshihisa; Kajimoto, Yoshinaga; Inoue, Yutaka; Ikegami, Yoji; Kuroiwa, Toshihiko

    2015-01-01

    Primary brain tumors occur in around 250,000 people per year globally. Survival rates in primary brain tumors depend on the type of tumor, patient's age, the extent of surgical tumor removal, and other factors. Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma and meningiomas, whereas clinical application of photodynamic therapy (PDT) to brain tumor therapy has just recently started. Both PDD and PDT are achieved by a photon-induced physicochemical reaction, which is induced by the excitation of porphyrins exposed to light. In fluorescence-guided gross-total resection, PDD can be achieved by the administration of 5-aminolevulinic acid (5-ALA) as the precursor of protoporphyrin IX (PpIX). Exogenously administered ALA induces biosynthesis and accumulation of PpIX, a natural photosensitizer, in cancer cells. However, ATP-binding cassette transporter ABCG2 plays a critical role in regulating the cellular accumulation of porphyrins in cancer cells and thereby its expression and function can affect the efficacy of PDD and PDT. In response to the photoreaction of porphyrins leading to oxidative stress, the nuclear factor erythroid-derived 2-related transcription factor can transcriptionally upregulate ABCG2, which may reduce the efficacy of PDD and PDT. On the other hand, certain protein kinase inhibitors potentially enhance the efficacy of PDD and PDT by blocking ABCG2-mediated porphyrin efflux from cancer cells. In this context, it is of great interest to develop ABCG2 inhibitors that can be applied to PDD or PDT for the therapy of brain tumor and other tumors.

  14. Rapid and automatic detection of brain tumors in MR images

    NASA Astrophysics Data System (ADS)

    Wang, Zhengjia; Hu, Qingmao; Loe, KiaFock; Aziz, Aamer; Nowinski, Wieslaw L.

    2004-04-01

    An algorithm to automatically detect brain tumors in MR images is presented. The key concern is speed in order to process efficiently large brain image databases and provide quick outcomes in clinical setting. The method is based on study of asymmetry of the brain. Tumors cause asymmetry of the brain, so we detect brain tumors in 3D MR images using symmetry analysis of image grey levels with respect to the midsagittal plane (MSP). The MSP, separating the brain into two hemispheres, is extracted using our previously developed algorithm. By removing the background pixels, the normalized grey level histograms are calculated for both hemispheres. The similarity between these two histograms manifests the symmetry of the brain, and it is quantified by using four symmetry measures: correlation coefficient, root mean square error, integral of absolute difference (IAD), and integral of normalized absolute difference (INAD). A quantitative analysis of brain normality based on 42 patients with tumors and 55 normals is presented. The sensitivity and specificity of IAD and INAD were 83.3% and 89.1%, and 85.7% and 83.6%, respectively. The running time for each symmetry measure for a 3D 8bit MR data was between 0.1 - 0.3 seconds on a 2.4GHz CPU PC.

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

    ClinicalTrials.gov

    2010-03-15

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

  16. Crossing the barrier: treatment of brain tumors using nanochain particles.

    PubMed

    Karathanasis, Efstathios; Ghaghada, Ketan B

    2016-09-01

    Despite advancements in surgery and radiotherapy, the aggressive forms of brain tumors, such as gliomas, are still uniformly lethal with current therapies offering only palliation complicated by significant toxicities. Gliomas are characteristically diffuse with infiltrating edges, resistant to drugs and nearly inaccessible to systemic therapies due to the brain-tumor barrier. Currently, aggressive efforts are underway to further understand brain-tumor's microenvironment and identify brain tumor cell-specific regulators amenable to pharmacologic interventions. While new potent agents are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. To tackle the drug delivery issues, a multicomponent chain-like nanoparticle has been developed. These nanochains are comprised of iron oxide nanospheres and a drug-loaded liposome chemically linked into a 100-nm linear, chain-like assembly with high precision. The nanochain possesses a unique ability to scavenge the tumor endothelium. By utilizing effective vascular targeting, the nanochains achieve rapid deposition on the vascular bed of glioma sites establishing well-distributed drug reservoirs on the endothelium of brain tumors. After reaching the target sites, an on-command, external low-power radiofrequency field can remotely trigger rapid drug release, due to mechanical disruption of the liposome, facilitating widespread and effective drug delivery into regions harboring brain tumor cells. Integration of the nanochain delivery system with the appropriate combination of complementary drugs has the potential to unfold the field and allow significant expansion of therapies for the disease where success is currently very limited. WIREs Nanomed Nanobiotechnol 2016, 8:678-695. doi: 10.1002/wnan.1387 For further resources related to this article, please visit the WIREs website.

  17. PDE5 inhibitors enhance tumor permeability and efficacy of chemotherapy in a rat brain tumor model.

    PubMed

    Black, Keith L; Yin, Dali; Ong, John M; Hu, Jinwei; Konda, Bindu M; Wang, Xiao; Ko, MinHee K; Bayan, Jennifer-Ann; Sacapano, Manuel R; Espinoza, Andreas; Irvin, Dwain K; Shu, Yan

    2008-09-16

    The blood-brain tumor barrier (BTB) significantly limits delivery of therapeutic concentrations of chemotherapy to brain tumors. A novel approach to selectively increase drug delivery is pharmacologic modulation of signaling molecules that regulate BTB permeability, such as those in cGMP signaling. Here we show that oral administration of sildenafil (Viagra) and vardenafil (Levitra), inhibitors of cGMP-specific PDE5, selectively increased tumor capillary permeability in 9L gliosarcoma-bearing rats with no significant increase in normal brain capillaries. Tumor-bearing rats treated with the chemotherapy agent, adriamycin, in combination with vardenafil survived significantly longer than rats treated with adriamycin alone. The selective increase in tumor capillary permeability appears to be mediated by a selective increase in tumor cGMP levels and increased vesicular transport through tumor capillaries, and could be attenuated by iberiotoxin, a selective inhibitor for calcium-dependent potassium (K(Ca)) channels, that are effectors in cGMP signaling. The effect by sildenafil could be further increased by simultaneously using another BTB "opener", bradykinin. Collectively, this data demonstrates that oral administration of PDE5 inhibitors selectively increases BTB permeability and enhances anti-tumor efficacy for a chemotherapeutic agent. These findings have significant implications for improving delivery of anti-tumor agents to brain tumors. PMID:18674521

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  1. Tl-201 and Tc-99m-Sestamibi SPECT for brain tumor detection: Comparison using MRI coregistration

    SciTech Connect

    Darcourt, J.; Itti, L.; Chang, L.

    1994-05-01

    Tl-201 (Tl) brain SPECT has been validated for the differential diagnosis of high versus low grade gliomas and recurrence versus radiation necrosis. We compared this technique to Tc-99m-Sestamibi (MIBI) SPECT in 9 patients (pts) with brain tumors using MRI coregistration. Pts were injected with 4 mCi of Tl and brain SPECT was performed using a dedicated brain system. This was immediately following by an injection of 20 mCi of MIBI and a brain SPECT using the same camera and with the pt in the same position. Four pts were studied for the diagnosis of radiation necrosis vs. tumor recurrence (2 had biopsy proven recurrence); 5 pts were studied for primary tumor evaluation: 2 meningiomas, 1 oligodendroglioma, 1 low-grade astrocytoma, 1 cysticercosis. Coregistration was performed for every pt by 3D surface fitting of the inner skull MIBI contour to the MRI brain surface extracted automatically. ROIs were drawn on the MRI and applied to the coregistered MIBI and Tl images for tumor to non-tumor ratios T/NT calculations. There was a tight correlation between MIBI and Tl T/NT (r-0.96) and a 1.5 threshold separated radiation necrosis from recurrence and low from high grade primary tumors. Therefore, the data already available on Tl brain tumor imaging can be used with MIBI SPECT with the advantage of a better image quality (2.5 to 4 times more counts).

  2. Incidence of brain tumors in rats fed aspartame.

    PubMed

    Ishii, H

    1981-03-01

    The brain tumorigenicity of aspartame (APM) and of its diketopiperazine (DKP) was studied in 860 SCL Wistar rats. APM at dietary levels of 1 g/kg, 2 gK/, 4 g/kg or APM + DKP (3:1) 4 g/kg was fed for 104 weeks. One atypical astrocytoma was found in a control rat and 2 astrocytomas, 2 oligodendrogliomas and 1 ependymoma were scattered among the 4 test groups. There was no significant difference in the incidence of brain tumors between control and test groups. It is concluded that neither AMP nor DKP caused brain tumors in rats in this study.

  3. Tumor-like lesions of the brain

    PubMed Central

    2009-01-01

    Abstract Differentiation between tumors and tumor-like lesions of the central nervous system is essential for planning adequate treatment and for estimating outcome and future prognosis. Neuroimaging fulfills an essential role in the correct differentiation between both entities. The radiologist should be aware of all non-neoplastic pathologies and diseases that may mimic tumors. High-end anatomic and functional neuroimaging tools integrating multiple modalities and clinical correlation is mandatory. In the current review, frequent tumor-like lesions are discussed. PMID:19965288

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  5. Optical detection of brain tumors using quantum dots

    NASA Astrophysics Data System (ADS)

    Toms, Steven A.; Daneshvar, Hamid; Muhammad, Osman; Jackson, Heather; Vogelbaum, Michael A.; Bruchez, Marcel

    2005-11-01

    Introduction: Brain tumor margin detection remains a challenging problem in the operative resection of gliomas. A novel nanoparticle, a PEGylated quantum dot, has been shown to be phagocytized by macrophages in vivo. This feature may allow quantum dots to co-localize with brain tumors and serve as an optical aid in the surgical resection of brain tumors. Methods: Sprague-Daly rats were injected intracranially with C6 gliosarcoma cell lines to establish tumors. Two weeks after implantation of brain tumors, PEGylated quantum dots emitting at 705 nm (PEG-705 QD) were injected via the tail vein. Twenty-four hours post PEG-705 QD injection, the animals were sacrificed and their tissues examined. Results: PEGylated quantum dots are avidly phagocytized by macrophages and are taken up by liver, spleen and lymph nodes. Macrophages and microglia co-localize with glioma cells, carrying the optical nanoparticle, the quantum dot. Excitation of the PEG-705 quantum dots gives off a deep red fluorescence detectable with charge coupled device (CCD) cameras, optical spectroscopy units, and in dark field fluorescence microscopy. Conclusions: PEG-705QDs co-localize with brain tumors and may serve as an optical adjunct to aid in the operative resection of gliomas. The particles may be visualized in surgery with CCD cameras or detected by optical spectroscopy.

  6. Possibilities of new therapeutic strategies in brain tumors.

    PubMed

    Bouffet, Eric; Tabori, Uri; Huang, Annie; Bartels, Ute

    2010-06-01

    Advances in the management of pediatric brain tumors have been less successful than in other areas of pediatric oncology. This gap in outcome is essentially related to specific aspects of these tumors in this age group such as the fact that the surrounding brain is still developing, vital structures limit aggressive attempts at removing infiltrating lesions, drug penetration into the central nervous system is often poor and short and long term toxicities of some treatments to the surrounding brain are significant. This review describes new therapeutic strategies and their impact in the pediatric neuro-oncology practice. Although the number of new active antineoplastic agents has been limited during the last decade, significant improvements in the chemotherapeutic management of pediatric brain tumors have been observed. These relate to the optimization of chemotherapy protocols, the development of new schedules of administration such as metronomic schedules, sequential high dose chemotherapy, concomitant administration of chemotherapy and radiation, or the introduction of intrathecal or intraventricular chemotherapy in specific protocols. Technological advances in radiotherapy allow delivering optimal doses to the target volume while decreasing the volume of normal surrounding tissue receiving radiation. As a consequence, conformal radiation therapy currently plays a major role in the management of several pediatric brain tumors, including in infants where radiation has been traditionally avoided. The role of molecularly targeted agents is still unclear and a number of phase I and II trials are ongoing to better define the future of these new therapies in pediatric brain tumors.

  7. Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI Measurements.

    PubMed

    Zhang, H; Zhang, G; Oudkerk, M

    2012-03-01

    This study evaluated the roles of different dynamic susceptibility contrast magnetic imaging (DSC MRI) measurements in discriminating between brain metastases derived from four common primary carcinomas. Thirty-seven patients with brain metastases were enrolled. Relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor and peritumoral edema were measured. Metastases were grouped by their primary tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and peritumoral edema of all brain metastases (n=37) were 2.79 ± 1.73, 2.56 ± 2.11, 1.21 ± 0.48 and 1.05 ± 0.53, 0.86 ± 0.40, 1.99 ± 0.41, respectively. The tumoral rCBV (5.26 ± 1.89) and rCBF (5.32 ± 3.28) of renal metastases were greater than those of the other three metastases (P<0.05). The tumoral rMTT (1.58 ± 0.77) of breast metastases was statistically greater than that (0.96 ± 0.31) of gastrointestinal metastases (P=0.013). No statistical difference was found between peritumoral rCBV, rCBF and rMTT (P>0.05). Evaluating various DSC MRI measurements can provide complementary hemodynamic information on brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate between brain metastases originating from different primary carcinomas. The peritumoral DSC MRI measurements had limited value in discriminating between brain metastases.

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  9. Clinical application of PET for the evaluation of brain tumors

    SciTech Connect

    Coleman, R.E.; Hoffman, J.M.; Hanson, M.W.; Sostman, H.D.; Schold, S.C. )

    1991-04-01

    The combination of FDG and PET has demonstrated clinical utility in the evaluation of patients with brain tumors. At the time of diagnosis, FDG PET provides information concerning the degree of malignancy and patient prognosis. After therapy, FDG PET is able to assess persistence of tumor, determine degree of malignancy, monitor progression, differentiate recurrence from necrosis, and assess prognosis. Other studies using PET provide information that may be clinically useful. Determination of tumor blood flow and permeability of the blood-brain barrier may help in the selection of appropriate therapy. Amino acid imaging using 11C-methionine is being evaluated in patients with brain tumors and provides different information than FDG imaging.52 references.

  10. Factors affecting intellectual outcome in pediatric brain tumor patients

    SciTech Connect

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

    1987-11-01

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

  11. Orthotopic models of pediatric brain tumors in zebrafish.

    PubMed

    Eden, C J; Ju, B; Murugesan, M; Phoenix, T N; Nimmervoll, B; Tong, Y; Ellison, D W; Finkelstein, D; Wright, K; Boulos, N; Dapper, J; Thiruvenkatam, R; Lessman, C A; Taylor, M R; Gilbertson, R J

    2015-03-26

    High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34 °C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34 °C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice. PMID:24747973

  12. Expression of β-adrenergic receptors in pediatric malignant brain tumors

    PubMed Central

    SARDI, IACOPO; GIUNTI, LAURA; BRESCI, CECILIA; BUCCOLIERO, ANNA MARIA; DEGL’INNOCENTI, DUCCIO; CARDELLICCHIO, STEFANIA; BARONI, GIANNA; CASTIGLIONE, FRANCESCA; ROS, MARTINA DA; FIORINI, PATRIZIO; GIGLIO, SABRINA; GENITORI, LORENZO; ARICÒ, MAURIZIO; FILIPPI, LUCA

    2013-01-01

    β-adrenergic receptors (β-ARs) are G protein-coupled receptors that activate signal transduction pathways involved in angiogenesis, resulting in enhanced tumor vascularization and more aggressive growth. In this study, we evaluated the expression of β-ARs in a population of 12 children affected by malignant primary brain tumors. We found a significant expression of β1- and β2-ARs in all 12 samples as well as the 3 cell lines tested (U87MG, T98G and DAOY). The mean absolute β1-AR mRNA level standardized to GAPDH was 5.81 (range, -7.91 to 11.29) for brain tumors and 8.59 (range, 6.046 to 12.59) for cell lines (U87MG, DAOY and T98G), respectively. The mean absolute β2-AR mRNA level was 4.74 (range, −9.30 to 8.45) for tumor specimens and 7.64 (range, 5.85 to 8.88) for cell lines. These real-time quantitative (qRT)-PCR expression data were confirmed by immunohistochemical analysis. Our study evaluated the presence of β1- and β2-ARs in malignant pediatric brain tumors and brain tumor cell lines. PMID:23255924

  13. Primary spinal primitive neuroectodermal tumor on MR imaging.

    PubMed

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

  14. Primary spinal primitive neuroectodermal tumor on MR imaging

    PubMed Central

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

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

    PubMed

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

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

  16. Primary hepatic neuroendocrine tumor: A case report and literature review

    PubMed Central

    Song, Jeong Eun; Kim, Byung Seok; Lee, Chang Hyeong

    2016-01-01

    Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and difficult to distinguish from other liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma, based on medical imaging findings. A 70-year-old man was referred for evaluation of liver mass incidentally discovered on abdominal computed tomography. The characteristic finding from dynamic liver magnetic resonance imaging led to a diagnosis of HCC. The patient underwent right hepatectomy. Histopathological and immunohistochemical examination revealed grade 2 neuroendocrine tumor. The postoperative 24-h urinary excretion of 5-hydroxy-indolacetic acid was within the normal range. Further imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. This case shows that the diagnosis of PHNET is a medical challenge, requiring differentiation of PHNETs other hepatic masses and exclusion of occult primary neuroendocrine tumors. The diagnosis of PHNET can be ascertained after long term follow-up to exclude another primary origin. PMID:27574614

  17. Research of the multimodal brain-tumor segmentation algorithm

    NASA Astrophysics Data System (ADS)

    Lu, Yisu; Chen, Wufan

    2015-12-01

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

  18. Simian virus 40 transformation, malignant mesothelioma and brain tumors

    PubMed Central

    Qi, Fang; Carbone, Michele; Yang, Haining; Gaudino, Giovanni

    2011-01-01

    Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis. PMID:21955238

  19. Pediatric brain tumor treatment: growth consequences and their management.

    PubMed

    Mostoufi-Moab, Sogol; Grimberg, Adda

    2010-09-01

    Tumors of the central nervous system, the most common solid tumors of childhood, are a major source of cancer-related morbidity and mortality in children. Survival rates have improved significantly following treatment for childhood brain tumors, with this growing cohort of survivors at high risk of adverse medical and late effects. Endocrine morbidities are the most prominent disorder among the spectrum of longterm conditions, with growth hormone deficiency the most common endocrinopathy noted, either from tumor location or after cranial irradiation and treatment effects on the hypothalamic/pituitary unit. Deficiency of other anterior pituitary hormones can contribute to negative effects on growth, body image and composition, sexual function, skeletal health, and quality of life. Pediatric and adult endocrinologists often provide medical care to this increasing population. Therefore, a thorough understanding of the epidemiology and pathophysiology of growth failure as a consequence of childhood brain tumor, both during and after treatment, is necessary and the main focus of this review.

  20. Prediction of brain tumor progression using a machine learning technique

    NASA Astrophysics Data System (ADS)

    Shen, Yuzhong; Banerjee, Debrup; Li, Jiang; Chandler, Adam; Shen, Yufei; McKenzie, Frederic D.; Wang, Jihong

    2010-03-01

    A machine learning technique is presented for assessing brain tumor progression by exploring six patients' complete MRI records scanned during their visits in the past two years. There are ten MRI series, including diffusion tensor image (DTI), for each visit. After registering all series to the corresponding DTI scan at the first visit, annotated normal and tumor regions were overlaid. Intensity value of each pixel inside the annotated regions were then extracted across all of the ten MRI series to compose a 10 dimensional vector. Each feature vector falls into one of three categories:normal, tumor, and normal but progressed to tumor at a later time. In this preliminary study, we focused on the trend of brain tumor progression during three consecutive visits, i.e., visit A, B, and C. A machine learning algorithm was trained using the data containing information from visit A to visit B, and the trained model was used to predict tumor progression from visit A to visit C. Preliminary results showed that prediction for brain tumor progression is feasible. An average of 80.9% pixel-wise accuracy was achieved for tumor progression prediction at visit C.

  1. Immune factors and viral interactions in brain cancer etiology and outcomes, The 2016 Brain Tumor Epidemiology Consortium Meeting report.

    PubMed

    Johnson, Kimberly J; Hainfellner, Johannes A; Lau, Ching C; Scheurer, Michael E; Woehrer, Adelheid; Wiemels, Joseph

    2016-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that aims to advance development of multicenter and interdisciplinary collaborations that focus on research related to the etiology, outcomes, and prevention of brain tumors. The 17th annual BTEC meeting was held in Barcelona, Spain on June 21 - 23, 2016. The meeting focused on immune and viral factors that influence brain tumor development. Fundamentals of innate and adaptive immunity were reviewed, the role of immune checkpoint inhibitors in primary and secondary brain tumors was addressed, vaccination strategies for glioma treatment were presented, and the potential contribution of immune dysfunction and viruses tropic for glial cells in gliomagenesis was discussed. Further contributions addressed the risk of non-ionizing radiation, molecular and birth characteristics on brain tumor induction/outcomes, and patterns of care and effects of different treatments on brain tumor survival in the real world setting. The next BTEC meeting will be held in June 2017 in Banff, Canada, and will focus on brain tumor epidemiology in the era of precision medicine.
. PMID:27546018

  2. Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: the past decade and where we are heading.

    PubMed Central

    Levin, V. A.

    1999-01-01

    Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging, neurosurgery, neuroanesthesia, radiotherapy, and chemotherapy for CNS tumors. Unfortunately, our progress has not yet met our expectations. Because of the infiltrative nature of most primary brain tumors, neurosurgery can never be expected to be curative for the majority of gliomas. Because infiltrative tumors interdigitate with normal brain cells and are not highly sensitive to irradiation, one cannot expect radiotherapy to be curative without serious damage to normal brain cells. The hope for a cure, then, rests with chemotherapy. Those who administer chemotherapy to patients with CNS tumors fully expect that, in time, long-term survival and, ultimately, the cure will become an everyday reality. To achieve that reality, however, new treatment concepts and drugs are needed. PMID:11550304

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

    PubMed Central

    Bhowmik, Arijit; Ghosh, Mrinal Kanti

    2015-01-01

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

  4. Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor.

    PubMed

    Wu, Jason Boyang; Shi, Changhong; Chu, Gina Chia-Yi; Xu, Qijin; Zhang, Yi; Li, Qinlong; Yu, John S; Zhau, Haiyen E; Chung, Leland W K

    2015-10-01

    Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic anion-transporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors.

  5. Primary pediatric cardiac tumors: a 17 year experience.

    PubMed

    Sallee, D; Spector, M L; van Heeckeren, D W; Patel, C R

    1999-03-01

    We reviewed 22 cases of primary pediatric cardiac tumors followed at our institution from January 1981 through November 1997, analyzing them by subtype, age and manner of presentation, location, associated findings, interventions, and clinical course. Rhabdomyomas were the most common (11), followed by intrapericardial teratomas (2), myxomas (1), fibromas (1), hemangiomas (1), mesotheliomas (1), and rhabdomyosarcomas (1), with 4 undetermined tumors. The majority (77%) of tumors were diagnosed before the age of one year, including six prenatally. The most common presentations were murmurs (5), arrhythmias (5), and abnormal screening fetal ultrasound examinations (4). Tumors were located most frequently in the right ventricle (13) and left ventricle (7), with multiple tumors being present in 10 cases. Eight patients (36%) had associated arrhythmias or conduction abnormalities, and of the 11 patients with rhabdomyomas, tuberous sclerosis was diagnosed in 8. Eight patients underwent cardiac catheterization, including two for electrophysiologic study with radiofrequency ablation, and seven patients had complete or partial tumor resection. The follow-up period ranged from 2 months to 15 years, and there were 3 tumor-related deaths. Therefore, despite the benign histology of most primary pediatric cardiac tumors, there may be significant associated morbidity and occasional mortality. As echocardiographic techniques such as fetal ultrasonography have continued to improve, however, these cardiac tumors have increasingly been detected early before significant symptoms develop.

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

    PubMed Central

    Rajesh Sharma, R.; Marikkannu, P.

    2015-01-01

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

  7. HFE polymorphisms affect survival of brain tumor patients.

    PubMed

    Lee, Sang Y; Slagle-Webb, Becky; Sheehan, Jonas M; Zhu, Junjia; Muscat, Joshua E; Glantz, Michael; Connor, James R

    2015-03-01

    The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

  8. Nonlinear microscopy, infrared, and Raman microspectroscopy for brain tumor analysis

    NASA Astrophysics Data System (ADS)

    Meyer, Tobias; Bergner, Norbert; Bielecki, Christiane; Krafft, Christoph; Akimov, Denis; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Dietzek, Benjamin; Popp, Jürgen

    2011-02-01

    Contemporary brain tumor research focuses on two challenges: First, tumor typing and grading by analyzing excised tissue is of utmost importance for choosing a therapy. Second, for prognostication the tumor has to be removed as completely as possible. Nowadays, histopathology of excised tissue using haematoxylin-eosine staining is the gold standard for the definitive diagnosis of surgical pathology specimens. However, it is neither applicable in vivo, nor does it allow for precise tumor typing in those cases when only nonrepresentative specimens are procured. Infrared and Raman spectroscopy allow for very precise cancer analysis due to their molecular specificity, while nonlinear microscopy is a suitable tool for rapid imaging of large tissue sections. Here, unstained samples from the brain of a domestic pig have been investigated by a multimodal nonlinear imaging approach combining coherent anti-Stokes Raman scattering, second harmonic generation, and two photon excited fluorescence microscopy. Furthermore, a brain tumor specimen was additionally analyzed by linear Raman and Fourier transform infrared imaging for a detailed assessment of the tissue types that is required for classification and to validate the multimodal imaging approach. Hence label-free vibrational microspectroscopic imaging is a promising tool for fast and precise in vivo diagnostics of brain tumors.

  9. Diagnosis and surgical treatment of childhood brain tumors.

    PubMed

    Wilson, C B

    1975-03-01

    As the most frequent solid tumor occurring in childhood, brain tumors constitute an important segment of pediatric oncology. Neurologic manifestations may be deceptively mild and easily overlooked or misinterpreted, particularly in the very young, because of the remarkable resiliency of the immature central nervous system and the skull's ability to expand throughout the pre-adolescent years. The majority of childhood tumors produce increased intracranial pressure, usually the consequence of obstructive hydrocephalus. Specific neurologic deficits correspond to the tumor's location. The posterior fossa harbors two-thirds of childhood tumors, and each of the four common tumors in this location produces a characteristic syndrome. Supratentorial tumors occupy the cerebral hemisphere, the suprasellar area, and the pineal gland. Diagnostic studies have reached a state of great sophistication and precise anatomical localization. Surgery, either alone or with adjuvant radiotherapy, cures no more than one-third of all tumors; for the remainder, it has a diagnostic and palliative role. The introduction of operative microsurgery has advanced the art, particularly in the surgical treatment of craniopharyngiomas and pinealomas, but any significant improvement in the treatment of brain tumors as a group seems unlikely to be achieved by surgery alone.

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus.

    PubMed

    Todo, T; Rabkin, S D; Sundaresan, P; Wu, A; Meehan, K R; Herscowitz, H B; Martuza, R L

    1999-11-20

    Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells were used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response. Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated by the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.

  13. Primary hepatic carcinoid tumor: case report and literature review

    PubMed Central

    Camargo, Éden Sartor; Viveiros, Marcelo de Melo; Corrêa, Isaac José Felippe; Robles, Laercio; Rezende, Marcelo Bruno

    2014-01-01

    Primary hepatic carcinoid tumors are extremely rare neoplasms derived from hormone-producing neuroendocrine cells. It is difficult to make their diagnosis before biopsy, surgical resection or necropsy. A recent publication described only 94 cases of these tumors. There is no sex predilection and apparently it has no association with cirrhosis or preexisting hepatic disease. The most effective treatment is hepatectomy, and resection is determined by size and location of the lesions. PMID:25628206

  14. Training stem cells for treatment of malignant brain tumors

    PubMed Central

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

    2014-01-01

    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 patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

  15. Progress on the diagnosis and evaluation of brain tumors

    PubMed Central

    Gao, Huile

    2013-01-01

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

  16. Dysphagia outcomes in patients with brain tumors undergoing inpatient rehabilitation.

    PubMed

    Wesling, Michele; Brady, Susan; Jensen, Mary; Nickell, Melissa; Statkus, Donna; Escobar, Nelson

    2003-01-01

    The purpose of this retrospective study was to compare functional dysphagia outcomes following inpatient rehabilitation for patients with brain tumors with that of patients following a stroke. Group 1 (n = 24) consisted of consecutive admissions to the brain injury program with the diagnosis of brain tumor and dysphagia. Group 2 (n = 24) consisted of matched, consecutive admissions, with the diagnosis of acute stroke and dysphagia. Group 2 was matched for age, site of lesion, and initial composite cognitive FIM score. The main outcome measures for this study included the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale, length of stay, hospital charges, and medical complications. Results showed that swallowing gains made by both groups as evaluated by the admission and discharge ASHA NOMS levels were considered to be statistically significant. The differences for length of stay, total hospital charges, and speech charges between the two groups were not considered to be statistically significant. Three patients in the brain tumor group (12.5%) demonstrated dysphagia complications of either dehydration or pneumonia during their treatment course as compared to 0% in the stroke group. This study confirms that functional dysphagia gains can be achieved for patients with brain tumors undergoing inpatient rehabilitation and that they should be afforded the same type and intensity of rehabilitation for their swallowing that is provided to patients following a stroke.

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

    PubMed

    Gainotti, Guido

    2012-06-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Tumor-infiltrating lymphocytes expressing IOT-10 marker. An immunohistochemical study of a series of 185 brain tumors.

    PubMed

    Zurita, M; Vaquero, J; Coca, S; Oya, S; Garcia, N

    1993-04-01

    The presence of IOT-10-positive lymphocytes among the tumor-infiltrating-lymphocyte (TIL) population was studied in a series of 185 brain tumors. In most of the tumors, IOT-10-positive lymphocytes were identified, but generally they were scarce and masked among the tumor cells, suggesting that NK-cells exercise a poor participation in the tissular response against brain tumors. Isolated tumor cells showing IOT-10-positivity were found in low-grade astrocytomas, neurinomas and medulloblastomas. IOT-10-positivity on both tumor neuropil and tumor cells was considered a characteristic finding in oligodendrogliomas. The number of IOT-10-positive NK-cells in brain metastases and in cerebellar hemangioblastomas was comparatively greater than in other types of brain tumor. Since in brain metastases, the presence of IOT-10-positive NK-cells can be related to the tissular response to an extracerebral malignancy, their considerable presence in cerebellar hemangioblastomas is an enigmatic finding that deserves further attention.

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

    PubMed Central

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

    2015-01-01

    Automatic classification of tissue types of region of interest (ROI) plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor) in T1-weighted contrast-enhanced MRI (CE-MRI) images. Spatial pyramid matching (SPM), which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM), and bag-of-words (BoW) model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI. PMID:26447861

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

    PubMed

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

    2015-11-01

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

  3. [Primary prevention of urologic tumors: prostate cancer].

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  4. American brain tumor patients treated with BNCT in Japan

    SciTech Connect

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

    1995-11-01

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

  5. Preoperative embolization of primary bone tumors: A case control study

    PubMed Central

    Jha, Roushan; Sharma, Raju; Rastogi, Shishir; Khan, Shah Alam; Jayaswal, Arvind; Gamanagatti, Shivanand

    2016-01-01

    AIM: To study the safety and effectiveness of preoperative embolization of primary bone tumors in relation to intraoperative blood loss, intraoperative blood transfusion volume and surgical time. METHODS: Thirty-three patients underwent preoperative embolization of primary tumors of extremities, hip or vertebrae before resection and stabilization. The primary osseous tumors included giant cell tumors, aneurysmal bone cyst, osteoblastoma, chondroblastoma and chondrosarcoma. Twenty-six patients were included for the statistical analysis (embolization group) as they were operated within 0-48 h within preoperative embolization. A control group (non-embolization group, n = 28) with bone tumor having similar histological diagnosis and operated without embolization was retrieved from hospital record for statistical comparison. RESULTS: The mean intraoperative blood loss was 1300 mL (250-2900 mL), the mean intraoperative blood transfusion was 700 mL (0-1400 mL) and the mean surgical time was 221 ± 76.7 min for embolization group (group I, n = 26). Non-embolization group (group II, n = 28), the mean intraoperative blood loss was 1800 mL (800-6000 mL), the mean intraoperative blood transfusion was 1400 mL (700-8400 mL) and the mean surgical time was 250 ± 69.7 min. On comparison, statistically significant (P < 0.001) difference was found between embolisation group and non-embolisation group for the amount of blood loss and requirement of blood transfusion. There was no statistical difference between the two groups for the surgical time. No patients developed any angiography or embolization related complications. CONCLUSION: Preoperative embolization of bone tumors is a safe and effective adjunct to the surgical management of primary bone tumors that leads to reduction in intraoperative blood loss and blood transfusion volume. PMID:27158424

  6. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

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

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

    MedlinePlus

    ... are at best rough estimates. Your child’s doctor knows your child’s situation and is your best source of information on this topic. Last Medical Review: 08/12/2014 Last Revised: 01/21/2016 Back to top » Guide Topics What Is Brain/CNS Tumors In Children? Causes, Risk Factors, and ...

  8. Learning Profiles of Survivors of Pediatric Brain Tumors

    ERIC Educational Resources Information Center

    Barkon, Beverly

    2009-01-01

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

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

    PubMed

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

    2011-02-01

    Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P < 0.001). Because increased numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation.

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

    PubMed Central

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

    2015-01-01

    Effective blood–brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (~6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. PMID:25818456

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

    PubMed

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

    2015-06-01

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

  12. Cranial nerve root entry zone primary cerebellopontine angle gliomas: a rare and poorly recognized subset of extraparenchymal tumors.

    PubMed

    Arnautovic, K I; Husain, M M; Linskey, M E

    2000-09-01

    With the exception of patients with neurofibromatosis type II, pediatric extraparenchymal cerebellopontine angle (CPA) tumors of any sort are extremely rare. Most gliomas encountered in the CPA in either children or adults involve the CPA as exophytic extensions of primary brain stem and/or cerebellar tumors. We encountered an unusual case of a giant CPA pilocytic astrocytoma arising from the proximal trigeminal nerve, completely separate from the brain stem. A nine-year-old girl with no evidence for any neurocutaneous syndrome, presented with headaches, mild obstructive hydrocephalus, trigeminal hypesthesia and a subtle peripheral facial paresis. Pre-operative neuroimaging suggested a petroclival meningioma. The tumor was completely resected via a right pre-sigmoid, retro-labyrinthine, subtemporal, transtentorial ('petrosal') approach, using intraoperative neurophysiological monitoring, with minimal morbidity. This appears to be the first reported case of a pediatric primary CPA glioma and the seventh reported case of primary CPA glioma, overall. It represents the second reported case of a primary CPA pilocytic astrocytoma. Given the findings in this case and the six other cases of primary CPA gliomas reported in the literature, as well as the results of histological studies of normal cranial nerves, we hypothesize that the point of origin of these rare and unusual tumors is the root entry zone of the involved cranial nerves. The differential diagnosis of primary CPA tumors should be expanded to include cranial nerve root entry zone primary CPA gliomas.

  13. Ablation techniques for primary and metastatic liver tumors

    PubMed Central

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-01

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

    Klinger, Neil V.

    2016-01-01

    Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors. PMID:27807473

  18. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    PubMed Central

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. PMID:23502426

  19. MIF Maintains the Tumorigenic Capacity of Brain Tumor-Initiating Cells by Directly Inhibiting p53.

    PubMed

    Fukaya, Raita; Ohta, Shigeki; Yaguchi, Tomonori; Matsuzaki, Yumi; Sugihara, Eiji; Okano, Hideyuki; Saya, Hideyuki; Kawakami, Yutaka; Kawase, Takeshi; Yoshida, Kazunari; Toda, Masahiro

    2016-05-01

    Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, brain tumor-initiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. ©2016 AACR. PMID:26980763

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

    PubMed

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

    2012-01-01

    Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression. PMID:21813362

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

    PubMed

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

    2015-08-01

    Within the past three decades, the significance of banking human cancer tissue for the advancement of cancer research has grown exponentially. The purpose of this article is to detail our experience in collecting brain tumor specimens in collaboration with the University of Miami/Sylvester Tissue Bank Core Facility (UM-TBCF), to ensure the availability of high-quality samples of central nervous system tumor tissue for research. Successful tissue collection begins with obtaining informed consent from patients following institutional IRB and federal HIPAA guidelines, and it needs a well-trained professional staff and continued maintenance of high ethical standards and record keeping. Since starting in 2011, we have successfully banked 225 brain tumor specimens for research. Thus far, the most common tumor histology identified among those specimens has been glioblastoma (22.1%), followed by meningioma (18.1%). The majority of patients were White, non-Hispanics accounting for 45.1% of the patient population; Hispanic/Latinos accounted for 23%, and Black/African Americans accounted for 14%, which represent the particular population of the State of Florida according to the 2010 census data. The most common tumors found in each subgroup were as follows: Black/African American, glioblastoma and meningioma; Hispanic, metastasis and glioblastoma; White, glioblastoma and meningioma. The UM-TBCF is a valuable repository, offering high-quality tumor samples from a unique patient population. PMID:26280502

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

    PubMed

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

    2015-04-01

    Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

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

    PubMed

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

    2015-08-01

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

  4. Primary malignancy, secondary malignancy and semimalignancy of bone tumors.

    PubMed

    Uehlinger, E

    1976-01-01

    1. Bone tumors in contrast to tumors in soft tissue, show a wide variety of clinical behavior qualified by the expressions semimalignancy, low grade of malignancy, sarcomatous degeneration and primarily benign bone tumors and bone lesions. 2. The term semimalignancy is characterized by local invasive and destructive tumor growth with a tendency to recur locally but no hematogeneous spreading. Semimalignancy requires wide en-bloc resection of amputation. 3. The term low grade malignancy is used to describe a tumor of very slow growth and with very late metastasis. Low-grade malignancy requires resection with careful preservation of functional structures. 4. The term secondary malignancy means the sarcomatous degeneration of a primarily benign lesion or bone tumor. This transformation is enhanced by irradiation and probably by acceleration of the normal turnover of bone tissue. In Paget's disease sarcomatous degeneration is to be expected in 2 percent of cases and in fibrous dysplasia in 0.5 percent of cases. 5. Sarcomatous degeneration of bone infarcts is rare, but an increase is to be expected due to an increased frequency of bone infarcts caused by long-term treatment with cortisone. 6. Primary bone tumors and recurrences show the same structure and cytology. In a minority of cases the recurrences are less differentiated; in a very few cases the recurrences are more highly differentiated and have a better prognosis than the initial lesion. PMID:1070716

  5. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

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

  6. Identification of internalizing human single chain antibodies targeting brain tumor sphere cells

    PubMed Central

    Zhu, Xiaodong; Bidlingmaier, Scott; Hashizume, Rintaro; James, C. David; Berger, Mitchel S.; Liu, Bin

    2010-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor and there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease, and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive media, and exhibit enhanced tumor initiating ability and resistance to therapy. We report here the identification of internalizing human single chain antibodies (scFvs) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope-positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly, as well as scFvs that target the CD133 positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular non-selective media. Taken together, these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library, which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment. PMID:20587664

  7. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

    PubMed Central

    Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

    2015-01-01

    Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

  8. Emerging techniques and technologies in brain tumor imaging.

    PubMed

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

    2014-10-01

    The purpose of this report is to describe the state of imaging techniques and technologies for detecting response of brain tumors to treatment in the setting of multicenter clinical trials. Within currently used technologies, implementation of standardized image acquisition and the use of volumetric estimates and subtraction maps are likely to help to improve tumor visualization, delineation, and quantification. Upon further development, refinement, and standardization, imaging technologies such as diffusion and perfusion MRI and amino acid PET may contribute to the detection of tumor response to treatment, particularly in specific treatment settings. Over the next few years, new technologies such as 2(3)Na MRI and CEST imaging technologies will be explored for their use in expanding the ability to quantitatively image tumor response to therapies in a clinical trial setting.

  9. Rare presentation of four primary pediatric cardiac tumors.

    PubMed

    Schaffer, Lauren R; Caltharp, Shelley A; Milla, Sarah S; Kogon, Brian F; Cundiff, Caitlin A; Dalal, Aarti; Quigley, Phillip C; Shehata, Bahig M

    2016-01-01

    Pediatric cardiac tumors are extremely rare and usually benign. We selected four unique cases of pediatric cardiac tumors from a 15-year period at our institution. The four chosen cases represent unique, rare primary tumors of the heart. Our selection includes a case of Rosai Dorfman disease without systemic involvement, which is, to our knowledge, the second case of isolated cardiac Rosai Dorfman disease in a child. We present a case of subtotal replacement of myocardium by granulocytic sarcoma with minimal bone marrow involvement, representing the first reported case in a child manifested as hypertrophic cardiomyopathy, as well as a case of a primary synovial sarcoma arising from the atrioventricular (AV) node, representing the fourth reported pediatric case of a cardiac synovial sarcoma, and it is the first to arise from the AV node. Finally, we present a primary congenital infantile fibrosarcoma of the heart, which is, to our knowledge, the first confirmed cardiac congenital infantile fibrosarcoma. These four cases represent the need for continued inclusion of rare cardiac conditions in a clinician's differential diagnosis. Furthermore, they present the need for more in-depth molecular and genomic analysis of pediatric cardiac tumors in order to identify their etiopathogenesis.

  10. Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment

    PubMed Central

    Hatipoglu, Gökçe; Hock, Stefan W; Weiss, Ruth; Fan, Zheng; Sehm, Tina; Ghoochani, Ali; Buchfelder, Michael; Savaskan, Nicolai E; Eyüpoglu, Ilker Y

    2015-01-01

    the brain tumor microenvironment, revealing novel aspects for adjuvant approaches and new clinical assessment criteria when applied to brain tumor patients. PMID:25458015

  11. Optical spectroscopy for stereotactic biopsy of brain tumors

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  12. Pros and cons of current brain tumor imaging

    PubMed Central

    Ellingson, Benjamin M.; Wen, Patrick Y.; van den Bent, Martin J.; Cloughesy, Timothy F.

    2014-01-01

    Over the past 20 years, very few agents have been approved for the treatment of brain tumors. Recent studies have highlighted some of the challenges in assessing activity in novel agents for the treatment of brain tumors. This paper reviews some of the key challenges related to assessment of tumor response to therapy in adult high-grade gliomas and discusses the strengths and limitations of imaging-based endpoints. Although overall survival is considered the “gold standard” endpoint in the field of oncology, progression-free survival and response rate are endpoints that hold great value in neuro-oncology. Particular focus is given to advancements made since the January 2006 Brain Tumor Endpoints Workshop, including the development of Response Assessment in Neuro-Oncology criteria, the value of T2/fluid-attenuated inversion recovery, use of objective response rates and progression-free survival in clinical trials, and the evaluation of pseudoprogression, pseudoresponse, and inflammatory response in radiographic images. PMID:25313235

  13. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  14. Gliosarcoma: A rare primary CNS tumor. Presentation of two cases

    PubMed Central

    Pardo, José; Murcia, Mauricio; García, Felip; Alvarado, Arnaldo

    2010-01-01

    Summary Introduction Gliosarcoma is a very rare primary mixed tumor in the central nervous system, with a biphasic pattern consisting of glial and malignant mesenchymal elements. Its onset is between the fourth and sixth decade of life, and it has a male/female ratio of 1.8/1. Here we present two cases of Gliosarcoma treated in our department. Discussion The monoclonal or biclonal origin of its biphasic nature is still subject to debate; hence the importance of its diagnosis and histogenesis. Results Standard treatment consists in surgical resection of the tumor followed in some cases by external radiotherapy and chemotherapy. PMID:24376932

  15. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma.

  16. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor.

    PubMed

    Gleason, James Benjamin; Tashtoush, Basheer; Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  17. Histogram analysis of ADC in brain tumor patients

    NASA Astrophysics Data System (ADS)

    Banerjee, Debrup; Wang, Jihong; Li, Jiang

    2011-03-01

    At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, post-contrast T1) were registered to the corresponding DTI scan at patient's first visit. Conventionally, hyper-intensity regions on T1-post contrast images are believed to represent the core tumor region while regions highlighted by FLAIR may overestimate tumor size. Thus we annotated tumor regions on the T1-post contrast scans and ADC intensity values for pixels were extracted inside tumor regions as defined on T1-post scans. We fit a mixture Gaussian (MG) model for the extracted pixels using the Expectation-Maximization (EM) algorithm, which produced a set of parameters (mean, various and mixture coefficients) for the MG model. This procedure was performed for each visits resulting in a series of GM parameters. We studied the parameters fitted for ADC and see if they can be used as indicators for tumor progression. Additionally, we studied the ADC characteristics in the peri-tumoral region as identified by hyper-intensity on FLAIR scans. The results show that ADC histogram analysis of the tumor region supports the two compartment model that suggests the low ADC value subregion corresponding to densely packed cancer cell while the higher ADC value region corresponding to a mixture of viable and necrotic cells with superimposed edema. Careful studies of the composition and relative volume of the two compartments in tumor

  18. Primary malignant chest wall tumors: analysis of 40 patients

    PubMed Central

    2014-01-01

    Background Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. Methods We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Results Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Conclusion Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality. PMID:24947314

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

    PubMed

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

    2016-07-01

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

  20. Pediatric Brain Tumor Treatment: Growth Consequences and their Management

    PubMed Central

    Mostoufi-Moab, Sogol; Grimberg, Adda

    2014-01-01

    Tumors of the central nervous system, the most common solid tumors of childhood, are a major source of cancer-related morbidity and mortality in children. Survival rates have improved significantly following treatment for childhood brain tumors, with this growing cohort of survivors at high risk of adverse medical and late effects. Endocrine morbidities are the most prominent disorder among the spectrum of long-term conditions, with growth hormone deficiency the most common endocrinopathy noted, either from tumor location or after cranial irradiation and treatment effects on the hypothalamic/pituitary unit. Deficiency of other anterior pituitary hormones can contribute to negative effects on growth, body image and composition, sexual function, skeletal health, and quality of life. Pediatric and adult endocrinologists often provide medical care to this increasing population. Therefore, a thorough understanding of the epidemiology and pathophysiology of growth failure as a consequence of childhood brain tumor, both during and after treatment, is necessary and the main focus of this review. PMID:21037539

  1. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed

    PubMed Central

    Sukheeja, Deepti; Mehta, Jayanti

    2016-01-01

    Dysembryoplastic neuroepithelial tumor (DNET) is a recently described, morphologically unique, and surgically curable low-grade brain tumor which is included in the latest WHO classification as neuronal and mixed neuronal-glial tumor. It is usually seen in children and young adults. The importance of this particular entity is that it is a surgically curable neuroepithelial neoplasm. When recognized, the need for adjuvant radiotherapy and chemotherapy is obviated. We hereby present a case report of an 8-year-old male child who presented with intractable seizures and parieto-occipital space occupying lesion. Histologically, the tumor exhibited features of WHO grade I dysembryoplastic neuroepithelial tumor which was further confirmed by immunohistochemistry. PMID:27057233

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

    PubMed

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

    2013-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new modality capable of imaging the electrical properties of human body using MRI phase information in conjunction with external current injection. Recent in vivo animal and human MREIT studies have revealed unique conductivity contrasts related to different physiological and pathological conditions of tissues or organs. When performing in vivo brain imaging, small imaging currents must be injected so as not to stimulate peripheral nerves in the skin, while delivery of imaging currents to the brain is relatively small due to the skull's low conductivity. As a result, injected imaging currents may induce small phase signals and the overall low phase SNR in brain tissues. In this study, we present numerical simulation results of the use of head MREIT for brain tumor detection. We used a realistic three-dimensional head model to compute signal levels produced as a consequence of a predicted doubling of conductivity occurring within simulated tumorous brain tissues. We determined the feasibility of measuring these changes in a time acceptable to human subjects by adding realistic noise levels measured from a candidate 3 T system. We also reconstructed conductivity contrast images, showing that such conductivity differences can be both detected and imaged. PMID:23737862

  3. Numerical Simulations of MREIT Conductivity Imaging for Brain Tumor Detection

    PubMed Central

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

    2013-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new modality capable of imaging the electrical properties of human body using MRI phase information in conjunction with external current injection. Recent in vivo animal and human MREIT studies have revealed unique conductivity contrasts related to different physiological and pathological conditions of tissues or organs. When performing in vivo brain imaging, small imaging currents must be injected so as not to stimulate peripheral nerves in the skin, while delivery of imaging currents to the brain is relatively small due to the skull's low conductivity. As a result, injected imaging currents may induce small phase signals and the overall low phase SNR in brain tissues. In this study, we present numerical simulation results of the use of head MREIT for brain tumor detection. We used a realistic three-dimensional head model to compute signal levels produced as a consequence of a predicted doubling of conductivity occurring within simulated tumorous brain tissues. We determined the feasibility of measuring these changes in a time acceptable to human subjects by adding realistic noise levels measured from a candidate 3 T system. We also reconstructed conductivity contrast images, showing that such conductivity differences can be both detected and imaged. PMID:23737862

  4. Secondary optic nerve tumors.

    PubMed

    Christmas, N J; Mead, M D; Richardson, E P; Albert, D M

    1991-01-01

    Secondary tumors of the optic nerve are more common than primary optic nerve tumors. The involvement of the optic nerve may arise from direct invasion from intraocular malignancies, from hematopoietic malignancy, from meningeal carcinomatosis, or from distant primary tumors. Orbital tumors rarely invade the optic nerve, and brain tumors involve it only in their late stages.

  5. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.

    PubMed

    Blumenthal, Deborah T; Yalon, Michal; Vainer, Gilad W; Lossos, Alexander; Yust, Shlomit; Tzach, Lior; Cagnano, Emanuela; Limon, Dror; Bokstein, Felix

    2016-09-01

    Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

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

    ClinicalTrials.gov

    2016-05-17

    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

  7. Drug response in organoids generated from frozen primary tumor tissues

    PubMed Central

    Walsh, Alex J.; Cook, Rebecca S.; Sanders, Melinda E.; Arteaga, Carlos L.; Skala, Melissa C.

    2016-01-01

    Primary tumor organoids grown in three-dimensional culture provide an excellent platform for studying tumor progression, invasion, and drug response. However, organoid generation protocols require fresh tumor tissue, which limits organoid research and clinical use. This study investigates cellular morphology, viability, and drug response of organoids derived from frozen tissues. The results demonstrate that viable organoids can be grown from flash-frozen and thawed tissue and from bulk tissues slowly frozen in DMSO supplemented media. While the freezing process affects the basal metabolic rate of the cells, the optical metabolic imaging index correlates between organoids derived from fresh and frozen tissue and can be used to detect drug response of organoids grown from frozen tissues. The slow, DMSO frozen tissue yielded organoids with more accurate drug response than the flash frozen tissues, and thus bulk tissue should be preserved for subsequent organoid generation by slow freezing in DMSO supplemented media. PMID:26738962

  8. A dual neural network ensemble approach for multiclass brain tumor classification.

    PubMed

    Sachdeva, Jainy; Kumar, Vinod; Gupta, Indra; Khandelwal, Niranjan; Ahuja, Chirag Kamal

    2012-11-01

    The present study is conducted to develop an interactive computer aided diagnosis (CAD) system for assisting radiologists in multiclass classification of brain tumors. In this paper, primary brain tumors such as astrocytoma, glioblastoma multiforme, childhood tumor-medulloblastoma, meningioma and secondary tumor-metastases along with normal regions are classified by a dual level neural network ensemble. Two hundred eighteen texture and intensity features are extracted from 856 segmented regions of interest (SROIs) and are taken as input. PCA is used for reduction of dimensionality of the feature space. The study is performed on a diversified dataset of 428 post contrast T1-weighted magnetic resonance images of 55 patients. Two sets of experiments are performed. In the first experiment, random selection is used which may allow SROIs from the same patient having similar characteristics to appear in both training and testing simultaneously. In the second experiment, not even a single SROI from the same patient is common during training and testing. In the first experiment, it is observed that the dual level neural network ensemble has enhanced the overall accuracy to 95.85% compared with 91.97% of single level artificial neural network. The proposed method delivers high accuracy for each class. The accuracy obtained for each class is: astrocytoma 96.29%, glioblastoma multiforme 96.15%, childhood tumor-medulloblastoma 90%, meningioma 93.00%, secondary tumor-metastases 96.67% and normal regions 97.41%. This study reveals that dual level neural network ensemble provides better results than the single level artificial neural network. In the second experiment, overall classification accuracy of 90.4% was achieved. The generalization ability of this approach can be tested by analyzing larger datasets. The extensive training will also further improve the performance of the proposed dual network ensemble. Quantitative results obtained from the proposed method will assist the

  9. Boron neutron capture therapy of brain tumors: Enhanced survival following intracarotid injection of sodium borocaptate with or without blood-brain barrier disruption

    SciTech Connect

    Yang, W.; Barth, R.F.; Rotaru, J.H.

    1997-02-01

    Sodium borocaptate (Na{sub 2}B{sub 12}H{sub 11}SH or BSH) has been used clinically for boron neutron capture therapy (BNCT) of patients with primary brain tumors. The purpose of the present study was to determine if tumor uptake of BSH and efficacy of BNCT could be enhanced in F98 glioma-bearing rats by intracarotid (i.c.) injection of the compound with or without blood-brain barrier disruption (BBB-D). 56 refs., 4 figs., 3 tabs.

  10. Brain tumor segmentation in MRI based on fuzzy aggregators

    NASA Astrophysics Data System (ADS)

    Zhu, Yan; Liao, Qingmin; Dou, Weibei; Ruan, Su

    2005-07-01

    Magnetic Resonance Image (MRI) is widely used in radiology diagnosis, especially in pathology detection in human brain. Most of the methods now applied to automatically segment brain tumors rely on T1-weighted sequences exclusively despite the fact that the imaging agent is multi-spectral. The work focuses on the integration or fusion of information provided by each sequence, i.e. T1, T2 and PD. Based on the fuzzy aggregators proposed in fuzzy theory, a system integrating all these information is established. The paper discusses some famous operators, their properties and application in tumor segmentation. In particular, Davies-Bouldin index is used to determine the parameters of the parametric operations. The result shows the importance of data fusion in segmentation process, discovers that T-norms are less robust to noise compared with mean operators. Meanwhile, weights allocated illustrate the order of importance of each spectrum in pathology detection, and are in agreement with their characteristic.

  11. Primary gastrointestinal stromal tumor of the liver: A case report

    PubMed Central

    Luo, Xiao-Li; Liu, Dan; Yang, Jian-Jun; Zheng, Min-Wen; Zhang, Jing; Zhou, Xiao-Dong

    2009-01-01

    We report a case of primary gastrointestinal stromal tumor (GIST) of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound (CEUS) revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography (CT) showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CD117. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT. PMID:19653356

  12. Asparagine Depletion Potentiates the Cytotoxic Effect of Chemotherapy Against Brain Tumors

    PubMed Central

    Panosyan, Eduard H.; Wang, Yuntao; Xia, Peng; Lee, Wai-Nang Paul; Pak, Youngju; Laks, Dan R.; Lin, Henry J.; Moore, Theodore B.; Cloughesy, Timothy F.; Kornblum, Harley I.; Lasky, Joseph L.

    2014-01-01

    Targeting amino acid metabolism has therapeutic implications for aggressive brain tumors. Asparagine is an amino acid that is synthesized by normal cells. However, some cancer cells lack asparagine synthetase (ASNS), the key enzyme for asparagine synthesis. Asparaginase (ASNase) contributes to eradication of acute leukemia by decreasing asparagine levels in serum and cerebrospinal fluid. However, leukemic cells may become ASNase-resistant by up-regulating ASNS. High expression of ASNS has also been associated with biological aggressiveness of other cancers, including gliomas. Here, the impact of enzymatic depletion of asparagine on proliferation of brain tumor cells was determined. ASNase was used as monotherapy or in combination with conventional chemotherapeutic agents. Viability assays for ASNase-treated cells demonstrated significant growth reduction in multiple cell lines. This effect was reversed by glutamine in a dose-dependent manner -- as expected, because glutamine is the main amino group donor for asparagine synthesis. ASNase treatment also reduced sphere formation by medulloblastoma and primary glioblastoma cells. ASNase-resistant glioblastoma cells exhibited elevated levels of ASNS mRNA. ASNase co-treatment significantly enhanced gemcitabine or etoposide cytotoxicity against glioblastoma cells. Xenograft tumors in vivo showed no significant response to ASNase monotherapy and little response to temozolomide (TMZ) alone. However, combinatorial therapy with ASNase and TMZ resulted in significant growth suppression for an extended duration of time. Taken together, these findings indicate that amino acid depletion warrants further investigation as adjunctive therapy for brain tumors. PMID:24505127

  13. Thallium-201 brain tumor imaging: a comparative study with pathologic correlation

    SciTech Connect

    Kaplan, W.D.; Takvorian, T.; Morris, J.H.; Rumbaugh, C.L.; Connolly, B.T.; Atkins, H.L.

    1987-01-01

    In patients with gliomas who were stable or improving, we noted a disparity between clinical status and computed tomography (CT) brain scan results. To elucidate this finding, 29 patients were sequentially scanned with 2.0 mCi of /sup 201/Tl (5-30 min), 20 mCi (/sup 99m/Tc)gluceptate (GH) (3-4 hr) and 7-10 mCi 67Ga (48-72 hr). A total of 198 images were obtained. A set of three scans at a midpoint in follow up was selected for analysis. Seven patients who died had neuropathologic data available; brain sections were reconstructed to match radionuclide views without knowledge of image results. In the seven patients with autopsy data, /sup 201/Tl offered the most accurate correlation with viable tumor. Gallium-67 gave similar results in patients not receiving steroids. Technetium-99m GH scans could not allow differentiation between tumor, necrosis, and edema. Similarly, the CT scan could not routinely differentiate between fibrotic, nonfibrotic, necrotic, and neoplastic tissue. In the 22 patients without autopsy data, /sup 201/Tl scans commonly showed smaller and more focal abnormal uptake when compared with (/sup 99m/Tc)GH and /sup 67/Ga scans. Thallium-201 scans more accurately reflect viable tumor burden than other radionuclide studies of primary brain tumors, are minimally affected by concomitant steroid administration, can be performed immediately following tracer administration, and complement the anatomic data obtained from CT scans.

  14. Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

    NASA Astrophysics Data System (ADS)

    Vatansever, Fatma; Kawakubo, Masayoshi; Chung, Hoon; Hamblin, Michael R.

    2013-02-01

    We have previously shown that photodynamic therapy mediated by a vascular regimen of benzoporphyrin derivative and 690nm light is capable of inducing a robust immune response in the mouse CT26.CL25 tumor model that contains a tumor-rejection antigen, beta-galactosidase (β-gal). For the first time we show that PDT can stimulate the production of serum IgG antibodies against the β-gal antigen. It is known that a common cause of death from cancer, particularly lung cancer, is brain metastases; especially the inoperable ones that do not respond to traditional cytotoxic therapies either. We asked whether PDT of a primary tumor could stimulate immune response that could attack the distant brain metastases. We have developed a mouse model of generating brain metastases by injecting CT26.CL25 tumor cells into the brain as well as injecting the same cancer cells under the skin at the same time. When the subcutaneous tumor was treated with PDT, we observed a survival advantage compared to mice that had untreated brain metastases alone.

  15. Primary extragastrointestinal stromal tumor of the pleura: A case report

    PubMed Central

    ZHANG, CAI-QING; LU, DE-GAN; LIU, QING-FA; XIAO, WEI

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The stomach and small intestine are the most common sites of occurrence. GISTs are mesenchymal neoplasms originating from the interstitial cells of Cajal (ICCs), and are characterized by positivity for cluster of differentiation (CD) 117, also known as proto-oncogene c-Kit. While the majority of GISTs develop in the alimentary tract, in rare cases they may also be found in extragastrointestinal tissues. This type of GIST is known as an extragastrointestinal stromal tumor (EGIST). Despite the fact that EGISTs have been reported in the mesentery, omentum and retroperitoneum, primary intrathoracic EGISTs, arising from the pleura or lungs, are rare. The patient presented in the current study was a 40-year-old man, who presented with a cough and pyrexia, with pleural effusion on the left side. Multiple nodules throughout the parietal pleura were identified by thoracoscopy and a diagnosis of primary GIST of pleura was established, since they were positive for CD117 and discovered on GIST-1 and there was no evidence of gastrointestinal tumors. Subsequently, the patient was administered with imatinib and had no signs of disease recurrence 2 years later. PMID:27123077

  16. Early and multiple origins of metastatic lineages within primary tumors

    PubMed Central

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G.; Schlessinger, Joseph; Lifton, Richard P.; Rimm, David L.; Townsend, Jeffrey P.

    2016-01-01

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  17. Early and multiple origins of metastatic lineages within primary tumors.

    PubMed

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G; Schlessinger, Joseph; Lifton, Richard P; Rimm, David L; Townsend, Jeffrey P

    2016-02-23

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  18. Hematoporphyrin-derivative photodynamic in-vitro sensitivity testing for brain tumors

    NASA Astrophysics Data System (ADS)

    Plattner, Michael; Bernwick, Walter; Kostron, Herwig

    1993-03-01

    Brain tumors of various histologies were subjected to an in-vitro photodynamic-sensitivity test. The studies were performed on primary cultures of human glioblastomas, meningiomas, and ependymomas, which were exposed to increasing concentrations of hematoporphyrin derivative and 60 J/cm2 delivered by an argon-dye laser at 632 nm. A growth inhibition of 75% was demonstrated at a concentration of 25 (mu) g and 10 (mu) g HPD/ml medium for two different glioblastomas, respectively. A growth inhibition of 75% was observed in the ependymoma line at 10 and 50 (mu) g HPD/ml with and without light, respectively. The meningioma demonstrated a 75% inhibition already at (mu) g and 75 (mu) g/ml medium with and without light, respectively. These results demonstrate a significant difference in the response of brain tumors to photodynamic treatment (PDT). In vitro-PDT-assay should be taken into account if clinical application of PDT is considered.

  19. Drosophila neural stem cells in brain development and tumor formation.

    PubMed

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

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

    PubMed

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

    2015-12-30

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

  1. Heavy Metals and Epigenetic Alterations in Brain Tumors

    PubMed Central

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

    2014-01-01

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

  2. Sigma and opioid receptors in human brain tumors

    SciTech Connect

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

    1990-01-01

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

  3. Primary tumors of the trachea. Results of radiation therapy

    SciTech Connect

    Fields, J.N.; Rigaud, G.; Emami, B.N.

    1989-06-15

    From 1959 to 1986, 24 patients with primary malignant tumors of the trachea received radiotherapy as all or part of treatment. Common presentations included respiratory symptoms in 20 patients and hemoptysis in 15. Thirteen patients had squamous carcinomas with undifferentiated and adenoid cystic cancers in five and four patients, respectively. Overall actuarial survival was 45% at 1 year, 25% at 5 years, and 13% at 10 years. Survival was significantly correlated to histologic type (adenoid cystic versus squamous, P less than 0.03), but not to tumor extent or to patient age or sex. Local control was attained in 10 of 24 patients overall and was more frequent for patients with tumors localized to the trachea and for patients who were treated with combined surgery and radiotherapy. For the 18 patients treated with radiotherapy alone, complete response (CR) was seen to be significantly (P less than 0.001) related to dose: six of seven (86%) patients receiving greater than or equal to 6000 cGy attained CR versus one of 11 (9%) receiving less than 6000 cGy. Three patients developed complications related to radiotherapy. Radiotherapy can provide durable local control of localized tracheal tumors and should be considered for medically inoperable patients with localized tumors and for patients with high risk of recurrence after resection.

  4. [One Case about Primary Mediastinal Primary Mediastinal Tumor 
with Mediastinal Sarcoma and Literature Review].

    PubMed

    Du, Jinchen; Li, Qingxin; Chao, Dong; Ban, Yulian; Li, Qunqun

    2016-09-20

    Primary mediastinal seminoma is a kind of germ cell malignancy outside the gonads, and it's rarer with sarcoma component. This disease which has no special clinical manifestations and imaging characteristics is difficult to identify with other mediastinal tumors and mediastinal type lung cancer. This paper reported a case of primary mediastinal seminoma with mediastinal sarcoma. Through the analysis of the diagnosis and treatment process in this patient, we will make a comprehensive review of the disease. PMID:27666557

  5. The p53 gene and protein in human brain tumors

    SciTech Connect

    Louis, D.N. )

    1994-01-01

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

  6. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors.

    PubMed

    Lee, Yi-Yen; Yang, Yi-Ping; Huang, Ming-Chao; Wang, Mong-Lien; Yen, Sang-Hue; Huang, Pin-I; Chen, Yi-Wei; Chiou, Shih-Hwa; Lan, Yuan-Tzu; Ma, Hsin-I; Shih, Yang-Hsin; Chen, Ming-Teh

    2014-01-01

    Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133(+) cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133(+)) cells are still unclear. We have previously shown that ATRT-CD133(+) cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133(+) cells than in ATRT-CD133(-) cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133(+) cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133(-) cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. PMID:24816458

  7. The time course of steroid action on blood-to-brain and blood-to-tumor transport of 82Rb: A positron emission tomographic study

    SciTech Connect

    Jarden, J.O.; Dhawan, V.; Moeller, J.R.; Strother, S.C.; Rottenberg, D.A.

    1989-03-01

    Blood-to-brain and blood-to-tumor transport rate constants for Rb (K1) and apparent tissue blood volume (Vb) were estimated in 8 patients with primary or metastatic brain tumors before and approximately 6 hours after a 100-mg intravenous bolus injection of dexamethasone using /sup 82/Rb and positron emission tomography. Eight additional patients were studied to evaluate test-retest variability and repositioning errors. Six hours following dexamethasone administration tumor K1 (but not Vb) was significantly reduced compared with contralateral control brain regions (p less than 0.03). These data are consistent with our previously published 24-hour-postdexamethasone data and suggest that comparable effects of corticosteroids on brain/tumor capillaries may be observed at 5 to 6 and 24 hours. The time course of dexamethasone-induced alterations in brain/tumor capillary permeability supports the view that these alterations may be responsible for at least some of the antiedema effects of corticosteroids.

  8. Jaw tumor in primary hyperparathyroidism is not always a brown tumor

    PubMed Central

    Ennazk, Laila; El Mghari, Ghizlane; El Ansari, Nawal

    2016-01-01

    Summary Primary hyperparthyrodism (PHPT) is a common endocrine disease. It results from an inappropriate parathyroid hormone (PTH) secretion relative to serum ionized calcium level. Clinical manifestation of severe PHPT include bone disease called osteitis fibrosa cystica which reflects an increase osteoclastic resorption and osteoblastic activity. This high bone turnover is responsible of the occurrence of osteoclastomas, also named “brown tumors” (1). Rarely, PHPT may occur in inherited forms with association to fibrous jaw tumor that are unrelated to hyperparathyroidism. In this uncommon disease: hyperparathyroidism-jaw tumor (HPT-JT) syndrome, parathyroid tumor is frequently malignant and usually associated with nonendocrine malignancies (2). We report a case of a HPT-JT syndrome to focus on the differential diagnosis with brown tumors. PMID:27252751

  9. Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer.

    PubMed

    Ray, Saurabh; Dacosta-Byfield, Stacey; Ganguli, Arijit; Bonthapally, Vijayveer; Teitelbaum, April

    2013-08-01

    Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

  10. Radiosurgery in the management of pediatric brain tumors.

    PubMed

    Raco, A; Raimondi, A J; D'Alonzo, A; Esposito, V; Valentino, V

    2000-05-01

    A total of 114 patients with benign and malignant intracranial tumors were treated by Valentino at the Flaminia Radiosurgical Center using a Philips 6-MeV linear accelerator between 1987 and 1995. The tumor locations break down as follows: 36 in the cerebral hemispheres, 14 in the region of the hypothalamus/optic chiasm, 21 in the III ventricle/pineal region, 3 in the basal ganglia, 27 in the posterior fossa, 13 in the brain stem. Seventy-nine patients had multivariate/combined treatment consisting of surgery or biopsy followed by chemotherapy, radiotherapy and/or radiosurgery. Thirty-five were not operated on or biopsied but were treated primarily by radiosurgery, which was associated with chemotherapy and conventional radiotherapy. The short- and long-term results were evaluated separately for each pathology in an attempt to derive guidelines for future treatment. For tumors of the pineal region, we are of the opinion that radiosurgery is the treatment of choice in children and that more than one-third of patients can be cured by this means. The remaining patients require surgery and/or chemotherapy in addition. For medulloblastomas radiosurgery may be useful to control local recurrence if coupled with chemotherapy. In the case of ependymomas, partly because of the extreme malignancy of the lesions in our series, radiosurgery did not succeed in controlling local recurrence. We fear that limiting treatment to radiosurgery, rather than prescribing conventional radiotherapy when indicated, could permit CNS seeding. For craniopharyngiomas radiosurgery proved useful for controlling solid remnants. In glial tumors radiosurgery helped either to "sterilize" the tumor bed after removal or to treat remnants of the lesions in critical areas; for diffuse brain stem gliomas it should be considered the treatment of choice.

  11. Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

    PubMed

    Seppala, N; Cala, A; Klebe, S

    2009-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

  12. Image updating for brain deformation compensation in tumor resection

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

    ClinicalTrials.gov

    2016-08-15

    Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

  15. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution

    PubMed Central

    Huh, Jimi; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

    2015-01-01

    Objective To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ≥ 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results Among the 70 patients (mean age, 35.8 ± 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. PMID:26175577

  16. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1987-04-01

    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.

  18. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

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

    2016-07-15

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

  19. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

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

    2016-07-15

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

  20. What primary microcephaly can tell us about brain growth.

    PubMed

    Cox, James; Jackson, Andrew P; Bond, Jacquelyn; Woods, Christopher G

    2006-08-01

    Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental disorder that causes a great reduction in brain growth in utero. MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size. At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ). Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation. Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans. The aim of this article is to review what has been learnt about the rare condition primary microcephaly and the information this provides about normal brain growth. PMID:16829198

  1. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images

    PubMed Central

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

    2016-01-01

    Image enhancement techniques are able to improve the contrast and visual quality of magnetic resonance (MR) images. However, conventional methods cannot make up some deficiencies encountered by respective brain tumor MR imaging modes. In this paper, we propose an adaptive intuitionistic fuzzy sets-based scheme, called as AIFE, which takes information provided from different MR acquisitions and tries to enhance the normal and abnormal structural regions of the brain while displaying the enhanced results as a single image. The AIFE scheme firstly separates an input image into several sub images, then divides each sub image into object and background areas. After that, different novel fuzzification, hyperbolization and defuzzification operations are implemented on each object/background area, and finally an enhanced result is achieved via nonlinear fusion operators. The fuzzy implementations can be processed in parallel. Real data experiments demonstrate that the AIFE scheme is not only effectively useful to have information from images acquired with different MR sequences fused in a single image, but also has better enhancement performance when compared to conventional baseline algorithms. This indicates that the proposed AIFE scheme has potential for improving the detection and diagnosis of brain tumors. PMID:27786240

  2. Round Randomized Learning Vector Quantization for Brain Tumor Imaging.

    PubMed

    Sheikh Abdullah, Siti Norul Huda; Bohani, Farah Aqilah; Nayef, Baher H; Sahran, Shahnorbanun; Al Akash, Omar; Iqbal Hussain, Rizuana; Ismail, Fuad

    2016-01-01

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

  3. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    PubMed Central

    2016-01-01

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

  4. Semi-automatic brain tumor segmentation by constrained MRFs using structural trajectories.

    PubMed

    Zhao, Liang; Wu, Wei; Corso, Jason J

    2013-01-01

    Quantifying volume and growth of a brain tumor is a primary prognostic measure and hence has received much attention in the medical imaging community. Most methods have sought a fully automatic segmentation, but the variability in shape and appearance of brain tumor has limited their success and further adoption in the clinic. In reaction, we present a semi-automatic brain tumor segmentation framework for multi-channel magnetic resonance (MR) images. This framework does not require prior model construction and only requires manual labels on one automatically selected slice. All other slices are labeled by an iterative multi-label Markov random field optimization with hard constraints. Structural trajectories-the medical image analog to optical flow and 3D image over-segmentation are used to capture pixel correspondences between consecutive slices for pixel labeling. We show robustness and effectiveness through an evaluation on the 2012 MICCAI BRATS Challenge Dataset; our results indicate superior performance to baselines and demonstrate the utility of the constrained MRF formulation. PMID:24505807

  5. A prospective study of neuropsychological sequelae in children with brain tumors.

    PubMed

    Bordeaux, J D; Dowell, R E; 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. PMID:3343496

  6. Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries.

    PubMed

    McCarthy, Bridget J; Shibui, Soichiro; Kayama, Takamasa; Miyaoka, Etsuo; Narita, Yoshitaka; Murakami, Michiko; Matsuda, Ayako; Matsuda, Tomohiro; Sobue, Tomotaka; Palis, Bryan E; Dolecek, Therese A; Kruchko, Carol; Engelhard, Herbert H; Villano, J Lee

    2012-09-01

    Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004-2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004-2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984-2000) and (4) the US National Cancer Data Base (1990-2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.

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

    PubMed

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

    2011-01-01

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

  8. Identifying the needs of brain tumor patients and their caregivers.

    PubMed

    Parvataneni, Rupa; Polley, Mei-Yin; Freeman, Teresa; Lamborn, Kathleen; Prados, Michael; Butowski, Nicholas; Liu, Raymond; Clarke, Jennifer; Page, Margaretta; Rabbitt, Jane; Fedoroff, Anne; Clow, Emelia; Hsieh, Emily; Kivett, Valerie; Deboer, Rebecca; Chang, Susan

    2011-09-01

    The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers' questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were "very important" but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients' lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value < 0.001). This study provides insights into areas to improve services for brain tumor patients and their caregivers. The caregivers' highest amount of burden is placed on their emotional needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients' treatment process.

  9. Statistical feature selection for enhanced detection of brain tumor

    NASA Astrophysics Data System (ADS)

    Chaddad, Ahmad; Colen, Rivka R.

    2014-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Confidence-based ensemble for GBM brain tumor segmentation

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Absence of human cytomegalovirus infection in childhood brain tumors

    PubMed Central

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

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients’ neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

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

    PubMed

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

    2015-10-01

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

  15. Contrast medium accumulation and washout in canine brain tumors and irradiated normal brain: a CT study of kinetics

    SciTech Connect

    Fike, J.R.; Cann, C.E.

    1984-04-01

    Kinetics of an iodinated contrast medium were evaluated quantitatively as a function of time up to one hour after intravenous infusion in the brains of dogs with experimentally induced radiation damage and dogs with spontaneous brain tumor. Radiation damage was characterized by an increase in iodine accumulation soon after the infusion, while tumor concentration of iodine either showed no change or decreased with time. These results suggest that contrast kinetic studies may be useful in differentiating radiation damage to normal brain tissue from a malignant brain tumor.

  16. Infant Brain Tumors: Incidence, Survival, and the Role of Radiation Based on Surveillance, Epidemiology, and End Results (SEER) Data

    SciTech Connect

    Bishop, Andrew J.; McDonald, Mark W.; Chang, Andrew L.; Esiashvili, Natia

    2012-01-01

    Purpose: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Results: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). Conclusion: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation

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

    PubMed

    Hottinger, Andreas F; Pacheco, Patricia; Stupp, Roger

    2016-10-01

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

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

    PubMed Central

    Pacheco, Patricia

    2016-01-01

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

  19. Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for Brain Metastases.

    PubMed

    Kao, Johnny; Darakchiev, Boramir; Conboy, Linda; Ogurek, Sara; Sharma, Neha; Ren, Xuemin; Pettit, Jeffrey

    2015-10-01

    Despite significant technical advances in radiation delivery, conventional whole brain radiation therapy (WBRT) has not materially changed in the past 50 years. We hypothesized that IMRT can selectively spare uninvolved brain and scalp with the goal of reducing acute and late toxicity. MRI/CT simulation image registration was performed. We performed IMRT planning to simultaneously treat the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans. Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while IMRT planning was performed. Seventeen consecutive patients with brain metastases with RPA class I and II disease with no leptomeningeal spread were treated with IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2 Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p < 0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p = 0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6 patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8 months (range: 5 to 15 months), the median overall survival was 5.4 months. Four patients relapsed within the brain, one within the PTV37.5 and three outside the PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose distributions and preserves partial hair coverage in the majority of patients. Further studies are warranted to determine whether the increased utilization of resources needed for IMRT are appropriate in this setting.

  20. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

    PubMed

    Li, Fang; Liu, Xinjian; Sampson, John H; Bigner, Darell D; Li, Chuan-Yuan

    2016-09-01

    Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. ©2016 AACR. PMID:27364552

  1. Bystander effect-mediated therapy of experimental brain tumor by genetically engineered tumor cells.

    PubMed

    Namba, H; Tagawa, M; Iwadate, Y; Kimura, M; Sueyoshi, K; Sakiyama, S

    1998-01-01

    Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, followed by administration of ganciclovir (GCV), generates the "bystander effect," in which HSV-tk-negative wild-type cells, as well as HSV-tk-expressing cells, are killed by GCV. To eradicate an intracranial tumor by this bystander effect, we injected the tumor cells transduced with the HSV-tk gene (TK cells) in the vicinity of the preimplanted wild-type tumor and then administered GCV. Wild-type 9L-gliosarcoma cells (1 x 10[5]) were implanted into the brain of syngeneic Fisher rats. On the next day, rats were injected with TK cells (1 x 10(5) or 3 x 10[5]) or medium alone at the same brain coordinate and then treated with GCV or saline. Administration of GCV significantly prolonged the survival of the rats injected with TK cells compared with that injected with medium alone (p < 0.01). Reduction in tumor size and retardation of tumor growth were observed by serial magnetic resonance imaging in the rats that received the combination of TK cells and GCV. The results show that the bystander effect is also achieved in vivo even when TK cells and wild-type cells are not simultaneously implanted. This treatment modality circumvents potential risks accompanied with in vivo gene transfer. Because there remained substantially no HSV-tk-positive cells in the recurrent tumors, this modality offers a "safe" therapeutic strategy against human malignant gliomas. PMID:9458237

  2. Label-Free Delineation of Brain Tumors by Coherent Anti-Stokes Raman Scattering Microscopy in an Orthotopic Mouse Model and Human Glioblastoma

    PubMed Central

    Tamosaityte, Sandra; Leipnitz, Elke; Geiger, Kathrin D.; Schackert, Gabriele; Koch, Edmund; Steiner, Gerald; Kirsch, Matthias

    2014-01-01

    Background Coherent anti-Stokes Raman scattering (CARS) microscopy provides fine resolution imaging and displays morphochemical properties of unstained tissue. Here, we evaluated this technique to delineate and identify brain tumors. Methods Different human tumors (glioblastoma, brain metastases of melanoma and breast cancer) were induced in an orthotopic mouse model. Cryosections were investigated by CARS imaging tuned to probe C-H molecular vibrations, thereby addressing the lipid content of the sample. Raman microspectroscopy was used as reference. Histopathology provided information about the tumor's localization, cell proliferation and vascularization. Results The morphochemical contrast of CARS images enabled identifying brain tumors irrespective of the tumor type and properties: All tumors were characterized by a lower CARS signal intensity than the normal parenchyma. On this basis, tumor borders and infiltrations could be identified with cellular resolution. Quantitative analysis revealed that the tumor-related reduction of CARS signal intensity was more pronounced in glioblastoma than in metastases. Raman spectroscopy enabled relating the CARS intensity variation to the decline of total lipid content in the tumors. The analysis of the immunohistochemical stainings revealed no correlation between tumor-induced cytological changes and the extent of CARS signal intensity reductions. The results were confirmed on samples of human glioblastoma. Conclusions CARS imaging enables label-free, rapid and objective identification of primary and secondary brain tumors. Therefore, it is a potential tool for diagnostic neuropathology as well as for intraoperative tumor delineation. PMID:25198698

  3. Quality of life in patients with primary and metastatic brain cancer as reported in the literature using the EORTC QLQ-BN20 and QLQ-C30.

    PubMed

    Chiu, Leonard; Chiu, Nicholas; Zeng, Liang; Zhang, Liying; Popovic, Marko; Chow, Ronald; Lam, Henry; Poon, Michael; Chow, Edward

    2012-12-01

    The objective of this study is to compare the differences in quality of life (QoL) as assessed by the QLQ-BN20 and QLQ-C30 in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted over the OvidSP platform in MEDLINE (1980-2012) and EMBASE (1980-2012). Studies in which the QLQ-BN20 was used as a QoL assessment for patients with malignant brain tumors (either metastatic or primary) were included in the study. Articles were included if they reported scores of at least one subscale of the QLQ-C30 or QLQ-BN20. The weighted means of the QLQ-BN20 and QLQ-C30 subscales were calculated based on sample size for included studies. Weighted analysis of variance was conducted to compare these scores in primary and metastatic brain patients. A p-value of < 0.05 was considered statistically significant. A total of 14 studies (16 arms: three brain metastases and 13 primary brain tumors) were identified and included in the data analysis. Fifteen of the 16 arms included QLQ-C30 scores along with QLQ-BN20 scores. Performance status of patients in both cohorts was similar. Patients with primary brain tumors and brain metastases had the following findings: physical functioning (weighted mean: 79.18 vs 74.93), global QoL (61.88 vs 59.44), role functioning (67.37 vs 75.00) and emotional functioning (70.44 vs 71.86); but none of them were statistically significantly different. Only cognitive functioning from the QLQ-C30 was significantly worse in patients with primary brain tumors (p-value = 0.0199). Despite cognitive function being significantly worse in patients with primary brain tumors, patients with metastatic brain tumors and patients with primary brain tumors have very similar QoL profiles. The study is limited by the large discrepancy in cohort sizes (1260 patients with primary brain cancer vs 183 patients with brain metastases) and the lack of clinical data.

  4. The modern brain tumor operating room: from standard essentials to current state-of-the-art.

    PubMed

    Barnett, Gene H; Nathoo, Narendra

    2004-01-01

    It is just over a century since successful brain tumor resection. Since then the diagnosis, imaging, and management of brain tumors have improved, in large part due to technological advances. Similarly, the operating room (OR) for brain tumor surgery has increased in complexity and specificity with multiple forms of equipment now considered necessary as technical adjuncts. It is evident that the theme of minimalism in combination with advanced image-guidance techniques and a cohort of sophisticated technologies (e.g., robotics and nanotechnology) will drive changes in the current OR environment for the foreseeable future. In this report we describe what may be regarded today as standard essentials in an operating room for the surgical management of brain tumors and what we believe to be the current 'state-of-the-art' brain tumor OR. Also, we speculate on the additional capabilities of the brain tumor OR of the near future. PMID:15527078

  5. Blood-tissue barrier of human brain tumors: correlation of scintigraphic and ultrastructural finding: concise communication

    SciTech Connect

    Front, D.; Israel, O.; Kohn, S.; Nir, I.

    1984-04-01

    Through the first 2 hr, uptake of (Tc-99m)pertechnetate and of Co-57 bleomycin were assessed in 29 brain tumors and were correlated with the ultrastructure of the tumor's capillary endothelium. No difference in uptake was found between the two tracers. Permeability of brain tumors to these agents was found to be governed by the same ultrastructural features that determine permeability in experimental brain tumors: the type of junction between contiguous endothelial cells in the capillaries. That uptake of (Tc-99m)pertechnetate and of Co-57 bleomycin depends on tumor capillary ultrastructure (which determines the permeability) suggests the possibility of the use of radiopharmaceuticals as in vivo indicators of tumor permeability. Brain scintigraphy may help to assess brain-tumor availability to non-lipid-soluble chemotherapeutic drugs.

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

    PubMed

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

    2015-10-14

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

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

    PubMed Central

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

    2016-01-01

    Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a non-destructive, label-free optical method, to reveal glioma infiltration in animal models. Here we show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ=0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density and protein:lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density and protein:lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Importantly, quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery. PMID:26468325

  8. Primary retroperitoneal mucinous tumors: a clinicopathologic study of 18 cases.

    PubMed

    Roma, Andres Anibal; Malpica, Anais

    2009-04-01

    Primary retroperitoneal mucinous tumors (PRMTs) are uncommon neoplasms occurring almost exclusively in women. PRMTs are divided into mucinous cystadenoma (MC), mucinous borderline tumors or tumors of low malignant potential (MLMP), and mucinous carcinomas (MCas). In this retrospective study, we present the clinicopathologic features of 18 such cases, the largest series to date. All patients were women, ranging in age from 20 to 63 years (mean 38.6 y). All except 2 patients presented with an enlarged mass during a routine examination or by self-palpation. All tumors were located exclusively in the retroperitoneum, with histologic or clinical confirmation of the lack of ovarian involvement. The tumors ranged from 7 to 26 cm (mean 13.2 cm). The gross appearance was variable: unilocular cyst with a thin wall (4 cases), predominantly cystic with papillary areas or nodule(s) (8 cases), multiloculated cyst with or without nodules (1 case each), and predominantly solid with cystic areas (4 cases). Histologically, there were 2 cases of MC, 7 of MLMP (7 cases; 3 of them with intraepithelial carcinoma and 1 with microinvasion), and 9 of MCas (9 cases, 5 of them associated with MLMP and 1 associated with MC). Three of the MCas had areas of anaplastic or sarcomatoid carcinoma whereas 1 had an associated sarcoma. Immunohistochemical studies were performed in 6 cases. Cytokeratin 7 was diffusely positive in all cases studied, whereas cytokeratin 20 and cytokeratin 17 were focally positive in 4 and 2 cases, respectively. All patients underwent surgical resection of the entire tumor. Two patients with MCa and sarcoma or sarcomatoid carcinoma received chemotherapy. Follow-up was available in 16 cases, ranging from 1 to 148 months (mean 40 mo, median 22 mo). Two patients died of disease at 5 and 9 months; both had MCa with anaplastic carcinoma or sarcoma. Three patients with MCa were alive with disease at 14, 26, and 58 months. The remaining patients were alive with no evidence of

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

    SciTech Connect

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

    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

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

    MedlinePlus

    ... brain and spinal cord tumors in children What’s new in research and treatment for brain and spinal ... an investigational method, and studies are continuing. Other new treatment strategies Researchers are also testing some newer ...

  11. Is outpatient brain tumor surgery feasible in India?

    PubMed

    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. PMID:27625225

  12. Integrated proteomic platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors: a preliminary study.

    PubMed

    Martelli, Claudia; Iavarone, Federica; D'Angelo, Luca; Arba, Morena; Vincenzoni, Federica; Inserra, Ilaria; Delfino, Daniela; Rossetti, Diana Valeria; Caretto, Marta; Massimi, Luca; Tamburrini, Gianpiero; Di Rocco, Concezio; Caldarelli, Massimo; Messana, Irene; Castagnola, Massimo; Sanna, Maria Teresa; Desiderio, Claudia

    2015-06-01

    A top-down/bottom-up integrated proteomic approach based on LC-MS and 2-DE analysis was applied for comparative characterization of medulloblastoma and pilocytic astrocytoma posterior cranial fossa pediatric brain tumor tissues. Although rare, primary brain tumors are the most frequent solid tumors in the pediatric age. Among them the medulloblastoma is the prevalent malignant tumor in childhood while pilocytic astrocytoma is the most common, rarely showing a malignant progression. Due to the limited availability of this kind of sample, the study was applied to pooled tumor tissues for a preliminary investigation. The results showed different proteomic profiles of the two tumors and evidenced interesting differential expression of several proteins and peptides. Top-down proteomics of acid-soluble fractions of brain tumor homogenates ascribed a potential biomarker role of malignancy to β- and α-thymosins and their truncated proteoforms and to C-terminal truncated (des-GG) ubiquitin, resulting exclusively detected or over-expressed in the highly malignant medulloblastoma. The bottom-up proteomics of the acid-soluble fraction identified several proteins, some of them in common with 2-DE analysis of acid-insoluble pellets. Peroxiredoxin-1, peptidyl-prolyl cis-trans isomerase A, triosephosphate isomerase, pyruvate kinase PKM, tubulin beta and alpha chains, heat shock protein HSP-90-beta and different histones characterized the medulloblastoma while the Ig kappa chain C region, serotransferrin, tubulin beta 2A chain and vimentin the pilocytic astrocytoma. The two proteomic strategies, with their pros and cons, well complemented each other in characterizing the proteome of brain tumor tissues and in disclosing potential disease biomarkers to be validated in a future study on individual samples of both tumor histotypes. PMID:25909245

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

    PubMed

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

    2016-02-01

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

  14. The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors.

    PubMed

    Alexiou, George A; Vartholomatos, George; Stefanaki, Kalliopi; Lykoudis, Efstathios G; Patereli, Amalia; Tseka, Georgia; Tzoufi, Meropi; Sfakianos, George; Prodromou, Neofytos

    2015-01-01

    Cell cycle analysis by flow cytometry has not been adequately studied in pediatric brain tumors. We investigated the value of a modified rapid (within 6 min) cell cycle analysis protocol for the characterization of malignancy of pediatric brain tumors and for the differentiation of neoplastic from nonneoplastic tissue for possible intraoperative application. We retrospectively studied brain tumor specimens from patients treated at our institute over a 5-year period. All tumor samples were histopathologically verified before flow-cytometric analysis. The histopathological examination of permanent tissue sections was the gold standard. There were 68 brain tumor cases. All tumors had significantly lower G0/G1 and significantly higher S phase and mitosis fractions than normal brain tissue. Furthermore low-grade tumors could be differentiated from high-grade tumors. DNA aneuploidy was detected in 35 tumors. A correlation between S phase fraction and Ki-67 index was found in medulloblastomas and anaplastic ependymomas. Rapid cell cycle analysis by flow cytometry is a promising method for the identification of neoplastic tissue intraoperatively. Low-grade tumors could be differentiated from high-grade tumors. Thus, cell cycle analysis can be a valuable adjunct to the histopathological evaluation of pediatric brain tumors, whereas its intraoperative application warrants further investigation. PMID:26287721

  15. Intraoperative brain tumor resection cavity characterization with conoscopic holography

    NASA Astrophysics Data System (ADS)

    Simpson, Amber L.; Burgner, Jessica; Chen, Ishita; Pheiffer, Thomas S.; Sun, Kay; Thompson, Reid C.; Webster, Robert J., III; Miga, Michael I.

    2012-02-01

    Brain shift compromises the accuracy of neurosurgical image-guided interventions if not corrected by either intraoperative imaging or computational modeling. The latter requires intraoperative sparse measurements for constraining and driving model-based compensation strategies. Conoscopic holography, an interferometric technique that measures the distance of a laser light illuminated surface point from a fixed laser source, was recently proposed for non-contact surface data acquisition in image-guided surgery and is used here for validation of our modeling strategies. In this contribution, we use this inexpensive, hand-held conoscopic holography device for intraoperative validation of our computational modeling approach to correcting for brain shift. Laser range scan, instrument swabbing, and conoscopic holography data sets were collected from two patients undergoing brain tumor resection therapy at Vanderbilt University Medical Center. The results of our study indicate that conoscopic holography is a promising method for surface acquisition since it requires no contact with delicate tissues and can characterize the extents of structures within confined spaces. We demonstrate that for two clinical cases, the acquired conoprobe points align with our model-updated images better than the uncorrected images lending further evidence that computational modeling approaches improve the accuracy of image-guided surgical interventions in the presence of soft tissue deformations.

  16. Pediatric brain tumors in a low/middle income country: does it differ from that in developed world?

    PubMed

    Ezzat, Sameera; Kamal, Mohamed; El-Khateeb, Nada; El-Beltagy, Mohamed; Taha, Hala; Refaat, Amal; Awad, Madeha; Abouelnaga, Sherif; Zaghloul, Mohamed Saad

    2016-01-01

    Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries. PMID:26514358

  17. Pediatric brain tumors in a low/middle income country: does it differ from that in developed world?

    PubMed

    Ezzat, Sameera; Kamal, Mohamed; El-Khateeb, Nada; El-Beltagy, Mohamed; Taha, Hala; Refaat, Amal; Awad, Madeha; Abouelnaga, Sherif; Zaghloul, Mohamed Saad

    2016-01-01

    Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries.

  18. Rare Primary Central Nervous System Tumors Encountered in Pediatrics.

    PubMed

    Kramer, Kim

    2016-10-01

    As part of the special issue on Pediatric Neuro-Oncology, this article will focus on 4 of the rarer tumors in this spectrum, including atypical teratoid rhabdoid tumors, embryonal tumors with multilayered rosettes, choroid plexus tumors, and pleomorphic xanthoastrocytoma. Incidence and current understanding of the molecular pathogenesis of these tumors are discussed, and avenues of therapy both current and prospective are explored.

  19. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    PubMed

    Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David; Kozielski, Kristen L; Kim, Jennifer E; Seng, Michael; Abbadi, Sara; Schiapparelli, Paula; Sarabia-Estrada, Rachel; Vescovi, Angelo; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J; Quinones-Hinojosa, Alfredo

    2016-09-01

    There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies. PMID:27240162

  20. Gonadal status in male survivors following childhood brain tumors.

    PubMed

    Schmiegelow, M; Lassen, S; Poulsen, H S; Schmiegelow, K; Hertz, H; Andersson, A M; Skakkebaek, N E; Müller, J

    2001-06-01

    correlation between inhibin B and total testicular volume (r(s) = 0.63; P < 0.0001). Stepwise backward multiple linear regression analysis showed the best-fit model to predict inhibin B levels included total testicular volume (P = 0.002) and CT (P = 0.09). Median basal LH in the RT-only group was significantly lower, compared with controls (3.44 vs. 2.45 IU/L; P = 0.0001) indicating secondary hypogonadism, and in both the RT + CT group and the RT-only group, levels of testosterone were significantly lower, compared with our reference population (12.8 vs. 21.9 nmol/L; P = 0.001, and 14.7 vs. 21.9 nmol/L; P = 0.0003), respectively. In conclusion these data suggest that cranial irradiation for a childhood brain tumor may affect the HP axis, and adjuvant CT can reduce inhibin B indicating primary gonadal damage. Thus, such patients may have normal or even low levels of FSH despite damage to the seminiferous epithelium, and because the fertility status by a semen analysis for psychological reasons can be difficult to obtain in this group of patients, we suggest inhibin B as the most useful direct serum marker of spermatogenesis in the follow-up of individuals who have received both cranial irradiation and gonadotoxic chemotherapy. However, because the number of patients with RT + CT and RT only are small, these data must be confirmed in further studies.

  1. CT and angiography of primary extradural juxtasellar tumors

    SciTech Connect

    Moore, T.; Ganti, S.R.; Mawad, M.E.; Hilal, S.K.

    1985-09-01

    The computed tomographic and angiographic features of 15 histologically proven primary extradural juxtasellar tumors were retrospectively reviewed. Five chordomas were characterized by prominent bone erosion and a significant posterior fossa component. Four trigeminal nerve neuromas each demonstrated bone erosion centered about Meckel's cave and moderate to marked contrast enhancement. Two cavernous sinus meningiomas revealed moderate contrast enhancement, expansion of the cavernous sinus, and moderate angiographic stain. Two cavernous hemangiomas of the cavernous sinus were intensely enhancing and demonstrated angiographic stain. Opacification of the sphenoid sinus with prominent bone destruction and lack of contrast enhancement was characteristic of a sphenoid sinus mucocele. The dural reflection could be directly visualized or indirectly inferred in each case.

  2. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    PubMed

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

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

    SciTech Connect

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

    2008-03-15

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

  4. Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors.

    PubMed

    Nobusawa, Sumihito; Hirato, Junko; Sugai, Tsutomu; Okura, Naoki; Yamazaki, Tatsuya; Yamada, Seiji; Ikota, Hayato; Nakazato, Yoichi; Yokoo, Hideaki

    2016-02-01

    Atypical teratoid/rhabdoid tumors (AT/RT) are rare, aggressive, embryonal brain tumors that occur most frequently in very young children; they are characterized by rhabdoid cells and loss of INI1 protein nuclear expression. Here, we report the case of a 24-year-old man with a left frontal lobe tumor that was composed mainly of rhabdoid cells showing loss of INI1 nuclear reactivity and polyphenotypic immunohistochemical expression, with a small INI1-positive component of ependymoma. Array comparative genomic hybridization separately conducted for each histologically distinct component revealed 22 shared identical copy number alterations, including loss of heterozygosity of chromosome 22q containing the INI1 locus. Furthermore, we found the C11orf95-RELA fusion gene, the genetic hallmark of supratentorial ependymomas, not only in the ependymoma component but also in the AT/RT component by fluorescence in situ hybridization analysis, suggesting that the AT/RT cells secondarily progressed from the preexisting ependymoma cells. A second genetic inactivating event in the INI1 gene was not detected in the AT/RT component. There are several reported cases of AT/RT (or INI1-negative rhabdoid tumors) arising in the setting of other primary brain tumors (gangliogliomas, pleomorphic xanthoastrocytomas, and high-grade gliomas), but the present case PMID:26769252

  5. Pattern of primary tumors and tumor-like lesions of bone in children: retrospective survey of biopsy results

    PubMed Central

    Özkan, Esra Akyüz; Göret, Ceren Canbey; Özdemir, Zeynep Tuğba; Yanık, Serdar; Doğan, Meryem; Gönültaş, Aylin; Akkoca, Ayşe Neslin

    2015-01-01

    Background: Although primary bone tumors are relatively uncommon, they constitute the most important tumors in patients less than 20 years. We aimed to determine the frequencies of primary bone tumors and tumor-like lesions of bone and the anatomical sites of their occurrence. Methods: A retrospective review of histopathology reports of all bone specimens received in a private pathology laboratory in Istanbul between 2009 and 2015. Results: A total of 57 patients (aged 5 to 18 years) with a mean of 13.12 years were studied. Thirty five patients (61.4%) were males and 22 (38.6%) were females. Fifty five (94.4%) of the tumors were benign. Osteochondroma was the commonest tumor accounting for 31 cases (54.3%) followed by osteoid osteoma, 9 cases (15.7%). Chondrosarcoma observed in two patients and Ewing sarcoma in one patient as malignant tumors. Of the 57 bone tumors 13 (22.8%) occurred in the upper extremities, while 44 (77.2%) were in the lower extremities. Proximal humerus was the most commonly involved site in upper extremity tumors, with osteochondromas representing the most frequent type of tumor (4 patients; 7%). In the lower extremities again osteochondromas were the most common type of tumor (8 cases, 14%), with the femur being the most common site of involvement (18 patients, 31.5%). Of the patients with tumor-like lesions; four patients had fibrous dysplasia, 4 patients had non-ossified fibromas, 4 patients had simple bone cysts and 3 had aneurismal bone cyst. Conclusion: This study showed that primary bone tumors were mainly benign, settled predominantly in the lower extremities mostly in the femur with a male preponderance. Osteochondroma was the most common benign bone tumor. We didn’t observed osteosarcoma, which is the most frequent malignant bone tumor. PMID:26617888

  6. Cognitive dysfunction in children with brain tumors at diagnosis

    PubMed Central

    Studer, Martina; Ritter, Barbara Catherine; Steinlin, Maja; Leibundgut, Kurt; Heinks, Theda

    2015-01-01

    Background Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo‐ and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS). Methods Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1–16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self‐report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status. Results Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement. Conclusion Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school. Pediatr Blood Cancer 2015;62:1805–1812. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc. PMID:26053691

  7. Household pesticides and risk of pediatric brain tumors.

    PubMed Central

    Pogoda, J M; Preston-Martin, S

    1997-01-01

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

  8. Collective behavior of brain tumor cells: The role of hypoxia

    NASA Astrophysics Data System (ADS)

    Khain, Evgeniy; Katakowski, Mark; Hopkins, Scott; Szalad, Alexandra; Zheng, Xuguang; Jiang, Feng; Chopp, Michael

    2011-03-01

    We consider emergent collective behavior of a multicellular biological system. Specifically, we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. In the first set of experiments, cell migration away from a tumor spheroid was investigated. The second set of experiments was performed in a typical wound-healing geometry: Cells were placed on a substrate, a scratch was made, and cell migration into the gap was investigated. Experiments show a surprising result: Cells under normal and hypoxic conditions have migrated the same distance in the “spheroid” experiment, while in the “scratch” experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.

  9. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary. PMID:23022824

  10. Accumulation of silver nanoparticles by cultured primary brain astrocytes

    NASA Astrophysics Data System (ADS)

    Luther, Eva M.; Koehler, Yvonne; Diendorf, Joerg; Epple, Matthias; Dringen, Ralf

    2011-09-01

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO3 already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  11. Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy.

    PubMed

    Morrone, Fernanda B; Gehring, Marina P; Nicoletti, Natália F

    2016-09-01

    Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca(2+) by modulating the driving force for Ca(2+) entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca(2+)-influx and an indirect activator of voltage-gated Ca(2+)-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca(2+), and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas. PMID:27418672

  12. Magnetic resonance spectroscopy for detection of choline kinase inhibition in the treatment of brain tumors

    PubMed Central

    Kumar, Manoj; Arlauckas, Sean P.; Saksena, Sona; Verma, Gaurav; Ittyerah, Ranjit; Pickup, Stephen; Popov, Anatoliy V.; Delikatny, Edward J.; Poptani, Harish

    2015-01-01

    Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both pre-clinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines. In vivo MRS studies of rats with intra-cranial F98-derived brain tumors showed a significant decrease in tumor total choline concentration after treatment with MN58b. High resolution MRS of tissue extracts confirmed that this decrease was due to a significant reduction in phosphocholine. Concomitantly, a significant increase in poly-unsaturated lipid resonances was also observed in treated tumors, indicating apoptotic cell death. Magnetic resonance imaging (MRI) based volume measurements demonstrated a significant growth arrest in the MN58b-treated tumors in comparison to saline-treated controls. Histologically, MN58b-treated tumors showed decreased cell density, as well as increased apoptotic cells. These results suggest that inhibition of choline kinase can be used as an adjuvant to chemotherapy in the treatment of brain tumors and that decreases in total choline observed by MRS can be used as an effective phamacodynamic biomarker of treatment response. PMID:25657334

  13. Current and future strategies for the treatment of malignant brain tumors.

    PubMed

    Castro, M G; Cowen, R; Williamson, I K; David, A; Jimenez-Dalmaroni, M J; Yuan, X; Bigliari, A; Williams, J C; Hu, J; Lowenstein, P R

    2003-04-01

    Glioblastoma (GB) is the most common subtype of primary brain tumor in adults. These tumors are highly invasive, very aggressive, and often infiltrate critical neurological areas within the brain. The mean survival time after diagnosis of GB has remained unchanged during the last few decades, in spite of advances in surgical techniques, radiotherapy, and also chemotherapy; patients' survival ranges from 9 to 12 months after initial diagnosis. In the same time frame, with our increasing understanding and knowledge of the physiopathology of several cancers, meaningful advances have been made in the treatment and control of several cancers, such as breast, prostate, and hematopoietic malignancies. Although a number of the genetic lesions present in GB have been elucidated and our understanding of the progressions of this cancer has increased dramatically over the last few years, it has not yet been possible to harness this information towards developing effective cures. In this review, we will focus on the classical ways in which GB is currently being treated, and will introduce a novel therapeutic modality, i.e., gene therapy, which we believe will be used in combination with classical treatment strategies to prolong the life-span of patients and to ultimately be able to control and/or cure these brain tumors. We will discuss the use of several vector systems that are needed to introduce the therapeutic genes within either the tumor mass, if these are not resectable, or the tumor bed, after successful tumor resection. We also discuss different therapeutic modalities that could be exploited using gene therapy, i.e., conditional cytotoxic approach, direct cytotoxicity, immunotherapy, inhibition of angiogenesis, and the use of pro-apoptotic genes. The advantages and disadvantages of each of the current vector systems available to transfer genes into the CNS are also discussed. With the advances in molecular techniques, both towards the elucidation of the physiopathology

  14. Impedance spectroscopy--an outstanding method for label-free and real-time discrimination between brain and tumor tissue in vivo.

    PubMed

    Jahnke, Heinz-Georg; Heimann, Axel; Azendorf, Ronny; Mpoukouvalas, Konstantinos; Kempski, Oliver; Robitzki, Andrea A; Charalampaki, Patra

    2013-08-15

    Until today, brain tumors especially glioblastoma are difficult to treat and therefore, results in a poor survival rate of 0-14% over five years. To overcome this problem, the development of novel therapeutics as well as optimization of neurosurgical procedures to remove the tumor tissue are subject of intensive research. The main problem of the tumor excision, as the primary clinical intervention is the diffuse infiltration of the tumor cells in unaltered brain tissue that complicates the complete removal of residual tumor cells. In this context, we are developing novel approaches for the label-free discrimination between tumor tissue and unaltered brain tissue in real-time during the surgical process. Using our impedance spectroscopy-based measurement system in combination with flexible microelectrode arrays we could successfully demonstrate the discrimination between a C6-glioma and unaltered brain tissue in an in vivo rat model. The analysis of the impedance spectra revealed specific impedance spectrum shape characteristics of physiologic neuronal tissue in the frequency range of 10-500 kHz that were significantly different from the tumor tissue. Moreover, we used an adapted equivalent circuit model to get a deeper understanding for the nature of the observed effects. The impedimetric label-free and real-time discrimination of tumor from unaltered brain tissue offers the possibility for the implementation in surgical instruments to support surgeons to decide, which tissue areas should be removed and which should be remained.

  15. Low Level Primary Blast Injury in Rodent Brain

    PubMed Central

    Pun, Pamela B. L.; Kan, Enci Mary; Salim, Agus; Li, Zhaohui; Ng, Kian Chye; Moochhala, Shabbir M.; Ling, Eng-Ang; Tan, Mui Hong; Lu, Jia

    2011-01-01

    The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure (BOP) exposure of either 48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross histopathology of the brains showed that cortical neurons were “darkened” and shrunken with narrowed vasculature in the cerebral cortex day 1 after blast with signs of recovery at day 4 and day 7 after blast. TUNEL-positive cells were predominant in the white matter of the brain at day 1 after blast and double-labeling of brain tissue showed that these DNA-damaged cells were both oligodendrocytes and astrocytes but were mainly not apoptotic due to the low caspase-3 immunopositivity. There was also an increase in amyloid precursor protein immunoreactive cells in the white matter which suggests acute axonal damage. In contrast, Iba-1 staining for macrophages or microglia was not different from control post-blast. Blast exposure altered the expression of over 5786 genes in the brain which occurred mostly at day 1 and day 4 post-blast. These genes were narrowed down to 10 overlapping genes after time-course evaluation and functional analyses. These genes pointed toward signs of repair at day 4 and day 7 post-blast. Our findings suggest that the BOP levels in the study resulted in mild cellular injury to the brain as evidenced by acute neuronal, cerebrovascular, and white matter perturbations that showed signs of resolution. It is unclear whether these perturbations exist at a milder level or normalize completely and will need more investigation. Specific changes in gene expression may be further evaluated to understand the mechanism of blast-induced neurotrauma. PMID

  16. Neuropsychological assessment of individuals with brain tumor: comparison of approaches used in the classification of impairment.

    PubMed

    Dwan, Toni Maree; Ownsworth, Tamara; Chambers, Suzanne; Walker, David G; Shum, David H K

    2015-01-01

    Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains, or global index) and source of reference (i.e., norms, controls, and pre-morbid functioning). This study aimed to compare rates of impairment according to different classification approaches. Participants were 44 individuals (57% female) with a primary brain tumor diagnosis (mean age = 45.6 years) and 44 matched control participants (59% female, mean age = 44.5 years). All participants completed a test battery that assesses pre-morbid IQ (Wechsler adult reading test), attention/processing speed (digit span, trail making test A), memory (Hopkins verbal learning test-revised, Rey-Osterrieth complex figure-recall), and executive function (trail making test B, Rey-Osterrieth complex figure copy, controlled oral word association test). Results indicated that across the different sources of reference, 86-93% of participants were classified as impaired at a test-specific level, 61-73% were classified as impaired at a domain-specific level, and 32-50% were classified as impaired at a global level. Rates of impairment did not significantly differ according to source of reference (p > 0.05); however, at the individual participant level, classification based on estimated pre-morbid IQ was often inconsistent with classification based on the norms or controls. Participants with brain tumor performed significantly poorer than matched controls on tests of neuropsychological functioning, including executive function (p = 0.001) and memory (p < 0.001), but not attention/processing speed (p > 0.05). These results highlight the need to examine individuals' performance across a multi-faceted neuropsychological test battery to avoid over- or under-estimation of impairment.

  17. Neuropsychological Assessment of Individuals with Brain Tumor: Comparison of Approaches Used in the Classification of Impairment

    PubMed Central

    Dwan, Toni Maree; Ownsworth, Tamara; Chambers, Suzanne; Walker, David G.; Shum, David H. K.

    2015-01-01

    Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains, or global index) and source of reference (i.e., norms, controls, and pre-morbid functioning). This study aimed to compare rates of impairment according to different classification approaches. Participants were 44 individuals (57% female) with a primary brain tumor diagnosis (mean age = 45.6 years) and 44 matched control participants (59% female, mean age = 44.5 years). All participants completed a test battery that assesses pre-morbid IQ (Wechsler adult reading test), attention/processing speed (digit span, trail making test A), memory (Hopkins verbal learning test-revised, Rey–Osterrieth complex figure-recall), and executive function (trail making test B, Rey–Osterrieth complex figure copy, controlled oral word association test). Results indicated that across the different sources of reference, 86–93% of participants were classified as impaired at a test-specific level, 61–73% were classified as impaired at a domain-specific level, and 32–50% were classified as impaired at a global level. Rates of impairment did not significantly differ according to source of reference (p > 0.05); however, at the individual participant level, classification based on estimated pre-morbid IQ was often inconsistent with classification based on the norms or controls. Participants with brain tumor performed significantly poorer than matched controls on tests of neuropsychological functioning, including executive function (p = 0.001) and memory (p < 0.001), but not attention/processing speed (p > 0.05). These results highlight the need to examine individuals’ performance across a multi-faceted neuropsychological test battery to avoid over- or under-estimation of impairment. PMID:25815271

  18. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease. PMID:24096737

  19. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease.

  20. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea

    SciTech Connect

    Perantoni, A.O.; Rice, J.M.; Reed, C.D.; Watatani, M.; Wenk, M.L.

    1987-09-01

    Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). The authors prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and form schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogen was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified in cultured cell lines derived from EtNU-induced neurogenic tumors appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain.

  1. Imaging features of primary tumors of the spine: A pictorial essay

    PubMed Central

    Patnaik, Sujata; Jyotsnarani, Y; Uppin, Shantiveer G; Susarla, Rammurti

    2016-01-01

    Primary tumors of spine are rare accounting for less than 5% of new bone tumors diagnosed every year. These tumors may exhibit characteristic imaging features that can help in early diagnosis and improved prognosis. Plasmacytoma/multiple myeloma and lymphoproliferative tumors are the most common malignant primary spinal tumors. Hemangioma is the most common benign tumor of the spine. Computed tomography is useful to assess tumor matrix and osseous change. Magnetic resonance is useful to study associated soft tissue extension, marrow infiltration, and intraspinal extension. Confusing one tumor with the other based on only imaging findings is not uncommon. However, radiologic manifestations of these tumors need to be correlated with the age, sex, location, and presentation to arrive at a close clinical diagnosis. PMID:27413280

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

    PubMed

    Angeli, Stelios; Stylianopoulos, Triantafyllos

    2016-06-14

    Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35% spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning. PMID:27086116

  3. Trends and Outcomes in the Treatment of Gliomas Based on Data during 2001–2004 from the Brain Tumor Registry of Japan

    PubMed Central

    NARITA, Yoshitaka; SHIBUI, Soichiro

    2015-01-01

    The committee of Brain Tumor Registry of Japan (BTRJ) was founded in 1973 and conducts surveys and analyses of incidence, therapeutic methods, and treatment outcomes of primary and metastatic brain tumors with the cooperation of the Japan Neurosurgical Society members. Newly diagnosed 3,000–4,000 primary brain tumors and 600–1,000 brain metastases patients were enrolled in each year. This report describes the trends and treatment outcomes of gliomas from BTRJ volume 13, including 13,431 patients with primary brain tumors who newly started treatment from 2001 to 2004. Data from 382 diffuse astrocytomas (DAs), 121 oligodendrogliomas (OLs), 90 oligoastrocytomas (OAs), 513 anaplastic astrocytomas (AAs), 126 anaplastic oligodendrogliomas (AOs), 106 anaplastic oligoastrocytomas (AOAs), and 1,489 glioblastomas (GBMs) were analyzed for overall survival (OS) and progression free survival (PFS) depending on age, symptoms, Karnofsky performance status, location of the tumor, extent of resection (EOR), initial radiotherapy and chemotherapy. The 5-year PFS rates of the patients with DA, OL + OA, AA, AO + AOA, and GBM were 57.0%, 74.6%, 28.7%, 54.0%, and 9.2%, and the 5-year OS rates were 75.0%, 90.0%, 41.1%, 68.2%, and 10.1%, respectively. Higher EOR ≥ 75% in DA and OL + OA and that ≥ 50% in AA, AO + AOA, and GBM significantly prolonged OS. Complications and cause of death were also reported. BTRJ had been edited for all the patients, researchers, and especially for clinicians at bedside to give useful information about brain tumors and to contribute to the advances in brain tumor treatment. This report revealed various clinical problematic issues pertaining to the diagnosis and treatment of gliomas. PMID:25797780

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  6. Second primary tumors following radiotherapy for childhood cancer

    SciTech Connect

    Hawkins, M.M. )

    1990-11-01

    Among a cohort of 9,279 survivors of childhood neoplasms other than retinoblastoma treated in Britain before 1980, the cumulative risk of a second primary tumor (SPT) by 25 years from 3-year survival was 3.7%. This corresponds to about five times the number expected from rates of cancer occurring in the general population. In the absence of both radiotherapy and chemotherapy, there was four times the expected number of subsequent cancers. The risk of an SPT associated with radiotherapy but not chemotherapy and both radiotherapy and chemotherapy were 6 and 9 times that expected, respectively. There is evidence that radiotherapy was involved in the development of many of the SPT's observed. However, case-control investigations are required to examine the relationship between relative risk of an SPT and therapy in detail. Secondary leukemia appears to occur more frequently among more recently diagnosed children with cancer. It is important to continue to monitor the occurrence of SPT's with a view to identifying the least carcinogenic therapies that are consistent with not compromising survival prospects.

  7. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

    PubMed Central

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-01-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10. PMID:27022231

  8. The protons of space and brain tumors: I. Clinical and dosimetric considerations

    SciTech Connect

    Dalrymple, G.V.; Nagle, W.A.; Moss, A.J.; Cavin, L.A.; Broadwater, J.R.; McGuire, E.L.; Eason, C.S. ); Mitchell, J.C.; Hardy, K.A.; Wood, D.H.; and others

    1989-05-15

    Almost 25 years ago a large group of Rhesus monkeys were irradiated with protons (32--2300 MeV). The experiments were designed: (1) To estimate the RBE of protons, {bold per} {bold se}, and (2) To provide some estimate of the hazards of the radiation environment of space. The initial results showed the RBE to be about 1.0 for acute radiation effects (mortality, hematologic changes, etc). The colony has been maintained at Brooks AFB, TX since irradiation. The survivors of 55 MeV proton irradiation have developed a very high incidence of Glioblastoma multiforme, a highly malignant primary brain tumor. These tumors appeared 1--20 yrs after surface doses of 400--800 rads. Reconstruction of the dosimetry suggests that some areas within the brain may have received doses of 1500--2500 rads. More than 30 radiation induced Glioblastomas have been reported in human patients who had received therapeutic head irradiation. The radiation doses required to induce Glioblastoma were of the same order of magnitude as required to induce Glioblastoma in the Rhesus monkey.

  9. The protons of space and brain tumors: I. Clinical and dosimetric considerations

    NASA Astrophysics Data System (ADS)

    Dalrymple, G. V.; Nagle, W. A.; Moss, A. J.; Cavin, L. A.; Broadwater, J. R.; McGuire, E. L.; Eason, C. S.; Mitchell, J. C.; Hardy, K. A.; Wood, D. H.; Salmon, Y. A.; Yochmowitz, M. G.

    1989-05-01

    Almost 25 years ago a large group of Rhesus monkeys were irradiated with protons (32-2300 MeV). The experiments were designed: 1) To estimate the RBE of protons, per se, and 2) To provide some estimate of the hazards of the radiation environment of space. The initial results showed the RBE to be about 1.0 for acute radiation effects (mortality, hematologic changes, etc). The colony has been maintained at Brooks AFB, TX since irradiation. The survivors of 55 MeV proton irradiation have developed a very high incidence of Glioblastoma multiforme, a highly malignant primary brain tumor. These tumors appeared 1-20 yrs after surface doses of 400-800 rads. Reconstruction of the dosimetry suggests that some areas within the brain may have received doses of 1500-2500 rads. More than 30 radiation induced Glioblastomas have been reported in human patients who had received therapeutic head irradiation. The radiation doses required to induce Glioblastoma were of the same order of magnitude as required to induce Glioblastoma in the Rhesus monkey.

  10. Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

    PubMed

    Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

    2016-08-01

    Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making. PMID:27476845

  11. Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

    PubMed

    Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

    2016-08-01

    Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

  12. Regional blood-to-tissue transport in RT-9 brain tumors.

    PubMed

    Molnar, P; Blasberg, R G; Horowitz, M; Smith, B; Fenstermacher, J

    1983-06-01

    Regional blood-to-tissue transport, expressed as a unidirectional transfer rate constant (K), was measured in experimental RT-9 brain tumors using 14C-alpha-aminoisobutyric acid (AIB) and quantitative autoradiographic techniques. The magnitude of K depends on the permeability, surface area, and blood flow of the tissue capillaries. The transfer rate constant was variable within tumor tissue (range 0.001 to 0.178 ml/gm/min) and depended on tumor size, location (intraparenchymal, meningeal, or choroid plexus associated), and to a lesser extent on necrosis and cyst formation. Brain adjacent to tumor had higher K values, particularly around larger tumors (0.004 to 0.014 ml/gm/min), than corresponding brain regions in the contralateral hemisphere (0.001 to 0.002 ml/gm/min). Estimates of the fractional extraction of AIB by intraparenchymal tumors were between 0.008 and 0.4 ml/gm/min. Values of fractional extraction in this range indicate that tumor capillaries are not freely permeable to this solute. The values of K measured with AIB in this study, for the most part, approximate the permeability-surface area product of tumor and brain capillaries. The experimental data suggest that the permeability-surface area characteristics of the microvasculature in small RT-9 tumors are similar to those of the host tissue, whereas the microvasculature of larger RT-9 tumors is influenced more by intrinsic tumor factors.

  13. Evaluation of Organs at Risk’s Dose in External Radiotherapy of Brain Tumors

    PubMed Central

    Nazemi-Gelyan, Hamideh; Hasanzadeh, Hadi; Makhdumi, Yasha; Abdollahi, Sara; Akbari, Fatemeh; Varshoee-Tabrizi, Fatemeh; Almasrou, Hamzeh; Nikoofar, Alireza; Rezaei-Tavirani, Mostafa

    2015-01-01

    Background Radiotherapy plays an important role in the management of most malignant and many benign primary central nervous system (CNS) tumors. Radiotherapy affects both tumor cells and uninvolved normal cells; so, it is important to estimate absorbed dose to organs at risk in this kind of treatment. The aim of this study was to determine the absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland in frontal lobe brain tumors radiotherapy based on treatment planning system (TPS) calculation and direct measurement on the phantom. Methods A head and neck phantom was constructed using natural human bone and combination of paraffin wax and Sodium Chloride (NaCl) as tissue-equivalent material. Six cylinders were made of phantom material which had cavities to insert Thermoluminescent Dosimeters (TLDs) at several depths in order to measure absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland. Three routine conventional plans associated with tumors of this region and a new purposed technique were performed on the phantom and dose distribution and absorbed dose to critical organs were compared using treatment planning system (TPS) calculation and direct measurement on the phantom. Results Absorbed doses were measured with calibrated TLDs and are expressed in centigray (cGy). In all techniques absorbed dose to all organs except the lenses were at their tolerance dose levels and in the new purposed technique, absorbed dose to chiasma was significantly reduced. Conclusion Our findings showed differences in the range of 1-5% in all techniques between TPS calculation and direct measurements for all organs except submandibular glands and thyroid. Because submandibular glands and thyroid are far from primary radiation field, TLD reading in these regions although small but differs from TPS calculation which shows very smaller doses. This might be due to scattered radiation which is not well considered

  14. Characterization of brain inflammation during primary amoebic meningoencephalitis.

    PubMed

    Cervantes-Sandoval, Isaac; Serrano-Luna, José de Jesús; García-Latorre, Ethel; Tsutsumi, Víctor; Shibayama, Mineko

    2008-09-01

    Naegleria fowleri is a free-living amoeba and the etiologic agent of primary amoebic meningoencephalitis (PAM). Trophozoites reach the brain by penetrating the olfactory epithelium, and invasion of the olfactory bulbs results in an intense inflammatory reaction. The contribution of the inflammatory response to brain damage in experimental PAM has not been delineated. Using both optical and electron microscopy, we analyzed the morphologic changes in the brain parenchyma due to inflammation during experimental PAM. Several N. fowleri trophozoites were observed in the olfactory bulbs 72 h post-inoculation, and the number of amoebae increased rapidly over the next 24 h. Eosinophils and neutrophils surrounding the amoebae were then noted at later times during infection. Electron microscopic examination of the increased numbers of neutrophils and the interactions with trophozoites indicated an active attempt to eliminate the amoebae. The extent of inflammation increased over time, with a predominant neutrophil response indicating important signs of damage and necrosis of the parenchyma. These data suggest a probable role of inflammation in tissue damage. To test the former hypothesis, we used CD38-/- knockout mice with deficiencies in chemotaxis to compare the rate of mortality with the parental strain, C57BL/6J. The results showed that inflammation and mortality were delayed in the knockout mice. Based on these results, we suggest that the host inflammatory response and polymorphonuclear cell lysis contribute to a great extent to the central nervous system tissue damage. PMID:18374627

  15. Characterization of brain inflammation during primary amoebic meningoencephalitis.

    PubMed

    Cervantes-Sandoval, Isaac; Serrano-Luna, José de Jesús; García-Latorre, Ethel; Tsutsumi, Víctor; Shibayama, Mineko

    2008-09-01

    Naegleria fowleri is a free-living amoeba and the etiologic agent of primary amoebic meningoencephalitis (PAM). Trophozoites reach the brain by penetrating the olfactory epithelium, and invasion of the olfactory bulbs results in an intense inflammatory reaction. The contribution of the inflammatory response to brain damage in experimental PAM has not been delineated. Using both optical and electron microscopy, we analyzed the morphologic changes in the brain parenchyma due to inflammation during experimental PAM. Several N. fowleri trophozoites were observed in the olfactory bulbs 72 h post-inoculation, and the number of amoebae increased rapidly over the next 24 h. Eosinophils and neutrophils surrounding the amoebae were then noted at later times during infection. Electron microscopic examination of the increased numbers of neutrophils and the interactions with trophozoites indicated an active attempt to eliminate the amoebae. The extent of inflammation increased over time, with a predominant neutrophil response indicating important signs of damage and necrosis of the parenchyma. These data suggest a probable role of inflammation in tissue damage. To test the former hypothesis, we used CD38-/- knockout mice with deficiencies in chemotaxis to compare the rate of mortality with the parental strain, C57BL/6J. The results showed that inflammation and mortality were delayed in the knockout mice. Based on these results, we suggest that the host inflammatory response and polymorphonuclear cell lysis contribute to a great extent to the central nervous system tissue damage.

  16. 18F-FDG PET and MR Imaging Associations Across a Spectrum of Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

    PubMed Central

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

    2014-01-01

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

  17. Primary Hyperparathyroidism with Extensive Brown Tumors and Multiple Fractures in a 20-Year-Old Woman

    PubMed Central

    Choi, Ju Hee; Kim, Kyoung Jin; Lee, Ye Jin; Kim, Sun Hwa; Kim, Sin Gon; Jung, Kwang Yoon; Choi, Dong Seop

    2015-01-01

    A brown tumor is a benign fibrotic, erosive bony lesion caused by localized, rapid osteoclastic turnover, resulting from hyperparathyroidism. Although brown tumors are one of the most pathognomonic signs of primary hyperparathyroidism, they are rarely seen in clinical practice. In this report, we present a case of 20-year-old woman with recurrent fractures and bone pain. Plain digital radiographs of the affected bones revealed multiple erosive bone tumors, which were finally diagnosed as brown tumors associated with primary hyperparathyroidism due to a parathyroid adenoma. This case shows that multiple, and clinically severe form of brown tumors can even occur in young patients. PMID:26354493

  18. Neonatal vitamin D and childhood brain tumor risk.

    PubMed

    Bhatti, Parveen; Doody, David R; Mckean-Cowdin, Roberta; Mueller, Beth A

    2015-05-15

    Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however, the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (<15 years at diagnosis; born 1991 or later) were identified. A total of 247 birth year-, sex- and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 g), there was evidence of increasing risk of CBT with increasing 25(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (ORs) and 95% confidence intervals (CIs) for the second (7.7-<11.0 ng/mL), third (11.0-<14.7 ng/mL) and fourth (14.7-37.0) quartiles of 25(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CIs for the second, third and fourth quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1, circulating levels of which have been associated with vitamin D and accelerated fetal growth.

  19. CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype.

    PubMed

    Duregon, Eleonora; Senetta, Rebecca; Pittaro, Alessandra; Verdun di Cantogno, Ludovica; Stella, Giulia; De Blasi, Pierpaolo; Zorzetto, Michele; Mantovani, Cristina; Papotti, Mauro; Cassoni, Paola

    2015-10-01

    Brain metastases develop in one-third of patients with non-small-cell lung cancer and are associated with a dismal prognosis, irrespective of surgery or chemo-radiotherapy. Pathological markers for predicting outcomes after surgical resection and radiotherapy responsiveness are still lacking. Caveolin 1 has been associated with chemo- and radioresistance in various tumors, including non-small-cell lung cancer. Here, caveolin 1 expression was assessed in a series of 69 brain metastases from non-small-cell lung cancer and matched primary tumors to determine its role in predicting survival and radiotherapy responsiveness. Only caveolin 1 expression in brain metastasis was associated with poor prognosis and an increased risk of death (log rank test, p = 0.015). Moreover, in the younger patients (median age of <54 years), caveolin 1 expression neutralized the favorable effect of young age on survival compared with the older patients. Among the radiotherapy-treated patients, an increased risk of death was detected in the group with caveolin 1-positive brain metastasis (14 out of 22 patients, HR=6.839, 95% CI 1.849 to 25.301, Wald test p = 0.004). Overall, caveolin 1 expression in brain metastasis from non-small-cell lung cancer is independently predictive of worse outcome and radioresistance and could become an additional tool for personalized therapy in the critical subset of brain-metastatic non-small-cell lung cancer patients.

  20. Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients

    PubMed Central

    Peng, Hao; Chen, Lei; Tang, Ling-Long; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared. PMID:26934649

  1. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

    PubMed

    Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, H K; Philip, M

    1996-01-01

    We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

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

    PubMed

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

    2015-09-20

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

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

    PubMed

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

    2015-09-20

    Pediatric neuro-oncology has undergone an exciting and dramatic transformation during the past 5 years. This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors and survival of patients with these tumors. Advanced genomic analysis of the entire spectrum of pediatric brain tumors has heralded an era in which stakeholders in the pediatric neuro-oncology community are being challenged to reconsider their current research and diagnostic and treatment strategies. The incorporation of this new information into the next-generation treatment protocols will unleash new challenges. This review succinctly summarizes the key advances in our understanding of the common pediatric brain tumors (ie, medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma, and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid tumor and CNS primitive neuroectodermal tumor). The potential impact of this new information on future clinical protocols also is discussed. Cutting-edge genomics technologies and the information gained from such studies are facilitating the identification of molecularly defined subgroups within patients with particular pediatric brain tumors. The number of evaluable patients in each subgroup is small, particularly in the subgroups of rare diseases. Therefore, international collaboration will be crucial to draw meaningful conclusions about novel approaches to treating pediatric brain tumors. PMID:26304884

  4. Primary gonadal damage following treatment of brain tumors in childhood

    SciTech Connect

    Ahmed, S.R.; Shalet, S.M.; Campbell, R.H.; Deakin, D.P.

    1983-10-01

    Gonadal function was studied in two groups of children previously treated for medulloblastoma with surgery followed by postoperative craniospinal irradiation. In group 1 but not in group 2, the children also received adjuvant chemotherapy for one to two years. All children in group 1 received a nitrosourea (BCNU or CCNU), plus vincristine in four and procarbazine in three patients. The nine children in group 1 showed clinical and biochemical evidence of gonadal damage with elevated serum FSH concentrations and, in the boys, small testes for their stage of pubertal development. In group 2 (n . 8), each child had completed pubertal development normally, the boys had adult sized testes and the girls regular menses. Gonadotropin values were normal in all eight children. We conclude that nitrosoureas were responsible for the gonadal damage in the children in group 1, with procarbazine also contributing to the damage in the three children who received this drug. In view of the limited proved value of adjuvant chemotherapy with nitrosoureas in the treatment of medulloblastoma, recognition of this serious complication of cytotoxic drug therapy may necessitate reassessing in which subgroups of children with medulloblastoma the benefits of adjuvant chemotherapy outweigh the complications.

  5. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    Introduction Timely diagnosis of brain tumors could considerably affect the process of patient treatment. To do so, para-clinical methods, particularly MRI, cannot be ignored. MRI has so far answered significant questions regarding tumor characteristics, as well as helping neurosurgeons. In order to detect the tumor cellularity, neuro-surgeons currently have to sample specimens by biopsy and then send them to the pathology unit. The aim of this study is to determine the tumor cellularity in the brain. Methods In this cross-sectional study, 32 patients (18 males and 14 females from 18–77 y/o) were admitted to the neurosurgery department of Shohada-E Tajrish Hospital in Tehran, Iran from April 2012 to February 2014. In addition to routine pulse sequences, T2W Multi echo pulse sequences were taken and the images were analyzed using the MATLAB software to determine the brain tumor cellularity, compared with the biopsy Results These findings illustrate the need for more T2 relaxation time decreases, the higher classes of tumors will stand out in the designed table. In this study, the results show T2 relaxation time with a 85% diagnostic weight, compared with the biopsy, to determine the brain tumor cellularity (p<0.05). Conclusion Our results indicate that the T2 relaxation time feature is the best method to distinguish and present the degree of intra-axial brain tumors cellularity (85% accuracy compared to biopsy). The use of more data is recommended in order to increase the percent accuracy of this techniques. PMID:27757181

  7. [A brain tumor automatic assisted-diagnostic system based on medical image shape analysis].

    PubMed

    Wang, Li-Li; Yang, Jie

    2005-03-01

    This paper covers a brain tumor assisted diagnosis system based on medical image analysis. The system supplements the PACS functions such as display of medical images and database inquiry, segments slice in real-time using the algorithm of fuzzy region competition, extracts shape feature factors such as contour label, compactness, moment, Fourier Descriptor, chord length, radius and other medical data on the brain tumor image with irregular contour feature after segmentation and then feeds to Bayesian network in order to sort the brain tumor for the implementation of automatic assisted diagnosis. PMID:16011110

  8. [Graph-based interactive three-dimensional segmentation of magnetic resonance images of brain tumors].

    PubMed

    Li, Wei; Chen, Wu-fan

    2009-01-01

    We propose a graph-based three-dimensional (3D) algorithm to automatically segment brain tumors from magnetic resonance images (MRI). The algorithm uses minimum s/t cut criteria to obtain a global optimal result of objective function formed according to Markov Random Field Model and Maximum a posteriori (MAP-MRF) theory, and by combining the expectation-maximization (EM) algorithm to estimate the parameters of mixed Gaussian model for normal brain and tumor tissues. 3D segmentation results of brain tumors are fast achieved by our algorithm. The validation of the algorithm was tested and showed good accuracy and adaptation under simple interactions with the physicians. PMID:19218135

  9. [Two Surgical Techniques for Metastatic Brain Tumors:Minimum Resection and Removal with Safety Margin].

    PubMed

    Nakasu, Yoko; Mitsuya, Koichi; Hayashi, Nakamasa; Ito, Ichiro

    2016-03-01

    Successful resection of cerebral metastases is based on good basic neurosurgical techniques, in conjunction with technologies for tumor localization. A clear understanding about the border zone pathology of metastatic lesions leads to two different techniques for safe and effective tumor removal. There is no capsule or pseudocapsule around the metastatic brain tumors. The border zone is widely heterogeneous, especially in lesions after stereotactic irradiation. Resection can be performed in a circumferential and en bloc fashion with sufficient safety margin of the normal brain in non-eloquent area. However, enucleation should be done without surrounding brain damage in and near eloquent areas.

  10. Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement.

    PubMed

    Bui, Loan; Hendricks, Alissa; Wright, Jamie; Chuong, Cheng-Jen; Davé, Digant; Bachoo, Robert; Kim, Young-Tae

    2016-01-01

    Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53-/-, p53-/- PTEN-/-, p53-/- Braf, and p53-/- PTEN-/- Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. PMID:27184621

  11. Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

    PubMed Central

    Bui, Loan; Hendricks, Alissa; Wright, Jamie; Chuong, Cheng-Jen; Davé, Digant; Bachoo, Robert; Kim, Young-tae

    2016-01-01

    Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53−/−, p53−/− PTEN−/−, p53−/− Braf, and p53−/− PTEN−/− Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. PMID:27184621

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  13. Nanoparticle-Mediated Photothermal Therapy of Brain Tumors

    NASA Astrophysics Data System (ADS)

    Makkouk, Amani R.; Madsen, Steen J.

    Nanoparticles (10-1,000 nm diameter) have been investigated for use in numerous diagnostic and therapeutic applications. Gold nanoparticles are particularly appealing due to their biological inertness and the ability to conjugate a wide variety of ligands to their surface. Additionally, their optical properties can be tuned through variations of their size, shape, and composition. For example, gold-silica nanoshells, consisting of a spherical dielectric silica core (100-120 nm diameter) surrounded by a 10-20 nm gold shell, have a strong resonant absorption at approximately 800 nm where light has significant penetration in biological tissues. Following light absorption, surface electrons are photoexcited and the resultant heated electron gas is dissipated to the surrounding medium causing thermal damage. The ability of nanoparticles to convert optical energy to thermal energy makes them ideally suited for photothermal therapy (PTT). This review focuses on the utility of gold-silica nanoshells in PTT of brain tumors. PTT has proven effective in a number of in vitro and in vivo studies. Of particular clinical relevance are results demonstrating PTT efficacy in an orthotopic canine model.

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

    PubMed Central

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

    2016-01-01

    Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments. PMID:26898606

  15. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  16. Total En Bloc Spondylectomy for Primary and Metastatic Spine Tumors.

    PubMed

    Mesfin, Addisu; El Dafrawy, Mostafa H; Jain, Amit; Hassanzadeh, Hamid; Kebaish, Khaled M

    2015-11-01

    This study reports the surgical and clinical outcomes of spinal tumors managed with total en bloc spondylectomy. The authors searched their prospectively maintained database for patients undergoing total en bloc spondylectomy between 2001 and 2013. Ten patients (9 men, 1 woman; average age, 50.7 years; range, 42-68 years) were identified. The authors obtained demographic information, surgical outcomes (estimated blood loss, complications), and clinical outcomes (recurrence, survival). All patients had pain and were classified as American Spinal Injury Association grade E. The lesions were located in the thoracic (8 patients) and lumbar (2 patients) spine. Anterior column reconstruction was performed with strut allograft (7 patients), mesh cage (2 patients), and polymethyl methacrylate (1 patient). An average of 2.3 (range, 2-4) of 6 portions of the vertebrae were involved, according to the Kostuik classification. Mean estimated blood loss, operative time, and hospital stay were 3.5 L, 500 minutes, and 7.8 days, respectively. Perioperative complications included pleural tear (2 patients) and aortic tear, vena cava tear, retained sponge, pulmonary embolism, urinary tract infection, pneumothorax, anterior column support failure, and prominent instrumentation requiring removal (1 patient each). Postoperatively, all patients remained classified as American Spinal Injury Association grade E. Two patients had recurrence at distant spinal segments, and 1 had a new lesion in the thigh. Five patients had died (mean, 34.5 months after surgery), and 5 were alive a mean of 19.6 months after surgery (range, 6-48 months). Total en bloc spondylectomy is challenging, but in appropriately selected patients, it can be used to treat primary and metastatic spinal lesions.

  17. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

    PubMed Central

    Robey, Ian F.; Nesbit, Lance A.

    2013-01-01

    The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P < 0.01). Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs). To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (P ≤ 0.003). Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX). The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion. PMID:23936808

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Mutational analysis of multiple tumor suppressor 1 (MTS1) gene in human primary breast tumors and established breast tumor cell lines

    SciTech Connect

    Xu, L.; Sgroi, D.; Sterner, C.

    1994-09-01

    A putative tumor suppressor gene on the short arm of human chromosome 9 has been identified recently and named as multiple tumor suppressor 1 (MTS1). MTS1 is identical to the previously identified cyclin-dependent kinase-4 inhibitor gene p16, a cell cycle regulatory protein. Frequent homozygous deletions of MTS1 gene has been documented recently in cell lines derived from different types of tumors including breast tumors, suggesting that MTS1 is a tumor suppressor gene that is probably involved in a variety of human tumors. To determine the frequency of MTS1 mutations in primary breast tumors, we screened 39 primary breast tumors (16 lobular carcinoma and 23 ductal carcinoma) and 5 established breast tumor cell lines by utilizing single stranded conformational polymorphism (SSCP) analysis. SSCP analysis was carried out for all 3 exons of the MTS1 gene utilizing primers in the flanking intronic sequences. Two of the five breast cancer tumor cell lines analyzed exhibited deletion of the entire MTS1 gene. However, only one of the thirty-nine primary breast tumors revealed a potential SSCP variation in exon 2 of the MTS1 gene which is currently characterized by sequencing. SSCP analysis also revealed two intragenic polymorphisms, one in exon 2 and one in the 3{prime} untranslated region, that could be used to assay allelic loss directly at the MTS1 locus. These results suggest that the mutation of the MTS1 gene may not be a critical genetic change in the formation of primary breast cancer, and the deletions observed in breast tumor cell lines may be due to product of cell growth in vitro.

  3. Validation of the Mishel's uncertainty in illness scale-brain tumor form (MUIS-BT).

    PubMed

    Lin, Lin; Acquaye, Alvina A; Vera-Bolanos, Elizabeth; Cahill, Jennifer E; Gilbert, Mark R; Armstrong, Terri S

    2012-11-01

    The Mishel uncertainty in illness scale (MUIS) has been used extensively with other solid tumors throughout the continuum of illness. Interventions to manage uncertainty have been shown to improve mood and symptoms. Patients with primary brain tumors (PBT) face uncertainty related to diagnosis, prognosis, symptoms and response. Modifying the MUIS to depict uncertainty in PBT patients will help define this issue and allow for interventions to improve quality of life. Initially, 15 experts reviewed the content validity of the MUIS-brain tumor form (MUIS-BT). Patients diagnosed with PBT then participated in the study to test validity and reliability. Data was collected at one point in time. Six out of 33 items in the original MUIS were modified to better describe PBT patients' uncertainty. 32 of the 186 patients in the second-stage of the study were newly diagnosed with PBT, 85 were on treatment, and 69 were followed-up without active treatment. The validity of the MUIS-BT was demonstrated by its correlations with mood states (P < 0.01) and symptom severity (P < 0.01) and interference (P < 0.01). The MUIS-BT measures four constructs: ambiguity/inconsistency, unpredictability of disease prognosis, unpredictability of symptoms and other triggers, and complexity. Cronbach's alphas of the four subscales were 0.90, 0.77, 0.75 and 0.65, respectively. The 33-item MUIS-BT demonstrated adequate select measures of validity and reliability in PBT patients. Based on this initial validation and significant correlations with symptom distress and mood states, further understanding of uncertainty and evaluation of measures to help manage patients' uncertainty can be evaluated which in turn may improve coping and quality of life.

  4. Selective ablation of rat brain tumors by boron neutron capture therapy

    SciTech Connect

    Coderre, J.; Joel, D. ); Rubin, P.; Freedman, A.; Hansen, J.; Wooding, T.S. Jr.; Gash, D. )

    1994-03-30

    Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X-rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. Longterm X-ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injuries the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT. 50 refs., 8 figs., 1 tab.

  5. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival

    PubMed Central

    Wainwright, Derek A.; Balyasnikova, Irina V.; Chang, Alan L.; Ahmed, Atique U.; Moon, Kyung-Sub; Auffinger, Brenda; Tobias, Alex L.; Han, Yu; Lesniak, Maciej S.

    2012-01-01

    Purpose Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM is the accumulation of immunosuppressive and tumor-promoting CD4+FoxP3+GITR+ regulatory T cells (Tregs). Here, we investigated the role of indoleamine 2,3 dioxygenase (IDO) in brain tumors and the impact on Treg recruitment. Experimental Design To determine the clinical relevance of IDO expression in brain tumors, we first correlated patient survival to the level of IDO expression from resected glioma specimens. We also used novel orthotopic and transgenic models of glioma to study how IDO affects Tregs. The impact of tumor-derived and peripheral IDO expression on Treg recruitment, GITR expression and long-term survival was determined. Results Downregulated IDO expression in glioma predicted a significantly better prognosis in patients. Co-incidently, both IDO -competent and -deficient mice showed a survival advantage bearing IDO-deficient brain tumors, when compared to IDO-competent brain tumors. Moreover, IDO-deficiency was associated with a significant decrease in brain-resident Tregs, both in orthotopic and transgenic mouse glioma models. IDO-deficiency was also associated with lower GITR expression levels on Tregs. Interestingly, the long-term survival advantage conferred by IDO-deficiency was lost in T cell-deficient mice. Conclusions These clinical and pre-clinical data confirm that IDO expression increases the recruitment of immunosuppressive Tregs which leads to tumor outgrowth. In contrast, IDO deficiency decreases Treg recruitment and enhances T cell-mediated tumor rejection. Thus, the data suggest a critical role for IDO-mediated immunosuppression in glioma and supports the continued investigation of IDO-Treg interactions in the context of brain tumors. PMID:22932670

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

    SciTech Connect

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

    1993-09-01

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

  7. AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

    ClinicalTrials.gov

    2016-03-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

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

    PubMed

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

    2013-07-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines. PMID:23743802

  9. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of breast

    PubMed Central

    Srivastava, Smita; Arora, Jyoti; Parakh, Anushri; Goel, Ruchika Kumar

    2016-01-01

    Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year-old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography–computed tomography. PMID:27413270

  10. Primary renal carcinoid tumor: case report and review of the literature

    PubMed Central

    Li, Bin; Cui, Tongyue; Ban, Ziqin; Luo, Lei; Sun, Lijiang

    2016-01-01

    Objective The aim of this case report is to discuss the clinicopathological features of a patient with a primary renal carcinoid tumor. Methods We report on the clinical and pathological information of one case of a patient with a primary renal carcinoid tumor as well as review relative literature. Results The patient was diagnosed with a renal tumor when she received physical examination, and exhibited no positive symptoms. The diameter of tumor was 5 cm, the cross surface of the tumor was light yellow and firm, and the central part was soft with hemorrhage and necrosis. Immunohistochemical staining revealed strong and diffuse staining with synaptophysin, chromogranin A, and neuron-specific enolase. Conclusion A primary renal carcinoid tumor is extremely rare. Surgical resection is a preferred therapeutic method. PMID:26966374

  11. Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.

    PubMed

    Sneed, P K; Russo, C; Scharfen, C O; Prados, M D; Malec, M K; Larson, D A; Lamborn, K R; Lamb, S A; Voss, B; Weaver, K A; Phillips, T L; Gutin, P H; Wara, W M; Edwards, M S

    1996-06-01

    A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

  12. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  13. The blood-brain barrier in primary CNS lymphomas: ultrastructural evidence of endothelial cell death.

    PubMed Central

    Molnár, P. P.; O'Neill, B. P.; Scheithauer, B. W.; Groothuis, D. R.

    1999-01-01

    The vasculature of 24 primary CNS B-cell lymphomas that were not related to acquired immunodeficiency syndrome was systematically studied by electron microscopy. Seven low-grade astrocytic tumors were included for comparison. Classical electron microscopy features of apoptosis were found in lymphoma cells of 21 of 22 subjects. Capillaries of gliomas and lymphomas showed changes reported previously: variability of endothelial cell (EC)-thickness and number, basal lamina thickness and duplication, and fenestrations. Primary CNS B-cell lymphoma ECs showed two distinctive populations of electron-dense and electron-lucent cells. The electron-dense ECs occurred in 38% of all capillaries, with changes consisting of chromatin condensation in bizarre and contracted nuclei, cytoplasmic shrinkage with markedly increased electron density, and dilatation of the endoplasmic reticulum. We interpreted these changes as indicative of apoptosis. Cell death eventually resulted in complete disintegration of the endothelium with frank discontinuities of the EC component of the blood-tumor barrier in capillaries and postcapillary venules. Another population of ECs had increased cell volume, conspicuous cytoplasmic electron lucency, dispersed organelles, scattered vesicles, and apical stress fibers. We interpreted these changes as indicative of cellular regeneration. Individual apoptotic ECs often lay next to normal or regenerating ECs. Neither type of EC change was observed in gliomas, which also lacked perivascular neoplastic lymphocytic cuffing. We believe that these populations of ECs, which have not been described in other disorders affecting the blood-brain barrier, may be induced by cytokines released from necrotic and/or apoptotic tumor lymphocytes and may explain the unusual imaging characteristics of primary CNS B-cell lymphomas treated with corticosteroids. PMID:11550310

  14. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor.

    PubMed

    van Niekerk, Catharina C; Vooijs, G Peter; Bulten, Johan; van Dijck, Jos A A M; Verbeek, Andre L M

    2007-03-01

    Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based study, we used data from the Netherlands Nationwide Network for Registry of histo- and cytopathology (PALGA) and the Netherlands Cancer Registry (NCR). Data of the ovarian cancer as well as data on previous or later cancers were obtained. Age-specific cancer rates from the NCR were used to calculate expected numbers of cancer. Between 1987 and 1993, histopathology reports were identified of 4577 patients with primary epithelial malignant or primary borderline malignant ovarian cancers and its longitudinal data. As the database may lack detailed information on histopathology, a recent sample of 789 patients diagnosed with ovarian cancer in 1996-2003 was comprehensively studied as well. In the eventual data analysis of 5366 patients, 244 cases (4.5%) of concurrent primary malignancy were reported in the same year that the malignant epithelial ovarian tumor had been diagnosed against 51 expected. The observed vs expected ratio was 4.8 and the 95% confidence interval (CI) (4.3-5.5). For cancer of the uterus/endometrium the observed vs expected ratio was 62.3 (95% CI 52.5-73.5). For skin, breast, colorectal, urinary bladder, renal and cervical cancer the ratio was also larger than unity. The elevated risk of concurrent cancer may lead to clinical screening protocols. The findings on endometrial cancer may prompt research on common etiologies and biomarkers.

  15. Primary pulmonary solitary fibrous tumour with brain metastases.

    PubMed

    Ozeki, Naoki; Kawaguchi, Koji; Taniguchi, Tetsuo; Yokoi, Kohei

    2014-02-01

    Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1×1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients.

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

    PubMed

    Kim, Minjae; Kim, Ho Sung

    2016-01-01

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

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

    MedlinePlus

    ... associated with cranial or spinal nerve schwannomas, especially vestibular schwannomas (acoustic neuromas), which almost always occur on ... possible increased risk of brain tumors or of vestibular schwannomas in adults with cell phone use, but ...

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

    PubMed

    Kim, Minjae; Kim, Ho Sung

    2016-01-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response. PMID:27587949

  19. Combining microbubbles and ultrasound for drug delivery to brain tumors: current progress and overview.

    PubMed

    Liu, Hao-Li; Fan, Ching-Hsiang; Ting, Chien-Yu; Yeh, Chih-Kuang

    2014-01-01

    Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality. Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival. Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery. MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors. Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment. In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy.

  20. Combining Microbubbles and Ultrasound for Drug Delivery to Brain Tumors: Current Progress and Overview

    PubMed Central

    Liu, Hao-Li; Fan, Ching-Hsiang; Ting, Chien-Yu; Yeh, Chih-Kuang

    2014-01-01

    Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality. Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival. Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery. MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors. Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment. In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy. PMID:24578726

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

    PubMed Central

    Kim, Minjae

    2016-01-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response. PMID:27587949

  2. Neonatal Vitamin D and Childhood Brain Tumor Risk

    PubMed Central

    Bhatti, Parveen; Doody, David R.; Mckean-Cowdin, Roberta; Mueller, Beth A.

    2014-01-01

    Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (< 15 years at diagnosis; born 1991 or later) were identified. 247 birth year, sex and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25-(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 grams), there was evidence of increasing risk of CBT with increasing 25-(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (OR) and 95% Confidence Intervals (CI) for the 2nd (7.7-< 11.0 ng/mL), 3rd (11.0-<14.7 ng/mL) and 4th (14.7-37.0) quartiles of 25-(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CI for the 2nd, 3rd and 4th quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1 (IGF-1), circulating levels of which have been associated with vitamin D and accelerated fetal growth. PMID:25348494

  3. Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

    PubMed Central

    Momeni, Mazdak; Kolev, Valentin; Costin, Dan; Mizrachi, Howard H.; Chuang, Linus; Warner, Richard R.P.; Gretz, Herbert F.

    2012-01-01

    INTRODUCTION A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp. PMID:23127865

  4. Brain Metastases as Presenting Feature in 'Burned Out' Testicular Germ Cell Tumor

    PubMed Central

    Brunet, Bryan

    2016-01-01

    Testicular germ cell tumors (TGCTs) are the most common malignancy in males aged 20 to 39, and the incidence is increasing. TGCTs have a tendency to grow rapidly with a high risk of metastatic spread. TGCTs generally present with a palpable testicular mass, yet may present less commonly with symptoms arising from metastatic disease.  A 24-year-old otherwise healthy male presented with progressive headaches. Initial imaging reported a single mass in the right frontal lobe. Complete surgical resection revealed suspicion for metastatic poorly differentiated carcinoma with an inconclusive immunohistochemical profile. Further staging scans revealed pulmonary and pelvic tumor deposits. Tumor markers with alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase were not elevated. Follow-up cranial magnetic resonance imaging revealed intracranial disease progression and he underwent whole brain radiation therapy. Additional outside pathology consultation for chromosomal analysis revealed features consistent with a TGCT. A scrotal ultrasound revealed a minimally atrophic right testicle. With evidence supporting the potential for response to chemotherapeutic treatment in TGCT, the patient was started on cisplatin and etoposide. Bleomycin was planned for the second cycle of chemotherapy if his pulmonary function improved.  A salient feature of all invasive TGCTs is a gain in material in the short arm of chromosome 12, and is diagnostic if present. Although the initial pathology revealed a non-diagnostic metastatic tumor, further testing revealed amplification of chromosome 12p. The examination of poorly differentiated carcinomas of an unknown primary site using light microscopy and immunohistochemical profiling alone may be inadequate, and should undergo molecular chromosomal analysis. This case is presented for its unconventional presentation and rarity of occurrence. It brings forward the discussion of both the commonality of TGCT in young male

  5. Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases

    PubMed Central

    Jakubovic, Raphael; Sahgal, Arjun; Ruschin, Mark; Pejović-Milić, Ana; Milwid, Rachael; Aviv, Richard I.

    2015-01-01

    Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID:26269612

  6. P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration.

    PubMed

    Iusuf, Dilek; Teunissen, Sebastiaan F; Wagenaar, Els; Rosing, Hilde; Beijnen, Jos H; Schinkel, Alfred H

    2011-06-01

    P-glycoprotein (P-gp, ABCB1) is a highly efficient drug efflux pump expressed in brain, liver, and small intestine, but also in tumor cells, that affects pharmacokinetics and confers therapy resistance for many anticancer drugs. The aim of this study was to investigate the impact of P-gp on tamoxifen and its primary active metabolites, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen. We used in vitro transport assays and Abcb1a/1b(-/-) mice to investigate the impact of P-gp on the oral availability and brain penetration of tamoxifen and its metabolites. Systemic exposure of tamoxifen and its metabolites after oral administration of tamoxifen (50 mg/kg) was not changed in the absence of P-gp. However, brain accumulation of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen were modestly, but significantly (1.5- to 2-fold), increased. Endoxifen, however, displayed a 9-fold higher brain penetration at 4 h after administration. Endoxifen was transported by P-gp in vitro. Upon direct oral administration of endoxifen (20 mg/kg), systemic exposure was slightly decreased in Abcb1a/1b(-/-) mice, but brain accumulation of endoxifen was dramatically increased (up to 23-fold at 4 h after administration). Shortly after high-dose intravenous administration (5 or 20 mg/kg), endoxifen brain accumulation was increased only 2-fold in Abcb1a/1b(-/-) mice compared with wild-type mice, suggesting a partial saturation of P-gp at the blood-brain barrier. Endoxifen, the clinically most relevant metabolite of tamoxifen, is a P-gp substrate in vitro and in vivo, where P-gp limits its brain penetration. P-gp might thus be relevant for tamoxifen/endoxifen resistance of P-gp-positive breast cancer and tumors positioned behind a functional blood-brain barrier. PMID:21378205

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

    PubMed

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

    2016-01-01

    Chemotherapies active in preclinical studies frequently fail in the clinic due to lack of efficacy, which limits progress for rare cancers since only small numbers of patients are available for clinical trials. Thus, a preclinical drug development pipeline was developed to prioritize potentially active regimens for pediatric brain tumors spanning from in vitro drug screening, through intracranial and intra-tumoral pharmacokinetics to in vivo efficacy studies. Here, as an example of the pipeline, data are presented for the combination of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in three pediatric brain tumor models. The in vitro activity of nine novel therapies was tested against tumor spheres derived from faithful mouse models of Group 3 medulloblastoma, ependymoma, and choroid plexus carcinoma. Agents with the greatest in vitro potency were then subjected to a comprehensive series of in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies culminating in preclinical efficacy trials in mice harboring brain tumors. The nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) markedly reduced the proliferation in vitro of all three brain tumor cell types at nanomolar concentrations. Detailed intracranial PK studies confirmed that systemically administered FdCyd exceeded concentrations in brain tumors necessary to inhibit tumor cell proliferation, but no tumor displayed a significant in vivo therapeutic response. Despite promising in vitro activity and in vivo PK properties, FdCyd is unlikely to be an effective treatment of pediatric brain tumors, and therefore was deprioritized for the clinic. Our comprehensive and integrated preclinical drug development pipeline should reduce the attrition of drugs in clinical trials. PMID:26518542

  8. Distribution of hematoporphyrin derivative in the rat 9l gliosarcoma brain tumor analyzed by digital video fluorescence microscopy.

    PubMed

    Boggan, J E; Walter, R; Edwards, M S; Borcich, J K; Davis, R L; Koonce, M; Berns, M W

    1984-12-01

    A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors. PMID:6239014

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

    PubMed

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

    1987-01-01

    In the surgery of meningiomas one of the most delicate problems is the separation of the tumor from the brain surface. The authors generally recommend microsurgery to preserve the brain surface anatomically and functionally. For this purpose we have developed a new surgical technique according to our concepts of tissue care. After excavating the tumor from inside the tumor brain surface was separated by repeated "water jets" into the tumor arachnoideal space. The "water jet" was produced by an ordinary bulb syringe. The front pressure of the jets was 300-1000 mm of water and the side pressure 100-300 mm of water. In the tumor-arachnoideal space the spreading water (phys. NaCl) separates the brain from the tumor with utmost care. We operated on 55 meningiomas of different types with the "water jet" technique. The immediate results were anatomically excellent. Intraoperative and postoperative acute and late edemas appeared only in a few cases. The functions of the nearby brain were generally preserved. The surgery was uneventful when the tumor surface was smooth and the tumor was spherical. When the tumor surface was uneven, one part of the tumor extended under the dura as a thin layer or the tumor was multilobulated with expanded vessels between the lobules, more microseparation was necessary. We compared the results of the "water jet" technique with the results of the "pre-water jet" series. The surgery with the "water jet" technique was much shorter and its results were better than those of microsurgery alone. PMID:3668608

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

    PubMed

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

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors. PMID:23208215

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    PubMed

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

    2012-12-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-21

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

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

    PubMed Central

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

    2016-01-01

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

  16. Peptide-based method for detection of metastatic transformation in primary tumors of breast cancer.

    PubMed

    Li, Hao; Huang, Yue; Yu, Yue; Li, Weiwei; Yin, Yongmei; Li, Genxi

    2015-09-15

    Detection of metastatic activity before the onset of the actual metastasis can be a promising method to combat metastasis, the foremost cause of death in cancer. Therefore, in this work, we have developed an assay method for the detection of metastatic tumor cells in primary tumor, by using a protein of the metastatic cell signaling as the biomarker. In this assay, a peptide-based probe targeting the marker protein and a sensitive nanoparticle doped graphene nanolabel are combined to enable the detection of metastatic cells. Consequently, the metastatic cells can be specifically detected and discriminated from primary tumor cells. By applying this assay method to clinical samples of primary tumor, a low amount of metastatic activity can be detected in the tumor sites, which may suggest the activity of local metastatic transformation. So, these results may point to the prospect of using the proposed method for controlling metastatic cancer.

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

    PubMed

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

    2011-12-01

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

  18. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  19. Primary Pulmonary Salivary Gland-type Tumors: A Review and Update.

    PubMed

    Falk, Nadja; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar A

    2016-01-01

    Pulmonary salivary gland-type tumors (SGT) comprise a very small proportion of primary lung neoplasms. The most common tumors among this group are mucoepidermoid carcinoma and adenoid cystic carcinoma. Contrary to the head and neck region, benign SGT such as pleomorphic adenomas are exceedingly rare in the pulmonary system. More recently, 2 additional SGT, namely hyalinizing clear cell carcinoma and salivary duct-like carcinoma were recognized as primary lung tumors expanding the spectrum of SGT that have been described to originate in the tracheobronchial system. Primary pulmonary SGT must be clinically excluded from metastatic salivary gland neoplasms as their morphology is indistinguishable from that of their salivary gland counterparts. Little is known about the clinical behavior and best treatment approach for these unusual tumors. In this review, we provide a comprehensive summary of primary pulmonary SGT with particular emphasis on morphologic characteristics and latest developments in terms of immunohistochemical and molecular techniques.

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

    PubMed

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

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

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

    PubMed Central

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

    2016-01-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

  2. Recent patents on imaging nanoprobes for brain tumor diagnosis and therapy.

    PubMed

    Qi, Lifeng; Zheng, Shu; Lin, Biaoyang

    2010-06-01

    Multifunctional nanoprobes, such as nanocrystals, nanoshells, and luminescent nanomaterials, have been developed for imaging biological processes; such