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Sample records for brain tumor stem-like

  1. 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

  2. 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

  3. Gene transfection in primary stem-like cells of giant cell tumor of bone.

    Science.gov (United States)

    Singh, Shalini; Mak, Isabella; Power, Patricia; Cunningham, Melissa; Cunnigham, Melissa; Turcotte, Robert; Ghert, Michelle

    2010-01-01

    The neoplastic stem-like stromal cell of giant cell tumor of bone (GCT) survives for multiple passages in primary culture with a stable phenotype, and exhibits multipotent characteristics. The pathophysiology of this tumor has been studied through the primary culture of these cells. However, successful gene transfer of these cells has not been reported to date. In this short report, we describe the development of the first reported technique that results in efficient gene transfection in primary stem-like cells of GCT.

  4. HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells

    NARCIS (Netherlands)

    Nishizawa, Satoshi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Takahashi, Akari; Tamura, Yasuaki; Mori, Takashi; Kanaseki, Takayuki; Kamiguchi, Kenjiro; Asanuma, Hiroko; Morita, Rena; Sokolovskaya, Alice; Matsuzaki, Junichi; Yamada, Ren; Fujii, Reona; Kampinga, Harm H.; Kondo, Toru; Hasegawa, Tadashi; Hara, Isao; Sato, Noriyuki

    2012-01-01

    Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB

  5. The Brain Microenvironment Preferentially Enhances the Radioresistance of CD133+ Glioblastoma Stem-like Cells

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    Muhammad Jamal

    2012-02-01

    Full Text Available Brain tumor xenografts initiated from glioblastoma (GBM CD133+ tumor stem-like cells (TSCs are composed of TSC and non-TSC subpopulations, simulating the phenotypic heterogeneity of GBMs in situ. Given that the discrepancies between the radiosensitivity of GBM cells in vitro and the treatment response of patients suggest a role for the microenvironment in GBM radioresistance, we compared the response of TSCs and non-TSCs irradiated under in vitro and orthotopic conditions. As a measure of radioresponse determined at the individual cell level, γH2AX and 53BP1 foci were quantified in CD133+ cells and their differentiated (CD133- progeny. Under in vitro conditions, no difference was detected between CD133+ and CD133- cells in foci induction or dispersal after irradiation. However, irradiation of orthotopic xenografts initiated from TSCs resulted in the induction of fewer γH2AX and 53BP1 foci in CD133+ cells compared to their CD133- counterparts within the same tumor. Xenograft irradiation resulted in a tumor growth delay of approximately 7 days with a corresponding increase in the percentage of CD133+ cells at 7 days after radiation, which persisted to the onset of neurologic symptoms. These results suggest that, although the radioresponse of TSCs and non-TSCs does not differ under in vitro growth conditions, CD133+ cells are relatively radioresistant under intracerebral growth conditions. Whereas these findings are consistent with the suspected role for TSCs as a determinant of GBM radioresistance, these data also illustrate the dependence of the cellular radioresistance on the brain microenvironment.

  6. Transcriptional profiling of adult neural stem-like cells from the human brain.

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    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  7. Chemical Library Screening and Structure-Function Relationship Studies Identify Bisacodyl as a Potent and Selective Cytotoxic Agent Towards Quiescent Human Glioblastoma Tumor Stem-Like Cells.

    Directory of Open Access Journals (Sweden)

    Maria Zeniou

    Full Text Available Cancer stem-like cells reside in hypoxic and slightly acidic tumor niches. Such microenvironments favor more aggressive undifferentiated phenotypes and a slow growing "quiescent state" which preserves them from chemotherapeutic agents that essentially target proliferating cells. Our objective was to identify compounds active on glioblastoma stem-like cells, including under conditions that mimick those found in vivo within this most severe and incurable form of brain malignancy. We screened the Prestwick Library to identify cytotoxic compounds towards glioblastoma stem-like cells, either in a proliferating state or in more slow-growing "quiescent" phenotype resulting from non-renewal of the culture medium in vitro. Compound effects were assessed by ATP-level determination using a cell-based assay. Twenty active molecules belonging to different pharmacological classes have thus been identified. Among those, the stimulant laxative drug bisacodyl was the sole to inhibit in a potent and specific manner the survival of quiescent glioblastoma stem-like cells. Subsequent structure-function relationship studies led to identification of 4,4'-dihydroxydiphenyl-2-pyridyl-methane (DDPM, the deacetylated form of bisacodyl, as the pharmacophore. To our knowledge, bisacodyl is currently the only known compound targeting glioblastoma cancer stem-like cells in their quiescent, more resistant state. Due to its known non-toxicity in humans, bisacodyl appears as a new potential anti-tumor agent that may, in association with classical chemotherapeutic compounds, participate in tumor eradication.

  8. Chemical Library Screening and Structure-Function Relationship Studies Identify Bisacodyl as a Potent and Selective Cytotoxic Agent Towards Quiescent Human Glioblastoma Tumor Stem-Like Cells.

    Science.gov (United States)

    Zeniou, Maria; Fève, Marie; Mameri, Samir; Dong, Jihu; Salomé, Christophe; Chen, Wanyin; El-Habr, Elias A; Bousson, Fanny; Sy, Mohamadou; Obszynski, Julie; Boh, Alexandre; Villa, Pascal; Assad Kahn, Suzana; Didier, Bruno; Bagnard, Dominique; Junier, Marie-Pierre; Chneiweiss, Hervé; Haiech, Jacques; Hibert, Marcel; Kilhoffer, Marie-Claude

    2015-01-01

    Cancer stem-like cells reside in hypoxic and slightly acidic tumor niches. Such microenvironments favor more aggressive undifferentiated phenotypes and a slow growing "quiescent state" which preserves them from chemotherapeutic agents that essentially target proliferating cells. Our objective was to identify compounds active on glioblastoma stem-like cells, including under conditions that mimick those found in vivo within this most severe and incurable form of brain malignancy. We screened the Prestwick Library to identify cytotoxic compounds towards glioblastoma stem-like cells, either in a proliferating state or in more slow-growing "quiescent" phenotype resulting from non-renewal of the culture medium in vitro. Compound effects were assessed by ATP-level determination using a cell-based assay. Twenty active molecules belonging to different pharmacological classes have thus been identified. Among those, the stimulant laxative drug bisacodyl was the sole to inhibit in a potent and specific manner the survival of quiescent glioblastoma stem-like cells. Subsequent structure-function relationship studies led to identification of 4,4'-dihydroxydiphenyl-2-pyridyl-methane (DDPM), the deacetylated form of bisacodyl, as the pharmacophore. To our knowledge, bisacodyl is currently the only known compound targeting glioblastoma cancer stem-like cells in their quiescent, more resistant state. Due to its known non-toxicity in humans, bisacodyl appears as a new potential anti-tumor agent that may, in association with classical chemotherapeutic compounds, participate in tumor eradication.

  9. Brain Tumors

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    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 ...

  10. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment.

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    Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan; Torchilin, Vladimir P

    2016-06-01

    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types.

  11. Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells.

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    Rao, Wei; Wang, Hai; Han, Jianfeng; Zhao, Shuting; Dumbleton, Jenna; Agarwal, Pranay; Zhang, Wujie; Zhao, Gang; Yu, Jianhua; Zynger, Debra L; Lu, Xiongbin; He, Xiaoming

    2015-06-23

    Tumor reinitiating cancer stem-like cells are responsible for cancer recurrence associated with conventional chemotherapy. We developed a doxorubicin-encapsulated polymeric nanoparticle surface-decorated with chitosan that can specifically target the CD44 receptors of these cells. This nanoparticle system was engineered to release the doxorubicin in acidic environments, which occurs when the nanoparticles are localized in the acidic tumor microenvironment and when they are internalized and localized in the cellular endosomes/lysosomes. This nanoparticle design strategy increases the cytotoxicity of the doxorubicin by six times in comparison to the use of free doxorubicin for eliminating CD44(+) cancer stem-like cells residing in 3D mammary tumor spheroids (i.e., mammospheres). We further show these nanoparticles reduced the size of tumors in an orthotopic xenograft tumor model with no evident systemic toxicity. The development of nanoparticle system to target cancer stem-like cells with low systemic toxicity provides a new treatment arsenal for improving the survival of cancer patients.

  12. Canine mammary tumors contain cancer stem-like cells and form spheroids with an embryonic stem cell signature.

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    Ferletta, Maria; Grawé, Jan; Hellmén, Eva

    2011-01-01

    We have investigated the presence of tentative stem-like cells in the canine mammary tumor cell line CMT-U229. This cell line is established from an atypical benign mixed mammary tumor, which has the property of forming duct-like structures in collagen gels. Stem cells in mammary glands are located in the epithelium; therefore we thought that the CMT-U229 cell line would be suitable for detection of tentative cancer stem-like cells. Side population (SP) analyses by flow cytometry were performed with cells that formed spheroids and with cells that did not. Flow cytometric, single sorted cells were expanded and re-cultured as spheroids. The spheroids were paraffin embedded and characterized by immunohistochemistry. SP analyses showed that spheroid forming cells (retenate) as well as single cells (filtrate) contained SP cells. Sca1 positive cells were single cell sorted and thereafter the SP population increased with repeated SP analyses. The SP cells were positively labeled with the cell surface-markers CD44 and CD49f (integrin alpha6); however the expression of CD24 was low or negative. The spheroids expressed the transcription factor and stem cell marker Sox2, as well as Oct4. Interestingly, only peripheral cells of the spheroids and single cells were positive for Oct4 expression. SP cells are suggested to correspond to stem cells and in this study, we have enriched for tentative tumor stem-like cells derived from a canine mammary tumor. All the used markers indicate that the studied CMT-U229 cell line contains SP cells, which in particular have cancer stem-like cell characteristics.

  13. Brain tumor - primary - adults

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

  14. A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.

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    Burgos-Ojeda, Daniela; McLean, Karen; Bai, Shoumei; Pulaski, Heather; Gong, Yusong; Silva, Ines; Skorecki, Karl; Tzukerman, Maty; Buckanovich, Ronald J

    2013-06-15

    Human tumor vessels express tumor vascular markers (TVM), proteins that are not expressed in normal blood vessels. Antibodies targeting TVMs could act as potent therapeutics. Unfortunately, preclinical in vivo studies testing anti-human TVM therapies have been difficult to do due to a lack of in vivo models with confirmed expression of human TVMs. We therefore evaluated TVM expression in a human embryonic stem cell-derived teratoma (hESCT) tumor model previously shown to have human vessels. We now report that in the presence of tumor cells, hESCT tumor vessels express human TVMs. The addition of mouse embryonic fibroblasts and human tumor endothelial cells significantly increases the number of human tumor vessels. TVM induction is mostly tumor-type-specific with ovarian cancer cells inducing primarily ovarian TVMs, whereas breast cancer cells induce breast cancer specific TVMs. We show the use of this model to test an anti-human specific TVM immunotherapeutics; anti-human Thy1 TVM immunotherapy results in central tumor necrosis and a three-fold reduction in human tumor vascular density. Finally, we tested the ability of the hESCT model, with human tumor vascular niche, to enhance the engraftment rate of primary human ovarian cancer stem-like cells (CSC). ALDH(+) CSC from patients (n = 6) engrafted in hESCT within 4 to 12 weeks whereas none engrafted in the flank. ALDH(-) ovarian cancer cells showed no engraftment in the hESCT or flank (n = 3). Thus, this model represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.

  15. Brain tumor - children

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

  16. Understanding Brain Tumors

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

  17. Osteopontin Overexpression Induced Tumor Progression and Chemoresistance to Oxaliplatin through Induction of Stem-Like Properties in Human Colorectal Cancer

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    Lui Ng

    2015-01-01

    Full Text Available Colorectal cancer (CRC is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expression in vitro and correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.

  18. Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

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    Roberta Lotti

    2016-01-01

    Full Text Available Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC originate from alterations in keratinocyte stem cells (KSC gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD and non-RAD (NRAD cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin, while it increases the level of differentiation markers (K10, involucrin. Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

  19. Cholangiocarcinoma Stem-like Cells Shapes Tumor-initiating Niche by Regulating Associated Macrophages

    DEFF Research Database (Denmark)

    Raggi, Chiara; Correnti, Margherita; Sica, Antonio

    2016-01-01

    to cooperate in supporting tumor initiation may facilitate the development of new therapeutic approaches. Considering that human cholangiocarcinoma represents a clinical emergency, it is essential to move to predictive models to understand the adaptive process of macrophage component (imprinting, polarization...

  20. Brain Tumors (For Parents)

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

  1. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain.

    Science.gov (United States)

    Xing, Fei; Kobayashi, Aya; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Pandey, Puspa R; Hirota, Shigeru; Wilber, Andrew; Mo, Yin-Yuan; Moore, Brian E; Liu, Wen; Fukuda, Koji; Iiizumi, Megumi; Sharma, Sambad; Liu, Yin; Wu, Kerui; Peralta, Elizabeth; Watabe, Kounosuke

    2013-03-01

    Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the brain highly expressed IL-1β which then 'activated' surrounding astrocytes. This activation significantly augmented the expression of JAG1 in the astrocytes, and the direct interaction of the reactivated astrocytes and cancer stem-like cells (CSCs) significantly stimulated Notch signalling in CSCs. We also found that the activated Notch signalling in CSCs up-regulated HES5 followed by promoting self-renewal of CSCs. Furthermore, we have shown that the blood-brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis in vivo. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re-establish their niche for their self-renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease.

  2. β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells

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    Bing Yan

    2013-01-01

    Full Text Available Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. β-Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs showed enhanced proliferation capacity compared to their CD44− counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro. These cells were also more superior in spheroid colony formation (in vitro and tumorigenicity (in vivo and positively associated with microvessel density (in vivo. β-Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro. β-Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. β-Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.

  3. Differentially expressed miRNAs in cancer-stem-like cells: markers for tumor cell aggressiveness of pancreatic cancer.

    Science.gov (United States)

    Bao, Bin; Ali, Shadan; Ahmad, Aamir; Li, Yiwei; Banerjee, Sanjeev; Kong, Dejuan; Aboukameel, Amro; Mohammad, Ramzi; Van Buren, Eric; Azmi, Asfar S; Sarkar, Fazlul H

    2014-08-15

    Pancreatic cancer (PC) is one of the most deadly cancers. The higher mortality is in part due to treatment resistance and early onset of metastasis. The existence of cancer-stem-like cells (CSLCs) has been widely accepted to be responsible for tumor aggressiveness in PC. Emerging evidence suggests that CSLCs have the capacity for increased cell growth, cell migration/invasion, metastasis, and treatment resistance, which leads to poor clinical outcome. However, the molecular role of CSLCs in tumor development and progression is poorly understood. Therefore, mechanistic understanding, and targeted killing of CSLCs may provide a newer therapeutic strategy for the treatment of PC. It has been well accepted that microRNAs (miRNAs) play critical roles during tumor development and progression through deregulation of multiple genes. Moreover, deregulated expression of miRNAs may also play a key role in the regulation of CSLC characteristics and functions. Here we show that isolated CD44(+)/CD133(+)/EpCAM(+) cells (triple-marker-positive cells) from human PC cell lines, MiaPaCa-2 and L3.6pl cells, display aggressive characteristics, such as increased cell growth, clonogenicity, cell migration, and self-renewal capacity, which is consistent with overexpression of CSLC signatures/markers. We also found deregulated expression of over 400 miRNAs, including let-7, miR-30, miR-125b, and miR-335, in CSLCs. As a proof-of-concept, knockdown of miR-125b resulted in the inhibition of tumor cell aggressiveness of CSLCs (triple-marker-positive cells), consistent with the downregulation of CD44, EpCAM, EZH2, and snail. These results clearly suggest the importance of miRNAs in the regulation of CSLC characteristics, and may serve as novel targets for therapy.

  4. 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 ...

  5. Epidemiology of Brain Tumors.

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    McNeill, Katharine A

    2016-11-01

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

  6. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  7. Pediatric Brain Tumor Foundation

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

  8. Brain Tumor Surgery

    Science.gov (United States)

    ... Meningitis Brain swelling Stroke Excess fluid in the brain Coma Death Recovery Time Recovery time depends on: The procedure performed. The part of the brain where the tumor is/was located. The areas ...

  9. Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth

    DEFF Research Database (Denmark)

    Hamerlik, Petra; Lathia, Justin D; Rasmussen, Rikke;

    2012-01-01

    glioma stem-like cells (GSCs), whose viability, self-renewal, and tumorigenicity rely, at least in part, on signaling through the VEGF-VEGFR2-Neuropilin-1 (NRP1) axis. We find that the limited impact of bevacizumab-mediated VEGF blockage may reflect ongoing autocrine signaling through VEGF-VEGFR2-NRP1......, which is associated with VEGFR2-NRP1 recycling and a pool of active VEGFR2 within a cytosolic compartment of a subset of human GBM cells. Whereas bevacizumab failed to inhibit prosurvival effects of VEGFR2-mediated signaling, GSC viability under unperturbed or radiation-evoked stress conditions...

  10. 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].

  11. Protein phosphatase 2A mediates dormancy of glioblastoma multiforme-derived tumor stem-like cells during hypoxia.

    Directory of Open Access Journals (Sweden)

    Christoph P Hofstetter

    Full Text Available PURPOSE: The hypoxic microenvironment of glioblastoma multiforme (GBM is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A, a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied. EXPERIMENTAL DESIGN: Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry. RESULTS: In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002. Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002. PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009. In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs. CONCLUSIONS: Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy.

  12. Linking of mPGES-1 and iNOS activates stem-like phenotype in EGFR-driven epithelial tumor cells.

    Science.gov (United States)

    Terzuoli, Erika; Finetti, Federica; Costanza, Filomena; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2017-03-01

    Inflammatory prostaglandin E-2 (PGE-2) favors cancer progression in epithelial tumors characterized by persistent oncogene input. However, its effects on tumor cell stemness are poorly understood at molecular level. Here we describe two epithelial tumor cells A431 and A459, originating from human lung and skin tumors, in which epithelial growth factor (EGF) induces sequential up-regulation of mPGES-1 and iNOS enzymes, producing an inflammatory intracellular milieu. We demonstrated that concerted action of EGF, mPGES-1 and iNOS causes sharp changes in cell phenotype demonstrated by acquisition of stem-cell features and activation of the epithelial-mesenchymal transition (EMT). When primed with EGF, epithelial tumor cells transfected with mPGES-1 or iNOS to ensure steady enzyme levels display major stem-like and EMT markers, such as reduction in E-cadherin with a concomitant rise in vimentin, ALDH-1, CD133 and ALDH activity. Tumorsphere studies with these cells show increased sphere number and size, enhanced migratory and clonogenic capacity and sharp changes in EMT markers, indicating activation of this process. The concerted action of the enzymes forms a well-orchestrated cascade where expression of iNOS depends on overexpression of mPGES-1. Indeed, we show that through its downstream effectors (PGE-2, PKA, PI3K/Akt), mPGES-1 recruits non-canonical transcription factors, thus facilitating iNOS production. In conclusion, we propose that the initial event leading to tumor stem-cell activation may be a leveraged intrinsic mechanism in which all players are either inherent constituents (EGF) or highly inducible proteins (mPGES-1, iNOS) of tumor cells. We suggest that incipient tumor aggressiveness may be moderated by reducing pivotal input of mPGES-1.

  13. Brain Tumors and Fatigue

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

  14. Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway.

    Science.gov (United States)

    An, Hyunsook; Kim, Ji Young; Lee, Nahyun; Cho, Youngkwan; Oh, Eunhye; Seo, Jae Hong

    2015-10-30

    Cancer stem cells (CSCs) play important roles in the formation, growth and recurrence of tumors, particularly following therapeutic intervention. Salinomycin has received recent attention for its ability to target breast cancer stem cells (BCSCs), but the mechanisms of action involved are not fully understood. In the present study, we sought to investigate the mechanisms responsible for salinomycin's selective targeting of BCSCs and its anti-tumor activity. Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27(kip1) nuclear accumulation. Mammosphere formation assays revealed that salinomycin suppresses self-renewal of ALDH1-positive BCSCs and downregulates the transcription factors Nanog, Oct4 and Sox2. TUNEL analysis of MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis. Our findings shed further light on the mechanisms responsible for salinomycin's effects on BCSCs.

  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. Single cell dual adherent-suspension co-culture micro-environment for studying tumor-stromal interactions with functionally selected cancer stem-like cells.

    Science.gov (United States)

    Chen, Yu-Chih; Zhang, Zhixiong; Fouladdel, Shamileh; Deol, Yadwinder; Ingram, Patrick N; McDermott, Sean P; Azizi, Ebrahim; Wicha, Max S; Yoon, Euisik

    2016-08-07

    Considerable evidence suggests that cancer stem-like cells (CSCs) are critical in tumor pathogenesis, but their rarity and transience has led to much controversy about their exact nature. Although CSCs can be functionally identified using dish-based tumorsphere assays, it is difficult to handle and monitor single cells in dish-based approaches; single cell-based microfluidic approaches offer better control and reliable single cell derived sphere formation. However, like normal stem cells, CSCs are heavily regulated by their microenvironment, requiring tumor-stromal interactions for tumorigenic and proliferative behaviors. To enable single cell derived tumorsphere formation within a stromal microenvironment, we present a dual adherent/suspension co-culture device, which combines a suspension environment for single-cell tumorsphere assays and an adherent environment for co-culturing stromal cells in close proximity by selectively patterning polyHEMA in indented microwells. By minimizing dead volume and improving cell capture efficiency, the presented platform allows for the use of small numbers of cells (cells). As a proof of concept, we co-cultured single T47D (breast cancer) cells and primary cancer associated fibroblasts (CAF) on-chip for 14 days to monitor sphere formation and growth. Compared to mono-culture, co-cultured T47D have higher tumorigenic potential (sphere formation rate) and proliferation rates (larger sphere size). Furthermore, 96-multiplexed single-cell transcriptome analyses were performed to compare the gene expression of co-cultured and mono-cultured T47D cells. Phenotypic changes observed in co-culture correlated with expression changes in genes associated with proliferation, apoptotic suppression, tumorigenicity and even epithelial-to-mesechymal transition. Combining the presented platform with single cell transcriptome analysis, we successfully identified functional CSCs and investigated the phenotypic and transcriptome effects induced by

  17. Brain tumors in infants

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    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.

  18. 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.

  19. CXCL12 MODULATION OF CXCR4 AND CXCR7 ACTIVITY IN HUMAN GLIOBLASTOMA STEM-LIKE CELLS AND REGULATION OF THE TUMOR MICROENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Roberto eWurth

    2014-05-01

    Full Text Available Chemokines are crucial autocrine and paracrine players in tumor development. In particular, CXCL12, through its receptors CXCR4 and CXCR7, affects tumor progression by controlling cancer cell survival, proliferation and migration, and, indirectly, via angiogenesis or recruiting immune cells.Glioblastoma (GBM is the most prevalent primary malignant brain tumor in adults and despite current multimodal therapies it remains almost incurable. The aggressive and recurrent phenotype of GBM is ascribed to high growth rate, invasiveness to normal brain, marked angiogenesis, ability to escape the immune system and resistance to standard of care therapies. Tumor molecular and cellular heterogeneity severely hinders GBM therapeutic improvement. In particular, a subpopulation of chemo- and radio-therapy resistant tumorigenic cancer stem–like cells (CSCs is believed to be the main responsible for tumor cell dissemination to the brain.GBM cells display heterogeneous expression levels of CXCR4 and CXCR7 that are overexpressed in CSCs, representing a molecular correlate for the invasive potential of GBM. The microenvironment contribution in GBM development is increasingly emphasized. An interplay exists between CSCs, differentiated GBM cells, and the microenvironment, mainly through secreted chemokines (e.g. CXCL12 causing recruitment of fibroblasts, endothelial, mesenchymal and inflammatory cells to the tumor, via specific receptors such as CXCR4.This review covers recent developments on the role of CXCL12/CXCR4-CXCR7 networks in GBM progression and the potential translational impact of their targeting. The biological and molecular understanding of the heterogeneous GBM cell behavior, phenotype and signaling is still limited. Progress in the identification of chemokine-dependent mechanisms that affect GBM cell survival, trafficking and chemo-attractive functions, opens new perspectives for development of more specific therapeutic approaches that include

  20. EGFR Amplification and Glioblastoma Stem-Like Cells

    Directory of Open Access Journals (Sweden)

    Katrin Liffers

    2015-01-01

    Full Text Available Glioblastoma (GBM, the most common malignant brain tumor in adults, contains a subpopulation of cells with a stem-like phenotype (GS-cells. GS-cells can be maintained in vitro using serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor-2, and heparin. However, this method does not conserve amplification of the Epidermal Growth Factor Receptor (EGFR gene, which is present in over 50% of all newly diagnosed GBM cases. GS-cells with retained EGFR amplification could overcome the limitations of current in vitro model systems and contribute significantly to preclinical research on EGFR-targeted therapy. This review recapitulates recent methodological approaches to expand stem-like cells from GBM with different EGFR status in order to maintain EGFR-dependent intratumoral heterogeneity in vitro. Further, it will summarize the current knowledge about the impact of EGFR amplification and overexpression on the stem-like phenotype of GBM-derived GS-cells and different approaches to target the EGFR-dependent GS-cell compartment of GBM.

  1. Tumor Microenvironment in the Brain

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 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...

  3. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... Classification of Tumors of the Central Nervous System Purchase WHO Blue Book NBTS Official Statement Questions and ... Privacy Copyright Site Search Search term Submit Submit Facebook Twitter YouTube Flickr

  4. 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.

  5. 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.

  6. Childhood brain tumor epidemiology: a brain tumor epidemiology consortium review.

    Science.gov (United States)

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

    2014-12-01

    Childhood brain tumors are the most common pediatric solid tumor and include several histologic subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. Cancer Epidemiol Biomarkers Prev; 23(12); 2716-36. ©2014 AACR.

  7. Brain tumor survivors speak out.

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    Carlson-Green, Bonnie

    2009-01-01

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

  8. Monitoring Radiographic Brain Tumor Progression

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    John H. Sampson

    2011-03-01

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

  9. In vitro and in vivo antiproliferative activity of metformin on stem-like cells isolated from spontaneous canine mammary carcinomas: translational implications for human tumors

    OpenAIRE

    Barbieri, Federica; Thellung, Stefano; Ratto, Alessandra; Carra, Elisa; Marini, Valeria; Fucile, Carmen; Bajetto, Adriana; Pattarozzi, Alessandra; Würth, Roberto; Gatti, Monica; Campanella, Chiara; Vito, Guendalina; Mattioli, Francesca; Pagano, Aldo; Daga, Antonio

    2015-01-01

    Background Cancer stem cells (CSCs) are considered the cell subpopulation responsible for breast cancer (BC) initiation, growth, and relapse. CSCs are identified as self-renewing and tumor-initiating cells, conferring resistance to chemo- and radio-therapy to several neoplasias. Nowadays, th (about 10mM)e pharmacological targeting of CSCs is considered an ineludible therapeutic goal. The antidiabetic drug metformin was reported to suppress in vitro and in vivo CSC survival in different tumors...

  10. Podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome.

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    Zev A Binder

    Full Text Available Glioblastoma multiforme (GBM is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared transcript profiles from a GBM oncosphere line before and after differentiation. Bioinformatic analysis of the gene expression profiles identified podocalyxin-like protein (PODXL, a protein highly expressed in human embryonic stem cells, as a potential marker of undifferentiated GBM stem-like cells. The loss of PODXL expression upon differentiation of GBM stem-like cell lines was confirmed by quantitative real-time PCR and flow cytometry. Analytical flow cytometry of numerous GBM oncosphere lines demonstrated PODXL expression in all lines examined. Knockdown studies and flow cytometric cell sorting experiments demonstrated that PODXL is involved in GBM stem-like cell proliferation and oncosphere formation. Compared to PODXL-negative cells, PODXL-positive cells had increased expression of the progenitor/stem cell markers Musashi1, SOX2, and BMI1. Finally, PODXL expression directly correlated with increasing glioma grade and was a marker for poor outcome in patients with GBM. In summary, we have demonstrated that PODXL is expressed in GBM stem-like cells and is involved in cell proliferation and oncosphere formation. Moreover, high PODXL expression correlates with increasing glioma grade and decreased overall survival in patients with GBM.

  11. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Kobayashi, Alisa [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Maeda, Takeshi [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Fu, Qibin [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Oikawa, Masakazu [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yang, Gen, E-mail: gen.yang@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Konishi, Teruaki, E-mail: tkonishi@nirs.go.jp [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Uchihori, Yukio [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); and others

    2015-03-15

    Highlights: • Existence of radiation induced bystander effects (RIBE) between cancer stem-like cells (CSCs) and non stem-like cancer cells (NSCCs) in human fibrosarcoma HT1080 cells. • Existence of significant difference in generation and response of bystander signals between CSCs and NSCCs. • CSCs are significantly less sensitive to NO scavenger than that of NSCCs in terms of DNA double strand breaks induced by RIBE. - Abstract: Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy.

  12. Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity.

    Science.gov (United States)

    Chen, Chia-Lin; Tsukamoto, Hidekazu; Machida, Keigo

    2014-07-01

    This review article discusses the importance and oncogenic signaling pathways of tumor-initiating cells (TICs) in several etiologies of hepatocellular carcinomas (HCCs) induced by hepatitis C virus (HCV), alcohol, obesity and/or chemicals. Stem cells may be present in cancer tissue, and a hierarchy of cells is formed, as is the case for normal tissue. Tumor formation, growth and propagation are maintained by a small proportion of cells with stem cell-like properties. TICs are present in alcohol-fed HCV transgenic mice, diethylnitrosamine/phenobarbital-treated mice (chemical carcinogenesis) and Spnb2 +/- mice (defective TGF-β signal). Alcohol/obesity-associated endotoxemia induces the stem cell marker Nanog through TLR4 signaling to generate TICs and liver tumors in several HCC models. The oncogenic pathway (such as the STAT3 and TLR4-NANOG pathway) and mechanism of generation of TICs of HCCs associated with HCV, alcohol and obesity are discussed. Understanding the molecular stemness signaling and cellular hierarchy and defining key TIC-specific genes will accelerate the development of novel biomarkers and treatment strategies. This review highlights recent advances in understanding the pathogenesis of liver TICs and discusses unanswered questions about the concept of liver TICs. (This project was supported by NIH grants 1R01AA018857 and P50AA11999).

  13. Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Stobbe Olsen, Marie-Louise;

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor among adults. Despite recent treatment progress, most patients succumb to their disease within 2 years of diagnosis. Current research has highlighted the importance of a subpopulation of cells, assigned brain...... cancer stem-like cells (bCSC), to play a pivotal role in GBM malignancy. bCSC are identified by their resemblance to normal neural stem cells (NSC), and it is speculated that the bCSC have to be targeted in order to improve treatment outcome for GBM patients. One hallmark of GBM is aberrant expression...... and activation of the epidermal growth factor receptor (EGFR) and expression of a deletion variant EGFRvIII. In the normal brain, EGFR is expressed in neurogenic areas where also NSC are located and it has been shown that EGFR is involved in regulation of NSC proliferation, migration, and differentiation...

  14. 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.

  15. Surgical management of pediatric brain tumors.

    Science.gov (United States)

    Heuer, Gregory G; Jackson, Eric M; Magge, Suresh N; Storm, Phillip B

    2007-12-01

    Brain tumors are the most common cause of cancer-related death and the second most common form of cancer in pediatric patients. Many of these tumors are treated primarily with surgery, either alone or in combination with radiation or chemotherapy. Recent advances have lead to greater survival and decreased morbidities in childhood brain tumor patients. A full understanding of the biology and primary treatment modalities for the particular tumor are essential for any professional treating these patients, including the neurosurgeon. Each tumor type has features in common with, and unique from, other tumors that need to be understood prior to undertaking a rational treatment plan. This article summarizes some of these features.

  16. Cell Mediated Photothermal Therapy of Brain Tumors.

    Science.gov (United States)

    Hirschberg, Henry; Madsen, Steen J

    2017-03-01

    Gold based nanoparticles with strong near infra-red (NIR) absorption are ideally suited for photothermal therapy (PTT) of brain tumors. The goal of PTT is to induce rapid heating in tumor tissues while minimizing thermal diffusion to normal brain. PTT efficacy is sensitively dependent on both nanoparticle concentration and distribution in tumor tissues. Nanoparticle delivery via passive approaches such as the enhanced permeability and retention (EPR) effect is unlikely to achieve sufficient nanoparticle concentrations throughout tumor volumes required for effective PTT. A simple approach for improving tumor biodsitribution of nanoparticles is the use of cellular delivery vehicles. Specifically, this review focuses on the use of monocytes/macrophages (Mo/Ma) as gold nanoparticle delivery vectors for PTT of brain tumors. Although the efficacy of this delivery approach has been demonstrated in both in vitro and animal PTT studies, its clinical potential for the treatment of brain tumors remains uncertain.

  17. Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells.

    Science.gov (United States)

    Kathagen, Annegret; Schulte, Alexander; Balcke, Gerd; Phillips, Heidi S; Martens, Tobias; Matschke, Jakob; Günther, Hauke S; Soriano, Robert; Modrusan, Zora; Sandmann, Thomas; Kuhl, Carsten; Tissier, Alain; Holz, Mareike; Krawinkel, Lutz A; Glatzel, Markus; Westphal, Manfred; Lamszus, Katrin

    2013-11-01

    Fluctuations in oxygen tension during tissue remodeling impose a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastoma, the most common malignant brain tumor, possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. We identified a reciprocal metabolic switch between the pentose phosphate pathway (PPP) and glycolysis in glioblastoma stem-like (GS) cells. Expression of PPP enzymes is upregulated by acute oxygenation but downregulated by hypoxia, whereas glycolysis enzymes, particularly those of the preparatory phase, are regulated inversely. Glucose flux through the PPP is reduced under hypoxia in favor of flux through glycolysis. PPP enzyme expression is elevated in human glioblastomas compared to normal brain, especially in highly proliferative tumor regions, whereas expression of parallel preparatory phase glycolysis enzymes is reduced in glioblastomas, except for strong upregulation in severely hypoxic regions. Hypoxia stimulates GS cell migration but reduces proliferation, whereas oxygenation has opposite effects, linking the metabolic switch to the "go or grow" potential of the cells. Our findings extend Warburg's observation that tumor cells predominantly utilize glycolysis for energy production, by suggesting that PPP activity is elevated in rapidly proliferating tumor cells but suppressed by acute severe hypoxic stress, favoring glycolysis and migration to protect cells against hypoxic cell damage.

  18. 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.

  19. 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...

  20. 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.)

  1. 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.

  2. 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.

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.)

  9. 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).

  10. Tumor cerebral e gravidez Brain tumors and pregnancy

    Directory of Open Access Journals (Sweden)

    José Carlos Lynch

    2007-12-01

    Full Text Available O diagnóstico de um tumor cerebral durante a gravidez é um fato raro que coloca a mãe e o concepto em risco de vida. OBJETIVO: Avaliar a melhor forma de conduzir uma paciente grávida portadora de um tumor cerebral. MÉTODO: Realizamos análise retrospectiva dos prontuários e imagens de seis pacientes grávidas portadoras de tumor cerebral. RESULTADOS: Vários tipos histológicos de tumor cerebral podem estar associados à gravidez. O meningioma é o mais freqüente. Nessa série não observamos óbito cirúrgico materno. Em duas pacientes, o parto ocorreu antes da craniotomia e em outras quatro o parto foi realizado após a neurocirurgia. CONCLUSÃO: O momento mais adequado para a realização da craniotomia para remoção tumoral irá depender da gravidade do quadro neurológico, do tipo histológico presumível da lesão, e da idade gestacional do embrião.BACKGROUND: Despite not being a common fact, the occurrence of brain tumors during pregnancy poses a risk to both the mother and infant. AIM: To identify the best medical procedure to be followed for a pregnant patient harboring a brain tumor. METHOD: The records of 6 patients with brain tumors, diagnosed during pregnancy were examined. RESULTS: Several types of brain tumors have been associated with pregnancy, but the meningioma is, by far, the most frequent. It seems that pregnancy aggravates the clinical course of intracranial tumors. There were no operative mortality in these series. In 2 patients the labor occurred before the craniotomy and in others, the delivery occurred after the surgery. CONCLUSION: The best moment to recommend the craniotomy and the neurosurgical removal of the tumor will depend of the mother’s neurological condition, the tumor histological type as well as the gestational age.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

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

  12. Impact of Microenvironment and Stem-Like Plasticity in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Raggi, Chiara; Invernizzi, Pietro; Andersen, Jesper Bøje

    2014-01-01

    Clinical complexity, anatomic diversity and molecular heterogeneity of cholangiocarcinoma (CCA) represent a major challenge in the assessment of effective targeted therapies. Molecular and cellular mechanisms underlying diversity of CCA growth patterns remain a key issue and a clinical concern...... or tumor microenvironment (TME) likely promotes initiation and progression of this malignancy contributing to its heterogeneity. This review will emphasize the dynamic interplay between stem-like intrinsic and TME-extrinsic pathways, which may represent novel options for multi-targeted therapies in CCA....

  13. GLCM textural features for Brain Tumor Classification

    Directory of Open Access Journals (Sweden)

    N S Zulpe

    2012-05-01

    Full Text Available Automatic recognition system for medical images is challenging task in the field of medical image processing. Medical images acquired from different modalities such as Computed Tomography (CT, Magnetic Resonance Imaging (MRI, etc which are used for the diagnosis purpose. In the medical field, brain tumor classification is very important phase for the further treatment. Human interpretation of large number of MRI slices (Normal or Abnormal may leads to misclassification hence there is need of such a automated recognition system, which can classify the type of the brain tumor. In this research work, we used four different classes of brain tumors and extracted the GLCM based textural features of each class, and applied to two-layered Feed forward Neural Network, which gives 97.5% classification rate.

  14. Confronting pediatric brain tumors: parent stories.

    Science.gov (United States)

    McMillan, Gigi

    2014-01-01

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

  15. MRI Brain Tumor Segmentation Methods- A Review

    OpenAIRE

    Gursangeet, Kaur; Jyoti, Rani

    2016-01-01

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

  16. Adult stem-like cells in kidney

    Institute of Scientific and Technical Information of China (English)

    Keiichi Hishikawa; Osamu Takase; Masahiro Yoshikawa; Taro Tsujimura; Masaomi Nangaku; Tsuyoshi Takato

    2015-01-01

    Human pluripotent cells are promising for treatmentfor kidney diseases, but the protocols for derivationof kidney cell types are still controversial. Kidneytissue regeneration is well confirmed in several lowervertebrates such as fish, and the repair of nephronsafter tubular damages is commonly observed after renalinjury. Even in adult mammal kidney, renal progenitorcell or system is reportedly presents suggesting thatadult stem-like cells in kidney can be practical clinicaltargets for kidney diseases. However, it is still unclearif kidney stem cells or stem-like cells exist or not. Ingeneral, stemness is defined by several factors suchas self-renewal capacity, multi-lineage potency andcharacteristic gene expression profiles. The definiteuse of stemness may be obstacle to understand kidneyregeneration, and here we describe the recent broadfindings of kidney regeneration and the cells thatcontribute regeneration.

  17. 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.

  18. 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.

  19. [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.

  20. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

    DEFF Research Database (Denmark)

    Schonberg, David L; Miller, Tyler E; Wu, Qiulian;

    2015-01-01

    Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progeni......Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue......-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators......, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable...

  1. The Immuno-therapy with Dendritic Cells Sensitized with mRNA from Breast tumor Stem-like Cells for Breast Carcinoma%乳腺癌干细胞样细胞mRNA致敏的树突状细胞疫苗免疫治疗研究

    Institute of Scientific and Technical Information of China (English)

    郑秋红; 谢云青; 刘健; 应敏刚

    2012-01-01

    Objective To investigate the induced immuno-reaction in vitro of dendritic cell vaccine sensitized with nucleic-acid antigen from breast tumor stem-like cells. Method The breast tumor MCF-7 stem-like cells were cultured and enriched in serum-free medium containing defined growth factors, and were confirmed by the identification of cellular surface markers by flow cytometer analysis, by clone-forming capability test with a soft agar assay, and by tumorigenic ability test in vivo using an NOD-SCID mouse model. The mRNAs were amplified by using T7 mMessage mMACHINE kit with total RNA template extracted from MCF-7 stem-like cells. The peripheral blood dendritic cells were transfected with the mRNA and their activities of inducing CTL were measured by MTT method. Result The breast tumor stem-like cells with CD44/CD24 phenotype could be cultured and enriched (90. 17%) in the defined serum-free medium and demonstrate strong tumorigenicity after being challenged into NOD/SCID mouse. The dendritic cells, when loaded with nucleic-acid antigen, could express specific cellular surface markers of CD80/CD83/CD86 and HLA-DR at high level. The dendritic cells, which were transfected with mRNA from the suspension, low-differentiation breast tumor stem-like cells, in comparison with the adhesive, differentiated breast tumor stem-like cells, possessed stronger capability to induce TCL mediated killing of target cells (P<0. 01). Conclusion The dendritic cells, which were sensitized with mRNA derived from breast tumor stem-like cells, could induce strong CTL targeting breast tumor stem-like cells in vitro. It may provide a new choice of clinical immuno-therapy for breast carcinoma.%目的 观察乳腺癌干细胞样细胞核酸抗原致敏的树突状细胞疫苗体外诱导免疫反应作用.方法 利用含有生长因子的无血清培养基悬浮培养法富集MCF-7乳腺癌干细胞样细胞,经单克隆形成、表面标记检测、NOD-SCID小鼠成瘤等实验鉴定后,采用T7

  2. Brain tumors: Special characters for research and banking

    Directory of Open Access Journals (Sweden)

    Majid Kheirollahi

    2015-01-01

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

  3. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  4. O6-Methylguanine-Methyltransferase (MGMT Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions

    Directory of Open Access Journals (Sweden)

    Lucie Karayan-Tapon

    2012-06-01

    Full Text Available Glioblastoma (GBM is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ. However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.

  5. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

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

    Science.gov (United States)

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

    2000-01-01

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

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

    OpenAIRE

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

    2015-01-01

    Background A possible risk factor for brain tumor might be measles, since late neurologic sequelae are part of measles pathology. Subacute sclerosing panencephalitis, a devastating neurologic illness, is prone to develop years after measles infection. Methods Because measles damage to the brain might increase the risk of brain tumor, we examined the relationship of measles incidence in 1960 and brain tumor incidence in 50 US States and the District of Columbia, 2004-2007. Data on number of ca...

  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. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

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

    2017-01-01

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

  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. Paclitaxel-Fe3O4 nanoparticles inhibit growth of CD138–  CD34– tumor stem-like cells in multiple myeloma-bearing mice

    Directory of Open Access Journals (Sweden)

    Yang C

    2013-04-01

    Full Text Available Cuiping Yang,1,3,* Jing Wang,2,* Dengyu Chen,1,* Junsong Chen,1 Fei Xiong,4 Hongyi Zhang,1 Yunxia Zhang,2 Ning Gu,4 Jun Dou11Department of Pathogenic Biology and Immunology, Medical School, 2Department of Gynecology and Obstetrics, Zhongda Hospital, Southeast University, Nanjing, 3Department of Pathogenic Biology and Immunology, School of Basic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 4School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China*These authors contributed equally to this workBackground: There is growing evidence that CD138– CD34– cells may actually be tumor stem cells responsible for initiation and relapse of multiple myeloma. However, effective drugs targeted at CD138– CD34– tumor stem cells are yet to be developed. The purpose of this study was to investigate the inhibitory effect of paclitaxel-loaded Fe3O4 nanoparticles (PTX-NPs on CD138– CD34– tumor stem cells in multiple myeloma-bearing mice.Methods: CD138– CD34– cells were isolated from a human U266 multiple myeloma cell line using an immune magnetic bead sorting method and then subcutaneously injected into mice with nonobese diabetic/severe combined immunodeficiency to develop a multiple myeloma-bearing mouse model. The mice were treated with Fe3O4 nanoparticles 2 mg/kg, paclitaxel 4.8 mg/kg, and PTX-NPs 0.64 mg/kg for 2 weeks. Tumor growth, pathological changes, serum and urinary interleukin-6 levels, and molecular expression of caspase-3, caspase-8, and caspase-9 were evaluated.Results: CD138– CD34– cells were found to have tumor stem cell characteristics. All the mice developed tumors in 40 days after injection of 1 × 106 CD138– CD34– tumor stem cells. Tumor growth in mice treated with PTX-NPs was significantly inhibited compared with the controls (P <  0.005, and the groups that received nanoparticles alone (P < 0.005 or paclitaxel alone (P < 0.05. In addition

  12. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    Science.gov (United States)

    2012-03-21

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

  13. 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.)

  14. 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)

  15. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.

    Science.gov (United States)

    Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Fortner, Karen A; Viapiano, Mariano S; Jaworski, Diane M

    2015-08-01

    Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth.

  16. Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem-like cells and increased maternal oxidative environment

    Science.gov (United States)

    Many adult chronic diseases might be programmed during early life by maternal nutritional history. Here, we evaluated effects of maternal high fat diet on mammary gland development and tumor formation in adult progeny. Female Wnt-1 transgenic mice exposed to high fat (HFD, 45% kcal fat) or control C...

  17. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

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

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    ... cells in the brain. They transmit chemical and electric signals that determine thought, memory, emotion, speech, muscle movement, ... brain and spinal cord. This helps neurons send electric signals through the axons. Tumors starting in these cells ...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Characterization of glioma stem-like cells from human glioblastomas.

    Science.gov (United States)

    Yamamuro, Shun; Okamoto, Yutaka; Sano, Emiko; Ochiai, Yushi; Ogino, Akiyoshi; Ohta, Takashi; Hara, Hiroyuki; Ueda, Takuya; Nakayama, Tomohiro; Yoshino, Atsuo; Katayama, Yoichi

    2015-07-01

    Glioma stem-like cells (GSCs) could have potential for tumorigenesis, treatment resistance, and tumor recurrence (GSC hypothesis). However, the mechanisms underlying such potential has remained elusive and few ultrastructural features of the cells have been reported in detail. We therefore undertook observations of the antigenic characteristics and ultrastructural features of GSCs isolated from human glioblastomas. Tumor spheres formed by variable numbers of cells, exhibiting a variable appearance in both their size and shape, were frequently seen in GSCs expressing the stem cell surface markers CD133 and CD15. Increased cell nucleus atypia, mitochondria, rough endoplasmic reticulum, coated vesicles, and microvilli, were noted in the GSCs. Furthermore, cells at division phases and different phases of the apoptotic process were occasionally observed. These findings could imply that GSCs have certain relations with human neural stem cells (NSCs) but are primitively different from undifferentiated NSCs. The data may provide support for the GSC hypothesis, and also facilitate the establishment of future glioblastoma treatments targeting GSCs.

  5. 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

  6. Growth Patterns of Microscopic Brain Tumors

    CERN Document Server

    Sander, L M; Sander, Leonard M.; Deisboeck, Thomas S.

    2002-01-01

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

  7. 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.

  8. 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.

  9. 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

  10. Proteomic analysis of human Sonic Hedgehog (SHH) medulloblastoma stem-like cells.

    Science.gov (United States)

    Ronci, Maurizio; Catanzaro, Giuseppina; Pieroni, Luisa; Po, Agnese; Besharat, Zein Mersini; Greco, Viviana; Levi Mortera, Stefano; Screpanti, Isabella; Ferretti, Elisabetta; Urbani, Andrea

    2015-06-01

    Human medulloblastoma (MB) is a malignant brain tumor that comprises four distinct molecular subgroups including the Sonic Hedgehog (SHH)-MB group. A leading cause of the SHH subgroup is an aberrant activation of the SHH pathway, a developmental signaling that regulates postnatal development of the cerebellum by promoting the mitotic expansion of granule neural precursors (GNPs) in the external granule layer (EGL). The abnormal SHH signaling pathway drives not only SHH-MB but also its cancer stem-like cells (SLCs), which represent a fraction of the tumor cell population that maintain cancer growth and have been associated with high grade tumors. Here, we report the first proteomic analysis of human SHH-MB SLCs before and after Retinoic Acid (RA)-induced differentiation. A total of 994 nLC-MS buckets were statistically analysed returning 68 modulated proteins between SLCs and their differentiated counterparts. Heat Shock Protein 70 (Hsp70) was one of the proteins that characterized the protein profile of SLCs. By means of Ingenuity Pathway Analysis (IPA), Genomatix analysis and extending the network obtained using the differentially expressed proteins we found a correlation between Hsp70 and the NF-κB complex. A key driver of the SHH-MB group is cMET whose downstream proliferation/survival signalling is indeed via PI3K/Akt/NF-κB. We confirmed the results of the proteomic analysis by western blot, underlining that a P-p65/NF-κB activatory complex is highly expressed in SLCs. Taking together these results we define a new protein feature of SHH-MB SLCs.

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

    Science.gov (United States)

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

    2014-05-01

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

  12. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-01-17

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

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

    Science.gov (United States)

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

    2013-06-01

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

  14. 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.

  15. 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

  16. Clinical topographical correlation upon brain tumors in children

    Directory of Open Access Journals (Sweden)

    A.M. Dolgov

    2014-01-01

    Full Text Available The aim of the study was to explore the most characteristic clinical manifestations of brain tumors in children, depending on their localization, and to detect the earliest of them. Patients and methods. A total of 56 children (32 boys and 24 girls with brain tumor, aged from 1.5 months to 15 years, were examined. The time elapsed between the onset of disease to the emergence of clinical symptoms was assessed. Neurological symptomatology was compared to the localization of a tumor diagnosed using neuroimaging techniques (computed tomography or magnetic resonance imaging and during surgery. Surgery was performed in 18 children (in all of them, localization of the process was observed in the posterior cranial fossa, PCF. Results. The highest incidence of brain tumors was revealed in children aged 3–13 years; most patients became ill at the age between 3 and 6 years. Tumors of the PCF predominated in terms of their localization (67.9% of cases. Intracerebral tumors of the hemispheres or vermis were observed in most (63.2% patients with tumors of the PCF. In 11 (61% of the 18 operated children with subtentorial tumors, astrocytomas of various degrees of differentiation and medulloblastomas were detected using the histological examination. Tumors of the IV ventricle were ependymal. Tumors of the cerebral hemispheres (19.6%, of the pineal and chiasmosellar regions (8.9% predominated among supratentorial tumors. The time between the emergence of initial symptoms of a disease and admission to hospital ranged from 1 month to 3 years. The most characteristic and earliest symptoms for tumors of the PCF and brain ventricles were headache, nausea and vomiting. For tumors of the cerebellar vermis and hemispheres, these symptoms included impairment of the coordination of movements and the muscle tone change. For brain stem tumors, these symptoms included dysfunction of the cranial nerves. For tumors of the cerebral hemispheres, these were seizures and motor

  17. 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

  18. 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.

  19. Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors

    Directory of Open Access Journals (Sweden)

    Seyfried Thomas N

    2005-08-01

    Full Text Available Abstract Background Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (OL and the Arg tRNA. Methods In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. Results Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. Conclusion None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors.

  20. Stem Cells and the Origin and Propagation of Brain Tumors

    OpenAIRE

    2008-01-01

    In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of “cancer stem cells” that is crucial for tumor maintenance or propagation. While all these concepts are interesting and provide insi...

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

    Science.gov (United States)

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

    2016-12-01

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

  2. Isolation of stem-like cells from spontaneous feline mammary carcinomas: Phenotypic characterization and tumorigenic potential

    Energy Technology Data Exchange (ETDEWEB)

    Barbieri, Federica; Wurth, Roberto [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy); Ratto, Alessandra; Campanella, Chiara; Vito, Guendalina [Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D' Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Piazza Borgo Pila, 16129, Genova (Italy); Thellung, Stefano [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy); Daga, Antonio [Laboratory of Translational Oncology, IRCCS Azienda Ospedaliera Universitaria San Martino - IST- Istituto Nazionale Ricerca sul Cancro, L.go R. Benzi, 10, 16132 Genova Italy (Italy); Cilli, Michele [Animal Facility, IRCCS Azienda Ospedaliera Universitaria San Martino - IST- Istituto Nazionale Ricerca sul Cancro, L.go R. Benzi, 10, 16132 Genova Italy (Italy); Ferrari, Angelo [Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D' Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Piazza Borgo Pila, 16129, Genova (Italy); Florio, Tullio, E-mail: tullio.florio@unige.it [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy)

    2012-04-15

    Current carcinogenesis theory states that only a small subset of tumor cells, the cancer stem cells or tumor initiating cells (TICs), are responsible for tumor formation and progression. Human breast cancer-initiating cells have been identified as CD44-expressing cells, which retain tumorigenic activity and display stem cell-like properties. Spontaneous feline mammary carcinoma (FMC) is an aggressive cancer, which shows biological similarities to the human tumor counterpart. We report the isolation and phenotypic characterization of FMC-derived stem/progenitor cells, showing in vitro self-renewal, long-lasting proliferation and in vivo tumorigenicity. Twenty-one FMC samples were collected, histologically classified and characterized for the expression of Ki67, EGFR, ER-{alpha} and CD44, by immunohistochemistry. By culture in stem cell permissive conditions, we isolated, from 13 FMCs, a CD44-positive subpopulation able to survive and proliferate in vitro as mammospheres of different sizes and morphologies. When injected in NOD/SCID mice, FMC stem-like cells initiate tumors, generating cell heterogeneity and recapitulating the original histotype. In serum-containing medium, spheroid cells showed differentiation properties as shown by morphological changes, the loss of CD44 expression and tumorigenic potential. These data show that stem-defined culture of FMC enriches for TICs and validate the use of these cells as a suitable model for comparative oncology studies of mammary biology and testing therapeutic strategies aimed at eradicating TICs. -- Highlights: Black-Right-Pointing-Pointer Feline mammary carcinoma contain a sub-population of stem-like cells expressing CD44 Black-Right-Pointing-Pointer These grow as spheres in serum-free medium and self-renew Black-Right-Pointing-Pointer Isolated stem-like cancer cells initiate tumor in immunodeficient mice Black-Right-Pointing-Pointer Xenografted tumors are phenotypically similar to the original tumor Black

  3. 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.

  4. Labeled Putrescine as a Probe in Brain Tumors

    Science.gov (United States)

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

    1983-08-01

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

  5. 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

  6. State of the art survey on MRI brain tumor segmentation.

    Science.gov (United States)

    Gordillo, Nelly; Montseny, Eduard; Sobrevilla, Pilar

    2013-10-01

    Brain tumor segmentation consists of separating the different tumor tissues (solid or active tumor, edema, and necrosis) from normal brain tissues: gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). In brain tumor studies, the existence of abnormal tissues may be easily detectable most of the time. However, accurate and reproducible segmentation and characterization of abnormalities are not straightforward. In the past, many researchers in the field of medical imaging and soft computing have made significant survey in the field of brain tumor segmentation. Both semiautomatic and fully automatic methods have been proposed. Clinical acceptance of segmentation techniques has depended on the simplicity of the segmentation, and the degree of user supervision. Interactive or semiautomatic methods are likely to remain dominant in practice for some time, especially in these applications where erroneous interpretations are unacceptable. This article presents an overview of the most relevant brain tumor segmentation methods, conducted after the acquisition of the image. Given the advantages of magnetic resonance imaging over other diagnostic imaging, this survey is focused on MRI brain tumor segmentation. Semiautomatic and fully automatic techniques are emphasized.

  7. 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....

  8. 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.

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

    Science.gov (United States)

    Ostrom, Quinn T; Barnholtz-Sloan, Jill S

    2011-06-01

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

  10. 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

  11. 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.)

  12. Mathematical modeling of brain tumors: effects of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Powathil, G [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Kohandel, M [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Sivaloganathan, S [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1 (Canada); Oza, A [Center for Mathematical Medicine, Fields Institute for Research in Mathematical Sciences, Toronto, Ontario M5T 3J1 (Canada); Milosevic, M [Radiation Medicine Program, Princess Margaret Hospital, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada)

    2007-06-07

    Gliomas, the most common primary brain tumors, are diffusive and highly invasive. The standard treatment for brain tumors consists of a combination of surgery, radiation therapy and chemotherapy. Over the past few years, mathematical models have been applied to study untreated and treated brain tumors. In an effort to improve treatment strategies, we consider a simple spatio-temporal mathematical model, based on proliferation and diffusion, that incorporates the effects of radiotherapeutic and chemotherapeutic treatments. We study the effects of different schedules of radiation therapy, including fractionated and hyperfractionated external beam radiotherapy, using a generalized linear quadratic (LQ) model. The results are compared with published clinical data. We also discuss the results for combination therapy (radiotherapy plus temozolomide, a new chemotherapy agent), as proposed in recent clinical trials. We use the model to predict optimal sequencing of the postoperative (combination of radiotherapy and adjuvant, neo-adjuvant or concurrent chemotherapy) treatments for brain tumors.

  13. Childhood Brain and Spinal Cord Tumors Treatment Overview

    Science.gov (United States)

    ... the following: Brain Tumor Signs and Symptoms Morning headache or headache that goes away after vomiting . Frequent nausea and ... Cancer Late Effects of Treatment for Childhood Cancer Adolescents and Young Adults with Cancer Children with Cancer: ...

  14. General Information about Childhood Brain and Spinal Cord Tumors

    Science.gov (United States)

    ... the following: Brain Tumor Signs and Symptoms Morning headache or headache that goes away after vomiting . Frequent nausea and ... Cancer Late Effects of Treatment for Childhood Cancer Adolescents and Young Adults with Cancer Children with Cancer: ...

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

    Science.gov (United States)

    ... tumor. This still requires making an incision and drilling a small hole into the skull. The biopsy ... requests, please see our Content Usage Policy . Early Detection, Diagnosis, and Staging Can Brain and Spinal Cord ...

  16. 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.

  17. 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

  18. 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.

  19. The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells.

    Science.gov (United States)

    Boyle, S T; Ingman, W V; Poltavets, V; Faulkner, J W; Whitfield, R J; McColl, S R; Kochetkova, M

    2016-01-07

    The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.

  20. Nanocarrier drugs in the treatment of brain tumors

    Institute of Scientific and Technical Information of China (English)

    Tereza Cerna; Marie Stiborova; Vojtech Adam; Rene Kizek; Tomas Eckschlager

    2016-01-01

    Nanoparticle-mediated targeted delivery of drugs might signiifcantly reduce the dosage and optimize their release properties, increase speciifcity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modiifcation of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.

  1. 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

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  4. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells

    OpenAIRE

    Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong,; Maawy, Ali; Hassanein, Mohamed K.; Uehara, Fuminari; MIWA, SHINJI; Yano, Shuya; Momiyama, Masashi; Suetsugu, Atsushi; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

    2013-01-01

    The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC50 values of stem-like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC50 values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In cont...

  7. Remission of invasive, cancer stem-like glioblastoma xenografts using lentiviral vector-mediated suicide gene therapy.

    Directory of Open Access Journals (Sweden)

    Peter C Huszthy

    Full Text Available BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP and vesicular stomatitis virus glycoprotein (VSV-G pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001 compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery

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

    Science.gov (United States)

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

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

  9. Novel anticancer activity of phloroglucinol against breast cancer stem-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rae-Kwon; Uddin, Nizam [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Hyun, Jin-Won [College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of); Kim, Changil [Department of Biotechnology, Konkuk University, Chungju 380-701 (Korea, Republic of); Suh, Yongjoon, E-mail: hiswork@hanmail.net [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae, E-mail: sj0420@hanyang.ac.kr [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2015-08-01

    Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44{sup +} cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β-catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse. - Highlights: • Phloroglucinol suppresses in vivo tumor formation. • Phloroglucinol sensitizes breast cancer cells to anticancer agents. • Phloroglucinol inhibits breast cancer stem-like cells. • Phloroglucinol inhibits PI3K/AKT and KRAS/RAF/ERK signaling pathways.

  10. Brain and Spinal Tumors: Hope through Research

    Science.gov (United States)

    ... which can trigger neurological conditions and symptoms including hyperthyroidism and Cushing’s syndrome (the harmful over-production of the hormone cortisol). Treatment options include tumor resection, radiation therapy, and drug ...

  11. 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.

  12. Primary intracranial Parachordoma: An unusual tumor in brain

    Directory of Open Access Journals (Sweden)

    Rajesh K Ghanta

    2014-01-01

    Full Text Available Background: Parachordomas are rare soft tissue tumors commonly occurring in limbs, chest, Abdomen, and back. The World Health Organization (WHO classification includes parachordomas in the same group as mixed tumors and myoepitheliomas. Exact histogenesis of this tumor is unclear. Case Description: A 52-year-old male presented with headache and blurring of vision since one month. Preoperative computed tomography (CT scan of brain revealed left parieto-occipital tumor extending up to the trigone. Total excision of the tumor was done. Histopathologically, the tumor was composed of relatively uniform cells with eosinophilic cytoplasm in a myxoid stroma and with cartilaginous and osseous metaplasia. The tumoral cells were immunoreactive for cytokeratin, epithelial membrane antigen (EMA, S-100, and vimentin. The constellation of findings revealed the tumor to be parachordoma. Magnetic resonance imaging (MRI brain during follow-up at one year showed no recurrent tumor. No adjuvant therapy was given to this patient. Conclusion: This is the first reported case of primary intracranial parachordoma. It is difficult to diagnose the lesion preoperatively by imaging alone. Long-term follow-up is necessary in view of few reports in literature of recurrence and metastasis, of parachordomas in other anatomical locations.

  13. Epigallocatechin-3-gallate inhibits stem-like inflammatory breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Nora D Mineva

    Full Text Available Inflammatory Breast Cancer (IBC is a highly aggressive form of cancer characterized by high rates of proliferation, lymphangiogenesis and metastasis, and an overall poor survival. As regular green tea consumption has been associated with improved prognosis of breast cancer patients, including decreased risk of recurrence, here the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG were tested on two IBC lines: SUM-149 and SUM-190. EGCG decreased expression of genes that promote proliferation, migration, invasion, and survival. Consistently, growth, invasive properties, and survival of IBC cells were reduced by EGCG treatment. EGCG also reduced lymphangiogenesis-promoting genes, in particular VEGF-D. Conditioned media from EGCG-treated IBC cells displayed decreased VEGF-D secretion and reduced ability to promote lymphangiogenesis in vitro as measured by hTERT-HDLEC lymphatic endothelial cell migration and tube formation. Tumorsphere formation by SUM-149 cells was robustly inhibited by EGCG, suggesting effects on self-renewal ability. Stem-like SUM-149 cells with high aldehyde dehydrogenase (ALDH activity, previously implicated in poor patient prognosis, were isolated. EGCG treatment reduced growth and induced apoptosis of the stem-like SUM-149 cells in culture. In an orthotopic mouse model, EGCG decreased growth of pre-existing tumors derived from ALDH-positive stem-like SUM-149 cells and their expression of VEGF-D, which correlated with a significant decrease in peritumoral lymphatic vessel density. Thus, EGCG inhibits the overall aggressive IBC phenotype. Reduction of the stem-like cell compartment by EGCG may explain the decreased risk of breast cancer recurrence among green tea drinkers. Recent clinical trials demonstrate the efficacy of green tea polyphenol extracts in treatment of prostate cancer and lymphocytic leukemia with low toxicity. Given the poor prognosis of IBC patients, our findings suggest further exploration

  14. Bilateral Symmetry Information for Brain Tumor Detection

    Directory of Open Access Journals (Sweden)

    Krunal J Pimple,

    2014-03-01

    Full Text Available Image segmentation is used to separate an image into several “meaningful” parts. It is an old research topic, which started around 1970, but there is still no robust solution toward it. There are two main reasons; the first is that the content variety of images is too large, and the second one is that there is no benchmark standard to judge the performance. Various subjects that are paired usually are not identically the same, asymmetry is perfectly normal but sometimes asymmetry can benoticeable too much. Structural and functional asymmetry in the human brain and nervous system is reviewed in a historical perspective. Brain asymmetry is one of such examples, which is a difference in size or shape, or both. Asymmetry analysis of brain has great importance because it is not only indicator for brain cancer but also predict future potential risk for the same. In our work, we have concentrated to segment the anatomical regions of brain, isolate the two halves of brain and to investigate each half for the presence of asymmetry of anatomical regions in MRI.

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

    Directory of Open Access Journals (Sweden)

    Manjula S

    2010-01-01

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

  16. 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)

  17. Histone modification as a drug resistance driver in brain tumors

    Institute of Scientific and Technical Information of China (English)

    Guifa Xi; Barbara Mania-Farnell; Ting Lei; Tadanori Tomita

    2016-01-01

    Patients with brain tumors, specificaly, malignant forms such as glioblastoma, meduloblas-toma and ependymoma, exhibit dismal survival rates despite advances in treatment strategies. Chemotherapeutics, the primary adjuvant treatment for human brain tumors folowing surgery, commonly lack eficacy due to either intrinsic or acquired drug resistance. New treatments tar-geting epigenetic factors are being explored. Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation, apoptosis, gene transcription, and DNA replication and repair. This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors. Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.

  18. Automated Brain Tumor Segmentation on MR Images Based on Neutrosophic Set Approach

    OpenAIRE

    Mohan J; Krishnaveni V; Yanhui Huo

    2015-01-01

    Brain tumor segmentation for MR images is a difficult and challenging task due to variation in type, size, location and shape of tumors. This paper presents an efficient and fully automatic brain tumor segmentation technique. This proposed technique includes non local preprocessing, fuzzy intensification to enhance the quality of the MR images, k - means clustering method for brain tumor segmentation.

  19. 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.

  20. Gonadal status in male survivors following childhood brain tumors

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jun Cheng

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

  9. Analysis of p53- immunoreactivity in astrocytic brain tumors

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    Shinkarenko T.V.

    2016-12-01

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

  10. Implementing Tumor Detection and Area Calculation in Mri Image of Human Brain Using Image Processing Techniques

    OpenAIRE

    Sunil L. Bangare; Madhura Patil

    2015-01-01

    This paper is based on the research on Human Brain Tumor which uses the MRI imaging technique to capture the image. In this proposed work Brain Tumor area is calculated to define the Stage or level of seriousness of the tumor. Image Processing techniques are used for the brain tumor area calculation and Neural Network algorithms for the tumor position calculation. Also in the further advancement the classification of the tumor based on few parameters is also expected. Proposed wor...

  11. Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis

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    C. Parker Gibbs

    2005-11-01

    Full Text Available Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called “sarcospheres,” in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44 as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.

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

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    Veiseh, Omid

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

  13. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

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    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.

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

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    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.

  15. American brain tumor patients treated with BNCT in Japan

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

    1995-11-01

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

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

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    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.

  17. Application of nanoparticles in brain tumor treatment

    CERN Document Server

    Caruso, Gerardo; Raudino, Giuseppe

    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.

  18. 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.

  19. Drug delivery using nanoparticles for cancer stem-like cell targeting

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    Bing eLu

    2016-04-01

    Full Text Available The theory of cancer stem-like cell (or cancer stem cell, CSC has been established to explain how tumor heterogeneity arises and contributes to tumor progression in diverse cancer types. CSCs are believed to drive tumor growth and elicit resistance to conventional therapeutics. Therefore, CSCs are becoming novel target in both medical researches and clinical studies. Emerging evidences showed that nanoparticles effectively inhibit many types of CSCs by targeting various specific markers (aldehyde dehydrogenases, CD44, CD90, and CD133 and signaling pathways (Notch, Hedgehog, and TGF-β, which are critically involved in CSC function and maintenance. In this review, we briefly summarize the current status of CSC research and review a number of state-of-the-art nanomedicine approaches targeting CSC. In addition, we discuss emerging therapeutic strategies using epigenetic drugs to eliminate CSCs and inhibit cancer cell reprogramming.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  1. 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.

  2. Delayed cell death associated with mitotic catastrophe in γ-irradiated stem-like glioma cells

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    Esser Norbert

    2011-06-01

    Full Text Available Abstract Background and Purpose Stem-like tumor cells are regarded as highly resistant to ionizing radiation (IR. Previous studies have focused on apoptosis early after irradiation, and the apoptosis resistance observed has been attributed to reduced DNA damage or enhanced DNA repair compared to non-stem tumor cells. Here, early and late radioresponse of patient-derived stem-like glioma cells (SLGCs and differentiated cells directly derived from them were examined for cell death mode and the influence of stem cell-specific growth factors. Materials and methods Primary SLGCs were propagated in serum-free medium with the stem-cell mitogens epidermal growth factor (EGF and fibroblast growth factor-2 (FGF-2. Differentiation was induced by serum-containing medium without EGF and FGF. Radiation sensitivity was evaluated by assessing proliferation, clonogenic survival, apoptosis, and mitotic catastrophe. DNA damage-associated γH2AX as well as p53 and p21 expression were determined by Western blots. Results SLGCs failed to apoptose in the first 4 days after irradiation even at high single doses up to 10 Gy, but we observed substantial cell death later than 4 days postirradiation in 3 of 6 SLGC lines treated with 5 or 10 Gy. This delayed cell death was observed in 3 of the 4 SLGC lines with nonfunctional p53, was associated with mitotic catastrophe and occurred via apoptosis. The early apoptosis resistance of the SLGCs was associated with lower γH2AX compared to differentiated cells, but we found that the stem-cell culture cytokines EGF plus FGF-2 strongly reduce γH2AX levels. Nonetheless, in two p53-deficient SLGC lines examined γIR-induced apoptosis even correlated with EGF/FGF-induced proliferation and mitotic catastrophe. In a line containing CD133-positive and -negative stem-like cells, the CD133-positive cells proliferated faster and underwent more γIR-induced mitotic catastrophe. Conclusions Our results suggest the importance of delayed

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

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

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

  4. 3D Brain Tumors and Internal Brain Structures Segmentation in MR Images

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    P.NARENDRAN

    2012-02-01

    Full Text Available The main topic of this paper is to segment brain tumors, their components (edema and necrosis and internal structures of the brain in 3D MR images. For tumor segmentation we propose a framework that is a combination of region-based and boundary-based paradigms. In this framework, segment the brain using a method adapted for pathological cases and extract some global information on the tumor by symmetry based histogram analysis. We propose a new and original method that combines region and boundary information in two phases: initialization and refinement. The method relies on symmetry-based histogram analysis. The initial segmentation of the tumor is refined relying on boundary information of the image. We use a deformable model which is again constrained by the fused spatial relations of the structure. The method was also evaluated on 10 contrast enhanced T1-weighted images to segment the ventricles, caudate nucleus and thalamus.

  5. Brain Tumor Segmentation Based on Random Forest

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    László Lefkovits

    2016-09-01

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

  6. 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.

  7. Perivascular Wall Tumor in the Brain of a Dog

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    Margaret Cohn-Urbach

    2015-01-01

    Full Text Available A 9-year-old spayed female German shepherd mixed-breed dog presented for seizures. Magnetic resonance imaging revealed an irregularly marginated intraparenchymal cerebral mass. Microscopic examination of brain tissue collected postmortem demonstrated perivascular whorling and interwoven bundles of spindle-shaped cells. On immunohistochemistry, the tumor cells tested positive for vimentin and negative for factor VIII-related antigen, CD18, CD45, CD3, CD20, GFAP, S-100, and desmin. Immunohistochemistry results, in combination with histopathologic morphology, were suggestive of a perivascular wall tumor. To the authors’ knowledge, this is the first case report to utilize both histopathology and immunohistochemistry to describe a perivascular wall tumor in the brain of a dog.

  8. 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.

  9. 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

  10. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

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    Marco Mineo

    2016-06-01

    Full Text Available Long non-coding RNAs (lncRNAs have an undefined role in the pathobiology of glioblastoma multiforme (GBM. These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2 as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context.

  11. The long non-coding RNA – HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches

    Science.gov (United States)

    Mineo, Marco; Ricklefs, Franz; Rooj, Arun K.; Lyons, Shawn M.; Ivanov, Pavel; Ansari, Khairul I.; Nakano, Ichiro; Chiocca, E. Antonio; Godlewski, Jakub; Bronisz, Agnieszka

    2016-01-01

    Long-non-coding RNAs (lncRNAs) have an undefined role in the pathobiology of glioblastoma multiforme (GBM). These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs) that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) as a subtype-specific hypoxia inducible lncRNA, up-regulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal and hypoxia-dependent molecular reprogramming. Amongst the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Down-regulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome/targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context. PMID:27264189

  12. Clinicopathological pattern of brain tumors: A 3-year study in a tertiary care hospital in India

    OpenAIRE

    Sajeeb Mondal; Rajashree Pradhan; Subrata Pal; Biswajit Biswas; Arindam Banerjee; Debosmita Bhattacharyya

    2016-01-01

    Background: Brain tumors are heterogeneous group of neoplasms, affecting different age groups. Although some studies have been published regarding pathological pattern of brain tumors from different countries of the world and also from India, comprehensive clinicopathological studies from Eastern India is lacking. Aims: The aim of this study was to observe recent incidence of different brain tumors and to study clinical and histopathological spectrum of brain tumors in Eastern India. Material...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk.The study...... cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways....

  14. 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...

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

    Science.gov (United States)

    Castillo, Mauricio

    2014-11-01

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

  16. 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...

  17. 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.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Zi Jun Meng

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    2016-11-21

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

  2. 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)

  3. Brain congenital tumors of atypical presentation. Tumores cerebrales congenitos de presentacion atipica

    Energy Technology Data Exchange (ETDEWEB)

    Borden Ferre, F.; Menor Serrano, F.; Martinez Fernandez, M.; Moreno Flores, A.; Poyatos, C. (Hospital La Fe. Valencia (Spain))

    1994-01-01

    We present four cases of brain tumor within the first year of life, with atypical clinical and radiological onset. Two astrocytomas of the visual pathway presented with visual changes without involving the ventricular system. The other two, not histologically confirmed, were located in the medial portion of the temporal lobe, the first sign of which was a cyanotic crisis.

  4. Disulfiram targets cancer stem-like properties and the HER2/Akt signaling pathway in HER2-positive breast cancer.

    Science.gov (United States)

    Kim, Ji Young; Cho, Youngkwan; Oh, Eunhye; Lee, Nahyun; An, Hyunsook; Sung, Daeil; Cho, Tae-Min; Seo, Jae Hong

    2016-08-28

    HER2-positive breast tumors are known to harbor cancer stem-like cell populations and are associated with an aggressive tumor phenotype and poor clinical outcomes. Disulfiram (DSF), an anti-alcoholism drug, is known to elicit cytotoxicity in many cancer cell types in the presence of copper (Cu). The objective of the present study was to investigate the mechanism of action responsible for the induction of apoptosis by DSF/Cu and its effect on cancer stem cell properties in HER2-positive breast cancers in vitro and in vivo. DSF/Cu treatment induced apoptosis, associated with a marked decrease in HER2, truncated p95HER2, phospho-HER2, HER3, phospho-HER3 and phospho-Akt levels, and p27 nuclear accumulation. This was accompanied by the eradication of cancer stem-like populations, concomitant with the suppression of aldehyde dehydrogenase 1 (ALDH1) activity and mammosphere formation. DSF administration resulted in a significant reduction in tumor growth and an enhancement of apoptosis, as well as HER2 intracellular domain (ICD) and ALDH1A1 downregulation. Our results demonstrate that DSF/Cu induces apoptosis and eliminates cancer stem-like cells via the suppression of HER2/Akt signaling, suggesting that DSF may be potentially effective for the treatment of HER2-positive cancers.

  5. Classification of Brain Tumor Using Support Vector Machine Classfiers

    Directory of Open Access Journals (Sweden)

    Dr.D. J. Pete

    2014-03-01

    Full Text Available Magnetic resonance imagi ng (MRI is an imaging technique that has played an important role in neuro science research for studying brain images. Classification is an important part in order to distinguish between normal patients and those who have the possibility of having abnormalities or tumor. The proposed method consists of two stages: feature extraction and classification. In first stage features are extracted from images using GLCM. In the next stage, extracted features are fed as input to Kernel-Based SVM classifier. It classifies the images between normal and abnormal along with Grade of tumor depending upon features. For Brain MRI images; features extracted with GLCM gives 98% accuracy with Kernel-Based SVM Classifiesr. Software used is MATLAB R2011a.

  6. 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.

  7. Specific features of epilepsy in children with brain tumors

    Directory of Open Access Journals (Sweden)

    G. V. Kalmykova

    2015-01-01

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

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

    Science.gov (United States)

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

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

  9. Perivascular Wall Tumor in the Brain of a Dog

    OpenAIRE

    Margaret Cohn-Urbach; Annie Chen; Gary Haldorson; Stephanie Thomovsky

    2015-01-01

    A 9-year-old spayed female German shepherd mixed-breed dog presented for seizures. Magnetic resonance imaging revealed an irregularly marginated intraparenchymal cerebral mass. Microscopic examination of brain tissue collected postmortem demonstrated perivascular whorling and interwoven bundles of spindle-shaped cells. On immunohistochemistry, the tumor cells tested positive for vimentin and negative for factor VIII-related antigen, CD18, CD45, CD3, CD20, GFAP, S-100, and desmin. Immunohistoc...

  10. 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.

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

    Science.gov (United States)

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

    2013-12-01

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

  12. 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.

  13. Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.

    Directory of Open Access Journals (Sweden)

    Malgorzata Sztiller-Sikorska

    Full Text Available BACKGROUND: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. METHODS: We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. FINDINGS: Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF and proto-oncogene c-MYC. CONCLUSION: Selected anti-clonogenic compounds might be further investigated as potential adjuvants

  14. Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells.

    Science.gov (United States)

    Zhu, Thant S; Costello, Mark A; Talsma, Caroline E; Flack, Callie G; Crowley, Jessica G; Hamm, Lisa L; He, Xiaobing; Hervey-Jumper, Shawn L; Heth, Jason A; Muraszko, Karin M; DiMeco, Francesco; Vescovi, Angelo L; Fan, Xing

    2011-09-15

    One important function of endothelial cells in glioblastoma multiforme (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLC). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of NOTCH signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of NOTCH ligands. Here, we report a corroboration of this concept with a demonstration that NOTCH ligands are expressed in endothelial cells adjacent to NESTIN and NOTCH receptor-positive cancer cells in primary GBMs. Coculturing human brain microvascular endothelial cells (hBMEC) or NOTCH ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of NOTCH ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that NOTCH activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment.

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

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.

    Science.gov (United States)

    Han, Dan; Wu, Gang; Chang, Chan; Zhu, Fang; Xiao, Yin; Li, Qiuhui; Zhang, Tao; Zhang, Liling

    2015-12-01

    Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway.

  18. Brain CT of non-pineal intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hang Young; Chung, Eun Cheul; Lee, Dong Ho; Choo, In Wook; Chang, Kee Hyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1986-02-15

    19 cases of non-pineal intracranial germ cell tumors were reviewed retrospectively with both radiologic and clinical features. The results were as follows: 1. The age distribution was 8 to 32 year old (16 year old of mean age) and the sex distribution shows male predominance (15:4). 2. The histopathologic diagnosis includes 11 cases of germinoma, 2 case of mixed germ cell tumor, 1 case of embryonal cell carcinoma and 5 cases of unknown. 3. The location of tumors was the sarsaparilla region in 8 cases, the left basal ganglia and thalamus in 5 cases, and the right frontal lobe in 1 case. Among 11 cases of germinoma, 6 cases involve the sarsaparilla region and 3 cases the left basal ganglia and thalamus. 4. In clinical features, there were visual disturbance, diabetes indispose, increased ICP signs, motor weakness, hormonal disorders, and personal changes in order. 5. In tumor marker study of 6 cases of germinoma, 5 cases show increase in HCG titer, but all 6 cases were normal in AFP titer. 6. In brain CT, most of all revealed well-defined homogeneous high density with or without small central low density and homogeneous enhancement at solid portion, and there was calcification in only case with mixed germ cell tumor.

  19. Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy targeting cancer stem-like cells in humanized mice.

    Science.gov (United States)

    Kozlowska, Anna K; Kaur, Kawaljit; Topchyan, Paytsar; Jewett, Anahid

    2016-07-01

    Based on data obtained from oral, pancreatic and lung cancers, glioblastoma, and melanoma, we have established that natural killer (NK) cells target cancer stem-like cells (CSCs). CSCs displaying low MHC class I, CD54, and PD-L1 are killed by cytotoxic NK cells and are differentiated by split anergized NK cells through both membrane bound and secreted forms of TNF-α and IFN-γ. NK cells select and differentiate both healthy and transformed stem-like cells, resulting in target cell maturation and shaping of their microenvironment. In our recent studies, we have observed that oral, pancreatic, and melanoma CSCs were capable of forming large tumors in humanized bone marrow, liver, thymus (hu-BLT) mice with fully reconstituted human immune system. In addition, major human immune subsets including NK cells, T cells, B cells, and monocytes were present in the spleen, bone marrow, peripheral blood, and tumor microenvironment. Similar to our previously published in vitro data, CSCs differentiated with split anergized NK cells prior to implantation in mice formed smaller tumors. Intravenous injection of functionally potent osteoclast-expanded NK cells inhibited tumor growth through differentiation of CSCs in humanized mice. In this review, we present current approaches, advances, and existing limitations in studying interactions of the immune system with the tumor, in particular NK cells with CSCs, using in vivo preclinical hu-BLT mouse model. In addition, we discuss the use of osteoclast-expanded NK cells in targeting cancer stem-like tumors in humanized mice-a strategy that provides a much-needed platform to develop effective cancer immunotherapies.

  20. Anatomy of the Brain

    Science.gov (United States)

    ... Menu Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ... form Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ...

  1. 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.

  2. 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

  3. 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.

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

    Science.gov (United States)

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

    2016-10-27

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

  5. 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.

  6. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    Science.gov (United States)

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

    2016-11-01

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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Yang Jiao

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

  9. 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.

  10. Cisplatin selects for stem-like cells in osteosarcoma by activating Notch signaling.

    Science.gov (United States)

    Yu, Ling; Fan, Zhengfu; Fang, Shuo; Yang, Jian; Gao, Tian; Simões, Bruno M; Eyre, Rachel; Guo, Weichun; Clarke, Robert B

    2016-05-31

    Notch signaling regulates normal stem cells and is also thought to regulate cancer stem cells (CSCs). Recent data indicate that Notch signaling plays a role in the development and progression of osteosarcoma, however the regulation of Notch in chemo-resistant stem-like cells has not yet been fully elucidated. In this study we generated cisplatin-resistant osteosarcoma cells by treating them with sub-lethal dose of cisplatin, sufficient to induce DNA damage responses. Cisplatin-resistant osteosarcoma cells exhibited lower proliferation, enhanced spheroid formation and more mesenchymal characteristics than cisplatin-sensitive cells, were enriched for Stro-1+/CD117+ cells and showed increased expression of stem cell-related genes. A similar effect was observed in vivo, and in addition in vivo tumorigenicity was enhanced during serial transplantation. Using several publicly available datasets, we identified that Notch expression was closely associated with osteosarcoma stem cells and chemotherapy resistance. We confirmed that cisplatin-induced enrichment of osteosarcoma stem cells was mediated through Notch signaling in vitro, and immunohistochemistry showed that cleaved Notch1 (NICD1) positive cells were significantly increased in a relapsed xenograft which had received cisplatin treatment. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signalling inhibited cisplatin-enriched osteosarcoma stem cell activity in vitro, including Stro-1+/CD117+ double positive cells and spheroid formation capacity. The Notch inhibitor DAPT also prevented tumor recurrence in resistant xenograft tumors. Overall, our results show that cisplatin induces the enrichment of osteosarcoma stem-like cells through Notch signaling, and targeted inactivation of Notch may be useful for the elimination of CSCs and overcoming drug resistance.

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

    Science.gov (United States)

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

    2013-11-01

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

  12. 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.

  13. Notch signals in the endothelium and cancer "stem-like" cells: opportunities for cancer therapy

    Directory of Open Access Journals (Sweden)

    Gu Jian-Wei

    2012-04-01

    Full Text Available Abstract Anti-angiogenesis agents and the identification of cancer stem-like cells (CSC are opening new avenues for targeted cancer therapy. Recent evidence indicates that angiogenesis regulatory pathways and developmental pathways that control CSC fate are intimately connected, and that endothelial cells are a key component of the CSC niche. Numerous anti-angiogenic therapies developed so far target the VEGF pathway. However, VEGF-targeted therapy is hindered by clinical resistance and side effects, and new approaches are needed. One such approach may be direct targeting of tumor endothelial cell fate determination. Interfering with tumor endothelial cells growth and survival could inhibit not only angiogenesis but also the self-replication of CSC, which relies on signals from surrounding endothelial cells in the tumor microenvironment. The Notch pathway is central to controlling cell fate both during angiogenesis and in CSC from several tumors. A number of investigational Notch inhibitors are being developed. Understanding how Notch interacts with other factors that control endothelial cell functions and angiogenesis in cancers could pave the way to innovative therapeutic strategies that simultaneously target angiogenesis and CSC.

  14. Cathepsin K cleavage of SDF-1α inhibits its chemotactic activity towards glioblastoma stem-like cells.

    Science.gov (United States)

    Hira, Vashendriya V V; Verbovšek, Urška; Breznik, Barbara; Srdič, Matic; Novinec, Marko; Kakar, Hala; Wormer, Jill; der Swaan, Britt Van; Lenarčič, Brigita; Juliano, Luiz; Mehta, Shwetal; Van Noorden, Cornelis J F; Lah, Tamara T

    2017-03-01

    Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1α (SDF-1α), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches. Furthermore, we aimed to prove that SDF-1α cleavage by CatK inactivates SDF-1α and inhibits the invasion of GSLCs. We performed mass spectrometric analysis of cleavage products of SDF-1α after proteolysis by CatK. We demonstrated that CatK cleaves SDF-1α at 3 sites in the N-terminus, which is the region of SDF-1α that binds to its receptors. Confocal imaging of human GBM tissue sections confirmed co-localization of SDF-1α and CatK in GSLC niches. In accordance, 2D and 3D invasion experiments using CXCR4/CXCR7-expressing GSLCs and GBM cells showed that SDF-1α had chemotactic activity whereas CatK cleavage products of SDF-1α did not. Besides, CXCR4 inhibitor plerixafor inhibited invasion of CXCR4/CXCR7-expressing GSLCs. In conclusion, CatK can cleave and inactivate SDF-1α. This implies that CatK activity facilitates migration of GSLCs out of niches. We propose that activation of CatK may be a promising strategy to prevent homing of GSLCs in niches and thus render these cells sensitive to chemotherapy and radiation.

  15. Clinicopathological pattern of brain tumors: A 3-year study in a tertiary care hospital in India

    Directory of Open Access Journals (Sweden)

    Sajeeb Mondal

    2016-01-01

    Full Text Available Background: Brain tumors are heterogeneous group of neoplasms, affecting different age groups. Although some studies have been published regarding pathological pattern of brain tumors from different countries of the world and also from India, comprehensive clinicopathological studies from Eastern India is lacking. Aims: The aim of this study was to observe recent incidence of different brain tumors and to study clinical and histopathological spectrum of brain tumors in Eastern India. Materials and Methods: The present study was a cross-sectional observational study involving 130 cases of brain tumors which were diagnosed during the 3-year study period (January 2010–December 2012. Data regarding clinical presentation and radiological features of all cases were collected from all patients. Histopathological diagnosis was correlated with clinical and radiological diagnosis. Results: We found 130 cases of brain tumor with a male preponderance. The cases were distributed in a wide age range from 4 years to 78 years with the mean age of 42.38 years. Most common tumor type in our study was neuroepithelial tumor (92 cases, 70.76%. Among the neuroepithelial tumors, most frequent subtype was astrocytic tumor (54 cases, 41.5%. The second most frequent brain tumor was meningioma (20 cases, 15.3%. We found higher incidence of oligodendroglial tumor (8.46% and medulloblastoma (7.69% in our series. Conclusion: Males are more predispose to brain tumors in comparison to females. Astrocytic tumors are most common subtype in Eastern India. However, the WHO Grade I neoplasms are more frequent brain tumors.

  16. 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%.

  17. 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).

  18. 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 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.

  19. Permeability of PEGylated Immunoarsonoliposomes Through In Vitro Blood Brain Barrier-Medulloblastoma Co-culture Models for Brain Tumor Therapy

    NARCIS (Netherlands)

    Al-Shehri, A.; Favretto, M.E.; Ioannou, P.V.; Romero, I.A.; Couraud, P.O.; Weksler, B.B.; Parker, T.L.; Kallinteri, P.

    2015-01-01

    PURPOSE: Owing to restricted access of pharmacological agents into the brain due to blood brain barrier (BBB) there is a need: 1. to develop a more representative 3-D-co-culture model of tumor-BBB interaction to investigate drug and nanoparticle transport into the brain for diagnostic and therapeuti

  20. FoxM1 Drives a Feed-forward STAT3-activation Signaling Loop that Promotes the Self-renewal and Tumorigenicity of Glioblastoma Stem-like Cells

    Science.gov (United States)

    Gong, Ai-hua; Wei, Ping; Zhang, Sicong; Yao, Jun; Yuan, Ying; Zhou, Ai-dong; Lang, Frederick F.; Heimberger, Amy B.; Rao, Ganesh; Huang, Suyun

    2015-01-01

    The growth factor PDGF controls the development of glioblastoma (GBM) but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database TCGA revealed that GBM express higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells. PMID:25832656

  1. 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

  2. Comparative expression study of the endo-G protein coupled receptor (GPCR repertoire in human glioblastoma cancer stem-like cells, U87-MG cells and non malignant cells of neural origin unveils new potential therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Marie Fève

    Full Text Available Glioblastomas (GBMs are highly aggressive, invasive brain tumors with bad prognosis and unmet medical need. These tumors are heterogeneous being constituted by a variety of cells in different states of differentiation. Among these, cells endowed with stem properties, tumor initiating/propagating properties and particularly resistant to chemo- and radiotherapies are designed as the real culprits for tumor maintenance and relapse after treatment. These cells, termed cancer stem-like cells, have been designed as prominent targets for new and more efficient cancer therapies. G-protein coupled receptors (GPCRs, a family of membrane receptors, play a prominent role in cell signaling, cell communication and crosstalk with the microenvironment. Their role in cancer has been highlighted but remains largely unexplored. Here, we report a descriptive study of the differential expression of the endo-GPCR repertoire in human glioblastoma cancer stem-like cells (GSCs, U-87 MG cells, human astrocytes and fetal neural stem cells (f-NSCs. The endo-GPCR transcriptome has been studied using Taqman Low Density Arrays. Of the 356 GPCRs investigated, 138 were retained for comparative studies between the different cell types. At the transcriptomic level, eight GPCRs were specifically expressed/overexpressed in GSCs. Seventeen GPCRs appeared specifically expressed in cells with stem properties (GSCs and f-NSCs. Results of GPCR expression at the protein level using mass spectrometry and proteomic analysis are also presented. The comparative GPCR expression study presented here gives clues for new pathways specifically used by GSCs and unveils novel potential therapeutic targets.

  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. Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications

    Science.gov (United States)

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

    2016-12-01

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

  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. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

    Science.gov (United States)

    Takaya, Akari; Hirohashi, Yoshihiko; Murai, Aiko; Morita, Rena; Saijo, Hiroshi; Yamamoto, Eri; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Tamura, Yasuaki; Takemasa, Ichiro; Kondo, Toru; Sato, Noriyuki; Torigoe, Toshihiko

    2016-01-01

    Human cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be isolated as side population (SP) cells, aldehyde dehydrogenase high (ALDHhigh) cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP) cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-18

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells.

    Science.gov (United States)

    Castro-Vega, Luis Jaime; Jouravleva, Karina; Ortiz-Montero, Paola; Liu, Win-Yan; Galeano, Jorge Luis; Romero, Martha; Popova, Tatiana; Bacchetti, Silvia; Vernot, Jean Paul; Londoño-Vallejo, Arturo

    2015-10-01

    There is a well-established association between aging and the onset of metastasis. Although the mechanisms through which age impinges upon the malignant phenotype remain uncharacterized, the role of a senescent microenvironment has been emphasized. We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state.

  10. 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

  11. Notch4+ cancer stem-like cells promote the metastatic and invasive ability of melanoma.

    Science.gov (United States)

    Lin, Xian; Sun, Baocun; Zhu, Dongwang; Zhao, Xiulan; Sun, Ran; Zhang, Yanhui; Zhang, Danfang; Dong, Xueyi; Gu, Qiang; Li, Yanlei; Liu, Fang

    2016-08-01

    Sphere formation in conditioned serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor (tumorospheres) is considered useful for the enrichment of cancer stem-like cells, also known as tumor-initiating cells. We used a gene expression microarray to investigate the gene expression profile of melanoma cancer stem-like cells (MCSLCs). The results showed that MCSLCs highly expressed the following Notch signaling pathway molecules: Notch3 (NM_008716), Notch4 (NM_010929), Dtx4 (NM_172442), and JAG2 (NM_010588). Immunofluorescence staining showed tumorosphere cells highly expressed Notch4. Notch4(high) B16F10 cells were isolated by FACS, and Western blotting showed that high Notch4 expression is related to the expression of epithelial-mesenchymal transition (EMT)-associated proteins. Reduced invasive and migratory properties concomitant with the downregulation of the EMT markers Twist1, vimentin, and VE-cadherin and the overexpression of E-cadherin was observed in human melanoma A375 and MUM-2B cells. In these cells, Notch4 was also downregulated, both by Notch4 gene knockdown and by application of the γ-secretase inhibitor, DAPT. Mechanistically, the re-overexpression of Twist1 by the transfection of cells with a Twist1 expression plasmid led to an increase in VE-cadherin expression and a decrease in E-cadherin expression. Immunohistochemical analysis of 120 human melanoma tissues revealed a significant correlation between the high expression of Notch4 and the metastasis of melanoma. Taken together, our findings indicate that Notch4+ MCSLCs trigger EMT and promote the metastasis of melanoma cells.

  12. Identification of T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens.

    Science.gov (United States)

    Rapp, Carmen; Warta, Rolf; Stamova, Slava; Nowrouzi, Ali; Geisenberger, Christoph; Gal, Zoltan; Roesch, Saskia; Dettling, Steffen; Juenger, Simone; Bucur, Mariana; Jungk, Christine; DaoTrong, Philip; Ahmadi, Rezvan; Sahm, Felix; Reuss, David; Fermi, Valentina; Herpel, Esther; Eckstein, Volker; Grabe, Niels; Schramm, Christoph; Weigand, Markus A; Debus, Juergen; von Deimling, Andreas; Unterberg, Andreas; Abdollahi, Amir; Beckhove, Philipp; Herold-Mende, Christel

    2017-03-22

    Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay. Altogether, 713 proteins were identified by LC-ESI-MS/MS mass spectrometry. After a thorough filtering process, 32 proteins were chosen for further analyses. Immunogenicity of corresponding peptides was tested ex vivo. A considerable number of these antigens induced T cell responses in GBM patients but not in healthy donors. Moreover, most of them were overexpressed in primary GBM and also highly expressed in recurrent GBM tissues. Interestingly, expression of the most frequent T cell target antigens could also be confirmed in quiescent, slow-cycling GSCs isolated in high purity by the DEPArray technology. Finally, for a subset of these T cell target antigens, an association between expression levels and higher T cell infiltration as well as an increased expression of positive immune modulators was observed. In summary, we identified novel immunogenic proteins, which frequently induce tumor-specific T cell responses in GBM patients and were also detected in vitro in therapy-resistant quiescent, slow-cycling GSCs. Stable expression of these T cell targets in primary and recurrent GBM support their suitability for future clinical use.

  13. Implementing Tumor Detection and Area Calculation in Mri Image of Human Brain Using Image Processing Techniques

    Directory of Open Access Journals (Sweden)

    Sunil L. Bangare

    2015-04-01

    Full Text Available This paper is based on the research on Human Brain Tumor which uses the MRI imaging technique to capture the image. In this proposed work Brain Tumor area is calculated to define the Stage or level of seriousness of the tumor. Image Processing techniques are used for the brain tumor area calculation and Neural Network algorithms for the tumor position calculation. Also in the further advancement the classification of the tumor based on few parameters is also expected. Proposed work is divided in to following Modules: Module 1: Image Pre-Processing Module 2: Feature Extraction, Segmentation using K-Means Algorithm and Fuzzy C-Means Algorithm Module 3: Tumor Area calculation & Stage detection Module 4: Classification and position calculation of tumor using Neural Network

  14. 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...

  15. Brain tumor segmentation based on a hybrid clustering technique

    Directory of Open Access Journals (Sweden)

    Eman Abdel-Maksoud

    2015-03-01

    This paper presents an efficient image segmentation approach using K-means clustering technique integrated with Fuzzy C-means algorithm. It is followed by thresholding and level set segmentation stages to provide an accurate brain tumor detection. The proposed technique can get benefits of the K-means clustering for image segmentation in the aspects of minimal computation time. In addition, it can get advantages of the Fuzzy C-means in the aspects of accuracy. The performance of the proposed image segmentation approach was evaluated by comparing it with some state of the art segmentation algorithms in case of accuracy, processing time, and performance. The accuracy was evaluated by comparing the results with the ground truth of each processed image. The experimental results clarify the effectiveness of our proposed approach to deal with a higher number of segmentation problems via improving the segmentation quality and accuracy in minimal execution time.

  16. Isolated angiitis in the hypothalamus mimicking brain tumor.

    Science.gov (United States)

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

    2008-01-01

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

  17. Isolation and characterization of cancer stem-like cells from MHCC97H Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Shanyong Yi; Kejun Nan; Aihua Yuan; Chuangxin Lu

    2009-01-01

    Objective:To identify and isolate CD133 positive cancer stem-like cells (CD133+ cells) from the highly invasive human hepatocellular carcinoma cell line(MHCC97H), and examine their potential for clonogenicity and tumorigenicity. Methods: CD133+ and CD133- cells were isolated from MHCC97H cell line by magnetic bead cell sorting(MACS), and the potentials of CD133+ cells for colony formation and tumorigenicity were evaluated by soft agar cloning and tumor formation following nude mice inoculation. Results:CD133+ cells represent a minority(0.5-2.0%) of the tumor cell population with a greater colony-forming efficiency and greater tumor production ability. The colony-forming efficiency of CD133+ cells in soft agar was significantly higher than CD133- cells(36.8±1.4 vs 12.9±0.8, P<0.05).After 6 weeks, 3/5 mice inoculated with 1 × 103 CD133+ cells, 4/5 with 1 × 104 CD133+ cells and 5/5 with 1 × 105 CD133+ cells developed detectable tumors at the injection site, while only one tumor was found in mice treated with same numbers of CD133- cells. Conclusion: CD133 may be a hallmark of liver cancer stem cells (CSC) in human hepatocellular carcinoma(HCC), because the CD133+ cells identified and isolated with anti-CD133 labeled magnetic beads from MHCC97H cell line exhibit high potentials for clonogenicity and tumorigenicity. These CD133+ cells might contribute to hepatocarcinogenesis, as well as the growth and recurrence of human HCC, and therefore may be a useful target for anti-cancer therapy.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 – 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year’s meeting, which will be held at the Mayo Clinic at Rochester, MN, USA. PMID:25518914

  20. 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

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

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...... by TNFR1 deficiency. Overall, these results suggest that TNFR1 is involved in the early establishment of the inflammatory response and that its deficiency causes a decreased inflammatory response and tissue damage following brain injury....

  2. 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...

  3. 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.

  4. Navigation-guided endoscopic biopsy for intraparenchymal brain tumor.

    Science.gov (United States)

    Tsuda, Kyoji; Ishikawa, Eiichi; Zaboronok, Alexander; Nakai, Kei; Yamamoto, Tetsuya; Sakamoto, Noriaki; Uemae, Yoji; Tsurubuchi, Takao; Akutsu, Hiroyoshi; Ihara, Satoshi; Ayuzawa, Satoshi; Takano, Shingo; Matsumura, Akira

    2011-01-01

    To evaluate the efficacy of intraparenchymal brain tumor biopsy using endoscopy and a navigation system (navigation-guided endoscopic biopsy) as a diagnostic tool, a case series of intraparenchymal tumor biopsies was reviewed. Navigation-guided endoscopic biopsy was applied in 9 cases, stereotactic needle biopsy in 16 cases, and open biopsy with or without navigation system in 34 cases. In all biopsy cases, 84.7% of biopsy points were sampled accurately, and 93.2% of diagnoses by biopsy were correct. Comparison of each type of biopsy showed that the resected volumes in navigation-guided endoscopic biopsy and open biopsy tended to be larger than those in stereotactic biopsy, and the mean operation time for the open biopsy procedure was the longest. To define the most applicable device or examination method to increase sampling accuracy, various factors were analyzed in 59 procedures. Navigation-guided endoscopic biopsy was the most accurate of the three types of biopsy, although the statistical difference was not significant. Older patients, histological diagnosis of high-grade glioma or malignant lymphoma, positive photodynamic diagnosis, and positive intraoperative pathology were significant factors in improving the sampling accuracy. Navigation-guided endoscopic biopsy could provide a larger sample volume within a relatively short operation time. The biopsy can be easily combined with both photodynamic diagnosis and intraoperative pathology, significantly improving the histological diagnostic yield.

  5. (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....

  6. 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.

  7. A mathematical model to elucidate brain tumor abrogation by immunotherapy with T11 target structure.

    Directory of Open Access Journals (Sweden)

    Sandip Banerjee

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

  8. The establishment and initial application of emotional disorder database in brain tumor patients

    Directory of Open Access Journals (Sweden)

    Hong-bo ZHANG

    2015-09-01

    Full Text Available  Objective To establish database for brain tumor patients with mood disorders and to explore the status and epidemiological characteristics of emotional function. Methods By using computer software, establish database of brain tumor with affective disorder based on clinical requirements. Record the data of 140 cases of brain tumors undergoing operation treatment, so as to found perfect public data platform and realize resource sharing. Results The clinical data of 140 brain tumor patients were successfully filled in the registration query system. The database provides simple and complex mood data queries for users to browse. Conclusions The mood disorder database for patients with brain tumors can provide related data samples and resources for basic and clinical research. Besides, it can effectively share clinical research data and reduce research costs. DOI: 10.3969/j.issn.1672-6731.2015.09.010

  9. Generation of Novel Thyroid Cancer Stem-Like Cell Clones: Effects of Resveratrol and Valproic Acid.

    Science.gov (United States)

    Hardin, Heather; Yu, Xiao-Min; Harrison, April D; Larrain, Carolina; Zhang, Ranran; Chen, Jidong; Chen, Herbert; Lloyd, Ricardo V

    2016-06-01

    Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies.

  10. Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC.

    Science.gov (United States)

    Shi, Mu-mu; Xiong, Yan-lei; Jia, Xin-shan; Li, Xin; Zhang, Li; Li, Xiao-lei; Wang, En-Hua

    2013-06-01

    Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.

  11. Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells.

    Science.gov (United States)

    Giraud, Julie; Failla, Laura M; Pascussi, Jean-Marc; Lagerqvist, Ebba L; Ollier, Jérémy; Finetti, Pascal; Bertucci, François; Ya, Chu; Gasmi, Imène; Bourgaux, Jean-François; Prudhomme, Michel; Mazard, Thibault; Ait-Arsa, Imade; Houhou, Leila; Birnbaum, Daniel; Pélegrin, André; Vincent, Charles; Ryall, James G; Joubert, Dominique; Pannequin, Julie; Hollande, Frédéric

    2016-06-15

    Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in regulating CSC phenotype in advanced colorectal cancer. Progastrin expression and secretion were highly enriched in colon CSC isolated from human colorectal cancer cell lines and colon tumor biopsies. Progastrin expression promoted CSC self-renewal and survival, whereas its depletion by RNA interference-mediated or antibody-mediated strategies altered the homeostatic proportions of CSC cells within heterogeneous colorectal cancer tumors. Progastrin downregulation also decreased the frequency of ALDH(high) cells, impairing their tumor-initiating potential, and inhibited the high glycolytic activity of ALDH(high) CSC to limit their self-renewal capability. Taken together, our results show how colorectal CSC maintain their tumor-initiating and self-renewal capabilities by secreting progastrin, thereby contributing to the tumor microenvironment to support malignancy. Cancer Res; 76(12); 3618-28. ©2016 AACR.

  12. 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.)

  13. 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...

  14. 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.

  15. 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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Human primary brain tumor cell growth inhibition in serum-free medium optimized for neuron survival.

    Science.gov (United States)

    Brewer, Gregory J; LeRoux, Peter D

    2007-07-09

    Glioblastoma is the most common primary brain tumor in adults from which about 15,000 patients die each year in the United States. Despite aggressive surgery, radiotherapy and chemotherapy, median survival remains only 1 year. Here we evaluate growth of primary human brain tumor cells in a defined nutrient culture medium (Neuregen) that was optimized for neuron regeneration. We hypothesized that Neuregen would inhibit tumor cell growth because of its ability to inhibit gliosis in rat brain. Tumor tissue was collected from 18 patients including 10 males and 8 females (mean age 60+/-12 years) who underwent craniotomy for newly diagnosed, histologically confirmed brain tumors. The tissue was shipped overnight in Hibernate transport medium. Tumor cells were isolated and plated in Neurobasal/serum or Neuregen on culture plastic. After 1 week, growth in Neuregen was significantly less in 9/10 glioblastoma multiforme cases, 5/5 meningioma cases and 3/3 cases of brain metastasis. Analysis of deficient formulations of Neuregen and formulations to which selected components were added back implicate no single active component. However, individual cases were sensitive to corticosterone, selenium, ethanolamine, fatty acids and/or antioxidants. Therefore, a defined culture medium that promotes neuron regeneration inhibits the growth of human primary glioblastoma, meningioma and metastatic tumor cells in culture. The possible in vivo efficacy of Neuregen for treatment of brain tumor resections remains to be determined.

  20. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

  3. Cerebral infarction mimicking brain tumor on Tc-99m tetrofosmin brain SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soon [College of Medicine, Dongguk Univ., Gyeongju (Korea, Republic of); Zeon, Seok Kil; Won, Kyoung Sook [School of Medicine, Keimyung Univ., Daegu (Korea, Republic of)

    2004-06-01

    A 43-year-old man was presented with persistent headache for two weeks. T2 weighted MR imaging showed high signal intensity with surrounding edema in the left frontal lobe. These findings were considered with intracranial tumor such as glioma or metastasis. Tc-99m tetrofosmin SPECT showed focal radiotracer accumulation in the left frontal lobe. The operative specimen contained cerebral infarction with organizing leptomeningeal hematoma by pathologist. Another 73-year-old man was hospitalized for chronic headache. Initial CT showed ill-defined hypodensity with mass effect in the right parietal lobe. Tc-99m tetrofosmin SPECT showed focal radiotracer uptake in the right parietal lobe. These findings were considered with low-grade glioma or infarction. Follow-up CT after 5 months showed slightly decreased in size of low density in the right parietal lobe, and cerebral infarction is more likely than others. Tc-99m tetrofosmin has been proposed as a cardiotracer of myocardial perfusion imaging and an oncotropic radiotracer. Tc-99 tetrofosmin SPECT image provides a better attractive alternative agent than TI-201 as a tumor-imaging agent, with characteristics such as high-energy flux, short half-life, favorable biodistribution, dosimetry and lower background radioactivity. We have keep in mind on the analysis of Tc-99m tetrofosmin imaging when cerebral infarction is being differentiated from brain tumor.

  4. 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

  5. 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.

  6. Objective evaluation of fourth ventricle displacement in brain CT findings. 4 cases of brain stem tumor

    Energy Technology Data Exchange (ETDEWEB)

    Okino, Fumiko; Eguchi, Tsuyako; Shinohara, Teruo; Hatano, Mitsunori (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1983-11-01

    Distance between the ridge of the sella turcica and the anterior wall of the fourth ventricle (a) and the distance between the ridge of the sella and the posterior pole in the occipital region (b) were measured on the slice visualizing the fourth ventricle and sella. The location of the fourth ventricle was expressed by a/b, and its normal value was calculated for comparison with that in a patient group. The a/b values of the control group were in the range of 0.33 and 0.48 with a mean +- SD of 0.41+-0.3 and was not subject to the influences of age, sex distinction, cranial shape or slicing direction. The a/b values of the patient group were all abnormal (more than mean +- 2SD of the control group) on initial CT and showed an increase with progress of the disease activity. Measurement of the a/b on brain CT was thought to serve as a useful indicator for early detection and follow-up of the course of lesions occupying the brain stem (especially brain stem tumors).

  7. Nanoparticle-Mediated Photothermal Therapy of Brain Tumors

    Science.gov (United States)

    Makkouk, Amani R.; Madsen, Steen J.

    Nanoparticles (10-1,000 nm diameter) have been investigated for use in numerous diagnostic and therapeutic applications. Gold nanoparticles are particularly appealing due to their biological inertness and the ability to conjugate a wide variety of ligands to their surface. Additionally, their optical properties can be tuned through variations of their size, shape, and composition. For example, gold-silica nanoshells, consisting of a spherical dielectric silica core (100-120 nm diameter) surrounded by a 10-20 nm gold shell, have a strong resonant absorption at approximately 800 nm where light has significant penetration in biological tissues. Following light absorption, surface electrons are photoexcited and the resultant heated electron gas is dissipated to the surrounding medium causing thermal damage. The ability of nanoparticles to convert optical energy to thermal energy makes them ideally suited for photothermal therapy (PTT). This review focuses on the utility of gold-silica nanoshells in PTT of brain tumors. PTT has proven effective in a number of in vitro and in vivo studies. Of particular clinical relevance are results demonstrating PTT efficacy in an orthotopic canine model.

  8. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Origins and clinical implications of the brain tumor stem cell hypothesis

    OpenAIRE

    2009-01-01

    With the advent of the cancer stem cell hypothesis, the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of “brain tumor stem cells” has offered an explanation for several long-standing conundrums on why brain tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of malignant gliomas, the prognosis of brain tumors remains dismal. The slow progre...

  11. Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells.

    Science.gov (United States)

    Shen, Dong; Guo, Cheng-Cheng; Wang, Jing; Qiu, Zhi-Kun; Sai, Ke; Yang, Qun-Ying; Chen, Yin-Sheng; Chen, Fu-Rong; Wang, Jie; Panasci, Lawrence; Chen, Zhong-Ping

    2015-11-01

    Glioma is one of the most common primary tumors of the central nervous system in adults. Glioblastoma (GBM) is the most lethal type of glioma, whose 5-year survival is 9.8% at best. Glioma stem-like cells (GSCs) play an important role in recurrence and treatment resistance. MGMT is a DNA repair protein that removes DNA adducts and therefore attenuates treatment efficiency. It has been reported that interferon-α/β (IFN-α/β) downregulates the level of MGMT and sensitizes glioma cells to temozolomide. In the present study, we assessed whether IFN-α/β is able to sensitize GSCs to temozolomide by modulating MGMT expression. Upon the treatment of IFN-α/β, the efficacy of temozolomide against MGMT‑positive GSCs was markedly enhanced by combination treatment with IFN-α/β when compared with the temozolomide single agent group, and MGMT expression was markedly decreased at the same time. Further mechanistic study showed that IFN-α/β suppressed the NF-κB activity, which further mediated the sensitization of MGMT‑positive GSCs to temozolomide. Our data therefore demonstrated that the application of IFN-α/β is a promising agent with which to enhance temozolomide efficiency and reduce drug resistance, and our findings shed light on improving clinical outcomes and prolonging the survival of patients with malignant gliomas.

  12. Accumulation efficiency of cancer stem-like cells post {gamma}-ray and proton irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Quan Yi; WangWeikang; Fu Qibin; Mei Tao; Wu Jingwen; Li Jia [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Yang, Gen, E-mail: gen.yang@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Wang Yugang [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China)

    2012-09-01

    Ionizing radiation (IR) has been proven to be a powerful medical treatment in cancer therapy. Rational and effective use of its killing power depends on understanding IR-mediated responses at the molecular, cellular and tissue levels. Increasing evidence supports that cancer stem-like cells (CSCs) play an important role in tumor regrowth and spread post radiotherapy, for they are resistant to various therapy methods including radiation. Presently, SW620 colon carcinoma monolayer culture cells were irradiated with {gamma}-rays and protons of 2 Gy. Then apoptosis, clonogenic survival and the expression of CD133{sup +} protein were examined. The results showed that there was no significantly difference either on long-term clonogenic survival or on short-term apoptosis ratio. However, compared with {gamma}-rays, irradiation with protons was less efficient to accumulate CSCs at the same dose, although both protons and {gamma}-rays can significantly accumulate the CD133{sup +} CSCs subpopulation. In addition, the results of sphere formation assay also confirmed that proton irradiation is less efficient in CSCs accumulation, suggesting proton irradiation might have higher efficiency in CSCs elimination for cancer radiotherapy.

  13. mir-300 promotes self-renewal and inhibits the differentiation of glioma stem-like cells

    KAUST Repository

    Zhang, Daming

    2014-01-28

    MicroRNAs (miRNAs) are small noncoding RNAs that have been critically implicated in several human cancers. miRNAs are thought to participate in various biological processes, including proliferation, cell cycle, apoptosis, and even the regulation of the stemness properties of cancer stem cells. In this study, we explore the potential role of miR-300 in glioma stem-like cells (GSLCs). We isolated GSLCs from glioma biopsy specimens and identified the stemness properties of the cells through neurosphere formation assays, multilineage differentiation ability analysis, and immunofluorescence analysis of glioma stem cell markers. We found that miR-300 is commonly upregulated in glioma tissues, and the expression of miR-300 was higher in GSLCs. The results of functional experiments demonstrated that miR-300 can enhance the self-renewal of GSLCs and reduce differentiation toward both astrocyte and neural fates. In addition, LZTS2 is a direct target of miR-300. In conclusion, our results demonstrate the critical role of miR-300 in GSLCs and its functions in LZTS2 inhibition and describe a new approach for the molecular regulation of tumor stem cells. © 2014 Springer Science+Business Media.

  14. 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

  15. 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

  16. 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.

  17. Clinical Application of {sup 18}F-FDG PET in Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Il Ki [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2008-12-15

    Primary brain tumor accounts for 1.4% of entire cancer. For males between the ages of 15 and 34 years, central nervous system tumors account for the leading cause of cancer death. 18F-FDG PET has been reported that it can provide important diagnostic information relating to tumor grading and differentiation from non- tumorous condition. In addition, the degree of FDG metabolism carries prognostic significance. By mapping the metabolic pattern of heterogeneous tumors, 18F-FDG PET can aid in targeting for stereotactic biopsy by selecting the subregions within the tumor that are most hypermetabolic and potentially have the highest grade. According to clinical research data, FDG PET is expected to be a helpful diagnostic tool in the management of brain tumors.

  18. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells

    Science.gov (United States)

    Liu, P; Brown, S; Goktug, T; Channathodiyil, P; Kannappan, V; Hugnot, J-P; Guichet, P-O; Bian, X; Armesilla, A L; Darling, J L; Wang, W

    2012-01-01

    Background: Glioblastoma multiforme (GBM) cells are resistant to anticancer drugs. Cancer stem cells (CSCs) are a key mediator of chemoresistance. We have reported that disulfiram (DS), an aldehyde dehydrogenase (ALDH) inhibitor, targets breast CSC-like cells. In this study, the effect of DS and combination of DS and gemcitabine (dFdC) on GBM cells and GBM stem-like cells was investigated. Methods: 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)-isobologram, western blot, luciferase reporter gene assay, electrophoretic mobility-shift assay and ALDH analysis were used in this study. Results: Disulfiram is cytotoxic in GBM cell lines in a copper (Cu)-dependent manner. Disulfiram/copper enhances the cytotoxicity of dFdC. Combination index-isobologram analysis indicates a synergistic effect between DS/Cu and dFdC. Disulfiram/copper induces reactive oxygen species (ROS), activates JNK and p38 pathways and inhibits nuclear factor-kappa B activity in GBM cell lines. Disulfiram/copper may trigger intrinsic apoptotic pathway via modulation of the Bcl2 family. Disulfiram/copper abolishes stem-like cell population in GBM cell lines. Conclusion: Our findings indicate that the cytotoxicity of DS/Cu and the enhancing effect of DS/Cu on the cytotoxicity of dFdC in GBM stem-like cells may be caused by induction of ROS and inhibition of both ALDH and the NFkB pathway. Both DS and dFdC can traverse the blood–brain barrier. Further study may lead them into GBM chemotherapy. PMID:23033007

  1. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Martins-Neves Sara R

    2012-04-01

    Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

  2. 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

    invasion and tumor stemness into account. METHODS: 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......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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  5. 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......), since infectious agents may pose a risk factor and a proposed mechanism is transferral of infectious agents from animals to humans....

  6. p21-activated kinase 1 determines stem-like phenotype and sunitinib resistance via NF-κB/IL-6 activation in renal cell carcinoma.

    Science.gov (United States)

    Zhu, Y; Liu, H; Xu, L; An, H; Liu, W; Liu, Y; Lin, Z; Xu, J

    2015-02-12

    The p21-activated kinase 1 (PAK1), a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility, has been shown to function as downstream node for various oncogenic signaling pathways to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, resulting in tumor formation and invasiveness. Although alterations in PAK1 expression and activity have been detected in various human malignancies, its potential biological and clinical significance in renal cell carcinoma (RCC) remains obscure. In this study, we found increased PAK1 and phosphorylated PAK1 levels in tumor tissues according to TNM stage progression. Elevated phosphorylated PAK1 levels associated with progressive features and indicated unfavorable overall survival (OS) as an independent adverse prognosticator for patients with RCC. Moreover, PAK1 kinase activation with constitutive active PAK1 mutant T423E promoted growth, colony formation, migration, invasion and stem-like phenotype of RCC cells, and vice versa, in PAK1 inhibition by PAK1 kinase inactivation with specific PAK1 shRNA, dead kinase PAK1 mutant K299R or allosteric inhibitor IPA3. Stem-like phenotype due to sunitinib administration via increased PAK1 kinase activation could be ameliorated by PAK1 shRNA, PAK1 mutant K299R and IPA3. Furthermore, nuclear factor-κB (NF-κB)/interleukin-6 (IL-6) activation was found to be responsible for PAK1-mediated stem-like phenotype following sunitinib treatment. Both IL-6 neutralizing antibody and IPA3 administration enhanced tumor growth inhibition effect of sunitinib treatment on RCC cells in vitro and in vivo. Our results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-κB/IL-6 activation in RCC, lending PAK1-mediated NF-κB/IL-6 activation considerable appeal as novel pharmacological therapeutic targets against sunitinib resistance.

  7. Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair.

    Science.gov (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann-Tzyy; Hsu, Shan-Hui

    2016-09-01

    Cell- and gene-based therapies have emerged as promising strategies for treating neurological diseases. The sources of neural stem cells are limited while the induced pluripotent stem (iPS) cells have risk of tumor formation. Here, we proposed the generation of self-renewable, multipotent, and neural lineage-related neural crest stem-like cells by chitosan substrate-mediated gene transfer of a single factor forkhead box D3 (FOXD3) for the use in neural repair. A simple, non-toxic, substrate-mediated method was applied to deliver the naked FOXD3 plasmid into human fibroblasts. The transfection of FOXD3 increased cell proliferation and up-regulated the neural crest marker genes (FOXD3, SOX2, and CD271), stemness marker genes (OCT4, NANOG, and SOX2), and neural lineage-related genes (Nestin, β-tubulin and GFAP). The expression levels of stemness marker genes and neural crest maker genes in the FOXD3-transfected fibroblasts were maintained until the fifth passage. The FOXD3 reprogrammed fibroblasts based on the new method significantly rescued the neural function of the impaired zebrafish. The chitosan substrate-mediated delivery of naked plasmid showed feasibility in reprogramming somatic cells. Particularly, the FOXD3 reprogrammed fibroblasts hold promise as an easily accessible cellular source with neural crest stem-like behavior for treating neural diseases in the future.

  8. 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.

  9. 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.

  10. The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yu-Ling Lin

    2013-01-01

    Full Text Available Glioblastoma multiforme (GBM is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

  11. 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.

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

    NARCIS (Netherlands)

    Graaf, N. de; Hew, J.M.; Fock, J.M.; Kamps, W.A.; Graaf, S.S.N. de

    2002-01-01

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

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

    NARCIS (Netherlands)

    Hew, JM; Fock, JM; Kamps, WA

    2002-01-01

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

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

    Science.gov (United States)

    Kashyap, Dheerendra; Sharma, Vikrant; Liu, Hanli

    2007-02-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

  16. Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells.

    Directory of Open Access Journals (Sweden)

    Raquel Ordóñez

    Full Text Available Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC, a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture. Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-β and contribute to CSC phenotype. We focused on the aberrant activation of TGF-β and Hh signalling pathways, confirming the inhibition of repressors of TGF-β pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells.

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

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

    2010-08-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jinwei Hu

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-12-01

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

  2. A Distinct Slow-Cycling Cancer Stem-like Subpopulation of Pancreatic Adenocarcinoma Cells is maintained in Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Dembinski, Jennifer L., E-mail: jennifer.dembinski@rr-research.no; Krauss, Stefan [Cellular and Genetic Therapy, Department of Microbiology, Cancer Stem Cell Innovation Center (CAST), Oslo University Hospital, Rikshospitalet, Oslo (Norway)

    2010-11-29

    Pancreatic adenocarcinoma has the worst prognosis of any major malignancy, with <5% of patients surviving five years. This can be contributed to the often late diagnosis, lack of sufficient treatment and metastatic spread. Heterogeneity within tumors is increasingly becoming a focus in cancer research, as novel therapies are required to target the most aggressive subpopulations of cells that are frequently termed cancer stem cells (CSCs). In the current study, we describe the identification of a slow-cycling cancer stem-like population of cells in vivo in BxPC-3 and Panc03.27 xenografts. A distinct slow-cycling label-retaining population of cells (DiI+/SCC) was found both at the edge of tumors, and in small circumscribed areas within the tumors. DiI+/SCC in these areas display an epithelial-to-mesenchymal transition (EMT) fingerprint, including an upregulation of the mesenchymal markers vimentin and N-cadherin and a loss of the epithelial marker E-cadherin. DiI+/SCC also displayed a critical re-localization of beta-catenin from the membrane to the nucleus. Additionally, the DiI+/SCC population was found to express the developmental signaling molecule sonic hedgehog. This study represents a novel step in defining the biological activities of a tumorigenic subpopulation within the heterogeneous tumor microenvironment in vivo. Understanding the interactions and functions of a CSC population within the context of the tumor microenvironment is critical to design targeted therapeutics.

  3. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy

    Science.gov (United States)

    Ji, Minbiao; Orringer, Daniel A.; Freudiger, Christian W.; Ramkissoon, Shakti; Liu, Xiaohui; Lau, Darryl; Golby, Alexandra J.; Norton, Isaiah; Hayashi, Marika; Agar, Nathalie Y.R.; Young, Geoffrey S.; Spino, Cathie; Santagata, Sandro; Camelo-Piragua, Sandra; Ligon, Keith L.; Sagher, Oren; Xie, X. Sunney

    2013-01-01

    Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. Here we describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from non-neoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and H&E microscopy for detection of glioma infiltration (κ=0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct. PMID:24005159

  4. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI).

    Science.gov (United States)

    Panigrahy, Ashok; Blüml, Stefan

    2009-11-01

    In this review, the basic magnetic resonance concepts used in the imaging approach of a pediatric brain tumor are described with respect to different factors including understanding the significance of the patient's age. Also discussed are other factors directly related to the magnetic resonance scan itself including evaluating the location of the tumor, determining if the lesion is extra-axial or intra-axial, and evaluating the contrast characteristics of the lesion. Of note, there are key imaging features of pediatric brain tumors, which can give information about the cellularity of the lesion, which can then be confirmed with advanced magnetic resonance imaging (MRI) techniques. The second part of this review will provide an overview of the major advanced MRI techniques used in pediatric imaging, particularly, magnetic resonance diffusion, magnetic resonance spectroscopy, and magnetic resonance perfusion. The last part of the review will provide more specific information about the use of advanced magnetic resonance techniques in the evaluation of pediatric brain tumors.

  5. Level set method with automatic selective local statistics for brain tumor segmentation in MR images.

    Science.gov (United States)

    Thapaliya, Kiran; Pyun, Jae-Young; Park, Chun-Su; Kwon, Goo-Rak

    2013-01-01

    The level set approach is a powerful tool for segmenting images. This paper proposes a method for segmenting brain tumor images from MR images. A new signed pressure function (SPF) that can efficiently stop the contours at weak or blurred edges is introduced. The local statistics of the different objects present in the MR images were calculated. Using local statistics, the tumor objects were identified among different objects. In this level set method, the calculation of the parameters is a challenging task. The calculations of different parameters for different types of images were automatic. The basic thresholding value was updated and adjusted automatically for different MR images. This thresholding value was used to calculate the different parameters in the proposed algorithm. The proposed algorithm was tested on the magnetic resonance images of the brain for tumor segmentation and its performance was evaluated visually and quantitatively. Numerical experiments on some brain tumor images highlighted the efficiency and robustness of this method.

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

    Science.gov (United States)

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

    2013-09-01

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

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

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

    2013-03-01

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

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

    Science.gov (United States)

    Vincent, S; DePace, D; Finkelstein, S

    1988-02-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

  10. Quantitative Apparent Diffusion Coefficients in the Characterization of Brain Tumors and Associated Peritumoral Edema

    Energy Technology Data Exchange (ETDEWEB)

    Server, A.; Schellhorn, T.; Nakstad, P.H. (Dept. of Neuroradiology, Div. of Radiology, Ullevaal Univ. Hospital, Univ. of Oslo, Oslo (Norway)); Kulle, B. (Epi-Gen Faculty Div. Akershus Univ. Hospital and Dept. of Biostatistics, Univ. of Oslo, Oslo (Norway)); Maehlen, J.; Kumar, T. (Dept. of Pathology, Ullevaal Univ. Hospital, Univ. of Oslo, Oslo (Norway)); Josefsen, R. (Dept. of Neurosurgery, Ullevaal Univ. Hospital, Univ. of Oslo, Oslo (Norway)); Langberg, C.W. (Cancer Centre, Ullevaal Univ. Hospital, Univ. of Oslo, Oslo (Norway))

    2009-07-15

    Background: Conventional magnetic resonance (MR) imaging has a number of limitations in the diagnosis of the most common intracranial brain tumors, including tumor specification and the detection of tumoral infiltration in regions of peritumoral edema. Purpose: To prospectively assess if diffusion-weighted MR imaging (DWI) could be used to differentiate between different types of brain tumors and to distinguish between peritumoral infiltration in high-grade gliomas, lymphomas, and pure vasogenic edema in metastases and meningiomas. Material and Methods: MR imaging and DWI was performed on 93 patients with newly diagnosed brain tumors: 59 patients had histologically verified high-grade gliomas (37 glioblastomas multiforme, 22 anaplastic astrocytomas), 23 patients had metastatic brain tumors, five patients had primary cerebral lymphomas, and six patients had meningiomas. Apparent diffusion coefficient (ADC) values of tumor (enhancing regions or the solid portion of tumor) and peritumoral edema, and ADC ratios (ADC of tumor or peritumoral edema to ADC of contralateral white matter, ADC of tumor to ADC of peritumoral edema) were compared with the histologic diagnosis. ADC values and ratios of high-grade gliomas, primary cerebral lymphomas, metastases, and meningiomas were compared by using ANOVA and multiple comparisons. Optimal thresholds of ADC values and ADC ratios for distinguishing high-grade gliomas from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Statistically significant differences were found for minimum and mean of ADC tumor and ADC tumor ratio values between metastases and high-grade gliomas when including only one factor at a time. Including a combination of in total four parameters (mean ADC tumor, and minimum, maximum and mean ADC tumor ratio) resulted in sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 72.9, 82.6, 91.5, and 54.3% respectively. In the ROC curve analysis

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

    Science.gov (United States)

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-11-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

  12. 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.

  13. 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...

  14. 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

  15. Segmentation of Brain Tumors in MRI Images Using Three-Dimensional Active Contour without Edge

    Directory of Open Access Journals (Sweden)

    Ali M. Hasan

    2016-11-01

    Full Text Available Brain tumor segmentation in magnetic resonance imaging (MRI is considered a complex procedure because of the variability of tumor shapes and the complexity of determining the tumor location, size, and texture. Manual tumor segmentation is a time-consuming task highly prone to human error. Hence, this study proposes an automated method that can identify tumor slices and segment the tumor across all image slices in volumetric MRI brain scans. First, a set of algorithms in the pre-processing stage is used to clean and standardize the collected data. A modified gray-level co-occurrence matrix and Analysis of Variance (ANOVA are employed for feature extraction and feature selection, respectively. A multi-layer perceptron neural network is adopted as a classifier, and a bounding 3D-box-based genetic algorithm is used to identify the location of pathological tissues in the MRI slices. Finally, the 3D active contour without edge is applied to segment the brain tumors in volumetric MRI scans. The experimental dataset consists of 165 patient images collected from the MRI Unit of Al-Kadhimiya Teaching Hospital in Iraq. Results of the tumor segmentation achieved an accuracy of 89% ± 4.7% compared with manual processes.

  16. 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.

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

    Science.gov (United States)

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

    2004-11-01

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

  18. Diffusion tensor magnetic resonance imaging of glial brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri, E-mail: ferda@fnplzen. [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Kastner, Jan [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Mukensnabl, Petr [Sikl' s Institute of Pathological Anatomy, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Choc, Milan [Department of Neurosurgery, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic); Horemuzova, Jana; Ferdova, Eva; Kreuzberg, Boris [Department of Radiology, Charles University Hospital Plzen, Medical Faculty Plzen, Alej Svobody 80, 304 60 Plzen (Czech Republic)

    2010-06-15

    Aim: To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods: A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results: A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion: Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the

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

    Science.gov (United States)

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

    2005-04-01

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

  20. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

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

    Science.gov (United States)

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

    2011-03-01

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

  2. Intraoperative fluorescence imaging for personalized brain tumor resection: Current state and future directions

    Directory of Open Access Journals (Sweden)

    Evgenii Belykh

    2016-10-01

    Full Text Available Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical theranostics. In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients, as well as future applications of recent laboratory and translational studies.Methods: Review of the literature.Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-ALA and ICG, less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine can be used for rapid tumor detection and pathological tissue examination. Other emerging agents such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.Conclusion: We are standing on the doorstep of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  5. Application of 3{sup 1P} MR spectroscopy to the brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Dong Ho; Choi, Sun Seob; Oh, Jong Young; Yoon, Seong Kuk; Kang, Myong Jin; Kim, Ki Uk [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2013-06-15

    To evaluate the clinical feasibility and obtain useful parameters of 3{sup 1P} magnetic resonance spectroscopy (MRS) study for making the differential diagnosis of brain tumors. Twenty-eight patients with brain tumorous lesions (22 cases of brain tumor and 6 cases of abscess) and 11 normal volunteers were included. The patients were classified into the astrocytoma group, lymphoma group, metastasis group and the abscess group. We obtained the intracellular pH and the metabolite ratios of phosphomonoesters/phosophodiesters (PME/PDE), PME/inorganic phosphate (Pi), PDE/Pi, PME/adenosine triphosphate (ATP), PDE/ATP, PME/phosphocreatine (PCr), PDE/PCr, PCr/ATP, PCr/Pi, and ATP/Pi, and evaluated the statistical significances. The brain tumors had a tendency of alkalization (pH = 7.28 ± 0.27, p = 0.090), especially the pH of the lymphoma was significantly increased (pH = 7.45 ± 0.32, p = 0.013). The brain tumor group showed increased PME/PDE ratio compared with that in the normal control group (p 0.012). The ratios of PME/PDE, PDE/Pi, PME/PCr and PDE/PCr showed statistically significant differences between each brain lesion groups (p < 0.05). The astrocytoma showed an increased PME/PDE and PME/PCr ratio. The ratios of PDE/Pi, PME/PCr, and PDE/PCr in lymphoma group were lower than those in the control group and astrocytoma group. The metastasis group showed an increased PME/PDE ratio, compared with that in the normal control group. We have obtained the clinically applicable 3{sup 1}'P MRS, and the pH, PME/PDE, PDE/Pi, PME/PCr, and PDE/PCr ratios are helpful for differentiating among the different types of brain tumors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Serduc, Raphael; Christen, Thomas; Farion, Regine; Bouchet, Audrey; Sanden, Boudewijn van der; Segebarth, Christoph; Remy, Chantal; Barbier, Emmanuel L [INSERM, U836, F38043 Grenoble (France); Laissue, Jean [Institute of Pathology, University of Bern (Switzerland); Braeuer-Krisch, Elke; Duc, Geraldine Le; Bravin, Alberto [European Synchrotron Radiation Facility, F38043 Grenoble (France)], E-mail: serduc@esrf.fr

    2008-07-07

    The aim of this work focuses on the description of the short-term response of a 9L brain tumor model and its vasculature to microbeam radiation therapy (MRT) using magnetic resonance imaging (MRI). Rat 9L gliosarcomas implanted in nude mice brains were irradiated by MRT 13 days after tumor inoculation using two orthogonal arrays of equally spaced 28 planar microbeams (25 {mu}m width, 211 {mu}m spacing and dose 500 Gy). At 1, 7 and 14 days after MRT, apparent diffusion coefficient, blood volume and vessel size index were mapped by MRI. Mean survival time after tumor inoculation increased significantly between MRT-treated and untreated groups (23 and 28 days respectively, log-rank test, p < 0.0001). A significant increase of apparent diffusion coefficient was observed 24 h after MRT in irradiated tumors versus non-irradiated ones. In the untreated group, both tumor size and vessel size index increased significantly (from 7.6 {+-} 2.2 to 19.2 {+-} 4.0 mm{sup 2} and +23%, respectively) between the 14th and the 21st day after tumor cell inoculation. During the same period, in the MRT-treated group, no difference in tumor size was observed. The vessel size index measured in the MRT-treated group increased significantly (+26%) between 14 and 28 days of tumor growth. We did not observe the significant difference in blood volume between the MRT-treated and untreated groups. MRT slows 9L tumor growth in a mouse brain but MRI results suggest that the increase in survival time after our MRT approach may be rather due to a cytoreduction than to early direct effects of ionizing radiation on tumor vessels. These results suggest that MRT parameters need to be optimized to further damage tumor vessels.

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

    Science.gov (United States)

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

    2015-01-01

    The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy.

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

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    2015-07-01

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

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

    Science.gov (United States)

    Mao, Xiao-Yuan; Dai, Jin-Xiang; Zhou, Hong-Hao; Liu, Zhao-Qian; Jin, Wei-Lin

    2016-05-31

    Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9-mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors.

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

    Science.gov (United States)

    Whelan, H T; Clanton, J A; Wilson, R E; Tulipan, N B

    1988-01-01

    A canine gliosarcoma model was used to study the effectiveness of magnetic resonance imaging (MRI) with gadolinium contrast enhancement in defining the histologic margins of brain tumors. The effectiveness of this technique was compared to conventional computed tomography (CT) using iodinated contrast enhancement. Cultured canine gliosarcoma cells were injected into the left hemisphere of adult mongrel dogs. The dogs developed brain tumors and progressive clinical signs. Serial MRI with and without gadolinium diethylene triamine penta-acetic acid was compared to serial CT with and without sodium iothalamate obtained on the same days. After the final scans, animals were sacrificed; the brains were removed and processed for routine histopathologic study. All tumors were visualized with contrast-enhanced MRI which proved most sensitive. Gadolinium di-ethylene triamine penta-acetic acid caused bright enhancement of tumors in a distribution that consistently corresponded to areas of pathologically proved tumor infiltration. Gross and microscopic autopsy findings correlated better with MRI than with CT which tended to produce poorer resolution and underrepresent the size of viable tumor. Gadolinium-enhanced MRI is more accurate than unenhanced MRI, unenhanced CT, or enhanced CT in defining the histologic margins of tumors.

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

    Science.gov (United States)

    Mittal, Sandeep; Shah, Aashit K; Barkmeier, Daniel T; Loeb, Jeffrey A

    2013-12-01

    Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many "systems" in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both.

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

    Science.gov (United States)

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

    2007-02-01

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

  13. Detection of Brain Tumor and Extraction of Texture Features using Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    Prof. Dilip Kumar Gandhi

    2012-10-01

    Full Text Available Brain Cancer Detection system is designed. Aim of this paper is to locate the tumor and determine the texture features from a Brain Cancer affected MRI. A computer based diagnosis is performed in order to detect the tumors from given Magnetic Resonance Image. Basic image processing techniques are used to locate the tumor region. Basic techniques consist of image enhancement, image bianarization, and image morphological operations. Texture features are computed using the Gray Level Co-occurrence Matrix. Texture features consists of five distinct features. Selective features or the combination of selective features will be used in the future to determine the class of the query image. Astrocytoma type of Brain Cancer affected images are used only for simplicity

  14. Atlas to patient registration with brain tumor based on a mesh-free method.

    Science.gov (United States)

    Diaz, Idanis; Boulanger, Pierre

    2015-08-01

    Brain atlas to patient registration in the presence of tumors is a challenging task because its presence cause brain structure deformations and introduce large intensity variation between the affected areas. This large dissimilarity affects the results of traditional registration methods based on intensity or shape similarities. In order to overcome these problems, we propose a novel method that brings closer the atlas and the patient's image by simulating the mechanical behavior of brain deformation under a tumor pressure. The proposed method use a mesh-free total Lagrangian Explicit Dynamic algorithm for the simulation of atlas deformation and a data driven model of the tumor using multi-modal MRI segmentation. Experimental results look structurally very similar to the patient's image and outperform two of the top ranking algorithms.

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

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  16. Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.

    Directory of Open Access Journals (Sweden)

    Hyunsook An

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC; however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705. Furthermore, interleukin-6 (IL-6-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

  17. Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.

    Science.gov (United States)

    An, Hyunsook; Kim, Ji Young; Oh, Eunhye; Lee, Nahyun; Cho, Youngkwan; Seo, Jae Hong

    2015-01-01

    Triple-negative breast cancer (TNBC) is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC); however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705). Furthermore, interleukin-6 (IL-6)-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

  18. Myeloid-Derived Suppressor Cells Endow Stem-like Qualities to Breast Cancer Cells through IL6/STAT3 and NO/NOTCH Cross-talk Signaling.

    Science.gov (United States)

    Peng, Dongjun; Tanikawa, Takashi; Li, Wei; Zhao, Lili; Vatan, Linda; Szeliga, Wojciech; Wan, Shanshan; Wei, Shuang; Wang, Yin; Liu, Yan; Staroslawska, Elzbieta; Szubstarski, Franciszek; Rolinski, Jacek; Grywalska, Ewelina; Stanisławek, Andrzej; Polkowski, Wojciech; Kurylcio, Andrzej; Kleer, Celina; Chang, Alfred E; Wicha, Max; Sabel, Michael; Zou, Weiping; Kryczek, Ilona

    2016-06-01

    Myeloid-derived suppressor cells (MDSC) contribute to immune suppression in cancer, but the mechanisms through which they drive metastatic progression are not fully understood. In this study, we show how MDSC convey stem-like qualities to breast cancer cells that coordinately help enable immune suppression and escape. We found that MDSC promoted tumor formation by enhancing breast cancer cell stem-like properties as well as by suppressing T-cell activation. Mechanistic investigations indicated that these effects relied upon cross-talk between the STAT3 and NOTCH pathways in cancer cells, with MDSC inducing IL6-dependent phosphorylation of STAT3 and activating NOTCH through nitric oxide leading to prolonged STAT3 activation. In clinical specimens of breast cancer, the presence of MDSC correlated with the presence of cancer stem-like cells (CSC) and independently predicted poor survival outcomes. Collectively, our work revealed an immune-associated mechanism that extrinsically confers cancer cell stemness properties and affects patient outcome. We suggest that targeting STAT3-NOTCH cross-talk between MDSC and CSC could offer a unique locus to improve cancer treatment, by coordinately targeting a coupled mechanism that enables cancer stemness and immune escape. Cancer Res; 76(11); 3156-65. ©2016 AACR.

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

    Energy Technology Data Exchange (ETDEWEB)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. (Univ. of Mississippi Medical Center, Jackson (USA))

    1990-10-01

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

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

    Science.gov (United States)

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

    1990-10-01

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

  1. Association between FAS and FASL genetic variants and risk of primary brain tumor.

    Science.gov (United States)

    Dalan, Altay Burak; Timirci-Kahraman, Ozlem; Turan, Saime; Kafadar, Ali Metin; Yaylim, Ilhan; Ergen, Arzu; Gormus, Uzay; Gulec-Yilmaz, Seda; Kaspar, Cigdem; Isbir, Turgay

    2014-06-01

    The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012-0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007-0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.

  2. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bonner, K.; Siegel, K.R.

    1988-04-01

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

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

    Science.gov (United States)

    Reza, S.; Iftekharuddin, K. M.

    2014-03-01

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

  5. 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.)

  6. Magnetic resonance imaging in assessment of treatment response of gamma knife for brain tumors

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao; ZHANG Xue-ning; ZHANG Yun-ting; YU Chun-shui; XU De-sheng

    2011-01-01

    Objective To review the applications of magnetic resonance imaging (MRI) techniques in assessing treatment response to gamma knife radiosurgery for brain tumors.Data sources Published articles about assessing treatment response to gamma knife radiosurgery for brain tumors were selected using PubMed. The search terms were "MRI", "gamma knife" and "brain tumors".Study selection Articles regarding the MRI techniques using for early assessment of treatment response of gamma knife were selected.Results MRI techniques, especially diffusion weighted imaging, perfusion weighted imaging, magnetic resonance spectroscopy, are useful for early assessment of treatment response of gamma knife by detecting the hemodynamic, metabolic, and cellular alterations. Moreover, they can also provide important information on prognosis.Conclusions Diffusion weighted imaging, perfusion weighted imaging and magnetic resonance spectroscopy can provide early assessment of treatment response of gamma knife for brain tumors, and also information of tumor progression or recurrence earlier than conventional MRI. But there are still many questions to be answered which should be based on the development and advancement of MRI and related disciplines.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2003-10-01

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

  9. Generation of neuronal progenitor cells in response to tumors in the human brain.

    Science.gov (United States)

    Macas, Jadranka; Ku, Min-Chi; Nern, Christian; Xu, Yuanzhi; Bühler, Helmut; Remke, Marc; Synowitz, Michael; Franz, Kea; Seifert, Volker; Plate, Karl H; Kettenmann, Helmut; Glass, Rainer; Momma, Stefan

    2014-01-01

    Data from transgenic mouse models show that neuronal progenitor cells (NPCs) migrate toward experimental brain tumors and modulate the course of pathology. However, the pathways whereby NPCs are attracted to CNS neoplasms are not fully understood and it is unexplored if NPCs migrate toward brain tumors (high-grade astrocytomas) in humans. We analyzed the tumor-parenchyma interface of neurosurgical resections for the presence of (NPCs) and distinguished these physiological cells from the tumor mass. We observed that polysialic acid neural cell adhesion molecule-positive NPCs accumulate at the border of high-grade astrocytomas and display a marker profile consistent with immature migratory NPCs. Importantly, these high-grade astrocytoma-associated NPCs did not carry genetic aberrations that are indicative of the tumor. Additionally, we observed NPCs accumulating in CNS metastases. These metastatic tumors are distinguished from neural cells by defined sets of markers. Transplanting murine glioma cells embedded in a cell-impermeable hollow fiber capsule into the brains of nestin-gfp reporter mice showed that diffusible factors are sufficient to induce a neurogenic reaction. In vitro, vascular endothelial growth factor (VEGF) secreted from glioma cells increases the migratory and proliferative behavior of adult human brain-derived neural stem and progenitor cells via stimulation of VEGF receptor-2 (VEGFR-2). In vivo, inhibiting VEGFR-2 signaling with a function-blocking antibody led to a reduction in NPC migration toward tumors. Overall, our data reveal a mechanism by which NPCs are attracted to CNS tumors and suggest that NPCs accumulate in human high-grade astrocytomas.

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

    Science.gov (United States)

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

    2005-01-01

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

  11. Brain tumor classification and segmentation using sparse coding and dictionary learning.

    Science.gov (United States)

    Salman Al-Shaikhli, Saif Dawood; Yang, Michael Ying; Rosenhahn, Bodo

    2016-08-01

    This paper presents a novel fully automatic framework for multi-class brain tumor classification and segmentation using a sparse coding and dictionary learning method. The proposed framework consists of two steps: classification and segmentation. The classification of the brain tumors is based on brain topology and texture. The segmentation is based on voxel values of the image data. Using K-SVD, two types of dictionaries are learned from the training data and their associated ground truth segmentation: feature dictionary and voxel-wise coupled dictionaries. The feature dictionary consists of global image features (topological and texture features). The coupled dictionaries consist of coupled information: gray scale voxel values of the training image data and their associated label voxel values of the ground truth segmentation of the training data. For quantitative evaluation, the proposed framework is evaluated using different metrics. The segmentation results of the brain tumor segmentation (MICCAI-BraTS-2013) database are evaluated using five different metric scores, which are computed using the online evaluation tool provided by the BraTS-2013 challenge organizers. Experimental results demonstrate that the proposed approach achieves an accurate brain tumor classification and segmentation and outperforms the state-of-the-art methods.

  12. IMPROVED HYBRID SEGMENTATION OF BRAIN MRI TISSUE AND TUMOR USING STATISTICAL FEATURES

    OpenAIRE

    S. Allin Christe; K. Malathy; A.Kandaswamy

    2010-01-01

    Medical image segmentation is the most essential and crucial process in order to facilitate the characterization and visualization of the structure of interest in medical images. Relevant application in neuroradiology is the segmentation of MRI data sets of the human brain into the structure classes gray matter, white matter and cerebrospinal fluid (CSF) and tumor. In this paper, brain image segmentation algorithms such as Fuzzy C means (FCM) segmentation and Kohonen means(K means) segmentati...

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

    Science.gov (United States)

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

    2016-08-01

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

  14. Immunofluorescent study of immunoglobulins and complement components in human brain tumors.

    Directory of Open Access Journals (Sweden)

    Kawakami,Yasuto

    1981-04-01

    Full Text Available Using a direct immunofluorescent method, histological locations of immunoglobulins (IgG, IgM, IgA and IgD of heavy chain, and kappa and lambda of light chain and complement components (C3 and C4 were studied in 78 brain tumors, which included 24 astrocytomas, 6 metastatic tumors, 5 medulloblastomas, 4 malignant lymphomas, 15 meningiomas, 8 schwannomas, 8 pituitary adenomas, and 8 other miscellaneous brain tumors. IgG-positive cells were observed in the perivascular regions of astrocytomas, but were more marked in those of high grade, metastatic tumors and meningiomas. Malignant lymphomas demonstrated IgG and IgM-positive cells accompanied by either kappa of lambda light chains. C3 and C4 were much less evident in these tumors. Pituitary adenomas showed slight positive stains for both immunoglobulins and complement components on the blood vessel walls, Immune reactions against brain tumors were discussed including the clinical application of autologous lymphocyte infusion in malignant gliomas and combination chemotherapy in intracranial malignant lymphomas.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Ursolic acid inhibits the proliferation of human ovarian cancer stem-like cells through epithelial-mesenchymal transition.

    Science.gov (United States)

    Zhang, Jie; Wang, Wenjing; Qian, Lin; Zhang, Qiuwan; Lai, Dongmei; Qi, Cong

    2015-11-01

    Ovarian cancer is the most frequent cause of cancer-related death among all gynecological cancers. Increasing evidence suggests that human ovarian cancer stem-like cells could be enriched under serum-free culture conditions. In the present study, SKOV3 ovarian epithelial cancer cells were cultured for sphere cells. Ursolic acid (UA) with triterpenoid compounds exist widely in food, medicinal herbs and other plants. Evidence shows that UA has anticancer activities in human ovarian cancer cells, but he role of UA in ovarian cancer stem cells (CSCs) remains unknown. The aim of the present study was to investigate the anticancer effects of UA in combination with cisplatin in ovarian CSCs (in vitro and in vivo), along with the molecular mechanism of action. Treatment with UA at various concentrations was examined in combination with cisplatin in human ovarian CSCs. MTT assay and flow cytometry were used for cell viability and apoptosis analysis, and qRT-PCR for stem cell markers and epithelial-mesenchymal transition (EMT) markers for mRNA expression. Transwell assay was employed to observe the migration and invasion of SKOV3 cells and SKOV3 sphere cells after treatment. Moreover, athymic BALB/c-nu nude mice were injected with SKOV3 sphere cells to obtain a xenograft model for in vivo studies. The results showed that CSCs possessed mesenchymal characteristics and EMT ability, and the growth of SKOV3 and sphere cells was significantly inhibited by UA. Transplanted tumors were significantly reduced after injection of UA and UA plus cisplatin. Furthermore, we found that UA could play a role in enhancing the sensitivity of CSCs to cisplatin resistance. Our findings suggested that UA is involved in EMT mechanism to affect the proliferation and apoptosis of human ovarian cancer stem-like cells and it is a potent anti-ovarian cancer agent.

  17. LGR5 positivity defines stem-like cells in colorectal cancer

    NARCIS (Netherlands)

    Hirsch, Daniela; Barker, Nick; McNeil, Nicole; Hu, Yue; Camps, Jordi; McKinnon, Katherine; Clevers, Hans; Ried, Thomas; Gaiser, Timo

    2014-01-01

    Like normal colorectal epithelium, colorectal carcinomas (CRCs) are organized hierarchically and include populations of cells with stem-like properties. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) is associated with these stem cells in normal colorectal epithelium; however, th

  18. 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

  19. Molecular imaging of brain tumors personal experience and review of the literature.

    Science.gov (United States)

    Schaller, Bernhard J; Cornelius, Jan F; Sandu, Nora; Buchfelder, Michael

    2008-12-01

    Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imaging of primary brain tumors therefore contain (i) primary brain tumor diagnosis, (ii) identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), and (iii) prediction of treatment response by measurement of tumor perfusion, or ischemia. The key-question remains whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival. Molecular imaging may identify early disease and differentiate benign from malignant lesions. Moreover, an early identification of treatment effectiveness could influence patient management by providing objective criteria for evaluation of therapeutic strategies for primary brain tumors. Specially, its novel potential to visualize metabolism and signal transduction to gene expression is used in reporter gene assays to trace the location and temporal level of expression of therapeutic and endogenous genes. The authors present here illustrative data of PET imaging: the thymidine kinase gene expression in experimentally transplanted F98 gliomas in cat brain indicates, that [(18)F]FHBG visualizes cells expressing TK-GFP gene in transduced gliomas as well as quantities and localizes transduced

  20. Single-photon emission computed tomography/computed tomography in brain tumors.

    Science.gov (United States)

    Schillaci, Orazio; Filippi, Luca; Manni, Carlo; Santoni, Riccardo

    2007-01-01

    Anatomic imaging procedures (computed tomography [CT] and magnetic resonance imaging [MRI]) have become essential tools for brain tumor assessment. Functional images (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]) can provide additional information useful during the diagnostic workup to determine the degree of malignancy and as a substitute or guide for biopsy. After surgery and/or radiotherapy, nuclear medicine examinations are essential to assess persistence of tumor, to differentiate recurrence from radiation necrosis and gliosis, and to monitor the disease. The combination of functional images with anatomic ones is of the utmost importance for a full evaluation of these patients, which can be obtained by means of imaging fusion. Despite the fast-growing diffusion of PET, in most cases of brain tumors, SPECT studies are adequate and provide results that parallel those obtained with PET. The main limitation of SPECT imaging with brain tumor-seeking radiopharmaceuticals is the lack of precise anatomic details; this drawback is overcome by the fusion with morphological studies that provide an anatomic map to scintigraphic data. In the past, software-based fusion of independently performed SPECT and CT or MRI demonstrated usefulness for brain tumor assessment, but this process is often time consuming and not practical for everyday nuclear medicine studies. The recent development of dual-modality integrated imaging systems, which allow the acquisition of SPECT and CT images in the same scanning session, and their co-registration by means of the hardware, has facilitated this process. In SPECT studies of brain tumors with various radiopharmaceuticals, fused images are helpful in providing the precise localization of neoplastic lesions, and in excluding the disease in sites of physiologic tracer uptake. This information is useful for optimizing diagnosis, therapy monitoring, and radiotherapy treatment planning, with a

  1. 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.

  2. Characterization of normal brain and brain tumor pathology by chisquares parameter maps of diffusion-weighted image data

    Energy Technology Data Exchange (ETDEWEB)

    Maier, Stephan E. E-mail: stephan@bwh.harvard.edu; Mamata, Hatsuho; Mulkern, Robert V

    2003-03-01

    Objective: To characterize normal and pathologic brain tissue by quantifying the deviation of diffusion-related signal from a simple monoexponential decay, when measured over a wider than usual range of b-factors. Methods and materials: Line scan diffusion imaging (LSDI), with diffusion weighting at multiple b-factors between 100 and 5000 s/mm{sup 2}, was performed on 1.5 T clinical scanners. Diffusion data of single slice sections were acquired in five healthy subjects and 19 brain tumor patients. In-patients, conventional T2-weighted and contrast-enhanced T1-weighted images were obtained for reference purposes. The chisquare ({chi}{sup 2}) error parameter associated with the monoexponential fits of the measured tissue water signals was then used to quantify the departure from a simple monoexponential signal decay on a pixel-by-pixel basis. Results: Diffusion-weighted images over a wider b-factor range than typically used were successfully obtained in all healthy subjects and patients. Normal and pathologic tissues demonstrated signal decays, which clearly deviate from a simple monoexponential behavior. The {chi}{sup 2} of cortical and deep grey matter was considerably lower than in white matter. In peritumoral edema, however, {chi}{sup 2} was 68% higher than in normal white matter. In highly malignant brain tumors, such as glioblastoma multiforme (GBM) or anaplastic astrocytoma, {chi}{sup 2} values were on average almost 400% higher than in normal white matter, while for one low grade astrocytoma and two cases of metastasis, {chi}{sup 2} was not profoundly different from the {chi}{sup 2} value of white matter. Maps of the {chi}{sup 2} values provide good visualization of spatial details. However, the tumor tissue contrast generated appeared in many cases to be different from the enhancement produced by paramagnetic contrast agents. For example, in cases where the contrast agent only highlighted the rim of the tumor, {chi}{sup 2} enhancement was present within the

  3. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Science.gov (United States)

    Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.

    2016-01-01

    Introduction Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported. PMID:28203179

  4. Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Eric D. Johnson

    2016-12-01

    Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

  5. 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.

  6. 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

    Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can...... 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......, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted...

  7. Can the standardized uptake value characterize primary brain tumors on FDG-PET?

    Energy Technology Data Exchange (ETDEWEB)

    Hustinx, R.; Smith, R.J.; Benard, F.; Bhatnagar, A.; Alavi, A. [Div. of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA (United States)

    1999-11-01

    The aim of this study was to evaluate the usefulness of measuring the standardized uptake value (SUV) in primary brain tumors on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. Two groups of patients were studied. Whole-brain glucose cerebral metabolic rates (wCMRs) and SUVs were obtained in 20 normal subjects. Twenty-seven patients with histology-proven malignant primary CNS tumors (high-grade gliomas n=22, primitive neuroectodermal tumors n=3, ependymomas n=2) were also studied. The degree of FDG uptake was assessed by visual inspection and thereafter regions of interest were placed over the lesion, the contralateral cortex and white matter and the whole brain. Average (avg) and maximum (max) pixel values were determined in each site. Based on these measurements, SUV, tumor to cortex (T/C) and tumor to white matter (T/WM) activity ratios were calculated. There was no correlation between wCMRs (4.55{+-}0.36 mg min{sup -1} 100 g{sup -1}) and wSUVs (5.41{+-}0.43) in the normal subjects (r=0.18, P=0.45). In the second group, 17 lesions were described as definitely and seven as probably malignant. However, SUVs in these tumors and in the contralateral cortex were not significantly different. Although the SUVs were generally higher in the tumor than in the contralateral white matter, there was a significant overlap between the values. The range of the SUVs was wide: 2.54-11.8 for the tumors, 2.98-9.96 for the cortex and 1.87-6.76 for the white matter. SUVs in the normal cortex were negatively correlated with blood glucose level at the time of the injection. SUVs in the whole brain and in the cortex were lower in patients previously treated by irradiation, even months after completion of the treatment. No correlation was detectable between any of the SUVs and the age of the patients, tumor type, time post injection, use of dexamethasone, patient weight, dose injected and visual score. With cutoff levels of 1.5 for T max/WM and 0.6 for T

  8. EXPRESSION OF SV40 Tag AND FORMATION Tag-p53 AND Tag-Rb COMPLEXES IN CHINESE BRAIN TUMORS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of SV40 Tag andformation of Tag-p53 and Tag-Rb complexes in Chinese brain tumors. Methods: SV40 large tumor antigen (Tag) were investigated by immunoprecipitation, silver staining and Western blot in 65 cases of Chinese brain tumors and 8 cases of normal brain tissues. Tag-p53 and Tag-Rb complexes were screened by the same way in 20 and 15 Tag positive tumor tissues respectively. Results: Tag was found in all of 8 ependymomas and 2 choroid plexus papillomas, 90% (9/10) of pituitary adenomas, 73% (11/15) of astrocytomas, 70% (7/10) of meningiomas, 50% (4/8) of glioblastoma multiform, 33% (2/6) of medulloblastomas, 5 oligodendrogliomas, 1 pineocytoma and 8 normal brain tissues were negative for Tag. Tag-p53 complex was detected in all of 20 Tag positive tumors as well as Tag-Rb complex in all of 15 Tag positive tumors. Conclusion: SV40 Tag is not only expressed in human brain tumors, but also it can form specific complexes with tumor suppressors p53 and Rb. SV40 is correlated to human brain tumorigenesis. The inactivation of p53 and Rb due to the formation of Tag-p53 and Tag-Rb complexes is possibly an important mechanism in the etiopathogenesis of human brain tumors.

  9. 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.

  10. Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Aiyu Zhu

    2016-03-01

    Full Text Available Background/Aims: Androgen receptor (AR, a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC. However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC

  11. 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.

  12. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    Science.gov (United States)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

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

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.

    1991-01-01

    Current progress on this research includes the synthesis of chemical structures for malignant brain tumors. These structures include boron-containing derivatives of lipophilic anticonvulsants and CNS depressants; carboranyl precursors of nucleic acids and related structures; and carboranyl amino acids. Cellular uptake and persistence studies have also been carried out with F98 rat glioma cells. 1 fig., 1 tab.

  14. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Science.gov (United States)

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  15. Interstitial laser thermotherapy: developments in the treatment of small deep-seated brain tumors.

    Science.gov (United States)

    Menovsky, T; Beek, J F; Roux, F X; Bown, S G

    1996-12-01

    New technical advances have made feasible the utilization of laser to destroy deep-seated brain tumors under real-time monitoring. Experience with interstitial laser thermotherapy (ILTT) in animal and clinical studies has been obtained. These studies are summarized and the future potential of ILTT in neurosurgery is discussed.

  16. Explorative study on the aftercare of pediatric brain tumor survivors: a parents' perspective

    NARCIS (Netherlands)

    Aukema, E.J.; Last, B.F.; Schouten-van Meeteren, A.Y.N.; Grootenhuis, M.A.

    2011-01-01

    Whilst the need for aftercare for long-term sequelae of brain tumor survivors is well known and evident, information from a parent's perspective is lacking on whether the need for aftercare is detected in time, and whether the aftercare is timely initiated and meets the needs for aftercare. A survey

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  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. Executive functions and social skills in survivors of pediatric brain tumor.

    Science.gov (United States)

    Wolfe, Kelly R; Walsh, Karin S; Reynolds, Nina C; Mitchell, Frances; Reddy, Alyssa T; Paltin, Iris; Madan-Swain, Avi

    2013-01-01

    Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper-and-pencil measures of social skills and real-world executive skills. Social functioning was related to a specific aspect of executive functions, that is, the survivors' variability in response time, such that inconsistent responding was associated with better parent-reported and survivor-reported social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed.

  20. Brain tumor delineation based on CT and MR imaging. Implications for radiotherapy treatment planning

    NARCIS (Netherlands)

    Heesters, M A; Wijrdeman, H K; Struikmans, H; Witkamp, T; Moerland, M A

    1993-01-01

    This paper deals with the impact MRI may have on radiotherapy treatment planning of brain tumors. The authors analyzed differences in size and position of treatment fields as indicated by three observers (two radiotherapists and one neuroradiologist) using CT or MR based radiotherapy planning proced

  1. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages.

    Science.gov (United States)

    Poggi, Geraldina; Liscio, Mariarosaria; Galbiati, Susanna; Adduci, Annarita; Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo; Clerici, Carlo Alfredo; Fossati-Bellani, Franca; Sommovigo, Michela; Castelli, Enrico

    2005-05-01

    Cognitive and psychological disorders are among the most frequently observed sequelae in brain tumor survivors. The goal of this work was to verify the presence of these disorders in a group of children and adolescents diagnosed with brain tumor before age 18 years, differentiate these disorders according to age of assessment, identify correlations between the two types of impairments and define possible associations between these impairments and clinical variables. The study involved 76 patients diagnosed with brain tumor before age 18 years. Three age groups were formed, and all the patients received a standardized battery of age-matched cognitive and psychological tests. According to our findings, all three groups present with cognitive and psychological-behavioral disorders. Their frequency varies according to age of onset and is strongly associated to time since diagnosis. The performance intelligence quotient (PIQ) was more impaired than the verbal intelligence quotient (VIQ). Internalizing problems, withdrawal and social problems were the most frequent psychological disorders. Correlations were found between cognitive impairment and the onset of the main psychological and behavioral disorders. These findings are relevant as they point out the long-term outcome of brain tumor survivors. Hence, the recommendation to diversify psychological interventions and rehabilitation plans according to the patients' age.

  2. 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...

  3. Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.

    Science.gov (United States)

    Biros, E; Kalina, I; Kohút, A; Bogyiová, E; Salagovic, J; Sulla, I

    2002-01-01

    The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

  4. In Vivo Follow-up of Brain Tumor Growth via Bioluminescence Imaging and Fluorescence Tomography

    Directory of Open Access Journals (Sweden)

    Coralie Genevois

    2016-10-01

    Full Text Available Reporter gene-based strategies are widely used in experimental oncology. Bioluminescence imaging (BLI using the firefly luciferase (Fluc as a reporter gene and d-luciferin as a substrate is currently the most widely employed technique. The present paper compares the performances of BLI imaging with fluorescence imaging using the near infrared fluorescent protein (iRFP to monitor brain tumor growth in mice. Fluorescence imaging includes fluorescence reflectance imaging (FRI, fluorescence diffuse optical tomography (fDOT, and fluorescence molecular Imaging (FMT®. A U87 cell line was genetically modified for constitutive expression of both the encoding Fluc and iRFP reporter genes and assayed for cell, subcutaneous tumor and brain tumor imaging. On cultured cells, BLI was more sensitive than FRI; in vivo, tumors were first detected by BLI. Fluorescence of iRFP provided convenient tools such as flux cytometry, direct detection of the fluorescent protein on histological slices, and fluorescent tomography that allowed for 3D localization and absolute quantification of the fluorescent signal in brain tumors.

  5. Taurolidine-Fibrin-Sealant-Matrix using spray application for local treatment of brain tumors.

    Science.gov (United States)

    Stendel, Ruediger; Scheurer, Louis; Schlatterer, Kathrin; Gminski, Richard; Möhler, Hanns

    2004-01-01

    Malignant gliomas tend to recur in the vast majority of cases. Recurrent gliomas may arise from vital tumor cells present in this zone around the resection margin. It appears promising to combine tumor resection with local chemotherapy using an antineoplastic, but non-toxic agent. Taurolidine exerts a selective antineoplastic effect by induction of programmed cell death and has anti-angiogenic activity. Fibrin sealant is completely degradable and firmly adheres to brain tissue, suggesting that it would provide a suitable matrix for taurolidine delivery--a Taurolidine-Fibrin-Sealant-Matrix (TFM)--in the local treatment of brain tumors. The potential of local delivery of taurolidine out of a fibrin sealant matrix was investigated. Taurolidine could be suspended homogeneously in both the thrombin and the procoagulant protein components of the fibrin sealant. The fibrin sealant matrix was a suitable carrier for the suspension of taurolidine at a concentration that ensured the release of therapeutically effective amounts of the drug over a period of 2 weeks in vitro. The antineoplastic action of taurolidine was not affected by embedding in the fibrin sealant matrix. The described drug delivery system may be suitable for local taurolidine treatment of brain tumors following complete or partial resection or of tumors that are non-resectable because of their location.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  9. In vivo pink-beam imaging and fast alignment procedure for rat brain tumor radiation therapy.

    Science.gov (United States)

    Nemoz, Christian; Kibleur, Astrid; Hyacinthe, Jean Noël; Berruyer, Gilles; Brochard, Thierry; Bräuer-Krisch, Elke; Le Duc, Géraldine; Brun, Emmanuel; Elleaume, Hélène; Serduc, Raphaël

    2016-01-01

    A fast positioning method for brain tumor microbeam irradiations for preclinical studies at third-generation X-ray sources is described. The three-dimensional alignment of the animals relative to the X-ray beam was based on the X-ray tomography multi-slices after iodine infusion. This method used pink-beam imaging produced by the ID17 wiggler. A graphical user interface has been developed in order to define the irradiation parameters: field width, height, number of angles and X-ray dose. This study is the first reporting an image guided method for soft tissue synchrotron radiotherapy. It allowed microbeam radiation therapy irradiation fields to be reduced by a factor of ∼20 compared with previous studies. It permitted more targeted, more efficient brain tumor microbeam treatments and reduces normal brain toxicity of the radiation treatment.

  10. Efficacy and toxicity in brain tumor treatment - quantitative Measurements using advanced MRI

    DEFF Research Database (Denmark)

    Ravn, Søren

    2016-01-01

    and are now being used for presurgical and radiation therapy (RT) planning. More advanced MRI sequences have gained attention. Sequences such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and functional magnetic resonance imaging (fMRI) have entered the clinical world concurrently......From the clinical introduction in the 1980s, MRI has grown to become an indispensable brain imaging modality, mainly due to its excellent ability to visualize soft tissues. Morphologically, T1- and T2-weighted brain tumor MRI have been part of routine diagnostic radiology for more than two decades...... with the introduction of magnets with higher field strength. Ongoing technical development has enabled a change from semiquantitative measurements to a true quantitative approach. This step is expected to have a great impact on the treatment of brain tumor patients in the future. The aim of this Ph.D. dissertation...

  11. Fusing in vivo and ex vivo NMR sources of information for brain tumor classification

    Science.gov (United States)

    Croitor-Sava, A. R.; Martinez-Bisbal, M. C.; Laudadio, T.; Piquer, J.; Celda, B.; Heerschap, A.; Sima, D. M.; Van Huffel, S.

    2011-11-01

    In this study we classify short echo-time brain magnetic resonance spectroscopic imaging (MRSI) data by applying a model-based canonical correlation analyses algorithm and by using, as prior knowledge, multimodal sources of information coming from high-resolution magic angle spinning (HR-MAS), MRSI and magnetic resonance imaging. The potential and limitations of fusing in vivo and ex vivo nuclear magnetic resonance sources to detect brain tumors is investigated. We present various modalities for multimodal data fusion, study the effect and the impact of using multimodal information for classifying MRSI brain glial tumors data and analyze which parameters influence the classification results by means of extensive simulation and in vivo studies. Special attention is drawn to the possibility of considering HR-MAS data as a complementary dataset when dealing with a lack of MRSI data needed to build a classifier. Results show that HR-MAS information can have added value in the process of classifying MRSI data.

  12. Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

    OpenAIRE

    Karabeber, Hazem; Huang, Ruimin; Iacono, Pasquale; Samii, Jason M.; Pitter, Ken; Holland, Eric C.; Kircher, Moritz F.

    2014-01-01

    The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imagi...

  13. Stereotactic radiation in primary brain tumors in children and adolescents.

    Science.gov (United States)

    Benk, V; Clark, B G; Souhami, L; Algan, O; Bahary, J; Podgorsak, E B; Freeman, C R

    1999-08-01

    To evaluate treatment outcome and morbidity of stereotactic external-beam irradiation (SEBI) in pediatric patients, we reviewed 14 children treated with SEBI, using a 10-MV isocentric linear accelerator at McGill University between 1988 and 1994. The median follow-up was 46 months (range 6-82 months). The median age was 14 years. There were 8 low-grade astrocytomas, 3 neuromas and 4 other histologies. Twelve patients received fractionated treatments. The median collimator diameter was 2.5 cm (range 1-5 cm). The median biological effective dose delivered to the entire tumor volume was 57 Gy for astrocytomas and 43 Gy for the other histologies. The overall actuarial survival rate and disease-free survival rate at 5 years were 83 and 62%, respectively. For the patients with low-grade astrocytomas, the 5-year survival and disease-free survival rates were 100 and 60%, respectively. Four children had recurrence at a median of 37 months. Four patients developed treatment-related complications: 1 had edema alone, 2 had necrosis and 1 had edema associated with necrosis. Neither the physical nor radiobiological parameters were predictive of the treatment outcome or the treatment complications. Stereotactic irradiation is a valid option for progressive nonresectable tumors in children.

  14. Secondary tics or tourettism associated with a brain tumor.

    Science.gov (United States)

    Luat, Aimee F; Behen, Michael E; Juhász, Csaba; Sood, Sandeep; Chugani, Harry T

    2009-12-01

    Tourette syndrome is generally considered to be a genetic disorder, but symptoms mimicking Tourette syndrome can be secondary to an underlying lesion disrupting the basal ganglia circuitry. Described here is a case of secondary tics, or tourettism, in a child with a large oligodendroglioma of the right temporal lobe extending to the basal ganglia. He presented with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and stimulant-induced tic disorder at the age of 11 years, and later also had also seizures. The family history was unremarkable. Cranial magnetic resonance imaging disclosed a right temporal lobe tumor extending to the basal ganglia. An alpha-[(11)C]methyl-l-tryptophan positron emission tomography scan showed asymmetric uptake in the basal ganglia and intense uptake in the tumor. He had a lesionectomy, and the histopathologic diagnosis was oligodendroglioma. Neuropsychologic testing after surgery revealed no attention-deficit hyperactivity disorder symptomatology, and only minimal features of obsessive-compulsive disorder. The present case provides additional evidence supporting the role of basal ganglia circuitry in the pathophysiology of tic disorder and its comorbid states. Children who present with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic disorder of late onset in the absence of family history should be further investigated with neuroimaging to exclude the presence of a secondary cause.

  15. P18.07PALLIATIVE SEDATION FOR BRAIN TUMOR PATIENTS AT THE END OF LIFE

    Science.gov (United States)

    Pace, A.; Villani, V.; Benincasa, D.; Di Pasquale, A.; Carapella, C.M.; Pompili, A.

    2014-01-01

    BACKGROUND: Therapeutic (or palliative) sedation in the context of palliative medicine is the monitored use of medications intended to induce a state of decreased or absent awareness (unconsciousness) in order to relieve the burden of otherwise intractable suffering in a manner that is ethically acceptable to the patient, family and health-care providers. There is a large debate about the use of palliative sedation, sometime defined as terminal sedation. There are very few data about the role of palliative sedation in brain tumor patients at the end of life. However, in brain tumor patients palliative sedation may be necessary in case of uncontrolled delirium, agitation, death rattle or refractory seizures. METHODS: We retrospectively analyzed the clinical records of patients assisted at home until death by the Regina Elena Cancer Institute Palliative Home Care for brain tumor patients. All patients died for brain tumor in the last 2 years (2012-2013) were included in this study. RESULTS: Out of 190 brain tumor patients assisted at home in 2012-2013, 108 died and were included in this study. All patients were affected by malignant glioma. Palliative sedation was utilized in 12 cases (11%). In 8 cases for the control of refractory seizures and in 4 cases for delirium. Given the lack of advanced directives and low competence of patients, the decision about sedation was discussed by the care team with caregivers and family members. Palliative sedation was started with midazolam 0.5-1 mg/hr and prolonged until symptoms' control. CONCLUSION: The use of palliative sedation is relatively frequent in the practice of a neuro-oncologic palliative team. The most frequent refractory symptoms in this population of patients were seizures and delirium. The process of end of life treatment decisions in neuro-oncology requires to be better defined.

  16. In vivo models of brain tumors: roles of genetically engineered mouse models in understanding tumor biology and use in preclinical studies.

    Science.gov (United States)

    Simeonova, Iva; Huillard, Emmanuelle

    2014-10-01

    Although our knowledge of the biology of brain tumors has increased tremendously over the past decade, progress in treatment of these deadly diseases remains modest. Developing in vivo models that faithfully mirror human diseases is essential for the validation of new therapeutic approaches. Genetically engineered mouse models (GEMMs) provide elaborate temporally and genetically controlled systems to investigate the cellular origins of brain tumors and gene function in tumorigenesis. Furthermore, they can prove to be valuable tools for testing targeted therapies. In this review, we discuss GEMMs of brain tumors, focusing on gliomas and medulloblastomas. We describe how they provide critical insights into the molecular and cellular events involved in the initiation and maintenance of brain tumors, and illustrate their use in preclinical drug testing.

  17. Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.

    Science.gov (United States)

    Sneed, P K; Stauffer, P R; Gutin, P H; Phillips, T L; Suen, S; Weaver, K A; Lamb, S A; Ham, B; Prados, M D; Larson, D A

    1991-02-01

    Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

  18. Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells.

    Science.gov (United States)

    Wei, Ming-Feng; Chen, Min-Wei; Chen, Ke-Cheng; Lou, Pei-Jen; Lin, Susan Yun-Fan; Hung, Shih-Chieh; Hsiao, Michael; Yao, Cheng-Jung; Shieh, Ming-Jium

    2014-07-01

    Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high resistance to current therapeutic strategies, including photodynamic therapy (PDT), leading to the recurrence and progression of colorectal cancer (CRC). In cancer, autophagy acts as both a tumor suppressor and a tumor promoter. However, the role of autophagy in the resistance of CSCs to PDT has not been reported. In this study, CSCs were isolated from colorectal cancer cells using PROM1/CD133 (prominin 1) expression, which is a surface marker commonly found on stem cells of various tissues. We demonstrated that PpIX-mediated PDT induced the formation of autophagosomes in PROM1/CD133(+) cells, accompanied by the upregulation of autophagy-related proteins ATG3, ATG5, ATG7, and ATG12. The inhibition of PDT-induced autophagy by pharmacological inhibitors and silencing of the ATG5 gene substantially triggered apoptosis of PROM1/CD133(+) cells and decreased the ability of colonosphere formation in vitro and tumorigenicity in vivo. In conclusion, our results revealed a protective role played by autophagy against PDT in CSCs and indicated that targeting autophagy could be used to elevate the PDT sensitivity of CSCs. These findings would aid in the development of novel therapeutic approaches for CSC treatment.

  19. MRI Brain Tumor Segmentation and Necrosis Detection Using Adaptive Sobolev Snakes

    Science.gov (United States)

    Nakhmani, Arie; Kikinis, Ron; Tannenbaum, Allen

    2014-01-01

    Brain tumor segmentation in brain MRI volumes is used in neurosurgical planning and illness staging. It is important to explore the tumor shape and necrosis regions at different points of time to evaluate the disease progression. We propose an algorithm for semi-automatic tumor segmentation and necrosis detection. Our algorithm consists of three parts: conversion of MRI volume to a probability space based on the on-line learned model, tumor probability density estimation, and adaptive segmentation in the probability space. We use manually selected acceptance and rejection classes on a single MRI slice to learn the background and foreground statistical models. Then, we propagate this model to all MRI slices to compute the most probable regions of the tumor. Anisotropic 3D diffusion is used to estimate the probability density. Finally, the estimated density is segmented by the Sobolev active contour (snake) algorithm to select smoothed regions of the maximum tumor probability. The segmentation approach is robust to noise and not very sensitive to the manual initialization in the volumes tested. Also, it is appropriate for low contrast imagery. The irregular necrosis regions are detected by using the outliers of the probability distribution inside the segmented region. The necrosis regions of small width are removed due to a high probability of noisy measurements. The MRI volume segmentation results obtained by our algorithm are very similar to expert manual segmentation. PMID:25302005

  20. Impacts of Blood-Brain Barrier in Drug Delivery and Targeting of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2012-02-01

    Full Text Available Introduction: Entry of blood circulating agents into the brain is highly selectively controlled by specific transport machineries at the blood brain barrier (BBB, whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. Methods: Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. Results: Brain capillary endothelial cells (BCECs form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics. Conclusion: The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent.

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

    Science.gov (United States)

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

    2016-01-01

    Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic aniontransporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors. PMID:26197410

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

    Science.gov (United States)

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

    2015-10-01

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

  3. Analysis of microRNA expression in canine mammary cancer stem-like cells indicates epigenetic regulation of transforming growth factor-beta signaling.

    Science.gov (United States)

    Rybicka, A; Mucha, J; Majchrzak, K; Taciak, B; Hellmen, E; Motyl, T; Krol, M

    2015-02-01

    Cancer stem cells (CSCs) display both unique self-renewal ability as well as the ability to differentiate into many kinds of cancer cells. They are supposed to be responsible for cancer initiation, recurrence and drug resistance. Despite the fact that a variety of methods are currently employed in order to target CSCs, little is known about the regulation of their phenotype and biology by miRNAs. The aim of our study was to assess miRNA expression in canine mammary cancer stem-like cells (expressing stem cell antigen 1, Sca-1; CD44 and EpCAM) sorted from canine mammary tumour cell lines (CMT-U27, CMT-309 and P114). In order to prove their stem-like phenotype, we conducted a colony formation assay that confirmed their ability to form colonies from a single cell. Profiles of miRNA expression were investigated using Agilent custom-designed microarrays. The results were further validated by real-time rt-PCR analysis of expression of randomly selected miRNAs. Target genes were indicated and analysed using Kioto Encyclopedia of Genes and Genomes (KEGG) and BioCarta databases. The results revealed 24 down-regulated and nine up-regulated miRNAs in cancer stem-like cells compared to differentiated tumour cells. According to KEGG and BioCarta databases, target genes (n=240) of significantly down-regulated miRNAs were involved in transforming growth factor-beta signaling, mitogen-activated protein kinases (MAPK) signaling pathway, anaplastic lymphoma receptor tyrosine kinase (ALK) and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A) pathways. The analysis of single-gene overlapping with different pathways showed that the most important genes were: TGFBR1, TGFBR2, SOS1, CHUK, PDGFRA, SMAD2, MEF2A, MEF2C and MEF2D. All of them are involved in tumor necrosis factor-beta signaling and may indicate its important role in cancer stem cell biology. Increased expression of TGFBR2, SMAD2, MEF2A and MEF2D in canine mammary cancer stem-like cells was further

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

  5. Activation of c-MET induces a stem-like phenotype in human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Geert J L H van Leenders

    Full Text Available Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'. We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.

  6. A Review of Fully Automated Techniques for Brain Tumor Detection From MR Images

    Directory of Open Access Journals (Sweden)

    Anjum Hayat Gondal

    2013-02-01

    Full Text Available Radiologists use medical images to diagnose diseases precisely. However, identification of brain tumor from medical images is still a critical and complicated job for a radiologist. Brain tumor identification form magnetic resonance imaging (MRI consists of several stages. Segmentation is known to be an essential step in medical imaging classification and analysis. Performing the brain MR images segmentation manually is a difficult task as there are several challenges associated with it. Radiologist and medical experts spend plenty of time for manually segmenting brain MR images, and this is a non-repeatable task. In view of this, an automatic segmentation of brain MR images is needed to correctly segment White Matter (WM, Gray Matter (GM and Cerebrospinal Fluid (CSF tissues of brain in a shorter span of time. The accurate segmentation is crucial as otherwise the wrong identification of disease can lead to severe consequences. Taking into account the aforesaid challenges, this research is focused towards highlighting the strengths and limitations of the earlier proposed segmentation techniques discussed in the contemporary literature. Besides summarizing the literature, the paper also provides a critical evaluation of the surveyed literature which reveals new facets of research. However, articulating a new technique is beyond the scope of this paper.

  7. Risk of brain tumors from wireless phone use.

    Science.gov (United States)

    Dubey, Rash Bihari; Hanmandlu, Madasu; Gupta, Suresh Kumar

    2010-01-01

    The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. Wireless communication has dramatically influenced our lifestyle; its impact on human health has not been completely assessed. Widespread concern continues in the community about the deleterious effects of radiofrequency radiations on human tissues and the subsequent potential threat of carcinogenesis. Exposure to low-frequency electromagnetic field has been linked to a variety of adverse health outcomes. This article surveys the results of early cell phone studies, where exposure duration was too short to expect tumor genesis, and 2 sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Hardell.

  8. Development of the Japanese version of the Pediatric Quality of Life Inventory™ Brain Tumor Module

    Directory of Open Access Journals (Sweden)

    Terasaki Mizuhiko

    2010-04-01

    Full Text Available Abstract Background The Pediatric Quality of Life Inventory™ (PedsQL™ is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL™ Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL™ Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents. Methods Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children. Results Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70 except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95. Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents. Evaluation of known-groups validity confirmed

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

    Directory of Open Access Journals (Sweden)

    Theodoros N Sergentanis

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

  10. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Singh Sandeep

    2012-09-01

    Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

  11. Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.

    Science.gov (United States)

    Morata-Tarifa, Cynthia; Jiménez, Gema; García, María A; Entrena, José M; Griñán-Lisón, Carmen; Aguilera, Margarita; Picon-Ruiz, Manuel; Marchal, Juan A

    2016-01-11

    Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.

  12. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  13. Neuroendoscopic Intervention for the Deep Midline Brain Tumors with Secondary Occlusive Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Ulugbek M. Asadullaev

    2015-06-01

    Full Text Available This article analyzes the results of a clinical examination of 102 patients (78/76.47% men and 24/23.53% women with a brain tumor (BT complicated with a secondary obstructive hydrocephalus (SOH. All the patients were divided into 3 groups according to the type of surgery. Group I included 38(37.2% patients who underwent Torkildsen's ventriculocisternostomy. Group II consisted of 34(33.3% patients who underwent endoscopic third ventriculocisternostomy (ETV with simultaneous endoscopic tumor removal. Group III included 30 (29.4% patients who underwent a two-stage intervention: ETV in the first stage, and the endoscopic tumor removal in the second stage. The distinct advantages of EVT with tumor removal in the second stage of the operation were revealed.

  14. 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.)

  15. Plasticity of cognitive functions before and after awake brain tumor surgery

    Directory of Open Access Journals (Sweden)

    Djaina Satoer

    2015-04-01

    Results: P1 and P2 showed opposite preoperative cognitive profiles. P1 obtained normal cognitive results and P2 had clinically significant impairments in all cognitive domains, (language, memory, attentional and executive deficits (z-score ≥-1.50. P3 and P4 also demonstrate opposite preoperative profiles. P4 obtained intact cognitive results, whereas P3 was impaired in memory and executive functions (z-score ≥-1.50. Intraoperatively, in both P3 and P4 positive language sites were found (left inferior frontal gyrus and left parietal lobe. At 3 months postoperatively, P3 presented language deficits followed by recovery at 12 months, whereas P4 appeared to have recovered at 3 months postoperatively from the observed premorbid impairments in memory and executive functioning (z-score <-1.50. Pathological examination revealed a slow growing brain tumor (low-grade in P1 and P3 and a fast growing brain tumor (high-grade in P2 and P4. Conclusion: In patients with similar brain tumor localizations, we found distinct cognitive profiles, possibly affected by different neural plasticity processes. Preoperatively, a favorable plasticity effect on cognition was found in P1 (temporoparietal area, potentially affected by tumor grade. Preserved cognitive functions was possibly facilitated by the slow growth rate of a low-grade tumor allowing functional reorganization (Mandonnet et al., 2003. However, P2 with a brain tumor in the same area showed preoperative deficits in several domains (language, memory and attention/executive functions. A faster growth rate of a high-grade tumor could have more aggressively affected cognition. In P3 and P4 with the same localization (insula, we found a different effect on the cognitive recovery process; at short term (3 months, improvement of the preoperatively observed cognitive impairments in a low-grade tumor P3, whereas a more gradual functional reorganization was found in language (3-12 months in P4, a high-grade tumor, contrasting Habets

  16. Utility of resting fMRI and connectivity in patients with brain tumor

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    Sandhya Manglore

    2013-01-01

    Full Text Available Background: Resting state (task independent Functional Magnetic Resonance Imaging (fMRI has opened a new avenue in cognitive studies and has found practical clinical applications. Materials and Methods: Resting fMRI analysis was performed in six patients with brain tumor in the motor cortex. For comparison, task-related mapping of the motor cortex was done. Connectivity analysis to study the connections and strength of the connections between the primary motor cortex, premotor cortex, and primary somatosensory cortex on the affected side was also performed and compared with the contralateral normal side and the controls. Results: Resting fMRI in patients with brain tumor in the motor cortex mapped the motor cortex in a task-free state and the results were comparable to the motor task paradigm. Decreased connectivity on the tumor-affected side was observed, as compared to the unaffected side. Conclusion: Resting fMRI and connectivity analysis are useful in the presurgical evaluation of patients with brain tumors and may help in uncooperative or pediatric patients. They can also prognosticate the postoperative outcome. This method also has significant applications due to the ease of image acquisition.

  17. 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.

  18. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

    Science.gov (United States)

    McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk.

  19. Epigenetics in clinical management of children and adolescents with brain tumors.

    Science.gov (United States)

    Morales La Madrid, Andres; Kieran, Mark W

    2017-02-03

    Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the "classic boxes" heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically differently. Given that epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to "risk-group" stratification and better prognostication. Also, it will help unveil key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we will review the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.

  20. Functional Assays for Specific Targeting and Delivery of RNA Nanoparticles to Brain Tumor

    Science.gov (United States)

    Lee, Tae Jin; Haque, Farzin; Vieweger, Mario; Yoo, Ji Young; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.

    2017-01-01

    Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy. Multifunctional RNA nanoparticles can be fabricated by bottom-up self-assembly of engineered RNA fragments harboring targeting (RNA aptamer or chemical ligand), therapeutic (siRNA, miRNA, ribozymes, and small molecule drugs), and imaging (fluorophore, radiolabels) modules. We have recently demonstrated that RNA nanoparticles can reach and target intracranial brain tumors in mice upon systemic injection with little or no accumulation in adjacent healthy brain tissues or in major healthy internal organs. Herein, we describe various functional imaging methods (fluorescence confocal microscopy, flow cytometry, fluorescence whole body imaging, and magnetic resonance imaging) to evaluate and monitor RNA nanoparticle targeting to intracranial brain tumors in mice. Such imaging techniques will allow in-depth evaluation of specifically delivered RNA therapeutics to brain tumors. PMID:25896001

  1. Brain tumors and CT scan in infants and children, (1). The impact on pediatric neuroradiology

    Energy Technology Data Exchange (ETDEWEB)

    Ohi, S.; Velasco, J.M. (Northwestern Univ., Chicago, IL (USA). Medical School)

    1980-10-01

    The dramatic change in the neuroradiological procedures have been noted after CT scan was introduced in the last several years. Remarkable decreasing numbers of angiographic, pneumoencephalographic and other invasive neuroradiologic studies as well as nuclear brain scan were also found in the pediatric neuroradiology. The authors analyzed the total numbers of these studies performed in the last several years in pediatric neurological/neurosurgical practice in the light of the impact of CT scan especially in the diagnostic procedures and treatments of brain tumor in children. Although the number of these procedures decreased up to 49% in plain skull X-ray, 54% in cerebral angiography, 70% in pneumoencephalography/ventriculography and 79% in nuclear brain scan after CT scan was installed in our results, it is extremely important to renew understanding of those characteristics in each special procedures. Cerebral angiography as well as pneumoencephalography may give the surgeon more precise ideas of the anatomical relationship between the lesion and other normal structures, especially in the posterior fossa tumor in which CT scan occassionally demonstrates only a gross finding. A case with false negative result and another case with a complicated anatomical structure in CT scan were presented. The significance of cerebral angiography and other invasive studies in the diagnosis and follow up of brain tumor in CT scan were discussed.

  2. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  3. Expression of cysteinyl leukotriene receptors in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators. Till now only CysLT receptor 1 (CysLT1) and CysLT receptor 2 (CysLT2) have been cloned. Although the existence of CysLT1 and CysLT2 in the brain has been demonstrated by Northern blot and RT-PCR analyses, the exact location of the receptors in the brain remains unknown. The objective

  4. Targeting Netrin-1 in glioblastoma stem-like cells inhibits growth, invasion, and angiogenesis.

    Science.gov (United States)

    Sanvoranart, Tanwarat; Supokawej, Aungkura; Kheolamai, Pakpoom; U-Pratya, Yaowalak; Poungvarin, Niphon; Sathornsumetee, Sith; Issaragrisil, Surapol

    2016-11-01

    Glioblastoma (GBM) is an aggressive malignant brain tumor that still lacks effective therapy. Glioblastoma stem cells (GBM-SCs) were identified to contribute to aggressive phenotypes and poor clinical outcomes for GBM. Netrin-1, an axon guidance molecule, has been found in several tumors in adults. However, the role of Netrin-1 in GBM-SCs remains largely unknown. In this study, CD133-positive U251 GBM cells were used as a putative GBM-SC population to identify the functions of Netrin-1. Using lentiviral transduction, Netrin-1 miR RNAi vectors were transduced into CD133-positive U251 cells. We demonstrated that cell proliferation and survival were decreased following targeted deletion of Netrin-1. Cell invasion was dramatically diminished in Netrin-1 knockdown GBM-SCs. Moreover, Netrin-1 knockdown GBM-SCs exhibited less proangiogenic activity. In conclusion, Netrin-1 may represent a therapeutic target in glioblastoma.

  5. Tumor-Like Lesions of the Brain in MRI and CT-scan

    Directory of Open Access Journals (Sweden)

    Gholamreza Bakhshandehpour

    2009-01-01

    Full Text Available "nIntroduction: The objective of this paper is to demonstrate a variety of non-neoplastic pathologies that may present with a mass effect and/or abnormal enhancement, thus simulating neoplasia. "nMaterials and Methods: We collected 77 cases of various tumor mimics from teaching files of three institutions. All patients presented with intra- and/or extra–axial lesions and imaging findings that could, potentially, mimic brain neoplasia. "nResults: Assessment of central nervous system pathology may be very challenging. The usual description of mass effect and abnormal enhancement, typical of brain neoplasia, can also be shared by a variety of non-neoplastic etiologies. Radiologists should be familiar with these tumor mimics, and shold be included as differential diagnoses. We categorized and these non-neoplastic lesions, which could potentially mimic extra-and/or intra- axial brain tumors, into the following groups: "n1 Normal variant (giant (tumefactive perivascular spaces "n2 Infection (tuberculosis, cysticercosis, and fungal lesions "n3 Syndromes (NF1, Rosai-Dorfman Syndrome, Lhermitte-Duclos, Krabbe Disease (adult type. "n4 Vascular lesions (vascular malformations, aneurysms and cerebral venous sinus thrombosis "n5 Autoimmune and inflammatory processes (MS, ADEM, encephalitis, sarcoidosis and PML "n6 Idiopathic (idiopathic hypertrophic pachymeningitis "n7 Congenital brain lesions (cortical dysgenesis and heterotopias "n8 Miscellaneous (postictal brain lesions "nConclusion: In this paper, we present a large collection of non-neoplastic tumor mimics. Awareness, understanding, and recognition of these mimics may permit the radiologist to play a significant role in the prevention of unwanted surgical interventions or extensive diagnostic evaluation procedures.  

  6. Isolation and Identification of Cancer Stem-Like Cells from Murine Melanoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Jun Dou; Kai Hu; Ning Gu; Meng Pan; Ping Wen; Yating Li; Quan Tang; Lili Chu; Fengshu Zhao; Chuilian Jiang; Weihua Hu

    2007-01-01

    In current study, cancer stem-like cells in the murine melanoma B16F10 cells were investigated. CD phenotypes of the B16F10 cells were analyzed by flow cytometry, and the specific CD phenotype cells from the B16F10 cells were isolated by MACS. Then we used colony formation assay in soft agar media, the cell growth assay in serum-free culture media as well as the tumorigenicity investigation of the specific CD phenotype cells in C57BL/6 mice,respectively, to identify cancer stem-like cells in the B16F10 cells. The results showed that the B16F10 cells could form spherical clones in serum-free culture media, and the rate of clonegenesis of CD133+, CD44+ and CD44+CD133+ cells was higher than that of CD133-, CD44- and CD44+CD133- cells in soft agar media, respectively.The tumorigenic potential of CD133+, CD44+, CD44+CD133+ cells and CD44+CD133+CD24+ cells was stronger than that of CD133-, CD44-, CD44+CD133- cells and CD44+CD133+CD24- cells in mice, respectively. In conclusion, the CD44+CD133+CD24+ cells have some biological properties of cancer stem-like cells or are highly similar to the characteristics of cancer stem cells (CSC). These results provide an important method for identifying cancer stem-like cells in B16F10 cells and for further cancer target therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-01

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

  8. Transforming Growth Factor-beta signal responding in hepatic stem-like cells

    Institute of Scientific and Technical Information of China (English)

    CUI Wei

    2008-01-01

    Objective To investigate the effects of TGF-β on the expressions and distribution of phosphorated Smad2/3 and Smad7 in hepatic stem-like cells. Methods Using immunogold transmission electron microscopy, we observed the expressions and distribution of phosphorated Smad2/3, and Smad7 before and after TGF-β1 (5 ng·mL-1) treatment for 4, 8, and 24 hours in hepatic stem-like cells (WB cells). In addition, we also detected the apoptosis status after TGF-β1 stimulation by transmission electron microscopy. Results TGF-β1 stimulation can result in expression increasing of phosphorated Smad2/3 in WB cells, and reach the peak at 8 h, especially in the nuclear. After treatment with TGF-β1 for 24 h, the nuclear expression of phosphorated Smad2/3 gradually decreased. Additionally, we found that TGF-β1 treatment also contributed to increasing in protein level and alteration in cellular distribution of Smad7 (translocation from the nucleus to the cytoplasm) in WB cells. Furthermore, we observed apoptotic body in WB cells after TGF-β1 treatment for 8 h. Conclusions These results indicate that TGF-β stimulation can alter the expression and cellular distribution of phosphorated Srnad2/3 and Smad7 which are its downstream molecular, suggesting hepatic stem-like cells own intact responding to TGF-β.

  9. JNK contributes to temozolomide resistance of stem-like glioblastoma cells via regulation of MGMT expression.

    Science.gov (United States)

    Okada, Masashi; Sato, Atsushi; Shibuya, Keita; Watanabe, Eriko; Seino, Shizuka; Suzuki, Shuhei; Seino, Manabu; Narita, Yoshitaka; Shibui, Soichiro; Kayama, Takamasa; Kitanaka, Chifumi

    2014-02-01

    While elimination of the cancer stem cell population is increasingly recognized as a key to successful treatment of cancer, the high resistance of cancer stem cells to conventional chemoradiotherapy remains a therapeutic challenge. O6-methylguanine DNA methyltransferase (MGMT), which is frequently expressed in cancer stem cells of glioblastoma, has been implicated in their resistance to temozolomide, the first-line chemotherapeutic agent against newly diagnosed glioblastoma. However, much remains unknown about the molecular regulation that underlies MGMT expression and temozolomide resistance of glioblastoma cancer stem cells. Here, we identified JNK as a novel player in the control of MGMT expression and temozolomide resistance of glioblastoma cancer stem cells. We showed that inhibition of JNK, either pharmacologically or by RNA interference, in stem-like glioblastoma cells derived directly from glioblastoma tissues reduces their MGMT expression and temozolomide resistance. Importantly, sensitization of stem-like glioblastoma cells to temozolomide by JNK inhibition was dependent on MGMT expression, implying that JNK controls temozolomide resistance of stem-like glioblastoma cells through MGMT expression. Our findings suggest that concurrent use of JNK inhibitors with temozolomide may be a rational therapeutic approach to effectively target the cancer stem cell population in the treatment of glioblastoma.

  10. Alpha shape theory for 3D visualization and volumetric measurement of brain tumor progression using magnetic resonance images.

    Science.gov (United States)

    Hamoud Al-Tamimi, Mohammed Sabbih; Sulong, Ghazali; Shuaib, Ibrahim Lutfi

    2015-07-01

    Resection of brain tumors is a tricky task in surgery due to its direct influence on the patients' survival rate. Determining the tumor resection extent for its complete information via-à-vis volume and dimensions in pre- and post-operative Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The active contour segmentation technique is used to segment brain tumors on pre-operative MR images using self-developed software. Tumor volume is acquired from its contours via alpha shape theory. The graphical user interface is developed for rendering, visualizing and estimating the volume of a brain tumor. Internet Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine the repeatability and reproducibility of tumor volume. Accuracy of the method is validated by comparing the estimated volume using the proposed method with that of gold-standard. Segmentation by active contour technique is found to be capable of detecting the brain tumor boundaries. Furthermore, the volume description and visualization enable an interactive examination of tumor tissue and its surrounding. Admirable features of our results demonstrate that alpha shape theory in comparison to other existing standard methods is superior for precise volumetric measurement of tumor.

  11. Nonrigid Registration of Brain Tumor Resection MR Images Based on Joint Saliency Map and Keypoint Clustering

    Directory of Open Access Journals (Sweden)

    Binjie Qin

    2009-12-01

    Full Text Available This paper proposes a novel global-to-local nonrigid brain MR image registration to compensate for the brain shift and the unmatchable outliers caused by the tumor resection. The mutual information between the corresponding salient structures, which are enhanced by the joint saliency map (JSM, is maximized to achieve a global rigid registration of the two images. Being detected and clustered at the paired contiguous matching areas in the globally registered images, the paired pools of DoG keypoints in combination with the JSM provide a useful cluster-to-cluster correspondence to guide the local control-point correspondence detection and the outlier keypoint rejection. Lastly, a quasi-inverse consistent deformation is smoothly approximated to locally register brain images through the mapping the clustered control points by compact support radial basis functions. The 2D implementation of the method can model the brain shift in brain tumor resection MR images, though the theory holds for the 3D case.

  12. Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors

    OpenAIRE

    Kinnula Vuokko L; Parkkila Seppo; Kallio Heini; Rodriguez Alejandra; Rantala Immo; Järvelä Sally; Soini Ylermi; Haapasalo Hannu

    2010-01-01

    Abstract Background Peroxiredoxins (Prxs) have recently been suggested to have a role in tumorigenesis. Methods We studied the expression of Prx I-VI and their relationship to patient survival in 383 grade II-IV diffuse astrocytic brain tumors. Results Prx I positivity was found in 68%, Prx II in 84%, Prx III in 90%, Prx IV in 5%, Prx V in 4% and Prx VI in 47% of the tumors. Prx I and Prx II expression decreased significantly with increasing malignancy grade (p < 0.001 and p < 0.001). Patient...

  13. Diagnostic performance of whole brain volume perfusion CT in intra-axial brain tumors: Preoperative classification accuracy and histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Xyda, Argyro, E-mail: argyro.xyda@med.uni-goettingen.de [Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Strasse 40, 37075 Goettingen (Germany); Department of Radialogy, University Hospital of Heraklion, Voutes, 71110 Heraklion, Crete (Greece); Haberland, Ulrike, E-mail: ulrike.haberland@siemens.com [Siemens AG Healthcare Sector, Computed Tomography, Siemensstr. 1, 91301 Forchheim (Germany); Klotz, Ernst, E-mail: ernst.klotz@siemens.com [Siemens AG Healthcare Sector, Computed Tomography, Siemensstr. 1, 91301 Forchheim (Germany); Jung, Klaus, E-mail: kjung1@uni-goettingen.de [Department of Medical Statistics, Georg-August University, Humboldtallee 32, 37073 Goettingen (Germany); Bock, Hans Christoph, E-mail: cbock@gmx.de [Department of Neurosurgery, Johannes Gutenberg University Hospital of Mainz, Langenbeckstraße 1, 55101 Mainz (Germany); Schramm, Ramona, E-mail: ramona.schramm@med.uni-goettingen.de [Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Strasse 40, 37075 Goettingen (Germany); Knauth, Michael, E-mail: michael.knauth@med.uni-goettingen.de [Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Strasse 40, 37075 Goettingen (Germany); Schramm, Peter, E-mail: p.schramm@med.uni-goettingen.de [Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Strasse 40, 37075 Goettingen (Germany)

    2012-12-15

    Background: To evaluate the preoperative diagnostic power and classification accuracy of perfusion parameters derived from whole brain volume perfusion CT (VPCT) in patients with cerebral tumors. Methods: Sixty-three patients (31 male, 32 female; mean age 55.6 ± 13.9 years), with MRI findings suspected of cerebral lesions, underwent VPCT. Two readers independently evaluated VPCT data. Volumes of interest (VOIs) were marked circumscript around the tumor according to maximum intensity projection volumes, and then mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability Ktrans perfusion datasets. A second VOI was placed in the contra lateral cortex, as control. Correlations among perfusion values, tumor grade, cerebral hemisphere and VOIs were evaluated. Moreover, the diagnostic power of VPCT parameters, by means of positive and negative predictive value, was analyzed. Results: Our cohort included 32 high-grade gliomas WHO III/IV, 18 low-grade I/II, 6 primary cerebral lymphomas, 4 metastases and 3 tumor-like lesions. Ktrans demonstrated the highest sensitivity, specificity and positive predictive value, with a cut-off point of 2.21 mL/100 mL/min, for both the comparisons between high-grade versus low-grade and low-grade versus primary cerebral lymphomas. However, for the differentiation between high-grade and primary cerebral lymphomas, CBF and CBV proved to have 100% specificity and 100% positive predictive value, identifying preoperatively all the histopathologically proven high-grade gliomas. Conclusion: Volumetric perfusion data enable the hemodynamic assessment of the entire tumor extent and provide a method of preoperative differentiation among intra-axial cerebral tumors with promising diagnostic accuracy.

  14. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  15. Outcome of supratentorial intraaxial extra ventricular primary pediatric brain tumors: A prospective study

    Directory of Open Access Journals (Sweden)

    Mohana Rao Patibandla

    2014-01-01

    Full Text Available Introduction: Tumors of the central nervous system (CNS are the second most frequent malignancy of childhood and the most common solid tumor in this age group. CNS tumors represent approximately 17% of all malignancies in the pediatric age range, including adolescents. Glial neoplasms in children account for up to 60% of supratentorial intraaxial tumors. Their histological distribution and prognostic features differ from that of adults. Aims and Objectives: To study clinical and pathological characteristics, and to analyze the outcome using the Engel′s classification for seizures, Karnofsky′s score during the available follow-up period of minimum 1 year following the surgical and adjuvant therapy of supratentorial intraaxial extraventricular primary pediatric (SIEPP brain tumors in children equal or less than 18 years. Materials and Methods: The study design is a prospective study done in NIMS from October 2008 to January 2012. All the patients less than 18 years of age operated for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from the study. Post operative CT or magnetic resonance imaging (MRI is done following surgery. Results and Analysis: There were 2, 8 and 20 patients in the age range of 0-2 years, >2-10 years and 10-18 years, respectively. There were 21 male patients and 9 female patients. Out of 30 patients, 16 had lesion in the temporal lobe, 6 in frontal lobe, 4 in thalamus, 3 in parietal lobe and 1 in occipital lobe. Out of 30 patients, 11 patients had malignant lesions and nineteen patients had benign lesions. Gross total excision could be achieved in 19 patients and subtotal in 11 patients. Seven patients had mortality and four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained same. Conclusions: SIEPP brain tumors have male preponderance, occur

  16. Occupational Neurobrucellosis Mimicking a Brain Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Hussein Algahtani

    2017-01-01

    Full Text Available Brucellosis is a zoonotic bacterial infection which is transmitted to humans from infected animals and is endemic in many parts of the world including Saudi Arabia. In this article, we report a case of occupational neurobrucellosis that presented with a space-occupying lesion mimicking a brain tumor. We stress on the importance of obtaining detailed social history including occupation to reach the diagnosis in several conditions including brucellosis. We also stress on taking universal precautions when handling any specimens. It may be advisable that manipulation of all unknown specimens arriving at the laboratory should occur in biological safety cabinet until a highly infectious organism is ruled out. Neurobrucellosis should be included in the differential diagnosis in patients presenting with solitary mass lesion mimicking brain tumor especially in endemic areas or high occupational risk group.

  17. Occupational Neurobrucellosis Mimicking a Brain Tumor: A Case Report and Review of the Literature

    Science.gov (United States)

    Abdulghani, Dina; Farhan, Roiya; Algahtani, Raghad

    2017-01-01

    Brucellosis is a zoonotic bacterial infection which is transmitted to humans from infected animals and is endemic in many parts of the world including Saudi Arabia. In this article, we report a case of occupational neurobrucellosis that presented with a space-occupying lesion mimicking a brain tumor. We stress on the importance of obtaining detailed social history including occupation to reach the diagnosis in several conditions including brucellosis. We also stress on taking universal precautions when handling any specimens. It may be advisable that manipulation of all unknown specimens arriving at the laboratory should occur in biological safety cabinet until a highly infectious organism is ruled out. Neurobrucellosis should be included in the differential diagnosis in patients presenting with solitary mass lesion mimicking brain tumor especially in endemic areas or high occupational risk group. PMID:28299214

  18. Peritumoral hemorrhage after radiosurgery for metastatic brain tumor; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Motozaki, Takahiko (Nishinomiya City General Hospital, Hyogo (Japan)); Ban, Sadahiko; Yamamoto, Toyoshiro; Hamasaki, Masatake

    1994-08-01

    An unusual case of peritumoral hemorrhage after radiosurgery for the treatment of metastatic brain tumor is reported. This 64-year-old woman had a history of breast cancer and underwent right mastectomy in 1989. She remained well until January 1993, when she started to have headache, nausea and speech disturbance, and was hospitalized on February 25, 1993. Neurological examination disclosed right hemiparesis and bilateral papilledema. CT scan and MR imaging showed a solitary round mass lesion in the left basal ganglia region. It was a well-demarcated, highly enhanced mass, 37 mm in diameter. Cerebral angiography confirmed a highly vascular mass lesion in the same location. She was treated with radiosurgery on March 8 (maximum dose was 20 Gy in the center and 10 Gy in the peripheral part of the tumor). After radiosurgery, she had an uneventful course and clinical and radiosurgical improvement could be detected. Her neurological symptoms and signs gradually improved and reduction of the tumor size and perifocal edema could be seen one month after radiosurgery. However, 6 weeks after radiosurgery, she suddenly developed semicoma and right hemiplegia. CT scan disclosed a massive peritumoral hemorrhage. Then, emergency craniotomy, evacuation of the hematoma and total removal of the tumor were performed on April 24. Histopathological diagnosis was adenocarcinoma. It was the same finding as that of the previous breast cancer. Histopathological examination revealed necrosis without tumor cells in the center and residual tumor cells in the peripheral part of the tumor. It is postulated that peritumoral hemorrhage was caused by hemodynamic changes in the vascular-rich tumor after radiosurgery and breakdown of the fragile abnormal vessels in the peripheral part of the tumor. (author).

  19. Hypothalamic tumor

    Science.gov (United States)

    Complications of brain surgery may include: Bleeding Brain damage Death (rarely) Infection Seizures can result from the tumor or from any surgical procedure on the brain. Hydrocephalus can occur with some tumors and ...

  20. Optimizing brain tumor resection. Midfield interventional MR imaging.

    Science.gov (United States)

    Alexander, E

    2001-11-01

    The development of the intraoperative MR imager represents an important example of creative vision and interdisciplinary teamwork. The result is a remarkable tool for neurosurgical applications. MRT allows surgical manipulation under direct visualization of the intracranial contents through the eye of the surgeon and through the volumetric images of the MR imaging system. This technology can be applied to cranial and spinal cases, and forseeably can encompass application to the entire gamut of neurosurgical efforts. The author's experience has been that this device is easy and comfortable for the surgeon to use. Image acquisition, giving views in the plane of choice, lasts no more than 2 to 60 seconds (depending on the imaging method), and does not increase the duration of a given procedure substantially. The author believes that the information received through intraoperative MR imaging scanning ultimately will contribute to decreasing the duration of surgery. Future possibilities include combining the intraoperative MR imager with other technologies, such as the endoscope, focused ultrasound, robotics, and the evaluation of brain function intraoperatively. The development of the intraoperative MR imager marks a significant advance in neurosurgery, an advance that will revolutionize intraoperative visualization as fully as the operating microscope. The combination of intraoperative visualization and precise surgical navigation is unparalleled, and its enhancement of surgical applications will be widespread. Considering the remarkable potential of the intraoperative MR imager for neurosurgical applications, optimal magnet design, image quality, and navigational methods are necessary to capitalize on the advantages of this revolutionary tool. The intraoperative MR imaging system that the author's team has developed and used has combined these features, and allows the performance of open surgical procedures without the need of patient or magnet repositioning. By

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

    OpenAIRE

    Curtin, James; King, Gwendalyn; Candolfi, Marianela; Greeno, Remy; Kroeger, Kurt; Lowenstein, Pedro; Castro,Maria

    2005-01-01

    Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implem...

  2. Frequency, Clinical Correlates, and Ratings of Behavioral Changes in Primary Brain Tumor Patients: A Preliminary Investigation

    OpenAIRE

    Simpson, Grahame K.; Eng-Siew eKoh; Diane eWhiting; Wright, Kylie M.; Teresa eSimpson; Rochelle eFirth; Lauren eGillett; Kathryn eYounan

    2015-01-01

    Purpose Few studies have addressed the specific behavioral changes associated with primary brain tumor (PBT). This paper will report on the frequency and demographic/clinical correlates of such behaviors, and the reliability of rating such behaviors among people with PBT, family informants, and clinicians. The association of behavioral changes and patient functional status will also be discussed. Methods A total of 57 patients with 37 family informants were recruited from two large...

  3. Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors

    DEFF Research Database (Denmark)

    Larsson, H B; Stubgaard, M; Frederiksen, Jette Lautrup Battistini;

    1990-01-01

    In this study quantitation of the degree of deficiency of the blood-brain barrier (BBB) in patients with multiple sclerosis or brain tumors, by using MRI, is shown to be possible. As a measure of permeability of the BBB to Gadolinium-DTPA (Gd-DTPA) the flux per unit of distribution volume per unit...

  4. Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

    Energy Technology Data Exchange (ETDEWEB)

    Shiroishi, Mark S.; Nelson, Marvin D. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Pediatric Radiology, Pittsburgh, PA (United States); Moore, Kevin R. [Primary Children' s Medical Center, Department of Radiology, Salt Lake City, UT (United States); Gilles, Floyd H. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Pathology, Los Angeles, CA (United States); Gonzalez-Gomez, Ignacio [All Children' s Hospital, Department of Pathology, St. Petersburg, FL (United States); Blueml, Stefan [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States)

    2015-09-15

    The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wron