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Sample records for brain tumor cell

  1. Brain tumor stem cell dancing

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2014-09-01

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

  2. Cancer stem cells and brain tumors

    OpenAIRE

    Pérez Castillo, Ana; Aguilar Morante, Diana; Morales-García, José A.; Dorado, Jorge

    2008-01-01

    Besides the role of normal stem cells in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Most current research on human tumors is focused on molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and, more recently, in solid tumors suggests that the tumor cell population is heterogeneous. In recent years, several groups have described the existence of a cancer stem cell population in different brain tumors. These neural cancer stem ...

  3. Brain Tumors

    Science.gov (United States)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

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

    OpenAIRE

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

    2013-01-01

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

  6. Brain tumor - primary - adults

    Science.gov (United States)

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

  7. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  8. Brain tumor stem cells as research and treatment targets

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM) is one of the most malignant forms of human cancer. Despite intensive treatment, the mean survival of GBM patients remains about 1 year. Recent cancer studies revealed that cancer tissues are pathologically heterogeneous and only a small population of cells has the specific ability to reinitiate cancer. This small cell population is called cancer stem cells (CSCs); in brain tumors these are known as brain tumor stem cells (BTSCs). The identification of BTSCs yielded new insights into chemo- and radioresistance, by which BTSCs can survive selectively and initiate recurrence. Research focused on BTSCs as treatment targets may contribute to the discovery of new therapeutic strategies. Clinical and basic research studies gradually led to improved outcomes in patients with brain tumors. Stupp et al. reported a mean survival of 14.6 months in glioblastoma multiforme (GBM) patients treated with radiotherapy plus temozolomide and 12.1 months in those subjected to radiotherapy alone. Earlier cancer therapies primarily targeted rapidly dividing cells but not minor populations of slowly dividing cells that contain BTSCs. Accumulating evidence suggests that BTSCs may represent an excellent tool for discovering new strategies to treat GBM patients. In this review, we present evidence supporting the CSC model of tumor progression, and discuss difficulties encountered in CSC research and experimental and therapeutic implications. (author)

  9. Brain tumor - children

    Science.gov (United States)

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

  10. Cancer Stem Cells in Brain Tumors and Their Lineage Hierarchy

    OpenAIRE

    Kong, Doo-Sik

    2012-01-01

    Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.

  11. Brain Tumors (For Parents)

    Science.gov (United States)

    ... 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 ...

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

    International Nuclear Information System (INIS)

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

  13. No Evidence Linking Cell Phone Use to Risk of Brain Tumors

    Science.gov (United States)

    ... Blood & Biologics Articulos en Espanol No Evidence Linking Cell Phone Use to Risk of Brain Tumors Printer-friendly ... Minimizing RF Exposure Do the radio waves that cell phones emit pose a threat to health? Although research ...

  14. Tumor Microenvironment in the Brain

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    Lorger, Mihaela [Leeds Institute of Molecular Medicine, University of Leeds, St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF (United Kingdom)

    2012-02-22

    In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.

  15. Metastatic Brain Tumors

    Directory of Open Access Journals (Sweden)

    Ersin Haciyakupoglu

    2014-04-01

    Full Text Available Metastatic tumor is secondary spread to the central nervous system of primer systemic cancers originating from tissues other than the central nervous system. In adults; there are metastases respectively from lungs, breasts, malign melanoma, renal cell carcinoma, colon and thyroid cancers. 30-60% of lung cancers metastasis to the brain. In children there are quite a few cerebral metastases. Most commonly leukemia, lymphoma, osteogenic sarcoma, rhabdomyosarcoma and germ cell tumors metastasis to the brain. %50 of malign melanoma, lung, breast and colon cancers intend to make multipl metastases but renal cell cancers intend to make solitary metastasis.While lung cancers metastasis to brain in 6-9 months after the definitive diagnosis, renal cancers in 1 year, colon cancers in 2 years, breast cancers and malign melanoma in 3 years metastasis to brain. In 6% of cases there are cerebral metastasis while there isn’t a symptom of a primary tumor. For treatment corticosteroids, surgery, Radiotherapy(RT, Chemotherapy(CT and Stereotactic Radiosurgery(SRS can be implemented. Small cell lung cancers, lymphoma, germ cell tumors are sensitive to RT and CT. Non small cell lung cancers, renal, colon cancers and malign melanoma are radioresistant. The purposes in the surgery of the metastatic brain tumors are; total resection of tumors without neurologic deficits, decreasing the intracranial pressure and decreasing the dose of postoperative radiotherapy. Key Words: Metastatic brain tumors, Stereotactic radiosurgery, Malign melanoma, Lung cancers, Renal cell carcinoma, Radiotherapy, Chemotherapy [Cukurova Med J 2014; 39(2.000: 191-202

  16. Childhood Brain Tumors

    Science.gov (United States)

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

  17. Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

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    Patrick N Harter

    2014-12-01

    Full Text Available Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9 is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS. Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status. Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells. Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re- assessment of potential TNFRSF9 functions in cell types other than

  18. Stem cell-based therapies for tumors in the brain: are we there yet?

    Science.gov (United States)

    Shah, Khalid

    2016-08-01

    Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. PMID:27282399

  19. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

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

  1. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

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

  2. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-03-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10{sup 12}nvt for BMGP and 2x10{sup 13}nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the {alpha}-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author).

  3. Pediatric Brain Tumor Foundation

    Science.gov (United States)

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

  4. Brain and Spinal Tumors

    Science.gov (United States)

    ... 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 ...

  5. Imaging of brain tumors

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Hangjun Ruan

    1999-11-01

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

  7. Epilepsy and Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhi-yi Sha

    2009-01-01

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

  8. Brain Tumor Statistics

    Science.gov (United States)

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

  9. Brain tumor - children

    Science.gov (United States)

    Glioblastoma multiforme - children; Ependymoma - children; Glioma - children; Astrocytoma - children; Medulloblastoma - children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children)

  10. MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells

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    Katarzyna Modzelewska

    2016-10-01

    Full Text Available Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase pathway. Modeling NRAS activation in embryonic OPCs generated malignant brain tumors in zebrafish that closely mimic the human oligoneural/NB-FOXR2 CNS-PNET subgroup by histology and comparative oncogenomics. The zebrafish CNS-PNET model was used to show that MEK inhibitors selectively eliminate Olig2+/Sox10+ CNS-PNET tumors in vivo without impacting normal brain development. Thus, MEK inhibitors represent a promising rationally designed therapy for children afflicted with oligoneural/NB-FOXR2 CNS-PNETs.

  11. Effect of dendritic cell vaccine therapy on lymphocyte subpopulation in refractory primary brain tumor

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    J Niu

    2015-01-01

    Full Text Available BACKGROUND: Dendritic cell (DC-based immunotherapy has the potential to induce an antitumor response within the immunologically privileged brain. AIMS: The aim of this study was to evaluate the short-term effect of DC vaccine therapy on lymphocyte subsets in patients with refractory primary brain tumor. MATERIALS AND METHODS: Eighteen cases with refractory primary brain tumor who refused any treatment against tumor within 6 months of the therapy, were referred to one medicine center, from January 2011 to October 2012. All patients received 1 × 107 tumor lysate–pulsed DC vaccinations both intradermal injection and intravenous infusion 3 times/week. RESULTS: There were increases of lymphocytes CD8+ (P = 0.002 and CD56+ (P = 4.207E-10, but no change of lymphocytes CD3+ (P = 0.651. Six patients were positive response of delayed-type hypersensitivity. There were improving of appetite in 14 cases and increasing of physical strength 17 cases. CONCLUSIONS: DC vaccine has the potential for inducing an immune cytotoxic effect directed toward tumor cells.

  12. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  13. Inhibition of brain tumor cell proliferation by alternating electric fields

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    Jeong, Hyesun; Oh, Seung-ick; Hong, Sunghoi, E-mail: shong21@korea.ac.kr, E-mail: radioyoon@korea.ac.kr [School of Biosystem and Biomedical Science, Korea University, Seoul 136-703 (Korea, Republic of); Sung, Jiwon; Jeong, Seonghoon; Yoon, Myonggeun, E-mail: shong21@korea.ac.kr, E-mail: radioyoon@korea.ac.kr [Department of Bio-convergence Engineering, Korea University, Seoul 136-703 (Korea, Republic of); Koh, Eui Kwan [Seoul Center, Korea Basic Science Institute, Seoul 136-713 (Korea, Republic of)

    2014-11-17

    This study was designed to investigate the mechanism by which electric fields affect cell function, and to determine the optimal conditions for electric field inhibition of cancer cell proliferation. Low-intensity (<2 V/cm) and intermediate-frequency (100–300 kHz) alternating electric fields were applied to glioblastoma cell lines. These electric fields inhibited cell proliferation by inducing cell cycle arrest and abnormal mitosis due to the malformation of microtubules. These effects were significantly dependent on the intensity and frequency of applied electric fields.

  14. Differential expression of human homeodomain TGIFLX in brain tumor cell lines.

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    Reza Raoofian

    2013-12-01

    Full Text Available Glioblastoma is the most common and the most lethal primary brain cancer. This malignancy is highly locally invasive, rarely metastatic and resistant to current therapies. Little is known about the distinct molecular biology of glioblastoma multiforme (GBM in terms of initiation and progression. So far, several molecular mechanisms have been suggested to implicate in GBM development. Homeodomain (HD transcription factors play central roles in the expression of genomic information in all known eukaryotes. The TGIFX homeobox gene was originally discovered in human adult testes. Our previous study showed implications of TGIFLX in prostate cancer and azoospermia, although the molecular mechanism by which TGIFLX acts is unknown. Moreover, studies reported that HD proteins are involved in normal and abnormal brain developments. We examined the expression pattern of TGIFLX in different human brain tumor cell lines including U87MG, A172, Daoy and 1321N1. Interestingly, real time RT-PCR and western blot analysis revealed a high level of TGIFLX expression in A172 cells but not in the other cell lines. We subsequently cloned the entire coding sequence of TGIFLX gene into the pEGFP-N1 vector, eukaryotic expression vector encoding eGFP, and transfected into the U-87 MG cell line. The TGIFLX-GFP expression was confirmed by real time RT-PCR and UV-microscopic analysis. Upon transfection into U87 cells, fusion protein TGIFLX-GFP was found to locate mainly in the nucleus. This is the first report to determine the nuclear localization of TGIFLX and evaluation of its expression level between different brain tumor cell lines. Our data also suggest that TGIFLX gene dysregulation could be involved in the pathogenesis of some human brain tumors.

  15. Exposure to 3G mobile phone signals does not affect the biological features of brain tumor cells

    OpenAIRE

    Liu, Yu-xiao; Li, Guo-Qing; Fu, Xiang-ping; Xue, Jing-hui; Ji, Shou-Ping; Zhang, Zhi-Wen; Zhang, Yi; Li, An-ming

    2015-01-01

    Background The increase in mobile phone use has generated concerns about possible risks to human health, especially the development of brain tumors. Whether tumor patients should continue to use mobile telephones has remained unclear because of a paucity of information. Herein, we investigated whether electromagnetic fields from mobile phones could alter the biological features of human tumor cells and act as a tumor-promoting agent. Methods Human glioblastoma cell lines, U251-MG and U87-MG, ...

  16. The Potential Impact of Biofield Treatment on Human Brain Tumor Cells: A Time-Lapse Video Microscopy

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Study background: Glioblastoma (GBM) is the most common subtype of primary brain tumor in adults. The aim was to evaluate the impact of biofield treatment potential on human GBM and non-GBM brain cells using two time-lapse video microscopy technique. Methods: The human brain tumor, GBM cultured cells were divided into two groups viz. GBM control and GBM treatment. Similarly, human normal brain cultured cells (non-GBM) were taken and divided into two groups viz. non- GBM control ...

  17. Understanding Brain Tumors

    Science.gov (United States)

    ... Our Mission Advance Research Clinical Trial Endpoints Defeat GBM Oligo Research Fund Pediatric Initiatives Funded Research & Accomplishments ... no symptoms when their brain tumor is discovered Recurrent headaches Issues with vision Seizures Changes in personality ...

  18. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  19. Comet assay as a predictive assay for radiosensitivity of two human brain tumor cell lines

    International Nuclear Information System (INIS)

    Micronucleus assay and comet assay were compared as a predictive assay for radiosensitivity of tumors. Two human brain tumor cell lines, Becker (derived from astrocytoma) and ONS76 (derived from medulloblastoma) were used. Colony methods as the gold standard showed ONS76 as radiosensitive and Becker as radioresistant cell lines. Micronucleus assay revealed no different radiosensitivity between them. With comet assay, Becker cells received irradiation showed less damage to the DNA and faster repair of the damage than ONS76 cells did. The results correlate with those from colony methods. Comet assay is simple and rapid method for clinical use and it has an advantage not to establish the primary culture. Moreover, the results of comet assay showed not only DNA damage but also repair from the damage. It is concluded that comet assay is a superior method than micronucleus assay and has a potent candidate for clinical predictive assay. (author)

  20. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  1. Definition of genetic events directing the development of distinct types of brain tumors from postnatal neural stem/progenitor cells.

    Science.gov (United States)

    Hertwig, Falk; Meyer, Katharina; Braun, Sebastian; Ek, Sara; Spang, Rainer; Pfenninger, Cosima V; Artner, Isabella; Prost, Gaëlle; Chen, Xinbin; Biegel, Jaclyn A; Judkins, Alexander R; Englund, Elisabet; Nuber, Ulrike A

    2012-07-01

    Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. PMID:22719073

  2. Anticancer Activity of β-Elemene and its Synthetic Analogs in Human Malignant Brain Tumor Cells

    OpenAIRE

    Li, Qingdi Quentin; Lee, Rebecca X.; LIANG, HUASHENG; ZHONG, YUHUA

    2013-01-01

    Malignant brain tumors are aggressive in both children and adults. Despite recent improvements in diagnostic techniques, therapeutic approaches remain disappointing and unsuccessful. There is an urgent need for promising anticancer agents to improve overall survival of patients with brain cancer. β-Elemene has been shown to have antiproliferative effects on many types of carcinomas. In this study, we compared the cytotoxic efficacy of β-elemene and its synthetic analogs in the brain tumor cel...

  3. Robust Cell Detection of Histopathological Brain Tumor Images Using Sparse Reconstruction and Adaptive Dictionary Selection.

    Science.gov (United States)

    Su, Hai; Xing, Fuyong; Yang, Lin

    2016-06-01

    Successful diagnostic and prognostic stratification, treatment outcome prediction, and therapy planning depend on reproducible and accurate pathology analysis. Computer aided diagnosis (CAD) is a useful tool to help doctors make better decisions in cancer diagnosis and treatment. Accurate cell detection is often an essential prerequisite for subsequent cellular analysis. The major challenge of robust brain tumor nuclei/cell detection is to handle significant variations in cell appearance and to split touching cells. In this paper, we present an automatic cell detection framework using sparse reconstruction and adaptive dictionary learning. The main contributions of our method are: 1) A sparse reconstruction based approach to split touching cells; 2) An adaptive dictionary learning method used to handle cell appearance variations. The proposed method has been extensively tested on a data set with more than 2000 cells extracted from 32 whole slide scanned images. The automatic cell detection results are compared with the manually annotated ground truth and other state-of-the-art cell detection algorithms. The proposed method achieves the best cell detection accuracy with a F1 score = 0.96.

  4. Brain tumors in infants

    Directory of Open Access Journals (Sweden)

    Seyyed Mohammad Ghodsi

    2015-01-01

    Full Text Available 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.

  5. Adult brain tumors

    International Nuclear Information System (INIS)

    Radiotherapy plays an important role in the management of adults with brain tumors. This refresher course will focus on a variety of benign and malignant brain neoplasms and how contemporary radiotherapy affects outcome. Successful outcome after radiotherapy requires that (1) there is no tumor extension beyond the selected target volume, (2) adequate dose is delivered to the target volume, and (3) normal tissue tolerance dose is not exceeded. For many neoplasms serial post-treatment scans may show little change, and success is often measured more by absence of tumor progression than by scan normalization. Three-dimensional treatment planning based on MRI or CT makes it possible to guarantee delivery of the full prescription dose to gross tumor while minimizing the volume of normal tissue receiving high dose. Acceptable dose conformity can often be achieved with 2-4 static beams or arcs, which is usually preferable to opposed lateral fields. Protocols involving substantial dose escalation require a large number of non-coplanar x-ray beams or particle therapy. This course will cover important concepts and techniques which relate to the treatment of brain tumors, including conformal radiotherapy, brachytherapy, radiosurgery, fractionated stereotactic radiotherapy, altered fractionation, inverse treatment planning, re-irradiation, and biologically effective dose (BED). Examples of planning solutions for a variety of tumor types, size and anatomical locations will be given. Note: I will incorporate examples of interesting, difficult and unusual cases from other practices as time permits, provided slides and descriptive materials are sent to me in advance of the course

  6. Intraaxial brain tumors

    International Nuclear Information System (INIS)

    The incidence of primary intracranial tumors in the United States is approximately 15,0000 new cases per year. It has been estimated that 80--85% of all intracranial tumors occur in adults; the majority are situated in the supratentorial compartment. In the pediatric population, intracranial tumors are extraordinarily common---the CNS is the second most common site of pediatric neoplasia. Excluding the first year of life and adolescence, the location of intracranial tumors in the pediatric age group is infratentorial in 60--70% of cases, of which 75% involve the cerebellum and 25% reside in the brainstem. The limitations of neuroimaging are often revealed by understanding the microscopic pathology of these lesions, just as the neuropathologist would find if he or she relied solely on gross pathology. The general correlation between pathology and imaging will be stressed in this paper. Innumerable schemes for tumor classification have been devised; unfortunately, no classification is perfect. For the purposes of this discussion, the author has modified the proposed classifications of tumors in an attempt to combine typical neuroanatomic sites with the complex divisions traditionally formed on the basis of histopathology, since it is well recognized that the clinical behavior of brain tumors can depend largely on their sites of origin

  7. Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.

    Science.gov (United States)

    Park, See-Hyoung; Yoon, Young Ii; Moon, Hyoungwon; Lee, Ga-Hyun; Lee, Byung-Heon; Yoon, Tae-Jong; Lee, Hak Jong

    2016-07-01

    Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

  8. Contribution of gap junctional communication between tumor cells and astroglia to the invasion of the brain parenchyma by human glioblastomas

    Directory of Open Access Journals (Sweden)

    Venance Laurent

    2005-02-01

    Full Text Available Abstract Background Gliomas are "intraparenchymally metastatic" tumors, invading the brain in a non-destructive way that suggests cooperation between glioma cells and their environment. Recent studies using an engineered rodent C6 tumor cell line have pointed to mechanisms of invasion that involved gap junctional communication (GJC, with connexin 43 as a substrate. We explored whether this concept may have clinical relevance by analyzing the participation of GJC in human glioblastoma invasion. Results Three complementary in vitro assays were used: (i seeding on collagen IV, to analyze homocellular interactions between tumor cells (ii co-cultures with astrocytes, to study glioblastoma/astrocytes relationships and (iii implantation into organotypic brain slice cultures, that mimic the three-dimensional parenchymal environment. Carbenoxolone, a potent blocker of GJC, inhibited cell migration in the two latter models. It paradoxically increased it in the first one. These results showed that homocellular interaction between tumor cells supports intercellular adhesion, whereas heterocellular glioblastoma/astrocytes interactions through functional GJC conversely support tumor cell migration. As demonstrated for the rodent cell line, connexin 43 may be responsible for this heterocellular functional coupling. Its levels of expression, high in astrocytes, correlated positively with invasiveness in biopsied tumors. Conclusions our results underscore the potential clinical relevance of the concept put forward by other authors based on experiments with a rodent cell line, that glioblastoma cells use astrocytes as a substrate for their migration by subverting communication through connexin 43-dependent gap junctions.

  9. A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells

    OpenAIRE

    Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

    2016-01-01

    Background Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells’ viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris conta...

  10. Immunomodulatory Effects of Hemagglutinin- (HA- Modified A20 B-Cell Lymphoma Expanded as a Brain Tumor on Adoptively Transferred HA-Specific CD4+ T Cells

    Directory of Open Access Journals (Sweden)

    Valentin P. Shichkin

    2014-01-01

    Full Text Available Previously, the mouse A20 B-cell lymphoma engineered to express hemagglutinin (HA antigen (A20HA was used as a systemic tumor model. In this work, we used the A20HA cells as a brain tumor. HA-specific CD4+ T cells were transferred intravenously in a tail vein 5 days after A20HA intracranial inoculation and analyzed on days 2, 9, and 16 after the adoptive transfer by different methods. The transferred cells demonstrated state of activation as early as day 2 after the adoptive transfer and most the of viable HA-specific cells became anergic on day 16. Additionally, symptoms of systemic immunosuppression were observed in mice with massive brain tumors at a late stage of the brain tumor progression (days 20–24 after the A20HA inoculation. Despite that, a deal of HA-specific CD4+ T cells kept the functional activity even at the late stage of A20HA tumor growth. The activated HA-specific CD4+ T cells were found also in the brain of brain-tumor-bearing mice. These cells were still responding to reactivation with HA-peptide in vitro. Our data support an idea about sufficient role of both the tumor-specific and -nonspecific mechanisms inducing immunosuppression in cancer patients.

  11. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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. PMID:26540346

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

    Science.gov (United States)

    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.

  14. Synthesis of tumor-targeted folate conjugated fluorescent magnetic albumin nanoparticles for enhanced intracellular dual-modal imaging into human brain tumor cells.

    Science.gov (United States)

    Wang, Xueqin; Tu, Miaomiao; Tian, Baoming; Yi, Yanjie; Wei, ZhenZhen; Wei, Fang

    2016-11-01

    Superparamagnetic iron oxide nanoparticles (SPIO NPs), utilized as carriers are attractive materials widely applied in biomedical fields, but target-specific SPIO NPs with lower toxicity and excellent biocompatibility are still lacking for intracellular visualization in human brain tumor diagnosis and therapy. Herein, bovine serum albumin (BSA) coated superparamagnetic iron oxide, i.e. γ-Fe2O3 nanoparticles (BSA-SPIO NPs), are synthesized. Tumor-specific ligand folic acid (FA) is then conjugated onto BSA-SPIO NPs to fabricate tumor-targeted NPs, FA-BSA-SPIO NPs as a contrast agent for MRI imaging. The FA-BSA-SPIO NPs are also labeled with fluorescein isothiocyanate (FITC) for intracellular visualization after cellular uptake and internalization by glioma U251 cells. The biological effects of the FA-BSA-SPIO NPs are investigated in human brain tumor U251 cells in detail. These results show that the prepared FA-BSA-SPIO NPs display undetectable cytotoxicity, excellent biocompatibility, and potent cellular uptake. Moreover, the study shows that the made FA-BSA-SPIO NPs are effectively internalized for MRI imaging and intracellular visualization after FITC labeling in the targeted U251 cells. Therefore, the present study demonstrates that the fabricated FITC-FA-BSA-SPIO NPs hold promising perspectives by providing a dual-modal imaging as non-toxic and target-specific vehicles in human brain tumor treatment in future.

  15. NANOROBOTS IN BRAIN TUMOR

    Directory of Open Access Journals (Sweden)

    Sayyed Tarannum, Garje Dattatray H

    2011-02-01

    Full Text Available Nanomedicine is the process of diagnosing, treating, and preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health, using molecular tools and molecular knowledge of the human body. In the relatively near term, nanomedicine can address many important medical problems by using nanoscale-structured materials and simple nanodevices that can be manufactured today, including the interaction of nanostructured materials with biological systems. The authors predict that technology-assisted medicine and robotics in particular, will have a significant impact over the next few decades. Robots will augment the surgeon’s motor performance, diagnosis capability, and senses with haptics (feel, augmented reality (sight, and ultrasound (sound. Robotic devices have been used in cardiac surgery, urology, fetal surgery, pediatrics, neurosurgery, orthopedics, and many other medical disciplines. In this article, we present the Nanorobot drug delivery to brain tumor, paying special attention to the transformation trends of organizations, and the integration of robots in brain tumor and underscoring potential repercussions which may deserve more attention and further research.

  16. Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors

    OpenAIRE

    Liu, Qinghai; Nguyen, David H.; DONG, QINGHUA; Shitaku, Peter; Chung, Kenneth; Liu, On Ying; Jonathan L Tso; Liu, Jason Y; Konkankit, Veerauo; Cloughesy, Timothy F.; Mischel, Paul S; Lane, Timothy F.; Liau, Linda M.; Stanley F Nelson; Tso, Cho-Lea

    2009-01-01

    Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD1...

  17. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

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

  18. Drug and cell encapsulation : Alternative delivery options for the treatment of malignant brain tumors

    NARCIS (Netherlands)

    Bhujbal, Swapnil V.; de Vos, Paul; Niclou, Simone P.

    2014-01-01

    Malignant brain tumors including glioblastoma are incurable cancers. Over the last years a number of promising novel treatment approaches have been investigated including the application of inhibitors of receptor tyrosine kinases and downstream targets, immune-based therapies and anti-angiogenic age

  19. Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions

    Science.gov (United States)

    Vik-Mo, Einar Osland; Sandberg, Cecilie; Olstorn, Havard; Varghese, Mercy; Brandal, Petter; Ramm-Pettersen, Jon; Murrell, Wayne; Langmoen, Iver Arne

    2010-01-01

    Traditional in vitro culturing of tumor cells has been shown to induce changes so that cultures no longer represent the tumor of origin. Serum-free culturing conditions are used in a variety of cancers to propagate stem-like cells in vitro. Limited reports, however, exist on the effects of such propagation. We have compared cells from brain tumor biopsies cultivated under serum-free conditions at passages 2 and 10 to describe the effects of in vitro culturing. We were able to establish cell lines from 7 of 10 biopsies from patients with glioblastoma. The cell lines adapted to conditions and had 2.2 times increased population doubling rate at later passages. Karyotyping and comparative genomic hybridization analysis revealed that all examined cell lines had cytogenetic aberrations commonly found in glioblastomas, and there were only minor differences between tumor and early and late passages in the same culture. Whole-transcriptome analysis shows that tumors had interindividual differences. Changes in the overall expression patterns through passaging were modest, with a significant change in only 14 genes; the variation among cultures was, however, reduced through passages. The ability to differentiate differed among tumors but was maintained throughout passaging. The cells initiated tumors upon transplantation to immunodeficient mice with differing phenotypes, but a given cell culture maintained tumor phenotype after serial cultivation. The cultures established maintained individual characteristics specific to culture identity. Thus, each cell culture reflects an image of the tumor—or a personalized model—from which it was derived and remains representative after moderate expansion. PMID:20843775

  20. Living with a Brain Tumor

    Science.gov (United States)

    ... when you have been diagnosed with a brain tumor diagnosis. Dealing with changes to your appearance – such as losing your hair or losing weight is difficult for most of us. Keep in mind that your life is not so much ... with a brain tumor may mean rethinking your work and professional goals, ...

  1. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

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

  2. Radiation-induced changes in nucleoid halo diameteres of aerobic and hypoxic SF-126 human brain tumor cells

    International Nuclear Information System (INIS)

    Nucleoid halo diameters were measured to assay changes in DNA supercoiling in human brain tumor cell line SF-126 after irradiation under aerobic or hypoxic conditions. In unirradiated aerobic cells, a typical propidium iodide titration curve showed that with increasing concentrations of propodium iodide, the halo diameter increased and then decreased with the unwinding and subsequent rewinding of DNA supercoils. In irradiated cells, the rewinding of DNA supercoils was inhibited, resulting in an increased halo diameter, in a radiation dose-dependent manner. To produce equal increases in halo diameter required about a threefold higher radiation dose in hypoxic cells than in aerobic cells. Quantitatively similiar differences in the radiation sensitivities of hypoxic and aerobic cells were demonstrated by a colony-forming efficiency assay. These findings suggest that the nucleoid halo assay may be used as a rapid measure of the inherent radiation sensitivity of human tumors. 22 refs., 5 figs

  3. DNA methylation and somatic mutations converge on cell cycle and define similar evolutionary histories in brain tumors

    Science.gov (United States)

    Johnson, Brett E.; Hong, Chibo; Hamilton, Emily G.; Bell, Robert J.A.; Smirnov, Ivan V.; Reis, Gerald F.; Phillips, Joanna J.; Barnes, Michael J.; Idbaih, Ahmed; Alentorn, Agusti; Kloezeman, Jenneke J.; Lamfers, Martine L. M.; Bollen, Andrew W.; Taylor, Barry S.; Molinaro, Annette M.; Olshen, Adam B.; Chang, Susan M.; Song, Jun S.; Costello, Joseph F.

    2015-01-01

    Summary The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution. PMID:26373278

  4. DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors.

    Science.gov (United States)

    Mazor, Tali; Pankov, Aleksandr; Johnson, Brett E; Hong, Chibo; Hamilton, Emily G; Bell, Robert J A; Smirnov, Ivan V; Reis, Gerald F; Phillips, Joanna J; Barnes, Michael J; Idbaih, Ahmed; Alentorn, Agusti; Kloezeman, Jenneke J; Lamfers, Martine L M; Bollen, Andrew W; Taylor, Barry S; Molinaro, Annette M; Olshen, Adam B; Chang, Susan M; Song, Jun S; Costello, Joseph F

    2015-09-14

    The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution. PMID:26373278

  5. Gene therapy for brain tumors.

    Science.gov (United States)

    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.

  6. Apples to origins: Identifying brain tumor stem cell genes by comparing transcriptomes of normal and cancer stem cells

    OpenAIRE

    Wortham, Matthew; Yan, Hai

    2012-01-01

    The mechanisms whereby medulloblastoma stem cells coordinate tumor propagation are poorly understood. Utilizing microarray analysis, Corno and colleagues draw parallels and distinctions between medulloblastoma stem cells from the Ptch+/− mouse and normal neural stem cells, identifying Ebf3 as a cancer stem cell-specific transcript critical for tumor growth.

  7. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  8. Oncogenic extracellular vesicles in brain tumor progression.

    Science.gov (United States)

    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

  9. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33–78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm3 (range, 0.01–35.1 cm3), and the mean marginal dose prescribed was 20.8 Gy (range, 12–25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 ± 0.4 months (95% confidence interval, 9.1–10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209–0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  10. Brain and Spinal Cord Tumors in Adults

    Science.gov (United States)

    ... 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 ...

  11. Intracranial germ cell tumor

    OpenAIRE

    Kreutz, J; Rausin, L.; Weerts, E; Tebache, M; Born, J; Hoyoux, C

    2010-01-01

    Germ cell tumours represent about 3 to 8% of pediatric brain tumours. Occurrence of diabetes insipidus is common in the case of suprasellar germ cell tumors. The diagnosis may be advanced by MRI owing to the location and relatively univocal characteristics of the lesion signal. The existence of a bifocal mass developed in both suprasellar region and pineal zone is highly suggestive of a germinoma. The most important notion is to recognize that at the time of diabetes insipidus diagnosis in a ...

  12. Recent developments in brain tumor predisposing syndromes.

    Science.gov (United States)

    Johansson, Gunnar; Andersson, Ulrika; Melin, Beatrice

    2016-01-01

    The etiologies of brain tumors are in the most cases unknown, but improvements in genetics and DNA screening have helped to identify a wide range of brain tumor predisposition disorders. In this review we are discussing some of the most common predisposition disorders, namely: neurofibromatosis type 1 and 2, schwannomatosis, rhabdoid tumor predisposition disorder, nevoid basal cell carcinoma syndrome (Gorlin), tuberous sclerosis complex, von Hippel-Lindau, Li-Fraumeni and Turcot syndromes. Recent findings from the GLIOGENE collaboration and the newly identified glioma causing gene POT1, will also be discussed. Genetics. We will describe these disorders from a genetic and clinical standpoint, focusing on the difference in clinical symptoms depending on the underlying gene or germline mutation. Central nervous system (CNS) tumors. Most of these disorders predispose the carriers to a wide range of symptoms. Herein, we will focus particularly on tumors affecting the CNS and discuss improvements of targeted therapy for the particular disorders. PMID:26634384

  13. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  14. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.

    Science.gov (United States)

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina

    2004-03-15

    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  15. Extra-axial brain tumors.

    Science.gov (United States)

    Rapalino, Otto; Smirniotopoulos, James G

    2016-01-01

    Extra-axial brain tumors are the most common adult intracranial neoplasms and encompass a broad spectrum of pathologic subtypes. Meningiomas are the most common extra-axial brain tumor (approximately one-third of all intracranial neoplasms) and typically present as slowly growing dural-based masses. Benign meningiomas are very common, and may occasionally be difficult to differentiate from more aggressive subtypes (i.e., atypical or malignant varieties) or other dural-based masses with more aggressive biologic behavior (e.g., hemangiopericytoma or dural-based metastases). Many neoplasms that typically affect the brain parenchyma (intra-axial), such as gliomas, may also present with primary or secondary extra-axial involvement. This chapter provides a general and concise overview of the common types of extra-axial tumors and their typical imaging features. PMID:27432671

  16. A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens.

    Science.gov (United States)

    Sun, Jing; Masterman-Smith, Michael D; Graham, Nicholas A; Jiao, Jing; Mottahedeh, Jack; Laks, Dan R; Ohashi, Minori; DeJesus, Jason; Kamei, Ken-ichiro; Lee, Ki-Bum; Wang, Hao; Yu, Zeta T F; Lu, Yi-Tsung; Hou, Shuang; Li, Keyu; Liu, Max; Zhang, Nangang; Wang, Shutao; Angenieux, Brigitte; Panosyan, Eduard; Samuels, Eric R; Park, Jun; Williams, Dirk; Konkankit, Vera; Nathanson, David; van Dam, R Michael; Phelps, Michael E; Wu, Hong; Liau, Linda M; Mischel, Paul S; Lazareff, Jorge A; Kornblum, Harley I; Yong, William H; Graeber, Thomas G; Tseng, Hsian-Rong

    2010-08-01

    The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform-microfluidic image cytometry (MIC)-capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured cell lines, we show simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt, and phospho-S6) within the oncogenic phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. To show the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking intertumoral and intratumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters that predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine. PMID:20631065

  17. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival

    Science.gov (United States)

    Vajkoczy, Peter; Knyazev, Pjotr; Kunkel, Andrea; Capelle, Hans-Holger; Behrndt, Sandra; von Tengg-Kobligk, Hendrik; Kiessling, Fabian; Eichelsbacher, Uta; Essig, Marco; Read, Tracy-Ann; Erber, Ralf; Ullrich, Axel

    2006-01-01

    Malignant gliomas remain incurable brain tumors because of their diffuse-invasive growth. So far, the genetic and molecular events underlying gliomagenesis are poorly understood. In this study, we have identified the receptor tyrosine kinase Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions. Furthermore, Axl is expressed at high levels in human malignant glioma. Inhibition of Axl signaling by overexpression of a dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis (growth inhibition >85%, P 72 days). A detailed analysis of the distinct hallmarks of glioma pathology, such as cell proliferation, migration, and invasion and tumor angiogenesis, revealed that inhibition of Axl signaling interfered with cell proliferation (inhibition 30% versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT, P < 0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively; P < 0.05). This study describes the identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. Our findings implicate Axl in gliomagenesis and validate it as a promising target for the development of approaches toward a therapy of these highly aggressive but, as yet, therapy-refractory, tumors. PMID:16585512

  18. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

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

  19. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

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

    1991-01-01

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

  20. Brain tumor and Gliadel wafer treatment

    Directory of Open Access Journals (Sweden)

    M Panigrahi

    2011-01-01

    Full Text Available Glioblastoma is a rapidly progressive and extremely fatal form of brain tumor with poor prognosis. It is the most common type of primary brain tumor. Even with the most aggressive conventional treatment that comprises surgery followed by radiotherapy and chemotherapy, most patients die within a year of diagnosis. Developments in molecular and cell biology have led to better understanding of tumor development, leading to novel treatment strategies including biological therapy and immunotherapy to combat the deadly disease. Targeted drug delivery strategies to circumvent the blood-brain barrier have shown efficiency in clinical trials. Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients.

  1. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Garsa, Adam A. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barani, Igor J. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Robinson, Clifford G., E-mail: crobinson@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-10-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

  2. Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells

    Directory of Open Access Journals (Sweden)

    Jung S.

    2011-10-01

    Full Text Available Tae-Ho Kim1*, Young-Il Jeong2*, Shu-Guang Jin2, Jian Pei2, Tae-Young Jung1, Kyung-Sub Moon1, In-Young Kim1, Sam-Suk Kang1, Shin Jung1,21Department of Neurosurgery, 2Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea *These authors contributed equally to this work. Background: Celecoxib, a cyclo-oxygenase (COX-2 inhibitor, has been reported to mediate growth inhibitory effects and to induce apoptosis in various cancer cell lines. In this study, we examined the potential effects of celecoxib on glioma cell proliferation, migration, and inhibition of COX-2 expression in vitro. Methods: Celecoxib was incorporated into poly DL-lactide-co-glycolide (PLGA nanoparticles for antitumor drug delivery. Results: PLGA nanoparticles incorporating celecoxib had spherical shapes and their particle sizes were in the range of 50–200 nm. Drug-loading efficiency was not significantly changed according to the solvent used, except for acetone. Celecoxib was released from the PLGA nanoparticles for more than 2 days, and the higher the drug content, the longer the duration of drug release. PLGA nanoparticles incorporating celecoxib showed cytotoxicity against U87MG tumor cells similar to that of celecoxib administered alone. Furthermore, celecoxib did not affect the degree of migration of U87MG cells. PLGA nanoparticles incorporating celecoxib showed dose-dependent cytotoxicity similar to that of celecoxib alone in C6 rat glioma cells. Western blot assay of the C6 cells showed that neither celecoxib alone nor PLGA nanoparticles incorporating celecoxib affected COX-2 expression. Conclusion: PLGA nanoparticles incorporating celecoxib had antitumor activity similar to that of celecoxib alone, even though these particles did not affect the degree of migration or COX-2 expression in the tumor cells. Keywords: celecoxib, cyclo

  3. [Chemotherapy for brain tumors in adult patients].

    Science.gov (United States)

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  5. Bioengineered 3D brain tumor model to elucidate the effects of matrix stiffness on glioblastoma cell behavior using PEG-based hydrogels.

    Science.gov (United States)

    Wang, Christine; Tong, Xinming; Yang, Fan

    2014-07-01

    Glioblastoma (GBM) is the most common and aggressive form of primary brain tumor with a median survival of 12-15 months, and the mechanisms underlying GBM tumor progression remain largely elusive. Given the importance of tumor niche signaling in driving GBM progression, there is a strong need to develop in vitro models to facilitate analysis of brain tumor cell-niche interactions in a physiologically relevant and controllable manner. Here we report the development of a bioengineered 3D brain tumor model to help elucidate the effects of matrix stiffness on GBM cell fate using poly(ethylene-glycol) (PEG)-based hydrogels with brain-mimicking biochemical and mechanical properties. We have chosen PEG given its bioinert nature and tunable physical property, and the resulting hydrogels allow tunable matrix stiffness without changing the biochemical contents. To facilitate cell proliferation and migration, CRGDS and a MMP-cleavable peptide were chemically incorporated. Hyaluronic acid (HA) was also incorporated to mimic the concentration in the brain extracellular matrix. Using U87 cells as a model GBM cell line, we demonstrate that such biomimetic hydrogels support U87 cell growth, spreading, and migration in 3D over the course of 3 weeks in culture. Gene expression analyses showed U87 cells actively deposited extracellular matrix and continued to upregulate matrix remodeling genes. To examine the effects of matrix stiffness on GBM cell fate in 3D, we encapsulated U87 cells in soft (1 kPa) or stiff (26 kPa) hydrogels, which respectively mimics the matrix stiffness of normal brain or GBM tumor tissues. Our results suggest that changes in matrix stiffness induce differential GBM cell proliferation, morphology, and migration modes in 3D. Increasing matrix stiffness led to delayed U87 cell proliferation inside hydrogels, but cells formed denser spheroids with extended cell protrusions. Cells cultured in stiff hydrogels also showed upregulation of HA synthase 1 and matrix

  6. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    Science.gov (United States)

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  7. Brain and Spinal Tumors: Hope through Research

    Science.gov (United States)

    ... and worsen as the tumor grows. The most obvious sign of a brain tumor in infants is ... blood flow, antidepressants to treat anxiety or ease depression that might occur following a tumor diagnosis, and ...

  8. Targeted Toxins in Brain Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Walter A. Hall

    2010-11-01

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

  9. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  10. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    OpenAIRE

    Panosyan, Eduard H.; IKEDA, ALAN K.; Chang, Vivian Y.; Laks, Dan R.; Charles L. Reeb; La Vette Bowles; Lasky, Joseph L.; Moore, Theodore B.

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal ...

  11. Malignant brain tumor treatments and hyperbaric oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Kohshi, Kiyotaka [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    2000-09-01

    Malignant brain tumor treatment and hyperbaric oxygenation: Combined hyperbaric oxygenation (HBO) therapy and radiation therapy of malignant gliomas is reviewed. Malignant glioma tissue is hypoxic, and the efficacy of radiation therapy is increased by raising the oxygen density in glioma tissue. Residual tumor was reduced by a radiation dose of approximately 40 Gy in many cases when radiation therapy was begun within 15 minutes after HBO. In the experiment in animal models with different hypoxic fractions (HFs) of cells (SCCVII and 9L gliosarcoma), the tumor reduction effect was more significant in the SCCVII model, which has a higher HF. When the SCCVII model was irradiated within 30 minutes after HBO, the improvement effect was more significant (1.60-1.78 times) than by irradiation alone. HBO was effective in the treatment of radionecrosis of the brain. However, there were some cases in which radionecrosis progressed when the HBO treatments were discontinued, and the optimal duration of HBO treatment should be determined. It is difficult to differentiate between radionecrosis and tumor recurrence after radiosurgery of a malignant intracranial tumor. When no lesion reduction is observed in response to HBO treatment and steroid administration for about one month, the lesion is concluded to be a recurrence of the tumor, and additional irradiation should be performed. HBO treatment in combination with chemotherapy is also discussed. (K.H.)

  12. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    Science.gov (United States)

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

    2005-07-01

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

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

    Science.gov (United States)

    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.

  14. Extracellular Vesicles in Brain Tumor Progression.

    Science.gov (United States)

    D'Asti, Esterina; Chennakrishnaiah, Shilpa; Lee, Tae Hoon; Rak, Janusz

    2016-04-01

    Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non-random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways

  15. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    Science.gov (United States)

    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

  16. Towards the application of alginate cell microencapsulation technologies to treat brain tumors

    NARCIS (Netherlands)

    Bhujbal, Swapnil

    2015-01-01

    Eén van de grootste uitdagingen in de oncologie is het vinden van een succesvolle behandeling tegen hersentumoren. Ondanks geavanceerde behandelingsmogelijkheden, zoals tumormassa debulking door middel van bestraling en chemotherapie, is tumor recidief onvermijdelijk, met een overleving van minder d

  17. 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

    Science.gov (United States)

    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

  18. The impact of dietary isoflavonoids on malignant brain tumors.

    Science.gov (United States)

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

    2014-08-01

    Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose-response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach. PMID:24898306

  19. Radiosensitized treatment of malignant brain tumors

    Science.gov (United States)

    Bloznelyte-Plesniene, Laima

    2003-12-01

    Around 12,000 deaths from glioblastoma occurs within the European Community annually. At present, the best available treatment for malignant brain tumors results in a median survival of patients of 15 months despite surgery, radiotherapy, and chemotherapy. The purpose of this paper is to review our results of radiosensitized treatment of malignant brain tumors.

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

    Science.gov (United States)

    ... tissues and cells, which can develop into different types of tumors. Neurons (nerve cells): These are the most important cells ... as long as several feet. Unlike many other types of cells that can grow and divide to repair damage from injury or disease, neurons in the brain and spinal cord largely stop ...

  1. Metaphyseal giant cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L.F.; Hemais, P.M.P.G.; Aymore, I.L.; Carmo, M.C.R. do; Cunha, M.E.P.R. da; Resende, C.M.C.

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed.

  2. Metaphyseal giant cell tumor

    International Nuclear Information System (INIS)

    Three cases of metaphyseal giant cell tumor are presented. A review of the literature is done, demostrating the lesion is rare and that there are few articles about it. Age incidence and characteristics of the tumor are discussed. (Author)

  3. Dynamic perfusion CT in brain tumors.

    Science.gov (United States)

    Yeung, Timothy Pok Chi; Bauman, Glenn; Yartsev, Slav; Fainardi, Enrico; Macdonald, David; Lee, Ting-Yim

    2015-12-01

    Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented.

  4. Nonislet Cell Tumor Hypoglycemia

    OpenAIRE

    Johnson Thomas; Salini C. Kumar

    2013-01-01

    Nonislet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia. It is characterized by increased glucose utilization by tissues mediated by a tumor resulting in hypoglycemia. NICTH is usually seen in large mesenchymal tumors including tumors involving the GI tract. Here we will discuss a case, its pathophysiology, and recent advances in the management of NICTH. Our patient was diagnosed with poorly differentiated squamous cell carcinoma of esophagus. He continued to be hypoglycemic ...

  5. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

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

  6. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

    Directory of Open Access Journals (Sweden)

    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  7. Brain tumors in children; Hirntumoren beim Kind

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-15

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

  8. Proteomic and immunologic analyses of brain tumor exosomes

    OpenAIRE

    Graner, Michael W.; Alzate, Oscar; Dechkovskaia, Angelika M.; Keene, Jack D.; Sampson, John H; Mitchell, Duane A; Bigner, Darell D.

    2009-01-01

    Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30–100 nm membranous vesicles released from many cell types into the extracellular milieu; surprisingly, exosomes are virtually unstudied in neuro-oncology. These microvesicles were used as vaccines in other tumor settings, but their immunological significance is unevaluated in brain tu...

  9. Brain tumors in patients primarly treated psychiatrically

    Directory of Open Access Journals (Sweden)

    Ignjatović-Ristić Dragana

    2011-01-01

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

  10. High-dose chemotherapy with autologous hematopoietic stem-cell rescue for pediatric brain tumor patients: a single institution experience from UCLA.

    Science.gov (United States)

    Panosyan, Eduard H; Ikeda, Alan K; Chang, Vivian Y; Laks, Dan R; Reeb, Charles L; Bowles, La Vette; Lasky, Joseph L; Moore, Theodore B

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999-2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n = 16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P < .01). Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions. PMID:21559259

  11. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    Directory of Open Access Journals (Sweden)

    Eduard H. Panosyan

    2011-01-01

    Full Text Available Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR. Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009. Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma, 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n=16. Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs. Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P<.01. Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions.

  12. Photodynamic Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    Akimoto, Jiro

    2016-04-15

    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

  13. Research on Perfusion CT in Rabbit Brain Tumor Model

    International Nuclear Information System (INIS)

    We investigated the vascular characteristics of tumors and normal tissue using perfusion CT in the rabbit brain tumor model. The VX2 carcinoma concentration of 1 x 107 cells/ml(0.1 ml) was implanted in the brain of nine New Zealand white rabbits (weight: 2.4 kg-3.0 kg, mean: 2.6 kg). The perfusion CT was scanned when the tumors were grown up to 5 mm. The tumor volume and perfusion value were quantitatively analyzed by using commercial workstation (advantage windows workstation, AW, version 4.2, GE, USA). The mean volume of implanted tumors was 316±181 mm3, and the biggest and smallest volumes of tumor were 497 mm3 and 195 mm3, respectively. All the implanted tumors in rabbits are single-nodular tumors, and intracranial metastasis was not observed. In the perfusion CT, cerebral blood volume (CBV) were 74.40±9.63, 16.8±0.64, 15.24±3.23 ml/100g in the tumor core, ipsilateral normal brain, and contralateral normal brain, respectively (p≤0.05). In the cerebral blood flow (CBF), there were significant differences between the tumor core and both normal brains (p≤0.05), but no significant differences between ipsilateral and contralateral normal brains (962.91±75.96 vs. 357.82±12.82 vs. 323.19±83.24 ml/100g/min). In the mean transit time (MTT), there were significant differences between the tumor core and both normal brains (p≤0.05), but no significant differences between ipsilateral and contralateral normal brains (4.37±0.19 vs. 3.02±0.41 vs. 2.86±0.22 sec). In the permeability surface (PS), there were significant differences among the tumor core, ipsilateral and contralateral normal brains (47.23±25.44 vs. 14.54±1.60 vs. 6.81±4.20 ml/100g/min)(p≤0.05). In the time to peak (TTP) were no significant differences among the tumor core, ipsilateral and contralateral normal brains. In the positive enhancement integral (PEI), there were significant differences among the tumor core, ipsilateral and contralateral brains (61.56±16.07 vs. 12.58±2.61 vs. 8.26±5

  14. Research on Perfusion CT in Rabbit Brain Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Bon Chul; Kwak, Byung Kook; Jung, Ji Sung [Dept. of Diagnostic Radiology, Chung Ang University Hospital, Seoul (Korea, Republic of); Lim, Cheong Hwan; Jung, Hong Ryang [Dept. of Radiological Science, Hanseo University, Seosan (Korea, Republic of)

    2012-06-15

    We investigated the vascular characteristics of tumors and normal tissue using perfusion CT in the rabbit brain tumor model. The VX2 carcinoma concentration of 1 x 10{sup 7} cells/ml(0.1 ml) was implanted in the brain of nine New Zealand white rabbits (weight: 2.4 kg-3.0 kg, mean: 2.6 kg). The perfusion CT was scanned when the tumors were grown up to 5 mm. The tumor volume and perfusion value were quantitatively analyzed by using commercial workstation (advantage windows workstation, AW, version 4.2, GE, USA). The mean volume of implanted tumors was 316{+-}181 mm{sup 3}, and the biggest and smallest volumes of tumor were 497 mm{sup 3} and 195 mm{sup 3}, respectively. All the implanted tumors in rabbits are single-nodular tumors, and intracranial metastasis was not observed. In the perfusion CT, cerebral blood volume (CBV) were 74.40{+-}9.63, 16.8{+-}0.64, 15.24{+-}3.23 ml/100g in the tumor core, ipsilateral normal brain, and contralateral normal brain, respectively (p{<=}0.05). In the cerebral blood flow (CBF), there were significant differences between the tumor core and both normal brains (p{<=}0.05), but no significant differences between ipsilateral and contralateral normal brains (962.91{+-}75.96 vs. 357.82{+-}12.82 vs. 323.19{+-}83.24 ml/100g/min). In the mean transit time (MTT), there were significant differences between the tumor core and both normal brains (p{<=}0.05), but no significant differences between ipsilateral and contralateral normal brains (4.37{+-}0.19 vs. 3.02{+-}0.41 vs. 2.86{+-}0.22 sec). In the permeability surface (PS), there were significant differences among the tumor core, ipsilateral and contralateral normal brains (47.23{+-}25.44 vs. 14.54{+-}1.60 vs. 6.81{+-}4.20 ml/100g/min)(p{<=}0.05). In the time to peak (TTP) were no significant differences among the tumor core, ipsilateral and contralateral normal brains. In the positive enhancement integral (PEI), there were significant differences among the tumor core, ipsilateral and

  15. Tumor cell metabolism

    Science.gov (United States)

    Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B´ez-Viveros, José Luis; Aguilar-Cazares, Dolores

    2011-01-01

    Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

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

    Science.gov (United States)

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

    2016-07-01

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

  17. Asymptomatic brain tumor detected at brain check-up

    Energy Technology Data Exchange (ETDEWEB)

    Onizuka, Masanari; Suyama, Kazuhiko; Shibayama, Akira; Hiura, Tsuyoshi; Horie, Nobutaka; Miyazaki, Hisaya [Sankoukai Miyazaki Hospital, Isahaya, Nagasaki (Japan)

    2001-09-01

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

  18. Therapeutic vaccines for malignant brain tumors

    Directory of Open Access Journals (Sweden)

    Michael P Gustafson

    2008-12-01

    Full Text Available Michael P Gustafson1, Keith L Knutson2, Allan B Dietz11Division of Transfusion Medicine; 2Department of Immunology, Mayo Clinic, Rochester, MN, USAAbstract: Malignant gliomas are the most common and aggressive form of brain tumors. Current therapy consists of surgical resection, followed by radiation therapy and concomitant chemotherapy. Despite these treatments, the prognosis for patients is poor. As such, investigative therapies including tumor vaccines have targeted this devastating condition. Recent clinical trials involving immunotherapy, specifically dendritic cell (DC based vaccines, have shown promising results. Overall, these vaccines are well tolerated with few documented side effects. In many patients receiving vaccines, tumor progression was delayed and the median overall survival of these patients was prolonged. Despite these encouraging results, several factors have limited the efficacy of DC vaccines. Here we discuss the potential of DC vaccines as adjuvant therapy and current obstacles of generating highly pure and potent DC vaccines in the context of malignant glioma. Taken together, the results from earlier clinical studies justify additional clinical trials aimed at improving the efficacy of DC vaccines.Keywords: malignant glioma, glioblastoma multiforme, vaccine, immunotherapy, dendritic cells

  19. Cognitive deficits in patients with brain tumor

    Institute of Scientific and Technical Information of China (English)

    SHEN Chao; BAO Wei-min; YANG Bo-jie; XIE Rong; CAO Xiao-yun; LUAN Shi-hai; MAO Ying

    2012-01-01

    Objective To discuss the present status and progress of clinical research on the cognitive effects caused by different types of brain tumors and common treatments.Data sources The data used in this review were mainly from PubMed articles published in English from 1990 to Febuary 2012.Research terms were "cognitive deficits" or "cognitive dysfunction".Study selection Articals including any information about brain tumor related cognitive deficits were selected.Results It is widely accepted that brain tumors and related treatments can impair cognitive function across manydomains,and can impact on patients' quality of life.Tumor localization,lateralization,surgery,drugs,radiotherapy and chemotherapy are all thought to be important factors in this process.However,some conflicting findings regarding brain tumor-related cognitive deficits have been reported.It can be difficult to determine the mechanism of these treatments,such as chemotherapy,antibiotics,antiepileptics,and steroids.Future research is needed to clarify these potential treatment effects.Conclusions Cognitive function is important for patients with brain tumor.Much more focus has been paid on this field.It should be regarded as an important prognostic index for the patients with brain tumor,and neuropsychological tests should be used in regular examinations.

  20. Dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Singhaniya Shikha

    2009-01-01

    Full Text Available Dentinogenic ghost cell tumor (DGCT is a rare tumorous form of calcifying odontogenic cyst and only a small number of cases have been described. It is a locally invasive neoplasm that is characterized by ameloblastoma-like epithelial islands, ghost cells and dentinoid. The present report describes a case of a 21-year-old male with a tumor in the posterior region of the mandible, showing features of DGCT.

  1. Olfactory ensheathing cell tumor

    Directory of Open Access Journals (Sweden)

    Ippili Kaushal

    2009-01-01

    Full Text Available Olfactory ensheathing cells (OECs are found in the olfactory bulb and olfactory nasal mucosa. They resemble Schwann cells on light and electron microscopy, however, immunohistochemical staining can distinguish between the two. There are less than 30 cases of olfactory groove schwannomas reported in the literature while there is only one reported case of OEC tumor. We report an OEC tumor in a 42-year-old male and discuss the pathology and origin of this rare tumor.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yoshinobu [Department of Neurosurgery, Kagawa National Children' s Hospital, Kagawa 765-8501 (Japan)], E-mail: ynakagawa0517@yahoo.co.jp; Kageji, Teruyoshi; Mizobuchi, Yoshifumi [Department of Neurosurgery, University of Tokushima, Tokushima 770-8503 (Japan); Kumada, Hiroaki [Department of Research Reactor, Japan Atomic Energy Research Institute, Ibaragi 319-1195 (Japan); Nakagawa, Yoshiaki [Department of Medical Informatics, Post Graduated School, Kyoto University, Kyoto (Japan)

    2009-07-15

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

  3. Multiple granular cell tumor.

    Science.gov (United States)

    Jones, J K; Kuo, T T; Griffiths, C M; Itharat, S

    1980-10-01

    Eleven cases of granular cell tumor were reviewed. In two of the cases multiple sites of involvement were seen. The tumor occurred in the oral cavity in both of these cases and each was initially wrongly diagnosed as squamous cell carcinoma. The most common site was the subcutaneous tissue (nine patients) and the tongue was involved in three cases. In one patient the parotid gland was involved. Eight of the patients were females and three were males; seven were black and four were white. The importance of differentiating between squamous cell carcinoma and granular cell tumor is stressed, as is the need for a simple wide surgical excision. PMID:7421377

  4. Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice.

    Directory of Open Access Journals (Sweden)

    Luis A Sanchez-Perez

    Full Text Available Temozolomide (TMZ is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed that recovery from chemotherapy-induced lymphopenia may actually be exploited to potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA TMZ resulted in markedly reduced CD4(+, CD8(+ T-cell and CD4(+Foxp3(+ TReg counts. Adoptive transfer of naïve CD8(+ T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8(+ T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ-but not lymphodepletive, NMA TMZ-led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain tumors.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. PMID:26749497

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

    Directory of Open Access Journals (Sweden)

    Yacoob Sulafa M

    2012-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

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

  9. Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage

    Science.gov (United States)

    Srivenugopal, Kalkunte S.

    2014-01-01

    The alcohol aversion drug disulfiram (DSF) reacts and conjugates with the protein-bound nucleophilic cysteines and is known to elicit anticancer effects alone or improve the efficacy of many cancer drugs. We investigated the effects of DSF on human O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein and chemotherapy target that removes the mutagenic O6-akyl groups from guanines, and thus confers resistance to alkylating agents in brain tumors. We used DSF, copper-chelated DSF or CuCl2–DSF combination and found that all treatments inhibited the MGMT activity in two brain tumor cell lines in a rapid and dose-dependent manner. The drug treatments resulted in the loss of MGMT protein from tumor cells through the ubiquitin-proteasome pathway. Evidence showed that Cys145, a reactive cysteine, critical for DNA repair was the sole site of DSF modification in the MGMT protein. DSF was a weaker inhibitor of MGMT, compared with the established O6-benzylguanine; nevertheless, the 24–36h suppression of MGMT activity in cell cultures vastly increased the alkylation-induced DNA interstrand cross-linking, G2/M cell cycle blockade, cytotoxicity and the levels of apoptotic markers. Normal mice treated with DSF showed significantly attenuated levels of MGMT activity and protein in the liver and brain tissues. In nude mice bearing T98 glioblastoma xenografts, there was a preferential inhibition of tumor MGMT. Our studies demonstrate a strong and direct inhibition of MGMT by DSF and support the repurposing of this brain penetrating drug for glioma therapy. The findings also imply an increased risk for alkylation damage in alcoholic patients taking DSF. PMID:24193513

  10. Permeability imaging in pediatric brain tumors

    OpenAIRE

    Lam, Sandi; Lin, Yimo; Warnke, Peter C.

    2014-01-01

    While traditional computed tomography (CT) and magnetic resonance (MR) imaging illustrate the structural morphology of brain pathology, newer, dynamic imaging techniques are able to show the movement of contrast throughout the brain parenchyma and across the blood-brain barrier (BBB). These data, in combination with pharmacokinetic models, can be used to investigate BBB permeability, which has wide-ranging applications in the diagnosis and management of central nervous system (CNS) tumors in ...

  11. Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes

    Directory of Open Access Journals (Sweden)

    Carlo Cusulin

    2015-07-01

    Full Text Available In glioblastoma multiforme (GBM, brain-tumor-initiating cells (BTICs with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.

  12. Proton MRS imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

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

    Science.gov (United States)

    Mathis, Sarah E; Alberico, Anthony; Nande, Rounak; Neto, Walter; Lawrence, Logan; McCallister, Danielle R; Denvir, James; Kimmey, Gerrit A; Mogul, Mark; Oakley, Gerard; Denning, Krista L; Dougherty, Thomas; Valluri, Jagan V; Claudio, Pier Paolo

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sarah E Mathis

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

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

    Directory of Open Access Journals (Sweden)

    Zheng Fan

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

  16. Astrocytes Directly Influence Tumor Cell Invasion and Metastasis In Vivo

    OpenAIRE

    Wang, Ling; Cossette, Stephanie M.; Rarick, Kevin R.; Gershan, Jill; Michael B Dwinell; Harder, David R.; Ramchandran, Ramani

    2013-01-01

    Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among wh...

  17. MRI and MRS of human brain tumors.

    Science.gov (United States)

    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).

  18. Stages of Adult Brain Tumors

    Science.gov (United States)

    ... Unknown Primary Treatment Colon Cancer Treatment Leukemia Home Page Melanoma Treatment Nasopharyngeal Cancer Treatment Non-Small Cell Lung Cancer Treatment Renal Cell Cancer Treatment Small Cell ...

  19. Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model

    International Nuclear Information System (INIS)

    Glioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments. The U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2–6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography. MMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells. Radiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent “U87-Fluc”was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate

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

    Science.gov (United States)

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

    2016-07-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment. PMID:26614346

  1. Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    Hua HU; Er-qing WEI; Gao CHEN; Jian-min ZHANG; Wei-ping ZHANG; Lei ZHANG; Qiu-fu GE; Hong-tian YAO; Wei DING; Zhong CHEN

    2005-01-01

    Aim: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2),one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. Methods: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. Results: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells.Conclusion: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

  2. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  3. General Information About Childhood Central Nervous System Germ Cell Tumors

    Science.gov (United States)

    ... germ cell tumors to form is near the pineal gland and in an area of the brain that ... of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in ...

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

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

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

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

    Science.gov (United States)

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

    . Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d'Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. * The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types

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

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    Manjula S

    2010-01-01

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

  7. Brain tumors induced in rats by human adenovirus type 12

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    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  8. Multidrug resistance (MDR) in brain tumors; its clinical importance

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. Z. [Thomas Jefferson Univ., Philadelphia (United States); Park, C. H.; Kim, S. M.; Cho, K. K.; Bai, M. S.; Yoon, S. N.; Cho, C. W.; Jin, Y. M.; Kim, Y. S. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    MDR is one of the important factors affecting chemotherapy in high grade brain malignancies. Especially it affects commonly used agents such as vincristine, VP16, VM26, and cisplatin. MDR1 gene encoded P-glycoprotein (Pgp) prevents intratumoral retention of such drugs by expelling them at the plasma membrance of brain tumor cells. Therefore, the objective of this study was to evaluate MDR in various brain tumors including metastatic tumors including metastatic tumors by dual isotope SPECT, Northern blotting or immunohistochemical staining (IHCS) using JSB-1 monoclonal antibody against MDR1 gene encoded Pgp. Twenty one patients with various brain tumors of primary, secondary, and recurrent tumors were included from 2 institutions. Whenever possible, surgical specimen from these patients were obtained to study MDR. SPET was performed with a tripple head system (Trionix, Twinsburg, Ohio or MultiSPECT 3, Siemens). Three millicuries of {sup 201}Tl chloride and 20 mCi of {sup 99m}Tc-sestamibi were adminstered and SPET was performed in about 15 min. Nineteen percent of patients had MIBI (-) and Tl (+) suggesting MDR (+). MIBI tumor uptake was higher in recurrence (6.67 +/- 1.3) than the stable original tumors (3.12 +/-0.77) (For {sup 201}Tl, 3.65 +/-2.2 Vs 1.5 +/-0.41). Three recurrent gliomas biopsied showed positive blotting and these patients failed several courses of chemotherapy. Six patients with various tumors such as oligodendroglioma, meningioma, recurrent G-M (2), and astrocytoma (2) were studied by IHCS, Weakly positive MDR was seen in one recurrent G-M and an astrocytoma case. Positive MDR was seen in the other recurrent G-M and a meningioma. In conclusion, MDR in brain tumors is detected successfully by dual isotope SPECT studies in a limited number of patients. MDR in benign brain tumors has no clinical significance since they are cured by surgical removal. However, we believe its presence in metastatic and high grade especially recurrent tumors is an

  9. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

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

  10. The delivery of BCNU to brain tumors.

    Science.gov (United States)

    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.

  11. MicroRNA and Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    MicroRNAs (miRNAs) were first described in 1993 by Lee and colleagues, and the term microRNA was only introduced in 2001 in a set of three articles in Science[1]. One of the biggest surprises in the past few years has been the emergence of miRNAs as a major new class of gene expression regulators. Recent studies suggest that miRNA alterations are involved in the initiation and progression of human cancer. The brain tumor,glioblastoma multiforme, is the most malignant and deadly form of gliomas.The prognosis is poor and the median survival with combined radiotherapy and chemotherapy is only 14.6 months. With the discovery of miRNA, the miRNA profiles may become useful biomarkers for brain tumor diagnostics,and miRNA therapy could be a powerful tool for brain tumor prevention and therapeutics. This review outlines the background of miRNA and its expression and therapeutic potential for brain tumors.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

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

  14. A Rare Malignant Fetal Brain Tumor.

    Science.gov (United States)

    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

  15. Brain tumors in childhood; Hirntumoren im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Sinzig, M.; Gasser, J.; Hausegger, K.A. [Landeskrankenhaus Klagenfurt, Kinderradiologie RZI, Klagenfurt (Austria); Jauk, B. [Landeskrankenhaus Klagenfurt, Abt. fuer Kinder- und Jugendheilkunde, Klagenfurt (Austria)

    2008-10-15

    Central nervous system (CNS) tumors are the most common solid neoplasms in childhood and the second most common malignancies after leukemia in the pediatric age group. Supratentorial tumors are more common in children younger than 2 years old and in adolescents, whereas in patients between 2 and 12 years of age brain tumors originating in the posterior fossa dominate. This implies a relationship between the type of tumor, its location and the age of the patient, which has to be considered in differential diagnoses. Medulloblastoma represents the most common malignant brain tumor in childhood. In the posterior fossa medulloblastomas are approximately as frequent as astrocytomas. Supratentorial astrocytomas are by far the main tumor type. In this report some typical CNS neoplasms in children are discussed and their neuroradiological features are demonstrated. (orig.) [German] Hirntumoren sind die haeufigsten soliden Tumoren des Kindesalters und repraesentieren nach den Leukaemien die zweithaeufigsten malignen Erkrankungen bei Kindern. Waehrend bei Kleinkindern und Adoleszenten supratentorielle Hirntumoren ueberwiegen, ist bei Patienten zwischen 2 und 12 Jahren haeufiger die hintere Schaedelgrube Ursprungsort dieser Malignome. Daraus geht hervor, dass gewisse Tumortypen eine gewisse Alterspraedilektion aufweisen, was neben der radiologischen Morphologie der Raumforderung fuer differenzialdiagnostische Ueberlegungen ueberaus hilfreich sein kann. Das Medulloblastom ist das haeufigste ZNS-Malignom des Kindesalters und repraesentiert zusammen mit zerebellaeren Astrozytomen auch den haeufigsten Tumortyp der hinteren Schaedelgrube. Supratentoriell stehen die Astrozytome ganz im Vordergrund. In dieser Arbeit werden einige typische kindliche infra- und supratentorielle Hirntumoren diskutiert und ihre neuroradiologischen Merkmale dargestellt. (orig.)

  16. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  17. Familial germ cell tumor

    OpenAIRE

    Sanju Cyriac; Rejeev Rajendranath; A. Robert Louis; Sagar, T. G.

    2012-01-01

    Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presenc...

  18. Brain Metastases in Patients With Germ Cell Tumors: Prognostic Factors and Treatment Options—An Analysis From the Global Germ Cell Cancer Group

    Science.gov (United States)

    Feldman, Darren R.; Lorch, Anja; Kramar, Andrew; Albany, Costantine; Einhorn, Lawrence H.; Giannatempo, Patrizia; Necchi, Andrea; Flechon, Aude; Boyle, Helen; Chung, Peter; Huddart, Robert A.; Bokemeyer, Carsten; Tryakin, Alexey; Sava, Teodoro; Winquist, Eric William; De Giorgi, Ugo; Aparicio, Jorge; Sweeney, Christopher J.; Cohn Cedermark, Gabriella; Powles, Thomas

    2016-01-01

    Purpose To define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT). Patients and Methods Data from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point. Results BM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P < .001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of α-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to 70% in group A and from 6% to 52% in group B. In group A, 99% of patients received chemotherapy; multimodality treatment or high-dose chemotherapy was not associated with statistically improved survival in multivariable analysis. In group B, only 54% of patients received chemotherapy; multimodality treatment was associated with improved survival compared with single-modality therapy (hazard ratio, 0.51; 95% CI, 0.36 to 0.73; P < .001), as was high-dose compared with conventional-dose chemotherapy (hazard ratio, 0.41; 95% CI, 0.24 to 0.70; P = .001). Conclusion Men with BM from GCT have poor OS, particularly if additional risk factors are present. High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM at relapse. PMID:26460295

  19. New Experimental Model of Brain Tumors in Brains of Adult Immunocompetent Rats

    OpenAIRE

    Baklaushev, Vladimir P.; Kavsan, Vadym M.; Balynska, Olena V; Yusubalieva, Gaukhar M.; Abakumov, Maxim A.; Chekhonin, Vladimir P.

    2012-01-01

    Aims: Xenograft models, namely heterotransplantation of human cancer cells or tumor biopsies into immunodeficient rodents are the major preclinical approach for the development of novel cancer therapeutics. However, in these models the animals must be used only after the severe systemic immune suppression in order to ensure graft survival. Thus, additional new human brain tumor models without immune suppression of the recipient rodent may be required. Place and Duration of Study: Laboratory o...

  20. Radiation treatment of brain tumors: Concepts and strategies

    Energy Technology Data Exchange (ETDEWEB)

    Marks, J.E. (Loyola Univ. of Chicago Stritch School of Medicine, Maywood, IL (USA))

    1989-01-01

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

  1. Extraovarian granulosa cell tumor

    Directory of Open Access Journals (Sweden)

    Paul Prabir

    2009-04-01

    Full Text Available Extraovarian granulosa cell tumor (GCT is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15cm x 16cm and another mesenteric mass of 8cm x 5cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

  2. Astrocytes directly influence tumor cell invasion and metastasis in vivo.

    Directory of Open Access Journals (Sweden)

    Ling Wang

    Full Text Available Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2 (MMP-2 and MMP-9 were partly responsible for the astrocyte media-induced tumor cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and invade in vitro. Further, injection of astrocyte media-conditioned breast cancer cells in mice showed increased invasive activity to the brain and other distant sites. More importantly, blocking the preconditioned tumor cells with broad spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells, in particular to the brain in vivo. Collectively, our data implicate astrocyte-derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration and invasion leading to brain metastasis.

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

    Science.gov (United States)

    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.

  4. Brain Tumor Detection Based On Symmetry Information

    OpenAIRE

    G., Narkhede Sachin; Khairnar, Vaishali

    2013-01-01

    Advances in computing technology have allowed researchers across many fields of endeavor to collect and maintain vast amounts of observational statistical data such as clinical data, biological patient data, data regarding access of web sites, financial data, and the like. This paper addresses some of the challenging issues on brain magnetic resonance (MR) image tumor segmentation caused by the weak correlation between magnetic resonance imaging (MRI) intensity and anatomical meaning. With th...

  5. Mapping of language brain areas in patients with brain tumors.

    Science.gov (United States)

    Hyder, Rasha; Kamel, Nidal; Boon, Tang Tong; Reza, Faruque

    2015-08-01

    Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them. PMID:26736340

  6. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Tomohiko, E-mail: matsutomo_llp@yahoo.co.jp [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan); Kogo, Kasei [Kumamoto Radiosurgery Clinic, Kumamoto (Japan); Oya, Natsuo [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan)

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  7. Familial germ cell tumor

    Directory of Open Access Journals (Sweden)

    Sanju Cyriac

    2012-01-01

    Full Text Available Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile.

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

    Science.gov (United States)

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

    2015-03-01

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

  9. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders;

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...

  10. Non-FDG PET imaging of brain tumors

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  11. Nuclear magnetic resonance imaging in brain tumors

    International Nuclear Information System (INIS)

    Full text: Magnetic resonance imaging (MRI) is a non-invasive imaging method based on the detecting signal from hydrogen nuclei of water molecules and fat. Performances of MRI are continuously increasing, and its domains of investigation of the human body are growing in both morphological and functional study. MRI also allows It also performing advanced management of tumours especially in the brain, by combining anatomical information (morphological MRI), functional (diffusion, perfusion and BOLD contrast) and metabolic (tissue composition in magnetic resonance spectroscopy (MRS)). The MRI techniques have an important role in cancerology. These techniques allow essential information for the diagnosis and answering therapist's questions before, during or after the treatment. The MR allows clarifying the localization of expanding processes, the differential diagnosis between brain tumour and a lesion confined by another structural aspect, the diagnosis of the tumoral aspect of a lesion, the histological ranking in case of glial tumour and the extension of its localization as well as the therapeutic follow-up (pre-therapeutic and post-therapeutics assessments). A better combination between the morphological, functional and metabolic studies, as well as integrating new technical developments, especially while using a multichannel bird cage coils the 3T magnet and suitable computing software, would allow significant improvements of the exploration strategies and management of brain tumors.

  12. Simulating ‘structure-function’ patterns of malignant brain tumors

    Science.gov (United States)

    Mansury, Yuri; Deisboeck, Thomas S.

    2004-01-01

    Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called ‘beaten-path advantage’ intensifies, i.e., rising ‘mechanical rewards’ for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed.

  13. Brain Tumors and Neurosurgeon Neuroradiologist Relations

    Directory of Open Access Journals (Sweden)

    Jalal Jalal Shokouhi

    2009-01-01

    Full Text Available "nToday the modality of choice for brain tumors is MRI with and without GD. "nGD injection needs during to stage T1, before injection and after injection for image subtracts to see the enhancement degree, detecting crystallized calcification, colloid and fat material also methemoglubin inside the tumor. "n- In case of thin layer seeding, GD MRI could be positive but T2 and FLAIR images could be negative "no mass effect". "n- For meningiomas if you do not want to inject contrast media please request plain CT SCAN that is stronger than non-contrasted MRI but GD MRI is the choice and better than both. "n- For small or micro-vestibular schwannoma do not request CT please request MRI with GD. "n- In craniopharyngioma request non-contrast CT with combination of MRI with and without GD. "n- For micro-adenoma request dynamic MRI "better than Dynamic CT" "n- please do not use axial CT and non-contrasted coronal CT for micro-adenoma". "n- Few infiltrative non-enhancing tumors need serial MRI to be differentiated from CVA. "n- For differentiation of tumor recurrency from radiotherapy necrosis MRS is necessary. "nOther lecture notes will be discussed in the round table.  

  14. Intraoperative MRI in pediatric brain tumors

    International Nuclear Information System (INIS)

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

  15. Intraoperative MRI in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  16. Positron Scanner for Locating Brain Tumors

    Science.gov (United States)

    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)

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

    Science.gov (United States)

    ... into the body, where they settle in the bone marrow and start making new blood cells. Although some children with certain brain or spinal cord tumors (such as medulloblastomas) have responded well ...

  18. An integrative view on sex differences in brain tumors

    OpenAIRE

    Sun, Tao; Plutynski, Anya; Ward, Stacey; Rubin, Joshua B.

    2015-01-01

    Sex differences in human health and disease can range from undetectable to profound. Differences in brain tumor rates and outcome are evident in males and females throughout the world and regardless of age. These observations indicate that fundamental aspects of sex determination can impact the biology of brain tumors. It is likely that optimal personalized approaches to the treatment of male and female brain tumor patients will require recognizing and understanding the ways in which the biol...

  19. 脑肿瘤干细胞来源及表面标记物研究的新进展%Progress in the source and surface markers of brain tumor stem cells

    Institute of Scientific and Technical Information of China (English)

    邱实; 谭晓华; 黄辉

    2012-01-01

    BACKGROUND: With the study of brain tumors, researchers have found that brain tumor stem cells (BTSCs) play an important role in tumor growth, development, recurrence and metastasis.OBJECTIVE: To review the source, biological characters and research progress of BCTCs.METHODS: The Wanfang database and ELSEVIER database were used to search the related articles about BTCTs published between January 1998 and January 2010 with the key words of "brain tumor stem cells" in Chinese and "brain tumor stem cells, BTCTs" in English. Totally 198 literatures were screened out, and finally 25 important articles were selected to review according to the inclusion criteria.RESULTS AND CONCLUSION: BTCTs may originate from mutation of neural stem cells, BTCTs have the character of self-renewal, multi-differentiation potency. CD133 and Nestin is the surface biomarker of BTCTs that has been widely used. Study of BTCTs is helpful to clarify the growth mechanism, biological character, clinical treatment and prognosis analysis of the brain tumor.%背景:随着对脑肿瘤研究逐步深化,肿瘤干细胞被发现在肿瘤生长、发展、复发和转移中起着不可或缺的独特作用.目的:综述脑肿瘤干细胞的来源、生物学特性以及研究进展.方法:应用计算机检索1998-01/2010-01万方数据库相关文章,检索词"脑肿瘤干细胞",并限定文章语言种类为中文.同时计算机检索1998-01/2010-01 ELSEVIER数据库相关文章,检索词"brain tumor stem cells,BTCTs",并限定文章语言种类为English.共检索到文献198篇,最终纳入符合标准的文献21篇.结果与结论:脑肿瘤干细胞可能来源于神经干细胞的突变,具有自我更新和多向分化潜能,CD133和Nestin是目前应用得最多的肿瘤干细胞表面标记物,脑肿瘤干细胞的研究对阐明脑肿瘤发生机制、生物学行为及临床治疗、预后判断都具有重要意义.

  20. CS-04STAT3 INVOLVEMENT IN AN EMT-LIKE PROCESS IN GLIOBLASTOMA BRAIN TUMOR INITIATING CELLS

    OpenAIRE

    Chesnelong, Charles; Luchman, Artee; Gregory Cairncross, J.; Weiss, Samuel

    2014-01-01

    Glioblastoma Multiforme (GBM) is the most aggressive subtype of brain tumour with a median survival of 15 months. Currently, GBM is managed by a combination of maximal safe resection followed by radiation and chemotherapy. However, GBM invariably recurs, highlighting the need to better delineate the basis of recurrent disease and develop novel more effective and targeted therapies. The Signal Transducer and Activator of Transcription 3 (STAT3) is abnormally active in GBM. A growing body of ev...

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

    Directory of Open Access Journals (Sweden)

    Yuuki Takashima

    2012-10-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed....... Mutagen sensitivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms...

  3. Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

    Science.gov (United States)

    Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

    2013-05-01

    Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

  4. Heavy metals and epigenetic alterations in brain tumors.

    Science.gov (United States)

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

    2014-12-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

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

  6. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

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

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

    Science.gov (United States)

    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

  8. Brain hyaluronan binding protein inhibits tumor growth

    Institute of Scientific and Technical Information of China (English)

    高锋; 曹曼林; 王蕾

    2004-01-01

    Background Great efforts have been made to search for the angiogenic inhibitors in avascular tissues. Several proteins isolated from cartilage have been proved to have anti-angiogenic or anti-tumour effects. Because cartilage contains a great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding proteins (HABP), therefore, we speculated that HABP might be one of the factors regulating vascularization in cartilage or anti-angiogenesis in tumours. The purpose of this research was to evaluale the effects of hyaluronan binding protein on inhibiting tumour growth both in vivo and vitro. Methods A unique protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned from human brain cDNA library. MDA-435 human breast cancer cell line was chosen as a transfectant. The in vitro underlying mechanisms were investigated by determining the possibilities of MDA-435/b-HABP colony formation on soft agar, the effects of the transfectant on the proliferation of endothelial cells and the expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos and nude mice. Results Colony formation assay revealed that the colonies formed by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than that of MDA-435 alone. Conclusions Human brain hyaluronan binding protein (b-HABP) may represent a new kind of naturally existing anti-tumour substance. This brain-derived glycoprotein may block tumour growth by inducing apoptosis of cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting proliferation of endothelial cells.

  9. Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

    Energy Technology Data Exchange (ETDEWEB)

    Marino, Ana-Maria [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Sofiadis, Anastasios [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Oncology-Pathology, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Baryawno, Ninib; Johnsen, John Inge [Department of Women' s and Children' s Health, Karolinska Institutet, Stockholm (Sweden); Larsson, Catharina [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Vukojevic, Vladana [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden)

    2011-07-22

    Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Science.gov (United States)

    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

  12. Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor

    Science.gov (United States)

    2016-05-04

    Solid Tumor; Adult Central Nervous System Germ Cell Tumor; Adult Rhabdomyosarcoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Ovarian Mixed Germ Cell Tumor; Previously Untreated Childhood Rhabdomyosarcoma; Recurrent Adult Brain Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Neuroblastoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  13. A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens

    OpenAIRE

    Sun, Jing; Masterman-Smith, Michael; Graham, Nicholas A; Jiao, Jing; Mottahedeh, Jack; Laks, Dan R.; Ohashi, Minori; DeJesus, Jason; Kamei, Ken-ichiro; Lee, Ki-Bum; Wang, Hao; Yu, Zeta T.F.; Lu, Yi-Tsung; Hou, Shuang; Li,Keyu

    2010-01-01

    The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform, Microfluidic Image Cytometry (MIC), capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000-2,800 cells. ...

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

    Science.gov (United States)

    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

  15. Bone Mineral Density Reduction Following Irradiation of Brain Tumors

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-11-01

    Full Text Available Total body bone mineral density (TBBMD was measured by X-ray absorptiometry in 46 brain tumor patients aged from 3.8 to 28.7 years (mean 14.9 y at a mean of 6.4 y (range 1.4-14.8 y after end of treatment for brain tumor.

  16. Anticonvulsant therapy in brain-tumor related epilepsy

    Directory of Open Access Journals (Sweden)

    Fröscher Walter

    2016-06-01

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

  17. Diagnosis and prognosis of brain tumors in clinical trials

    NARCIS (Netherlands)

    T.S. Gorlia (Thierry)

    2013-01-01

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

  18. Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

    Science.gov (United States)

    2016-04-28

    Adult Central Nervous System Germ Cell Tumor; Adult Ependymoblastoma; Adult Medulloblastoma; Adult Pineoblastoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Ependymoblastoma; Medulloepithelioma; Ototoxicity; Recurrent Adult Brain Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  19. Chemo-Predictive Assay for Targeting Cancer Stem-Like Cells in Patients Affected by Brain Tumors

    OpenAIRE

    Mathis, Sarah E.; Anthony Alberico; Rounak Nande; Walter Neto; Logan Lawrence; Danielle R McCallister; James Denvir; Gerrit A Kimmey; Mark Mogul; Gerard Oakley; Denning, Krista L.; Thomas Dougherty; Jagan V Valluri; Pier Paolo Claudio

    2014-01-01

    Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bul...

  20. Preliminary study of MR elastography in brain tumors

    International Nuclear Information System (INIS)

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

  1. A study of ICAM expression in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Hoon; Lee, Seung Hoon; Hong, Seok Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1995-12-01

    The purpose of this study is to test the possibility of using sICAM-1 as a marker for follow-up of treatment. The micro-ELISA method was adopted. The brain stem gliomas showed positive results in 67%. Overall, 23% of brain tumors showed positive results. It is possible that we can use sICAM-1 as a marker for metastatic brain tumors, and measurement after radiation therapy is not reliable. 6 refs. (Author) (Author).

  2. Brain Tumor Detection Based On Mathematical Analysis and Symmetry Information

    OpenAIRE

    G., Narkhede Sachin; Khairnar, Vaishali; Kadu, Sujata

    2014-01-01

    Image segmentation some of the challenging issues on brain magnetic resonance image tumor segmentation caused by the weak correlation between magnetic resonance imaging intensity and anatomical meaning.With the objective of utilizing more meaningful information to improve brain tumor segmentation,an approach which employs bilateral symmetry information as an additional feature for segmentation is proposed.This is motivated by potential performance improvement in the general automatic brain tu...

  3. Comparison of Swallowing Functions Between Brain Tumor and Stroke Patients

    OpenAIRE

    Park, Dae Hwan; Chun, Min Ho; Lee, Sook Joung; Song, Yoon Bum

    2013-01-01

    Objective To compare the swallowing functions according to the lesion locations between brain tumor and stroke patients. Methods Forty brain tumor patients and the same number of age-, lesion-, and functional status-matching stroke patients were enrolled in this study. Before beginning the swallowing therapy, swallowing function was evaluated in all subjects by videofluoroscopic swallowing study. Brain lesions were classified as either supratentorial or in-fratentorial. We evaluated the follo...

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

    Science.gov (United States)

    Chan, Vincy; Xiong, Chen; Colantonio, Angela

    2015-01-01

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

  5. Patent foramen ovale as a preferential mechanism for increasing the likelihood of brain tumor metastasis

    OpenAIRE

    Rigatelli, Gianluca; Rossi, Andrea; Dell'Avvocata, Fabio; Cardaioli, Paolo

    2011-01-01

    Metastases are the most common tumors of the central nervous system which may lie dormant behind the brain blood- barrier sheltering from chemiotherapeutic drugs, and whose presence usually indicates a poor prognosis. Development of brain metastases includes the intravasation of the cancer cells through the tumor blood vessels, their circulation within the venous system, passing through the pulmonary filter thus reaching the systemic circulation. Patent foramen ovale (PFO) is a natural commun...

  6. How do brain tumors alter functional connectivity? : A magnetoencephalography study

    NARCIS (Netherlands)

    Bartolomei, Fabrice; Bosma, Ingeborg; Klein, Martin; Baayen, Johannes C; Reijneveld, Jaap C; Postma, Tjeerd J; Heimans, Jan J; van Dijk, Bob W; de Munck, Jan C; de Jongh, Arent; Cover, Keith S; Stam, Cornelis J

    2006-01-01

    OBJECTIVE: This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks. METHODS: Functional connectivity was assessed by computing the synchronization likelihood in a broad band (0.5-60Hz) or in the g

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

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

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

  8. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    Science.gov (United States)

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

    2016-07-15

    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.

  9. Boron Neutron Capture Therapy for Malignant Brain Tumors

    Science.gov (United States)

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

    2016-01-01

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

  10. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    Science.gov (United States)

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

    2016-07-15

    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

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

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-02-01

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

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

    Science.gov (United States)

    Fontebasso, Adam M; Jabado, Nada

    2015-01-01

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

  14. Chemo-radiotherapy for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-05-01

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

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

    Science.gov (United States)

    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

  16. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  17. Infantile pericardial round cell tumor

    International Nuclear Information System (INIS)

    Cardiac malignancies presenting in infancy are rare. Desmoplastic small round cell tumor (DSRCT) is a rare occurrence in this age group. No case of intrapericardial DSRCT has been reported in the literature in infants

  18. Radiotherapy for pediatric brain tumors: Standards of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    The objectives of the course are to evaluate the role of radiation therapy in the treatment of pediatric brain tumors. Areas where the role is evolving will be identified, and the results of clinical trials which been mounted to clarify radiotherapy's role will be reviewed. Brain tumors are the second most common malignancy of childhood after leukemias and lymphomas. However, they remain the most common group of childhood tumors to require radiation therapy. Therefore, a thorough understanding of these tumors, and the appropriate role of surgery, radiation and chemotherapy is critical. Issues surrounding the management of sequelae are no less important. The role of radiotherapy for the treatment of these tumors is far different from that for adults. These differences relate to the profound potential for sequelae from therapy, the higher overall cure rates, and the utility of multimodality therapies. In addition, the rarity of childhood brain tumors compared with adults' makes them more difficult to study. In this session, the following issues will be reviewed; 1. Incidence of pediatric brain tumors, 2. General issues regarding symptoms, diagnosis, diagnostic tests and evaluation, 3. Importance of a team approach, 4. General issues regarding treatment sequelae, 5. Specific tumor types/entities; a. Cerebellar Astrocytomas b. Benign and malignant Gliomas including brainstem and chiasmatic lesions c. Primitive Neuroectodermal Tumors (PNET) and Medulloblastoma d. Ependymomas e. Craniopharyngiomas f. Germ cell tumors g. Miscellaneous and rare pediatric brain tumors 6. Management of sequelae 7. New and future directions a. Treatment of infants b. The expanding role of chemotherapy c. Advances in radiotherapy. The attendees will complete the course with a better understanding of the role that radiation therapy plays in the treatment of pediatric brain tumors. They will be knowledgeable in the foundation for that role, and the changes which are likely to take place in the

  19. Radiosurgery-induced brain tumor. Case report.

    Science.gov (United States)

    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.

  20. [Ovarian germ cell tumors in girls].

    Science.gov (United States)

    Nechushkina, I V; Karseladze, A I

    2015-01-01

    Morphological structure of tumor influences on the clinical course of the disease in children with germ cell tumors. Patients with ovarian dysgerminoma at the time of diagnosis are significantly older than patients with immature teratoma and yolk sac tumor. Immature teratoma and mixed germ cell tumors are significantly larger compared to other germ cell tumors. Yolk sac tumor and embryonal carcinoma are the most common cause of emergency surgical interventions and are accompanied by rupture of tumor capsule. PMID:26087605

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

    Directory of Open Access Journals (Sweden)

    Jingli Wang

    2003-07-01

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

  2. Air pollution from traffic and risk for brain tumors

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out to replic......PURPOSE: Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out...... to replicate that finding in a large nationwide case-control study. METHODS: We identified all 4,183 adult brain tumor cases in Denmark in the years 2000-2009 and 8,018 risk set sampled population controls matched on gender and year of birth. We extracted residential address histories and estimated mean...... and risk of brain tumors which was found in our previous study. The suggestion of an increased brain tumor risk at high exposures merits further attention as does the differing results according to tumor morphology....

  3. Rapid Detection of high-level oncogene amplifications in ultrasonic surgical aspirations of brain tumors

    Directory of Open Access Journals (Sweden)

    Truong Long N

    2012-06-01

    Full Text Available Abstract Background Genomic tumor information, such as identification of amplified oncogenes, can be used to plan treatment. The two sources of a brain tumor that are commonly available include formalin-fixed, paraffin-embedded (FFPE sections from the small diagnostic biopsy and the ultrasonic surgical aspiration that contains the bulk of the tumor. In research centers, frozen tissue of a brain tumor may also be available. This study compared ultrasonic surgical aspiration and FFPE specimens from the same brain tumors for retrieval of DNA and molecular assessment of amplified oncogenes. Methods Surgical aspirations were centrifuged to separate erythrocytes from the tumor cells that predominantly formed large, overlying buffy coats. These were sampled to harvest nuclear pellets for DNA purification. Four glioblastomas, 2 lung carcinoma metastases, and an ependymoma were tested. An inexpensive PCR technique, multiplex ligation-dependent probe amplification (MLPA, quantified 79 oncogenes using 3 kits. Copy number (CN results were normalized to DNA from non-neoplastic brain (NB in calculated ratios, [tumor DNA]/[NB DNA]. Bland-Altman and Spearman rank correlative comparisons were determined. Regression analysis identified outliers. Results Purification of DNA from ultrasonic surgical aspirations was rapid ( Conclusions Buffy coats of centrifuged ultrasonic aspirations contained abundant tumor cells whose DNA permitted rapid, multiplex detection of high-level oncogene amplifications that were confirmed in FFPE. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/1883718801686466

  4. Cortical Plasticity in the Setting of Brain Tumors.

    Science.gov (United States)

    Fisicaro, Ryan A; Jost, Ethan; Shaw, Katharina; Brennan, Nicole Petrovich; Peck, Kyung K; Holodny, Andrei I

    2016-02-01

    Cortical reorganization of function due to the growth of an adjacent brain tumor has clearly been demonstrated in a number of surgically proven cases. Such cases demonstrate the unmistakable implications for the neurosurgical treatment of brain tumors, as the cortical function may not reside where one may initially suspect based solely on the anatomical magnetic resonance imaging (MRI). Consequently, preoperative localization of eloquent areas adjacent to a brain tumor is necessary, as this may demonstrate unexpected organization, which may affect the neurosurgical approach to the lesion. However, in interpreting functional MRI studies, the interpreting physician must be cognizant of artifacts, which may limit the accuracy of functional MRI in the setting of brain tumors. PMID:26848558

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

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, Antonios (ed.)

    2011-07-01

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

  6. Childhood exposure to ionizing radiation and brain tumors

    International Nuclear Information System (INIS)

    Brain has been categorized into the low risk group of radiogenic tumors. However, recent epidemiologic studies on the cancer risks among children who received repeated CT scans, radiotherapies and A-bomb have revealed that low-to-moderate dose of ionizing radiation is effective to induce brain tumors. Ionizing radiation is more strongly associated with risk for meningiomas and schwannomas compared to gliomas. While risk of meningiomas is independent of age at the time of exposure, that of gliomas is profoundly high after neonatal and infantile exposures. Inherited susceptibility to brain tumors is suggested by family history or cancer prone syndromes. People with certain gene mutations such as RB, NF1 or PTCH1 are associated with enhanced cancer risk after radiotherapies. Genetic polymorphism of cancer-related genes on brain tumor risk deserves further investigation. (author)

  7. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings

  8. Brain Tumor Detection Based On Mathematical Analysis and Symmetry Information

    OpenAIRE

    Narkhede Sachin G.,; Prof. Vaishali Khairnar

    2014-01-01

    Image segmentation some of the challenging issues on brain magnetic resonance (MR) image tumor segmentation caused by the weak correlation between magnetic resonance imaging (MRI) intensity and anatomical meaning. With the objective of utilizing more meaningful information to improve brain tumor segmentation, an approach which employs bilateral symmetry information as an additional feature for segmentation is proposed. This is motivated by potential performance improvement in ...

  9. Angiogenesis-independent tumor growth mediated by stem-like cancer cells.

    NARCIS (Netherlands)

    Sakariassen, P.; Prestegarden, L.; Wang, J.; Skaftnesmo, K.O.; Mahesparan, R.; Molthoff, C.F.M.; Sminia, P.; Sundlisaeter, E.; Misra, A.; Tysnes, B.B.; Chekenya, M.; Peters, H.; Lende, G.; Kalland, K.H.; Oyan, A.M.; Petersen, K.; Jonassen, I.; Kogel, A.J. van der; Feuerstein, B.G.; Terzis, A.J.; Bjerkvig, R.; Enger, P.O.

    2006-01-01

    In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells ex

  10. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    Science.gov (United States)

    Zhao, Liya; Jia, Kebin

    2016-01-01

    Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness. PMID:27069501

  11. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

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

    International Nuclear Information System (INIS)

    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, T1-weighted unevenly enhancing, and T2-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

  13. Wavelet Based Image Fusion for Detection of Brain Tumor

    Directory of Open Access Journals (Sweden)

    CYN Dwith

    2013-01-01

    Full Text Available Brain tumor, is one of the major causes for the increase in mortality among children and adults. Detecting the regions of brain is the major challenge in tumor detection. In the field of medical image processing, multi sensor images are widely being used as potential sources to detect brain tumor. In this paper, a wavelet based image fusion algorithm is applied on the Magnetic Resonance (MR images and Computed Tomography (CT images which are used as primary sources to extract the redundant and complementary information in order to enhance the tumor detection in the resultant fused image. The main features taken into account for detection of brain tumor are location of tumor and size of the tumor, which is further optimized through fusion of images using various wavelet transforms parameters. We discuss and enforce the principle of evaluating and comparing the performance of the algorithm applied to the images with respect to various wavelets type used for the wavelet analysis. The performance efficiency of the algorithm is evaluated on the basis of PSNR values. The obtained results are compared on the basis of PSNR with gradient vector field and big bang optimization. The algorithms are analyzed in terms of performance with respect to accuracy in estimation of tumor region and computational efficiency of the algorithms.

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

    Science.gov (United States)

    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. SPECT quantitation of cobalt-57 bleomycin delivery to human brain tumors

    International Nuclear Information System (INIS)

    A newly developed and validated noninvasive quantitative SPECT method was used to measure the in vivo uptake of [57Co]bleomycin (Co-bleo) in 13 human brain tumors and the uptake of [/sup 99m/Tc]glucoheptonate (GH) in 23 brain tumors. Significant differences in tumor uptake were found. The tumor concentration over time, the tumor to blood radioactivity at 30 min and the tumor cumulative concentration of radioactivity showed marked differences even between tumors with the same histology. Only a weak correlation was found between tumor concentration of Co-bleo and of GH. Therefore, a simple imaging agent such as GH cannot, at the present time, serve as an indicator of individual tumor uptake and further experience with other agents is still necessary. Contrary to the generally held view, no correlation was found between the concentration of drug in the blood and its tumor concentration. It is suggested, therefore, that the level of a drug in the blood cannot be used as a criterion of the amount that will penetrate the tumor. Direct SPECT measurement of the concentration of the drug in the tumor itself should be performed. The bioavailability of a drug is critical in order for it to exert it tumoricidal effect. The results, showing marked differences in uptake between brain tumors, suggest that before chemotherapy is administered, uptake of the chemotherapeutic drug in the individual tumor to be treated should be assessed and comparisons should be made between the uptake of a series of drugs to determine which drug would be most efficacious on the basis of its uptake as well as its tumor cell killing potential

  16. THE ROLE OF GAP JUNCTIONS IN THE DEVELOPMENT OF ASTROCYTIC HUMAN BRAIN TUMOR

    Directory of Open Access Journals (Sweden)

    Grankina A. O.

    2015-01-01

    Full Text Available Recently, much attention is paid to research the role of cell-cell interactions by gap junctions in the process of malignant transformation and mechanisms of antitumor resistance. Meanwhile, the greatest interest is astrocytic tumors. Depending on the degree of malignancy, astrocytomas are divided into: pilocytic astrocytoma (Grade I, subependymal giant cell astrocytoma (Grade I, pleomorphic xanthoastrocytoma (Grade II, diffuse astrocytoma (Grade II, anaplastic astrocytoma (Grade III, glioblastoma (Grade IV gliomatosis cerebri (Grade IV. Information of literature devoted to astrocytic tumors (gliomas - the most common brain tumor in large part obtained in studies in cell cultures and different contradictions. Along with data on the reduction of glial tumors cells communicability through GJ, there is evidence of an opposite character - a functionally active GJ in gliomas and inhibition of tumor growth by reducing intercellular communicability by GJ. However, up to now there have been no studies of the effect and function of hemichannels in cancer cells, which would provide detailed information on: 1 the characteristic of presence and relative abundance of hemichannels in cancer cells; 2 evaluation of absorption / release of hemichannels mediated molecules in tumor cells than in non-tumor cells; 3 functional consequences of activation and blocking of hemichannels in tumor cells and 4 the prognostic value of the expression / activation of hemichannels in human malignancies

  17. Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

    DEFF Research Database (Denmark)

    Müller-Enbergs, Helmut; Hu, Jiong; Popp, Rüdiger;

    2012-01-01

    OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted ...

  18. Kinome Profiling in Pediatric Brain Tumors as a New Approach for Target Discovery

    NARCIS (Netherlands)

    Sikkema, Arend H.; Diks, Sander H.; den Dunnen, Wilfred F. A.; ter Elst, Arja; Scherpen, Frank J. G.; Hoving, Eelco W.; Ruijtenbeek, Rob; Boender, Piet J.; de Wijn, Rik; Kamps, Willem A.; Peppelenbosch, Maikel P.; de Bont, Eveline S. J. M.

    2009-01-01

    Progression in pediatric brain tumor growth is thought to be the net result of signaling through various protein kinase-mediated networks driving cell proliferation. Defining new targets for treatment of human malignancies, without a priori knowledge on aberrant cell signaling activity, remains exce

  19. Reprogramming Cells for Brain Repair

    OpenAIRE

    McKinnon, Randall D.; Alyx T. Guarino

    2013-01-01

    At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal c...

  20. ABT-751 in Treating Young Patients With Refractory Solid Tumors

    Science.gov (United States)

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Congenital Brain Tumors, a Series of Seven Patients

    Directory of Open Access Journals (Sweden)

    Farideh Nejat

    2007-05-01

    Full Text Available Objective: Congenital brain tumors are very rare. We review these tumors in patients younger than 2 months diagnosed in our Department. Material & Methods: Seven congenital brain tumors were diagnosed during five years. Clinical and radiological findings and prognosis are analyzed. Findings: The study included 5 female and two male infants. Two cases were diagnosed antenatally by means of ultrasonography. All patients presented with intracranial hypertension. The tumor was non-homogenous with cystic and solid components in all neuroimaging, except for the case with choroid plexus papilloma. Hydrocephalus was evident in all of them. Most findings were infra-tentorial lesions. There were three teratomas, one primitive neuro-ectodermal tumor, one ependymoblastoma and one choroid plexus papilloma. Six patients were operated on, with one intra-operative death. Two passed away postoperatively with aspiration pneumonia. One patient died due to complications of chemotherapy and another one due to tumor recurrence one year after surgery. Only the patient with choroid plexus papilloma is alive after 2 years. Conclusion: Today, the availability of noninvasive imaging procedures such as computerized tomography scan and magnetic resonance imaging has improved the diagnosis of congenital brain tumors. Inspite of development in prenatal diagnosis, appropriate pre and post operative management, the mortality associated with these tumors still remains high. The final prognosis in these patients is still discouraging despite early surgery and operative and anesthetic improvements. Choroid plexus papilloma accompanies the best prognosis, whereas teratoma and primitive neuroectodermal tumors have the worst prognosis.

  2. Evolution of Brain Tumor and Stability of Geometric Invariants

    Directory of Open Access Journals (Sweden)

    K. Tawbe

    2008-01-01

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

  3. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

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

    Science.gov (United States)

    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

  5. Tc-99m-MIBI brain SPECT in differentiating tumor recurrences from necrosis

    International Nuclear Information System (INIS)

    Brain SPECT using 99m-TC MIBI can distinguish between local tumor recurrence and radio necrosis of the primary brain tumor, whereas CT scan and MRI do not have this ability. 1. Is it possible to search for tumoral cells in the brain by using TC-99m MIBI? 2. How sensitive and specific is the SPECT in distinguishing the presence of active tumor in the brain and differentiating it from post-therapy necrosis? 3. Is it feasible to substitute this diagnostic modality for stereotactic biopsy surgery? Patients who presented to the neurosurgery clinic with the clinical manifestations of brain tumor relapse between 22nd August 1999 and 1.; February 2000 and were candidates for stereotactic biopsy were chosen. A 99m-TC MIBI SPECT was performed before biopsy. The total number of patients was 13. Five patients had the diagnosis of brain tumor by surgery and biopsy and had undergone a course of radiotherapy and chemotherapy. These patients were normal clinically and MIBI SPECT was done for the purpose of follow-up. Clinical manifestations consisted of, Weakness, Vertigo visual disorders, loss of consciousness, headache, aphasia and hemiparesis. The primary tumors were composed of a variety of lei sons including: grade I, II astrocytoma (62.5%), glioblastoma (25%) and medulloblastoma (12.5%). eight patients who had MIBI SPECT firstly and then had biopsy, brain tumor relapse was reported by both biopsy and SPECT in seven patients. This proved a 100% sensitivity and a 100% specificity for MIBI SPECT in differentiating, between tumor relapse and necrosis, a result comparable to stereotactic biopsy. Also in 5 patients with clinical evidence of remission, MIBI SPECT was negative for tumor recurrence in all. Patients who present with the clinical manifestations of brain tumor relapse, usually have a history of surgery, radiotherapy or chemotherapy and any invasive procedures like stereotactic biopsy on these patients carries a high risk for anesthesia and surgery, besides being costly

  6. Research of the multimodal brain-tumor segmentation algorithm

    Science.gov (United States)

    Lu, Yisu; Chen, Wufan

    2015-12-01

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

  7. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg;

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice......-floating spheroids, spheroids implanted into brain slices and tumors in vivo. CONCLUSION: The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we...

  8. A Comparison of Two Human Brain Tumor Segmentation Methods for MRI Data

    CERN Document Server

    Egger, Jan; Bauer, Miriam H A; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher

    2011-01-01

    The most common primary brain tumors are gliomas, evolving from the cerebral supportive cells. For clinical follow-up, the evaluation of the preoperative tumor volume is essential. Volumetric assessment of tumor volume with manual segmentation of its outlines is a time-consuming process that can be overcome with the help of computerized segmentation methods. In this contribution, two methods for World Health Organization (WHO) grade IV glioma segmentation in the human brain are compared using magnetic resonance imaging (MRI) patient data from the clinical routine. One method uses balloon inflation forces, and relies on detection of high intensity tumor boundaries that are coupled with the use of contrast agent gadolinium. The other method sets up a directed and weighted graph and performs a min-cut for optimal segmentation results. The ground truth of the tumor boundaries - for evaluating the methods on 27 cases - is manually extracted by neurosurgeons with several years of experience in the resection of glio...

  9. Novel Polyomavirus associated with Brain Tumors in Free-Ranging Raccoons, Western United States

    Science.gov (United States)

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

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010–May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons. PMID:23260029

  10. Imaging of non tumorous and tumorous human brain tissue with full-field optical coherence tomography

    CERN Document Server

    Assayag, Osnath; Devaux, Bertrand; Harms, Fabrice; Pallud, Johan; Chretien, Fabrice; Boccara, Claude; Varlet, Pascale

    2013-01-01

    A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\\mum resolution in 3D with a typical 200\\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low- grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a...

  11. Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

    Science.gov (United States)

    2013-09-27

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

  12. The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.

    Science.gov (United States)

    Lowenstein, P R; Castro, M G

    2016-01-01

    Malignant brain tumors are one of the most lethal cancers. They originate from glial cells which infiltrate throughout the brain. Current standard of care involves surgical resection, radiotherapy, and chemotherapy; median survival is currently ~14-20 months postdiagnosis. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1-derived thymidine kinase which converts ganciclovir into a compound only cytotoxic to dividing glioma cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine that attracts dendritic cells to the brain. HSV-1/ganciclovir killing of tumor cells releases tumor antigens that are taken up by dendritic cells within the brain tumor microenvironment. Tumor killing also releases HMGB1, an endogenous TLR2 agonist that activates dendritic cells. HMGB1-activated dendritic cells, loaded with glioma antigens, migrate to cervical lymph nodes to stimulate a systemic CD8+ T cells cytotoxic immune response against glioma. This immune response is specific to glioma tumors, induces immunological memory, and does neither cause brain toxicity nor autoimmune responses. An IND was granted by the FDA on 4/7/2011. A Phase I, first in person trial, to test whether reengineering the brain immune system is potentially therapeutic is ongoing. PMID:27288077

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

    Science.gov (United States)

    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.

  14. NK cells in the tumor microenvironment

    DEFF Research Database (Denmark)

    Larsen, Stine K; Gao, Yanhua; Basse, Per H

    2014-01-01

    The presence of natural killer (NK) cells in the tumor microenvironment correlates with outcome in a variety of cancers. However, the role of intratumoral NK cells is unclear. Preclinical studies have shown that, while NK cells efficiently kill circulating tumor cells of almost any origin......, they seem to have very little effect against the same type of tumor cells when these have extravasated. The ability to kill extravasated tumor cells is, however, is dependent of the level of activation of the NK cells, as more recent published and unpublished studies, discussed below, have demonstrated...... that interleukin-2-activated NK cells are able to attack well-established solid tumors....

  15. Treatment Option Overview (Adult Brain Tumors)

    Science.gov (United States)

    ... Unknown Primary Treatment Colon Cancer Treatment Leukemia Home Page Melanoma Treatment Nasopharyngeal Cancer Treatment Non-Small Cell Lung Cancer Treatment Renal Cell Cancer Treatment Small Cell ...

  16. General Information about Adult Brain Tumors

    Science.gov (United States)

    ... Unknown Primary Treatment Colon Cancer Treatment Leukemia Home Page Melanoma Treatment Nasopharyngeal Cancer Treatment Non-Small Cell Lung Cancer Treatment Renal Cell Cancer Treatment Small Cell ...

  17. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    Science.gov (United States)

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

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

    Science.gov (United States)

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

    OpenAIRE

    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 repo...

  20. Disseminated lesions of the central nervous system in course of pediatric brain tumors

    International Nuclear Information System (INIS)

    Neoplasms of the central nervous system (CNS) are, apart from leukemia, the most frequent malignant disorders in the childhood. Among the brain tumors, those of poorly differentiated cells - give metastatic lesions to the CNS. The aim of the paper was to evaluate the features of CT and MR images detecting dissemination of the primary brain tumors. From 1993 to 2005 in the Department of Radiology of the Polish Mother's Memorial Hospital - Research Institute, the disseminations to CNS were observed in 35 children who were previously operated for primary brain tumors. CT and MR examinations of the brain were performed in all patients (22 males and 13 females; age: 5 mo - 18 y) and MR imaging of the spinal cord was done in 18 children. Multiple metastases to the cerebral structures were detected more often (in 23 patients - 66%) as compared to single lesions. The most frequent disseminations were observed in patients with diagnosis of medulloblastoma - 13 children, PNET - 4 and pineoblastoma - 3 patients. Twelve children had single metastatic tumors (out of the primary neoplasm location): in the course of medulloblastoma - 6, and PNET - 2 patients. Eighteen MR examinations of the spinal canal showed disseminations of the brain tumors in 9 children; concomitant metastatic nodules in the brain were detected in 4 patients. CT and MR imaging of the CNS enables evaluating the dissemination of primary brain tumors in children. Any asymptomatic progression of the primary neoplastic disease may be detected by means of control diagnostic imaging, which reveals the tumor spread. Especially in patients with medulloblastoma and pineoblastoma, the spine MR imaging with gadolinium is mandatory. (author)

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

    OpenAIRE

    Manjula S; Monteiro Flama; Aroor Annaya; Rao Suryanarayan; Annaswamy Raja; Rao Anjali

    2010-01-01

    Background: Glycosylation of altered tumor cell in relation to cellular heterogeneity in human intracranial tumors remains relatively unexposed. Serum protein-bound carbohydrate, L-Fucose is reported to be overexpressed during tumor progression by many investigators. Therefore, there is a need to determine the diagnostic, prognostic, functional significance of glycoprotein elevations in various cases of tumors. Objective: The objective of the present study was to evaluate the clinical util...

  2. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  3. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain

    Directory of Open Access Journals (Sweden)

    Chiles Thomas C

    2008-05-01

    Full Text Available Abstract Background AMP-activated protein kinase (AMPK is a known physiological cellular energy sensor and becomes phosphorylated at Thr-172 in response to changes in cellular ATP levels. Activated AMPK acts as either an inducer or suppressor of apoptosis depending on the severity of energy stress and the presence or absence of certain functional tumor suppressor genes. Results Here we show that energy stress differentially affects AMPK phosphorylation and cell-death in brain tumor tissue and in tissue from contra-lateral normal brain. We compared TSC2 deficient CT-2A mouse astrocytoma cells with syngeneic normal astrocytes that were grown under identical condition in vitro. Energy stress induced by glucose withdrawal or addition of 2-deoxyglucose caused more ATP depletion, AMPK phosphorylation and apoptosis in CT-2A cells than in the normal astrocytes. Under normal energy conditions pharmacological stimulation of AMPK caused apoptosis in CT-2A cells but not in astrocytes. TSC2 siRNA treated astrocytes are hypersensitive to apoptosis induced by energy stress compared to control cells. AMPK phosphorylation and apoptosis were also greater in the CT-2A tumor tissue than in the normal brain tissue following implementation of dietary energy restriction. Inefficient mTOR and TSC2 signaling, downstream of AMPK, is responsible for CT-2A cell-death, while functional LKB1 may protect normal brain cells under energy stress. Conclusion Together these data demonstrates that AMPK phosphorylation induces apoptosis in mouse astrocytoma but may protect normal brain cells from apoptosis under similar energy stress condition. Therefore, using activator of AMPK along with glycolysis inhibitor could be a potential therapeutic approach for TSC2 deficient human malignant astrocytoma.

  4. Photon spectrum and absorbed dose in brain tumor

    International Nuclear Information System (INIS)

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

  5. Photon spectrum and absorbed dose in brain tumor

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  6. Neural Network Based Augmented Reality for Detection of Brain Tumor

    Directory of Open Access Journals (Sweden)

    P.Mithun

    2013-04-01

    Full Text Available The development in technology opened the door of fiction and reached reality. Major medical applications deals on robot-assisted surgery and image guided surgery. Because of this, substantial research is going on to implement Augmented Reality (AR in instruments which incorporate the surgeon’s intuitive capabilities. Augmented reality is the grouping of virtual entity or 3D stuffs which are overlapped on live camera feed information. The decisive aim of augmented reality is to enhancing the virtual video and a 3D object onto a real world on which it will raise the person’s conceptual understanding of the subject. In this paper we described a solution for initial prediction of tumour cells in MRI images of human brain using image processing technique the output of which will be the 3D slicedimage of the human brain. The sliced image is then virtually embedded on the top of human head during the time of surgery so that the surgeon can exactly locate the spot to be operated. Before augmenting the 3D sliced image Artificial neural network is used to select the appropriate image that contains tumor automatically in order to make the system more efficient.

  7. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  8. Gonadal status in male survivors following childhood brain tumors

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  9. A Comparative Study of Segmentation Methods for Brain tumor Detection

    OpenAIRE

    Smita Haribhau Zol

    2012-01-01

    This paper introduces a comparative study of three methods of automated medical image segmentation which can be used to locate volumetric objects such asbrain tumor in Magnetic Resonance Imaging (MRI) images and they are - Automated Medical Image Segmentation Using a New Deformable Surface Model, Brain Tumor Detection Using Segmentation Based on Neuro Fuzzy Technique, An Image Segmentation Method Based on a Discrete Version of the Topological Derivative.

  10. Clinical features of depressive disorders in patients with brain tumors

    Directory of Open Access Journals (Sweden)

    Ogorenko V.V.

    2014-03-01

    Full Text Available The aim of the study was to examine the structure of psychopathology and clinical features of depressive disorders in patients with brain oncopathology. Polymorphic mental disorders of various clinical content and severity in most cases not only are comorbid to oncological pathology of the brain, but most often are the first clinical signs of early tumors. The study was conducted using the following methods: clinical psychiatric, questionnaire Simptom Check List- 90 -Revised-SCL- 90 -R, Luscher test and mathematical processing methods. Sample included 175 patients with brain tumors with non-psychotic level of mental disorders. The peculiarities of mental disorders and psychopathological structure of nonpsychotic depressive disorders have been a clinical option of cancer debut in patients with brain tumors. We found that nonpsychotic depression is characterized by polymorphism and syndromal incompletion; this causes ambiguity of diagnoses interpretation on stages of diagnostic period. Features of depressive symptoms depending on the signs of malignancy / nonmalignancy of brain tumor were defined.

  11. Brain Tumor Detection Based On Mathematical Analysis and Symmetry Information

    Directory of Open Access Journals (Sweden)

    Narkhede Sachin G.,

    2014-02-01

    Full Text Available Image segmentation some of the challenging issues on brain magnetic resonance (MR image tumor segmentation caused by the weak correlation between magnetic resonance imaging (MRI intensity and anatomical meaning. With the objective of utilizing more meaningful information to improve brain tumor segmentation, an approach which employs bilateral symmetry information as an additional feature for segmentation is proposed. This is motivated by potential performance improvement in the general automatic brain tumor segmentation systems which are important for many medical and scientific applications. Brain Magnetic Resonance Imaging (MRI segmentation is a complex problem in the field of medical imaging despite various presented methods. MR image of human brain can be divided into several sub-regions especially soft tissues such as gray matter, white matter and cerebrospinal fluid. Although edge information is the main clue in image segmentation, it can’t get a better result in analysis the content of images without combining other information. Our goal is to detect the position and boundary of tumors automatically. Experiments were conducted on real pictures, and the results show that the algorithm is flexible and convenient.

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

    Science.gov (United States)

    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.

  13. A New Strategy of Drug Delivery: Electric Field Distribution in Brain Tumor Due to Electroporation

    OpenAIRE

    Shi, Junxing

    2014-01-01

    As the second leading cause of cancer-related deaths in children under 20, and the second leading cause of cancer-related deaths in males aged 20–39, there is a need to seek an effective treatment for brain tumors. While there may be various drugs for brain tumors, the problem is the lack of effective methods of delivery through cell membranes at a very specified and confined region. In order to tackle this specific problem of drug delivery, electroporation is introduced. Electroporation, the...

  14. MR spectroscopy in children: protocols and pitfalls in non-tumorous brain pathology

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Jacques F. [University Children' s Hospital Basel (UKBB), Basel (Switzerland)

    2016-06-15

    Proton nuclear magnetic resonance spectroscopy (MRS) delivers information about cell content and metabolism in a noninvasive manner. The diagnostic strength of MRS lies in its evaluation of pathologies in combination with conventional magnetic resonance imaging (MRI). MRS in children has been most widely used to evaluate brain conditions like tumors, infections, metabolic diseases or learning disabilities and especially in neonates with hypoxic-ischemic encephalopathy. This article reviews some basic theoretical considerations, routine procedures, protocols and pitfalls and will illustrate the range of spectrum alterations occurring in some non-tumorous pediatric brain pathologies. (orig.)

  15. Delayed contrast extravasation MRI for depicting tumor and non-tumoral tissues in primary and metastatic brain tumors.

    Directory of Open Access Journals (Sweden)

    Leor Zach

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

  16. BRAIN TUMOR CLASSIFICATION USING NEURAL NETWORK BASED METHODS

    OpenAIRE

    Kalyani A. Bhawar*, Prof. Nitin K. Bhil

    2016-01-01

    MRI (Magnetic resonance Imaging) brain neoplasm pictures Classification may be a troublesome tasks due to the variance and complexity of tumors. This paper presents two Neural Network techniques for the classification of the magnetic resonance human brain images. The proposed Neural Network technique consists of 3 stages, namely, feature extraction, dimensionality reduction, and classification. In the first stage, we have obtained the options connected with tomography pictures victimization d...

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

    Science.gov (United States)

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

    2012-03-01

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

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

    OpenAIRE

    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 als...

  19. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  20. Staging Childhood Brain and Spinal Cord Tumors

    Science.gov (United States)

    ... tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro ...

  1. The taxonomy of brain cancer stem cells: what's in a name?

    OpenAIRE

    Gutmann, David H.

    2014-01-01

    With the increasing recognition that stem cells play vital roles in the formation, maintenance, and potential targeted treatment of brain tumors, there has been an exponential increase in basic laboratory and translational research on these cell types. However, there are several different classes of stem cells germane to brain cancer, each with distinct capabilities and functions. In this perspective, we discuss the types of stem cells relevant to brain tumor pathogenesis, and suggest a nomen...

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

    International Nuclear Information System (INIS)

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

  3. Effect of tumor resection on the characteristics of functional brain networks

    NARCIS (Netherlands)

    Wang, H.; Douw, L.; Hernández, J.M.; Reijneveld, J.C.; Stam, C.J.; Van Mieghem, P.

    2010-01-01

    Brain functioning such as cognitive performance depends on the functional interactions between brain areas, namely, the functional brain networks. The functional brain networks of a group of patients with brain tumors are measured before and after tumor resection. In this work, we perform a weighted

  4. American brain tumor patients treated with BNCT in Japan

    Energy Technology Data Exchange (ETDEWEB)

    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. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2016-04-01

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

  6. Spectroscopy of brain tumors; Spektroskopie bei Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

    Raab, Peter; Lanfermann, Heinrich [Medizinische Hochschule Hannover (Germany). Inst. fuer Diagnostische und Interventionelle Neuroradiologie; Pilatus, Ulrich [Frankfurt Univ., Frankfurt am Main (Germany). Inst. fuer Neuroradiologie

    2008-09-15

    Metabolic imaging with NMR-spectroscopy has become a diagnostic tool that is used for the examination of cerebral pathologies. It is a non-invasive technique, which can detect and quantify biochemical changes. This paper describes the history of NMR-spectroscopy, its technical basis and possible areas of use for tumor diagnostics. An overview of the literature is given and upcoming developments are mentioned. (orig.)

  7. Application of nanoparticles in brain tumor treatment

    CERN Document Server

    Caruso, Gerardo

    2012-01-01

    Despite progress in surgery, radiotherapy, and chemotherapy, an effective treatment of gliomas does not yet exist. This new monograph in the ASME-Momentum Press series on Biomedical & Nanomedical Technologies book shows how nanotechnology could be used both to improve the treatment efficacy and to reduce the adverse side effects. It will explain how nanotechnology-based approaches to targeted delivery of drugs across the brain-blood barrier may potentially be engineered to carry out specific functions as needed.

  8. Reprogramming Cells for Brain Repair

    Directory of Open Access Journals (Sweden)

    Randall D. McKinnon

    2013-08-01

    Full Text Available At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair.

  9. Autophagy sensitivity of neuroendocrine lung tumor cells

    OpenAIRE

    HONG, SEUNG-KEUN; Kim, Jin-Hwan; Starenki, Dmytro; Park, Jong-In

    2013-01-01

    Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective treatments are available to cure NE lung tumors, demanding identification of biological features specific to these tumors. Here, we report that autophagy has an important role for NE lung tumor cell proliferation and survival. We found that the expression levels of...

  10. Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of (/sup 125/I)5-iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection

    Energy Technology Data Exchange (ETDEWEB)

    Conley, F.K.

    1982-08-01

    The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with (/sup 125/I)IdUrd, and 1x10/sup 5/ tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon.

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

    International Nuclear Information System (INIS)

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

  12. Genetic abnormality predicts benefit for a rare brain tumor

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs−/−) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  15. Within tumors, interactions between T cells and tumor cells are impeded by the extracellular matrix

    OpenAIRE

    Salmon, Hélène; Donnadieu, Emmanuel

    2012-01-01

    In principle, T cells can recognize and kill cancer cells. However, tumors have the ability to escape T cell attack. By imaging the dynamic behavior of T cells in human lung tumor explants, we have recently established the importance of the extracellular matrix in limiting access of T cells to tumor cells.

  16. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  17. Brain Tumors and Brain Tumor Research Progress in Image Classification%脑肿瘤及脑肿瘤图像分类的研究进展

    Institute of Scientific and Technical Information of China (English)

    俞海平; 邬立保

    2011-01-01

    Many methods of brain tumor classification,there is no uniform classification^! A variety of tumors and pathological features of the different tissue, the study of benign and malignant, and things are not the same characteristics. Usually can be classified as histological.-(l) Originated in glial tumors: astrocytoma, less support glial cell tumors, medulloblastoma, etc.(2) Originated in meningeal tumors: meningioma, meningeal sarcoma, arachnoid cyst.(3) Originated in the pituitary tumors: tired color cell adenoma, acidophilic, basophilic cell adenoma.(4) Originated in cranial nerve tumors: acoustic neuroma, trigeminal nerve sheath tumors and other tumors.(S) Originated from residual embryonic tissue: craniopharyngioma, chordoma, dermoid cyst (6) Originated in vascular cells: vascular tumors and vascular reticular cell tumor, etc.(7) Transfer or by other parts of the tumor invasion: a variety of metastatic tumors, and nasopharyn-geal carcinoma, etc.%脑肿瘤分类的方法很多,目前尚无统一的分类方法,并且各种肿瘤的组织发生与病理特征不同,其良性与恶性以及物学特性也不一样.通常按组织学可分类如下:(1)发源于神经胶质的肿瘤:星形细胞瘤、少支胶质细胞瘤、髓母细胞瘤等.(2)发源于脑膜的肿瘤:脑膜瘤、脑膜内瘤、蛛网膜囊肿等.(3)发源于垂体的肿瘤:厌色细胞腺瘤,嗜酸、嗜碱性细胞腺瘤.(4)发源于颅神经的肿瘤:听神经瘤、三叉神经瘤等各种神经鞘瘤.(5)发源于胚胎残余组织:颅咽管瘤、脊索瘤、皮样囊肿等.(6)发源于血管细胞:血管瘤及血管网织细胞瘤等.(7)由其它部位转移或侵入的肿瘤:各种转移瘤及鼻咽癌等.

  18. Atypical extragonadal germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mainak Deb

    2012-01-01

    Full Text Available Aim: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT with a subset analysis of those with atypical features. Materials and Methods: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. Results: Fifteen children aged 7 days to 15 years (median, 1.5 years were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1, anterior neck-thyroid gland (1, mediastinum (4, abdominothoracic extending through the esophageal hiatus (1, retroperitoneal (4 and sacrococcygeal (4. On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years, 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. Conclusions: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

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

    Science.gov (United States)

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

    2016-05-01

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

  20. Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

    Science.gov (United States)

    2015-04-28

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2011-03-01

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

  3. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, C.W.; Hasle, H.; Grønbæk, Kirsten

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

  4. Anti-angiogenic therapy in pediatric brain tumors : An effective strategy?

    NARCIS (Netherlands)

    Sie, Mariska; den Dunnen, Wilfred F. A.; Hoving, Eelco W.; de Bont, Eveline S. J. M.

    2014-01-01

    Brain tumors are still the leading cause of cancer morbidity and mortality among children, despite different therapeutic options including neurosurgery, chemotherapy and radiation. As angiogenesis is highly crucial in brain tumor growth and progression, numerous clinical trials evaluating diverse an

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

    International Nuclear Information System (INIS)

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

  6. Combined Flt3L/TK Gene Therapy Induces Immunological Surveillance Which Mediates an Immune Response Against a Surrogate Brain Tumor Neoantigen

    OpenAIRE

    King, Gwendalyn D; Muhammad, AKM Ghulam; Larocque, Daniel; Kelson, Kyle R; Xiong, Weidong; Liu, Chunyan; Sanderson, Nicholas SR; Kroeger, Kurt M.; Castro, Maria G; Pedro R Lowenstein

    2011-01-01

    Glioblastoma multiforme (GBM) is a primary brain tumor with a median survival of 14.6 months postdiagnosis. The infiltrative nature of GBM prevents complete resection and residual brain tumor cells give rise to recurrent GBM, a hallmark of this disease. Recurrent GBMs are known to harbor numerous mutations/gene rearrangements when compared to the primary tumor, which leads to the potential expression of novel proteins that could serve as tumor neoantigens. We have developed a combined immune-...

  7. Differential MRI Diagnosis Between Brain Abscess and Necrotic or Cystic Brain Tumors Using Diffusion Weighted Images

    Directory of Open Access Journals (Sweden)

    Zinat Miabi

    2009-01-01

    Full Text Available "nIntroduction: Differentiating brain abscesses from cystic or necrotic tumors by CT or MR imaging can be difficult. Difficulties in the diagnosis of intracranial abscess are mainly due to the combination of often unspecified clinical findings and similarities in the morphologic appearance of some intracranial mass lesions, such as cystic gliomas, metastases, and brain abscesses. Diffusion-weighted imaging provides a way to evaluate the diffusion properties of water molecules in tissue and has been used for diseases such as ischemia, tumors, epilepsy, and white matter disorders. The goal of this study was to evaluate the diagnostic utility of diffusion MRI to differentiate between brain abscesses and necrotic or cystic brain tumors. "nMaterials and Methods: MRI was performed in 17 patients (12 men and five women; age range, 19–74 years [mean, 55 years] with necrotic lesions and MR imaging evidence of ring-shaped enhancement after the injection of contrast material .In addition to standard MR sequences diffusion weighted MRI with apparent coefficient (ADC maps. "nResults: Eleven patients had tumors, and six had pyogenic abscesses. The tumors were glioblastomas (five patients, anaplastic astrocytoma (three patients, metastases (three patients, and primary malignancy, including lung (2 and breast (1 cancer. Surgical or stereotactic biopsies were obtained, and histologic studies were performed in all except one case (case 5. In the cases of abscess, bacteriologic analysis was also conducted. None of these lesions appeared hemorrhagic on T1-weighted images. "nConclusion: Diffusion-weighted imaging is useful for differentiating brain abscess from cystic or necrotic brain tumor, which is often difficult with conventional MR imaging. Diffusion-weighted imaging is useful as an additional imaging technique for establishing the differential diagnosis between brain abscesses and cystic or necrotic brain tumors. It requires less imaging time and is more

  8. Electron microscopic features of a brain tumor induced in hamster by BK virus, a human papova virus.

    Directory of Open Access Journals (Sweden)

    Tsuboi,Masahiro

    1979-12-01

    Full Text Available In order to locate the target cells for malignant transformation by BK virus (a human papova virus in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17 bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters.

  9. Caring for the brain tumor patient: Family caregiver burden and unmet needs

    OpenAIRE

    Schubart, Jane R.; Kinzie, Mable B.; Farace, Elana

    2008-01-01

    The rapid onset and progression of a brain tumor, cognitive and behavioral changes, and uncertainty surrounding prognosis are issues well known to health practitioners in neuro-oncology. We studied the specific challenges that family caregivers face when caring for patients experiencing the significant neurocognitive and neurobehavioral disorders associated with brain tumors. We selected 25 family caregivers of adult brain tumor patients to represent the brain tumor illness trajectory (crisis...

  10. Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.

    Science.gov (United States)

    Thorsen, Frits; Fite, Brett; Mahakian, Lisa M; Seo, Jai W; Qin, Shengping; Harrison, Victoria; Johnson, Sarah; Ingham, Elizabeth; Caskey, Charles; Sundstrøm, Terje; Meade, Thomas J; Harter, Patrick N; Skaftnesmo, Kai Ove; Ferrara, Katherine W

    2013-12-28

    Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  12. Granular Cell Tumor: An Uncommon Benign Neoplasm

    OpenAIRE

    Tirthankar Gayen; Anupam Das; Kaushik Shome; Debabrata Bandyopadhyay; Dipti Das; Abanti Saha

    2015-01-01

    Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

  13. Granular cell tumor: An uncommon benign neoplasm

    Directory of Open Access Journals (Sweden)

    Tirthankar Gayen

    2015-01-01

    Full Text Available Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

  14. Interstitial radiotherapy using photon radiosurgery system for brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Osami; Iseki, Hiroshi; Muragaki, Yoshihiro; Takakura, Kintomo [Tokyo Women`s Medical Coll. (Japan)

    1998-02-01

    The photon radiosurgery system is a miniature X ray generator that can be placed stereotactically and intraoperatively into intracranial tumors to deliver a single fraction of high dose interstitial irradiation. This battery powered device produces low energy X ray photons in a spherical and symmetrical pattern at the probe tip. Dose rates of up to 200 cGy/Mim are possibly allowing for the administration of 20 Gy to a lesion 3 cm in diameter in less than 1 hr. Background exposure is minimal and no special shielding of the patient or health care personnel is required. Thirty-two patients with brain tumor were treated in this method. There were no adverse effects. During the follow-up period of l-28 months, 3 of 4 patients with metastatic brain tumor died in several months after this treatment. Five recurrent cases of 21 patients with malignant glioma died in several months. We concluded interstitial radiotherapy using photon radiosurgery system for brain tumors is useful. (author)

  15. Skull-stripping for Tumor-bearing Brain Images

    CERN Document Server

    Bauer, Stefan; Reyes, Mauricio

    2012-01-01

    Skull-stripping separates the skull region of the head from the soft brain tissues. In many cases of brain image analysis, this is an essential preprocessing step in order to improve the final result. This is true for both registration and segmentation tasks. In fact, skull-stripping of magnetic resonance images (MRI) is a well-studied problem with numerous publications in recent years. Many different algorithms have been proposed, a summary and comparison of which can be found in [Fennema-Notestine, 2006]. Despite the abundance of approaches, we discovered that the algorithms which had been suggested so far, perform poorly when dealing with tumor-bearing brain images. This is mostly due to additional difficulties in separating the brain from the skull in this case, especially when the lesion is located very close to the skull border. Additionally, images acquired according to standard clinical protocols, often exhibit anisotropic resolution and only partial coverage, which further complicates the task. There...

  16. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

    Science.gov (United States)

    Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

    2015-01-01

    Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

  17. Functional imaging for brain tumors (perfusion, DTI and MR spectroscopy); Funktionelle Bildgebung bei Hirntumoren (Perfusion, DTI, MR-Spektroskopie)

    Energy Technology Data Exchange (ETDEWEB)

    Essig, M.; Giesel, F.; Stieltjes, B.; Weber, M.A. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie

    2007-06-15

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

  18. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-02-01

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

  1. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    International Nuclear Information System (INIS)

    High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors. Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy). In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy

  2. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    Directory of Open Access Journals (Sweden)

    Haveman Jaap

    2007-09-01

    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  3. Clinicopathological analysis of unusual rosette-forming glioneuronal tumor in brain parenchyma

    Directory of Open Access Journals (Sweden)

    Da-wei LIU

    2014-03-01

    lesion was observed to locate in brain parenchyma and there was no evidence of tumor infiltrating in ventricular system. Craniotomy was performed and the tumor was removed totally. Histological examination revealed that the tumor was distinctive in its juxtaposition of patterned neurocytic and pilocytic astroglial components. The neurocytic component showed the tumor cells had small, uniform round nuclei with scant cytoplasm and formed narrow perivascular pseudorosettes or Homer-Wright-like rosettes arrays of neurocytic nuclei around delicate eosinophilic neuropil cores. The glial component tended to exhibit pilocytic astrocytoma-like morphology with long, hair-like processes and Rosenthal fibers. Immunohistochemical staining showed that the tumor cells in glial component were diffusely positive for GFAP and S-100, but negative for NeuN, Syn and NSE. However, perivascular pseudorosettes or Homer-Wright-like rosettes were positive for Syn and Olig-2, and negative for GFAP. Ki-67 index was low and less than 1%. Based on clinical presentation and histological findings, a final histological diagnosis of RGNT in brain parenchyma, WHO grade Ⅰ, was made according to the criteria of WHO classification. The patient has not received chemotherapy and attended follow-up for 12 months, without any neurological deficit or signs of recurrence.  Conclusions RGNT is a rare tumor and classified as mixed neuronal-glial tumor. RGNT probably derives from a common progenitor cell originated from subependymal plate or brain parenchyma, able to differentiate toward both glial and neuronal phenotype. RGNT in brain parenchyma is also observed to have the similar biological behaviors and histopathological characteristics with its intra-ventricular counterpart. With similarities in histological findings, it may be difficult to differentiate RGNT from extraventricular neurocytoma, dysembry oplastic neuroepithelial tumor (DNT, and ependymoma with neuronal differentiation or neuropil-like islands

  4. HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy.

    Science.gov (United States)

    Gustafsson, Lotta; Hallgren, Oskar; Mossberg, Ann-Kristin; Pettersson, Jenny; Fischer, Walter; Aronsson, Annika; Svanborg, Catharina

    2005-05-01

    New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human alpha-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, alpha-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.

  5. Malignant transformation and treatment of cystic mixed germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    Yapeng Zhao; Hongyu Duan; Qinghui Zhang; Bingxin Shi; Hui Liang; Yuqi Zhang

    2016-01-01

    Objective: The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods: A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results: Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions: (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

  6. Evolution of cooperation among tumor cells.

    Science.gov (United States)

    Axelrod, Robert; Axelrod, David E; Pienta, Kenneth J

    2006-09-01

    The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

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

    Science.gov (United States)

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

    2008-05-01

    We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor. PMID:18450536

  8. Optimizing brain tumor resection. High-field interventional MR imaging.

    Science.gov (United States)

    Tummala, R P; Chu, R M; Liu, H; Truwit, C L; Hall, W A

    2001-11-01

    High-field strength iMRI guidance is an effective tool for brain tumor resection. Although its use lengthens the average time for a craniotomy, the reward is a more extensive tumor excision compared with conventional neurosurgery without an increased risk to the patient (Table 4). Although intraoperative patient transfer into and out of the magnet is cumbersome, the possibility for complete resection, especially for a low-grade glioma, makes the effort worthwhile. The cost and technical support required for this system presently limits its use to only a few sites worldwide. As with any technology, further refinements will make this system less expensive and more attainable. Practical consideration aside, high-field strength iMRI is presently [table: see text] the most effective tool available for brain tumor resection. Because of its novelty, future studies are necessary to determine if this technology lowers the incidence of and extends the duration to tumor recurrence as the preliminary data in children suggests. These are the ultimate measures of efficacy for any brain tumor treatment. Based on the rapid advancement of technology, will today's high-field strength interventional magnet become tomorrow's low-field system? Very high-field strength designs may improve diagnostic capabilities through higher resolution, but their interventional applications may be hindered by increased sensitivity for clinically insignificant abnormalities and decreased specificity for clinically relevant lesions. As new technology is developed, clinicians must continue to explore and refine the existing high-field strength iMRI to make it cost-effective and widely applicable.

  9. Tumor

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years)

  10. Linear-accelerator-based stereotactic irradiation for metastatic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Mitsuhiro; Katsui, Kuniaki; Yoshida, Atsushi [Okayama Univ. (Japan). School of Medicine] [and others

    2003-05-01

    To assess the safety and availability of stereotactic radiotherapy (SRT) for metastatic brain tumors, we reviewed 54 consecutive cases with a total of 118 brain metastases treated with linear-accelerator-based stereotactic irradiation (STI). Nineteen patients with a total of 27 brain tumors that were larger than 3 cm or close to critical normal tissues were treated with SRT. The marginal dose of SRT was 15-21 Gy (median 21 Gy) in 3 fractions for 3 days. The median marginal dose of stereotactic radiosurgery (SRS) was 20 Gy. Effective rates of imaging studies were 72.7% and 94.4%, and those of clinical symptoms were 46.7% and 55.6% for SRT and SRS, respectively. One-year and two-year survival rates of SRT were 40.9% and 17.6%, respectively, and the median follow-up period was 6.4 months. The one-year survival rate of SRS was 32.7%, with a median follow-up of 4.6 months. Fourteen cases (7 cases each) had recurrent tumors at STI sites. Early complications were observed in one case of SRT and 8 cases of SRS, and late complications occurred in 3 cases of SRS. There were no significant differences among effective rates, survival rates, median follow-up times, recurrence rates, and complications between SRT and SRS. We concluded that SRT is a safe, effective therapy for large or eloquent area metastases. (author)

  11. Cryo-ablation improves anti-tumor immunity through recovering tumor educated dendritic cells in tumor-draining lymph nodes

    Directory of Open Access Journals (Sweden)

    He XZ

    2015-03-01

    Full Text Available Xiao-Zheng He,1,2 Qi-Fu Wang,1,2 Shuai Han,3 Hui-Qing Wang,1,2 Yong-Yi Ye,1,2 Zhi-Yuan Zhu,1,2 Shi-Zhong Zhang1,2 1Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China Background: In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3+ and CD4+T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs. Methods: Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition. Results: DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10 and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo

  12. Changes in liver mitochondrial plasticity induced by brain tumor

    Directory of Open Access Journals (Sweden)

    Debien Emilie

    2006-10-01

    Full Text Available Abstract Background Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. Methods Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H2Ost were calculated from Nuclear Magnetic Resonance (NMR measurements. Results The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. Conclusion This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation.

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

    Science.gov (United States)

    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.

  14. Radiotherapy for pediatric brain tumors: Standard of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Objectives: To review the clinical characteristics of childhood brain tumors, including neurologic signs, neuroimaging and neuropathology. To critically assess indications for therapy relevant to presenting characteristics, age, and disease status. To discuss current management strategies including neurosurgery, radiation therapy, and chemotherapy. To analyze current clinical trials and future directions of clinical research. Brain tumors account for 20% of neoplastic diseases in children. The most common tumors include astrocytoma and malignant gliomas, medulloblastoma and supratentorial PNET's, ependymoma, craniopharyngioma, and intracranial germ cell tumors. Tumor type and clinical course are often correlated with age at presentation and anatomic site. The clinical characteristics and disease extent largely determine the relative merits of available 'standard' and investigational therapeutic approaches. Treatment outcome, including disease control and functional integrity, is dependent upon age at presentation, tumor type, and disease extent. An understanding of the clinical, neuroimaging, and histologic characteristics as they relate to decisions regarding therapy is critical to the radiation oncologist. Appropriate radiation therapy is central to curative therapy for a majority of pediatric brain tumor presentations. Technical advances in neurosurgery provide greater safety for 'gross total resection' in a majority of hemispheric astrocytomas and medulloblastomas. The relative roles of 'standard' radiation therapy and evolving chemotherapy for centrally located astrocytomas (e.g., diencephalic, optic pathway) need to be analyzed in the context of initial and overall disease control, neurotoxicities, and potential modifications in the risk:benefit ratio apparent in the introduction of precision radiation techniques. Modifications in radiation delivery are fundamental to current investigations in medulloblastoma; the rationale for contemporary and projected

  15. Multiclass imbalance learning:Improving classification of pediatric brain tumors from magnetic resonance spectroscopy

    OpenAIRE

    Zarinabad, Niloufar; Wilson, Martin P; Gill, Simrandip K.; Manias, Karen A; Davies, Nigel P; Peet, Andrew C

    2016-01-01

    PURPOSE: Classification of pediatric brain tumors from (1) H-magnetic resonance spectroscopy (MRS) can aid diagnosis and management of brain tumors. However, varied incidence of the different tumor types leads to imbalanced class sizes and introduces difficulties in classifying rare tumor groups. This study assessed different imbalanced multiclass learning techniques and compared the use of complete spectra and quantified metabolite profiles for classification of three main childhood brain tu...

  16. Tumors in murine brains studied by grating-based phase contrast microtomography

    Science.gov (United States)

    Schulz, Georg; Dominietto, Marco; Kovacs, Zsofia; Schmitz, Rüdiger; Hieber, Simone E.; Thalmann, Peter; Beckmann, Felix; Müller, Bert

    2014-09-01

    Angiogenesis, i.e. the formation of vessels, is one of the key processes during tumor development. The newly formed vessels transport oxygen and nutrients from the healthy tissue to the tumor and gives tumor cells the possibility to replicate. The principle of anti-angiogenic therapy is to block angiogenic process in order to stop tumor growth. The aim of the present study is the investigation of murine glioma vascular architecture at early (7 days), intermediate (10 and 15 days) and late (23 days) stage of growth by means of grating-based phase contrast microtomography. We demonstrate that this technique yields premium contrast between healthy and cancerous parts of murine brain tissues.

  17. Tumor-Related Methylated Cell-Free DNA and Circulating Tumor Cells in Melanoma

    OpenAIRE

    Salvianti, Francesca; Orlando, Claudio; Massi, Daniela; DE GIORGI, VINCENZO; Grazzini, Marta; Pazzagli, Mario; Pinzani, Pamela

    2016-01-01

    Solid tumor release into the circulation cell-free DNA (cfDNA) and circulating tumor cells (CTCs) which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma. The aim of the pres...

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

    International Nuclear Information System (INIS)

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

  19. Fetal dose estimates for radiotherapy of brain tumors during pregnancy

    International Nuclear Information System (INIS)

    Purpose: To determine clinically the fetal dose from irradiation of brain tumors during pregnancy and to quantitate the components of fetal dose using phantom measurements. Methods and Materials: Two patients received radiotherapy during pregnancy for malignant brain tumors. Case 1 was treated with opposed lateral blocked 10 x 15 cm fields and case 2 with 6 x 6 cm bicoronal wedged arcs, using 6 MV photons. Fetal dose was measured clinically and confirmed with phantom measurements using thermoluminescent dosimeters (TLDs). Further phantom measurements quantitated the components of scattered dose. Results: For case 1, both clinical and phantom measurements estimated fetal dose to be 0.09% of the tumor dose, corresponding to a total fetal dose of 0.06 Gy for a tumor dose of 68.0 Gy. Phantom measurements estimated that internal scatter contributed 20% of the fetal dose, leakage 20%, collimator scatter 33%, and block scatter 27%. For case 2, clinical and phantom measurements estimated fetal dose to be 0.04% of the tumor dose, corresponding to a total fetal dose of 0.03 Gy for a tumor dose of 78.0 Gy. Leakage contributed 74% of the fetal dose, internal scatter 13%, collimator scatter 9%, and wedge scatter 4%. Conclusions: When indicated, brain tumors may be irradiated to high dose during pregnancy resulting in fetal exposure < 0.10 Gy, conferring an increased but acceptable risk of leukemia in the child, but no other deleterious effects to the fetus after the fourth week of gestation. For our particular field arrangements and linear accelerators, internal scatter contributed a small component of fetal dose compared to leakage and scatter from the collimators and blocks, and 18 MV photons resulted in a higher estimated fetal dose than 6 MV photons due to increased leakage and collimator scatter. These findings are not universal, but clinical and phantom TLD measurements estimate fetal dose accurately for energies < 10 MV and should be taken for each pregnant patient

  20. [Utility of hyperbaric oxygenation in radiotherapy for malignant brain tumors--a literature review].

    Science.gov (United States)

    Beppu, Takaaki; Tanaka, Katsuyuki; Kohshi, Kiyotaka

    2009-06-01

    Over the past 50 years, hyperbaric oxygenation (HBO) therapy has been used in a wide variety of medical conditions; this theraphy causes an increase in oxygen tension in blood and tissues. In the treatment of malignant gliomas, HBO therapy is used for the radiosensitization of cells in combination with radiotherapy (RT). Further, HBO therapy is applied for the treatment and prevention of radiation-induced brain necrosis that is the most serious complication observed after radiosurgery. We reviewed the literature to evaluate the manner in which HBO therapy contributes to clinical fields in cases of RT administration for malignant brain tumors.

  1. CADrx for GBM Brain Tumors: Predicting Treatment Response from Changes in Diffusion-Weighted MRI

    Directory of Open Access Journals (Sweden)

    Matthew S. Brown

    2009-11-01

    Full Text Available The goal of this study was to develop a computer-aided therapeutic response (CADrx system for early prediction of drug treatment response for glioblastoma multiforme (GBM brain tumors with diffusion weighted (DW MR images. In conventional Macdonald assessment, tumor response is assessed nine weeks or more post-treatment. However, we will investigate the ability of DW-MRI to assess response earlier, at five weeks post treatment. The apparent diffusion coefficient (ADC map, calculated from DW images, has been shown to reveal changes in the tumor’s microenvironment preceding morphologic tumor changes. ADC values in treated brain tumors could theoretically both increase due to the cell kill (and thus reduced cell density and decrease due to inhibition of edema. In this study, we investigated the effectiveness of features that quantify changes from pre- and post-treatment tumor ADC histograms to detect treatment response. There are three parts to this study: first, tumor regions were segmented on T1w contrast enhanced images by Otsu’s thresholding method, and mapped from T1w images onto ADC images by a 3D region of interest (ROI mapping tool using DICOM header information; second, ADC histograms of the tumor region were extracted from both pre- and five weeks post-treatment scans, and fitted by a two-component Gaussian mixture model (GMM. The GMM features as well as standard histogram-based features were extracted. Finally, supervised machine learning techniques were applied for classification of responders or non-responders. The approach was evaluated with a dataset of 85 patients with GBM under chemotherapy, in which 39 responded and 46 did not, based on tumor volume reduction. We compared adaBoost, random forest and support vector machine classification algorithms, using ten-fold cross validation, resulting in the best accuracy of 69.41% and the corresponding area under the curve (Az of 0.70.

  2. Assessment of functional status in children with brain tumors

    International Nuclear Information System (INIS)

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

  3. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  4. Mast cells in mammalian brain.

    Science.gov (United States)

    Dropp, J J

    1976-01-01

    Mast cells, which had until recently been believed to be not present in the mammalian brain, were studied in the brains of 29 mammalian species. Although there was considerable intraspecific and interspecific variation, mast cells were most numerous within the leptomeninges (especially in those overlying the cerebrum and the dorsal thalamus - most rodents, most carnivores, chimpanzees, squirrel monkeys and elephant), the cerebral cortex (most rodents, tiger, fox, chimpanzee, tarsier, and elephant) and in many nuclei of the dorsal thalamus (most rodents, tiger, lion, and fox). In some mammals, mast cells were also numerous in the stroma of the telencephalic choroid plexuses (chimpanzee, squirrel monkey), the putamen and the claustrum (chimpanzee), the subfornical organ (pack rat, tiger, chimpanzee), the olfactory peduncles (hooded rat, albino rat), the stroma of the diencephalic choroid plexus (lion, chimpanzee, squirrel monkey), the pineal organ (chimpanzee, squirrel monkey), some nuclei of the hypothalamus (tiger), the infundibulum (hooded rat, tiger, fox) the area postrema (pack rat, chinchilla, lion, spider monkey, chimpanzee, fox) and some nuclei and tracts of the metencephalon and the myelencephalon (tiger). Neither the sex of the animal nor electrolytic lesions made in the brains of some of the animals at various times prior to sacrifice appeared to effect the number and the distribution of mast cells. Age-related changes in mast cell number and distribution were detected in the albino rat. PMID:961335

  5. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  6. The Impact of Neural Stem Cell Biology on CNS Carcinogenesis and Tumor Types

    Directory of Open Access Journals (Sweden)

    K. M. Kurian

    2011-01-01

    Full Text Available The incidence of gliomas is on the increase, according to epidemiological data. This increase is a conundrum because the brain is in a privileged protected site behind the blood-brain barrier, and therefore partially buffered from environmental factors. In addition the brain also has a very low proliferative potential compared with other parts of the body. Recent advances in neural stem cell biology have impacted on our understanding of CNS carcinogenesis and tumor types. This article considers the cancer stem cell theory with regard to CNS cancers, whether CNS tumors arise from human neural stem cells and whether glioma stem cells can be reprogrammed.

  7. Tumor Evasion from T Cell Surveillance

    Directory of Open Access Journals (Sweden)

    Katrin Töpfer

    2011-01-01

    Full Text Available An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.

  8. Radiosurgery in the management of pediatric brain tumors.

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    the use of the intensity information in the training images. Experiments on public benchmark data of patients suffering from low- and high-grade gliomas show that the method performs well compared to current state-of-the-art methods, while not being tied to any specific imaging protocol.......In this paper, we present a fully automated generative method for brain tumor segmentation in multi-modal magnetic resonance images. The method is based on the type of generative model often used for segmenting healthy brain tissues, where tissues are modeled by Gaussian mixture models combined...

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

    International Nuclear Information System (INIS)

    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

  11. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    Science.gov (United States)

    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.

  12. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    Directory of Open Access Journals (Sweden)

    Siti Norul Huda Sheikh Abdullah

    2016-01-01

    Full Text Available 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.

  13. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  14. Giant cell tumor of the mandible

    Directory of Open Access Journals (Sweden)

    G V V Giri

    2015-01-01

    Full Text Available Giant cell tumor (GCT of bone is a distinctive neoplasm characterized by abundance of multinucleated giant cells scattered throughout the stroma of mononuclear cells. Its importance lies in recognizing and differentiating the characteristic histology, which at times may mimic several other bone tumors and endocrine disorders ranging from locally aggressive giant cell granulomas to hyperparathyroidism to malignant tumors. The jaw bones account for less than 1% of the lesion.In a literature search, we found only five cases of GCT of jaw bones based on the new criteria. We present a rare case of GCT of the mandible which occurred in a 12-year-old female.

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

    Directory of Open Access Journals (Sweden)

    James F Curtin

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

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

    Science.gov (United States)

    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.

  18. Criteria for the evaluation of brachytherapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Thirty two patients with recurrent or unresectable malignant brain tumors were treated by interstitial brachytherapy with Ir-192 seeds. After-loading catheters were stereotactically implanted under local anesthesia using a Brown-Roberts-wells (BRW) CT guided stereotactic system. The response to the therapy was followed by serial CT and MRI scans and evaluated three months after implantation by the standard criteria for the evaluation of chemotherapy because there is no set of criteria available for radiation therapy. After interstitial brachytherapy, the most commonly observed CT and MRI finding was central low attenuation, that is, the central enhanced tumor replaced by the radiation necrosis. Three months after the treatment, these findings were observed in 23 patients out of 32 patients on the CT and MRI. We observed complete response (CR) in 6 of 32 patients, partial response (PR) in 9, no change (NC) in 7 and progressive disease (PD) in 9. In 6 CR patients, the tumor disappeared by three months after treatment. In 15 patients of 17 NC and PD patients, the central low attenuation was observed and their prognosis was better than those without central necrosis. The results suggested the standard criteria for the evaluation of chemotherapy, such as CR, PR etc, cannot be applicable to our series because the tumor mass replaced by necrotic tissue and remained as a mass lesion in most cases and new criteria in consideration of this low attenuation on CT and MRI will be needed for the evaluation of brachytherapy on neuroimagings. (author)

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

    Science.gov (United States)

    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.

  20. Combined therapy of radiotherapy and chemotherapy on brain tumor

    International Nuclear Information System (INIS)

    The subjects were 52 patients (5-78 years, average 51.4 years) with primary brain tumor treated in 4 institutes in Chugoku and Shikoku districts during 3 years from April 1991. Histopathologically, the subject diseases were glioblastoma in 16, well differentiated glioblastoma in 19, brain primary lymphoma in 9, and malignant meningioma in 5. In the glioblastoma group, 14 received surgery, radiotherapy, and chemotherapy at the first admission. Three patients who survived more than 1 year and 6 patients who died within 1 year were compared. No significant difference was observed in terms of radiotherapy between the both groups. In the astrocytoma and oligodendroglioma groups, 16 patients received radiotherapy and chemotherapy as the initial treatment, and 14 underwent several course of maintenance therapy. In the comparison between 7 patients who died within 3 years from the first treatment and 9 patients surviving more than 3 years, no significant difference was observed in terms of radiation doses. (S.Y.)

  1. CellTracks cytometer for detection of circulating tumor cells

    NARCIS (Netherlands)

    Tibbe, A.G.J.; Kooi, van der A.; Groot, de M.R.; Vermes, I.

    2003-01-01

    Introduction: In patients with carcinomas, tumor cells are shed into the circulation. The number of the circulating tumor cells is low and technology is needed that has sufficient sensitivity and specificity to enumerate and characterize these cells. The CellTracks system was developed to provide an

  2. Isolation, cultivation and identification of brain glioma stem cells by magnetic bead sorting

    Institute of Scientific and Technical Information of China (English)

    Xiuping Zhou; Chao Zheng; Qiong Shi; Xiang Li; Zhigang Shen; Rutong Yu

    2012-01-01

    This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

  3. Effusion cytomorphology of small round cell tumors

    OpenAIRE

    Katsuhide Ikeda; Koji Tsuta

    2016-01-01

    Background: Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT neoplastic cells in the effusion fluid is very rare. We reported the cytomorphological findings of SRCTs in effusion cytology, and performed statistical and mathematical analyses for a purpose to distinguish SRCTs. Materials and Methods: We analyzed the cytologic findings of effusion samples from 40 SRCT cases and...

  4. Diagnostic study with CT and MR on the metastasis of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Miyagami, Mitsusuke; Kasahara, Eishi; Tazoe, Makoto; Tsubokawa, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine)

    1990-08-01

    Forty cases of malignant brain tumors with metastasis which involved 14 malignant gliomas, 15 medulloblastomas and 11 germ cell tumors were studied on CT and MRI. In malignant glioma, transventricular metastasis was seen most frequently, estimating 8 cases (57%) of 14 malignant gliomas with metastasis and showing ependymal-subependymal enhancement on contrast-enhanced CT (CECT). Most of the medulloblastoma with metastasis demonstrated diffuse subarachnoid seeding in the craniospinal space and on image analysis diffuse sulcal-cisternal enhancement was characterized. Trans-ventricular metastasis in medulloblastoma was less than in malignant glioma showing 3 cases (20%) of 15 medulloblastomas, which in most cases showed a nodular tumor in the ventricular wall by metastasis. There were six patients who, on the first admission, were found to have germ cell tumors of the broad infiltrating type with multiple lesions. The tumor sites of metastasis were different from those with malignant gliomas, being frequently localized in the pineal and/or the suprasellar region, on the ventricular wall and in the basal ganglia. Metastasis to a remote area in germ cell tumors was to spinal cords, to the ventricular wall and basal cistern around the brain stem by CSF dissemination, to the lung by hematogenous metastasis and to the peritoneal wall or organs through V-P shunt tube. T{sub 1}-weighted Gd-DTPA MRI was more useful and sensitive than CECT for diagnosis of the leptomeningeal metastasis, particularly for sulcal-cisternal and spinal metastasis. It will be used more often as the first choice for diagnosis of intrathecal metastasis in the future. (author).

  5. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  6. Deleted in Malignant Brain Tumors 1 is up-regulated in bacterial endocarditis and binds to components of vegetations

    DEFF Research Database (Denmark)

    Müller, Hanna; Renner, Marcus; Helmke, Burkhard M;

    2009-01-01

    OBJECTIVE: Bacterial endocarditis is a frequent infectious cardiac disease, especially in patients with congenital or acquired heart defects. It is characterized by bacterial colonization of the heart valves and the appearance of vegetations consisting of fibrin, blood cells, and bacteria...... be linked to the development of vegetations. METHODS: Heart tissue of 19 patients with bacterial endocarditis and 10 controls without bacterial endocarditis was analyzed by immunohistochemistry. The effect of human recombinant Deleted in Malignant Brain Tumors 1 on erythrocyte aggregation was measured using...... an automated red blood cell aggregometer MA1. Binding of human recombinant Deleted in Malignant Brain Tumors 1 to erythrocyte membranes, platelets, fibrin, and fibrinogen was analyzed by Western blotting and enzyme-linked immunosorbent assay. RESULTS: Deleted in Malignant Brain Tumors 1 expression was up...

  7. Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix.

    Directory of Open Access Journals (Sweden)

    Cheryl V Rahman

    Full Text Available INTRODUCTION: Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid (PLGA/poly(ethylene glycol (PEG microparticles. METHODS: PLGA/PEG microparticle-based matrices were molded around an ex vivo brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. In vitro toxicity of the polymer was assessed using tumor and endothelial cells and drug release from trichostatin A-, etoposide- and methotrexate-loaded matrices was determined. To verify activity of released agents, tumor cells were seeded onto drug-loaded matrices and viability assessed. RESULTS: PLGA/PEG matrices can be molded around a pseudo-resection cavity wall with no polymer-related artifact on clinical scans. The polymer withstands fractionated radiotherapy, with no disruption of microparticle structure. No toxicity was evident when tumor or endothelial cells were grown on control matrices in vitro. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period in vitro and etoposide released over 3 days in vivo, with released agents retaining cytotoxic capabilities. PLGA/PEG microparticle-based matrices molded around a resection cavity wall are distinguishable in clinical scanning modalities. Matrices are non-toxic in vitro suggesting good biocompatibility in vivo. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release. CONCLUSION: The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors.

  8. Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Justin D Lathia

    Full Text Available High-grade gliomas (World Health Organization grade III anaplastic astrocytoma and grade IV glioblastoma multiforme, the most prevalent primary malignant brain tumors, display a cellular hierarchy with self-renewing, tumorigenic cancer stem cells (CSCs at the apex. While the CSC hypothesis has been an attractive model to describe many aspects of tumor behavior, it remains controversial due to unresolved issues including the use of ex vivo analyses with differential growth conditions. A CSC population has been confirmed in malignant gliomas by preferential tumor formation from cells directly isolated from patient biopsy specimens. However, direct comparison of multiple tumor cell populations with analysis of the resulting phenotypes of each population within a representative tumor environment has not been clearly described. To directly test the relative tumorigenic potential of CSCs and non-stem tumor cells in the same microenvironment, we interrogated matched tumor populations purified from a primary human tumor transplanted into a xenograft mouse model and monitored competitive in vivo tumor growth studies using serial in vivo intravital microscopy. While CSCs were a small minority of the initial transplanted cancer cell population, the CSCs, not the non-stem tumor cells, drove tumor formation and yielded tumors displaying a cellular hierarchy. In the resulting tumors, a fraction of the initial transplanted CSCs maintained expression of stem cell and proliferation markers, which were significantly higher compared to the non-stem tumor cell population and demonstrated that CSCs generated cellular heterogeneity within the tumor. These head-to-head comparisons between matched CSCs and non-stem tumor cells provide the first functional evidence using live imaging that in the same microenvironment, CSCs more than non-stem tumor cells are responsible for tumor propagation, confirming the functional definition of a CSC.

  9. P03.09PHARMACOLOGICAL MODULATION OF BLOOD-BRAIN BARRIER: FUTURE STRATEGY FOR TREATMENT OF BRAIN TUMORS

    OpenAIRE

    Sardi, I.; Cardellicchio, S.; Iorio, A.L.; da Ros, M.; la Marca, G.; Giunti, L.; Massimino, M.; L. Genitori

    2014-01-01

    A prerequisite for the efficacy of chemotherapy is that it reaches the tumor mass at a therapeutic concentration. In brain tumors this phenomenon is hampered by the presence of the blood brain barrier (BBB) which limits the spread of chemotherapeutic agents within the brain. It is lately emerged as this Multi Drug Resistance (MDR) phenomenon is explained through the cooperation of P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2), two “gatekeeper" transporters th...

  10. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette;

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared......The discovery of tumor stem cells being highly resistant against therapy makes new demands to model systems suitable for evaluation of the effects of new drugs on tumor stem cells. The aim of the present study was therefore to develop an in vivo-like in vitro glioblastoma model for testing...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Ekokobe eFonkem; Paul eBricker; Diana eMungall; Jose eAceves; Eromata eEbwe; Wei eTang; Batool F. Kirmani

    2013-01-01

    Levetiracetam, tradename Keppra, is a new second generation antiepileptic drug that is being used increasingly in brain tumor patients. In patients suffering with brain tumors, seizures are one of the leading neurologic complications seen in more than 30% of patients. Levetiracetam is a pyrollidine-derivative drug, which has a unique mechanism of action. Unlike other antiepileptic drugs, Levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting calcium release. Brain tumor...

  13. [Untoward side effects of chemoradiotherapy in children with malignant brain tumors].

    Science.gov (United States)

    Morozova, S K; Begun, I V; Spivak, L V; Radiuk, K A; Papkevich, I I; Savich, T V; Pershaĭ, E B; Vashkevich, T I; Aleĭnikova, O V

    2002-01-01

    Untoward side-effects of chemoradiotherapy were compared in 48 children treated for brain tumors and those in remission lasting from less than 12 months to 11 years. The investigation concerned disturbances in the neurologic, endocrine, cardiovascular, urinary, hepatobiliary and psychic systems; neurologic ones proved the most frequent. No cases of heart failure were reported among patients with brain tumors during remission. Hormonal study revealed inhibited thyroid function in brain tumor sufferers. PMID:12455363

  14. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  15. Treatment-related changes in functional connectivity in brain tumor patients : a magnetoencephalography study

    NARCIS (Netherlands)

    Douw, Linda; Baayen, Hans; Bosma, Ingeborg; Klein, Martin; Vandertop, Peter; Heimans, Jan; Stam, Kees; de Munck, Jan; Reijneveld, Jaap

    2008-01-01

    Widespread disturbances in resting state functional connectivity between remote brain areas have been demonstrated in patients with brain tumors. Functional connectivity has been associated with neurocognitive deficits in these patients. Thus far, it is unknown how (surgical) treatment affects funct

  16. Preclinical validation of electrochemotherapy as an effective treatment for brain tumors

    DEFF Research Database (Denmark)

    Agerholm-Larsen, Birgit; Iversen, Helle K; Ibsen, Per;

    2011-01-01

    eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor...... treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment...... treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to...

  17. Metastatic Brain Tumors: A Retrospective Review in East Azarbyjan (Tabriz

    Directory of Open Access Journals (Sweden)

    Zinat Miabi

    2011-02-01

    Full Text Available A set of one hundred and twenty nine patients with known primary malignancy and suspected brain metastasis was reviewed in present study. The patients were selected among patients presented to the MRI section of Imam Khomeini Hospital or a private MRI center in Tabriz (Iran. Primary tumor site, clinical manifestations, number and site of lesions were identified in this patient population. The primary tumor site was breast in 55 patients (42.6%, followed by lung (40.3%, kidney (7.7%, colorectal (4.6%, lymphoma (3.1% and melanoma (1.5%. Most patients were presented with features of increased intracranial pressure (headaches and vomiting, seizures and focal neurologic signs. Single brain metastasis occurred in 16.3% of patients, while multiple lesions accounted for 83.7% of patients. Ninety seven patients had supratentorial metastases (75.2%. Twenty cases (15.5% had metastases in both compartments. Infratentorial lesions were observed only in twelve patients (9.3%.

  18. Is outpatient brain tumor surgery feasible in India?

    Science.gov (United States)

    Turel, Mazda K; Bernstein, Mark

    2016-01-01

    The current trend in all fields of surgery is towards less invasive procedures with shorter hospital stays. The reasons for this change include convenience to patients, optimal resource utilization, and cost saving. Technological advances in neurosurgery, aided by improvements in anesthesia, have resulted in surgery that is faster, simpler, and safer with excellent perioperative recovery. As a result of improved outcomes, some centers are performing brain tumor surgery on an outpatient basis, wherein patients arrive at the hospital the morning of their procedure and leave the hospital the same evening, thus avoiding an overnight stay in the hospital. In addition to the medical benefits of the outpatient procedure, its impact on patient satisfaction is substantial. The economic benefits are extremely favorable for the patient, physician, as well as the hospital. In high volume centers, a day surgery program can exist alongside those for elective and emergency surgeries, providing another pathway for patient care. However, due to skepticism surrounding the medicolegal aspects, and how radical the concept at first sounds, these procedures have not gained widespread popularity. We provide an overview of outpatient brain tumor surgery in the western world, discussing the socioeconomic, medicolegal, and ethical issues related to its adaptability in a developing nation. PMID:27625225

  19. Endocrine abnormalities after radiation therapy for brain tumors in children

    Energy Technology Data Exchange (ETDEWEB)

    Aida, Toshimitsu; Sugimoto, Shinji; Abe, Hiroshi; Fujieda, Kenji; Matsuura, Nobuo (Hokkaido Univ., Sapporo (Japan). School of Medicine)

    1990-12-01

    Endocrine evaluations were performed in 5 children, previously treated for brain tumors which did not directly involve the hypothalamic-pituitary axis, who had received cranial irradiation 2 to 4 years earlier. Their rate of growth was considerably reduced during the year following the completion of cranial irradiation. Impaired growth hormone (GH) responses to an insulin tolerance test (ITT) were observed in all 6 and to an arginine tolerance test (ATT) in 5 children. Three children had a prolonged response of thyroid-stimulating hormone (TSH) to thyrotrophin releasing hormone (TRH). The remaining pituitary functions were essentially normal. Four children received human GH therapy. The growth rate of each was improved by GH therapy, but 2 of the 4 were still short with a standing height standard deviation score (SDS) below 2. Close monitoring of the growth and hormonal status of children with brain tumors treated with cranial irradiation is necessary, and the timing of the initiation of GH therapy is very important for partial or complete restoration of the normal growth rate. (author).

  20. Combined local blood–brain barrier opening and systemic methotrexate for the treatment of brain tumors

    OpenAIRE

    Cooper, Itzik; Last, David; Guez, David; Sharabi, Shirley; Elhaik Goldman, Shirin; Lubitz, Irit; Daniels, Dianne; Salomon,Sharona; Tamar, Gregory; Tamir, Tzur; Mardor, Ronni; Fridkin, Mati; Shechter, Yoram; Mardor, Yael

    2015-01-01

    Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood–brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically ...

  1. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer

    OpenAIRE

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G. William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand–receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma.

  2. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer.

    Science.gov (United States)

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  3. Fetal brain tumors: Prenatal diagnosis by ultrasound and magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Hérbene; José; Milani; Edward; Araujo; Júnior; Sérgio; Cavalheiro; Patrícia; Soares; Oliveira; Wagner; Jou; Hisaba; Enoch; Quinderé; Sá; Barreto; Maurício; Mendes; Barbosa; Luciano; Marcondes; Nardozza; Antonio; Fernandes; Moron

    2015-01-01

    Congenital central nervous system tumors diagnosed during pregnancy are rare, and often have a poor prognosis. The most frequent type is the teratoma. Use of ultrasound and magnetic resonance image allows the suspicion of brain tumors during pregnancy. However, the definitive diagnosis is only confirmed after birth by histology. The purpose of this mini-review article is to describe the general clinical aspects of intracranial tumors and describe the main fetal brain tumors.

  4. Thoughts about cancer stem cells in solid tumors.

    Science.gov (United States)

    La Porta, Caterina Am

    2012-03-26

    Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance. A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. In recent years, the cancer stem cell (CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective. Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. On the other hand, the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations. In the present review, recent papers published on CSCs in solid tumors (breast, prostate, brain and melanoma) are discussed, highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor. A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed. The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer. Developing diagnostic/prognostic tools to follow cancer development is also a challenge. In this connection it would be useful to develop a multidisciplinary approach combining mathematics, physics and biology which merges experimental approaches and theory. Biological models alone are probably unable to resolve the problem completely.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

  6. Characterization of cell suspensions from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.

    1985-07-10

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs.

  7. General Information about Extragonadal Germ Cell Tumors

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  8. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  9. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  10. Genetic instability in nerve sheath cell tumors

    DEFF Research Database (Denmark)

    Rogatto, Silvia Regina; Casartelli, Cacilda; Rainho, Claudia Aparecida;

    1995-01-01

    by the presence of polyploid cells with inconsistent abnormalities, endoreduplications and telomeric associations resulting in dicentric chromosomes. It is probable that these cytogenetic abnormalities represent some kind of evolutionary advantage for the in vitro progression of nerve sheath tumors....

  11. Radiation therapy for intracranial germ cell tumors. Predictive value of tumor response as evaluated by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko; Toita, Takafumi; Kakinohana, Yasumasa; Yamaguchi, Keiichiro; Miyagi, Koichi; Kinjo, Toshihiko; Yamashiro, Katsumi; Sawada, Satoshi [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine

    1997-07-01

    This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response during radiation therapy can predict achievement of primary local with radiation therapy alone. Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy). Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years. Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and 100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone and initial tumor volume. The rate of tumor volume response to irradiation assessed by CT was significantly different in those patients who relapsed compared to those who did not relapse. Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy alone. (author)

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

    Science.gov (United States)

    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

  13. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  14. Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells

    DEFF Research Database (Denmark)

    Müller, Hanna; Nagel, Christian; Weiss, Christel;

    2015-01-01

    between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro. METHODS: We examined by ELISA VEGF levels in 120 tracheal aspirates of 57 preterm and term infants and tested for correlation with different perinatal factors as well...... were determined via ELISA in the supernatant of the unstimulated cells and after stimulation with LPS, TNFα and Phorbol-12-myristate-13-acetate (PMA). RESULTS: The VEGF levels in the tracheal aspirates of preterm and term infants were significantly correlated with DMBT1 levels (p = 0...

  15. Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

    Science.gov (United States)

    2016-02-10

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  16. Comparison between neuroimaging classifications and histopathological diagnoses using an international multicenter brain tumor magnetic resonance imaging database.

    NARCIS (Netherlands)

    Julia-Sape, M.; Acosta, D.M.; Majos, C.; Moreno-Torres, A.; Wesseling, P.; Acebes, J.J.; Griffiths, J.R.; Arus, C.

    2006-01-01

    OBJECT: The aim of this study was to estimate the accuracy of routine magnetic resonance (MR) imaging studies in the classification of brain tumors in terms of both cell type and grade of malignancy. METHODS: The authors retrospectively assessed the correlation between neuroimaging classifications a

  17. Pre Operative Brain Mapping with Functional MRI in Patient with Brain Tumors: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Sina Hooshmand

    2010-05-01

    Full Text Available Background/Objective: Functional Magnetic Resonance Imaging (fMRI plays a significant role in pre-neurosurgical planning at present. FMRI is a possible candidate to replace invasive methods for determination of the language dominant hemisphere and cortical areas associated with language and memory. We used this method to explore language and motor functions in healthy volunteers before creating standard paradigms for Persian language. In this study, we used the standard protocol of language and motor brain mapping in patients harboring brain tumors."nPatients and Methods: Ten patients with brain tumor were included in this study. Each subject performed three to five language related tasks during fMRI scan and also one motor related task. These tasks included; "Word Generation" (WG, "Object Naming" (ON, and "Word Reading" (WR, "Word Production" (WP and "Reverse Word Reading" (RWR. They also performed the thumb apposition task for activating primary sensory-motor areas. Fifteen continuous slices were acquired, and data analysis was carried out using FSL 4.1. After evaluating the individual results, the lateralization index (LI for each subject-task was calculated and the dominant hemisphere for language production was reported. Also localization of critical language areas in the cerebral cortex was performed and the coordinates of epicenter for language production in Broca's area was calculated."nResults: We found that WP, RWR, and WG activate language related areas in the dominant hemisphere robustly in patients with brain tumors and can predict the dominant hemisphere along with eloquent language cortices. However, ON and WR fail to delineate these activation areas optimally. In addition, the results reveal that higher activation intensities are obtained by WP in the frontal lobe including Broca's area, whereas RWR leads to the highest LI among all examined tasks. In patients harboring brain tumors, precise lateralization and

  18. Structural and theoretical studies on rhodium and iridium complexes with 5-nitrosopyrimidines. Effects on the proteolytic regulatory enzymes of the renin-angiotensin system in human tumoral brain cells.

    Science.gov (United States)

    Illán-Cabeza, Nuria A; Jiménez-Pulido, Sonia B; Ramírez-Expósito, María J; García-García, Antonio R; Peña-Ruiz, Tomás; Martínez-Martos, José M; Moreno-Carretero, Miguel N

    2015-02-01

    The reactions of [RhCl(CO)(PPh3)2], [RhCl(CO)2]2 and [IrCl(CO)(PPh3)2] with different 5-nitrosopyrimidines afforded sixteen complexes which have been structurally characterized by elemental analysis, IR and NMR ((1)H and (13)C) spectral methods and luminescence spectroscopy. The crystal and molecular structures of [Rh(III)Cl(VIOH-1)2(PPh3)], [Rh(III)Cl(DVIOH-1)2(PPh3)] and [Rh(II)(DVIOH-1)2(PPh3)2] have been established from single crystal x-ray structure analyses. The three complexes are six-coordinated with both violurato ligands into an equatorial N5,O4-bidentate fashion, but with different mutually arrangements. Theoretical studies were driven on the molecular structure of [Rh(III)Cl(VIOH-1)2(PPh3)] to assess the nature of the metal-ligand interaction as well as the foundations of the cis-trans (3L-2L) isomerism. An assortment of density functional (SOGGA11-X, B1LYP, B3LYP, B3LYP-D3 and wB97XD) has been used, all of them leading to a similar description of the target system. Thus, a topological analysis of the electronic density within AIM scheme and the study of the Mulliken charges yield a metal-ligand link of ionic character. Likewise, it has been proved that the cis-trans isomerism is mainly founded on that metal-ligand interaction with the relativistic effects playing a significant role. Although most of the compounds showed low direct toxicity against the human cell lines NB69 (neuroblastoma) and U373-MG (astroglioma), they differently modify in several ways the renin-angiotensin system (RAS)-regulating proteolytic regulatory enzymes aminopeptidase A (APA), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP). Therefore, these complexes could exert antitumor activity against both brain tumor types, acting through the paracrine regulating system mediated by tissue RAS rather than exerting a direct cytotoxic effect on tumor cells.

  19. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy.

  20. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Harford-Wright

    Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

  1. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

    Directory of Open Access Journals (Sweden)

    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  2. Osteoclastic giant cell tumor of the pancreas: an immunohistochemical study

    DEFF Research Database (Denmark)

    Dizon, M A; Multhaupt, H A; Paskin, D L;

    1996-01-01

    A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor.......A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor....

  3. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  4. Metabolomics and proteomics studies of brain tumors : a chemometric bioinformatics approach

    OpenAIRE

    Mörén, Lina

    2015-01-01

    The WHO classification of brain tumors is based on histological features and the aggressiveness of the tumor is classified from grade I to IV, where grade IV is the most aggressive. Today, the correlation between prognosis and tumor grade is the most important component in tumor classification. High grade gliomas, glioblastomas, are associated with poor prognosis and a median survival of 14 months including all available treatments. Low grade meningiomas, usually benign grade I tumors, are in...

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

    OpenAIRE

    Uematsu, Hidemasa; Maeda, Masayuki

    2006-01-01

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

  6. Cognitive dysfunction in children with brain tumors at diagnosis

    Science.gov (United States)

    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. Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement.

    Science.gov (United States)

    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

  8. Brain tumor epilepsy: A reappraisal and six remaining issues to be debated.

    OpenAIRE

    Vercueil, Laurent

    2011-01-01

    International audience Epilepsy associated with brain tumors presents with specific features deserving medical attention. Although commonly reported in patients with brain tumor, either as revealing mode or as a remote complication, limited knowledge is available regarding their epidemiology, clinical evolution, surgical outcome, physiopathology and treatment, providing only clues for clinical management. Seizures appear even more threatening for patients and caregivers, providing seizures...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  10. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    Science.gov (United States)

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults.

  11. Apoptin: specific killer of tumor cells?

    Science.gov (United States)

    Tavassoli, M; Guelen, L; Luxon, B A; Gäken, J

    2005-08-01

    In the early 1990s it was discovered that the VP3/Apoptin protein encoded by the Chicken Anemia virus (CAV) possesses an inherent ability to specifically kill cancer cells. Apoptin was found to be located in the cytoplasm of normal cells while in tumor cells it was localized mainly in the nucleus.(1) These differences in the localization pattern were suggested to be the main mechanism by which normal cells show resistance to Apoptin-mediated cell killing. Although the mechanism of action of Apoptin is presently unknown, it seems to function by the induction of programmed cell death (PCD) after translocation from the cytoplasm to the nucleus and arresting the cell cycle at G2/M, possibly by interfering with the cyclosome.(2) In addition, cancer specific phosphorylation of Threonine residue 108 has been suggested to be important for Apoptin's function to kill tumor cells.(3) In contrast to the large number of publications reporting that nuclear localization, induction of PCD and phosphorylation of Apoptin is restricted to cancer cells, several recent studies have shown that Apoptin has the ability to migrate to the nucleus and induce PCD in some of the normal cell lines tested. There is evidence that high protein expression levels as well as the cellular growth rate may influence Apoptin's ability to specifically kill tumor cells. Thus far both in vitro and in vivo studies indicate that Apoptin is a powerful apoptosis inducing protein with a promising prospective utility in cancer therapy. However, here we show that several recent findings contradict some of the earlier results on the tumor specificity of Apoptin, thus creating some controversy in the field. The aim of this article is to review the available data, some published and some unpublished, which either agree or contradict the reported "black and white" tumor cell specificity of Apoptin. Understanding what factors appear to influence its function should help to develop Apoptin into a potent anti

  12. Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells.

    Science.gov (United States)

    Chi, Lianhua; Na, Moon-Hee; Jung, Hyun-Kyung; Vadevoo, Sri Murugan Poongkavithai; Kim, Cheong-Wun; Padmanaban, Guruprasath; Park, Tae-In; Park, Jae-Yong; Hwang, Ilseon; Park, Keon Uk; Liang, Frank; Lu, Maggie; Park, Jiho; Kim, In-San; Lee, Byung-Heon

    2015-07-10

    A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to lung tumor. IL4RPep-1 preferentially bound to H226 lung tumor cells which express higher levers of IL-4R compared to H460 lung tumor cells which express less IL-4R. Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were the key binding determinants. IL4RPep-1-labeled liposomes containing doxorubicin were more efficiently internalized in H226 cells and effectively delivered doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence imaging of nude mice subcutaneously xenotransplanted with H226 tumor cells indicated that IL4RPep-1-labeled liposomes accumulate more efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes. Interestingly, expression of IL-4R was high in vascular endothelial cells of tumor, while little was detected in vascular endothelial cells of control organs including the liver. IL-4R expression in cultured human vascular endothelial cells was also up-regulated when activated by a pro-inflammatory cytokine tumor necrosis factor-α. Moreover, the up-regulation of IL-4R expression was observed in primary human lung cancer tissues. These results indicate that IL-4R-targeting nanocarriers may be a useful strategy to enhance drug delivery through the recognition of IL-4R in both tumor cells and tumor endothelial cells. PMID:25979323

  13. Spectrum of pediatric brain tumors in India: A multi-institutional study

    Directory of Open Access Journals (Sweden)

    Ayushi Jain

    2011-01-01

    Full Text Available Background : Till date there is no published multi-institutional data regarding the epidemiological profile of pediatric brain tumors in India. Aim : The present retrospective study analyses the histological spectrum of pediatric age group brain tumors in seven tertiary care hospitals in India. Material and Methods : Data regarding frequencies of various primary brain tumors (diagnosed according to the World Health Organization (WHO classification, in 3936 pediatric patients (<18 yrs of age, was collected from seven tertiary care hospitals in India.Results : The most common primary pediatric brain tumors were astrocytic tumors (34.7%, followed by medulloblastoma and supratentorial primitive neuro-ectodermal tumors (22.4%, craniopharyngiomas (10.2% and ependymal tumors (9.8%. The most common astrocytic tumor was pilocytic astrocytoma. In comparison to adults, oligodendrogliomas and lymphomas were rare in children. Conclusions : Our study is the first such report on the histological spectrum of brain tumors in children in India. Except for a slightly higher frequency of craniopharyngiomas, the histological profile of pediatric brain tumors in India is similar to that reported in the Western literature.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  15. Tumor cure and tumor cell survival kinetics after photoradiation treatment in vivo in two experimental mouse tumor systems

    International Nuclear Information System (INIS)

    To study the question whether tumor destruction by photoradiation therapy (PRT) in vivo is due to direct tumor cell kill or whether it is a consequence of damage to the tumor support structures, the authors have used the EMT-6 and RIF in vivo-in vitro tumor systems, which allow colony formation survival assay of tumor cells treated with PRT in vivo. The EMT-6 tumor showed no significant reduction in tumor cell clonogenicity at the completion of PRT at doses which are curative to the tumor. However, when the tumors were allowed to remain in situ for varying lengths of time (1-24 h) after PRT, tumor cell death occurred rapidly and progressively. Very similar tumor cell survival kinetics were found in RIF tumors, although cure of these tumors by PRT is rare. The pattern of tumor cell death following PRT in vivo closely matches that of tumors deprived of oxygen, implying that one of the major factors leading to tumor destruction by PRT may be the shut-down of tumor vasculature, which has been shown to be one of the initial effects of PRT

  16. 3-D in vivo brain tumor geometry study by scaling analysis

    Science.gov (United States)

    Torres Hoyos, F.; Martín-Landrove, M.

    2012-02-01

    A new method, based on scaling analysis, is used to calculate fractal dimension and local roughness exponents to characterize in vivo 3-D tumor growth in the brain. Image acquisition was made according to the standard protocol used for brain radiotherapy and radiosurgery, i.e., axial, coronal and sagittal magnetic resonance T1-weighted images, and comprising the brain volume for image registration. Image segmentation was performed by the application of the k-means procedure upon contrasted images. We analyzed glioblastomas, astrocytomas, metastases and benign brain tumors. The results show significant variations of the parameters depending on the tumor stage and histological origin.

  17. EXPRESSION OF IL-13Ra2 GENE IN HUMAN BRAIN TUMORS

    Institute of Scientific and Technical Information of China (English)

    WU An-hua; TIE Xin-xin; WANG Yun-jie; YANG Guo-rui

    2005-01-01

    Objective: To investigate the expression of IL-13Ra2 gene in brain tumors. Methods: Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results: IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion:Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.

  18. Fast detection of MYCN copy number alterations in brain neuronal tumors by real-time PCR.

    Science.gov (United States)

    Malakho, S G; Korshunov, A; Stroganova, A M; Poltaraus, A B

    2008-01-01

    Increased MYCN gene copy number is a characteristic property of neurogenic tumors. Fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (array-CGH) are traditionally used to determine MYCN amplification for tumor stratification. A unique ability of real-time quantitative polymerase chain reaction (qPCR) to determine gene copy number, even within a small percent of observed tumor cells, and can be more appropriate. MYCN genomic copy number from 44 human brain tumors (22 medulloblastomas and 22 neurocytomas) was determined by means of FISH, array-CGH, and qPCR. By qPCR, with the original set of oligonucleotides, 17 out of 44 (38.6%) tumors were found to contain a 1.3- to 2.9-fold increase of MYCN defined as low-level gain. An absolute qPCR method was used to get high accuracy of results. Strong correlation was observed between the three methods: for medulloblastomas, r=1 (Pgain and amplification). PMID:18348317

  19. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    Science.gov (United States)

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  20. The Human Cell Surfaceome of Breast Tumors

    Directory of Open Access Journals (Sweden)

    Júlia Pinheiro Chagas da Cunha

    2013-01-01

    Full Text Available Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors.

  1. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  2. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  3. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Schmalz, Philip G.R. [Surgical and Molecular Neuro-Oncology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States); Howard Hughes Medical Institute, National Institutes of Health Research Scholars Program, Bethesda, MD 20892 (United States); Shen, Michael J.; Park, John K., E-mail: parkjk@ninds.nih.gov [Surgical and Molecular Neuro-Oncology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-02-10

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed.

  4. MethPed: an R package for the identification of pediatric brain tumor subtypes

    OpenAIRE

    Ahamed, Mohammad Tanvir; Danielsson, Anna; Nemes, Szilárd; Carén, Helena

    2016-01-01

    Background DNA methylation profiling of pediatric brain tumors offers a new way of diagnosing and subgrouping these tumors which improves current clinical diagnostics based on histopathology. We have therefore developed the MethPed classifier, which is a multiclass random forest algorithm, based on DNA methylation profiles from many subgroups of pediatric brain tumors. Results We developed an R package that implements the MethPed classifier, making it easily available and accessible. The pack...

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

    OpenAIRE

    Meng, L.; Han, SJ; Rollins, MD; Gelb, AW; Chang, EF

    2016-01-01

    © Published by Elsevier Ltd. 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 invol...

  6. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    OpenAIRE

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K. R.; Cerami, A

    1990-01-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weig...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Uematsu, Hidemasa [University of Fukui, Department of Radiology, Faculty of Medical Sciences, Fukui (Japan); Maeda, Masayuki [Mie University School of Medicine, Department of Radiology, Mie (Japan)

    2006-01-01

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

  10. Ultrasound features of orbital granular cell tumor.

    Science.gov (United States)

    Ayres, Bernadete; Miller, Neil R; Eberhart, Charles G; Dibernardo, Cathy W

    2009-01-01

    The authors report the echographic characteristics of a rare orbital granular cell tumor and correlate these findings with histopathology. A 56-year-old woman presented with proptosis. Complete ophthalmic and ultrasound examinations were performed. Ultrasound revealed an oval, well-outlined orbital mass in the intraconal space with low-medium reflectivity and regular internal structure. An orbitotomy with complete excision of the tumor was performed. Histopathologic evaluation showed sheets and nests of cells with abundant eosinophilic and granular cytoplasm in a uniform distribution throughout the lesion. The echographic characteristics correlated well with the morphologic surgical findings and the histologic architecture. This is the first report describing the echographic characteristics of orbital granular cell tumor.

  11. Risk assessment of thyroid follicular cell tumors.

    OpenAIRE

    Hill, R. N.; Crisp, T M; Hurley, P M; Rosenthal, S L; Singh, D. V.

    1998-01-01

    Thyroid follicular cell tumors arise in rodents from mutations, perturbations of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1)...

  12. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors.

    Science.gov (United States)

    Wyckoff, Jeffrey B; Wang, Yarong; Lin, Elaine Y; Li, Jiu-feng; Goswami, Sumanta; Stanley, E Richard; Segall, Jeffrey E; Pollard, Jeffrey W; Condeelis, John

    2007-03-15

    Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.

  13. The Role of Surgery, Radiosurgery and Whole Brain Radiation Therapy in the Management of Patients with Metastatic Brain Tumors

    Directory of Open Access Journals (Sweden)

    Thomas L. Ellis

    2012-01-01

    Full Text Available Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS, whole brain radiation therapy (WBRT, and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer.

  14. Tumor-associated macrophages promote tumor cell proliferation in nasopharyngeal NK/T-cell lymphoma

    OpenAIRE

    Liu, Yixiong; Fan, Linni; Wang, Yingmei; Li, Peifeng; Zhu, Jin; Wang, Lu; Zhang, Weichen; Zhang, Yuehua; Huang, Gaosheng

    2014-01-01

    Objective: To explore the relationship between the number of tumor-associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T-cell lymphoma. Methods: Immunohistochemistry was used to reconfirm the diagnosis of nasal NK/T-cell lymphoma and detect the numbers of TAMs and the ki-67 label index of the tumor cells in all 31 cases. In addition, 12 cases of inflammatory cases were collected as c...

  15. Infratentorial brain metastases of pediatric non-epithelial malignant tumors: three case reports.

    Science.gov (United States)

    Osawa, Shin-ichiro; Kumabe, Toshihiro; Saito, Ryuta; Sonoda, Yukihiko; Niizuma, Hidetaka; Watanabe, Mika; Tominaga, Teiji

    2011-04-01

    Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

  16. Impedance spectroscopy--an outstanding method for label-free and real-time discrimination between brain and tumor tissue in vivo.

    Science.gov (United States)

    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.

  17. Distribution of alarin in the mouse brain and in tumors of the central nervous system

    International Nuclear Information System (INIS)

    Alarin is a 25 amino acid peptide that belongs to the galanin neuropeptide family and is a splice variant of the galanin-like peptide (GALP) gene. It was first identified in gangliocytes of neuroblastic tumors and recently, alarin was demonstrated to stimulate food intake as well as the hypothalamic-pituitary-gonadal axis in rodents. However, mRNA and protein expression of alarin in the central nervous system have not been described yet. Therefore, we investigated GALP/alarin promoter activity using a transgenic reporter mouse model. This mouse model expresses YFP when the GALP/alarin promoter is active and therefore is a suitable tool to indicate nuclei where GALP/alarin mRNA is expressed. Immunohistochemical analysis of YFP expression in these transgenic mice revealed a wide distribution of GALP/alarin promoter activity throughout the whole murine brain. As the promoter activity studies cannot discriminate between GALP and alarin expression the next aim was to determine the distribution of alarin peptide- in the adult murine brain with an anti-alarin antibody. The specificity of the antibody against alarin was demonstrated by the absence of labeling after pre-absorption of the antiserum with synthetic alarin peptide and in transgenic mouse brains depleted of cells expressing the GALP/alarin gene. In wild type animals alarin-like immunoreacitivity (alarin-LI) was observed in different areas of the murine brain including the accessory olfactory bulb, medial preoptic area and the hypothalamus. Furthermore, immunohistochemical analysis of alarin expression in peripheral tissues revealed high alarin levels in the testis of adult mice, whereas no alarin-Li was detected in the oesophagus of mice and trachea of rats. The galanin peptide family is known to play a role in cancer and alarin was first described in human neuroblastic tumors. Therefore, alarin expression in different CNS-tumor types was determined in the present study. Immunohistochemical analysis of a variety

  18. Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy

    OpenAIRE

    Ye, Jian; Peng, Guangyong

    2015-01-01

    Understanding molecular mechanisms involved in creating and sustaining the tumor suppressive microenvironment is critical for the development of novel antitumor therapeutic strategies. We have identified the induction of T cell senescence as a novel mechanism utilized by human tumor cells to induce immune suppression, and provided a new strategy using TLR8 ligands to reverse tumor immunosuppressive effects for tumor immunotherapy.

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

    Science.gov (United States)

    2016-01-22

    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

  20. Effect of expression of P-glycoprotein on technetium-99m methoxyisobutylisonitrile single photon emission computed tomography of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Yasushi; Matsumura, Akira; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    2002-08-01

    The expression of P-glycoprotein was investigated imunohistochemically in 26 brain tumor tissues and compared with the findings of technetium-99m methoxyisobutylisonitrile single photon emission computed tomography ({sup 99m}Tc-MIBI SPECT) to clarify the effect of P-glycoprotein on the diagnostic accuracy. P-glycoprotein labeling index of both tumor cells and vascular endothelial cells showed no clear relationship with the findings of {sup 99m}Tc-MIBI SPECT imaging. Expression of P-glycoprotein has no effect on the diagnostic accuracy of {sup 99m}Tc-MIBI SPECT. (author)

  1. Apoptin: Specific killer of tumor cells?

    OpenAIRE

    Tavassoli, M; Guelen, L.; Luxon, B. A.; Gäken, J

    2005-01-01

    In the early 1990s it was discovered that the VP3/Apoptin protein encoded by the Chicken Anemia virus (CAV) possesses an inherent ability to specifically kill cancer cells. Apoptin was found to be located in the cytoplasm of normal cells while in tumor cells it was localized mainly in the nucleus.1 These differences in the localization pattern were suggested to be the main mechanism by which normal cells show resistance to Apoptin-mediated cell killing. Although the mechanism of action of Apo...

  2. Management of nonfunctioning islet cell tumors

    Institute of Scientific and Technical Information of China (English)

    Han Liang; Pu Wang; Xiao-Na Wang; Jia-Cang Wang; Xi-Shan Hao

    2004-01-01

    AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years.METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests.RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twentyeight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%),nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients.Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than :10 cm were positive prognostic factors in females younger than 30years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007.CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are

  3. Ovarian Germ Cell Tumors Treatment

    Science.gov (United States)

    ... c) cancer cells are found in the pelvic peritoneum. In stage I , cancer is found in one ... in the abdomen ) or in washings of the peritoneum ( tissue lining the peritoneal cavity). Stage II Enlarge ...

  4. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    Science.gov (United States)

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

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

    Science.gov (United States)

    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

  6. Numeric Investigation of Brain Tumor Influence on the Current Distributions During Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Song, Bo; Wen, Peng; Ahfock, Tony; Li, Yan

    2016-01-01

    This study constructed a series of high-resolution realistic human-head models with brain tumors, and numerically investigated the influence of brain tumor's location and grade on the current distributions, under different electrode montages during tDCS. The threshold area and the peak current density were also derived and analyzed in the region of interest. The simulation result showed that it is safe to apply tDCS on the patients with brain tumors to treat their neuropsychiatric conditions and cancer pain caused by the tumor; although considerable changes of the current distributions are induced by the presence of a brain tumor. In addition, several observations on the global and local influences of tumor grade and possible edema have been made as well. These findings should be helpful for researchers and clinical doctors to treat patients with brain tumors. This study is also the first numerical study to fill in the gap of tDCS applications on the patients with brain tumors.

  7. In situ entry of oligonucleotides into brain cells can occur through a nucleic acid channel

    NARCIS (Netherlands)

    Shi, Fuxin; Gounko, Natasha V.; Wang, Xiaoqin; Ronken, Eric; Hoekstra, Dick

    2007-01-01

    Brain tissue has become a challenging therapeutic target, in part because of failure of conventional treatments of brain tumors and a gradually increasing number of neurodegenerative diseases. Because antisense oligonucleotides are readily internalized by neuronal cells in culture, these compounds c

  8. Induction of brain tumors by a newly isolated JC virus (Tokyo-1 strain).

    OpenAIRE

    Nagashima, K.; Yasui, K; Kimura, J; Washizu, M.; Yamaguchi, K.; Mori, W.

    1984-01-01

    A newly isolated virus from a patient with progressive multifocal leukoencephalopathy (PML) (Tokyo-1 strain) was found serologically identical to JC virus (Mad-1 strain) and showed high neurooncogenicity in hamsters. Twenty-one animals inoculated intracerebrally with the virus developed brain tumors during a period that averaged 5 months. The tumors were cerebellar medulloblastoma (n = 20); plexus tumor (n = 2) occurred in 1 animal as a single tumor and in another in combination with a medull...

  9. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  10. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  11. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology. PMID:23980681

  12. Evaluation of therapeutic effects of radiosurgery using 99 Tcm-MIBI brain SPECT in patients with brain tumor

    Institute of Scientific and Technical Information of China (English)

    FAN Yi-xiang; SHI Wei-min; PENG Wu-he

    2002-01-01

    Objective: To evaluate the therapeutic effects of radiosurgery on brain tumor using 99Tcm-MIBI brain single-photon emission computed tomography (SPECT). Methods : Fifteen normal volunteers and 49patients with brain tumor underwent 99Tcm-MIBI brain SPECT, and the tumor to non-tumor ratio (T/N)was calculated and compared before and after radiosurgery. The patients were regrouped according to different schedules for postoperative reexamination, and diagnostic sensitivity and specificity of 99Tcm-MIBI SPECT evaluated against that of conventional CT and magnetic resonance imaging. Results: After radiosurgery, the lesions were reduced or even disappeared in 22 cases, and tumor remnants or recurrence were found in 27 cases. The sensitivity, specificity and accuracy of 99Tcm-MIBI brain SPECT were 85.2%, 68. 2% and 77.6%,respectively. The sensitivity of postoperative 99Tcm-MIBI brain SPECT at 5.8 months was 92%, significantly higher than that at 3.1 months (89%, u=2. 2545, P<0. 05), and its accuracy was also higher than those at3. 1 months (u=2. 5927, P<0. 05) and at 9. 4 months (u=2. 1760, P<0. 05). The preoperative T/N ratio averaged 9.5±7. 6, significantly lowered to 2.9±5.1 postoperatively (t=4. 4373, P<0. 001). T/N ratio of recurrence group was remarkably higher than those of tumor remnants group (t=2. 1496, P<0. 05), edema group (t= 9. 2186, P<0. 001) and cicatrization group (t= 6. 3906, P<0. 001). Conclusion: 99Tcm-MIBI brain SPECT is more accurate than CT in distinguishing tumor residuals from benign lesions such as edema and cicatrization. At about 6 months after radiosurgery, 99Tcm-MIBI SPECT can obtain optimal diagnostic effects.

  13. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar;

    2011-01-01

    hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...... synthesis, and growth of these cells in vivo induced a >200-fold increase in ADAM12 expression. Our observation that ADAM12 expression is significantly higher in the terminal duct lobular units (TDLUs) adjacent to human breast carcinoma compared with TDLUs found in normal breast tissue supports our......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...

  14. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  15. Redefining circulating tumor cells by image processing

    NARCIS (Netherlands)

    Ligthart, S.T.

    2012-01-01

    Circulating tumor cells (CTC) in the blood of patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. However, CTC are very heterogeneous in size and shape, and are present at very low frequencies. Missing or misjudging a few events may have great cons

  16. Human Nerual Stem Cells for Brain Repair

    OpenAIRE

    Kim, Seung U.; Lee, Hong J.; In H Park; Chu, Kon; Lee, Soon T.; Kim, Manho; Roh, Jae K.; Kim, Seung K.; Wang, Kyu C.

    2008-01-01

    Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases including Parkinson disease, Huntington disease, amyotrophic lateral sclerosis (ALS), Alzheimer disease, multiple sclerosis (MS), stroke, spinal cord injury and brain cancer. In recent years, neurons and glial cells have successfully been generated from neural stem cells, a...

  17. Thyroid function after treatment of brain tumors in children.

    Science.gov (United States)

    Ogilvy-Stuart, A L; Shalet, S M; Gattamaneni, H R

    1991-11-01

    In 134 children who had been treated for a brain tumor not involving the hypothalamic-pituitary axis, thyroid function was assessed up to 24 years after treatment with cranial or craniospinal irradiation. In addition, 78 children received up to 2 years of cytotoxic chemotherapy. Of 85 children who received craniospinal irradiation, 30 (35%) had abnormalities of thyroid function, and 10 (20%) of 49 who received cranial irradiation had such abnormalities. Frank hypothyroidism developed in three children and thyrotoxicosis in one. Thirty-six children had an elevated thyroid-stimulating hormone level in the presence of a normal thyroxine level; in 16 of them the thyroid-stimulating hormone level subsequently returned to normal. Twenty-eight children who were treated between 1960 and 1970 were excluded from the analysis. Of 34 children who received cranial irradiation, five had thyroid dysfunction and 24 of 72 who received craniospinal irradiation had such dysfunction (p = 0.013). Thyroid dysfunction was present in 4 of 35 children who received no chemotherapy and in 25 of 71 who received chemotherapy (p = 0.014). Direct irradiation plus chemotherapy was more damaging than irradiation alone. These data confirm the high incidence of thyroid dysfunction when the thyroid gland is included in the radiation field. However, in a high proportion, the thyroid abnormalities are minor and revert to normal with time; life-long replacement therapy with thyroxine may be unnecessary. PMID:1941379

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

    Science.gov (United States)

    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.

  19. Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Toshiyuki Ishiwata; Yoko Matsuda; Zenya Naito

    2011-01-01

    Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

  20. Nanoparticles and synchrotron light for brain tumors therapy

    International Nuclear Information System (INIS)

    Gliomas treatment is still a serious challenge in medicine. Available treatments are mainly palliative and patients' survival is increased by a few months only. An original radiotherapy technique consists in increasing the dose delivered to the tumor by loading it with high Z atoms before an irradiation with low energy X-rays (50-100 keV). Preclinical studies have been conducted using iodine contrast agent (CA) (Z=53) and 50 keV X-rays. The increase of the animals' survival leads today to the beginning of clinical trials (phases I and II) at the medical beamline of the European synchrotron, where the available monochromatic and intense photons beam is well suited for this treatment. The use of intravenously injected CA is however insufficient for curing rat's bearing glioma. Indeed, the contrast agent's accumulation is limited by the presence of the BBB and it remains extracellular. Metallic nanoparticles (NPs) appear interesting for improving the treatment efficacy. During this work, three different types of NPs have been studied: GdNPs (3 nm), AuNPs (13 nm) and PtNPs (6 nm). Their toxicity and internalization have been evaluated in vitro on F98 rodent glioma cells. Cells' survival has also been measured after different irradiation conditions in presence of these NPs and with monochromatic photons beams. Several mechanisms implicated in the treatment have been highlighted by the study of the cells' response dependence to the incident particles energy and to the sub cellular NPs distribution during irradiation. For identical concentrations, NPs were more efficient in cells killing than CA, illustrating their microdosimetric potential. The effect was also preferential for low energy X-rays, indicating that photoactivation of heavy atoms plays a role in the cells' death. GdNPs and PtNPs have also lead to an effect in combination to high energy photons (1.25 MeV), indicating that another mechanism may also increase the cell

  1. Fate of tumor cells injected into left ventricle of heart in BALB/c mice: role of natural killer cells

    DEFF Research Database (Denmark)

    Basse, P; Hokland, P; Heron, I;

    1988-01-01

    The arrest, retention, and elimination (i.e., clearance) of radiolabeled YAC-1 lymphoma cells injected either iv or into the left ventricle (LV) of the heart were studied in male BALB/c mice, with special emphasis on the role of natural killer (NK) cells. After iv injection YAC-1 cells were...... arrested and, to a large extent, destroyed in the lungs, which contain the first capillary bed that iv injected tumor cells meet. After LV injection the initial distribution of the tumor cells, which depends on the distribution of cardiac output at the time of injection, was estimated by use...... of radiolabeled microspheres. Using this technique, we have shown that LV-injected tumor cells, in contrast to iv injected tumor cells, were not arrested in the first capillary bed that they encountered but passed viably through the microvasculature of the brain, heart, kidneys, intestinal tract, and to some...

  2. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain.

    Science.gov (United States)

    Palmieri, Diane; Bronder, Julie L; Herring, Jeanne M; Yoneda, Toshiyuki; Weil, Robert J; Stark, Andreas M; Kurek, Raffael; Vega-Valle, Eleazar; Feigenbaum, Lionel; Halverson, Douglas; Vortmeyer, Alexander O; Steinberg, Seth M; Aldape, Kenneth; Steeg, Patricia S

    2007-05-01

    Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy is associated with a devastating complication: the development of central nervous system (brain) metastases. Herein, we present Her-2 expression trends from resected human brain metastases and data from an experimental brain metastasis assay, both indicative of a functional contribution of Her-2 to brain metastatic colonization. Of 124 archival resected brain metastases from breast cancer patients, 36.2% overexpressed Her-2, indicating an enrichment in the frequency of tumor Her-2 overexpression at this metastatic site. Using quantitative real-time PCR of laser capture microdissected epithelial cells, Her-2 and epidermal growth factor receptor (EGFR) mRNA levels in a cohort of 12 frozen brain metastases were increased up to 5- and 9-fold, respectively, over those of Her-2-amplified primary tumors. Co-overexpression of Her-2 and EGFR was also observed in a subset of brain metastases. We then tested the hypothesis that overexpression of Her-2 increases the colonization of breast cancer cells in the brain in vivo. A subclone of MDA-MB-231 human breast carcinoma cells that selectively metastasizes to brain (231-BR) overexpressed EGFR; 231-BR cells were transfected with low (4- to 8-fold) or high (22- to 28-fold) levels of Her-2. In vivo, in a model of brain metastasis, low or high Her-2-overexpressing 231-BR clones produced comparable numbers of micrometastases in the brain as control transfectants; however, the Her-2 transfectants yielded 3-fold greater large metastases (>50 microm(2); P < 0.001). Our data indicate that Her-2 overexpression increases the outgrowth of metastatic tumor cells in the brain in this model system. PMID:17483330

  3. Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Chen; Chung-Wei Wu; Wen-Chen Wang; Li-Min Lin; Yuk-Kwan Chen

    2013-01-01

    We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

  4. Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor

    OpenAIRE

    Shukun Shen; Wenjun Yang; Zhugang Wang; Xia Lei; Liqun Xu; Yang Wang; Lizhen Wang; Lei Huang; Zhiwei Yu; Xinhong Zhang; Jiang Li; Yan Chen; Xiaoping Zhao; Xuelai Yin; Chenping Zhang

    2011-01-01

    Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44(high) (CD44(hi)) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi) tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a...

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

    Science.gov (United States)

    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.

  6. Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF for targeting brain tumors

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2014-01-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS, 2AL Polenov Russian Scientific Research Institute of Neurosurgery, 3Research Institute of Highly Pure Biopreparations, 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, 5IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, RussiaAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs conjugated with recombinant human epidermal growth factor (SPION–EGF were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION–EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION–EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION–EGF conjugates in animals provided receptor-mediated targeted delivery across the blood–brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P<0.001. SPION

  7. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

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

    Directory of Open Access Journals (Sweden)

    Jennifer A MacDiarmid

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

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Classification of brain tumor extracts by high resolution ¹H MRS using partial least squares discriminant analysis

    Directory of Open Access Journals (Sweden)

    A.V. Faria

    2011-02-01

    Full Text Available High resolution proton nuclear magnetic resonance spectroscopy (¹H MRS can be used to detect biochemical changes in vitro caused by distinct pathologies. It can reveal distinct metabolic profiles of brain tumors although the accurate analysis and classification of different spectra remains a challenge. In this study, the pattern recognition method partial least squares discriminant analysis (PLS-DA was used to classify 11.7 T ¹H MRS spectra of brain tissue extracts from patients with brain tumors into four classes (high-grade neuroglial, low-grade neuroglial, non-neuroglial, and metastasis and a group of control brain tissue. PLS-DA revealed 9 metabolites as the most important in group differentiation: γ-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine, glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out cross-validation showed that PLS-DA was efficient in group characterization. The metabolic patterns detected can be explained on the basis of previous multimodal studies of tumor metabolism and are consistent with neoplastic cell abnormalities possibly related to high turnover, resistance to apoptosis, osmotic stress and tumor tendency to use alternative energetic pathways such as glycolysis and ketogenesis.

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

    Directory of Open Access Journals (Sweden)

    Ekokobe eFonkem

    2013-10-01

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

  12. The biology of circulating tumor cells.

    Science.gov (United States)

    Pantel, K; Speicher, M R

    2016-03-10

    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice.

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

    Science.gov (United States)

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

    2013-07-01

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

  14. NMR exposure sensitizes tumor cells to apoptosis.

    Science.gov (United States)

    Ghibelli, L; Cerella, C; Cordisco, S; Clavarino, G; Marazzi, S; De Nicola, M; Nuccitelli, S; D'Alessio, M; Magrini, A; Bergamaschi, A; Guerrisi, V; Porfiri, L M

    2006-03-01

    NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3-66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95-102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8-2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies. PMID:16528477

  15. Coriocarcinoma manifestando-se inicialmente como um tumor cerebral Metastatic cerebral chorioncarcinoma simulating a primary brain tumor

    Directory of Open Access Journals (Sweden)

    José Alberto G. da Silva

    1971-09-01

    Full Text Available Os autores descrevem um caso de coriocarcinoma cerebral metastático, removido cirurgicamente, ocorrendo numa paciente de 19 anos e localizado na porção posterior do lobo frontal esquerdo. Um estudo retrospectivo da paciente revelou apenas discreta perda sangüínea pelos genitais, iniciada algumas semanas após o delivramento de uma criança normal, ocorrido quatro meses antes. O exame colpocitológico da secreção cérvico-vaginal revelou uma classe V de Papanicolau (positivo para células neoplásicas malignas, tendo ulteriormente a paciente sido submetida à histerectomia total com anexectomia bilateral. Um pequeno tumor de aspecto hemorrágico-necrótico foi encontrado na cavidade uterina, tendo o exame histológico mostrado tratar-se de coriocarcinoma. Os autores tecem considerações clínico-patológicas sobre o coriocarcinoma. com especial referência às lesões metastáticas cerebrais.A case of a metastatic cerebral chorioncarcinoma in the posterior aspect of the left frontal lobe of a 19-years-old woman is reported. After neurosurgical excision of the brain tumor a retrospective study of the patient was carried out as far as the gynecologic complaints were concerned. The patient complained only of little blood loss through the genitals started some weeks after the birth of a normal child four months ago. A smear vaginal preparation showed the presence of atypical epithelial cells (class V of Papanicolau. A total hysterectomy associated with bilateral anexectomy was performed. A small hemorrhagic tumor was detected within the uterus and a histological examination showed a chorioncarcinoma invading the miometrium. The clinico-pathological aspects of the chorioncarcinoma with special emphasis to cerebral metastases are discussed.

  16. MR imaging of intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masayuki; Takashima, Tsutomu; Akakura, Yukari (Kanazawa Univ. (Japan). School of Medicine) (and others)

    1994-04-01

    MRI of 13 patients with intracranial germ cell tumor (GCT) was performed with a 1.5 T superconductive scanner. T1-and T2-weighted images (T1WI and T2WI) and Gd-DTPA-enhanced T1-weighted images (Gd-T1WI) were obtained. On T1WI and T2WI, five germinomas and one teratoma were homogeneously isointense with gray matter. Two germinomas with cystic component exhibited markedly hypointense and hyperintense areas, respectively. Three teratomas were heterogeneous on both sequences due to cystic portion, fat, and hemorrhage. Yolk sac tumor (YST) was isointense on T1WI and heterogeneous on T2WI. On Gd-T1WI, five germinomas and YST were homogeneously enhanced. All but one of the others were heterogeneously enhanced. There were increased AFP in YST and increased HCG in malignant teratoma. Differential diagnosis of GCT may be possible with MRI. However, tumor markers should be taken into consideration. (author).

  17. In-silico oncology: an approximate model of brain tumor mass effect based on directly manipulated free form deformation

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stefan; Mang, Andreas; Toma, Alina; Buzug, Thorsten M. [University of Luebeck (Germany). Institute of Medical Engineering

    2010-12-15

    The present work introduces a novel method for approximating mass effect of primary brain tumors. The spatio-temporal dynamics of cancerous cells are modeled by means of a deterministic reaction-diffusion equation. Diffusion tensor information obtained from a probabilistic diffusion tensor imaging atlas is incorporated into the model to simulate anisotropic diffusion of cancerous cells. To account for the expansive nature of the tumor, the computed net cell density of malignant cells is linked to a parametric deformation model. This mass effect model is based on the so-called directly manipulated free form deformation. Spatial correspondence between two successive simulation steps is established by tracking landmarks, which are attached to the boundary of the gross tumor volume. The movement of these landmarks is used to compute the new configuration of the control points and, hence, determines the resulting deformation. To prevent a deformation of rigid structures (i.e. the skull), fixed shielding landmarks are introduced. In a refinement step, an adaptive landmark scheme ensures a dense sampling of the tumor isosurface, which in turn allows for an appropriate representation of the tumor shape. The influence of different parameters on the model is demonstrated by a set of simulations. Additionally, simulation results are qualitatively compared to an exemplary set of clinical magnetic resonance images of patients diagnosed with high-grade glioma. Careful visual inspection of the results demonstrates the potential of the implemented model and provides first evidence that the computed approximation of tumor mass effect is sensible. The shape of diffusive brain tumors (glioblastoma multiforme) can be recovered and approximately matches the observations in real clinical data. (orig.)

  18. Diagnostic value of circulating tumor cells in cerebrospinal fluid

    OpenAIRE

    Ning Mu; Chunhua Ma; Rong Jiang; Yuan Lv; Jinduo Li; Bin Wang; Liwei Sun

    2016-01-01

    To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining–fluorescence in situ hybridization (TM-iFISH).

  19. Multifunctional Nucleic Acids for Tumor Cell Treatment

    DEFF Research Database (Denmark)

    Pofahl, Monika; Wengel, Jesper; Mayer, Günter

    2014-01-01

    We report on a multifunctional nucleic acid, termed AptamiR, composed of an aptamer domain and an antimiR domain. This composition mediates cell specific delivery of antimiR molecules for silencing of endogenous micro RNA. The introduced multifunctional molecule preserves cell targeting, anti......-proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor targeting...

  20. Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity1

    OpenAIRE

    Liu, Zuqiang; Kim, Jin H.; Falo, Louis D.; You, Zhaoyang

    2009-01-01

    Treg from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4+ T cell activity is comparable to Treg from naïve mice (naïve Treg), only tumor Treg suppress naïve CD8+ T cell activation and DC function. Neither tumor Treg nor naïve Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. This is consistent with the observation that, in this ...

  1. Cerebral and brain stem Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Breidahl, W.H. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Ives, F.J. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Khangure, M.S. (Dept. of Magnetic Resonance Imaging, Sir Charles Gairdner Hospital, Nedlands (Australia))

    1993-05-01

    Two patients with central nervous system manifestations of Langerhans cell histiocytosis, both with brain stem involvement, are reported. The onset of symptoms was at an age when the diagnosis might not have been considered. (orig.)

  2. Cerebral and brain stem Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Two patients with central nervous system manifestations of Langerhans cell histiocytosis, both with brain stem involvement, are reported. The onset of symptoms was at an age when the diagnosis might not have been considered. (orig.)

  3. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  4. Granular cell tumors of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Kayani Naila

    2007-03-01

    Full Text Available Abstract Background Granular cell tumors (GCTs are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. Materials and methods We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. Results Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100 and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13, neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin and sarcoma (desmin, vimentin markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. Conclusion We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively.

  5. Primary, non-exophytic, optic nerve germ cell tumors.

    Science.gov (United States)

    DiLuna, Michael L; Two, Aimee M; Levy, Gillian H; Patel, Toral; Huttner, Anita J; Duncan, Charles C; Piepmeier, Joseph M

    2009-12-01

    Tumors of the optic chiasm are relatively uncommon and usually associated with phakomatoses such as neurofibromatosis. Even more rare is the presentation of a primary, non-exophytic, isolated optic chiasm germ cell tumor (GCT). These tumors have imaging characteristics nearly indistinguishable from optic chiasmatic gliomas (OCGs). Herein we describe two cases of young men who presented with similar findings of progressive, painless visual loss and hypothalamic-pituitary-adrenal axis dysfunction including diabetes insipidus. Brain imaging was non-diagnostic and suggestive of an OCG. Pathology demonstrated GCTs in each case highlighting the importance of biopsy confirmation of the diagnosis. Both patients underwent a pterional craniotomy and sub-frontal approach to the optic chiasm. The chiasm was diffusely enlarged and discolored in each case without evidence of sellar, suprasellar or perichiasmatic pathology. Pathology demonstrated a malignant mixed GCT in the first patient and a germinoma in the second. This case series highlights the importance of tissue biopsy for patients with progressive symptoms from optic chiasm tumors. Furthermore, this is the first report of a primary, non-exophytic malignant mixed GCT. As the treatment regimens differ widely between optic chiasm GCTs and chiasm gliomas, tissue diagnosis is important. PMID:19554263

  6. Endothelial cell-derived interleukin-6 regulates tumor growth

    International Nuclear Information System (INIS)

    Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells

  7. Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A.

    Science.gov (United States)

    Hubert, Christopher G; Bradley, Robert K; Ding, Yu; Toledo, Chad M; Herman, Jacob; Skutt-Kakaria, Kyobi; Girard, Emily J; Davison, Jerry; Berndt, Jason; Corrin, Philip; Hardcastle, Justin; Basom, Ryan; Delrow, Jeffery J; Webb, Thomas; Pollard, Steven M; Lee, Jeongwu; Olson, James M; Paddison, Patrick J

    2013-05-01

    To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These screens identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, as compared with untransformed neural stem cells (NSCs) and fibroblasts. Given PHF5A's known involvement in facilitating interactions between the U2 snRNP complex and ATP-dependent helicases, we examined cancer-specific roles in RNA splicing. We found that in GSCs, but not untransformed controls, PHF5A facilitates recognition of exons with unusual C-rich 3' splice sites in thousands of essential genes. PHF5A knockdown in GSCs, but not untransformed NSCs, astrocytes, or fibroblasts, inhibited splicing of these genes, leading to cell cycle arrest and loss of viability. Notably, pharmacologic inhibition of U2 snRNP activity phenocopied PHF5A knockdown in GSCs and also in NSCs or fibroblasts overexpressing MYC. Furthermore, PHF5A inhibition compromised GSC tumor formation in vivo and inhibited growth of established GBM patient-derived xenograft tumors. Our results demonstrate a novel viability requirement for PHF5A to maintain proper exon recognition in brain tumor-initiating cells and may provide new inroads for novel anti-GBM therapeutic strategies. PMID:23651857

  8. IGFBP2 promotes glioma tumor stem cell expansion and survival

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, David, E-mail: dhs.zfs@gmail.com [College of Medicine, The University of Arizona (United States); Hsieh, Antony [The McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine (United States); Stea, Baldassarre [Department of Radiation Oncology, The University of Arizona (United States); Ellsworth, Ron [College of Medicine, The University of Arizona (United States)

    2010-06-25

    IGFBP2 is overexpressed in the most common brain tumor, glioblastoma (GBM), and its expression is inversely correlated to GBM patient survival. Previous reports have demonstrated a role for IGFBP2 in glioma cell invasion and astrocytoma development. However, the function of IGFBP2 in the restricted, self-renewing, and tumorigenic GBM cell population comprised of tumor-initiating stem cells has yet to be determined. Herein we demonstrate that IGFBP2 is overexpressed within the stem cell compartment of GBMs and is integral for the clonal expansion and proliferative properties of glioma stem cells (GSCs). In addition, IGFBP2 inhibition reduced Akt-dependent GSC genotoxic and drug resistance. These results suggest that IGFBP2 is a selective malignant factor that may contribute significantly to GBM pathogenesis by enriching for GSCs and mediating their survival. Given the current dearth of selective molecular targets against GSCs, we anticipate our results to be of high therapeutic relevance in combating the rapid and lethal course of GBM.

  9. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  10. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...... and younger sister, but only the proband has so far developed malignancy. The clinical phenotype in the boy is suggestive of Li-Fraumeni syndrome, but the family does not strictly conform to the canonical definition. Udgivelsesdato: 2008-Mar...

  11. Characteristics of children's brain tumors%儿童颅脑肿瘤的特点

    Institute of Scientific and Technical Information of China (English)

    曹利华

    2013-01-01

    Childrens brain tumors are the common tumors in children, which males are frequently affected than females, and most of patients are children aged 5-14 years old. The incidence rate of infratentorial tumor is higher than that of supratentorial tumor. The cases of infratentorial tumor in children accounted for 60% , and the main part is the fourth ventricle, followed by cerebellar hemisphere and cerebellar vermis, which often occurred in posterior fossa and near the midline. The main part of supratentorial tumor is the cerebral hemispheres, followed by the third ventricle and lateral ventricle. The clinical symptoms of childhood brain tumors are different with the size, characteristics, location and the damage around brain structure. The histopathological types of children's brain tumors are significantly different from that in adults. The benign tumors rarely happen in children, but the incidence rate of glioma in children is greatly higher than that in adults. The mostly pathological types were astrocytoma, medulloblastoma, ependy-moma, germ cell tumor and craniopharyngioma. The diagnosis of brain tumor in children should pay attention to the pediatric clinical characteristics, atypical clinical manifestation and detailed medical history, especially the correct and complete symptoms. Then according to the actual situation, it is urgent to carry out the necessary examination, to confirm the diagnosis and reduce the early misdiagnosis rate. The imaging examination plays a very important role in the diagnosis of children's brain tumors, so CT and MR examinations should be carried out in suspected cases as soon as possible. Surgical resection is the first choice, and reasonable postoperative radiotherapy can consolidate the operation effect and prolong survival duration. The radiotherapy accompanied with chemotherapy can improve the curative effect in malignant tumor patients after surgery.%目的 儿童颅脑肿瘤为常见的儿童肿瘤.以5~ 14岁组患儿居

  12. A correlative study on the functional disturbances and the organic changes in patients with brain tumors

    International Nuclear Information System (INIS)

    In a total of 132 patients with supratentorial tumors, tumor localization, pathology, and the presence of low density area surrounding the tumor were examined in relation to cerebral function, using conventional EEG, topographic EEG, computed tomography (CT), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). For superficial tumors, meningioma had less EEG abnormalities than glioma, regardless of the presence of low density area. Slow wave focus as shown by topographic EEG corresponded well with tumor localization detected on CT. For deep-seated tumors, topographic EEG showed diffuse δ waves and θ waves along the median. In 7 patients with meningioma, there was no uniform cerebral blood flow within the tumor; however, low blood flow surrounding the tumor was detected on CT, regardless of the presence of low density area. In 4 patients with intra-axial tumors, low blood flow was detected both within and surrounding the tumor. Location of tumors, as detected on CT, was well coincident with areas of decreased local cerebral blood flow and slow waves, as detected on topographic EEG. MRI was more reliable than CT in disclosing brain tumors, peritumoral edemas, and involvement of brain stem. (Namekawa, K)

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

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

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

  14. Deregulation of c-myc and SV40Tag causing brain tumor in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Deregulated expressions of both c-myc and simian virus 40 large T antigen (SV40Tag) are consistent features of lots of tumors. To investigate whether the expression of c-myc and SV40Tag in mouse might help develop a model of human tumor, we generated c-myc transgenics by inserting human c-myc gene into pTRE2 of Tet-On system. We obtained conditional expression of SV40Tag transgenics by the Tet-On system from Yangzhou University. Crossing the c-myc transgenic mouse with the SV40Tag transgenic mice to generate bitransgenics we got double-transgenic mice expressing c-myc and SV40Tag by the Tet-On system. After being treated with doxycycline continuously, single-transgenic SV40Tag mice developed brain tumor infrequently (3 of 84, 3.6%) with a long onset (185 d on average). In contrast, double-transgenic c-myc/SV40Tag mice developed brain tumor with a short onset (96 days on average) and a 41% brain tumor incidence rate (7 of 17, 41%). This tumor was assumed to be medulloblastoma. Our experiments suggest that deregulated expression of c-myc and SV40Tag in brain might generate a mouse model of human brain tumor that recapitulates some features of human medulloblastoma.

  15. Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles.

    Science.gov (United States)

    Wei, Lin; Guo, Xi-Ying; Yang, Ting; Yu, Min-Zhi; Chen, Da-Wei; Wang, Jian-Cheng

    2016-08-20

    Treatment of brain tumor remains a great challenge worldwide. Development of a stable, safe, and effective siRNA delivery system which is able to cross the impermeable blood-brain barrier (BBB) and target glioma cells is necessary. This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system. In vitro cellular uptake experiments demonstrated a higher intracellular fluorescence intensity of siRNA in brain microvascular endothelial cells (BMVECs) and U87 glioma cells when treated with T7-LPC/siRNA NPs compared with PEG-LPC/siRNA NPs. In the co-culture model of BMVECs and U87 cells, a significant down-regulation of EGFR protein expression occurred in the U87 glioma cells after treatment with the T7-LPC/siEGFR NPs. Moreover, the T7-LPC/siRNA NPs had an advantage in penetrating into a deep region of the tumor spheroid compared with PEG-LPC/siRNA NPs. In vivo imaging revealed that T7-LPC/siRNA NPs accumulated more specifically in brain tumor tissues than the non-targeted NPs. Also, in vivo tumor therapy experiments demonstrated that the longest survival period along with the greatest downregulation of EGFR expression in tumor tissues was observed in mice with an intracranial U87 glioma treated with T7-LPC/siEGFR NPs compared with mice receiving other formulations. Therefore, we believe that these transferrin receptor-mediated core-shell nanoparticles are an important potential siRNA delivery system for brain tumor-targeted therapy.

  16. Endothelial cell pseudopods and angiogenesis of breast cancer tumors

    OpenAIRE

    Sun LuZhe; Short Nicholas; Cameron Ivan L; Hardman W Elaine

    2005-01-01

    Abstract Background A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm3, it developed a well-vascularized capsule. Histological sections of tumors greater than...

  17. Coloring brain tumor with multi-potent micellar nanoscale drug delivery system

    Science.gov (United States)

    Chong, Kyuha; Choi, Kyungsun; Kim, EunSoo; Han, Eun Chun; Lee, Jungsul; Cha, Junghwa; Ku, Taeyun; Yoon, Jonghee; Park, Ji Ho; Choi, Chulhee

    2012-10-01

    Brain tumor, especially glioblastoma multiforme (GBM), is one of the most malignant tumors, which not only demands perplexing treatment approaches but also requires potent and effective treatment modality to deal with recurrence of the tumor. Photodynamic therapy (PDT) is a treatment which has been recommended as a third-level treatment. We are trying to investigate possibility of the PDT as an efficient adjuvant therapeutic modality for the treatment of brain tumor. Inhibition of tumor progression with photosensitizer was verified, in vitro. With micellar nanoscale drug delivery system, localization of the tumor was identified, in vivo, which is able to be referred as photodynamic diagnosis. With consequent results, we are suggesting photodynamic diagnosis and therapy is able to be performed simultaneously with our nanoscale drug delivery system.

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

    Science.gov (United States)

    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.

  19. Usefulness of three-dimensional MR images of brain tumors for surgical simulation

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the usefulness of three-dimensional (3D) MR imaging of brain tumors for surgical planning. Sixty-nine patients with various tumors of the brain were included in the present study. Using a volume-rendering (VR) method on an independent workstation, 3D-MR images were obtained with the fast-spoiled gradient recalled acquisition in the steady state (SPGR) sequence after Gd-DTPA administration. VR images could show an exact relationship between the surface of the brain and major vessels. However, in patients with deeply located tumors, VR images did not necessarily provide sufficient information as to the relationship between the tumor and vessels. In combination with a surface-rendering method, 3D-MR imaging could demonstrate the exact relationships among the tumors, major vessels, and surface of the brain. In tumors without contrast enhancement, this method was able to show 3D images of tumors with surrounding structures. For neurosurgeons, 3D-MR images were useful for understanding the surface anatomy and surrounding structures of the tumors prior to surgery. These images were also helpful in explaining the condition of the disease to patients and their families. (author)

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

    Directory of Open Access Journals (Sweden)

    Waldemar Debinski

    Full Text Available Interleukin 13 receptor alpha 2 (IL-13RA2 is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels