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Sample records for glioblastoma mimicking cerebral

  1. Glioblastoma mimicking a cerebral contusion: A case report

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    LI, XINWEI; WANG, KUN; ZHANG, ANLING; SONG, ZHENGFEI; YANG, SHUXU; QIAN, CONG; WANG, YIRONG

    2013-01-01

    A 61-year-old male presented with a rare case of glioblastoma mimicking a cerebral contusion subsequent to collapsing. The patient had been medicated for hypertension for seven years and diabetes for eight years prior to hospitalization. Brain computed tomography (CT) revealed a cerebral contusion and intracerebral hemorrhage (ICH) in the left temporal region. The patient was initially administered intravenous drugs to reduce the intracranial pressure following the diagnosis of a cerebral con...

  2. Comparison of solitary cerebral metastasis and glioblastoma multiform

    International Nuclear Information System (INIS)

    Kim, Hyun Cheol; Choi, Woo Suk; Kim, Eui Jong; Oh, Joo Hyeong; Yoon, Yup

    1996-01-01

    The purpose of this study is to evaluate the MR images of solitary cerebral metastasis and glioblastoma multiform to determine the differential findings. Ten cases of solitary cerebral metastasis and 14 cases of glioblastoma multiform were retrospectively reviewed, all of which were proved by pathologically. The MR findings were compared in regard to tumor size and location, degree of edema, enhancement pattern, and shape of rime enhancement. Mean maximum diameter or solitary cerebral metastasis was 3.85 cm(s.d. 1.47). Metastatic lesions were located in corticomedullary junction(70%) with cerebellum in 2 cases. The locations of glioblastoma multiform were white matter(64%) without cerebellar involvement and the mean maximum diameter was 5.43 cm(s.d. 0.99). In solitary cerebral metastasis, the size of edema was larger than the tumor diameter in 50%, but glioblastoma multiform did not show severe degree of edema. Rim enhancement seen in 7 cases of solitary cerebral metastasis showed unilocular shape and complete rim in 6 cases, and even thickness and smooth inner margine in 5 cases. However, rim enhancement seen in 11 cases of glioblastoma multiform showed multilocular appearance with septa in all cases, incomplete rim in 5 cases, and uneven thickness and irregular inner margin in 10 cases. Tumor location, degree of edema, and rim enhancement pattern on Gd-enhanced MR may be useful in differentiation between solitary cerebral metastasis and glioblastoma multiform

  3. Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature

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    Luciani, L?a; Dubourg, Gr?gory; Graillon, Thomas; Honnorat, Estelle; Lepidi, Hubert; Drancourt, Michel; Seng, Piseth; Stein, Andreas

    2016-01-01

    Background Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. Case presentation A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was per...

  4. Herpes Simplex Virus (HSV-1 Encephalitis Mimicking Glioblastoma: Case Report and Review of the Literature

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    Burke A. Cunha

    2014-12-01

    Full Text Available Glioblastoma multiforme (GBM often presents as a brain mass with encephalitis. In a patient with GBM, subsequent presentation with new onset encephalitis may be due to another GBM or Herpes simplex virus 1 (HSV-1 encephalitis. We present a case of HSV-1 encephalitis mimicking GBM in a patient with previous GBM.

  5. Abscess within a glioblastoma: mimicking a matryoshka doll.

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    Kishore, Kislay; Beniwal, Manish; Rao, Shilpa; Rao, K V L N; Vazhayil, Vikas; Srinivas, Dwarkanath; Somanna, Sampath

    2018-02-14

    Abscess co-existing within a brain tumor is a rare entity. Case reports in literature primarily consist of sellar pathology and parenchymal lesions including meningioma, glioma, and metastases. We report a case of glioblastoma with an intra-tumoral abscess in a middle-aged lady with no prior invasive procedure or systemic focus of infection. A 45-year old lady presented with new onset generalized seizures and rapidly progressive left hemiparesis. Imaging showed right frontal necrotic lesion with peripherally enhancing wall with solid component posteriorly. There was no diffusion restriction within the lesion. She was non-toxic and there was no systemic focus of infection. With the provisional diagnosis of malignant glioma, she underwent surgical resection of the lesion. A differential of abscess, however, was considered pre-operatively because of the rapid increase in the size of the lesion. At surgery, there was a pus-filled cavity with few areas of greyish, soft, flimsy wall and thrombosed veins. This raised a strong suspicion of a co-existing abscess within a malignant glioma and was confirmed by histopathological and microbiological examination. It is important for neurosurgeons to be aware of this rare entity. The treatment protocol remains controversial and is primarily guided by expert opinion. It is important to aggressively treat the patient with antibiotics followed by adjuvant therapy for malignancy. The timing and administration of adjuvant therapy are unclear. We suggest a delay of chemotherapy until at least 4 weeks of therapy with sensitive antibiotics. Copyright © 2018. Published by Elsevier Inc.

  6. Necrosis de médula espinal, edema cerebral y glioblastoma

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    Iglesias Rozas, José Rafael, 1942-

    1987-01-01

    Cinco imágenes de una necrosis de la médula espinal, un edema cerebral y un glioblastoma en una paciente de 76 años. Five pictures of a spinal cord necrosis, a cerebral edema and a glioblastoma in a 76-year-old female patient.

  7. Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

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    Luciani, Léa; Dubourg, Grégory; Graillon, Thomas; Honnorat, Estelle; Lepidi, Hubert; Drancourt, Michel; Seng, Piseth; Stein, Andreas

    2016-07-07

    Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

  8. Severe cerebral edema following nivolumab treatment for pediatric glioblastoma: case report.

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    Zhu, Xiao; McDowell, Michael M; Newman, William C; Mason, Gary E; Greene, Stephanie; Tamber, Mandeep S

    2017-02-01

    Nivolumab is an immune checkpoint inhibitor (ICI) currently undergoing Phase III clinical trials for the treatment of glioblastoma. The authors present the case of a 10-year-old girl with glioblastoma treated with nivolumab under compassionate-use guidelines. After the first dose of nivolumab the patient developed hemiparesis, cerebral edema, and significant midline shift due to severe tumor necrosis. She was managed using intravenous dexamethasone and discharged on a dexamethasone taper. The patient's condition rapidly deteriorated after the second dose of nivolumab, demonstrating hemiplegia, seizures, and eventually unresponsiveness with a fixed and dilated left pupil. Computed tomography of her brain revealed malignant cerebral edema requiring emergency decompressive hemicraniectomy. Repeat imaging demonstrated increased size of the lesion, reflecting immune-mediated inflammation and tumor necrosis. The patient remained densely hemiplegic, but became progressively more interactive and was ultimately extubated. She resumed nivolumab several weeks later, but again her condition deteriorated with headache, vomiting, swelling at the craniectomy site, and limited right-sided facial movement following the sixth dose. MRI demonstrated severe midline shift and uncal herniation despite her craniectomy. Her condition gradually declined, and she died several days later under "do not resuscitate/do not intubate" orders. To the authors' knowledge, this represents the first case of malignant cerebral edema requiring operative intervention following nivolumab treatment for glioblastoma in a pediatric patient.

  9. Cerebral peritumoral oedema study: Does a single dynamic MR sequence assessing perfusion and permeability can help to differentiate glioblastoma from metastasis?

    International Nuclear Information System (INIS)

    Lehmann, Pierre; Saliou, Guillaume; Marco, Giovanni de; Monet, Pauline; Souraya, Stoquart-Elsankari; Bruniau, Alexis; Vallée, Jean Noel; Ducreux, Denis

    2012-01-01

    Our purpose was to differentiate glioblastoma from metastasis using a single dynamic MR sequence to assess perfusion and permeability parameters. 24 patients with glioblastoma or cerebral metastasis with peritumoral oedema were recruited and explored with a 3 T MR unit. Post processing used DPTools software. Regions of interest were drawn around contrast enhancement to assess relative cerebral blood volume and permeability parameters. Around the contrast enhancement Glioblastoma present high rCBV with modification of the permeability, metastasis present slight modified rCBV without modification of permeability. In conclusion, peritumoral T2 hypersignal exploration associating morphological MR and functional MR parameters can help to differentiate cerebral metastasis from glioblastoma.

  10. Spontaneous Cervical Epidural Hematoma with Hemiparesis Mimicking Cerebral Stroke

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    Mehmet Tiryaki

    2014-01-01

    Full Text Available Aim. Spontaneous cervical epidural hematoma (SCEH is defined as an epidural hematoma that does not have an etiological explanation. The most common site for SCEH is cervicothoracic area. Early diagnosis and treatment are important for prognosis and good results. In this paper, we aimed to present a case who complains of sudden weakness on right extremities imitating cerebral stroke and that neuroimaging reveals spontaneous cervical epidural hematoma. Case. A 72-year-old woman was admitted to our hospital with acute neck pain and loss of strength on right extremities. On neurological examination, the patient had right hemiparesis. PT, aPTT, and INR results were 50.5, 42.8, and 4.8, respectively. Cranial MRI was in normal limits. Spinal MRI revealed a lesion that extends from C4 to C7 located on the right side and compatible with epidural hematoma. The patient was operated after normalization of INR values. Conclusion. Even though SCEH is a rare condition, it can cause severe morbidity and mortality. Early diagnosis and treatment are quiet important for prognosis. SCEH can easily be mistaken for stroke as with other pathologies and this diagnosis should come to mind especially in patients who have diathesis of bleeding.

  11. Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning.

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    Exeli, Ann-Katrin; Kellner, Daniel; Exeli, Lukas; Steininger, Phil; Wolf, Frank; Sedlmayer, Felix; Deutschmann, Heinz

    2018-02-06

    To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients. Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing. Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 - 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 - 8%). We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing.

  12. Glioblastoma multiforme subterfuge as acute cerebral hemorrhage: A case report and literature review

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    Seidu A. Richard

    2018-04-01

    Full Text Available Hemorrhagic related Glioblastoma multiforme (GBM are rare and characterizes with severe clinical scuffle. The etiology of this presentation although not well known is believed to be multifactorial. We present a case as well as review on the pathogenesis of evolution of the hematoma into ring enhancing features of GBM on imaging studies. We present a case of 28 years old man who suddenly went into coma for 9 hours preceded with seizures that latest for 10 minutes. He had no focal neurological signs. CT-Scans images indicated acute cerebral hemorrhage near the frontal horn of the left ventricle with brain edema about the hemorrhagic lesion and MRI done a week later revealed a cerebral ring enhancing lesion. The lesion was partially resected during surgery and immunohistochemical staining confirmed GBM (WHO, grade 4. The diagnosis of intratumoral hemorrhage in GBM was very challenging at the initial stages but with time the hematoma evolved into ring enhancing images typical of GBM. It’s not every intracranial hematoma that is of pure vascular origin.

  13. The role of cerebral blood flow gradient in peritumoral edema for differentiation of glioblastomas from solitary metastatic lesions.

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    Lin, Lin; Xue, Yunjing; Duan, Qing; Sun, Bin; Lin, Hailong; Huang, Xinming; Chen, Xiaodan

    2016-10-18

    Differentiation of glioblastomas from solitary brain metastases using conventional MRI remains an important unsolved problem. In this study, we introduced the conception of the cerebral blood flow (CBF) gradient in peritumoral edema-the difference in CBF values from the proximity of the enhancing tumor to the normal-appearing white matter, and investigated the contribution of perfusion metrics on the discrimination of glioblastoma from a metastatic lesion. Fifty-two consecutive patients with glioblastoma or a solitary metastatic lesion underwent three-dimensional arterial spin labeling (3D-ASL) before surgical resection. The CBF values were measured in the peritumoral edema (near: G1; Intermediate: G2; Far: G3). The CBF gradient was calculated as the subtractions CBFG1 -CBFG3, CBFG1 - CBFG2 and CBFG2 - CBFG3. A receiver operating characteristic (ROC) curve analysis was used to seek for the best cutoff value permitting discrimination between these two tumors. The absolute/related CBF values and the CBF gradient in the peritumoral regions of glioblastomas were significantly higher than those in metastases(P edema appears to be a more promising ASL perfusion metrics in differentiating high grade glioma from a solitary metastasis.

  14. Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients.

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    Jafari-Khouzani, Kourosh; Emblem, Kyrre E; Kalpathy-Cramer, Jayashree; Bjørnerud, Atle; Vangel, Mark G; Gerstner, Elizabeth R; Schmainda, Kathleen M; Paynabar, Kamran; Wu, Ona; Wen, Patrick Y; Batchelor, Tracy; Rosen, Bruce; Stufflebeam, Steven M

    2015-06-01

    This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. DSC-MRI is highly repeatable in high-grade glioma patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients12

    Science.gov (United States)

    Jafari-Khouzani, Kourosh; Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Bjørnerud, Atle; Vangel, Mark G.; Gerstner, Elizabeth R.; Schmainda, Kathleen M.; Paynabar, Kamran; Wu, Ona; Wen, Patrick Y.; Batchelor, Tracy; Rosen, Bruce; Stufflebeam, Steven M.

    2015-01-01

    OBJECTIVES This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. METHODS Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. RESULTS CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. CONCLUSIONS DSC-MRI is highly repeatable in high-grade glioma patients. PMID:26055170

  16. Transient neurological deficits mimicking left middle cerebral artery infarct after carotid artery stenting without associated imaging findings: A case report

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    Melek Kandemir

    2017-08-01

    Full Text Available Various complications have been reported after carotid artery stenting. Ischemic lesions and hyperperfusion syndrome are well-known complications, and new cerebral microembolic lesions detected via diffusion-weighted imaging are observed in almost all patients. We describe a case who developed transient neurological deficits immediately after stenting without additional imaging findings. A 64-year-old male underwent carotid artery stenting complicated by transient neurological deficits mimicking a left middle cerebral artery infarction. The complication occurred immediately after stenting, but the symptoms resolved within less than 48 h. Magnetic resonance imaging findings showed no signs of a new infarct, no hemorrhage, and no high signal intensity in the meninges. We conclude that the most likely pathogenesis of this complication was vasogenic edema because of vasoparalysis of the local vessels, resulting from hemodynamic changes occurring after stenting and/or biochemical effects of repeated contrast agent administration.

  17. Tectal glioblastoma Glioblastoma tetal

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    Feres Chaddad Neto

    2007-12-01

    Full Text Available Brain stem gliomas are a heterogeneous group of neoplasms arising mostly in paediatric patients. Tectal plate gliomas represent a particular type of brain stem tumours usually with a benign, indolent clinical course, presenting with signs of raised intracranial hipertension due to supra-tentorialhydrocephalous caused by aqueductal stenosis. Seldom high-grade lesions arise in this location with tremendous therapeutic implications. When a malignant tumour is clinically and radiographically suspected a biopsy should be performed to obtain histhological confirmation. Treatment is then planned in a case-by-case basis. We present the case of a glioblastoma of the tectal plate in a 22 years-old woman operated upon by a supracerebellar-infratentorial approach.Os gliomas do tronco cerebral são um grupo heterogêneo de neoplasias que acometem habitualmente crianças. Os gliomas da placa quadrigeminal representam um tipo particular de tumores do tronco cerebral, habitualmente com um curso benigno e indolente, surgindo com sinais de hipertensão intracraniana devido a hidrocefalia supra-tentorial provocada por compressão do aqueduto cerebral. Raramente surgem lesões de alto grau nesta região, mas as implicações terapêuticas são tremendas. Quando existe suspeita clínica e imagiológica de que se trata de lesão maligna, esta deve ser biopsada para se obter confirmação histológica. O tratamento deve então ser planejado caso a caso. Apresentamos o caso de glioblastoma da placa quadrigeminal em uma paciente de 22 anos intervencionado por via supracerebelar-infratentorial.

  18. Gyriform Infarction in Cerebral Air Embolism: Imaging Mimicker of Status Epilepticus.

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    Malhotra, Konark; Rayi, Appaji

    2017-01-01

    Cerebral air embolism (CAE) is a potentially fatal iatrogenic complication related to common procedures including central venous catheter (CVC) removal. We report an interesting case of CAE related to CVC removal that was further complicated with status epilepticus. Neuroimaging of CAE and status epilepticus could pose diagnostic dilemmas and require consideration of wide diagnostic differentials. We discuss the clinical presentation, mechanism, and diagnostic approach, especially neuroimaging to differentiate various etiologies in CAE patients.

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

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    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.

  20. Insulin-like growth factor 1 deficiency exacerbates hypertension-induced cerebral microhemorrhages in mice, mimicking the aging phenotype.

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    Tarantini, Stefano; Valcarcel-Ares, Noa M; Yabluchanskiy, Andriy; Springo, Zsolt; Fulop, Gabor A; Ashpole, Nicole; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-06-01

    Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1 f/f  + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment. In IGF-1-deficient mice, the same level of hypertension led to significantly earlier onset and increased incidence and neurological consequences of CMHs, as compared to control mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Previous studies showed that in aging, increased oxidative stress-mediated matrix metalloprotease (MMP) activation importantly contributes to the pathogenesis of CMHs. Thus, it is significant that hypertension-induced cerebrovascular oxidative stress and MMP activation were increased in IGF-1-deficient mice. We found that IGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and extracellular matrix remodeling, which together with the increased MMP activation likely also contributes to increased fragility of intracerebral arterioles. Collectively, IGF-1 deficiency promotes the pathogenesis of CMHs, mimicking the aging phenotype, which likely contribute to its deleterious effect on cognitive function. Therapeutic strategies that upregulate IGF-1 signaling in the cerebral vessels and/or reduce microvascular oxidative stress, and MMP activation may be useful for the prevention of CMHs, protecting cognitive function in high-risk elderly patients. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. Atypical unilateral posterior reversible encephalopathy syndrome mimicking a middle cerebral artery infarction

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    Camidag, Ilkay [Dept. of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkmenistan); Cho, Yang Je; Park, Mina; Lee, Seung Koo [Yonsei University Severance Hospital, Seoul (Korea, Republic of)

    2015-10-15

    Posterior reversible encephalopathy syndrome (PRES) is usually a reversible clinical and radiological entity associated with typical features on brain MR or CT imaging. However, the not-so-uncommon atypical radiological presentations of the condition are also present and they may go unrecognised as they are confused with other conditions. Here, we report a very rare case of atypical, unilateral PRES in a 49-year-old uremic, post-transplant female patient who presented with seizures. Initial MRI showed high-grade occlusion of the left middle cerebral artery (MCA) and lesions suggestive of subacute infarction in the ipsilateral frontotemporoparietal lobe. Patient symptoms had resolved a day after the onset without any specific treatment but early follow-up CT findings suggested hemorrhagic transformation. Follow-up MRI performed 2 years later showed complete disappearence of the lesions and persisting MCA occlusion.

  2. Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy

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    Stadlbauer, Andreas, E-mail: andi@nmr.at [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany); Department of Radiology and Nuclear Medicine, Medical University Vienna, Währinger Gürtel 18-20, A-1097 Vienna (Austria); Pichler, Petra [First Department of Internal Medicine, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Poelten (Austria); Karl, Marianne [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Brandner, Sebastian [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany); Lerch, Claudia [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Renner, Bertold [Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen (Germany); Heinz, Gertraud [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria)

    2015-06-15

    Highlights: • Antiangiogenic therapy can lead to a decreased in CBV in normal brain tissue. • Responding and pseudoresponding lesions to AAT showed a similar CBV decrease. • Cho and NAA allowed for a distinction of responding and pseudoresponding lesions. • Cr ratios are not suited for evaluation of antiangiogenic therapy response. • Responders to AAT may have an increased risk for remote progression of the GBM. - Abstract: Objectives: To evaluate the usefulness of quantitative advanced magnetic resonance imaging (MRI) methods for assessment of antiangiogenic therapy (AAT) response in recurrent glioblastoma multiforme (GBM). Methods: Eighteen patients with recurrent GBM received bevacizumab and 18 patients served as control group. Baseline MRI and two follow-up examinations were acquired every 3–5 months using dynamic susceptibility-weighted contrast (DSC) perfusion MRI and {sup 1}H-MR spectroscopic imaging ({sup 1}H-MRSI). Maps of absolute cerebral blood volume (aCBV) were coregistered with choline (Cho) and N-acetyl-aspartate (NAA) concentrations and compared to usually used relative parameters as well as controls. Results: Perfusion significantly decreased in responding and pseudoresponding GBMs but also in normal appearing brain after AAT onset. Cho and NAA concentrations were superior to Cr-ratios in lesion differentiation and showed a clear gap between responding and pseudoresponding lesions. Responders to AAT exceptionally frequently (6 out of 8 patients) showed remote GBM progression. Conclusions: Quantification of CBV reveals changes in normal brain perfusion due to AAT, which were not described so far. DSC perfusion MRI seems not to be suitable for differentiation between response and pseudoresponse to AAT. However, absolute quantification of brain metabolites may allow for distinction due to a clear gap at 6–9 months after therapy onset.

  3. Cerebral blood volume calculated by dynamic susceptibility contrast-enhanced perfusion MR imaging: preliminary correlation study with glioblastoma genetic profiles.

    Directory of Open Access Journals (Sweden)

    Inseon Ryoo

    Full Text Available To evaluate the usefulness of dynamic susceptibility contrast (DSC enhanced perfusion MR imaging in predicting major genetic alterations in glioblastomas.Twenty-five patients (M:F = 13∶12, mean age: 52.1±15.2 years with pathologically proven glioblastoma who underwent DSC MR imaging before surgery were included. On DSC MR imaging, the normalized relative tumor blood volume (nTBV of the enhancing solid portion of each tumor was calculated by using dedicated software (Nordic TumorEX, NordicNeuroLab, Bergen, Norway that enabled semi-automatic segmentation for each tumor. Five major glioblastoma genetic alterations (epidermal growth factor receptor (EGFR, phosphatase and tensin homologue (PTEN, Ki-67, O6-methylguanine-DNA methyltransferase (MGMT and p53 were confirmed by immunohistochemistry and analyzed for correlation with the nTBV of each tumor. Statistical analysis was performed using the unpaired Student t test, ROC (receiver operating characteristic curve analysis and Pearson correlation analysis.The nTBVs of the MGMT methylation-negative group (mean 9.5±7.5 were significantly higher than those of the MGMT methylation-positive group (mean 5.4±1.8 (p = .046. In the analysis of EGFR expression-positive group, the nTBVs of the subgroup with loss of PTEN gene expression (mean: 10.3±8.1 were also significantly higher than those of the subgroup without loss of PTEN gene expression (mean: 5.6±2.3 (p = .046. Ki-67 labeling index indicated significant positive correlation with the nTBV of the tumor (p = .01.We found that glioblastomas with aggressive genetic alterations tended to have a high nTBV in the present study. Thus, we believe that DSC-enhanced perfusion MR imaging could be helpful in predicting genetic alterations that are crucial in predicting the prognosis of and selecting tailored treatment for glioblastoma patients.

  4. Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Hye Jin; Kim, Woo Jin [Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2013-09-15

    Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

  5. Amnesia due to bilateral hippocampal glioblastoma

    International Nuclear Information System (INIS)

    Shimauchi, M.; Wakisaka, S.; Kinoshita, K.

    1989-01-01

    The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a 'butterfly' lesion, it is unusual for it to invade the limbic system selectively to this extent. (orig.)

  6. Intra-operative radiation therapy for malignant brain tumours: rationale, method, and treatment results of cerebral glioblastomas

    International Nuclear Information System (INIS)

    Matsutani, M.; Nakamura, O.; Nagashima, T.

    1994-01-01

    In radiation therapy for malignant brain tumours, the dose of radiation that can be safely delivered to a tumour is limited by the radiation tolerance of the adjacent normal brain tissue. Among various radiation modalities to produce local tumour eradication without unacceptable complications, we chose a large, single irradiation dose during the operation (intra-operative radiation therapy, IORT). In contrast to X-ray or Cobalt-60 gamma ray irradiation, IORT with a high-energy electron beam delivered by the Shimadzu 20 MeV betatron provides acceptable dose homogeneity with rapid fall-off of the radiation dose beyond the treatment volume. Thus, IORT has the advantage of precise demarcation of the target volume, minimum damage to surrounding normal tissues, and a high absorbed target dose (15-25 Gy in 5-10 min). On the basis of our experience with 170 patients treated by IORT, we established the treatment indications and method in patients with malignant brain tumours. IORT with a dose of 15-25 Gy was delivered to widely resected tumours followed by external radiation therapy. No acute or subacute complications were observed. Treatment results of 30 patients with glioblastoma treated by IORT (mean 18.3 Gy) combined with external radiation therapy (mean 58.5 Gy) resulted in a median survival of 119 weeks and a 2-year survival rate of 61 %. (authors)

  7. Amnesia due to bilateral hippocampal glioblastoma. MRI finding

    Energy Technology Data Exchange (ETDEWEB)

    Shimauchi, M.; Wakisaka, S.; Kinoshita, K. (Miyazaki Medical Coll., Kiyotake (Japan). Dept. of Neurosurgery)

    1989-11-01

    The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a 'butterfly' lesion, it is unusual for it to invade the limbic system selectively to this extent. (orig.).

  8. Acute Ischemic Stroke Secondary to Glioblastoma

    Science.gov (United States)

    Pina, Sofia; Carneiro, Ângelo; Rodrigues, Tiago; Samões, Raquel; Taipa, Ricardo; Melo-Pires, Manuel; Pereira, Cláudia

    2014-01-01

    Summary Glioblastoma is a malignant infiltrative glial tumor occurring most often over 50 years of age, with diverse clinical presentations. We describe a case of temporal lobe glioblastoma with a rare presentation as an acute ischemic stroke, discussing the imaging and histopathological findings, and reviewing the literature. A 77-year-old woman had sudden onset of left hemiparesis and hemihypoesthesia. The neuroradiological studies revealed an acute ischemic lesion in the right lenticulostriate arteries territory and a right anterior temporal lobe tumor, enhancing heterogeneously after contrast with enhancement of the right middle cerebral artery wall. Histopathological analysis of the resected temporal lesion revealed a glioblastoma multiforme with tumoral infiltration of the vascular wall. Glioblastoma should be considered in the etiology of acute ischemic stroke, where neuroimaging plays an important diagnostic role, enabling a more immediate therapeutic approach, with a consequent impact on survival. PMID:24571837

  9. Radiologic findings in patients treated with boron neutron capture therapy for glioblastoma multiforme within EORTC trial 11961

    NARCIS (Netherlands)

    Vos, Maaike J.; Turowski, Bernd; Zanella, Friedhelm E.; Paquis, Philippe; Siefert, Axel; Hideghéty, Katalin; Haselsberger, Klaus; Grochulla, Frank; Postma, Tjeerd J.; Wittig, Andrea; Heimans, Jan J.; Slotman, Ben J.; Vandertop, W. Peter; Sauerwein, Wolfgang

    2005-01-01

    PURPOSE: To assess the occurrence and development of cerebral radiologic changes (cerebral atrophy and white matter lesions) in patients treated with boron neutron capture therapy (BNCT) for primary supratentorial glioblastoma multiforme within the European Organization for Research and Treatment of

  10. Cerebral toksoplasmose primaert diagnosticeret som tumor

    DEFF Research Database (Denmark)

    Cortsen, M E; Skøt, J; Skriver, E B

    1992-01-01

    Three cases of cerebral toxoplasmosis as the presenting manifestation of AIDS are reported. The initial diagnoses were brain tumors because of the cerebral mass lesions which resembled glioblastoma. In the light of the increasing occurrence of AIDS, attention is drawn to cerebral toxoplasmosis...

  11. Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

    International Nuclear Information System (INIS)

    Server, Andres; Nakstad, Per H.; Orheim, Tone E.D.; Graff, Bjoern A.; Josefsen, Roger; Kumar, Theresa

    2011-01-01

    Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

  12. Acute ischemic stroke secondary to glioblastoma. A case report.

    Science.gov (United States)

    Pina, Sofia; Carneiro, Ângelo; Rodrigues, Tiago; Samões, Raquel; Taipa, Ricardo; Melo-Pires, Manuel; Pereira, Cláudia

    2014-02-01

    Glioblastoma is a malignant infiltrative glial tumor occurring most often over 50 years of age, with diverse clinical presentations. We describe a case of temporal lobe glioblastoma with a rare presentation as an acute ischemic stroke, discussing the imaging and histopathological findings, and reviewing the literature. A 77-year-old woman had sudden onset of left hemiparesis and hemihypoesthesia. The neuroradiological studies revealed an acute ischemic lesion in the right lenticulostriate arteries territory and a right anterior temporal lobe tumor, enhancing heterogeneously after contrast with enhancement of the right middle cerebral artery wall. Histopathological analysis of the resected temporal lesion revealed a glioblastoma multiforme with tumoral infiltration of the vascular wall. Glioblastoma should be considered in the etiology of acute ischemic stroke, where neuroimaging plays an important diagnostic role, enabling a more immediate therapeutic approach, with a consequent impact on survival.

  13. [Biology molecular of glioblastomas].

    Science.gov (United States)

    Franco-Hernández, C; Martínez-Glez, V; Rey, J A

    2007-10-01

    Glioblastomas, the most frequent and malignant human brain tumors, may develop de novo (primary glioblastoma) or by progression from low-grade or anapalsic astrocytoma (secondary glioblastoma). The molecular alteration most frequent in these tumor-like types is the loss of heterozygosity on chromosome 10, in which several genes have been identified as tumors suppressor. The TP53/MDM2/P14arf and CDK4/RB1/ P16ink4 genetic pathways involved in cycle control are deregulated in the majority of gliomas as well as genes that promote the cellular division, EGFR. Finally the increase of growth and angiogenics factors is also involved in the development of glioblastomas. One of the objectives of molecular biology in tumors of glial ancestry is to try to find the genetic alterations that allow to approach better the classification of glioblastomas, its evolution prediction and treatment. The new pathmolecular classification of gliomas should improve the old one, especially being concerned about the oncogenesis and heterogeneity of these tumors. It is desirable that this classification had clinical applicability and integrates new molecular findings with some known histological features with pronostic value. In this paper we review the most frequent molecular mechanisms involved in the patogenesis of glioblastomas.

  14. Autopsy findings in a long-term survivor with glioblastoma multiforme. Case report

    International Nuclear Information System (INIS)

    Yamada, Shozo; Endo, Yuzo; Takada, Koji; Usui, Masaaki; Hara, Mitsuru; Hirose, Takanori.

    1998-01-01

    Autopsy detected no tumor tissues in a patient who died 6.5 years after the diagnosis of glioblastoma multiforme. A 54-year-old male developed left hemiparesis one month prior to admission. Computed tomography demonstrated a cystic lesion in the right frontal region with irregular ring-like enhancement. The tumor was extensively removed together with the surrounding tissues followed by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous administration of interferon-β. Histological examination confirmed the diagnosis of glioblastoma multiform. He died of accidental head trauma 6.5 years after surgery. Autopsy of the brain detected no evidence of glioblastoma multiform. The only findings were cerebral edema and hematoma caused by head trauma, as well as histological changes due to radiation damage. This case apparently confirms the histological disappearance of tumor tissue in a long-term survivor with glioblastoma multiform. (author)

  15. Nanotechnology Applications for Glioblastoma

    Science.gov (United States)

    Nduom, Edjah; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G.

    2012-01-01

    Synopsis Glioblastoma remains one of the most difficult cancers to treat and represents the most common primary malignancy of the brain. While conventional treatments have found modest success in reducing the initial tumor burden, infiltrating cancer cells beyond the main mass are responsible for tumor recurrence and ultimate patient demise. Targeting the residual infiltrating cancer cells requires the development of new treatment strategies. The emerging field of cancer nanotechnology holds much promise in the use of multifunctional nanoparticles for the imaging and targeted therapy of GBM.. Nanoparticles have emerged as potential “theranostic” agents that can permit the diagnosis and therapeutic treatment of GBM tumors. A recent human clinical trial with magnetic nanoparticles has provided feasibility and efficacy data for potential treatment of GBM patients with thermotherapy. Here we examine the current state of nanotechnology in the treatment of glioblastoma and interesting directions of further study. PMID:22748656

  16. Role of bevacizumab therapy in the management of glioblastoma

    Directory of Open Access Journals (Sweden)

    Scott J Peak

    2010-04-01

    Full Text Available Scott J Peak, Victor A LevinNeuro-Oncology Program, Department of Neurosurgery and Neuroscience, Kaiser Permanente, Redwood City, CA, USAAbstract: Glioblastoma is one of the most common primary brain tumors and one of the most difficult to treat. In population-based studies only 30% of patients will survive 1 year and in the most efficacious surgery, irradiation, and chemotherapy clinical trials approximately 20% will live 2 years. Bevacizumab is a recombinant, antivascular epidermal growth factor receptor (VEGF monoclonal antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic brain edema; the consequences are that bevacizumab reduces the rate of glioblastoma tumor growth and its associated tumoral edema, thereby improving quality of life and survival for patients suffering from cerebral glioblastoma. In this review, we will summarize the studies that led to the use of bevacizumab in glioblastoma and the potential side-effects and complications that can be associated with its use and, finally, new opportunities for drug combinations with bevacizumab.Keywords: chemotherapy, VEGF, edema, central nervous system

  17. Dopamine signaling: target in glioblastoma

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk

    2014-01-01

    Roč. 5, č. 5 (2014), 1116-1117 ISSN 1949-2553 Institutional support: RVO:68378050 Keywords : Dopamine signaling * glioblastoma * MAPK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

  18. A prospective PET study of patients with glioblastoma multiforme

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Blinkenberg, M; Lassen, U

    2006-01-01

    OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy (carmu...... compared with structural imaging in the prospective evaluation of GBM. We found a difference in metabolic increase and tumor growth between the two treatment regimens, although this finding has limited relevance due to the design of the study.......OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy...... (carmustine, cisplatine and etoposide) and radiotherapy. Positron emission tomography (PET) was used to measure tumor- and cerebral metabolism. CT or MRI was used to estimate tumor volume by measurements of tumor area. RESULTS: Tumor metabolism was not increased during chemotherapy (P = 0.71), but increased...

  19. A comprehensive profile of recurrent glioblastoma

    DEFF Research Database (Denmark)

    Campos, B.; Olsen, Lars Rønn; Urup, T.

    2016-01-01

    In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkab...

  20. Supratentorial glioblastoma multiforme with spinal metastases

    Directory of Open Access Journals (Sweden)

    Abhidha Shah

    2010-01-01

    Full Text Available Glioblastoma multiforme is the most common malignant brain tumor in adults. Metastasis of intracranial glioblastoma via the cerebrospinal fluid to the spine is a rare occurrence. We present two cases of glioblastoma multiforme with spinal leptomeningeal spread who presented with back pain and paraparesis.

  1. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zi-xuan [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Rao, Wei [Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Huan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Nan-ding [Department of Cardiology, Xi' an Traditional Chinese Medicine Hospital, Xi' an, 710032 (China); Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Zong-ren, E-mail: zongren@fmmu.edu.cn [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China)

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  2. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    International Nuclear Information System (INIS)

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-01-01

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion

  3. Eosinophils in glioblastoma biology

    Directory of Open Access Journals (Sweden)

    Curran Colleen S

    2012-01-01

    Full Text Available Abstract Glioblastoma multiforme (GBM is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review.

  4. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: warren.mason@uhn.ca [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)

    2013-08-22

    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  5. Emerging Biomarkers in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Warren P. Mason

    2013-08-01

    Full Text Available Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6-methlyguanine-DNA-methyltransferase (MGMT promoter and deoxyribonucleic acid (DNA methylation, loss of heterozygosity (LOH of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH mutations, epidermal growth factor receptor (EGFR, epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1, vascular endothelial growth factor (VEGF, tumor suppressor protein p53, phosphatase and tensin homolog (PTEN, p16INK4a gene, cytochrome c oxidase (CcO, phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA], microRNAs (miRNAs, cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  6. Marcadores de angiogénesis, inflamación y coagulación en pacientes con glioblastoma

    OpenAIRE

    Reynés Muntaner, Gaspar

    2017-01-01

    Facultad de Medicina y Odontología Departamento de Medicina Programa de Doctorado 3042 Medicina Tesis Doctoral Marcadores de angiogénesis, inflamación y coagulación en pacientes con glioblastoma Presentada por: Gaspar Reynés Muntaner Dirigida por: Dra. Ana Lluch Hernández Dr. Jaime Font de Mora Saínz Dra. Vicenta Martínez Sales RESUMEN Valencia, mayo de 2017 El glioblastoma (GB) es el tumor cerebral maligno más frecuente y...

  7. Xanthogranulomatous cholecystitis mimicking gallbladder cancer.

    Science.gov (United States)

    Ewelukwa, Ofor; Ali, Omair; Akram, Salma

    2014-05-08

    Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer.

  8. Bacterial Carriers for Glioblastoma Therapy

    Directory of Open Access Journals (Sweden)

    Nalini Mehta

    2017-03-01

    Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

  9. Cerebral Palsy

    Science.gov (United States)

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  10. Multicystic Hepatocarcinoma Mimicking Liver Abscess

    Directory of Open Access Journals (Sweden)

    Evangelos Falidas

    2013-01-01

    Full Text Available The diagnosis of hepatocellular carcinoma (HCC became easier in relation to the improved radiological examinations; however, the neoplasm may occur under atypical presentations mimicking other benign or malignant processes. Multicystic HCC mimicking a liver abscess associated with septic-type fever and leukocytosis is rare, has a poor prognosis, and poses diagnostic and therapeutic dilemmas. We present the case of an 80-year-old patient, who presented with fever, leukocytosis, and large cystic masses involving right and left lobes of the liver initially considered abscesses and finally diagnosed as HCC after open drainage and liver biopsy. Although the patient died on the tenth postoperative day due to pulmonary oedema, the authors emphasize the high index of suspicion needed in the diagnosis of this unusual presentation of HCC.

  11. Two Unusual Aspects of Posterior Reversible Encephalopathy Syndrome Mimicking Primary and Secondary Brain Tumor Lesions

    Directory of Open Access Journals (Sweden)

    Mazamaesso Tchaou

    2015-01-01

    Full Text Available The posterior reversible encephalopathy syndrome (PRES is a rare clinical-radiological entity well described with typical clinical and radiological manifestations. Atypical presentation, especially in imaging, exists. The authors report here two cases of posterior reversible encephalopathy in which imaging aspects were atypical, mimicking, in the first case, hemorrhagic cerebral metastasis of cholangiocarcinoma and, in the second case, a brain tumor. The diagnosis has been retrospectively rectified due to clinical and radiological outcome.

  12. Propionic acidemia mimicking diabetic ketoacidosis.

    Science.gov (United States)

    Dweikat, Imad M; Naser, Enas N; Abu Libdeh, Abdulsalam I; Naser, Osama J; Abu Gharbieh, Najwan N; Maraqa, Nizar F; Abu Libdeh, Bassam Y

    2011-05-01

    Propionic acidemia manifesting with hyperglycemia is rare. Few cases have been reported mainly of the neonatal-onset form associated with high mortality. We report a 9-month-old Palestinian boy who manifested with coma, severe hyperglycemia and ketoacidosis mimicking diabetic ketoacidosis. Family history of unexplained infant deaths was helpful in reaching the correct diagnosis. In response to therapy, the patient regained consciousness without neurologic deficits and had normal examination. This is, to our knowledge, the first case report of late-onset propionic acidemia that had this presentation and survived. Copyright © 2010 The Japanese Society of Child Neurology. All rights reserved.

  13. Combining Immunotherapy with Standard Glioblastoma Therapy

    Science.gov (United States)

    This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.

  14. Contribución del microentorno a la quimiorresistencia de células iniciadoras de glioblastoma en modelos in vitro

    OpenAIRE

    Fernández Fuente, Gonzalo

    2017-01-01

    En este trabajo, hemos estudiado la biología de los Glioblastomas, el tumor cerebral primario más frecuente en adultos y que representa uno de los tipos tumorales más agresivos y letales que se conocen en el ser humano. En este contexto, hemos analizado la quimiorresistencia a distintos grupos de fármacos tanto en cultivos primarios como líneas de Glioblastoma tanto en modelos en 2 como en 3 dimensiones. Nuestros resultados muestran como algunas de las propiedades de la matriz extracelular co...

  15. Histoplasmosis mimicking metastatic spinal tumour.

    Science.gov (United States)

    Liu, Bing; Qu, Liyan; Zhu, Jian; Yang, Zhengming; Yan, Shigui

    2017-08-01

    Histoplasmosis is an infection caused by a fungus called Histoplasma. Diagnosis of histoplasmosis is based on the culture of biological samples and detection of fungus in tissues. Histoplasmosis can mimic malignant lesions. We report a 65-year-old, immunocompetent, male patient with back pain. We describe the main clinical and radiological characteristics in our patient who had vertebral histoplasmosis that mimicked cancer. A computed tomography scan showed lytic lesions of the right side of T4, T5, and T6 vertebral bodies. Magnetic resonance imaging displayed abnormal marrow signals in T4, T5, and T6 vertebral bodies (low signal on T1, high on T2 and short time inversion recovery (STIR)). Which was mimicking malignancy, such as haematological malignancy and metastatic bone cancer. Therefore, thoracic spinal surgery using the anterior approach was performed. An intraoperative frozen section examination and routine postoperative pathology showed thoracic histoplasmosis infection. Treatment of histoplasmosis was performed with oral itraconazole. The lesions did not progress and the patient symptomatically improved at a follow-up of 26 months.

  16. Molecular heterogeneity in glioblastoma: potential clinical implications

    Directory of Open Access Journals (Sweden)

    Nicole Renee Parker

    2015-03-01

    Full Text Available Glioblastomas, (grade 4 astrocytomas, are aggressive primary brain tumors characterized by histopathological heterogeneity. High resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

  17. Immunotherapy for the Treatment of Glioblastoma

    Science.gov (United States)

    Thomas, Alissa A.; Ernstoff, Marc S.; Fadul, Camilo E.

    2012-01-01

    Glioblastoma, the most aggressive primary brain tumor, thrives in a microenvironment of relative immunosuppression within the relatively immune-privileged central nervous system. Despite treatments with surgery, radiation therapy, and chemotherapy, prognosis remains poor. The recent success of immunotherapy in the treatment of other cancers has renewed interest in vaccine therapy for the treatment of gliomas. In this article, we outline various immunotherapeutic strategies, review recent clinical trials data, and discuss the future of vaccine therapy for glioblastoma. PMID:22290259

  18. Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare differential diagnosis in Central Europe

    Energy Technology Data Exchange (ETDEWEB)

    Sabel, M.; Weber, F. [Dept. of Neurosurgery, Heinrich-Heine Univ. Duesseldorf (Germany); Neuen-Jacob, E. [Dept. of Neuropathology, Heinrich-Heine Univ. Duesseldorf (Germany); Vogt, C. [Dept. of Internal Medicine, Heinrich-Heine Univ. Duesseldorf (Germany)

    2001-03-01

    A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/{mu}l) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis. (orig.)

  19. Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare differential diagnosis in Central Europe

    International Nuclear Information System (INIS)

    Sabel, M.; Weber, F.; Neuen-Jacob, E.; Vogt, C.

    2001-01-01

    A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/μl) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis. (orig.)

  20. Cerebral vasculitis

    International Nuclear Information System (INIS)

    Greenan, T.J.; Grossman, R.I.

    1990-01-01

    This paper reviews retrospectively MR, CT, and angiographic findings in patients with cerebral vasculitis in order to understand the strengths and weaknesses of the various imaging modalities, as well as the spectrum of imaging abnormalities in this disease entity. Studies were retrospectively reviewed in 12 patients with cerebral vasculitis proved by means of angiography and/or brain biopsy

  1. Molecular biology of glioblastoma: Classification and mutational locations.

    Science.gov (United States)

    Soomro, Shahid Hussain; Ting, Li Rui; Qing, Yang Yi; Ren, Mingxin

    2017-09-01

    Glioblastomas are regarded as the most common malignant brain tumours with great morphological and genetical heterogeneity. They comprise 12% to 15% of all intracranial tumours, with its peak observed in the 8th decade of life. The five-year survival is only 5%. Primary glioblastomas are more common in elders while secondary glioblastomas mostly involve younger people. Based upon gene expression profile, researchers have classified glioblastomas into several subtypes. Genetic mutations provide an advanced standard platform essential for diagnosis, therapeutic remedies and prognosis of glioblastomas. Common mutations observed in glioblastomas are loss of heterozygosity at 10q followed by epidermal growth factor receptor amplification (34%) and others. Vascular occlusion model and tumour stem cell model can explain the possible mechanism in glioblastomas pathogenesis. This review highlights glioblastomas' classifications, genetic mutations, pathogenesis and prognosis of different sub-types.

  2. Cerebral infarctions due to CNS infection with Enterobacter sakazakii

    International Nuclear Information System (INIS)

    Gallagher, P.G.; Ball, W.S.

    1991-01-01

    Recent reports have implicated Enterobacter sakazakii, a gram-negative enteric bacillus, in neonatal sepsis and meningitis. Cases of severe central nervous system involvement, including ventriculitis, brain abscess, infarction, and cyst formation, have been described. We present serial head CT findings in a case of neonatal E. sakazakii meningitis complicated by a ring enhancing cerebral infarction which mimicked abscess formation. In meningitis secondary to this agent, a recognized pattern of cerebral hypodensity with or without cystic degeneration late in the course of the infection is likely to represent cerebral infarction rather than an abscess especially if there is a lack of culture evidence of a bacterial infection. (orig.)

  3. Cerebral infarctions due to CNS infection with Enterobacter sakazakii

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, P.G. (Cincinnati Univ., OH (USA). Dept. of Pediatrics Children' s Hospital Medical Center, Cincinnati, OH (USA)); Ball, W.S. (Cincinnati Univ., OH (USA). Dept. of Radiology Children' s Hospital Medical Center, Cincinnati, OH (USA))

    1991-02-01

    Recent reports have implicated Enterobacter sakazakii, a gram-negative enteric bacillus, in neonatal sepsis and meningitis. Cases of severe central nervous system involvement, including ventriculitis, brain abscess, infarction, and cyst formation, have been described. We present serial head CT findings in a case of neonatal E. sakazakii meningitis complicated by a ring enhancing cerebral infarction which mimicked abscess formation. In meningitis secondary to this agent, a recognized pattern of cerebral hypodensity with or without cystic degeneration late in the course of the infection is likely to represent cerebral infarction rather than an abscess especially if there is a lack of culture evidence of a bacterial infection. (orig.).

  4. New perspectives in glioblastoma antiangiogenic therapy

    Directory of Open Access Journals (Sweden)

    Alisa Madalina Popescu

    2015-12-01

    Full Text Available Glioblastoma (GB is highly vascularised tumour, known to exhibit enhanced infiltrative potential. One of the characteristics of glioblastoma is microvascular proliferation surrounding necrotic areas, as a response to a hypoxic environment, which in turn increases the expression of angiogenic factors and their signalling pathways (RAS/RAF/ERK/MAPK pathway, PI3K/Akt signalling pathway and WTN signalling cascade. Currently, a small number of anti-angiogenic drugs, extending glioblastoma patients survival, are available for clinical use. Most medications are ineffective in clinical therapy of glioblastoma due to acquired malignant cells or intrinsic resistance, angiogenic receptors cross-activation and redundant intracellular signalling, or the inability of the drug to cross the blood-brain barrier and to reach its target in vivo . Researchers have also observed that GB tumours are different in many aspects, even when they derive from the same tissue, which is the reason for personalised therapy. An understanding of the molecular mechanisms regulating glioblastoma angiogenesis and invasion may be important in the future development of curative therapeutic approaches for the treatment of this devastating disease.

  5. Advance Care Planning in Glioblastoma Patients

    Directory of Open Access Journals (Sweden)

    Lara Fritz

    2016-11-01

    Full Text Available Despite multimodal treatment with surgery, radiotherapy and chemotherapy, glioblastoma is an incurable disease with a poor prognosis. During the disease course, glioblastoma patients may experience progressive neurological deficits, symptoms of increased intracranial pressure such as drowsiness and headache, incontinence, seizures and progressive cognitive dysfunction. These patients not only have cancer, but also a progressive brain disease. This may seriously interfere with their ability to make their own decisions regarding treatment. It is therefore warranted to involve glioblastoma patients early in the disease trajectory in treatment decision-making on their future care, including the end of life (EOL care, which can be achieved with Advance Care Planning (ACP. Although ACP, by definition, aims at timely involvement of patients and proxies in decision-making on future care, the optimal moment to initiate ACP discussions in the disease trajectory of glioblastoma patients remains controversial. Moreover, the disease-specific content of these ACP discussions needs to be established. In this article, we will first describe the history of patient participation in treatment decision-making, including the shift towards ACP. Secondly, we will describe the possible role of ACP for glioblastoma patients, with the specific aim of treatment of disease-specific symptoms such as somnolence and dysphagia, epileptic seizures, headache, and personality changes, agitation and delirium in the EOL phase, and the importance of timing of ACP discussions in this patient population.

  6. Adoptive Cell Therapies for Glioblastoma

    Directory of Open Access Journals (Sweden)

    Kevin James Bielamowicz

    2013-11-01

    Full Text Available Glioblastoma (GBM is the most common and most aggressive primary brain malignancy and, as it stands, is virtually incurable. With the current standard-of-care, maximum feasible surgical resection followed by radical radiotherapy and adjuvant temozolomide, survival rates are at a median of 14.6 months from diagnosis in molecularly unselected patients(1. Collectively, the current knowledge suggests that the continued tumor growth and survival is in part due to failure to mount an effective immune response. While this tolerance is subtended by the tumor being utterly self, it is to a great extent due to local and systemic immune compromise mediated by the tumor. Different cell modalities including lymphokine-activated killer (LAK cells, natural killer (NK cells, cytotoxic T lymphocytes (CTL, and transgenic chimeric antigen receptor (CAR- or αβ T cell receptor (TCR grafted T cells are being explored to recover and or redirect the specificity of the cellular arm of the immune system towards the tumor complex. Promising phase I/II trials of such modalities have shown early indications of potential efficacy while maintaining a favorable toxicity profile. Efficacy will need to be formally tested in phase II/III clinical trials. Given the high morbidity and mortality of GBM, it is imperative to further investigate and possibly integrate such novel cell-based therapies into the current standards-of-care and herein we collectively assess and critique the state-of-the-knowledge pertaining to these efforts.

  7. Treatment of Glioblastoma in Older Adults.

    Science.gov (United States)

    Braun, Kelly; Ahluwalia, Manmeet S

    2017-10-26

    Glioblastoma is the most common primary malignant brain tumor diagnosed in the USA and is associated with a poor prognosis. The outcomes in elderly patients (more than 65 years of age) are worse when compared to those younger than age 65 at the time of diagnosis. Older patients are not always offered treatments that would otherwise be considered standard of care due to comorbidities and concerns about toxicity and tolerability. The initial European Organization for Research and Treatment of Cancer study that led to approval of temozolomide in glioblastoma excluded patients more than 70 years of age. This review outlines challenges that arise in the treatment of glioblastoma in the elderly population and discusses results of recent studies that established the role of adjuvant chemotherapy in addition to radiation and surgery. There is evidence that these patients can benefit from a more aggressive and safe resection, from hypofractionated radiation treatments, and from adjuvant temozolomide.

  8. Walking ability in patients with glioblastoma

    DEFF Research Database (Denmark)

    Liljehult, Monique Mesot; Buus, Lise; Mesot Liljehult, Jacob

    2017-01-01

    ability and 1 year mortality. Data were gathered from prospective recordings in a brain cancer database supplemented by retrospective review of electronic patient records. We included 109 patients with glioblastoma, 47 women and 62 men with mean age 65 years. At admission 84 patients were tested with Berg......Primary brain tumors frequently cause considerable functional impairments and the survival time when diagnosed with glioblastoma is 14.6 months. The aim of this study was to examine if baseline postural control and walking ability in patients with glioblastoma could predict long term walking...... higher in patients who lost their ability to walk within 4-8 months of the first admission. This study showed that Berg Balance Scale has some ability to predict the loss of walking ability 4-8 months after admission. This could be an important indicator pin pointing patients most in need of more...

  9. Cerebral Paragonimiasis.

    Science.gov (United States)

    Miyazaki, I

    1975-01-01

    The first case of cerebral paragonimiasis was reported by Otani in Japan in 1887. This was nine years after Kerbert's discovery of the fluke in the lungs of Bengal tigers and seven years after a human pulmonary infection by the fluke was demonstrated by Baelz and Manson. The first case was a 26-year-old man who had been suffering from cough and hemosputum for one year. The patient developed convulsive seizures with subsequent coma and died. The postmortem examination showed cystic lesions in the right frontal and occipital lobes. An adult fluke was found in the occipital lesion and another was seen in a gross specimen of normal brain tissue around the affected occipital lobe. Two years after Otani's discovery, at autopsy a 29-year-old man with a history of Jacksonian seizure was reported as having cerebral paragonimiasis. Some time later, however, it was confirmed that the case was actually cerebral schistosomiasis japonica. Subsequently, cases of cerebral paragonimiasis were reported. However, the majority of these cases were not confirmed histologically. It was pointed out that some of these early cases were probably not Paragonimus infection. After World War II, reviews as well as case reports were published. Recently, investigations have been reported from Korea, with a clinicla study on 62 cases of cerebral paragonimiasis seen at the Neurology Department of the National Medical Center, Seoul, between 1958 and 1964. In 1971 Higashi described a statistical study on 105 cases of cerebral paragonimiasis that had been treated surgically in Japan.

  10. Hyaluronidase allergy mimicking orbital cellulitis.

    Science.gov (United States)

    Raichura, Nirav D; Alam, Md Shahid; Jaichandran, V V; Mistry, Saurabh; Mukherjee, Bipasha

    2017-10-20

    Hyaluronidase enzyme is a common additive with local anesthetic agent to facilitate faster permeation of the anesthetic in periocular tissues during ophthalmic surgery. We report a series of five subjects presenting with clinical features mimicking orbital cellulitis following peribulbar anesthesia and consequently diagnosed with hyaluronidase hypersensitivity. The study was conducted at a tertiary eye care center in Southern India. It was a retrospective interventional case series. We retrospectively reviewed the case records of patients diagnosed as and treated for hyaluronidase allergy from 2011 to 2015. The presenting features included periocular edema, proptosis, and restriction of ocular movements. The symptoms appeared immediately after the injection to as late as 6 days after the surgery. All patients underwent comprehensive ophthalmic evaluation, relevant investigations, and dermal allergy tests. All five patients tested positive for hyaluronidase. Patients were treated with antihistaminics, systemic steroids, and emergency orbital decompression, when required. In majority of the patients, symptoms resolved in 3-5 days. Clinically, hyaluronidase allergy may mimic orbital cellulitis, which in the context of a recent intraocular surgery may be alarming for both the patient and the surgeon. However, with prompt intervention, the prognosis is extremely favorable in cases of hyaluronidase allergy. It is important for ophthalmic surgeons and anesthetists to recognize and differentiate this entity from the more serious vision threatening conditions.

  11. Advances in Glioblastoma Multiforme Treatment: New Models for Nanoparticle Therapy

    Directory of Open Access Journals (Sweden)

    Elif Ozdemir-Kaynak

    2018-03-01

    Full Text Available The most lethal form of brain cancer, glioblastoma multiforme, is characterized by rapid growth and invasion facilitated by cell migration and degradation of the extracellular matrix. Despite technological advances in surgery and radio-chemotherapy, glioblastoma remains largely resistant to treatment. New approaches to study glioblastoma and to design optimized therapies are greatly needed. One such approach harnesses computational modeling to support the design and delivery of glioblastoma treatment. In this paper, we critically summarize current glioblastoma therapy, with a focus on emerging nanomedicine and therapies that capitalize on cell-specific signaling in glioblastoma. We follow this summary by discussing computational modeling approaches focused on optimizing these emerging nanotherapeutics for brain cancer. We conclude by illustrating how mathematical analysis can be used to compare the delivery of a high potential anticancer molecule, delphinidin, in both free and nanoparticle loaded forms across the blood-brain barrier for glioblastoma.

  12. Secretome Signature of Invasive Glioblastoma Multiforme

    OpenAIRE

    Formolo, Catherine A.; Williams, Russell; Gordish-Dressman, Heather; MacDonald, Tobey J.; Lee, Norman H.; Hathout, Yetrib

    2011-01-01

    The incurability of malignant glioblastomas is mainly attributed to their highly invasive nature coupled with resistance to chemo- and radiation therapy. Because invasiveness is partially dictated by the proteins these tumors secrete we used SILAC to characterize the secretomes of four glioblastoma cell lines (LN18, T98, U118 and U87). Although U87 and U118 cells both secreted high levels of well-known invasion promoting proteins, a Matrigel invasion assay showed U87 cells to be eight times m...

  13. Coordination of glioblastoma cell motility by PKCι

    Directory of Open Access Journals (Sweden)

    Baldwin R Mitchell

    2010-09-01

    Full Text Available Abstract Background Glioblastoma is one of the deadliest forms of cancer, in part because of its highly invasive nature. The tumor suppressor PTEN is frequently mutated in glioblastoma and is known to contribute to the invasive phenotype. However the downstream events that promote invasion are not fully understood. PTEN loss leads to activation of the atypical protein kinase C, PKCι. We have previously shown that PKCι is required for glioblastoma cell invasion, primarily by enhancing cell motility. Here we have used time-lapse videomicroscopy to more precisely define the role of PKCι in glioblastoma. Results Glioblastoma cells in which PKCι was either depleted by shRNA or inhibited pharmacologically were unable to coordinate the formation of a single leading edge lamellipod. Instead, some cells generated multiple small, short-lived protrusions while others generated a diffuse leading edge that formed around the entire circumference of the cell. Confocal microscopy showed that this behavior was associated with altered behavior of the cytoskeletal protein Lgl, which is known to be inactivated by PKCι phosphorylation. Lgl in control cells localized to the lamellipod leading edge and did not associate with its binding partner non-muscle myosin II, consistent with it being in an inactive state. In PKCι-depleted cells, Lgl was concentrated at multiple sites at the periphery of the cell and remained in association with non-muscle myosin II. Videomicroscopy also identified a novel role for PKCι in the cell cycle. Cells in which PKCι was either depleted by shRNA or inhibited pharmacologically entered mitosis normally, but showed marked delays in completing mitosis. Conclusions PKCι promotes glioblastoma motility by coordinating the formation of a single leading edge lamellipod and has a role in remodeling the cytoskeleton at the lamellipod leading edge, promoting the dissociation of Lgl from non-muscle myosin II. In addition PKCι is required

  14. Does gender matter in glioblastoma?

    Science.gov (United States)

    Verger, E; Valduvieco, I; Caral, Ll; Pujol, T; Ribalta, T; Viñolas, N; Boget, T; Oleaga, L; Blanco, Y; Graus, F

    2011-10-01

    BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series.

  15. Structural and advanced imaging in predicting MGMT promoter methylation of primary glioblastoma: a region of interest based analysis.

    Science.gov (United States)

    Han, Yu; Yan, Lin-Feng; Wang, Xi-Bin; Sun, Ying-Zhi; Zhang, Xin; Liu, Zhi-Cheng; Nan, Hai-Yan; Hu, Yu-Chuan; Yang, Yang; Zhang, Jin; Yu, Ying; Sun, Qian; Tian, Qiang; Hu, Bo; Xiao, Gang; Wang, Wen; Cui, Guang-Bin

    2018-02-21

    The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients. Ninety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher's exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables. MGMT promoter methylation was associated with tumor location and necrosis (P MGMT promoter methylation in primary glioblastoma. The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860; sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%; specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC and rCBF resulted in the highest AUC of 0.914. ADC and rCBF are promising imaging biomarkers in clinical routine to predict the MGMT promoter methylation in primary glioblastoma patients.

  16. Radiation induced glioblastoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Naoki; Kayama, Takamasa; Sakurada, Kaori; Saino, Makoto; Kuroki, Akira [Yamagata Univ. (Japan). School of Medicine

    2000-05-01

    We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. A autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and secondary glioblastoma. (author)

  17. [Nursing strategy in the face of glioblastoma].

    Science.gov (United States)

    Lorenzini, Stéphanie

    2017-02-01

    Hospitalisation forces patients with glioblastoma and their family to face a new life made up of numerous constraints and uncertainties. In this context of anxiety, nursing care is based on global support which combines technical, organisational and relational skills. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. PICTORIAL REVIEW Glioblastoma multiforme has many faces

    African Journals Online (AJOL)

    anaplastic astrocytomas that undergo de-differentiation.4 Glioblastoma is the most common brain tumour, accounting for 12 - 15% of intracranial neoplasms and 50 - 60% of astrocytic tumours.4. Imaging. MR imaging is crucial in lesion characterisation. Lesions are typically hypo-intense on T1WI and hyperintense on T2WI ...

  19. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H

    2013-01-01

    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  20. Irinotecan and bevacizumab in recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Hasselbalch, Benedikte; Stockhausen, Marie-Thérése

    2011-01-01

    INTRODUCTION: Glioblastoma multiforme (GBM) is the most common high grade primary brain tumor in adults. Despite significant advances in treatment, the prognosis remains poor. Bevacizumab (BVZ) and irinotecan (CPT-11) are currently being investigated in the treatment of GBM patients. Although...

  1. Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy.

    Science.gov (United States)

    Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred

    2008-11-25

    Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of (10)B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

  2. Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy

    Directory of Open Access Journals (Sweden)

    Ciofani Gianni

    2008-01-01

    Full Text Available Abstract Boron neutron capture therapy (BNCT is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of10B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

  3. Cerebral Hypoxia

    Science.gov (United States)

    ... off. When hypoxia lasts for longer periods of time, it can cause coma, seizures, and even brain death. In brain death, there is no measurable activity in the brain, although cardiovascular function is preserved. Life support is required for respiration. × Definition Cerebral hypoxia ...

  4. PCDH10 is required for the tumorigenicity of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Echizen, Kanae [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Nakada, Mitsutoshi, E-mail: mnakada@med.kanazawa-u.ac.jp [Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-8641 (Japan); Hayashi, Tomoatsu [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Sabit, Hemragul; Furuta, Takuya [Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-8641 (Japan); Nakai, Miyuki; Koyama-Nasu, Ryo; Nishimura, Yukiko; Taniue, Kenzui [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Morishita, Yasuyuki [Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Hirano, Shinji [Department of Neurobiology and Anatomy, Kochi Medical School, Kochi University, Okoh-cho, Nangoku-City, Kochi 783-8505 (Japan); Terai, Kenta [Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Todo, Tomoki; Ino, Yasushi; Mukasa, Akitake; Takayanagi, Shunsaku; Ohtani, Ryohei; Saito, Nobuhito [Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Akiyama, Tetsu, E-mail: akiyama@iam.u-tokyo.ac.jp [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)

    2014-01-31

    Highlights: • PCDH10 is required for the proliferation, survival and self-renewal of glioblastoma cells. • PCDH10 is required for glioblastoma cell migration and invasion. • PCDH10 is required for the tumorigenicity of glioblastoma cells. • PCDH10 may be a promising target for the therapy of glioblastoma. - Abstract: Protocadherin10 (PCDH10)/OL-protocadherin is a cadherin-related transmembrane protein that has multiple roles in the brain, including facilitating specific cell–cell connections, cell migration and axon guidance. It has recently been reported that PCDH10 functions as a tumor suppressor and that its overexpression inhibits proliferation or invasion of multiple tumor cells. However, the function of PCDH10 in glioblastoma cells has not been elucidated. In contrast to previous reports on other tumors, we show here that suppression of the expression of PCDH10 by RNA interference (RNAi) induces the growth arrest and apoptosis of glioblastoma cells in vitro. Furthermore, we demonstrate that knockdown of PCDH10 inhibits the growth of glioblastoma cells xenografted into immunocompromised mice. These results suggest that PCDH10 is required for the proliferation and tumorigenicity of glioblastoma cells. We speculate that PCDH10 may be a promising target for the therapy of glioblastoma.

  5. Diffuse glioblastoma resembling acute hemorrhagic leukoencephalitis.

    Science.gov (United States)

    Schettino, Carla; Caranci, Ferdinando; Lus, Giacomo; Signoriello, Elisabetta; Eoli, Marica; Anghileri, Elena; Pollo, Bianca; Melone, Mariarosa A B; Di Iorio, Giuseppe; Finocchiaro, Gaetano; Ugga, Lorenzo; Tedeschi, Enrico

    2017-10-01

    We report the case of a young man with sudden onset of diplopia after an upper respiratory tract infection. Based on the first radiological findings acute hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis, was suspected and treatment with high dose intravenous dexamethasone was started but it was stopped for intolerance. The patient clinically worsened, developing gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later showed severe progression of the disease with subependymal dissemination. After brain biopsy of the right temporal lesion the histological diagnosis was glioblastoma. These findings suggest that MRI features of acute hemorrhagic leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma. This case underscores the importance of considering diffuse glioma in the differential diagnosis of atypical signs and symptoms of acute hemorrhagic leukoencephalitis and underlines the relevant role of integrating neuroradiologic findings with neuropathology.

  6. Isolated ovarian tuberculosis mimicking ovarian carcinoma: Case ...

    African Journals Online (AJOL)

    Although genitourinary tuberculosis is common, reports of isolated ovarian tuberculosis are rare. However, its presentation can mimick that of an ovarian tumour, leading to diagnostic difficulties. A woman of 17 years presented with chronic pelvic pain, weight loss, a right ovarian mass on ultrasound, and a significantly ...

  7. Uncomplicated bifid Meckle's diverticulum mimicking recurrent ...

    African Journals Online (AJOL)

    It was excised with V shaped ileal wall. Histopathology showed features of Meckel's diverticulum without any Gastric or pancreatic tissue in mucosa. Clinicians should be wary of a bifid meckel's diverticulum as a very rare anomaly that can be symptomatic mimicking appendicitis. Keywords: Bifid, Meckel's, Diverticulitis ...

  8. Right paratesticular abscess mimicking neonatal testicular torsion ...

    African Journals Online (AJOL)

    U.O. Ezomike

    Right paratesticular abscess mimicking neonatal testicular torsion and caused by Proteus mirabilis. U.O. Ezomikea,∗. , M.A. Ituena, S.C. Ekpemoa, S.O. Ekenzeb a Department of Surgery, Federal Medical Centre Umuahia, Abia State, Nigeria b Sub-Department of Pediatric Surgery, University of Nigeria Teaching Hospital, ...

  9. Acute dystonia mimicking angioedema of the tongue

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Pallesen, Kristine A U; Bygum, Anette

    2013-01-01

    We report a case of acute dystonia of the face, jaw and tongue caused by metoclopramide and mimicking angioedema. The patient had attacks for several years before the correct diagnosis was made and we present the first ever published video footage of an attack. This adverse drug reaction is known...

  10. Peripancreatic fat necrosis mimicking pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thurnher, M.M.; Schima, W.; Turetschek, K.; Thurnher, S.A. [Vienna Univ. (Austria). Inst. fuer Radiologie; Fuegger, R. [Dept. of Surgery, University of Vienna (Austria); Oberhuber, G. [Dept. of Pathology, University of Vienna (Austria)

    2001-06-01

    A case of peripancreatic fat necrosis, after an episode of acute pancreatitis, which mimicked pancreatic cancer with lymph node metastases, is presented. We describe the imaging findings with helical CT scanning and with unenhanced and mangafodipir-enhanced MR imaging, with special emphasis on the differential diagnoses. (orig.)

  11. Iliacus Abscess with Radiculopathy Mimicking Herniated Nucleus ...

    African Journals Online (AJOL)

    2016-05-02

    May 2, 2016 ... radiculopathy mimicking herniated nucleus pulposus: Aadditional diagnostic value of magnetic resonance imaging. Niger J Clin Pract. 2017;20:392-3. This is an open access article distributed under the terms of the Creative Commons. Attribution-Non Commercial-Share Alike 3.0 License, which allows ...

  12. HOTAIR is a therapeutic target in glioblastoma

    OpenAIRE

    Zhou, Xuan; Ren, Yu; Zhang, Jing; Zhang, Chuanbao; Zhang, Kailiang; Han, Lei; Kong, Lingping; Wei, Jianwei; Chen, Luyue; Yang, Jingxuan; Wang, Qixue; Zhang, Jianning; Yang, Yuqi; Jiang, Tao; Li, Min

    2015-01-01

    HOTAIR is a negative prognostic factor and is overexpressed in multiple human cancers including glioblastoma multiform (GBM). Survival analysis of Chinese Glioma Genome Atlas (CGGA) patient data indicated that high HOTAIR expression was associated with poor outcome in GBM patients. NLK (Nemo-like kinase), a negative regulator of the ?-catenin pathway, was negatively correlated with HOTAIR expression. When the ?-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest a...

  13. Tumor stem cells from glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Z. N. Nikiforova

    2016-01-01

    Full Text Available Glioblastoma multiforme, a World Health Organization grade IV malignant glioma, is the most common and lethal primary brain tumor with the median survival of approximately 15–25 months after treatment. Glioblastoma multiforme has been shown to be resistant to radiotherapy and chemotherapy and invariably recurs following surgical resection and chemoradiation. The characteristics of this tumor are exemplified by heterogeneous cell population with diverse biologic properties and genetic changes, the ability to form cancer stem cells (CSC and divided into four molecular subtypes – proneural, neural, classical and mesenchymal. Despite some success, the mechanisms leading to the formation of the most malignant tumor subtype are unclear. The aim of this review was a synthesis of modern information about the role and biological characteristics of tumor stem cells in tumor progression and the pathogenesis of glioblastoma multiforme. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, adhesion, survival, resistance to standard cancer treatment and metastatic potential. The presence of aberrant signaling pathways (Notch, Hedgehog-Gli, Wnt/β-catenin, TGF-β/SMAD, PI3K/Akt/mTOR, both in the tumor and in the population of CSC, the dysregulation of microRNAs (miR-21, miR-128, miR-326, miR-34a, influence of epithelial-to-mesenchymal transition explains the availability of typical biological characteristics of the CSC. One needs to consider the influence of the therapy on normal stem cells in the development of drugs directed against the CSC. Regulatory mechanisms and markers found over the last decade can be used as the basis for creation of the new drugs with targeted action in the treatment of glioblastoma multiforme.

  14. Biomarker-based prognostic stratification of young adult glioblastoma.

    Science.gov (United States)

    Zhang, Rui-Qi; Shi, Zhifeng; Chen, Hong; Chung, Nellie Yuk-Fei; Yin, Zi; Li, Kay Ka-Wai; Chan, Danny Tat-Ming; Poon, Wai Sang; Wu, Jinsong; Zhou, Liangfu; Chan, Aden Ka-Yin; Mao, Ying; Ng, Ho-Keung

    2016-01-26

    While the predominant elderly and the pediatric glioblastomas have been extensively investigated, young adult glioblastomas were understudied. In this study, we sought to stratify young adult glioblastomas by BRAF, H3F3A and IDH1 mutations and examine the clinical relevance of the biomarkers. In 107 glioblastomas aged from 17 to 35 years, mutually exclusive BRAF-V600E (15%), H3F3A-K27M (15.9%), H3F3A-G34R/V (2.8%) and IDH1-R132H (16.8%) mutations were identified in over half of the cases. EGFR amplification and TERTp mutation were only detected in 3.7% and 8.4% in young adult glioblastomas, respectively. BRAF-V600E identified a clinically favorable subset of glioblastomas with younger age, frequent CDKN2A homozygous deletion, and was more amendable to surgical resection. H3F3A-K27M mutated glioblastomas were tightly associated with midline locations and showed dismal prognosis. IDH1-R132H was associated with older age and favorable outcome. Interestingly, tumors with positive PDGFRA immunohistochemical expression exhibited poorer prognosis and identified an aggressive subset of tumors among K27M mutated glioblastomas. Combining BRAF, H3F3A and IDH1 mutations allowed stratification of young adult glioblastomas into four prognostic subgroups. In summary, our study demonstrates the clinical values of stratifying young adult glioblastomas with BRAF, H3F3A and IDH1 mutations, which has important implications in refining prognostic classification of glioblastomas.

  15. [Nutritional status in patients with recurrent glioblastoma].

    Science.gov (United States)

    Gokcek, D; Tran, J-D; Gonzalez-Aguilar, A; Alentorn, A; Liou, A; Delattre, J-Y; Idbaih, A

    2013-11-01

    Nutritional status is a major clinical parameter in multiple cancers. Indeed, nutritional status is a prognostic factor and a predictor of response and toxicity to treatments in breast and lung cancers for instance. To our knowledge, in patients suffering from malignant primary brain tumors, nutritional status has been poorly investigated. Nutritional status of 26 glioblastoma patients relapsing after a first line of treatment was studied. The body mass index (BMI), the prognostic inflammatory and nutritional index (PINI) and the instant nutritional score (INS) were assessed. The BMI was abnormal in 12 patients, two were malnourished while 10 were overweight. The BMI was not correlated to age of patients. Overweight status did not impact patient survival but it was associated with reduced performance status. The PINI was abnormal in three patients. Finally, the INS was abnormal in 24 patients, noted 2 (n=22) or 4 (n=4). Our results were not in favor of systematic nutritional support in patients with recurrent glioblastoma after a first line of treatment. Being overweight does not influence prognosis but may influence performance status. Steroid therapy and chemotherapy (inducing sodium and water retention and lymphopenia) weaken the relevance of BMI and INS for nutritional assessment in patients with recurrent glioblastoma. Further studies using additional nutritional tests in larger, independent and prospective cohorts of patients are warranted to obtain more details. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Secretome signature of invasive glioblastoma multiforme.

    Science.gov (United States)

    Formolo, Catherine A; Williams, Russell; Gordish-Dressman, Heather; MacDonald, Tobey J; Lee, Norman H; Hathout, Yetrib

    2011-07-01

    The incurability of malignant glioblastomas is mainly attributed to their highly invasive nature coupled with resistance to chemo- and radiation therapy. Because invasiveness is partially dictated by the proteins these tumors secrete we used SILAC to characterize the secretomes of four glioblastoma cell lines (LN18, T98, U118 and U87). Although U87 and U118 cells both secreted high levels of well-known invasion promoting proteins, a Matrigel invasion assay showed U87 cells to be eight times more invasive than U118 cells, suggesting that additional proteins secreted by U87 cells may contribute to the highly invasive phenotype. Indeed, we identified a number of proteins highly or exclusively expressed by U87 cells as compared to the less invasive cell lines. The most striking of these include ADAM9, ADAM10, cathepsin B, cathepsin L1, osteopontin, neuropilin-1, semaphorin-7A, suprabasin, and chitinase-3-like protein 1. U87 cells also expressed significantly low levels of some cell adhesion proteins such as periostin and EMILIN-1. Correlation of secretome profiles with relative levels of invasiveness using Pavlidis template matching further indicated potential roles for these proteins in U87 glioblastoma invasion. Antibody inhibition of CH3L1 reduced U87 cell invasiveness by 30%.

  17. [A case of cerebral embolism due to cardiac myxoma presenting with multiple cerebral microaneurysms detected on first MRI scans].

    Science.gov (United States)

    Sato, Takahiro; Saji, Naoki; Kobayashi, Kazuto; Shibazaki, Kensaku; Kimura, Kazumi

    2016-01-01

    A 64-year-old man developed right arm weakness and dysarthria, and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging of the brain showed a high intensity area in the frontal lobe. T2*-weighted images showed multiple spotty low intensity lesions in bilateral cerebral hemispheres, mimicking cerebral microbleeds. Cerebral angiography showed multiple aneurysms in the anterior, middle, posterior cerebral arteries and cerebellar arteries. Transthoracic echocardiography revealed a floating structure in the left atrial chamber, indicating cardiac myxoma. We diagnosed cardioembolic ischemic stroke due to left atrial myxoma. Cardiac surgery for excision of a left atrial myxoma was performed on the 3rd hospital day. Multiple aneurysms should be taken into account for differential diagnosis in patients with cardiac myxoma and with atypical spotty low intensity on T2*-weighted images.

  18. Different diagnostic values of imaging parameters to predict pseudoprogression in glioblastoma subgroups stratified by MGMT promoter methylation

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ra Gyoung [Catholic Kwandong University International St. Mary' s Hospital, Department of Radiology, Catholic Kwandong University College of Medicine, Incheon (Korea, Republic of); Kim, Ho Sung; Shim, Woo Hyun; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Paik, Wooyul [Dankook Unversity Hospital, Department of Radiology, Cheonan-si, Chungcheongnam-do (Korea, Republic of); Kim, Jeong Hoon [University of Ulsan College of Medicine, Asan Medical Center, Department of Neurosurgery, Seoul (Korea, Republic of)

    2017-01-15

    The aim of this study was to determine whether diffusion and perfusion imaging parameters demonstrate different diagnostic values for predicting pseudoprogression between glioblastoma subgroups stratified by O{sup 6}-mythylguanine-DNA methyltransferase (MGMT) promoter methylation status. We enrolled seventy-five glioblastoma patients that had presented with enlarged contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and initial area under the time signal-intensity curve (IAUC90). The results of the areas under the receiver operating characteristic curve (AUCs) with cross-validation were compared between MGMT methylation and unmethylation groups. MR imaging parameters demonstrated a trend toward higher accuracy in the MGMT promoter methylation group than in the unmethylation group (cross-validated AUCs = 0.70-0.95 and 0.56-0.87, respectively). The combination of MGMT methylation status with imaging parameters improved the AUCs from 0.70 to 0.75-0.90 for both readers in comparison with MGMT methylation status alone. The probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02 in the MGMT promoter methylation group. MR imaging parameters could be stronger predictors of pseudoprogression in glioblastoma patients with the methylated MGMT promoter than in patients with the unmethylated MGMT promoter. (orig.)

  19. Experimental study of hypoxia-imaging agent 99mTc-HL91 in mice bearing glioblastoma G422

    International Nuclear Information System (INIS)

    Zhou Ying; Qu Wanying; Yao Zhiming; Chen Fang; Zhu Ming; Zhu Lin

    1999-01-01

    Objective: To evaluate the ability of detecting cerebral tumor by 99m Tc-HL91 in mice bearing glioblastoma G422. Methods: Six model mice underwent static whole body planar imagings at once and at 1,2,3,4,6,7,8 h postinjection of 99m Tc-HL91. Three mice each were killed at 4 h and 8 h, respectively. the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around tumor, head, contralateral axilla and chest in whole body planar images, and the radioactivity ratios of tumor to head (T/H), contralateral axilla (T/A) and chest (T/C) were calculated. Results: Increased tumor activity was identified in static whole body planar images since 1 h postinjection. At 2h postinjection, T/H, T/A and T/C were 2.93 +- 0.51, 4.86 +- 0.79 and 2.00 +- 0.35 respectively, which were significantly higher than those at once and at 1h postinjection (P 99m Tc-HL91 in tumor tissue of mice bearing glioblastoma G422 is increased and clearance rate is decreased. 99m Tc-HL91 imaging is suitable for glioblastoma at 2 h postinjection. It is appropriate to image tumors in head, neck, thorax, bone and soft tissues, but not in abdominal area

  20. United Cerebral Palsy

    Science.gov (United States)

    ... your local affiliate Find your local affiliate United Cerebral Palsy United Cerebral Palsy (UCP) is a trusted resource for individuals with Cerebral Palsy and other disabilities and their networks. Individuals with ...

  1. Apoptotic Signaling Pathways in Glioblastoma and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Silvia Anahi Valdés-Rives

    2017-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most hostile type of brain cancer. Its aggressiveness is due to increased invasion, migration, proliferation, angiogenesis, and a decreased apoptosis. In this review, we discuss the role of key regulators of apoptosis in GBM and glioblastoma stem cells. Given their importance in the etiology and pathogenesis of GBM, these signaling molecules may represent potential therapeutic targets.

  2. 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.

  3. Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

    Directory of Open Access Journals (Sweden)

    Jason A. Ellis

    2015-01-01

    Full Text Available Effective treatment for glioblastoma (GBM will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.

  4. Therapeutic Advances using Combinational Therapy in the Treatment of Glioblastoma

    DEFF Research Database (Denmark)

    Staberg, Mikkel

    2017-01-01

    Glioblastoma is the most malignant brain tumor in adults. Median survival is only about 15 months despite aggressive treatment, consisting of surgery followed by radio- and chemotherapy, stressing the need for new therapies. Development of glioblastoma is thought to be a result of both genetic...... of glioblastoma cells, an effect that is even more pronounced when combined with traditional chemotherapeutic agents. The EGFR and Notch pathways are shown to be of great importance for glioblastoma cell survival and for the formation of new blood vessels, a process known as angiogenesis. Results presented herein...... suggests that targeting redundant signaling pathways can overcome required or initial treatment resistance, thus leading to improved tumor cell elimination. We hypothesize that future therapies will likely be a result of combination therapies for glioblastoma patients based on their molecular tumor profile...

  5. Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma.

    Science.gov (United States)

    Tateishi, Kensuke; Iafrate, A John; Ho, Quan; Curry, William T; Batchelor, Tracy T; Flaherty, Keith T; Onozato, Maristela L; Lelic, Nina; Sundaram, Sudhandra; Cahill, Daniel P; Chi, Andrew S; Wakimoto, Hiroaki

    2016-09-01

    Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma. The glycolytic dependency of Myc-driven glioblastoma was tested using (13)C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD(+) salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models. Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN-amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts. Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452-65. ©2016 AACR

  6. Different diagnostic values of imaging parameters to predict pseudoprogression in glioblastoma subgroups stratified by MGMT promoter methylation.

    Science.gov (United States)

    Yoon, Ra Gyoung; Kim, Ho Sung; Paik, Wooyul; Shim, Woo Hyun; Kim, Sang Joon; Kim, Jeong Hoon

    2017-01-01

    The aim of this study was to determine whether diffusion and perfusion imaging parameters demonstrate different diagnostic values for predicting pseudoprogression between glioblastoma subgroups stratified by O 6 -mythylguanine-DNA methyltransferase (MGMT) promoter methylation status. We enrolled seventy-five glioblastoma patients that had presented with enlarged contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and initial area under the time signal-intensity curve (IAUC90). The results of the areas under the receiver operating characteristic curve (AUCs) with cross-validation were compared between MGMT methylation and unmethylation groups. MR imaging parameters demonstrated a trend toward higher accuracy in the MGMT promoter methylation group than in the unmethylation group (cross-validated AUCs = 0.70-0.95 and 0.56-0.87, respectively). The combination of MGMT methylation status with imaging parameters improved the AUCs from 0.70 to 0.75-0.90 for both readers in comparison with MGMT methylation status alone. The probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02 in the MGMT promoter methylation group. MR imaging parameters could be stronger predictors of pseudoprogression in glioblastoma patients with the methylated MGMT promoter than in patients with the unmethylated MGMT promoter. • The glioblastoma subgroup was stratified according to MGMT promoter methylation status. • Diagnostic values of diffusion and perfusion parameters for predicting pseudoprogression were compared. • Imaging parameters showed higher diagnostic accuracy in the MGMT promoter methylation group. • Imaging parameters were independent to MGMT promoter methylation status for predicting

  7. Rhino cerebral mucormycosis in a patient with a myelodysplastic syndrome: Disease course as studied by CT

    International Nuclear Information System (INIS)

    Martin, M.T.; Marcos, F.; Villanueva, J.M.; Vicente, L.

    1996-01-01

    A case of richinocerebral mucormycosis is reported a patient with refractory sideroblastic anemia assessed by means of serial CT; the disorder initially mimicked bacterial rhino sinusitis, coursing later with sinonasal necrosis, orbital involvement and, finally, cerebral involvement. The CT findings are compared with those described in the literature. (Author) 8 refs

  8. Inhibition of TRF1 Telomere Protein Impairs Tumor Initiation and Progression in Glioblastoma Mouse Models and Patient-Derived Xenografts.

    Science.gov (United States)

    Bejarano, Leire; Schuhmacher, Alberto J; Méndez, Marinela; Megías, Diego; Blanco-Aparicio, Carmen; Martínez, Sonia; Pastor, Joaquín; Squatrito, Massimo; Blasco, Maria A

    2017-11-13

    Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find TRF1 upregulation in mouse and human GBM. Brain-specific Trf1 genetic deletion in GBM mouse models inhibited GBM initiation and progression, increasing survival. Trf1 deletion increased telomeric DNA damage and reduced proliferation and stemness. TRF1 chemical inhibitors mimicked these effects in human GBM cells and also blocked tumor sphere formation and tumor growth in xenografts from patient-derived primary GSCs. Thus, targeting telomeres throughout TRF1 inhibition is an effective therapeutic strategy for GBM. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Differentiation of brain abscesses from glioblastomas and metastatic brain tumors: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging before and after mathematic contrast leakage correction.

    Science.gov (United States)

    Toh, Cheng Hong; Wei, Kuo-Chen; Chang, Chen-Nen; Ng, Shu-Hang; Wong, Ho-Fai; Lin, Ching-Po

    2014-01-01

    To compare the diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MRI before and after mathematic contrast leakage correction in differentiating pyogenic brain abscesses from glioblastomas and/or metastatic brain tumors. Cerebral blood volume (CBV), leakage-corrected CBV and leakage coefficient K2 were measured in enhancing rims, perifocal edema and contralateral normal appearing white matter (NAWM) of 17 abscesses, 19 glioblastomas and 20 metastases, respectively. The CBV and corrected CBV were normalized by dividing the values in the enhancing rims or edema to those of contralateral NAWM. For each study group, a paired t test was used to compare the K2 of the enhancing rims or edema with those of NAWM, as well as between CBV and corrected CBV of the enhancing rims or edema. ANOVA was used to compare CBV, corrected CBV and K2 among three lesion types. The diagnostic performance of CBV and corrected CBV was assessed with receiver operating characteristic (ROC) curve analysis. The CBV and correction CBV of enhancing rim were 1.45±1.17 and 1.97±1.01 for abscesses, 3.85±2.19 and 4.39±2.33 for glioblastomas, and 2.39±0.90 and 2.97±0.78 for metastases, respectively. The CBV and corrected CBV in the enhancing rim of abscesses were significantly lower than those of glioblastomas and metastases (P = 0.001 and P = 0.007, respectively). In differentiating abscesses from glioblastomas and metastases, the AUC values of corrected CBV (0.822) were slightly higher than those of CBV (0.792). Mathematic leakage correction slightly increases the diagnostic performance of CBV in differentiating pyogenic abscesses from necrotic glioblastomas and cystic metastases. Clinically, DSC perfusion MRI may not need mathematic leakage correction in differentiating abscesses from glioblastomas and/or metastases.

  10. SMART Syndrome: Case report of a rare complication after cerebral radiation therapy

    International Nuclear Information System (INIS)

    Truntzer, P.; Salze, P.; Monjour, A.; Gaultier, C.; Ahle, G.; Guillerme, F.; Boutenbat, G.; Atlani, D.; Stilhart, B

    2012-01-01

    The authors report a 71-year-old woman case who developed, 7 years after a cerebral radiation therapy for a parieto-occipital glioblastoma, a stroke-like migraine attacks after radiotherapy syndrome (SMART syndrome), a rare complication characterized by reversible neurologic deficits with migraine described after cerebral irradiation. Transient gyri-form reversible enhancement is found on MRI during crises. This case report allows discussing the clinical, iconographic presentation and the clinical outcome of this syndrome at the light of the literature publication. (authors)

  11. Intracranial capillary hemangioma mimicking a dissociative disorder

    Directory of Open Access Journals (Sweden)

    Alexander Lacasse

    2012-01-01

    Full Text Available Capillary hemangiomas, hamartomatous proliferation of vascular endothelial cells, are rare in the central nervous system (CNS. Intracranial capillary hemangiomas presenting with reversible behavioral abnormalities and focal neurological deficits have rarely been reported. We report a case of CNS capillary hemangioma presenting with transient focal neurological deficits and behavioral abnormalities mimicking Ganser’s syndrome. Patient underwent total excision of the vascular malformation, resulting in complete resolution of his symptoms.

  12. Giant chondroid syringoma radiologically mimicking malignancy

    Directory of Open Access Journals (Sweden)

    Belkiz Uyar

    2013-01-01

    Full Text Available Chondroid syringoma, or mixed tumor of skin, is a relatively rare, usually benign sweat gland tumor, most often seen in the head-and-neck region. Rare malignant examples have been reported, commonly involving the extremities. We report here a case radiologically mimicking a malignant neoplasm, but histologically-proven benign subcutaneous chondroid syringoma, arising in the anterior aspect of the upper thigh of a 59-year-old male.

  13. Hydroxychloroquine-Associated Hyperpigmentation Mimicking Elder Abuse

    OpenAIRE

    Cohen, Philip R.

    2013-01-01

    Background Hydroxychloroquine may result in cutaneous dyschromia. Older individuals who are the victims of elder abuse can present with bruising and resolving ecchymoses. Purpose The features of hydroxychloroquine-associated hyperpigmentation are described, the mucosal and skin manifestations of elder abuse are reviewed, and the mucocutaneous mimickers of elder abuse are summarized. Case Report An elderly woman being treated with hydroxychloroquine for systemic lupus erythematosus developed d...

  14. Photochromic crystalline systems mimicking bio-functions.

    Science.gov (United States)

    Uchida, Kingo; Nishimura, Ryo; Hatano, Eri; Mayama, Hiroyuki; Yokojima, Satoshi

    2018-01-31

    Photoresponsive crystalline systems mimicking bio-functions are prepared using photochromic diarylethenes. Upon UV irradiation to a diarylethene crystal, the self-aggregated and needle-shaped crystals of photogenerated colored closed-ring isomer were generated on the surface. The rough surface showed the superhydrophobic lotus effect. By controlling the heating procedures, UV irradiation processes, and molecular structural modification, rose-petal effects of wetting, anti-reflective moth eye effect, and double-roughness structure mimicking the surface of lotus leaf were observed. By changing the molecular structure, superhydrophilic surface mimicking snail shell was photogenerated. We also found a derivative to form hollow crystals by sublimation. The crystals showed photosalient effect and the photo-response similar to impatiens was observed after small beads were packed in the hollow. These photoresponsive functions are unique, and they demonstrate a macroscopic response by assembling microscopic molecular movement of light. In the future, such a molecular assembly system will be a promising candidate for fabricating photoresponsive architectures and soft robots. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Is There Pseudoprogression in Secondary Glioblastomas?

    Energy Technology Data Exchange (ETDEWEB)

    Juratli, Tareq A., E-mail: Tareq.Juratli@uniklinikum-dresden.de [Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden (Germany); Engellandt, Kay [Institute of Neuroradiology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden (Germany); Lautenschlaeger, Tim [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center/Arthur G. James Cancer Hospital and Richard L. Solove Research Institute, The Ohio State University College of Medicine Columbus, Ohio (United States); Geiger, Kathrin D. [Institute of Neuropathology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden (Germany); Kummer, Rüdiger von; Cerhova, Jana [Institute of Neuroradiology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden (Germany); Chakravarti, Arnab [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center/Arthur G. James Cancer Hospital and Richard L. Solove Research Institute, The Ohio State University College of Medicine Columbus, Ohio (United States); Krex, Dietmar; Schackert, Gabriele [Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden (Germany)

    2013-12-01

    Purpose: Pseudoprogression (PP) during adjuvant treatment of glioblastoma (GBM) is frequent and is a clinically and radiologically challenging problem. While there are several reports of the frequency of PP in GBM cohorts including mainly patients with primary GBM, there are few data on the incidence of PP in patients with secondary glioblastomas (sGBM). Therefore, the goal of this study was to evaluate the frequency of PP in sGBM. Methods and Materials: We retrospectively evaluated the incidence of PP in adult patients with sGBM treated with chemoradiation therapy (CRTx) using temozolomide (TMZ) and sought to assess if there was an association between PP and MGMT promoter methylation status, IDH mutations status, or 1p/19q codeletion. The definition of PP according to the Response Assessment in Neuro-Oncology Working Group was used. Results: None of the evaluable 15 sGBM patients in our series demonstrated a PP. Of the 9 sGBM patients who received concomitant CRTx with TMZ, 6 patients had the methylated MGMT promoter, and 6 patients had IDH mutations. There also was no PP identified in sGBM patients who received sequential CRTx, irrespective of MGMT or IDH status. The median time of follow-up was 3.4 years after diagnosis of an sGBM, and the median overall survival was 18.2 months (range, 14.3-45.2 months). Three of 15 patients had previously received radiation therapy for their World Health Organization low-grade 2 glioma, while none of them had received chemotherapy at that stage. Conclusions: Based on this small series of sGBM patients treated with CRTx (concomitantly or sequentially) the frequency of PP appears to be very low in sGBM, even in those patients with methylated MGMT promoter or IDH mutations. Our results highlight the differences between primary glioblastomas and sGBM in particular as they relate to PP.

  16. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    International Nuclear Information System (INIS)

    Silva, Andrew Oliveira; Dalsin, Eloisa; Onzi, Giovana Ravizzoni; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido

    2016-01-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  17. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Andrew Oliveira, E-mail: andrewbiomed@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Dalsin, Eloisa, E-mail: dalsineloisa@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Onzi, Giovana Ravizzoni, E-mail: gioonzi@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Filippi-Chiela, Eduardo Cremonese, E-mail: eduardochiela@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Lenz, Guido, E-mail: lenz@ufrgs.br [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)

    2016-11-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  18. Statin use and survival following glioblastoma multiforme

    DEFF Research Database (Denmark)

    Gaist, David; Hallas, Jesper; Friis, Søren

    2014-01-01

    AIM: While some studies indicate a potential chemopreventive effect of statin use on the risk of glioma, the effect of statins on the prognosis of brain tumours has not yet been examined. We thus conducted a cohort study evaluating the influence of statin use on survival in patients...... with glioblastoma multiforme (GBM). METHODS: We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥2...... redeemed prescriptions) was matched to two statin non-users (

  19. MRI and the diagnosis of glioblastomas

    International Nuclear Information System (INIS)

    Bowe, S.

    2002-01-01

    This paper is based on an oral presentation given at the Sydney conference in February 2000. Two cases will be presented to demonstrate the use of this imaging modality in the diagnosis of glioblastomas, MRI has superior soft tissue imaging abilities making it ideal for imaging the brain. Conventional MRI is good for evaluating oedema and haemorrhage and offers high resolution without associated bone artefacts. However, as with all imaging modalities there are some disadvantages. Patients with pacemakers, certain types of metallic clips, or claustrophobia may not be suitable for an MRI scan. Copyright (2002) Australian Institute of Radiography

  20. Glioblastoma pediátrico: estudo clínico patológico de 12 casos com imunoistoquímica para proteína p53 Pediatric glioblastoma: a clinicopathological study of 12 cases with p53 protein immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Leonora Zozula Blind Pope

    2007-12-01

    Full Text Available Glioblastoma é um dos tumores primários mais letais do sistema nervoso central (SNC. Apesar dos significativos progressos, há poucas análises em crianças. Com o objetivo de avaliar localização, idade, sexo, sobrevida e imunoistoquímica para proteína p53, foram coletados casos de glioblastomas pediátricos do "Banco de Tumores do SNC de Curitiba", durante 1987-2003 e do Hospital Municipal Jesus, Rio de Janeiro, de 1970 a 1988. Doze preencheram os critérios de inclusão. A idade variou até 12 anos (média 7, sendo sete do sexo feminino e cinco do masculino. A sobrevida média foi 7,9 meses. Localizavam-se em hemisférios cerebrais (58,4%, mesencéfalo e tronco (33,3% e um no cerebelo. A imunoistoquímica demonstrou p53 positivo em 9 (75%. Em conclusão, glioblastoma tem comportamento semelhante entre crianças e adultos, sendo nestas menos freqüentes. Acomete hemisférios cerebrais com maior freqüência que estruturas infratentoriais, mostrando alta sensitividade com a imunomarcação para proteína p53, sendo nestes casos mais agressivos, com menor sobrevida.Glioblastoma is one of the most lethal central nervous system (CNS primary tumor. Although significant progress, only few analysis have been made in pediatric glioblastoma, which are less common and have worse prognosis than in adults. To evaluate gender, site, age, survival, and immunohistochemistry to p53, we selected cases of pediatric glioblastoma of "CNS Tumors Database in Curitiba", 1987-2003 and of the Hospital Municipal Jesus, Rio de Janeiro, 1970-1988. Twelve tumors were included. The age ranged from up to 12 years (median 7. There were 7 females and 5 males. The median survival was 7.9 months. Location was: cerebral hemispheres (58.4%, mesencephalon and brainstem (33.3% and one case in the cerebellum. Immunostained to p53 in 9 (75% cases. In conclusion, glioblastoma behaves similarly in children and adults. It is rare in children, affects both cerebral hemispheres more

  1. Bevacizumab for glioblastoma: current indications, surgical implications, and future directions

    Science.gov (United States)

    Castro, Brandyn A.; Aghi, Manish K.

    2016-01-01

    Initial enthusiasm after promising Phase II trials for treating recurrent glioblastomas with the antiangiogenic drug bevacizumab—a neutralizing antibody targeting vascular endothelial growth factor—was tempered by recent Phase III trials showing no efficacy for treating newly diagnosed glioblastomas. As a result, there is uncertainty about the appropriate indications for the use of bevacizumab in glioblastoma treatment. There are also concerns about the effects of bevacizumab on wound healing that neurosurgeons must be aware of. In addition, biochemical evidence suggests a percentage of tumors treated with bevacizumab for an extended period of time will undergo transformation into a more biologically aggressive and invasive phenotype with a particularly poor prognosis. Despite these concerns, there remain numerous examples of radiological and clinical improvement after bevacizumab treatment, particularly in patients with recurrent glioblastoma with limited therapeutic options. In this paper, the authors review clinical results with bevacizumab for glioblastoma treatment to date, ongoing trials designed to address unanswered questions, current clinical indications based on existing data, neurosurgical implications of bevacizumab use in patients with glioblastoma, the current scientific understanding of the tumor response to short- and long-term bevacizumab treatment, and future studies that will need to be undertaken to enable this treatment to fulfill its therapeutic promise for glioblastoma. PMID:25581938

  2. 5-ALA based photodynamic management of glioblastoma

    Science.gov (United States)

    Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

    2014-03-01

    Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

  3. BRM270, a Compound from Natural Plant Extracts, Inhibits Glioblastoma Stem Cell Properties and Glioblastoma Recurrence.

    Science.gov (United States)

    Jeon, Hee-Young; Park, Cheol Gyu; Ham, Seok Won; Choi, Sang-Hun; Lee, Seon Yong; Kim, Jung Yun; Seo, Sunyoung; Jin, Xiong; Kim, Jun-Kyum; Eun, Kiyoung; Kim, Eun-Jung; Kim, Hyunggee

    2017-09-01

    Glioblastoma multiforme (GBM) is one of the most aggressive and lethal human brain tumors, and the median survival of patients with GBM is only 14 months. Glioblastoma stem cells (GSCs) are regarded as a main cause of GBM recurrence, because of their self-renewal and drug resistance properties. Therefore, targeting GSCs is an important therapeutic strategy for GBM. In this study, we show the effects of BRM270, a compound from natural plant extracts, on GSCs in vitro and GBM recurrence in vivo. BRM270 induced apoptotic cell death and inhibited cell growth and "stemness" both in vitro and in vivo. Combining BRM270 treatment with concurrent chemoradiotherapy (CCRT) dramatically increased mice survival and tumor growth inhibition. Taken together, our results suggested that BRM270 synergizes with CCRT as a therapeutic agent to target GSCs.

  4. Cerebral Vasculitis

    Directory of Open Access Journals (Sweden)

    Fariborz Khorvash

    2017-02-01

    Full Text Available Introduction: Vasculitis is an inflammation systems may be involved of blood vessels due to various origins. Vessels of the peripheral and/or central nervous. Vasculitis of the CNS is rare and occurs in the context of systemic diseases or as primary angiitis of the CNS. Epidemiology: The overall incidence of primary vasculitis is about 40/1,000,000 persons [excluding giant cell (temporal arteritis, GCA]. Its incidence increases with age. The incidence of GCA is much higher (around 200/1,000,000 persons in the age group[50 years. Clinical Presentation: Clinical and pathological presentation in CNS vasculitis represents a wide spectrum. Among others, headache, cranial nerve affections, encephalopathy, seizures, psychosis, myelitis, stroke, intracranial haemorrhage and aseptic meningoencephalitis are described. Primary and secondary vasculitides leading more frequently to CNS manifestations are discussed. Primary and secondary Vasculitides: Including Giant Cell (Temporal Arteritis , Takayasu arteritis, Polyarteritis nodosa, Primary angiitis of the CNS, Wegener’s granulomatosis, and Connective tissue diseases, such as systemic lupus erythematosus (SLE, scleroderma, rheumatoid arthritis, mixed connective disease and Sjögren syndrome, are systemic immune-mediated diseases that lead to multiple organ affections. Cerebral Vasculitis: Imaging and Differential Diagnosis: Vasculitides represent a heterogeneous group of inflammatory diseases that affect blood vessel walls of varying calibers (inflammatory vasculopathy. Since the devastating symptoms of CNS vasculitis are at least partially reversible, early diagnosis and appropriate treatment are important. In order to establish a differential diagnosis clinical features, disease progression, age of onset, blood results, as well as CSF examinations have to be taken into consideration. Neuroimaging techniques, such as MRI and DSA, play a central role in the diagnosis and disease monitoring .The diagnostic

  5. Cerebral Alveolar Echinococcosis Concomitant with Liver and Lung Lesions in a Young Adult Patient: Case Report and Literature Review.

    Science.gov (United States)

    Batçık, Osman Ersegun; Öğrenci, Ahmet; Koban, Orkun; Ekşi, Murat Şakir; Bilge, Turgay

    2016-09-01

    We present the case of a 25-year-old male harboring multiple brain lesions mimicking tumor metastasis that were revealed to be caused by Echinococcus multilocularis. Cerebral echinococcosis with multiple lesions is rare and might be confused with a brain abscess, tuberculoma, or metastatic tumor disease. Brain magnetic resonance imaging and serological studies are helpful in the differential diagnosis. In case of E. multilocularis, cerebral invasion is the late stage of the disease that necessitates an aggressive treatment protocol.

  6. Unusual presentation of chondroblastoma mimicking Trevor's disease

    Directory of Open Access Journals (Sweden)

    Y Karkhur

    2017-01-01

    Full Text Available Chondroblastoma is a benign bone tumor, represents 1%–2% of all primary bone tumors, typically seen in patients 10–25-year-old and more common in males. It occurs most frequently in the distal femur, proximal tibia, and proximal humerus. Soft tissue extension is extremely rare. Adjacent joints may develop effusions, but the tumor mass protruding into the joint has never been seen in case of chondroblastoma. We report a rare case of intra-articular chondroblastoma arising from proximal tibia in a 16-year-old boy and growing into the knee joint mimicking an intra-articular osteochondroma.

  7. Acute Myelogenous Leukemia Mimicking Fulminant Periorbital Cellulitis

    Directory of Open Access Journals (Sweden)

    Abbas Bagheri

    2013-01-01

    Full Text Available Purpose: To report a patient who was referred for orbital cellulitis but was finally diagnosed with acute leukemia. Case Report: A 17-year-old boy presented with fever, periorbital erythema and swelling mimicking periorbital cellulitis. He underwent empiric antibiotic therapy. Complete blood counts revealed leukocytosis with a predominance of immature blast cells. Bone marrow aspiration confirmed the diagnosis of acute myelogenous leukemia. Chemotherapy was initiated resulting in resolution of signs and symptoms. Conclusion: Acute leukemia may mimic periorbital cellulitis and must be considered in the differential diagnosis.

  8. Central skeletal sarcoidosis mimicking metastatic disease

    International Nuclear Information System (INIS)

    Talmi, Danit; Smith, Stacy; Mulligan, Michael E.

    2008-01-01

    Sarcoidosis is a systemic disease that histologically typically shows non-caseating granulomas. The most common radiologic finding is hilar and mediastinal adenopathy. Patients with widely disseminated disease may show involvement of the peripheral appendicular skeleton in 1-13% of such cases. A primary skeletal presentation without other manifestations typical of the disease is rare. We present a case of sarcoidosis in a middle-aged Caucasian man in whom the disease presented with widespread lytic lesions in the axial skeleton and long bones, mimicking metastatic disease. There was no involvement of the peripheral skeleton, skin or lungs. (orig.)

  9. Pigmented poroid neoplasm mimicking nodular melanoma.

    Science.gov (United States)

    Mitsuishi, Tsuyoshi; Ansai, Shin-ichi; Ueno, Takashi; Kawana, Seiji

    2010-06-01

    We reported the case of a 92-year-old woman with a pigmented and non-pigmented surface of the pedunculated nodule on her lower leg. Microscopic examination revealed that this nodule consisted of a component of small, dark, homogenous, poroid cells and cuticular cells in the dermis. The histopathological features of the lesion were consistent with poroid neoplasm. Immunohistochemistry showed that HMB-45 and Melan-A were positive in malanocytes and melanophages of the pigmented areas. Unlike most poroid neoplasms, this case showed pigmented lesion mimicked nodular melanoma.

  10. Disseminated peritoneal leiomyomatosis mimicking ovarian torsion

    Directory of Open Access Journals (Sweden)

    Chau-Yang Tyan

    2015-01-01

    Full Text Available The presentation of disseminated peritoneal leiomyomatosis (DPL can be misleading. Herein, we present the case of a 42-year-old nulliparous female who had previously undergone a total hysterectomy and presented with an acute abdomen. A presumptive diagnosis of ovarian torsion was made based on the clinical findings and an ultrasonographic examination. A diagnostic laparoscopy was performed immediately. DPL was subsequently diagnosed based on an intra-operative frozen section during surgical exploration and the final histopathologic examination. This case illustrates an atypical presentation of DPL mimicking ovarian torsion.

  11. Hypertrophic Nonunion Humerus Mimicking an Enchondroma

    Directory of Open Access Journals (Sweden)

    N. K. Magu

    2014-01-01

    Full Text Available Introduction. Although fractures of humeral shaft show excellent results with conservative management, nonunion does occur. Case Report. We bring forth the case of a young male with a 1.5-year-old hypertrophic nonunion of the humerus mimicking an enchondroma. The initial X-ray images of the patient appeared to be an enchondroma, which only on further evaluation and histopathological analysis was diagnosed conclusively to be a hypertrophic nonunion. Discussion. Enchondromas are often incidentally diagnosed benign tumours. It is however not common to misdiagnose a hypertrophic nonunion to be an enchondroma. We present this case to highlight the unique diagnostic dilemma the treating team had to face.

  12. Dural Metastasis Mimicking Meningioma: An Interesting Case

    Directory of Open Access Journals (Sweden)

    Hamzaini Abdul Hamid

    2009-01-01

    Full Text Available Dural metastasis is a rare entity in clinical practice. We report a case of dural metastasis secondary to thyroid carcinoma, which on both preoperative CT and MRI and at surgery had the typical appearance of a meningioma. Histopathological findings confirmed metastatic follicular thyroid carcinoma as a primary site. Although rare, dural metastases can mimic a meningioma. Our experience in this case has led us to consider metastasis as a differential diagnosis even when a meningioma is suspected. We believe that reporting of the case of dural metastasis mimicking a meningioma may help clinicians in future.

  13. Giant Spermatocele Mimicking Hydrocele: A Case Report

    Directory of Open Access Journals (Sweden)

    Hsin-Chih Yeh

    2007-07-01

    Full Text Available Spermatoceles are usually asymptomatic and often found incidentally during physical examination. We report a case of giant spermatocele that mimicked a hydrocele. A 55-year-old man suffered from right scrotal enlargement for several years. As the heavy sensation and scrotal soreness worsened in recent months, he came to our outpatient clinic for help. Hydrocele was suspected due to transilluminating appearance of the scrotal content. Surgical exploration was arranged and a giant spermatocele was found. Total excision of the spermatocele was performed and the patient recovered well. The specimen was sent for pathology and spermatocele with spermatozoa was noted.

  14. Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres

    OpenAIRE

    Sciuscio D.; Diserens A. C.; van Dommelen K.; Martinet D.; Jones G.; Janzer R. C.; Pollo C.; Hamou M. F.; Kaina B.; Stupp R.; Levivier M.; Hegi M. E.

    2010-01-01

    PURPOSE: Quantitative methylation specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6 methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6 methyl guanine and has been shown ...

  15. Cerebral palsy.

    Science.gov (United States)

    Kent, Ruth M

    2013-01-01

    Cerebral palsy affects movement and posture causing activity limitation; it is a lifelong condition, with foreseeable complications. There are evidence-based interventions that will prevent participation restriction. Childhood interventions are generally delivered within multidisciplinary rehabilitation programs. Sadly young adults are often not transferred to an appropriate multidisciplinary adult neurodisability service. An unexplained neurological deterioration should warrant further investigation. Pain is an important underreported symptom and musculoskeletal complaints are prevalent. Disabled adults have less participation socially, in employment, marriage, and independent living related to health problems, discrimination, or lack of access to information, support, and equipment. Evidence-based interventions include a variety of modalities at all International Classification of Functioning, Disability, and Health levels to include support and adaptations. Rehabilitation interventions that have been shown to be effective include surgery in childhood, ankle-foot orthoses, strength training, and electrical stimulation. Management of spasticity is beneficial and has an evidence base. Orthotics and casting are also used. Systematic reviews of upper limb therapies also show the benefit of physical therapy exercise, strengthening, fitness training, and constraint therapy. Occupational therapy has a weaker evidence base than in other disabling conditions but many modalities are transferable. Speech therapy is effective although no specific intervention is better. Psychological wellbeing interventions, including improving self-efficacy, health knowledge, and coping skills, are beneficial. Management of continence, nutrition, and fatigue promote wellbeing. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Cellular Effects of the Antiepileptic Drug Valproic Acid in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Marita Eckert

    2017-12-01

    Full Text Available Background/Aims: Valproic acid (VPA, an anticonvulsant and mood-stabilizing drug is used to treat epileptic seizure of glioblastoma patients. Besides its antiepileptic activity, VPA has been attributed further functions that improve the clinical outcome of glioblastoma patients. Those comprise the inhibition of some histone deacetylase (HDAC isoforms which reportedly may result in radiosensitization. Retrospective analysis of patient data, however, could not unequivocally confirm a prolonged survival of glioblastoma patients receiving VPA. The present study aimed to identify potential VPA targets at the cellular level. Methods: To this end, the effect of VPA on metabolism, Ca2+-, biochemical and electro-signaling, cell-cycling, clonogenic survival and transfilter migration was analyzed in three human glioblastoma lines (T98G, U-87MG, U251 by MTT assay, Ca2+ imaging, immunoblotting, patch-clamp recording, flow cytometry, delayed plating colony formation and modified Boyden chamber assays, respectively. In addition, the effect of VPA on clonogenic survival of primary glioblastoma spheroid cultures treated with temozolomide and fractionated radiation was assessed by limited dilution assay. Results: In 2 of 3 glioblastoma lines, clinical relevant concentrations of VPA slightly slowed down cell cycle progression and decreased clonogenic survival. Furthermore, VPA induced Ca2+ signaling which was accompanied by pronounced K+ channel activity and transfilter cell migration. VPA did not affect metabolic NAD(PH formation or radioresistance of the glioblastoma lines. Finally, VPA did not impair clonogenic survival or radioresistance of temozolomide-treated primary spheroid cultures. Conclusions: Combined, our in vitro data do not propose a general use of VPA as a radiosensitizer in anti-glioblastoma therapy.

  17. Lomustine and Bevacizumab in Progressive Glioblastoma.

    Science.gov (United States)

    Wick, Wolfgang; Gorlia, Thierry; Bendszus, Martin; Taphoorn, Martin; Sahm, Felix; Harting, Inga; Brandes, Alba A; Taal, Walter; Domont, Julien; Idbaih, Ahmed; Campone, Mario; Clement, Paul M; Stupp, Roger; Fabbro, Michel; Le Rhun, Emilie; Dubois, Francois; Weller, Michael; von Deimling, Andreas; Golfinopoulos, Vassilis; Bromberg, Jacoline C; Platten, Michael; Klein, Martin; van den Bent, Martin J

    2017-11-16

    Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O 6 -methylguanine-DNA methyltransferase (MGMT) was assessed. Health-related quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival. A total of 437 patients underwent randomization. The median number of 6-week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; Pbevacizumab to lomustine affected neither health-related quality of life nor neurocognitive function. The MGMT status was prognostic. Despite somewhat prolonged progression-free survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an

  18. Clinical and Histologic Mimickers of Celiac Disease.

    Science.gov (United States)

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  19. A classic mimicker of systemic vasculitis.

    Science.gov (United States)

    Moreno-Ariño, Marc; Ortiz-Santamaria, Vera; Deudero Infante, Aída; Ayats Delgado, Montserrat; Novell Teixidó, Francesc

    2016-01-01

    Embolic and constitutional manifestations of intracavitary cardiac tumors are included within the classic mimickers of systemic vasculitis, especially in those in which there are no cardiac manifestations. We present a case report of atrial myxoma in which the patient only presented systemic symptoms and in whom an initial diagnostic approach of systemic vasculitis was made. We also performed a literature search of the cases described. A case report of atrial myxoma with atypical presentation manifested as a systemic disease with no concomitant cardiac symptoms is described. The case report is discussed and 11 cases of atrial myxoma pseudovasculitis described in the literature are reviewed, emphasizing their similarities and differences. Constitutional symptoms and cutaneous manifestations were the most common. Most of the cases showed partial response to glucococorticosteroid treatment, reinforcing the theory of the inflammatory role in its pathogenesis. Mean delayed time to diagnosis was 12.27 months. Atrial myxoma is a systemic vasculitis mimicker, this being difficult to diagnose in the absence of cardiac manifestations. This delay in diagnosis entails serious complications. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. Imaging findings of mimickers of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Tae Kyoung Kim

    2015-12-01

    Full Text Available Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.

  1. Ultrasound artifacts mimicking pleural sliding after pneumonectomy.

    Science.gov (United States)

    Cavaliere, Franco; Zamparelli, Roberto; Soave, Maurizio P; Gargaruti, Riccardo; Scapigliati, Andrea; De Paulis, Stefano

    2014-03-01

    To determine the presence of pleural sliding on chest ultrasonography (US) in a series of patients admitted to a surgical intensive care unit (SICU). Prospective, observational study. 16-bed SICU of a University hospital. 8 patients (7 men, 1 woman), aged 64 - 73 years (mean 67.5 yrs). Seven patients underwent pneumonectomy for pulmonary neoplasms; one patient underwent an atypical lung resection after having undergone a pneumonectomy one year before. None. Chest ultrasounds were performed during mechanical ventilation and spontaneous ventilation after endotracheal tube removal. In both examinations, pleural sliding was searched bilaterally in brightness mode (B-mode) and motion mode (M-mode) on the anterior thoracic wall in the least gravitationally dependent areas. During mechanical ventilation, pleural sliding was always absent on the side of the pneumonectomy and present on the other side. During spontaneous ventilation, some artifacts mimicking pleural sliding were noted on the side of the pneumonectomy both in B-mode and M-mode (presence of the seashore sign) in all patients, except for the one patient who had undergone a pneumonectomy one year earlier. Those artifacts became more pronounced during deep breaths. Ultrasound artifacts mimicking pleural sliding may be observed in the absence of the lung and may originate from the activity of intercostal muscles since they become more evident during deep breathing. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Photodynamic therapy of recurrent cerebral glioma

    Science.gov (United States)

    Zhu, Shu-Gan; Wu, Si-En; Chen, Zong-Qian; Sun, Wei

    1993-03-01

    Photodynamic therapy (PDT) was performed on 11 cases of recurrent cerebral glioma, including 3 cases of recurrent glioblastoma, 7 of recurrent anaplastic astrocytoma, and 1 recurrent ependymoma. Hematoporphyrin derivative (HPD) was administered intravenously at a dose of 4 - 7 mg/kg 5 - 24 hours before the operation. All patients underwent a craniotomy with a nearly radical excision of the tumor following which the tumor bed was irradiated with 630 nm laser light emitting either an argon pumped dye laser or frequency double YAG pumped dye laser for 30 to 80 minutes with a total dose of 50 J/cm2 (n equals 1), 100 J/cm2 (n equals 2), 200 J/cm2 (n equals 7), and 300 J/cm2 (n equals 1). The temperature was kept below 37 degree(s)C by irrigation. Two patients underwent postoperative radiotherapy. There was no evidence of increased cerebral edema, and no other toxicity by the therapy. All patients were discharged from the hospital within 15 days after surgery. We conclude that PDT using 4 - 7 mg/kg of HPD and 630 nm light with a dose of up to 300 J/cm2 can be used as an adjuvant therapy with no additional complications. Adjuvant PDT in the treatment of recurrent glioma is better than simple surgery.

  3. The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance

    Science.gov (United States)

    Siebzehnrubl, Florian A; Silver, Daniel J; Tugertimur, Bugra; Deleyrolle, Loic P; Siebzehnrubl, Dorit; Sarkisian, Matthew R; Devers, Kelly G; Yachnis, Antony T; Kupper, Marius D; Neal, Daniel; Nabilsi, Nancy H; Kladde, Michael P; Suslov, Oleg; Brabletz, Simone; Brabletz, Thomas; Reynolds, Brent A; Steindler, Dennis A

    2013-01-01

    Glioblastoma remains one of the most lethal types of cancer, and is the most common brain tumour in adults. In particular, tumour recurrence after surgical resection and radiation invariably occurs regardless of aggressive chemotherapy. Here, we provide evidence that the transcription factor ZEB1 (zinc finger E-box binding homeobox 1) exerts simultaneous influence over invasion, chemoresistance and tumourigenesis in glioblastoma. ZEB1 is preferentially expressed in invasive glioblastoma cells, where the ZEB1-miR-200 feedback loop interconnects these processes through the downstream effectors ROBO1, c-MYB and MGMT. Moreover, ZEB1 expression in glioblastoma patients is predictive of shorter survival and poor Temozolomide response. Our findings indicate that this regulator of epithelial-mesenchymal transition orchestrates key features of cancer stem cells in malignant glioma and identify ROBO1, OLIG2, CD133 and MGMT as novel targets of the ZEB1 pathway. Thus, ZEB1 is an important candidate molecule for glioblastoma recurrence, a marker of invasive tumour cells and a potential therapeutic target, along with its downstream effectors. Glioblastoma have a poor prognosis, mainly due to infiltrating and therapy resistant cells leading to cancer recurrence. Here, tumor formation, invasion and resistance are not independent but intertwined processes regulated by the EMT activator ZEB1. PMID:23818228

  4. A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.

    Directory of Open Access Journals (Sweden)

    Soumya Alige Mahabala Rao

    Full Text Available Anaplastic astrocytoma (AA; Grade III and glioblastoma (GBM; Grade IV are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.

  5. Bevacizumab for the treatment of glioblastoma.

    Science.gov (United States)

    Gil-Gil, Miguel J; Mesia, Carlos; Rey, Montserrat; Bruna, Jordi

    2013-01-01

    Glioblastoma (GBM) or grade IV glioma is the most common primary brain tumor in adults. Standard treatment median overall survival (OS) is only 14-15 months and less than 10% of patients will survive 5 years after diagnosis. There is no standard treatment in recurrent GBM and OS ranges from 3 to 9 months. GBM is 1 of the most vascularized human tumors and GBM cells produce vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF, has demonstrated activity in vitro and in phase II trials in relapse, as well as in 1 phase III trial as first line therapy. Bevacizumab also improves quality of life for patients suffering GBM. This paper reviews the mechanism of action of bevacizumab, its metabolism and pharmacokinetic profile. It summarizes the clinical studies in recurrent and newly diagnosed GBM, its potential side effects and complications and its place in therapy.

  6. Glioblastoma Multiforme Presenting as Spontaneous Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Cagatay Ozdol

    2014-06-01

    Full Text Available Brain tumors with concomitant intracerebral hemorrhage are rarely encountered. Hemorrhage as the initial presentation of a brain tumour may pose some diagnostic problems, especially if the tumour is small or the hemorrhage is abundant. We present a 47-year-old man who admitted to the emergency department with sudden onset headache, right blurred vision and gait disturbance. A non-contrast cranial computerized tomography scan performed immediately after his admission revealed a well circumscribed right occipitoparietal haematoma with intense peripheral edema causing compression of the ipsilateral ventricles. On 6th hour of his admission the patient%u2019s neurological status deteriorated and he subsequently underwent emergent craniotomy and microsurgical evacuation of the haematoma. The histopathological examination of the mass was consistent with a glioblastoma multiforme. Neoplasms may be hidden behind each case of spontaneous intracerebral hemorrhage. Histological sampling and investigation is mandatory in the presence of preoperative radiological features suggesting a neoplasm.

  7. Growth factors and kinases in glioblastoma growth

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Peña-Ortiz

    2016-10-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive type of brain cancer, having the highest invasion, migration, proliferation, and angiogenesis rates. Several signaling pathways are involved in the regulation of these processes including growth factors and their tyrosine kinase receptors, such as vascular endothelial growth factor (VEGF, transforming growth factor beta (TGFβ, fibroblast growth factor (FGF, platelet-derived growth factor (PDGF, and insulin-like growth factor–I (IGF–I. Different kinases and regulators also participate in signaling pathways initiated by growth factors, such as mitogen-activated kinases (MAPK, protein kinases C (PKC, phosphatidylinositol-3 kinases (PI3K, protein kinase B (PKB or Akt, glycogen synthase kinase 3β (GSK3β, the mTOR complex, and Bcl-2. In this review, we will focus on the role of these proteins as possible therapeutic targets in GBM.

  8. Glioblastoma Multiforme Therapy and Mechanisms of Resistance

    Directory of Open Access Journals (Sweden)

    Yulian P. Ramirez

    2013-11-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.

  9. Combination therapies in a patient-derived glioblastoma model : A step towards precision medicine

    NARCIS (Netherlands)

    L.M.E. Berghauser Pont (Lotte)

    2015-01-01

    markdownabstract__Abstract__ Glioblastoma is the most malignant primary brain tumor. Glioblastoma is originating from the supportive tissue of the brain, the glial cells. Despite increased research, mortality rates have not decreased significantly. Standard therapy consists of surgical resection,

  10. Mimicking Seawater For Culturing Marine Bacteria

    DEFF Research Database (Denmark)

    Rygaard, Anita Mac; Sonnenschein, Eva; Gram, Lone

    2015-01-01

    Only about 1% of marine bacteria have been brought into culture using traditional techniques. The purpose of this study was to investigate if mimicking the natural bacterial environment can increase culturability.We used marine substrates containing defined algal polymers or gellan gum...... 100-fold; from 8.5 x 101 CFU/ml to 5.2 x 103 CFU/ml, whereas addition of AHLs did not improve culturability on any of the media.The substitution of agar with gellan gum shows great promise for increasing culturability of marine bacteria, and further studies are ongoing. The AHLs used in this study...... were selected based on a previous study determining the most common AHLs produced by marine strains of the Vibrionaceae family. However, their effect on culturability could not be fully explained, so also here further studies are being carried out....

  11. Case report. Pityriasis versicolor mimicking Pityriasis rotunda.

    Science.gov (United States)

    Aste, Nicola; Pau, Monica; Aste, Natalia; Biggio, P

    2002-04-01

    Pityriasis versicolor is a common dermatomycosis, occurring throughout the world, characterized by irregular, slightly scaly patches, varying in color from red/light brown to white. Pityriasis rotunda, on the other hand, is an uncommon disease, reported in specific ethnic groups, and characterized by perfectly round or oval patches of varying color, with a scaly surface. The histologic pattern is that of ichthyosis vulgaris. We report here the case of a male patient, aged 31, from Sardinia (Italy), affected by Pityriasis versicolor mimicking Pityriasis rotunda. Mycological examination allowed us to formulate the correct diagnosis, and ensuing treatment with antifungal drugs was entirely successful. The authors, while pointing out the rarity of this case, stress the possibility that Pityriasis versicolor mimics Pityriasis rotunda and vice-versa, especially in those countries in which the two diseases are endemic. More widespread recourse to microscopic examination can help avoid the risk of mistaken diagnosis and consequent incorrect treatment.

  12. Orbital Lymphoma Mimicking Lacrimal Gland Pleomorphic Adenoma

    Directory of Open Access Journals (Sweden)

    Diego Strianese

    2013-09-01

    Full Text Available Purpose: To describe the case of a patient affected by orbital lymphoma mimicking pleomorphic adenoma of the lacrimal gland. Methods: This was a retrospective case report. Results: We present the case of a patient with 15-year history of slowly progressive left proptosis and inferomedial bulbar dislocation who had the presumptive diagnosis of lacrimal gland pleomorphic adenoma based on clinical and radiological features. The patient underwent lateral orbitotomy and lacrimal gland excision. Postoperative histological features were consistent with low-grade B-cell non-Hodgkin lymphoma. Conclusion: The accepted clinico-radiological criteria used for the diagnosis of lacrimal gland fossa lesions might have a certain false-positive rate, even in recent years. The initial surgical approach with the appropriate choice between fine-needle aspiration biopsies, intraoperative biopsies and lacrimal gland excisions might be a challenge.

  13. Orbital roof encephalocele mimicking a destructive neoplasm.

    Science.gov (United States)

    Alsuhaibani, Adel H; Hitchon, Patrick W; Smoker, Wendy R K; Lee, Andrew G; Nerad, Jeffrey A

    2011-01-01

    The purpose of this case report is to report an orbital roof encephalocele mimicking a destructive orbital neoplasm. Orbital roof encephalocele is uncommon but can mimic neoplasm. One potential mechanism for the orbital roof destruction is a post-traumatic "growing orbital roof fracture." The growing fracture has been reported mostly in children but can occur in adults. Alternative potential etiologies for the encephalocele are discussed, including Gorham syndrome. Orbital roof encephalocele is uncommon in adults, and the findings can superficially resemble an orbital neoplasm. Radiographic and clinical features that might suggest the correct diagnosis include a prior history of trauma, overlying frontal lobe encephalomalacia without significant mass effect or edema, and an orbital roof defect. The "growing fracture" mechanism may be a potential explanation for the orbital roof destruction in some cases.

  14. Development of tissue mimicking ultrasound phantom materials

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Sang Chul [Shinheung College, Uijeongbu (Korea, Republic of); Kong, Young Kun [Kyonggi University, Suwon (Korea, Republic of); Park, Ki Jung [Korea Food Drug Administration, Seoul (Korea, Republic of); Lee, Suk [Yonsei Medical Center, Seoul (Korea, Republic of)

    2003-06-15

    We carried out studies on develop of the ultrasound tissue mimicking materials (TMM) by synthesis of polymer urethane (C, CCR, TiO{sub 2}, tungsten, graphite, silver type). The major finding were as follows; (1) C type TMM was shown good homogeneity, penetration, gray scale like as liver tissue and propagated speed 1,540 m/s, attenuation 0.5 {approx} 0.7 dB/cm/MHz. (2) TiO{sub 2} type TMM was shown heterogeneous dot echo pattern. (3) Silver type TMM was appear good homogeneous echo pattern like as echo texture of thyroid gland. Therefor, C type TMM will be useful for ultrasound Q/A phantom materials and previous phantom materials.

  15. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    International Nuclear Information System (INIS)

    Lee, Chul Min; Lee, Seung Hun; Bae, Ji Yoon

    2015-01-01

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis

  16. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  17. Acute perimyocarditis mimicking transmural myocardial infarction

    Directory of Open Access Journals (Sweden)

    Omar Hesham R

    2009-12-01

    Full Text Available Abstract Although acute pericarditis has charachteristic electrocardiographic (ECG findings that differentiate it from acute ST segment elevation myocardial infarction (MI; in certain cases diagnosis is somewhat difficult especially when the ECG reveals focal instead of diffuse changes and moreover when pericarditis is associated with an underlying myocarditis causing elevation of the cardiac biomarkers therefore increasing the difficulty in differentiating between both enteties. This is especially important because adverse lethal side effect can occur if thrombolytic therapy is administered for a patient with acute pericarditis, or if a diagnosis of transmural MI is missed. In this case report we are describing an 18 year old male patient who presented with an acute onset of severe chest pain associated with focal ECG changes and elevated cardiac enzymes mimicking transmural MI. This report aims to sensitize readers to this debate and create awareness among cardiologists and intensivists with both presentations and how to reach an accurate diagnosis.

  18. Pelvic-peritoneal tuberculosis mimicking ovarian cancer

    International Nuclear Information System (INIS)

    Imtiaz, S.; Siddiqui, N.

    2012-01-01

    Pelvic-peritoneal tuberculosis is a common extrapulmonary site in young females mimicking an advanced ovarian malignancy. We present 2 cases with the classical triad of advanced-stage ovarian carcinoma-ascites, abdominopelvic masses and elevated serum CA-125 levels. Laparoscopic examination revealed peritoneal nodules which on biopsy showed granulomatous inflammation and no malignant cells. Patients were started on anti-tuberculous therapy and on follow-up their symptoms as well as CA-125 levels normalized. Medical awareness of peritoneal tuberculosis is lacking and many young women with this disease undergo unnecessary extended surgery. Diagnostic laparoscopy combined with peritoneal biopsy seems to be a sufficient and safe method to provide a definitive diagnosis for this curable infection. If left untreated, the disease may disseminate and result in significant organ dysfunctions particularly infertility. (author)

  19. Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma.

    Science.gov (United States)

    Prah, M A; Stufflebeam, S M; Paulson, E S; Kalpathy-Cramer, J; Gerstner, E R; Batchelor, T T; Barboriak, D P; Rosen, B R; Schmainda, K M

    2015-09-01

    For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques. The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naïve and pathologically proved glioblastoma multiforme (men = 20; mean age = 55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method. When ordered by the repeatability coefficient, methods using postprocessing leakage correction and ΔR2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor (P = .31), yet inferior in tumor for normalized relative CBV (P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%-20%) than normalized relative CBV estimates (24%-67%). The minimum number of participants needed to detect a change of 10% or 20% is 118-643 or 30-161 for normalized relative CBV and 109-215 or 28-54 for standardized relative CBV. The ΔR2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and

  20. Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Khalifa, J. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Tensaouti, F. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Chaltiel, L. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Biostatistics, Toulouse (France); Lotterie, J.A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Catalaa, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Radiology, Toulouse (France); Sunyach, M.P. [Centre Leon Berard, Department of Radiation Oncology, Lyon (France); Ibarrola, D. [CERMEP - Imagerie du Vivant, Lyon (France); Noel, G. [EA 3430, University of Strasbourg, Department of Radiation Oncology, Centre Paul Strauss, Strasbourg (France); Truc, G. [Centre Georges-Francois Leclerc, Department of Radiation Oncology, Dijon (France); Walker, P. [University of Burgundy, Laboratory of Electronics, Computer Science and Imaging (Le2I), UMR 6306 CNRS, Dijon (France); Magne, N. [Institut de cancerologie Lucien-Neuwirth, Department of Radiation Oncology, Saint-Priest-en-Jarez (France); Charissoux, M. [Department of Radiation Oncology, Institut du Cancer de Montpellier, Montpellier (France); Ken, S. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Medical Physics, Toulouse (France); Peran, P. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Berry, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Moyal, E.C. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Universite Toulouse III Paul Sabatier, Toulouse (France); INSERM U1037, Centre de Recherches contre le Cancer de Toulouse, Toulouse (FR); Laprie, A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (FR); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (FR); Universite Toulouse III Paul Sabatier, Toulouse (FR)

    2016-11-15

    To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t{sub end}; MR acquisitions performed at t{sub end-2M}, t{sub end-4M} and t{sub end-6M} (respectively 2, 4 and 6 months before t{sub end}) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∇B from t{sub end-4M} to t{sub end-2M} and ∇B from t{sub end-6M} to t{sub end-4M}. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F{sub h}P{sub g}) was a relevant biomarker. A ratio R(F{sub h}P{sub g}) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F{sub h}Pg) (≥0.61) was associated with more relapse at t{sub end} compared to low R(F{sub h}Pg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F{sub h}P{sub g} from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. (orig.)

  1. Prognostic value of combined visualization of MR diffusion and perfusion maps in glioblastoma.

    Science.gov (United States)

    Deike, Katerina; Wiestler, Benedikt; Graf, Markus; Reimer, Caroline; Floca, Ralf O; Bäumer, Philipp; Kickingereder, Philipp; Heiland, Sabine; Schlemmer, Heinz-Peter; Wick, Wolfgang; Bendszus, Martin; Radbruch, Alexander

    2016-02-01

    We analyzed whether the combined visualization of decreased apparent diffusion coefficient (ADC) values and increased cerebral blood volume (CBV) in perfusion imaging can identify prognosis-related growth patterns in patients with newly diagnosed glioblastoma. Sixty-five consecutive patients were examined with diffusion and dynamic susceptibility-weighted contrast-enhanced perfusion weighted MRI. ADC and CBV maps were co-registered on the T1-w image and a region of interest (ROI) was manually delineated encompassing the enhancing lesion. Within this ROI pixels with ADC values the 70th percentile (CBVmax) and the intersection of pixels with ADCmin and CBVmax were automatically calculated and visualized. Initially, all tumors with a mean intersection greater than the upper quartile of the normally distributed mean intersection of all patients were subsumed to the first growth pattern termed big intersection (BI). Subsequently, the remaining tumors' growth patterns were categorized depending on the qualitative representation of ADCmin, CBVmax and their intersection. Log-rank test exposed a significantly longer overall survival of BI (n = 16) compared to non-BI group (n = 49) (p = 0.0057). Thirty-one, four and 14 patients of the non-BI group were classified as predominant ADC-, CBV- and mixed growth group, respectively. In a multivariate Cox regression model, the BI-, CBV- and mixed groups had significantly lower adjusted hazard ratios (p-value, α(Bonferroni) < 0.006) when compared to the reference group ADC: 0.29 (0.0027), 0.11 (0.038) and 0.33 (0.0059). Our study provides evidence that the combination of diffusion and perfusion imaging allows visualization of different glioblastoma growth patterns that are associated with prognosis. A possible biological hypothesis for this finding could be the interpretation of the ADCmin fraction as the invasion-front of tumor cells while the CBVmax fraction might represent the vascular rich tumor border that is "trailing behind

  2. NETRIN-4 protects glioblastoma cells FROM temozolomide induced senescence.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Glioblastoma multiforme is the most common primary tumor of the central nervous system. The drug temozolomide (TMZ prolongs lifespan in many glioblastoma patients. The sensitivity of glioblastoma cells to TMZ is interfered by many factors, such as the expression of O-6-methylguanine-DNA methyltransferase (MGMT and activation of AKT signaling. We have recently identified the interaction between netrin-4 (NTN4 and integrin beta-4 (ITGB4, which promotes glioblastoma cell proliferation via activating AKT-mTOR signaling pathway. In the current work we have explored the effect of NTN4/ITGB4 interaction on TMZ induced glioblastoma cell senescence. We report here that the suppression of either ITGB4 or NTN4 in glioblastoma cell lines significantly enhances cellular senescence. The sensitivity of GBM cells to TMZ was primarily determined by the expression of MGMT. To omit the effect of MGMT, we concentrated on the cell lines devoid of expression of MGMT. NTN4 partially inhibited TMZ induced cell senescence and rescued AKT from dephosphorylation in U251MG cells, a cell line bearing decent levels of ITGB4. However, addition of exogenous NTN4 displayed no significant effect on TMZ induced senescence rescue or AKT activation in U87MG cells, which expressed ITGB4 at low levels. Furthermore, overexpression of ITGB4 combined with exogenous NTN4 significantly attenuated U87MG cell senescence induced by TMZ. These data suggest that NTN4 protects glioblastoma cells from TMZ induced senescence, probably via rescuing TMZ triggered ITGB4 dependent AKT dephosphorylation. This suggests that interfering the interaction between NTN4 and ITGB4 or concomitant use of the inhibitors of the AKT pathway may improve the therapeutic efficiency of TMZ.

  3. Age groups related glioblastoma study based on radiomics approach.

    Science.gov (United States)

    Li, Zeju; Wang, Yuanyuan; Yu, Jinhua; Guo, Yi; Zhang, Qi

    2017-12-01

    Glioblastoma is the most aggressive malignant brain tumor with poor prognosis. Radiomics is a newly emerging and promising technique to reveal the complex relationships between high-throughput medical image features and deep information of disease including pathology, biomarkers and genomics. An approach was developed to investigate the internal relationship between magnetic resonance imaging (MRI) features and the age-related origins of glioblastomas based on a quantitative radiomics method. A fully automatic image segmentation method was applied to segment the tumor regions from three dimensional MRI images. 555 features were then extracted from the image data. By analyzing large numbers of quantitative image features, some predictive and prognostic information could be obtained by the radiomics approach. 96 patients diagnosed with glioblastoma pathologically have been divided into two age groups (age groups (T test, p age difference (T test, p= .006). In conclusion, glioblastoma in different age groups present different radiomics-feature patterns with statistical significance, which indicates that glioblastoma in different age groups should have different pathologic, protein, or genic origins.

  4. Impact of radiotherapy delay on survival in glioblastoma.

    Science.gov (United States)

    Valduvieco, Izaskun; Verger, Eugènia; Bruna, Jordi; Caral, Lluís; Pujol, Teresa; Ribalta, Teresa; Boget, Teresa; Oleaga, Laura; Pineda, Estela; Graus, Francesc

    2013-04-01

    Previous studies in glioblastoma have concluded that there is no decrease in survival with increasing time to initiation of RT up to 6 weeks after surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6 weeks is not small in some countries. The aim of our study was to evaluate the effect of RT delay beyond 6 weeks on survival of patients who have undergone completed resection of a glioblastoma. We reviewed 107 consecutive glioblastoma patients who had a complete surgical resection at our hospital. Clinical data, including delay in initiation of RT, were prospectively collected. The impact of single parameters on overall survival was determined by univariate and multivariate analyses. According to univariate analysis, variables that had a prognostic influence on survival were age (p = 0.036), KPS (p = 0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before 42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance scale, additional treatment with chemotherapy, and initiation of RT before 6 weeks after surgery were favorable, independent prognostic factors of survival. Survival is significantly reduced in glioblastoma patients if RT is not initiated within the 6 weeks after complete resection of the tumor.

  5. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status

    Directory of Open Access Journals (Sweden)

    Thon N

    2013-09-01

    Full Text Available Niklas Thon,1 Simone Kreth,2 Friedrich-Wilhelm Kreth1 1Department of Neurosurgery, 2Department of Anaesthesiology, Hospital of the University of Munich, Campus Grosshadern, Munich, Germany Abstract: The identification of molecular genetic biomarkers considerably increased our current understanding of glioma genesis, prognostic evaluation, and treatment planning. In glioblastoma, the most malignant intrinsic brain tumor entity in adults, the promoter methylation status of the gene encoding for the repair enzyme O6-methylguanine-DNA methyltransferase (MGMT indicates increased efficacy of current standard of care, which is concomitant and adjuvant chemoradiotherapy with the alkylating agent temozolomide. In the elderly, MGMT promoter methylation status has recently been introduced to be a predictive biomarker that can be used for stratification of treatment regimes. This review gives a short summery of epidemiological, clinical, diagnostic, and treatment aspects of patients who are currently diagnosed with glioblastoma. The most important molecular genetic markers and epigenetic alterations in glioblastoma are summarized. Special focus is given to the physiological function of DNA methylation – in particular, of the MGMT gene promoter, its clinical relevance, technical aspects of status assessment, its correlation with MGMT mRNA and protein expressions, and its place within the management cascade of glioblastoma patients. Keywords: glioblastoma, MGMT, temozolomide, personalized treatment, outcome

  6. Heterogeneity maintenance in glioblastoma: a social network.

    Science.gov (United States)

    Bonavia, Rudy; Inda, Maria-del-Mar; Cavenee, Webster K; Furnari, Frank B

    2011-06-15

    Glioblastoma multiforme (GBM), the most common intracranial tumor in adults, is characterized by extensive heterogeneity at the cellular and molecular levels. This insidious feature arises inevitably in almost all cancers and has great significance for the general outcome of the malignancy, because it confounds our understanding of the disease and also intrinsically contributes to the tumor's aggressiveness and poses an obstacle to the design of effective therapies. The classic view that heterogeneity arises as the result of a tumor's "genetic chaos" and the more contemporary cancer stem cell (CSC) hypothesis tend to identify a single cell population as the therapeutic target: the prevailing clone over time in the first case and the CSC in the latter. However, there is growing evidence that the different tumor cell populations may not be simple bystanders. Rather, they can establish a complex network of interactions between each other and with the tumor microenvironment that eventually strengthens tumor growth and increases chances to escape therapy. These differing but complementary ideas about the origin and maintenance of tumor heterogeneity and its importance in GBM are reviewed here.

  7. Strategies in Gene Therapy for Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S., E-mail: mviapiano@partners.org [Department of Neurosurgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2013-10-22

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.

  8. Strategies in Gene Therapy for Glioblastoma

    International Nuclear Information System (INIS)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S.

    2013-01-01

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy

  9. Use of bevacizumab in recurrent glioblastoma.

    Science.gov (United States)

    Ghiaseddin, Ashley; Peters, Katherine B

    2015-01-01

    Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and mortality as compared with other malignancies. Standard treatment for GBM results in survival of 12.9 months (95% CI: 12.3-13.7 months) with a median progression-free survival of 7.2 months (95% CI: 6.4-8.2 months) in a modern GBM cohort. These aggressive tumors recur and treatment for recurrent GBM continues to have very poor outcomes. Prior to the use of bevacizumab, monoclonal antibody to VEGF, 6-month progression-free survival in clinical trials for recurrent GBM ranged from 9 to 15%. Trials utilizing bevacizumab and its subsequent US FDA approval have given more hope to recurrent GBM and this concise review discusses bevacizumab in recurrent GBM. This review focuses on time-to-event outcomes (overall survival, progression-free survival and 6-month progression-free survival) in clinical trials utilizing bevacizumab for the treatment of recurrent GBM. For this review, we have chosen to focus primarily on Phase II clinical trials that have been published and available in the literature (PubMed). While we focused primarily on time-to-event variables, toxicity and safety of bevacizumab is very important and this agent can be associated with serious life-threatening toxicities. We have included a general section of toxicities but for a more lengthy review please see the excellent study by Odia and colleagues.

  10. The Role of Hypoxia in Glioblastoma Invasion

    Directory of Open Access Journals (Sweden)

    Ana Rita Monteiro

    2017-11-01

    Full Text Available Glioblastoma multiforme (GBM, a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression.

  11. NTRK1 fusion in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Jinkuk Kim

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive form of brain tumor, yet with no targeted therapy with substantial survival benefit. Recent studies on solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA, and found that 3' exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA are fused to 5' exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC and brevican (BCAN. The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. NTRK1 is a mediator of the pro-survival signaling of nerve growth factor (NGF and is a known oncogene, found commonly altered in human cancer. While GBMs largely lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target.

  12. Cancer stem cell contribution to glioblastoma invasiveness.

    Science.gov (United States)

    Ortensi, Barbara; Setti, Matteo; Osti, Daniela; Pelicci, Giuliana

    2013-02-28

    Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. Its invasive nature currently represents the most challenging hurdle to surgical resection. The mechanism adopted by GBM cells to carry out their invasive strategy is an intricate program that recalls what takes place in embryonic cells during development and in carcinoma cells during metastasis formation, the so-called epithelial-to-mesenchymal transition. GBM cells undergo a series of molecular and conformational changes shifting the tumor toward mesenchymal traits, including extracellular matrix remodeling, cytoskeletal re-patterning, and stem-like trait acquisition. A deeper understanding of the mechanisms driving the whole infiltrative process represents the first step toward successful treatment of this pathology. Here, we review recent findings demonstrating the invasive nature of GBM cancer stem cells, together with novel candidate molecules associated with both cancer stem cell biology and GBM invasion, like doublecortin and microRNAs. These findings may affect the design of effective therapies currently not considered for GBM invasive progression.

  13. Targeting aggressive cancer stem cells in glioblastoma

    Directory of Open Access Journals (Sweden)

    Tracy Christina Seymour

    2015-07-01

    Full Text Available Glioblastoma (GBM is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12 to 15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem cells (GSCs within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggests that GSCs share critical signalling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors SOX2, OCT4 and NANOG demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse and achieve a cure for these patients.

  14. The response of human glioblastoma in culture to radiation

    International Nuclear Information System (INIS)

    Masuda, Koji; Aramaki, Ryoji; Takagi, Tosuke

    1980-01-01

    Cells from two human glioblastoma multiforme and one mouse glioma were grown in tissue cultures and their X-ray survival curve parameters were determined under oxygenated and hypoxic conditions. These were compared with the survival parameters for mouse fibroblasts (L5) and established cell lines from human carcinoma coli (HeLa S3) irradiated under identical conditions. There was no significant difference in response among the cell lines used. Repair of potentially lethal damage for human glioblastoma and HeLa S3 was assessed by the increase in survival which occurred as the cells were held in density inhibited stationary phase. The magnitude of repair of potentially lethal damage (slope modifying factors) for the glioblastoma and HeLa were 1.9 and 1.1, respectively. (author)

  15. Glioblastoma and the significance of MGMT gene methylation

    Directory of Open Access Journals (Sweden)

    Payam Izadpanahi

    2014-08-01

    Full Text Available In this research Glioblastoma has been studied as one of the most common brain tumors and a short review of the available therapeutic methods have presented including surgery, radiotherapy, chemotherapy and particularly adjuvant chemotherapy with temozolomide, as the most effective developed treatment. Moreover, MGMT gene promoter methylation has been introduced as an important predictive factor of treatment response to temozolamide. The different mechanisms of methylation and the availableliterature on its association with patient survival and disease recurrence have been summarized. Taken together, Glioblastoma is a tumor in which the MGMT gene expression can potentially deliver the highest amount of data in comparison to other tumors; as almost every related study has emphasized on the direct association between MGMT methylation and patient survival. Regarding this debate, the pseudoprogression pattern in Glioblastoma patients and the laboratory methods studying MGMT gene methylation have been examined. At the end of this review, the obstacles to its development have been briefly mentioned.

  16. Prognostic Value of YKL-40 in Patients with Glioblastoma: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Qin, Gang; Li, Xianfeng; Chen, Zilong; Liao, Guangcha; Su, Yu; Chen, Yaode; Zhang, Wei

    2017-07-01

    YKL-40 is the most highly expressed gene in glioblastoma compared with normal brain tissues. Previous studies assessing the association between YKL-40 and survival in glioblastoma patients reported varying magnitude of estimates. The objective of this meta-analysis was to determine the prognostic value of YKL-40 in glioblastoma patients. PubMed and Embase databases were searched for studies relating to YKL-40 and prognosis of glioblastoma patients. Studies reporting estimates for overall survival by YKL-40 expression in glioblastoma patients were considered eligible. A meta-analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) and 95 % confidence interval (95%CI). Eight studies were ultimately considered eligible and included into the meta-analysis. Those eight studies included 1241 glioblastoma patients. Meta-analysis of those studies showed that high YKL-40 expression was associated with worse overall survival in glioblastoma patients (HR = 1.46, 95%CI 1.33-1.61, P 40 expression was independently associated with worse overall survival in glioblastoma patients (HR = 1.50, 95%CI 1.35-1.66, P 40 expression and worse overall survival in glioblastoma patients. High YKL-40 expression is independently and markedly associated with worse overall survival in glioblastoma patients. YKL-40 is a good predictive biomarker of prognosis in glioblastoma patients.

  17. Nuclear receptor TLX inhibits TGF-β signaling in glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Erik; Zhai, Qiwei [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Zeng, Zhao-jun [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Molecular Biology Research Center, School of Life Sciences, Central South University, 110, Xiangya Road, Changsha, Hunan 410078 (China); Yoshida, Takeshi [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden); Funa, Keiko, E-mail: keiko.funa@gu.se [Sahlgrenska Cancer Center at the Sahlgrenska Academy, University of Gothenburg, Box 425, SE 405 30 Gothenburg (Sweden)

    2016-05-01

    TLX (also called NR2E1) is an orphan nuclear receptor that maintains stemness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-β (TGF-β) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-β has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-β signaling we wanted to find out if there is any interaction between TLX and TGF-β in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-β signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-β receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-β receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-β target genes. The interaction between TLX and TGF-β may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. - Highlights: • TLX knockdown enhances TGF-β dependent Smad signaling in glioblastoma cells • TLX knockdown increases the protein level of TGF-β receptor II. • TLX stabilizes and retains Smurf1 in the cytoplasm. • TLX enhances Smurf1-dependent ubiquitination and degradation of TGF-β receptor II.

  18. Signal transduction in cerebral arteries after subarachnoid hemorrhage-a phosphoproteomic approach

    DEFF Research Database (Denmark)

    Parker, Benjamin; Larsen, Martin Røssel; Povlsen, Gro Klitgaard

    2013-01-01

    quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected....... STAT3 inhibition partially mimicked these effects. The study shows that quantitative mass spectrometry is a strong approach to study in vivo vascular signaling. Moreover, it shows that targeting of ERK1/2 prevents delayed pathologic changes in cerebral arteries and improves outcome, and identifies SAH......-induced signaling components downstream and upstream of ERK1/2.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 May 2013; doi:10.1038/jcbfm.2013.78....

  19. [Infestation with Enterobius vermicularis mimicking appendicitis].

    Science.gov (United States)

    Levens, Afra M A; Schurink, Maarten; Koetse, Harma A; van Baren, Robertine

    2014-01-01

    Gastrointestinal infestation with the parasite Enterobius vermicularis is common in humans and is usually harmless. Anal pruritus is the most characteristic symptom, but the parasites can cause severe abdominal pain mimicking appendicitis. Early recognition can prevent an unnecessary appendectomy. A six-year-old girl reported to the accident and emergency department with pain in the lower right abdominal region. She was admitted and treated for suspected perforated appendix, following physical examination supplemented with an abdominal CT scan. After antibiotic treatment the symptoms disappeared as did the abscess, apart from a minor amount of residual infiltrate. She was then readmitted twice with recurrent abdominal pain without radiological evidence of an abdominal focus. We decided to conduct a diagnostic laparoscopy and an elective appendectomy à froid. During this procedure living worms were found in the appendix. Treatment with the anthelminthicum mebendazol was effective. Gastro-intestinal infestation with E. vermicularis is very common, especially in young children. This infestation is usually harmless, but can mimic appendicitis. This infestation is easily treatable with mebendazol.

  20. Hyperdense dots mimicking microcalcifications : Mammographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam Hyeon; Park, Jeong Mi; Goo, Hyun Woo; Bang, Sun Woo [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    1996-12-01

    To differentiate fine hyperdense dots mimicking microcalcifications from true microcalcifications on mammography. Mammograms showing hyperdense dots in ten patients (mean age, 59 years) were evaluated. Two radiologists were asked to differentiate with the naked eye the hyperdense dots seen on ten mammograms and proven microcalcifications seen on ten mammograms. Densitometry was also performed for all lesions and the contrast index was calculated. The shape and distribution of the hyperdense dots were evaluated and enquires were made regarding any history of breast disease and corresponding treatment. Biopsies were performed for two patients with hyperdense dots. Two radiologists made correct diagnoses in 19/20 cases(95%). The contrast index was 0.10-0.88 (mean 0.58) for hyperdense dots and 0.02-0.45 (mean 0.17) for true microcalcifications. The hyperdense dots were finer and homogeneously rounder than the microcalcifications. Distribution of the hyperdense dots was more superficial in subcutaneous fat (seven cases) and subareolar area (six cases). All ten patients with hyperdense dots had history of mastitis and abscesses and had been treated by open drainage (six cases) and/or folk remedy (four cases). In eight patients, herb patches had been attached. Biopsies of hyperdense dots did not show any microcalcification or evidence of malignancy. These hyperdense dots were seen mainly in older patients. Their characteristic density, shape, distribution and clinical history makes differential diagnosis from true microcalcifications easy and could reduce unnecessary diagnostic procedures such as surgical biopsy.

  1. Microfabricated adhesive mimicking gecko foot-hair

    Science.gov (United States)

    Geim, A. K.; Dubonos, S. V.; Grigorieva, I. V.; Novoselov, K. S.; Zhukov, A. A.; Shapoval, S. Yu.

    2003-07-01

    The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force ~10-7 N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of ~10 N cm-2: sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.

  2. Clinical significance of CRNDE transcript variants in glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Karrie M.Y. Kiang

    2017-06-01

    Full Text Available The long non-coding RNA CRNDE is an oncogene that promotes tumor growth in glioblastoma multiforme (GBM. At least five CRNDE transcript variants with possibly different functional roles have been described in recent studies. Here, we report our preliminary findings on the differential expressions of CRNDE transcript variants in GBM, and their prognostic significance. Our preliminary data suggest that different transcript variants of CRNDE might have different functions in GBM and should be further studied as potential biomarkers for clinical prognostication. Keywords: Long non-coding RNA, CRNDE, Transcript variant, Glioblastoma

  3. Micro RNAs as molecular markers of glioblastoma multiform

    International Nuclear Information System (INIS)

    Farace, M.G.; Finocchiaro, G.; Ricci Vitiani, L.

    2009-01-01

    The aim of this project was to unravel the role that miR-221 and miR-222, of which we had already demonstrated the specific differential expression in glioblastoma multiforme compared to normal brain, play in the control of cell proliferation, with the ultimate goal to provide new insights in the molecular basis of cancer. The results of our research allowed to identify an important molecular target for miRNA-221 and miR-222, highly expressed in glioblastoma multiforme tissues and cell lines, and to precisely recognize the mRNA regions responsible for this regulation

  4. Huge desmoid tumor of the anterior abdominal wall mimicking an ...

    African Journals Online (AJOL)

    Huge desmoid tumor of the anterior abdominal wall mimicking an intraabdominal mass in a postpartum woman: a case report. Khaled Trigui, Mahdi Bouassida, Houda Kilani, Mohamed Mongi Mighri, Selim Sassi, Fathi Chebbi, Hassen Touinsi, Sadok Sassi ...

  5. Fluctuations in Cerebral Hemodynamics

    National Research Council Canada - National Science Library

    Latka, Miroslaw

    2003-01-01

    We demonstrate that the scaling properties of intracranial pressure (ICP) fluctuations and fluctuations of blood flow velocity in middle cerebral arteries are characterized by two scaling exponents...

  6. Cerebral arteriovenous malformation

    Science.gov (United States)

    ... Alternative Names AVM - cerebral; Arteriovenous hemangioma; Stroke - AVM; Hemorrhagic stroke - AVM Patient Instructions Brain surgery - discharge Headache - what to ask your doctor Stereotactic ...

  7. Lung cancer: atypical brain metastases mimicking neurocysticercosis.

    Science.gov (United States)

    Mota, Patrícia Caetano; Reis, Carina; Pires, Nuno Filipe; Sousa, Graça; Chamadoira, Clara; Guimarães, Marcos; Castro, Lígia; Marques, Margarida; Gomes, Isabel

    2011-12-01

    The authors describe a case of a 47-year-old male smoker with a 3-month history of hearing loss, tinnitus and dizziness. Physical examination revealed neurosensory hearing loss. Small rounded hypodensities without mass effect were evident in a computed tomography scan of the head, confirmed by brain magnetic resonance imaging as multiple cystic lesions in both cerebral and cerebellar hemispheres, without perilesional edema or gadolinium enhancement, suggestive of neurocysticercosis. Extraparenchymal involvement was also noted. Albendazole and dexamethasone were started. As a chest radiograph showed a bilateral reticulonodular pattern, a bronchoscopy was performed showing normal results. However, transbronchial biopsy revealed lung adenocarcinoma. Thoracoabdominopelvic computed tomography scan showed secondary lung and bone lesions. Since brain lesions were not suggestive of secondary tumor lesions, a brain biopsy was performed confirming metastatic disease. This case illustrates some peculiar imagiological features of brain metastases in lung cancer, indicating that sometimes invasive procedures are required to establish a definitive diagnosis.

  8. Internal Carotid Artery Aneurysm Mimicking Peritonsillar Abscess

    Directory of Open Access Journals (Sweden)

    Jacek Brzost

    2015-01-01

    Full Text Available The extracranial internal carotid artery aneurysm (EICAA is an uncommon arterial lesion. Patients typically present with neurologic symptoms resulting from impaired cerebral perfusion and compression symptoms of cranial nerves. Often EICAA presents as a pulsatile neck mass, which is otherwise asymptomatic. We present a case of an 84-year-old female, who was initially referred to the Emergency Department for Otolaryngology with suspected peritonsillar abscess. The patient had a history of recent upper airway infection and cardiovascular comorbidities, including hypertension and ischaemic stroke complicated by extensive neurologic deficits. Physical examination revealed a compact, nonpulsatile mass in the lateral parapharyngeal space and local erythema of the mucosa. Duplex Doppler Ultrasonography and Computed Tomography revealed an atherosclerotic aneurysm of the right internal carotid artery, measuring 63×55×88 mm, stretching from the skull base to the angle of the mandible.

  9. Cerebral toxoplasmosis mimicking subacute meningitis in HIV-infected patients; a cohort study from Indonesia.

    Directory of Open Access Journals (Sweden)

    A Rizal Ganiem

    Full Text Available BACKGROUND: HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL, with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%. Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04-4.47 compared to those with a negative PCR. CONCLUSIONS/SIGNIFICANCE: Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available.

  10. Ruptured ectopic pregnancy mimicking acute pancreatitis.

    Science.gov (United States)

    Mitura, Kryspin; Romanczuk, Mikolaj

    2009-05-01

    Ectopic pregnancy may lead to massive haemorrhage, infertility or death. Prompt diagnosis and treatment are crucial to save patients who would otherwise die. Serum amylase and lipase measurements are known biochemical markers of pancreatic inflammation and a recognized finding that may help diagnose acute pancreatitis. To the best of our knowledge (Medline, Pubmed, Cochrane Library have been researched) the following study presents the first case of ruptured ectopic pregnancy accompanied by markedly elevated amylase and lipase levels mimicking acute pancreatitis ever reported. A previously healthy, nulliparous 35-year-old woman was admitted to hospital with a 2-day history of abdominal pain and vomiting. Her last menstrual period was 7 weeks before presentation. At the admission, the patient was hemodynamically stable. The abdomen was soft with tenderness in its mesogastric area. Blood tests revealed markedly elevated activities of the pancreatic enzymes. Acute pancreatitis was the early clinical diagnosis and subsequent therapy was initiated. After 12 hours the condition of the patient suddenly worsened. She was clinically shocked with pallor, hypotension and tachycardia. Laboratory tests revealed anaemia and increased activities of pancreatic enzymes. An ultrasound examination demonstrated an accumulation of intraperitoneal fluid in the pelvis. Subsequently, the patient was subjected to immediate laparotomy. The peritoneal cavity contained large amount of blood. A cystic mass was found and extracted from the ruptured and bleeding right fallopian tube. Histological examination confirmed a rupture of an ectopic pregnancy of a 6-week-old foetus with an intact gestational sac. The patient made an uneventful recovery and was discharged from hospital after 8 days. Our case proves that a misdiagnosed ruptured ectopic pregnancy in the event of elevated activities of pancreatic enzymes may lead to delayed diagnosis of haemorrhage to peritoneum, resulting in hemodynamic

  11. Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme.

    Science.gov (United States)

    Grossmann, Kenneth F; Colman, Howard; Akerley, Wallace A; Glantz, Michael; Matsuoko, Yuko; Beelen, Andrew P; Yu, Margaret; De Groot, John F; Aiken, Robert D; Olson, Jeffrey J; Olsen, Jeffery J; Evans, Brent A; Jensen, Randy L

    2012-11-01

    Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of verubulin were tested: 2.1, 2.7, and 3.3 mg/m(2) in a standard "3+3" design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m(2) cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m(2) cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m(2) with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.

  12. Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme.

    Science.gov (United States)

    Maroon, Joseph; Bost, Jeffrey; Amos, Austin; Zuccoli, Giulio

    2013-08-01

    Glioblastoma multiforme is the most common malignant primary brain tumor in adults and generally considered to be universally fatal. Glioblastoma multiforme accounts for 12% to 15% of all intracranial neoplasms and affects 2 to 3 adults per every 100,000 in the United States annually. In children glioblastoma multiforme accounts for only approximately 7% to 9% of central nervous system tumors. The mean survival rate in adults after diagnosis ranges from 12 to 18 months with standard therapy and 3 to 6 months without therapy. The prognosis in children is better compared to adult tumor onset with a mean survival of approximately 4 years following gross total surgical resection and chemotherapy. There have been few advances in the treatment of glioblastoma multiforme in the past 40 years beyond surgery, radiotherapy, chemotherapy, and corticosteroids. For this reason a restrictive calorie ketogenic diet, similar to that used in children to control drug resistant seizure activity, has been advanced as an alternative adjunctive treatment to help prolonged survival. This article reviews the science of tumor metabolism and discusses the mechanism of calorie restriction, cellular energy metabolism, and how dietary induced ketosis can inhibit cancer cell's energy supply to slow tumor growth.

  13. Nestin expression in the cell lines derived from glioblastoma multiforme

    International Nuclear Information System (INIS)

    Veselska, Renata; Kuglik, Petr; Cejpek, Pavel; Svachova, Hana; Neradil, Jakub; Loja, Tomas; Relichova, Jirina

    2006-01-01

    Nestin is a protein belonging to class VI of intermediate filaments that is produced in stem/progenitor cells in the mammalian CNS during development and is consecutively replaced by other intermediate filament proteins (neurofilaments, GFAP). Down-regulated nestin may be re-expressed in the adult organism under certain pathological conditions (brain injury, ischemia, inflammation, neoplastic transformation). Our work focused on a detailed study of the nestin cytoskeleton in cell lines derived from glioblastoma multiforme, because re-expression of nestin together with down-regulation of GFAP has been previously reported in this type of brain tumor. Two cell lines were derived from the tumor tissue of patients treated for glioblastoma multiforme. Nestin and other cytoskeletal proteins were visualized using imunocytochemical methods: indirect immunofluorescence and immunogold-labelling. Using epifluorescence and confocal microscopy, we described the morphology of nestin-positive intermediate filaments in glioblastoma cells of both primary cultures and the derived cell lines, as well as the reorganization of nestin during mitosis. Our most important result came through transmission electron microscopy and provided clear evidence that nestin is present in the cell nucleus. Detailed information concerning the pattern of the nestin cytoskeleton in glioblastoma cell lines and especially the demonstration of nestin in the nucleus represent an important background for further studies of nestin re-expression in relationship to tumor malignancy and invasive potential

  14. Rosmarinic Acid and Melissa officinalis Extracts Differently Affect Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Kristina Ramanauskiene

    2016-01-01

    Full Text Available Lemon balm (Melissa officinalis L. has many biological effects but especially important is its neuroprotective activity. The aim of the study is to produce different extracts of Melissa officinalis and analyse their chemical composition and biological properties on rat glioblastoma C6 cells. Results revealed that rosmarinic acid (RA is the predominant compound of lemon balm extracts. RA has cytotoxic effect on glioblastoma cells (LC50 290.5 μM after the incubation of 24 h and LC50 171.3 μM after 48 h. RA at concentration 80–130 μM suppresses the cell proliferation and has an antioxidant effect. 200 μM and higher concentrations of RA have a prooxidant effect and initiate cell death through necrosis. The aqueous extract of lemon balm is also enriched in phenolic compounds: protocatechuic, caftaric, caffeic, ferulic, and cichoric acids and flavonoid luteolin-7-glucoside. This extract at concentrations 50 μM–200 μM RA has cytotoxic activity and initiates cell death through apoptosis. Extracts prepared with 70% ethanol contain the biggest amount of active compounds. These extracts have the highest cytotoxic activity on glioblastoma cells. They initiate generation of intracellular ROS and cell death through apoptosis and necrosis. Our data suggest that differently prepared lemon balm extracts differently affect glioblastoma cells and can be used as neuroprotective agents in several therapeutic strategies.

  15. Target-specific delivery of doxorubicin to human glioblastoma cell ...

    Indian Academy of Sciences (India)

    Abdullah Tahir Bayraç

    2018-01-29

    Jan 29, 2018 ... aptamer-mediated drug delivery can be applied successfully for clinical use. Keywords. A-172; aptamer; doxorubicin; .... Although developed for one cell line, GMT-3 aptamer can recognize many glioblastoma cell ... lines were supplemented with 10% fetal bovine serum (FBS,. GIBCO.26140079) and 100 ...

  16. Target-specific delivery of doxorubicin to human glioblastoma cell ...

    Indian Academy of Sciences (India)

    Targeted drug delivery approaches have been implementing significant therapeutic gain for cancer treatment since lastdecades. Aptamers are one of the mostly used and highly selective targeting agents for cancer cells. Herein, we address anano-sized targeted drug delivery approach adorned with A-172 glioblastoma ...

  17. The integrated landscape of driver genomic alterations in glioblastoma

    Science.gov (United States)

    Frattini, Veronique; Trifonov, Vladimir; Chan, Joseph Minhow; Castano, Angelica; Lia, Marie; Abate, Francesco; Keir, Stephen T.; Ji, Alan X.; Zoppoli, Pietro; Niola, Francesco; Danussi, Carla; Dolgalev, Igor; Porrati, Paola; Pellegatta, Serena; Heguy, Adriana; Gupta, Gaurav; Pisapia, David J.; Canoll, Peter; Bruce, Jeffrey N.; McLendon, Roger E.; Yan, Hai; Aldape, Ken; Finocchiaro, Gaetano; Mikkelsen, Tom; Privé, Gilbert G.; Bigner, Darell D.; Lasorella, Anna; Rabadan, Raul; Iavarone, Antonio

    2013-01-01

    Glioblastoma remains one of the most challenging forms of cancer to treat. Here, we develop a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma. We find mutations with loss of heterozygosity of LZTR-1, an adaptor of Cul3-containing E3 ligase complexes. Mutations and deletions disrupt LZTR-1 function, which restrains self-renewal and growth of glioma spheres retaining stem cell features. Loss-of-function mutations of CTNND2 target a neural-specific gene and are associated with transformation of glioma cells along the very aggressive mesenchymal phenotype. We also report recurrent translocations that fuse the coding sequence of EGFR to several partners, with EGFR-SEPT14 as the most frequent functional gene fusion in human glioblastoma. EGFR-SEPT14 fusions activate Stat3 signaling and confer mitogen independency and sensitivity to EGFR inhibition. These results provide important insights into the pathogenesis of glioblastoma and highlight new targets for therapeutic intervention. PMID:23917401

  18. Radiation induced sarcoma after treatment of glioblastoma: case report

    International Nuclear Information System (INIS)

    Rosa, Victor Domingos Lisita; Anjos, Caroline Souza dos; Candido, Priscila Barile Marchi; Dias Junior, Antonio Soares; Santos, Evandro Airton Sordi dos; Godoy, Antonio Carlos Cavalcante; Saggioro, Fabiano P.; Carlotti Junior, Carlos Gilberto; Oliveira, Harley Francisco de; Peria, Fernanda Maris

    2016-01-01

    Introduction: Glioblastoma multiform is the most lethal central nervous system neoplasm, with a median survival of around 13 months and the worst prognosis among all gliomas. The therapeutic approach of glioblastoma consists in neurosurgery with maximum possible resection of tumor volume, followed by radiotherapy and chemotherapy. Radiotherapy reduces the risk of tumor recurrence through direct and indirect damage to tumor deoxyribonucleic acid. The long-term effects of radiation therapy include tissue necrosis, vasculopathy, and radiation-induced neoplasia. The most reported secondary intracranial malignant tumors include meningiomas, gliomas, and sarcomas. The latency period between skull radiotherapy and the appearance of radioinduced lesions varies in the literature from six months to 47 years, with an average of 18.7 years. Case report: The present report describes the appearance of high-grade spindle cell sarcoma after ten months in a patient who received glioblastoma treatment at Hospital das Clínicas of Ribeirão Preto of the University of São Paulo. Conclusion: The rarity of this association is probably due to the poor survival of patients with glioblastoma, thus limiting the time to development of secondary neoplasia

  19. Detection of MGMT promoter methylation in glioblastoma using pyrosequencing.

    Science.gov (United States)

    Xie, Hao; Tubbs, Raymond; Yang, Bin

    2015-01-01

    Recent clinical trials on patients with glioblastoma revealed that O(6)-Methylguanine-DNA methyltransferase (MGMT) methylation status significantly predicts patient's response to alkylating agents. In this study, we sought to develop and validate a quantitative MGMT methylation assay using pyrosequencing on glioblastoma. We quantified promoter methylation of MGMT using pyrosequencing on paraffin-embedded fine needle aspiration biopsy tissues from 43 glioblastoma. Using a 10% cutoff, MGMT methylation was identified in 37% cases of glioblastoma and 0% of the non-neoplastic epileptic tissue. Methylation of any individual CpG island in MGMT promoter ranged between 33% and 95%, with a mean of 65%. By a serial dilution of genomic DNA of a homogenously methylated cancer cell line with an unmethylated cell line, the analytical sensitivity is at 5% for pyrosequencing to detect MGMT methylation. The minimal amount of genomic DNA required is 100 ng (approximately 3,000 cells) in small fine needle biopsy specimens. Compared with methylation-specific PCR, pyrosequencing is comparably sensitive, relatively specific, and also provides quantitative information for each CpG methylation.

  20. MGMT promoter methylation in Peruvian patients with glioblastoma.

    Science.gov (United States)

    Belmar-Lopez, Carolina; Castaneda, Carlos A; Castillo, Miluska; García-Corrochano, Pamela; Orrego, Enrique; Meléndez, Barbara; Casavilca, Sandro; Flores, Claudio; Orrego, Enrique

    2018-01-01

    O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter methylation predicts the outcome and response to alkylating chemotherapy in glioblastoma. The aim of this study is to evaluate the prevalence of MGMT methylation in Peruvian glioblastoma cases. We evaluated retrospectively 50 cases of resected glioblastoma during the period 2008-2013 at Instituto Nacional de Enfermedades Neoplasicas in Peru. Samples consisted of paraffin embedded and frozen tumour tissue. MGMT -promoter methylation status and the expression level of MGMT gene were evaluated by methylation-specific PCR and real-time PCR, respectively. Unmethylated, methylated and partially methylated statuses were found in 54%, 20% and 26% of paraffin-embedded samples, respectively. Methylation status was confirmed in the Virgen de la Salud Hospital and frozen samples. There was an association between the status of MGMT -promoter methylation and the level of gene expression ( p = 0.001). Methylation was associated with increased progression-free survival ( p = 0.002) and overall survival (OS) ( p MGMT -promoter methylation frequency in Peruvian glioblastoma is similar to that reported in other populations and the detection test has been standardised.

  1. MGMT gene silencing and benefit from temozolomide in glioblastoma

    NARCIS (Netherlands)

    Hegi, ME; Diserens, A; Gorlia, T; Hamou, M; de Tribolet, N; Weller, M; Kros, JM; Hainfellner, JA; Mason, W; Mariani, L; Bromberg, JEC; Hau, P; Mirimanoff, RO; Cairncross, JG; Janzer, RC; Stupp, R

    2005-01-01

    BACKGROUND: Epigenetic silencing of the MGMT (O(sup 6)-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship

  2. Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

    DEFF Research Database (Denmark)

    Grodzik, Marta; Sawosz, Ewa; Wierzbicki, Mateusz

    2011-01-01

    The objective of the study was to determine the effect of carbon nanoparticles produced by different methods on the growth of brain tumor and the development of blood vessels. Glioblastoma multiforme cells were cultured on the chrioallantoic membrane of chicken embryo and after 7 days of incubati...

  3. Cerebral Palsy (For Teens)

    Science.gov (United States)

    ... Feelings Expert Answers Q&A Movies & More for Teens Teens site Sitio para adolescentes Body Mind Sexual Health ... Educators Search English Español Cerebral Palsy KidsHealth / For Teens / Cerebral Palsy What's in this article? What Is ...

  4. Cerebral Palsy (For Kids)

    Science.gov (United States)

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cerebral Palsy KidsHealth / For Kids / Cerebral Palsy What's in this article? What's CP? ...

  5. Glioblastoma: Análisis molecular y sus implicancias clínicas

    Directory of Open Access Journals (Sweden)

    Carlos A Castañeda

    Full Text Available El glioblastoma multiforme (GB es el tumor cerebral primario del sistema nervioso central (SNC más frecuente y más letal en la edad adulta. La evidencia epidemiológica indica que su incidencia es menor en la raza hispana. El tratamiento quirúrgico es la opción terapéutica preferente. Recientemente se han introducido nuevas estrategias que incrementan el volumen de resección. El uso de quimioterapia y radioterapia concurrentes mejora la supervivencia de los pacientes, aunque se asocia a toxicidad. La mejora en la comprensión de la biología molecular del GB ha permitido la identificación de biomarcadores predictivos de respuesta terapéutica y pronóstico, así como la identificación de dianas terapéuticas que han permitido el desarrollo de nuevas estrategias en el tratamiento de estos tumores. Entre los biomarcadores actualmente disponibles se encuentran la codelección 1p/19q, la mutación de IDH y la metilación del promotor O6- metilguanina DNA-metiltransferasa. La identificación de dianas terapéuticas permite el desarrollo de nuevas drogas y su evaluación posterior en ensayos clínicos, aunque ninguna de ellas ha sido validada prospectivamente en ensayos clínicos de fase III

  6. Interstitial photodynamic therapy and glioblastoma: light fractionation study on a preclinical model: preliminary results

    Science.gov (United States)

    Leroy, Henri-Arthur; Vermandel, Maximilien; Tétard, Marie-Charlotte; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas

    2015-03-01

    Background Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a local treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen to form cytotoxic species. Fractionation of light delivery may enhance treatment efficiency by restoring tissue oxygenation. Objectives To evaluate the efficiency of light fractionation using MRI imaging, including diffusion and perfusion, compared to histological data. Materials and Methods Thirty-nine "Nude" rats were grafted with human U87 cells into the right putamen. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomized in three groups: without illumination, with monofractionated illumination and the third one with multifractionated light. Treatment effects were assessed with early MRI including diffusion and perfusion sequences. The animals were eventually sacrificed to perform brain histology. Results On MRI, we observed elevated diffusion values in the center of the tumor among treated animals, especially in multifractionated group. Perfusion decreased around the treatment site, all the more in the multifractionated group. Histology confirmed our MRI findings, with a more extensive necrosis and associated with a rarified angiogenic network in the treatment area, after multifractionated PDT. However, we observed more surrounding edema and neovascularization in the peripheral ring after multifractionated PDT. Conclusion Fractionated interstitial PDT induced specific tumoral lesions. The multifractionated scheme was more efficient, inducing increased tumoral necrosis, but it also caused significant peripheral edema and neovascularization. Diffusion and perfusion MRI imaging were able to predict the histological lesions.

  7. HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Ingo Staudacher

    Full Text Available Glioblastoma (GB is associated with poor patient survival owing to uncontrolled tumor proliferation and resistance to apoptosis. Human ether-a-go-go-related gene K(+ channels (hERG; Kv11.1, KCNH2 are expressed in multiple cancer cells including GB and control cell proliferation and death. We hypothesized that pharmacological targeting of hERG protein would inhibit tumor growth by inducing apoptosis of GB cells. The small molecule hERG ligand doxazosin induced concentration-dependent apoptosis of human LNT-229 (EC50 = 35 µM and U87MG (EC50 = 29 µM GB cells, accompanied by cell cycle arrest in the G0/G1 phase. Apoptosis was associated with 64% reduction of hERG protein. HERG suppression via siRNA-mediated knock down mimicked pro-apoptotic effects of doxazosin. Antagonism of doxazosin binding by the non-apoptotic hERG ligand terazosin resulted in rescue of protein expression and in increased survival of GB cells. At the molecular level doxazosin-dependent apoptosis was characterized by activation of pro-apoptotic factors (phospho-erythropoietin-producing human hepatocellular carcinoma receptor tyrosine kinase A2, phospho-p38 mitogen-activated protein kinase, growth arrest and DNA damage inducible gene 153, cleaved caspases 9, 7, and 3, and by inactivation of anti-apoptotic poly-ADP-ribose-polymerase, respectively. In summary, this work identifies doxazosin as small molecule compound that promotes apoptosis and exerts anti-proliferative effects in human GB cells. Suppression of hERG protein is a crucial molecular event in GB cell apoptosis. Doxazosin and future derivatives are proposed as novel options for more effective GB treatment.

  8. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    Science.gov (United States)

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Effectiveness of Radiotherapy for Elderly Patients With Glioblastoma

    International Nuclear Information System (INIS)

    Scott, Jacob; Tsai, Ya-Yu; Chinnaiyan, Prakash; Yu, Hsiang-Hsuan Michael

    2011-01-01

    Purpose: Radiotherapy plays a central role in the definitive treatment of glioblastoma. However, the optimal management of elderly patients with glioblastoma remains controversial, as the relative benefit in this patient population is unclear. To better understand the role that radiation plays in the treatment of glioblastoma in the elderly, we analyzed factors influencing patient survival using a large population-based registry. Methods and Materials: A total of 2,836 patients more than 70 years of age diagnosed with glioblastoma between 1993 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Demographic and clinical variables used in the analysis included gender, ethnicity, tumor size, age at diagnosis, surgery, and radiotherapy. Cancer-specific survival and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using Cox regression. Results: Radiotherapy was administered in 64% of these patients, and surgery was performed in 68%. Among 2,836 patients, 46% received surgery and radiotherapy, 22% underwent surgery only, 18% underwent radiotherapy only, and 14% did not undergo either treatment. The median survival for patients who underwent surgery and radiotherapy was 8 months. The median survival for patients who underwent radiotherapy only was 4 months, and for patients who underwent surgery only was 3 months. Those who received neither surgery nor radiotherapy had a median survival of 2 months (p < 0.001). Multivariate analysis showed that radiotherapy significantly improved cancer-specific survival (hazard ratio [HR], 0.43, 95% confidence interval [CI] 0.38-0.49) after adjusting for surgery, tumor size, gender, ethnicity, and age at diagnosis. Other factors associated with Cancer-specific survival included surgery, tumor size, age at diagnosis, and ethnicity. Analysis using overall survival as the endpoint yielded very similar results. Conclusions: Elderly

  10. Restless legs syndrome mimicking S1 radiculopathy.

    Science.gov (United States)

    Zambelis, Th; Wolgamuth, B R; Papoutsi, S N; Economou, N T

    2016-01-01

    mimicking several pathological conditions, Restless Legs Syndrome prevalence on general population according to various large epidemiological studies and pathogenic hypotheses on the issue of Restless Legs Syndrome are discussed. Finally, by presenting another possible "RLS-mimic" our aim is to highlight the common misdiagnosis of Restless Legs Syndrome, which can mimic a variety of disorders, some of which are very common, such as an S1 radiculopathy, thus raising concern among doctors of various specialties addressed to by Restless Legs Syndrome sufferers, on the importance of proper diagnosis of the syndrome.

  11. Glioblastoma extracellular vesicles: reservoirs of potential biomarkers

    Directory of Open Access Journals (Sweden)

    Redzic JS

    2014-02-01

    Full Text Available Jasmina S Redzic,1 Timothy H Ung,2 Michael W Graner2 1Skaggs School of Pharmacy and Pharmaceutical Sciences, 2Department of Neurosurgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA Abstract: Glioblastoma multiforme (GBM is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis. The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated. Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI], and the diagnosis is validated by pathology, following surgical resection. The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression. Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data. Extracellular vesicles (EVs are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva. EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles. These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure. That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing. Here, we review

  12. Cerebral haematocrit measurement

    International Nuclear Information System (INIS)

    Loutfi, Issa.

    1987-01-01

    Regional cerebral haematocrit was measured in a group of sixteen subjects by the single-photon emission computerized tomography method. This group included three normal subjects as controls and thirteen patients affected with ischaemic cerebral disease presenting clinically with transient ischaemic attacks-six patients - or recent cerebral stroke - seven patients. Two intravenous radioactive tracers - technetium-99m labelled autologous red blood cells and Tc-99m human serum albumin were used. Cerebral tomographic imaging was performed using a rotating scintillation camera. The values of cerebral haematocrit obtained, taken as a ratio to venous haematocrit, range between 0.65-0.88 in the subjects studied. As a general finding in normal subjects and in patients with transient ischaemic attacks, no significant difference between right and left hemispheric haematocrit value was noted. However, in the group of patients affected with stroke, a significant difference in the right versus left hemispheric Hct was observed in 3 patients, the higher Hct value corresponding to the affected side. The clinical implication is on the emphasis of cerebral Hct measurement when the measurement of cerebral blood flow or volume is sought. Also the variation in regional Hct value observed in patients with stroke, above mentioned, points to a regulation mechanism of the blood composition for optimal oxygen delivery to the brain that is impaired in these patients. 14 refs. (Author)

  13. MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

    OpenAIRE

    Zhang, Kai-Liang; Zhou, Xuan; Han, Lei; Chen, Lu-Yue; Chen, Ling-Chao; Shi, Zhen-Dong; Yang, Ming; Ren, Yu; Yang, Jing-Xuan; Frank, Thomas S; Zhang, Chuan-Bao; Zhang, Jun-Xia; Pu, Pei-Yu; Zhang, Jian-Ning; Jiang, Tao

    2014-01-01

    Background Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown. Methods miR-566 expression levels were detected in glioma c...

  14. Ocular surface foreign bodies: novel findings mimicking ocular malignant melanoma.

    Science.gov (United States)

    Maudgil, A; Wagner, B E; Rundle, P; Rennie, I G; Mudhar, H S

    2014-11-01

    Malignant melanoma of the eye is an uncommon condition that is important to recognise. We describe three cases in which ocular foreign bodies have masqueraded as ocular malignant melanoma. Interventional case reports. Case 1 describes diathermy-induced carbon particle implantation, during plaque therapy for the treatment of uveal melanoma, mimicking recurrence with extra-scleral invasion. Case 2 shows a foreign body called 'mullite' mimicking conjunctival melanoma. Case 3 demonstrates a conjunctival foreign body called 'illite' that mimicked a limbal melanocytic lesion, clinically thought to be either melanocytoma or melanoma. This report highlights the importance of careful history taking, examination, and appropriate biopsy in cases of suspected malignant melanoma, to prevent unnecessary and potentially radical treatment.

  15. Deregulation of a STAT3-IL8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and Invasiveness

    Science.gov (United States)

    de la Iglesia, Núria; Konopka, Genevieve; Lim, Kah Leong; Nutt, Catherine L.; Bromberg, Jacqueline F.; Frank, David A.; Mischel, Paul S.; Louis, David N.; Bonni, Azad

    2009-01-01

    Inactivation of the tumor suppressor PTEN is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells including their proliferation and propensity for invasiveness remain poorly understood. Genetic studies suggest that the transcription factor STAT3 harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine IL8 as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3-inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8 whose deregulation plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. PMID:18524891

  16. Fulminant intravascular lymphomatosis mimicking acute haemorrhagic leukoencephalopathy.

    Science.gov (United States)

    Marino, D; Sicurelli, F; Cerase, A; Tripodi, S; Cintorino, M; Lazzi, S; Federico, A

    2012-09-15

    Intravascular lymphomatosis (IVL) is a rare non-Hodgkin's lymphoma, usually of B cell lineage, characterized by massive angiotropic growth. The clinical presentation of IVL may include changes in mental status, non-localizing neurological deficits, seizures, fever of unknown origin and skin changes. Because of its rarity and the absence of specific diagnostic procedures except for cerebral biopsy, diagnosis is often postmortem. Brain MRI usually shows non-specific abnormalities. The purpose of this case report is to increase the knowledge of clinical and neuroimaging features of IVL by describing the findings observed in a 71-year-old patient. A 71-year-old male was admitted for right hemiparesis, acute cognitive impairment and febricula. A bone marrow biopsy resulted normal. He then developed a rapid progressive impairment of his mental status and left hemisoma motor seizures. Brain CT and MRI were interpreted as consistent with acute haemorrhagic leukoencephalopathy (AHLE), including multiple areas of restricted diffusion without gadolinium enhancement and a small focal area of gadolinium enhancement in the left temporal lobe white matter. The patient died within a few days and the autopsy led to the diagnosis of IVL. IVL may present with a variety of clinical signs and symptoms, including stroke and hemiparesis. IVL may mimic AHLE at brain MRI. However, the evidence of multiple areas of restricted diffusion without gadolinium enhancement and of a small area of gadolinium enhancement could have led to the correct diagnosis. IVL should be added to the differential diagnosis of AHLE at brain MRI. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Neonatal appendicitis mimicking intestinal duplication: a case report

    Directory of Open Access Journals (Sweden)

    Saeki Isamu

    2012-09-01

    Full Text Available Abstract Introduction Acute appendicitis is a common disease in older children but rare in neonates. Case presentation We report the case of a 2-day-old Asian baby who suffered from neonatal appendicitis mimicking intestinal duplication. Laparoscopic appendectomy was successfully performed after the trans-umbilical division of adhesions, and the postoperative course was uneventful. Conclusion There are few reports describing abdominal masses caused by appendicitis mimicking intestinal duplication. The laparoscopic approach for neonatal appendicitis is considered to be a safe and useful therapeutic modality with good cosmetic results.

  18. Infiltração leptomeníngea por glioblastoma multiforme da medula cervicotorácica Leptomeningeal infiltration by glioblastoma multiformis of cervico-thoracic region of the spinal cord

    Directory of Open Access Journals (Sweden)

    A. Spina-França

    1969-03-01

    Full Text Available Estudo anátomo-clínico de caso de paciente com glioblastoma multiforme da porção cervicotorácica da medula espinhal. A partir da sede primitiva o tumor invadia o espaço sub-aracnóideo, formando manguito que envolvia a medula desde a dilatação cervical até a região lombar. Apesar do crescimento tão extenso no espaço sub-aracnóideo, não foram encontradas metástases leptomeníngeas à distância. Considerações são feitas sobre a freqüência com que o glioblastoma é observado entre os tumores medulares e sobre os modos pelos quais esse glioma costuma invadir as leptomeninges. Também no caso registrado foi verificada hipoglicorraquia, achado relatado com certa freqüência no comprometimento leptomeníngeo por neoplasias.The case of a 17 year old patient with glioblastoma multiformis of cervico-thoracic region of the spinal cord whose disease was first manifested almost 7 months prior to death is reported. Initial symptoms of sphincter disfunction were soon followed by clinical signs of transverse myelopathy in the upper thoracic region. A complete block of the spinal canal was found on manometric tests. The cerebrospinal fluid was xanthochromic and coagulated immediatly; total protein concentration was markedly increased and glycosis content was low. Descendent perimyelography showed that blocking was complete at the level of first thoracic vertebral body and that it was caused by an intramedullar expanding process. About two months before death symptoms referred to spinal cord impairment assumed an ascending character. Signs of peripheral motor neuron impairment appeared in the upper extremities. Progressive signs of intracranial hypertension appeared and preceeded death. A transient cardiac arrest and apnea occured. The patient, maintained under artificial respiration, remained in comatous state until death, two days later. Brain edema was found at post-morten examination. Cerebral meninges were normal. The upper portions of

  19. Neonatal Cerebral Sinovenous Thrombosis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-04-01

    Full Text Available The presentation, treatment, and outcome of neonatal cerebral sinovenous thrombosis (SVT were studied in 42 children, using neurology clinic records (1986-2005 at Indiana University School of Medicine.

  20. Cerebral Manifestations of Preeclampsia

    NARCIS (Netherlands)

    I.A. Brussé (Ingrid)

    2016-01-01

    textabstractThis thesis intends to describe and explain the course of clinical neurophysiological and neuropsychological parameters in patients with hypertensive disorders in pregnancy. We aimed to improve knowledge on cerebral pathophysiological mechanisms of preeclampsia related to signs and

  1. Demonstration of cerebral vessels by multiplane computed cerebral angiotomography

    International Nuclear Information System (INIS)

    Asari, Syoji; Satoh, Toru; Sakurai, Masaru; Yamamoto, Yuji; Sadamoto, Kazuhiko.

    1981-01-01

    1. Cerebral arteries and veins were demonstrated by multiplane computed cerebral angiotomography [combination of axial, modified coronal, half axial (Towne), and semisagittal planes]. The vessels which were demonstrated by various planes were as follows: Axial plane: Willis ring, middle cerebral arteries (horizontal and insular portions), anterior cerebral arteries (Horizontal and ascending portions), posterior cerebral arteries, basal vein of Rosenthal, internal cerebral veins (and the subependymal veins which join the ICV), and vein of Galen. Coronal plane: intermal carotid arteries (supraclinoid portion), anterior cerebral arteries (horizontal portion), middle cerebral arteries (horizontal and insular portions), lenticulostriate arteries, basal vein of Rosenthal (and the subependymal veins which join this vessel), internal cerebral veins, and vein of Galen. Half axial plane (Towne projection): basilar artery, vertebral arteries, posterior cerebral arteries, superior cerebellar arteries, middle cerebral arteries (horizontal portion), and anterior cerebral arteries (horizontal and ascending portions). Semisagittal plane: internal carotid artery (supraclinoid portion), posterior communicating artery, posterior carebral artery, superior cerebellar artery, internal cerebral vein, basal vein of Rosenthal, vein of Galen, and straight shinus. 2. A detailed knowledge of normal cerebrovascular structures acquired by computed tomography (CT) is essential in detecting and more precisely localizing lesions such as cerebrovascular disease, neoplasm or abscess, in differentiating these lesions from the normal contrast-enhanced structures, and in understanding the spatial relationship between the mass lesion and the neighboring vessels. In addition, it will be possible to discover such asymptomatic cerebrovascular diseases as non-ruptured aneurysms, arteriovenous malformations, and Moyamoya disease by means of computed cerebral angiotomography. (author)

  2. Acute ischemic cerebral attack

    OpenAIRE

    Franco-Garcia Samir; Barreiro-Pinto Belis

    2010-01-01

    The decrease of the cerebral blood flow below the threshold of autoregulation led to changes of cerebral ischemia and necrosis that traduce in signs and symtoms of focal neurologic dysfunction called acute cerebrovascular symdrome (ACS) or stroke. Two big groups according to its etiology are included in this category the hemorragic that constitue a 20% and the ischemic a 80% of cases. Great interest has wom the ischemic ACS because of its high social burden, being the third cause of no violen...

  3. Nanomedicine in cerebral palsy

    Science.gov (United States)

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. PMID:24204146

  4. Non-HTLV-I associated pleomorphic T-cell lymphoma of the brain mimicking post-vaccinal acute inflammatory demyelination.

    Science.gov (United States)

    Wanschitz, J; Hainfellner, J A; Simonitsch, I; Schnizer, M; Deisenhammer, E; Terunuma, H; Iwasaki, Y; Budka, H

    1997-02-01

    Two weeks after vaccination against tick-borne encephalitis (TBE), a 57-year-old female suddenly developed mental confusion and hemiparesis of the left side. Cranial MRI demonstrated extensive bilateral lesions in the fronto-parietal white matter of both hemispheres, suggesting an acute inflammatory demyelinating disease following vaccination. Despite administration of high-dose corticosteroids, the patient died 3 weeks after onset of neurological symptoms. Autopsy revealed diffuse infiltrates of a primary cerebral pleomorphic T-cell lymphoma of medium and large cell type. PCR on brain tissue for HTLV-I and serology for anti-HTLV-I antibodies in CSF and serum were negative; immunocytochemistry on brain tissue did not detect EBV-related antigen. This is the first recorded observation of a diffusely infiltrating primary central nervous system T-cell lymphoma, clinically and radiologically mimicking a fatal acute inflammatory demyelinating complication after vaccination.

  5. Advanced case of glioblastoma multiforme and pregnancy. An ethical dilemma.

    Science.gov (United States)

    Al-Rasheedy, Intisar M; Al-Hameed, Fahad M

    2015-10-01

    Glioblastoma multiforme (GBM) is the most common and malignant form of the glial tumors. Advanced and treated GBM is rarely associated with pregnancy for many reasons. Glioblastoma multiforme presenting during pregnancy carries unique challenges to the patient, baby, family, and health care providers. We describe an unusual case of advanced GBM that was treated with maximum doses of chemotherapy and radiations, and she became pregnant and presented at eighteenth weeks of gestation. Her medical management was associated with a significant ethical dilemma. We managed to deliver the baby safely through cesarean section at week 28 despite the critical condition of the mother. Unfortunately, the mother died 2 weeks post delivery. We concluded that although recurrent and treated GBM is rarely associated with pregnancy and carries dismal prognosis, but if it occurs, it can still be carried, and a multidisciplinary team work is the key for successful outcome.

  6. Targeting glioblastoma via intranasal administration of Ff bacteriophages.

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  7. Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

    Science.gov (United States)

    Bartolotti, Marco; Tosoni, Alicia; Poggi, Rosalba; Franceschi, Enrico

    2015-01-01

    Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events. PMID:25568148

  8. Multifaceted role of galectin-3 on human glioblastoma cell motility

    International Nuclear Information System (INIS)

    Debray, Charles; Vereecken, Pierre; Belot, Nathalie; Teillard, Peggy; Brion, Jean-Pierre; Pandolfo, Massimo; Pochet, Roland

    2004-01-01

    Astrocytic tumors' aggressiveness results from an imbalance between cell proliferation and cell death favoring growth, but also from the propensity of tumor cells to detach from the primary tumor site, migrate, and invade the surrounding parenchyma. Astrocytic tumor progression is known to be associated with an increased expression of galectin-3. We investigated in cell culture how galectin-3 expression affects astrocytoma cell motility. Galectin-3 deficient cells were obtained by stable transfection of the U373 glioblastoma cell line with a specific expression antisense plasmid. Cultured galectin-3 deficient glioblastoma cells showed increased motility potential on laminin and modifications in the cytoskeleton reorganization. In addition, c-DNA microarrays and quantitative immunofluorescence analysis showed that galectin-3 deficient U373 cells have an increased expression of integrins-α6 and -β1, proteins known to be implicated in the regulation of cell adhesion

  9. Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youkyung; Kim, Ji-hoon; Kim, Eunhee; Yim, Yoo Jeong; Sohn, Chul-Ho [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Park, Sung-Hye [Seoul National University, Department of Pathology, School of Medicine, Seoul (Korea); Chang, Kee-Hyun [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea); Seoul National University Medical Research Center, Neuroscience Research Institute, Seoul (Korea)

    2009-10-15

    Primary angiitis of the central nervous system (PACNS) is an extremely rare vasculitis of unknown etiology. The purpose of this study was to describe the initial and follow-up magnetic resonance (MR) imaging features of the tumor-mimicking PACNS. We retrospectively reviewed a total of 21 initial and follow-up brain MR images obtained in four patients with biopsy-proven PACNS mimicking brain tumor on MR images during the periods from 1 to 8.1 years. In the initial study, diffusion-weighted imaging (DWI; n=4), MR angiogram (n=4), conventional catheter angiogram (n=3), perfusion MR (n=1), and computed tomography (n=1) and proton MR spectroscopy (MRS; n=2) were included. The lesions of the brain were qualitatively assessed in terms of location, number, size, shape, signal intensity, absence or presence of hemorrhage, enhancement pattern, and changes on the follow-up studies. Initially, the lesion manifested as single suprasellar (n=1) and frontal hemispheric (n=1) mass and as multiple-enhancing lesions in the unilateral supratentorial hemisphere (n=2). A patient showed steno-occlusive lesions in the internal carotid and middle cerebral arteries. DWI, perfusion imaging, and MRS revealed inconsistent findings among the patients. On the follow-up studies, a patient had two relapses but there was either significant decrease in size and extent or disappearance of the lesions with immunosuppressive therapy in all patients. Tumor-mimicking PACNS shows variable features on initial MR images but shows good responses to appropriate immunosuppressive therapy on follow-up MR images. (orig.)

  10. Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells.

    Science.gov (United States)

    Chakrabarti, Mrinmay; Ray, Swapan K

    2015-12-10

    Glioblastoma is the most lethal brain tumor. Failure of conventional chemotherapies prompted the search for natural compounds for treatment of glioblastoma. Plant-derived flavonoids could be alternative medicine for inhibiting not only glioblastoma cells but also glioblastoma stem cells (GSC). Two plant-derived flavonoids are luteolin (LUT) and silibinin (SIL). We investigated anti-tumor mechanisms of LUT and SIL in different human glioblastoma cells and GSC and found significant synergistic inhibition of human glioblastoma LN18 and SNB19 cells and GSC following treatment with combination of 20µM LUT and 50µM SIL. Combination of 20µM LUT and 50µM SIL was more effective than a conventional chemotherapeutic agent (BCNU or TMZ). We continued our studies with SNB19 cells and GSC and found dramatic inhibition of cell migration from spheroids and also cell invasion through matrigel following treatment with combination of LUT and SIL. This combination was highly effective to block angiogenesis and survival pathways leading to induction of apoptosis. Inhibition of PKCα, XIAP, and iNOS ultimately caused induction of extrinsic and intrinsic pathways of apoptosis. Collectively, synergistic efficacy of LUT and SIL could be a promising therapy to inhibit cell migration and invasion and induce apoptosis in different glioblastoma cells including GSC. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Cerebral palsy and congenital malformations

    DEFF Research Database (Denmark)

    Garne, Ester; Dolk, Helen; Krägeloh-Mann, Inge

    2007-01-01

    AIM: To determine the proportion of children with cerebral palsy (CP) who have cerebral and non-cerebral congenital malformations. METHODS: Data from 11 CP registries contributing to the European Cerebral Palsy Database (SCPE), for children born in the period 1976-1996. The malformations were...... classified as recognized syndromes, chromosomal anomalies, cerebral malformations or non-cerebral malformations. Prevalence of malformations was compared to published data on livebirths from a European database of congenital malformations (EUROCAT). RESULTS: Overall 547 out of 4584 children (11.9%) with CP...... were reported to have a congenital malformation. The majority (8.6% of all children) were diagnosed with a cerebral malformation. The most frequent types of cerebral malformations were microcephaly and hydrocephaly. Non-cerebral malformations were present in 97 CP children and in further 14 CP children...

  12. Indirect costs associated with glioblastoma: Experience at one hospital.

    Science.gov (United States)

    Undabeitia, J; Torres-Bayona, S; Samprón, N; Arrázola, M; Bollar, A; Armendariz, M; Torres, P; Ruiz, I; Caballero, M C; Egaña, L; Querejeta, A; Villanua, J; Pardo, E; Etxegoien, I; Liceaga, G; Urtasun, M; Michan, M; Emparanza, J I; Aldaz, P; Matheu, A; Úrculo, E

    2018-03-01

    Glioblastoma is the most common primary brain tumour. Despite advances in treatment, its prognosis remains dismal, with a mean survival time of about 14 months. Many articles have addressed direct costs, those associated with the diagnosis and treatment of the disease. Indirect costs, those associated with loss of productivity due to the disease, have seldom been described. We conducted a retrospective study in patients diagnosed with glioblastoma at Hospital Universitario Donostia between January 1, 2010 and December 31, 2013. We collected demographics, data regarding the treatment received, and survival times. We calculated the indirect costs with the human capital approach, adjusting the mean salaries of comparable individuals by sex and age and obtaining mortality data for the general population from the Spanish National Statistics Institute. Past salaries were updated to 2015 euros according to the annual inflation rate and we applied a discount of 3.5% compounded yearly to future salaries. We reviewed the records of 99 patients: 46 women (mean age 63.53) and 53 men (mean age 59.94); 29 patients underwent a biopsy and the remaining 70 underwent excisional surgery. Mean survival was 18.092 months for the whole series. The total indirect cost for the series was €11 080 762 (2015). Mean indirect cost per patient was €111 926 (2015). Although glioblastoma is a relatively uncommon type of tumour, accounting for only 4% of all cancers, its poor prognosis and potential sequelae generate disproportionately large morbidity and mortality rates which translate to high indirect costs. Clinicians should be aware of the societal impact of glioblastoma and indirect costs should be taken into account when cost effectiveness studies are performed to better illustrate the overall consequences of this disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. PKCι depletion initiates mitotic slippage-induced senescence in glioblastoma.

    Science.gov (United States)

    Restall, Ian J; Parolin, Doris A E; Daneshmand, Manijeh; Hanson, Jennifer E L; Simard, Manon A; Fitzpatrick, Megan E; Kumar, Ritesh; Lavictoire, Sylvie J; Lorimer, Ian A J

    2015-01-01

    Cellular senescence is a tumor suppressor mechanism where cells enter a permanent growth arrest following cellular stress. Oncogene-induced senescence (OIS) is induced in non-malignant cells following the expression of an oncogene or inactivation of a tumor suppressor. Previously, we have shown that protein kinase C iota (PKCι) depletion induces cellular senescence in glioblastoma cells in the absence of a detectable DNA damage response. Here we demonstrate that senescent glioblastoma cells exhibit an aberrant centrosome morphology. This was observed in basal levels of senescence, in p21-induced senescence, and in PKCι depletion-induced senescence. In addition, senescent glioblastoma cells are polyploid, Ki-67 negative and arrest at the G1/S checkpoint, as determined by expression of cell cycle regulatory proteins. These markers are all consistent with cells that have undergone mitotic slippage. Failure of the spindle assembly checkpoint to function properly can lead to mitotic slippage, resulting in the premature exit of mitotic cells into the G1 phase of the cell cycle. Although in G1, these cells have the replicated DNA and centrosomal phenotype of a cell that has entered mitosis and failed to divide. Overall, we demonstrate that PKCι depletion initiates mitotic slippage-induced senescence in glioblastoma cells. To our knowledge, this is the first evidence of markers of mitotic slippage directly in senescent cells by co-staining for senescence-associated β-galactosidase and immunofluorescence markers in the same cell population. We suggest that markers of mitotic slippage be assessed in future studies of senescence to determine the extent of mitotic slippage in the induction of cellular senescence.

  14. CAR T-Cell Therapies in Glioblastoma: A First Look.

    Science.gov (United States)

    Migliorini, Denis; Dietrich, Pierre-Yves; Stupp, Roger; Linette, Gerald P; Posey, Avery D; June, Carl H

    2018-02-01

    Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, an immunosuppressive microenvironment, and a partially permissive anatomic blood-brain barrier. Results from three first-in-man chimeric antigen receptor (CAR) T-cell trials targeting IL13Rα2, Her2/CMV, and EGFRvIII have recently been reported. Each one of these trials addresses important questions, such as T-cell trafficking to CNS, engraftment and persistence, tumor microenvironment remodeling, and monitoring of glioma response to CAR T cells. Objective radiologic responses have been reported. Here, we discuss and summarize the results of these trials and suggest opportunities for the field. Clin Cancer Res; 24(3); 535-40. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Longevity-Related Gene Transcriptomic Signature in Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Manal S. Fawzy

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM (grade IV astrocytoma has been assumed to be the most fatal type of glioma with low survival and high recurrence rates, even after prompt surgical removal and aggressive courses of treatment. Transcriptional reprogramming to stem cell-like state could explain some of the deregulated molecular signatures in GBM disease. The present study aimed to quantify the expression profiling of longevity-related transcriptional factors SOX2, OCT3/4, and NANOG to evaluate their diagnostic and performance values in high-grade gliomas. Forty-four specimens were obtained from glioblastoma patients (10 females and 34 males. Quantitative real-time polymerase chain reaction was applied for relative gene expression quantification. In silico network analysis was executed. NANOG and OCT3/4 mRNA expression levels were significantly downregulated while that of SOX2 was upregulated in cancer compared to noncancer tissues. Receiver operating characteristic curve analysis showed high diagnostic performance of NANOG and OCT3/4 than SOX2. However, the aberrant expressions of the genes studied were not associated with the prognostic variables in the current population. In conclusion, the current study highlighted the aberrant expression of certain longevity-associated transcription factors in glioblastoma multiforme which may direct the attention towards new strategies in the treatment of such lethal disease.

  16. Fenofibrate Induces Ketone Body Production in Melanoma and Glioblastoma Cells

    Science.gov (United States)

    Grabacka, Maja M.; Wilk, Anna; Antonczyk, Anna; Banks, Paula; Walczyk-Tytko, Emilia; Dean, Matthew; Pierzchalska, Malgorzata; Reiss, Krzysztof

    2016-01-01

    Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. PMID:26869992

  17. Quantitative radiomic profiling of glioblastoma represents transcriptomic expression.

    Science.gov (United States)

    Kong, Doo-Sik; Kim, Junhyung; Ryu, Gyuha; You, Hye-Jin; Sung, Joon Kyung; Han, Yong Hee; Shin, Hye-Mi; Lee, In-Hee; Kim, Sung-Tae; Park, Chul-Kee; Choi, Seung Hong; Choi, Jeong Won; Seol, Ho Jun; Lee, Jung-Il; Nam, Do-Hyun

    2018-01-19

    Quantitative imaging biomarkers have increasingly emerged in the field of research utilizing available imaging modalities. We aimed to identify good surrogate radiomic features that can represent genetic changes of tumors, thereby establishing noninvasive means for predicting treatment outcome. From May 2012 to June 2014, we retrospectively identified 65 patients with treatment-naïve glioblastoma with available clinical information from the Samsung Medical Center data registry. Preoperative MR imaging data were obtained for all 65 patients with primary glioblastoma. A total of 82 imaging features including first-order statistics, volume, and size features, were semi-automatically extracted from structural and physiologic images such as apparent diffusion coefficient and perfusion images. Using commercially available software, NordicICE, we performed quantitative imaging analysis and collected the dataset composed of radiophenotypic parameters. Unsupervised clustering methods revealed that the radiophenotypic dataset was composed of three clusters. Each cluster represented a distinct molecular classification of glioblastoma; classical type, proneural and neural types, and mesenchymal type. These clusters also reflected differential clinical outcomes. We found that extracted imaging signatures does not represent copy number variation and somatic mutation. Quantitative radiomic features provide a potential evidence to predict molecular phenotype and treatment outcome. Radiomic profiles represents transcriptomic phenotypes more well.

  18. Prognostic factors in recurrent glioblastoma patients treated with bevacizumab.

    Science.gov (United States)

    Schaub, Christina; Tichy, Julia; Schäfer, Niklas; Franz, Kea; Mack, Frederic; Mittelbronn, Michel; Kebir, Sied; Thiepold, Anna-Luisa; Waha, Andreas; Filmann, Natalie; Banat, Mohammed; Fimmers, Rolf; Steinbach, Joachim P; Herrlinger, Ulrich; Rieger, Johannes; Glas, Martin; Bähr, Oliver

    2016-08-01

    The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS ≥ 80 % (n = 25). In contrast, in patients with second recurrence and KPS < 80 %, OS was 3.6 months (n = 27). Our observational data support an early use of BEV in patients with good performance status. The benefit of co-treatment with IRI in our cohort seems to be the result of biased patient recruitment.

  19. MiRNA expression patterns predict survival in glioblastoma.

    Science.gov (United States)

    Niyazi, Maximilian; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Schulze-Osthoff, Klaus; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone; Belka, Claus

    2011-11-10

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  20. Outcome in unresectable glioblastoma: MGMT promoter methylation makes the difference.

    Science.gov (United States)

    Thon, Niklas; Thorsteinsdottir, Jun; Eigenbrod, Sabina; Schüller, Ulrich; Lutz, Jürgen; Kreth, Simone; Belka, Claus; Tonn, Jörg-Christian; Niyazi, Maximilian; Kreth, Friedrich Wilhelm

    2017-02-01

    In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008. Last follow-up was performed in June 2016. MGMT promoter methylation was determined using methylation-specific PCR (MSP) and sodium bisulfite sequencing. Analyses were done by intention to treat. Prognostic factors were obtained from proportional hazard models. At the time of the final analysis 55 patients showed progressive disease and 53 patients had died. MGMT promoter was methylated (unmethylated) in 30 (26) patients. Methylation of the MGMT promoter was the strongest favorable predictor for overall survival (OS, median: 20.3 vs. 7.3 months, p MGMT promoter methylation status is essential for patients' counseling, prognostic evaluation, and for the design of future trials dealing with unresectable glioblastomas.

  1. MiRNA expression patterns predict survival in glioblastoma

    Directory of Open Access Journals (Sweden)

    Niyazi Maximilian

    2011-11-01

    Full Text Available Abstract Background In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs from paraffin tissues followed by a bio-mathematical analysis was performed. Methods 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemotherapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. Results It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days (p = 0.01. The pattern and the prognostic power were both independent of the MGMT status. Conclusions At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  2. MiRNA expression patterns predict survival in glioblastoma

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Belka, Claus; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Osthoff, Klaus-Schulze; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone

    2011-01-01

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip 'Geniom ® Biochip MPEA homo-sapiens' was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required

  3. Fenofibrate induces ketone body production in melanoma and glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Maja M Grabacka

    2016-02-01

    Full Text Available Ketone bodies (beta-hydroxybutyrate, bHB, acetoacetate are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of nontransformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and down-regulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic therapeutic approaches against glioblastoma.

  4. Spinal MRI of vincristine neuropathy mimicking Guillain-Barre syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun Woo; Yoon, Hye-Kyung; Cho, Jae Min [Department of Radiology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710 (Korea); Sung, Ki Woong [Department of Paediatrics, Samsung Medical Centre, Seoul 135-710 (Korea)

    2003-11-01

    A 4.3-year-old girl with acute leukaemia, who was being treated with chemotherapy (including vincristine), developed paraplegia. Spinal MRI showed diffusely enhancing nerve roots on contrast-enhanced images. Spinal fluid analysis showed a normal protein level. Vincristine neuropathy mimicking Guillain-Barre syndrome is thought to be the cause of the MRI abnormalities. (orig.)

  5. Spinal MRI of vincristine neuropathy mimicking Guillain-Barre syndrome

    International Nuclear Information System (INIS)

    Chang, Yun Woo; Yoon, Hye-Kyung; Cho, Jae Min; Sung, Ki Woong

    2003-01-01

    A 4.3-year-old girl with acute leukaemia, who was being treated with chemotherapy (including vincristine), developed paraplegia. Spinal MRI showed diffusely enhancing nerve roots on contrast-enhanced images. Spinal fluid analysis showed a normal protein level. Vincristine neuropathy mimicking Guillain-Barre syndrome is thought to be the cause of the MRI abnormalities. (orig.)

  6. Large fibroadenoma mimicking malignancy | Smal | SA Journal of ...

    African Journals Online (AJOL)

    SA Journal of Radiology. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 8, No 1 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Large fibroadenoma mimicking malignancy. J Smal. Abstract.

  7. Endometriosis of the meso-appendix mimicking appendicitis: A case ...

    African Journals Online (AJOL)

    Although appendicitis is largely a clinical diagnosis, on occasions diagnostic modalities may be needed to aid with the diagnosis. Despite the use of adjuncts and exploratory surgery, the diagnosis may not be clear until a histological diagnosis is achieved. Endometriosis of the appendix mimicking appendicitis is one of ...

  8. Crystal structure and bio-mimicking of Catecholase activity

    Indian Academy of Sciences (India)

    Unprecedented hetero-geometric discrete copper(II) complexes: Crystal structure and bio-mimicking of Catecholase activity. ABHRANIL DE DHANANJAY DEY HARE RAM YADAV MILAN MAJI VINAYAK RANE R M KADAM ANGSHUMAN ROY CHOUDHURY BHASKAR BISWAS. Regular Article Volume 128 Issue 11 ...

  9. Trichophyton Schoenleinii-induced widespread tinea corporis mimicking parapsoriasis.

    Science.gov (United States)

    Mansouri, P; Farshi, S; Khosravi, A R; Naraghi, Z S; Chalangari, R

    2012-06-01

    We report a case of extensive tinea corporis in an 80-year-old woman on her forearms, thighs, legs, buttocks and trunk, mimicking parapsoriasis due to Trichophyton schoenleinii, without scalp involvement. Diagnosis of Trichophyton schoenleinii was confirmed by microscopy and mycological culture specimens. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Dysplastic bone disease mimicking exostoses of the ear canal ...

    African Journals Online (AJOL)

    We present a case of a 43-year-old man who attended the ENT clinic complaining of bilateral hearing loss. He had multiple bony swellings in both ear canals that mimicked exostoses. An audiogram showed bilateral symmetrical mixed hearing loss. Excision was carried out to facilitate the use of a hearing aid.

  11. African oral histoplasmosis mimicking lip carcinoma: case report ...

    African Journals Online (AJOL)

    A case of Iocalised African histoplasmosis with an unusual presentation in a 56 year old Nigerian farmer is reported. The lesion presented as an ulcer clinically mimicking squamous cell carcinoma of the lower lip. An incisional biopsy and culture studies confirmed African histoplasmosis and the utcer healed spontaneously ...

  12. Intracranial Gossypiboma Mimicking a Recurrent Low Grade Astrocytoma : Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Young; Koo, Joon Bum [Dept. of Radiology, Dongguk University Il-San Hospital, Iksan (Korea, Republic of)

    2011-05-15

    Gossypiboma is an inflammatory pseudomass formed by a retained surgical sponge or gauze with reactive tissue after surgery. Gossypiboma has been reported most frequently after abdominal or thoracic surgery. As such, gossypiboma following brain surgery is very rare. We report a case of gossypiboma mimicking tumor recurrence in the brain after a craniotomy and surgical excision of a low grade astrocytoma.

  13. Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy

    Science.gov (United States)

    Saran, Frank; Chinot, Olivier L.; Henriksson, Roger; Mason, Warren; Wick, Wolfgang; Cloughesy, Timothy; Dhar, Sunita; Pozzi, Emanuela; Garcia, Josep; Nishikawa, Ryo

    2016-01-01

    Background The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations. Methods Eligible patients received: radiotherapy and temozolomide plus bevacizumab/placebo, 6 cycles; a 4-week treatment break; temozolomide plus bevacizumab/placebo, 6 cycles; and bevacizumab/placebo until progression. Data on adverse events (AEs) were collected throughout. Results Bevacizumab-treated patients (n = 461) had a longer median safety follow-up time (12.3 vs 8.5 mo), and a higher proportion completed 6 cycles of maintenance temozolomide (64.6% vs 36.9%) versus placebo (n = 450). The incidences of relevant AEs (bevacizumab vs placebo, respectively) were: arterial thromboembolic events (5.9% vs 1.6%); cerebral hemorrhage (3.3% vs 2.0%); wound-healing complications (6.9% vs 4.7%); thrombocytopenia (34.1% vs 27.3%); radiotherapy-associated skin injury (8.2% vs 9.3%); alopecia (39.0% vs 36.0%); gastrointestinal perforation (including gastrointestinal abscesses and fistulae, 1.7% vs 0.4%); and radiotherapy-associated injury (0.4% vs 0.0%). Overall, 15.8% and 23.8% of bevacizumab- and placebo-treated patients had surgery (including biopsy) after progression. Within 30 days of postprogression surgery, AE incidence was 10.9% (bevacizumab) and 23.4% (placebo). Conclusion The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab. The increased AE incidence with bevacizumab did not impact patients' ability to receive standard-of-care treatment or to undergo

  14. Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Sminia, P.; Hulshof, M. C.; van der Kracht, A. H.; Leenstra, S.; Bosch, D. A.

    1997-01-01

    The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the

  15. Monitoring of cerebral haemodynamics in newborn infants

    DEFF Research Database (Denmark)

    Liem, K Djien; Greisen, Gorm

    2010-01-01

    The most important cerebrovascular injuries in newborn infants, particularly in preterm infants, are cerebral haemorrhage and ischemic injury. The typical cerebral vascular anatomy and the disturbance of cerebral haemodynamics play important roles in the pathophysiology. The term 'cerebral haemod...

  16. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sandhya eRavikumar

    2016-04-01

    Full Text Available We describe a case report of fulminant Guillain-Barré syndrome mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy (AMAN, a subtype of Guillain-Barré syndrome, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler ultrasound showed appropriate blood flow to the brain. Guillain-Barré syndrome rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and transcranial dopplers when uncertainty exists about the reliability of the clinical exam.

  17. Arteriovenous Malformation in Temporal Lobe Presenting as Contralateral Ocular Symptoms Mimicking Carotid-Cavernous Fistula

    Directory of Open Access Journals (Sweden)

    Fadzillah Mohd-Tahir

    2013-01-01

    Full Text Available Aim. To report a rare case of arteriovenous malformation in temporal lobe presenting as contralateral orbital symptoms mimicking carotid-cavernous fistula. Method. Interventional case report. Results. A 31-year-old Malay gentleman presented with 2-month history of painful progressive exophthalmos of his left eye associated with recurrent headache, diplopia, and reduced vision. Ocular examination revealed congestive nonpulsating 7 mm exophthalmos of the left eye with no restriction of movements in all direction. There was diplopia in left lateral gaze. Left IOP was elevated at 29 mmHg. Left eye retinal vessels were slightly dilated and tortuous. CT scan was performed and showed right temporal arteriovenous malformation with a nidus of 3.8 cm × 2.5 cm with right middle cerebral artery as feeding artery. There was dilated left superior ophthalmic vein of 0.9 mm in diameter with enlarged left cavernous sinus. MRA and carotid angiogram confirmed right temporal arteriovenous malformation with no carotid-cavernous fistula. Most of the intracranial drainage was via left cavernous sinus. His signs and symptoms dramatically improved following successful embolisation, completely resolved after one year. Conclusion. Intracranial arteriovenous malformation is rarely presented with primary ocular presentation. Early intervention would salvage the eyes and prevent patients from more disaster morbidity or fatality commonly due to intracranial haemorrhage.

  18. Prognostic value of plasma transforming growth factor-beta in patients with glioblastoma multiforme

    NARCIS (Netherlands)

    Hulshof, M. C.; Sminia, P.; Barten-van Rijbroek, A. D.; Gonzalez Gonzalez, D.

    2001-01-01

    We investigated whether the postoperative concentration of circulating transforming growth factor beta (TGF-beta) yields prognostic value in patients with glioblastoma multiforme (gbm). Blood was collected from 20 healthy volunteers and in 28 patients with mainly glioblastoma multiforme (gbm), both

  19. CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

    NARCIS (Netherlands)

    Goffart, Nicolas; Lombard, Arnaud; Lallemand, François; Kroonen, Jérôme; Nassen, Jessica; Di Valentin, Emmanuel; Berendsen, Sharon; Dedobbeleer, Matthias; Willems, Estelle; Robe, Pierre; Bours, Vincent; Martin, Didier; Martinive, Philippe; Maquet, Pierre; Rogister, Bernard

    2017-01-01

    Background. Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line,

  20. Analysis of fractional anisotropy facilitates differentiation of glioblastoma and brain metastases in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Bette, Stefanie, E-mail: stefanie.bette@tum.de [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Huber, Thomas; Wiestler, Benedikt; Boeckh-Behrens, Tobias [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Zimmer, Claus; Kirschke, Jan S. [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

    2016-12-15

    Purpose: Differentiating glioblastoma from brain metastases is important for therapy planning. Diffusion tensor imaging (DTI) was described as a promising tool, however with conflicting results. Aim: of this study was to analyze the clinical utility of DTI for the differentiation of brain metastases and glioblastoma. Methods: 294 patients (165 glioblastoma, 129 brain metastases) with preoperative DTI were included in this retrospective study. Fractional anisotropy (FA) was measured via regions of interest (ROIs) in the contrast-enhancing tumor, the necrosis and the FLAIR-hyperintense non-enhancing peritumoral region (NEPTR). Two neuroradiologists classified patient cases as glioblastoma or brain metastases without and with knowledge of FA values. Results: Glioblastoma showed significantly higher FA{sub contrast} (median glioblastoma = 0.33, metastases = 0.23; P < 0.001) whereas no significant difference was observed for FA{sub NEPTR} (0.21 vs. 0.22; P = 0.28) and for FA{sub necrosis} (0.17 vs. 0.18, P = 0.37). FA improved diagnostic accuracy of the neuroradiologists significantly from an AUC of 0.84/0.85 (Reader1/Reader2) to 0.89/0.92. Conclusions: Glioblastoma show significantly higher FA values in the contrast enhancing tumor part than brain metastases. Implementation of a ROI-based measurement of FA values and FA color maps in clinical routine helps to differentiate between glioblastoma and brain metastases.

  1. Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins

    NARCIS (Netherlands)

    Hira, Vashendriya V. V.; Wormer, Jill R.; Kakar, Hala; Breznik, Barbara; van der Swaan, Britt; Hulsbos, Renske; Tigchelaar, Wikky; Tonar, Zbynek; Khurshed, Mohammed; Molenaar, Remco J.; van Noorden, Cornelis J. F.

    2018-01-01

    In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell-derived factor-1α (SDF-1α),

  2. Clinico-pathological studies of CSF dissemination of glioblastoma and medulloblastoma

    International Nuclear Information System (INIS)

    Kato, Kyozo; Yoshida, Jun; Kageyama, Naoki

    1986-01-01

    Clinico-pathological findings of CSF dissemination which was diagnosed on CT scan, were studied on 13 cases of glioblastoma and 9 cases of medulloblastoma. The type of CSF dissemination and the prognosis of patients were both different between glioblastoma and medulloblastoma. In the former, the dissemination was predominantly in ventricular walls and in the latter, in basal cisterns. The mean survival time after the diagnosis of dissemination is 6 months of glioblastoma as compared with 13 months of medulloblastoma. The Pathological studies show that subependymal and/or subpial infiltration of tumor cells, and thickness of arachnoid membrane by marked mesodermal reaction were demonstrated in cases of glioblastoma. On the contrary, tumor cells of medulloblastoma grow markedly in the subarachnoid space and/or on the ependymal layers. From these pathological findings of CSF dissemination, it will be resulted that the prognosis of glioblastoma is much more poor that of medulloblastoma. (author)

  3. Pro-inflammatory gene expression in solid glioblastoma microenvironment and in hypoxic stem cells from human glioblastoma

    Directory of Open Access Journals (Sweden)

    Santoro Antonio

    2011-04-01

    Full Text Available Abstract Background Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM. The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs, hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype. Methods From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB. GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior. Results A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3 were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas, less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells. Conclusions In human solid glioblastoma we have

  4. Cerebral hemodynamics in migraine

    DEFF Research Database (Denmark)

    Hachinski, V C; Olesen, Jes; Norris, J W

    1977-01-01

    Clinical and angiographic findings in migraine are briefly reviewed in relation to cerebral hemodynamic changes shown by regional cerebral blood flow (rCBF) studies. Three cases of migraine studied by the intracarotid xenon 133 method during attacks are reported. In classic migraine, with typical...... prodromal symptoms, a decrease in cerebral blood flow has been demonstrated during the aura. Occasionally, this flow decrease persists during the headache phase. In common migraine, where such prodromata are not seen, a flow decrease has not been demonstrated. During the headache phase of both types...... of migraine, rCBF has usually been found to be normal or in the high range of normal values. The high values may represent postischemic hyperemia, but are probably more frequently secondary to arousal caused by pain. Thus, during the headache phase rCBF may be subnormal, normal or high. These findings do...

  5. Duplicated middle cerebral artery

    Science.gov (United States)

    Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

    2009-01-01

    Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion. PMID:22140405

  6. Diaschisis with cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Slater, R.; Reivich, M.; Goldberg, H.; Banka, R.; Greenberg, J.

    1977-01-01

    Fifteen patients admitted to Philadelphia General Hospital with acute strokes had repeated measurements of cerebral blood flow measured by the /sup 133/X inhalation method. A progressive decline in cerebral blood flow in both hemispheres was observed during the first week after infarction in twelve of these patients. This decline could be partially explained by loss of autoregulation, but could not be correlated with level of consciousness, clinical status of PCO2. This progressive decline in flow in the non-ischemic hemisphere indicates a process more complex than a simple destruction of axonal afferants to neurons as implied by the term diaschisis. The flow changes in the non-ischemic hemisphere are likely caused by a combination of the immediate effects of decreased neuronal stimulation modified by loss of autoregulation, release of vasoactive substances, cerebral edema, and other factors.

  7. Neuroimaging of cerebral vasculitis

    International Nuclear Information System (INIS)

    Wengenroth, M.; Saam, T.; Haehnel, S.

    2016-01-01

    Cerebral vasculitis can have a variety of origins. Furthermore, there are no vasculitis-specific symptoms or imaging signs and vasculitis of the CNS can mimic many other neurological diseases, which require different treatment approaches. Thus, the clinical and radiological diagnosis of cerebral vasculitis is challenging. Magnetic resonance imaging (MRI) and MR angiography (MRA) should be the radiological imaging methods of choice to assess the degree of parenchymal damage and to detect vessel wall changes. If the results are unclear digital subtraction angiography (DSA) should be pursued in order to also detect changes in medium sized vessels. Vasculitis of small vessels cannot be detected by vascular imaging and requires brain or leptomeningeal biopsy. In this review we present the current diagnostic approach and a variety of imaging findings in cerebral vasculitis and discuss the main radiological differential diagnoses. (orig.) [de

  8. Cerebral fat embolism

    International Nuclear Information System (INIS)

    Sakamoto, Toshihisa; Sawada, Yusuke; Yukioka, Tetsuo; Nishide, Kazuyuki; Yoshioka, Toshiharu

    1982-01-01

    A case of cerebral fat embolism is reported. A 18-year-old patient with multiple bone fractures was in semiconma immediately after an injury. Brain CT showed no brain swelling or intracranial hematoma. Hypoxemia and alcoholemia were noted on admission, which returned to normal without improvement of consciousness level. In addition, respiratory symptoms with positive radiographic changes, tachycardia, pyrexia, sudden drop in hemoglobin level, and sudden thrombocytopenia developed. These symptoms were compatible with Gurd's criteria of systemic fat embolism. Eight days after injury, multiple low density areas appeared on CT and disappeared within the subsequent two weeks, and subdural effusion with cerebral atrophy developed. These CT findings were not considered due to cerebral trauma. Diagnosis of cerebral fat embolism was made. The subdural effusion was drained. Neurologic and pulmonary recoveries took place slowly and one month following the injury the patient became alert and exhibited fully coordinated limb movement. The CT scans of the present case well corresponded with hitherto reported pathological findings. Petechiae in the white matter must have developed on the day of injury, which could not be detected by CT examination. It is suggested that some petechial regions fused to purpuras and then gradually resolved when they were detected as multiple low density areas on CT. CT in the purpuras phase would have shown these lesions as high density areas. These lesions must have healed with formation of tiny scars and blood pigment which were demonstrated as the disappearance of multiple low density areas by CT examination. Cerebral atrophy and subsequent subdural effusion developed as a result of demyelination. The patient took the typical clinical course of cerebral fat embolism and serial CT scans served for its assessment. (author)

  9. Interstitial photodynamic therapy and glioblastoma: Light fractionation in a preclinical model.

    Science.gov (United States)

    Leroy, Henri-Arthur; Vermandel, Maximilien; Vignion-Dewalle, Anne-Sophie; Leroux, Bertrand; Maurage, Claude-Alain; Duhamel, Alain; Mordon, Serge; Reyns, Nicolas

    2017-07-01

    Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues. To evaluate the efficiency of two light-fractionation schemes using immunohistological data. Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology. Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028). Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Noninvasive Tumor Grading of Glioblastomas Before Surgery Using Arterial Spin Labeling. A Cohort Study.

    Science.gov (United States)

    Gao, Fei; Guo, Rui; Hu, Xiao-Jing; Li, Chun-Jing; Li, Meng

    2015-12-01

    To assess the clinical value of using arterial spin labeling (ASL) technique preoperatively for non-invasive tumor grading in glioblastoma (GBM) patients. Forty-nine patients with GBMs were selected, including 21 patients with high-grade gliomas and 28 patients with low-grade gliomas. ASL perfusion imaging was performed with GE Signa Excite HD 3.0 T MR scanning system (GE Healthcare). Relative cerebral blood flow (rCBF) and relative tumor blood flow (rTBF) were quantified in all patients. Statistical analysis was performed with STATA version 12.0 software. Further, relevant human cohort studies published in Chinese and English languages were identified by database searches and screened. Data was extracted and meta-analysis was performed using Comprehensive Meta-analysis version 2.0 software. The ratios of rTBF to rCBF in the contralateral white matter, contralateral gray matter, and contralateral hemisphere of high-grade gliomas were higher than low-grade gliomas (all p 0.05) when 2 and 5 cm distances from tumor margin were compared. Importantly, rCBF values showed statistical differences when the 2 cm distance was compared with the 5 cm distance from tumor margin (all p < 0.05). Finally, meta-analysis results supported the conclusion that rCBF and rTBF values were significantly higher in high-grade GBM as compared to low-grade GBM. We present convincing data that ASL is highly effective in differentiating between high-grade and low-grade gliomas, and thus is a useful tool for preoperative evaluation of GBM.

  11. Parametric response maps of perfusion MRI may identify recurrent glioblastomas responsive to bevacizumab and irinotecan.

    Science.gov (United States)

    Aquino, Domenico; Di Stefano, Anna Luisa; Scotti, Alessandro; Cuppini, Lucia; Anghileri, Elena; Finocchiaro, Gaetano; Bruzzone, Maria Grazia; Eoli, Marica

    2014-01-01

    Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome. 42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged. An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38), whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04), and re-increased progressively when patients approached tumor progression. Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.

  12. Parametric response maps of perfusion MRI may identify recurrent glioblastomas responsive to bevacizumab and irinotecan.

    Directory of Open Access Journals (Sweden)

    Domenico Aquino

    Full Text Available Perfusion weighted imaging (PWI can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs with the Region Of Interest (ROI approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM, and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome.42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged.An increased blood volume in PRM (PRMCBV+ higher than 18% (first quartile after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045 and overall survival (OS; 38 versus 25 weeks, p = 0.016. After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38, whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04, and re-increased progressively when patients approached tumor progression.Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.

  13. Cytotoxic and Apoptogenic Effects of Cyanidin-3-Glucoside on the Glioblastoma Cell Line.

    Science.gov (United States)

    Hosseini, Masoumeh Mansoubi; Karimi, Aliasghar; Behroozaghdam, Mitra; Javidi, Mohammad Amin; Ghiasvand, Saeedeh; Bereimipour, Ahmad; Aryan, Hoda; Nassiri, Farbod; Jangholi, Ehsan

    2017-12-01

    Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary cerebral tumor. The median survival time is 15 months despite maximum treatment because the tumor is resistant to most therapeutic modalities. Several studies have indicated chemopreventive and chemotherapeutic activity of cyanidin-3-glucoside (C3G) as an anthocyanin component. We aimed to illustrate the cytotoxic and apoptogenic effects of C3G in the U87 cell line (human GBM cell line). Cytotoxic activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium assay after treatment with C3G at different concentrations in the U87 cell line. Cisplatin was used as a positive control for 24 and 48 hours. The percentage of apoptotic cells was determined using an Annexin V/propidium iodide assay, and the expression of bax, bcl2, and p53 genes was assessed using real-time polymerase chain reaction. Treatment of U87 cells with 40 μg/mL of C3G resulted in 32% apoptotic cells after 24 hours. To further confirm that C3G treatment induced apoptosis in U87 cells, RNA expression of bax, bcl2, and p53 genes was investigated after treatment. Real-time polymerase chain reaction indicated that the expression of bax and p53 increased, whereas the expression of bcl2 decreased. C3G had an apoptogenic effect in the GBM cell line. New information regarding the therapeutic effects of C3G in GBM could ultimately lead to the production of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  15. Is cerebral hemorrhage approaching?

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Hirokazu; Suzuki, Yukiko; Yoneyama, Takumi; Hamasuna, Ryouichi; Fujime, Kenichi; Goya, Tomokazu [Junwakai Memorial Hospital, Miyazaki (Japan)

    2001-09-01

    In Junwakai Memorial Hospital, from May, 2000 to April, 2001, 1042 patients underwent MRI examination to detect intracerebral microbleed (MB). This series included 481 hypertensive cases and 109 intra-cerebral and cerebellar hemorrhage patients. MB was identified by MRI GRASS image that detects hemosiderin with high sensitivity. The occurrence of MB is high in men and increased with the age. The hypertensive patients showed increased frequency of MB in proportion to the duration of hypertension. Almost all of the symptomatic cerebral and cerebellar hemorrhage cases showed multiple MBs except for massive hemorrhagic lesions. Therefore, MB can be an antecedant feature of the inpending symptomatic intracerebral and cerebellar hemorrhages. (author)

  16. miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS.

    Science.gov (United States)

    Fiore, Danilo; Donnarumma, Elvira; Roscigno, Giuseppina; Iaboni, Margherita; Russo, Valentina; Affinito, Alessandra; Adamo, Assunta; De Martino, Fabio; Quintavalle, Cristina; Romano, Giulia; Greco, Adelaide; Soini, Ylermi; Brunetti, Arturo; Croce, Carlo M; Condorelli, Gerolama

    2016-04-12

    Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12-14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma.

  17. Cerebral atrophic and degenerative changes following various cerebral diseases, (1)

    International Nuclear Information System (INIS)

    Kino, Masao; Anno, Izumi; Yano, Yuhiko; Anno, Yasuro.

    1980-01-01

    Patients having cerebral atrophic and degenerative changes following hypoglycemia, cerebral contusion, or cerebral hypoxia including cerebrovascular disorders were reported. Description was made as to cerebral changes visualized on CT images and clinical courses of a patient who revived 10 minutes after heart stoppage during neurosurgery, a newborn with asphyxia, a patient with hypoglycemia, a patient who suffered from asphyxia by an accident 10 years before, a patient with carbon monoxide poisoning at an acute stage, a patient who had carbon monoxide poisoning 10 years before, a patient with diffuse cerebral ischemic changes, a patient with cerebral edema around metastatic tumor, a patient with respiration brain, a patient with neurological sequelae after cerebral contusion, a patient who had an operation to excise right parietal lobe artery malformation, and a patient who was shooted by a machine gun and had a lead in the brain for 34 years. (Tsunoda, M.)

  18. Multimodal imaging based on MRI and PET reveals [{sup 18}F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Corroyer-Dulmont, Aurelien; Peres, Elodie A.; Gerault, Aurelie N.; Divoux, Didier; Toutain, Jerome; Ibazizene, Meziane; MacKenzie, Eric T.; Barre, Louisa; Bernaudin, Myriam; Petit, Edwige; Valable, Samuel [CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Caen (France); CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy et LDM-TEP Groups, GIP CYCERON, Caen (France); UNICAEN, UMR 6301 ISTCT, CERVOxy et LDM-TEP Groups, GIP CYCERON, Caen (France); Normandie Univ., Caen(France); Savina, Ariel; Bouquet, Fanny [Roche SAS, Boulogne-Billancourt (France)

    2016-04-15

    The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme. MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([{sup 18}F]FDG and [{sup 18}F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival. Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [{sup 18}F]FLT uptake, cerebral blood volume and oedema. [{sup 18}F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [{sup 18}F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy. The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [{sup 18}F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations. (orig.)

  19. An abdominal tuberculosis case mimicking an abdominal mass

    African Journals Online (AJOL)

    An abdominal tuberculosis case mimicking an abdominal mass. Derya Erdog˘ an a. , Yasemin Ta ¸scı Yıldız b. , Esin Cengiz Bodurog˘lu c and Naciye Go¨nu¨l Tanır d. Abdominal tuberculosis is rare in childhood. It may be difficult to diagnose as it mimics various disorders. We present a 12-year-old child with an unusual ...

  20. Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2017-07-15

    Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

  1. Localized IgG4-related Cholecystitis Mimicking Gallbladder Cancer.

    Science.gov (United States)

    Inoue, Tadahisa; Okumura, Fumihiro; Mizushima, Takashi; Nishie, Hirotada; Iwasaki, Hiroyasu; Anbe, Kaiki; Ozeki, Takanori; Kachi, Kenta; Fukusada, Shigeki; Suzuki, Yuta; Watanabe, Kazuko; Sano, Hitoshi

    2015-01-01

    We encountered a case of localized IgG4-cholecystitis mimicking gallbladder cancer with focal/segmental type1 autoimmune pancreatitis (AIP). In this case, we were unable to exclude a diagnosis of gallbladder cancer and thus performed radical cholecystectomy. Type1 AIP is often associated with gallbladder lesions, accompanied by generally diffuse, circumferential thickening of the gallbladder wall. Although localized IgG4-related cholecystitis is extremely rare, differentiating this condition from gallbladder cancer is often very difficult.

  2. A case of gallbladder mass: Malakoplakia (The tumor mimicker

    Directory of Open Access Journals (Sweden)

    Kanwaljeet Singh

    2017-01-01

    Full Text Available Diagnosis of malakoplakia presenting as gall bladder mass is a diagnostic dilemma faced by pathologists, radiologists, and surgeons. Malakoplakia is a rare inflammatory disorder and tumor mimicker usually occurring in the urinary tract, may occasionally be found in gall bladder. Here, we present a rare case, presenting as gall bladder mass in a known case of gallstone disease, clinically suspected as carcinoma and later turned out to be malakoplakia in gall bladder.

  3. A Q fever case mimicking crimean-congo haemorrhagic fever

    Directory of Open Access Journals (Sweden)

    O Karabay

    2011-01-01

    Full Text Available Coxiella burnetii is the bacterium that causes Q fever. Human infection is mainly transmitted from cattle, goats and sheep. The disease is usually self-limited. Pneumonia and hepatitis are the most common clinical manifestations. In this study, we present a case of Q fever from the western part of Turkey mimicking Crimean-Congo haemorrhagic fever (CCHF in terms of clinical and laboratory findings.

  4. Sarcoidosis breaching the fascia and mimicking a sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Hajime; Ikeda, Mitsuaki; Shimofusa, Ryouta [Department of Radiology, Numazu City Hospital, 550 Harunoki-aza, Higashishiiji, Numazu, Shizuoka 410-0302 (Japan); Terauchi, Masami [Department of Plastic Surgery, Numazu City Hospital, 550 Harunoki-aza, Higashishiiji, Numazu, Shizuoka 410-0302 (Japan); Eguchi, Masanobu [Department of Pathology, Numazu City Hospital, 550 Harunoki-aza, Higashishiiji, Numazu, Shizuoka 410-0302 (Japan)

    2002-12-01

    A 55-year-old woman complained of a subcutaneous mass in her left buttock. MR images revealed an ill-defined soft tissue mass that crossed the fascia of the gluteus maximus muscle. Some surrounding edema was noted. The lesion showed some contrast uptake after administration of Gd-DTPA. An excisional biopsy revealed sarcoidosis involving both the muscle and subcutaneous tissue across the fascia, mimicking a sarcoma. (orig.)

  5. Cerebral venous thrombosis

    NARCIS (Netherlands)

    Silvis, Suzanne M.; de Sousa, Diana Aguiar; Ferro, José M.; Coutinho, Jonathan M.

    2017-01-01

    Cerebral venous thrombosis (CVT) is an important cause of stroke in young adults. Data from large international registries published in the past two decades have greatly improved our knowledge about the epidemiology, clinical manifestations and prognosis of CVT. The presentation of symptoms is

  6. Cardiopulmonary-cerebral resuscitation

    African Journals Online (AJOL)

    The brain is the organ most sensitive to hypoxia. The brain cannot store oxygen and has a very limited capacity for anaerobic metabolism. Permanent brain damage will thus result after three to four minutes of total hypoxia at normal temperatures. Should cerebral blood flow be restored after such an incident, the patient may ...

  7. CASE REPORT Cerebral schistosomiasis

    African Journals Online (AJOL)

    0b013e3182704d1e]. 5. Sanelli PC, Lev MH, Gonzalez RG, Schaefer PW. Unique linear and nodular MR enhancement pattern in schistosomiasis of the central nervous system: Report of three patients. AJR 2001;177(6):1471-1474. Cerebral schistosomiasis.

  8. Glioblastoma in Children: A Single-Institution Experience

    International Nuclear Information System (INIS)

    Perkins, Stephanie M.; Rubin, Joshua B.; Leonard, Jeffrey R.; Smyth, Matthew D.; El Naqa, Issam; Michalski, Jeff M.; Simpson, Joseph R.; Limbrick, David L.; Park, Tae S.; Mansur, David B.

    2011-01-01

    Purpose: Current treatment recommendations for pediatric glioblastoma include surgery, chemotherapy, and radiation therapy. However, even with this multispecialty approach, overall survival remains poor. To assess outcome and evaluate treatment-related prognostic factors, we retrospectively reviewed the experience at our institution. Methods and Materials: Twenty-four glioblastoma patients under the age of 21 were treated with radiation therapy with curative intent at Washington University, St. Louis, from 1970 to 2008. Patients underwent gross total resection, subtotal resection or biopsy alone. Fourteen (58%) of the patients received chemotherapy. All patients received radiation therapy. Radiation consisted of whole-brain radiation therapy in 7 (29%) patients with a median dose of 50.4 Gy. Seventeen (71%) patients received three-dimensional conformal radiation therapy with a median dose of 54 Gy. Results: Median follow-up was 12.5 months from diagnosis. One and 2-year overall survival rates were 57% and 32%, respectively. Median overall survival was 13.5 months. There were no differences in overall survival based on patients' age, race, gender, tumor location, radiation volume, radiation dose, or the use of chemotherapy. There was a significant improvement in overall survival for patients in whom gross total resection was achieved (p = 0.023). Three patients were alive 5 years after gross total resection, and 2 patients were alive at 10 and 24 years after diagnosis. Conclusions: Survival for children with glioblastoma remains poor. Data from this and other studies demonstrate the importance of achieving a gross total resection. Continued investigation into new treatment options is needed in an attempt to improve outcome for these patients.

  9. Dengue fever mimicking acute appendicitis: A case report.

    Science.gov (United States)

    McFarlane, M E C; Plummer, J M; Leake, P A; Powell, L; Chand, V; Chung, S; Tulloch, K

    2013-01-01

    Dengue fever is an acute viral disease, which usually presents as a mild febrile illness. Patients with severe disease present with dengue haemorrhagic fever or dengue toxic shock syndrome. Rarely, it presents with abdominal symptoms mimicking acute appendicitis. We present a case of a male patient presenting with right iliac fossa pain and suspected acute appendicitis that was later diagnosed with dengue fever following a negative appendicectomy. A 13-year old male patient presented with fever, localized right-sided abdominal pain and vomiting. Abdominal ultrasound was not helpful and appendicectomy was performed due to worsening abdominal signs and an elevated temperature. A normal appendix with enlarged mesenteric nodes was found at surgery. Complete blood count showed thrombocytopenia with leucopenia. Dengue fever was now suspected and confirmed by IgM enzyme-linked immunosorbent assay against dengue virus. This unusual presentation of dengue fever mimicking acute appendicitis should be suspected during viral outbreaks and in patients with atypical symptoms and cytopenias on blood evaluation in order to prevent unnecessary surgery. This case highlights the occurrence of abdominal symptoms and complications that may accompany dengue fever. Early recognition of dengue fever mimicking acute appendicitis will avoid non-therapeutic operation and the diagnosis may be aided by blood investigations indicating a leucopenia, which is uncommon in patients with suppurative acute appendicitis. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. A role for the transcription factor HEY1 in glioblastoma

    DEFF Research Database (Denmark)

    Hulleman, Esther; Quarto, Micaela; Vernell, Richard

    2009-01-01

    , such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically upregulated in glioma......, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1...

  11. Glioblastoma, gadolinium (III) and NCT. An in vitro study

    International Nuclear Information System (INIS)

    Mercanti, D.; Casalbore, P.; Sanita, F.; Rosi, F.; Festinesi, A.; Pallini, R.; Gilbert, B.; Stasio, G. de

    2000-01-01

    We treated cultured human glioblastoma cells with gadolinium (III) [gadopentetic acid] and we found that: a) cells do internalise this element; b) gadolinium can be localised in the cells nuclei; c) exposure of the cultures to a neutron beam produced a significant and immediate cell death. Although cell survival was also influenced in the irradiated controls it was further reduced (about 50%) in cells pre-exposed to 10 mg/ml gadopentetic acid. We also found that Gd uptake, as measured by ICP-AES, was concentration dependent. (author)

  12. Glioblastoma Stem-Like Cells—Biology and Therapeutic Implications

    International Nuclear Information System (INIS)

    Gürsel, Demirkan B.; Shin, Benjamin J.; Burkhardt, Jan-Karl; Kesavabhotla, Kartik; Schlaff, Cody D.; Boockvar, John A.

    2011-01-01

    The cancer stem-cell hypothesis proposes that malignant tumors are likely to encompass a cellular hierarchy that parallels normal tissue and may be responsible for the maintenance and recurrence of glioblastoma multiforme (GBM) in patients. The purpose of this manuscript is to review methods for optimizing the derivation and culturing of stem-like cells also known as tumor stem cells (TSCs) from patient-derived GBM tissue samples. The hallmarks of TSCs are that they must be able to self-renew and retain tumorigenicity. The isolation, optimization and derivation of TSCs as outlined in this review, will be important in understanding biology and therapeutic applications related to these cells

  13. Recurrent cerebral thrombosis

    International Nuclear Information System (INIS)

    Iwamoto, Toshihiko; Abe, Shin-e; Kubo, Hideki; Hanyu, Haruo; Takasaki, Masaru

    1992-01-01

    Neuroradiological techniques were used to elucidate pathophysiology of recurrent cerebral thrombosis. Twenty-two patients with cerebral thrombosis who suffered a second attack under stable conditions more than 22 days after the initial stroke were studied. Hypertension, diabetes mellitus, and hypercholesterolemia were also seen in 20, 8, and 12 patients, respectively. The patients were divided into three groups according to their symptoms: (I) symptoms differed between the first and second strokes (n=12); (II) initial symptoms were suddenly deteriorated (n=6); and (III) symptoms occurring in groups I and II were seen (n=4). In group I, contralateral hemiparesis or suprabulbar palsy was often associated with the initial hemiparesis. The time of recurrent stroke varied from 4 months to 9 years. CT and MRI showed not only lacunae in both hemispheres, but also deep white-matter ischemia of the centrum semi-ovale. In group II, hemiparesis or visual field defect was deteriorated early after the initial stroke. In addition, neuroimaging revealed that infarction in the posterior cerebral artery was progressed on the contralateral side, or that white matter lesion in the middle artery was enlarged in spite of small lesion in the left cerebral hemisphere. All patients in group III had deterioration of right hemiparesis associated with aphasia. CT, MRI, SPECT, and angiography indicated deep white-matter ischemia caused by main trunk lesions in the left hemisphere. Group III seemed to be equivalent to group II, except for laterality of the lesion. Neuroradiological assessment of the initial stroke may help to predict the mode of recurrence, although pathophysiology of cerebral thrombosis is complicated and varies from patient to patient. (N.K.)

  14. Inhibitory Kinetics and Mechanism of Flavonoids Extracted from Cotinus coggygria Scop. Against Glioblastoma Cancer.

    Science.gov (United States)

    Wang, Gang; Wang, Jun-Jie; Du, Li; Fei, Li; To, Shing-Shun Tony

    2016-01-01

    This proposal seeks to study the potential therapeutic modality of chemoprevention and anticancer effects and mechanisms of the flavonoids from Cotinus coggygria Scop. on glioblastoma cancer. In the current study, the total flavonoids (TFs) isolated from Cotinus coggygria Scop. var. cinerea Engl. (Cotinus coggygria Scop.) and the major flavonoids of Cotinus coggygria Scop. (CCFs) were identified, and the inhibitory kinetics of TF and CCF on glioblastoma cell lines were calculated. We also investigated whether TF or CCF regulated the apoptotic mechanism in cellular models of glio-blastoma cells. Finally, we evaluated whether treatment with TF or CCF suppressed tumor growth and inhibited migration in orthotopic mouse models of glioblastoma in vivo. In this study, the CCFs were identified as rutin, myricetin, and fisetin. TF and CCF remarkably inhibited cell proliferation and downregulated the PI3K/Akt and ERK signaling pathway in glioblastoma cell lines. Furthermore, the mitochondrial caspase-dependent cascade was regulated by TF and myricetin. In addition, TF and myricetin exhibited significant antitumor effects on glioblastoma in vivo. Taken together, these results suggest that phytochemical and biological data provide evidence for the active components in Cotinus coggygria, and that the TFs are responsible for the anticancer effects on glioblastoma cell growth via induction of apoptosis. In addition, the representative compound myricetin could provide a clinically relevant therapeutic opportunity. Therefore, our data strongly suggest that myricetin-deprived CCF can serve as a potent chemopreventive herbal medicine.

  15. In vitro Analysis of Neurospheres Derived from Glioblastoma Primary Culture: A Novel Methodology Paradigm.

    Science.gov (United States)

    Pavon, Lorena Favaro; Marti, Luciana C; Sibov, Tatiana Tais; Malheiros, Suzana M F; Brandt, Reynaldo Andre; Cavalheiro, Sergio; Gamarra, Lionel F

    2014-01-07

    Glioblastomas are the most lethal primary brain tumor that frequently relapse or progress as focal masses after radiation, suggesting that a fraction of tumor cells are responsible for the tumor regrowth. The identification of a brain tumor cell subpopulation with potent tumorigenic activity supports the cancer stem cell hypothesis in solid tumors. The goal of this study is to determine a methodology for the establishment of primary human glioblastoma cell lines. Our aim is achieved by taking the following approaches: (i) the establishment of primary glioblastoma cell culture; (ii) isolation of neurospheres derived from glioblastoma primary cultures; (iii) selection of CD133 cells from neurospheres, (iv) formation of subspheres in the CD133-positive population, (v) study of the expression level of GFAP, CD133, Nestin, Nanog, CD34, Sox2, CD44, and CD90 markers on tumor subspheres. Hence, we described a successful method for isolation of CD133-positive cell population and establishment of glioblastoma neurospheres from this primary culture, which are more robust than the ones derived straight from the tumor. Pointed out that the neurospheres derived from glioblastoma primary culture showed 29% more cells expressing CD133 then the ones straight tumor-derived, denoting a higher concentration of CD133-positive cells in the neurospheres derived from glioblastoma primary culture. These CD133-positive fractions were able to further generate subspheres. The subspheres derived from glioblastoma primary culture presented a well-defined morphology while the ones derived from the fresh tumor were sparce and less robust. And the negative fraction of CD133 cells was unable to generate subspheres. The tumor subspheres expressed GFAP, CD133, Nestin, Nanog, CD44, and CD90. Also, the present study describes an optimization of neurospheres/subspheres isolation from glioblastoma primary culture by selection of CD133-positive adherent stem cell.

  16. MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance

    Science.gov (United States)

    Yip, Stephen; Miao, Jiangyong; Cahill, Daniel P.; Iafrate, A. John; Aldape, Ken; Nutt, Catherine L.; Louis, David N.

    2009-01-01

    Purpose Over the past few years, the alkylating agent temozolomide (TMZ) has become the standard-of-care therapy for patients with glioblastoma, the most common brain tumor. Recently, large-scale cancer genome sequencing efforts have identified a hypermutation phenotype and inactivating MSH6 mismatch repair gene mutations in recurrent, post-TMZ glioblastomas, particularly those growing more rapidly during TMZ treatment. This study aimed to clarify the timing and role of MSH6 mutations in mediating glioblastoma TMZ resistance. Experimental Design MSH6 sequence and microsatellite instability (MSI) status were determined in matched pre- and post-chemotherapy glioblastomas identified by The Cancer Genome Atlas (TCGA) as having post-treatment MSH6 mutations. TMZ-resistant lines were derived in vitro via selective growth under TMZ and the MSH6 gene was sequenced in resistant clones. The role of MSH6 inactivation in mediating resistance was explored using lentiviral shRNA knockdown and MSH6 reconstitution. Results MSH6 mutations were confirmed in post-treatment TCGA glioblastomas but absent in matched pre-treatment tumors. The post-treatment hypermutation phenotype displayed a signature bias toward CpC transitions and was not associated with MSI. In vitro modeling via exposure of an MSH6-wildtype glioblastoma line to TMZ resulted in resistant clones; one clone showed an MSH6 mutation, Thr1219Ile, that had been independently noted in two treated TCGA glioblastomas. Knockdown of MSH6 in the glioblastoma line U251 increased resistance to TMZ cytotoxicity and reconstitution restored cytotoxicity in MSH6-null glioma cells. Conclusions MSH6 mutations are selected for in glioblastomas during TMZ therapy both in vitro and in vivo, and are causally associated with TMZ resistance. PMID:19584161

  17. Parálisis cerebral Cerebral palsy

    Directory of Open Access Journals (Sweden)

    Jorge Malagon Valdez

    2007-01-01

    Full Text Available El término parálisis cerebral (PC engloba a un gran número de síndromes neurológicos clínicos, de etiología diversa. Estos síndromes se caracterizan por tener una sintomatología común: los trastornos motores. Algunos autores prefieren manejar términos como "encefalopatía fija", "encefalopatías no evolutivas". Se mencionan la utilidad de programas de intervención temprana y métodos especiales de rehabilitación, así como el manejo de las deficiencias asociadas como la epilepsia, deficiencia mental, trastornos del lenguaje, audición, visión, déficit de la atención que mejoran el pronóstico de manera significativa. El pronóstico también depende de la gravedad del padecimiento y de las manifestaciones asociadas.The term cerebral palsy (CP, is used for a great number of clinical neurological syndromes. The syndromes are characterized by having a common cause, motor defects. It is important, because they can cause a brain damage by presenting motor defects and some associated deficiencies, such as mental deficiency, epilepsy, language and visual defects and pseudobulbar paralysis, with the nonevolving fact. Some authors prefer using terms such as "non-evolving encephalopathies". In the treatment the utility of prevention programs of early stimulation and special rehabilitation methods, and treatment of associated deficiencies such as epilepsy, mental deficiency, language, audition and visual problems, and the attention deficit improve the prognosis in an important way. The prognosis depends on the severity of the disease and the associated manifestations.

  18. Enhancement of insulin-like growth factor 2 receptors in glioblastoma

    International Nuclear Information System (INIS)

    Sara, V.; Prisell, Per; Sjoegren, Barbro; Enberg, Goesta

    1986-01-01

    The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of 125 1-IGF-2 but not 125 1-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma. (author)

  19. A Phase 1 trial of intravenous boronophenylalanine-fructose complex in patients with glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Bergland, R.; Elowitz, E.; Chadha, M. [Beth Israel Medical Center, New York, NY (United States); Coderre, J.A.; Joel, D. [Brookhaven National Lab., Upton, NY (United States)

    1996-10-01

    Boron neutron capture therapy (BNCT) of glioblastoma multiforme was initially performed at the Brookhaven National Laboratory in the early 1950`s While this treatment for malignant brain tumors has continued in Japan, new worldwide interest has been stimulated by the development of new and more selective boron compounds. Boronophenylalanine (BPA) is a blood-brain barrier penetrating compound that has been used in BNCT of malignant melanomas. SPA has been employed experimentally in BNCT of rat gliosarcoma and has potential use in the treatment of human glioblastoma. As a preface to clinical BNCT trials, we studied the biodistribution of SPA in patients with glioblastoma.

  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. Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

    Science.gov (United States)

    Heffernan, John M.; Sirianni, Rachael W.

    2018-02-01

    Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

  2. Visualizing molecular profiles of glioblastoma with GBM-BioDP.

    Directory of Open Access Journals (Sweden)

    Orieta Celiku

    Full Text Available Validation of clinical biomarkers and response to therapy is a challenging topic in cancer research. An important source of information for virtual validation is the datasets generated from multi-center cancer research projects such as The Cancer Genome Atlas project (TCGA. These data enable investigation of genetic and epigenetic changes responsible for cancer onset and progression, response to cancer therapies, and discovery of the molecular profiles of various cancers. However, these analyses often require bulk download of data and substantial bioinformatics expertise, which can be intimidating for investigators. Here, we report on the development of a new resource available to scientists: a data base called Glioblastoma Bio Discovery Portal (GBM-BioDP. GBM-BioDP is a free web-accessible resource that hosts a subset of the glioblastoma TCGA data and enables an intuitive query and interactive display of the resultant data. This resource provides visualization tools for the exploration of gene, miRNA, and protein expression, differential expression within the subtypes of GBM, and potential associations with clinical outcome, which are useful for virtual biological validation. The tool may also enable generation of hypotheses on how therapies impact GBM molecular profiles, which can help in personalization of treatment for optimal outcome. The resource can be accessed freely at http://gbm-biodp.nci.nih.gov (a tutorial is included.

  3. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

    Science.gov (United States)

    Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

    2011-06-01

    Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

  4. Stem Cell Niches in Glioblastoma: A Neuropathological View

    Directory of Open Access Journals (Sweden)

    Davide Schiffer

    2014-01-01

    Full Text Available Glioblastoma (GBM stem cells (GSCs, responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.

  5. Blastomycosis and Histoplasmosis in a Patient with Glioblastoma Receiving Temozolomide.

    Science.gov (United States)

    Jbeli, Aiham H; Yu, John

    2016-10-01

    Malignant glioblastoma multiform (GBM) is the most common primary malignancy of the brain in the U.S. Temozolomide (TMZ) is the cornerstone of management along with surgical resection and radiotherapy. Because of the reduction in the CD4+ lymphocyte count as a side effect of TMZ use, this patient population is under risk for opportunistic infections like Pneumocystis jiroveci. A male patient with newly diagnosed glioblastoma multiform presented with non-productive cough and chest pain. Before presentation, the patient received the standard therapy including surgical resection, radiation and TMZ. Computerized tomography of the chest showed a very large cavitary lesion in the upper segment of the right lower lobe and multiple nodular lesions with some starting to cavitate. Cytology of the bronchioalveolar lavage with special stain showed large, broad based budding yeast-like cells, morphologically consistent with blastomyces and macrophages filled with yeast-like forms, morphologically consistent with histoplasma. The patient was treated with intraconazole intended for 12 months. To the best of our knowledge, our case represents the first documented case of lung infection with both blastomyces and histoplasma in a patient after receiving TMZ for newly diagnosed GBM. Copyright© South Dakota State Medical Association.

  6. Should elderly patients with glioblastoma be proposed to radiotherapy?

    International Nuclear Information System (INIS)

    Lopez, S.; Taillibert, S.; Idbaih, A.; Simon, J.M.; Mazeron, J.J.

    2008-01-01

    In glioblastoma multiform-patients, advanced age has been associated with poor prognosis and decreased tolerance to treatments. The optimal management, especially with irradiation, was not definitively determined in the eighth and ninth decades. The Association of French-speaking neuro-oncologists (Anocef) has recently conducted a randomized clinical trial comparing radiotherapy plus supportive care versus supportive care alone in such patients. Patients aged 70-years and older with newly diagnosed glioblastoma and a Karnofsky performance score of 70 or above were randomly assigned to receive focal irradiation in daily fraction of 1.8 Gy given five days per week for a total dose of 50 Gy plus supportive care or supportive care only. Radiotherapy resulted in a modest but significant improvement in overall survival without reducing quality of life or cognition. However, the optimal regimen of radiotherapy in this fragile population remains uncertain. Abbreviated course of radiotherapy (40 Gy in 15 fractions over 19 days) has been proposed. Analysis of preliminary results showed that efficacy and safety of this hypo-fractionated accelerated regimen compared favourably with those of classically fractionated treatments. Finally, the potential contribution of surgery and chemotherapy should be evaluated in prospective clinical trials. (authors)

  7. Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

    International Nuclear Information System (INIS)

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

    2011-01-01

    The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment. - Highlights: ► In this study, we evaluate the clinical outcome of boron neutron capture therapy (BNCT) for malignant brain tumors. ► We have treated 23 glioblastoma (GBM) patients with BNCT without any additional chemotherapy. ► Clinical results of BNCT in patients with GBM are superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.

  8. Genetics of Cerebral Vasospasm

    Directory of Open Access Journals (Sweden)

    Travis R. Ladner

    2013-01-01

    Full Text Available Cerebral vasospasm (CV is a major source of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH. It is thought that an inflammatory cascade initiated by extravasated blood products precipitates CV, disrupting vascular smooth muscle cell function of major cerebral arteries, leading to vasoconstriction. Mechanisms of CV and modes of therapy are an active area of research. Understanding the genetic basis of CV holds promise for the recognition and treatment for this devastating neurovascular event. In our review, we summarize the most recent research involving key areas within the genetics and vasospasm discussion: (1 Prognostic role of genetics—risk stratification based on gene sequencing, biomarkers, and polymorphisms; (2 Signaling pathways—pinpointing key inflammatory molecules responsible for downstream cellular signaling and altering these mediators to provide therapeutic benefit; and (3 Gene therapy and gene delivery—using viral vectors or novel protein delivery methods to overexpress protective genes in the vasospasm cascade.

  9. Applications of cerebral SPECT

    Energy Technology Data Exchange (ETDEWEB)

    McArthur, C., E-mail: claire.mcarthur@nhs.net [Department of Neuroradiology, Institute of Neurological Sciences, Glasgow (United Kingdom); Jampana, R.; Patterson, J.; Hadley, D. [Department of Neuroradiology, Institute of Neurological Sciences, Glasgow (United Kingdom)

    2011-07-15

    Single-photon emission computed tomography (SPECT) can provide three-dimensional functional images of the brain following the injection of one of a series of radiopharmaceuticals that crosses the blood-brain barrier and distributes according to cerebral perfusion, neurotransmitter, or cell density. Applications include differentiating between the dementias, evaluating cerebrovascular disease, preoperative localization of epileptogenic foci, diagnosing movement disorders, and evaluation of intracerebral tumours, while also proving a useful research tool. Unlike positronemission tomography (PET), SPECT imaging is widely available and can be performed in any department that has access to a rotating gamma camera. The purpose of this review is to demonstrate the utility of cerebral SPECT and increase awareness of its role in the investigation of neurological and psychiatric disorders.

  10. Cerebral palsy and aging

    OpenAIRE

    Haak, Peterson; Lenski, Madeleine; Hidecker, Mary Jo Cooley; Li, Min; Paneth, Nigel

    2009-01-01

    Cerebral palsy (CP), the most common major disabling motor disorder of childhood, is frequently thought of as a condition that affects only children. Deaths in children with CP, never common, have in recent years become very rare, unless the child is very severely and multiply disabled. Thus, virtually all children assigned the diagnosis of CP will survive into adulthood. Attention to the adult with CP has been sparse, and the evolution of the motor disorder as the individual moves through ad...

  11. Radiopharmaceuticals for cerebral studies

    International Nuclear Information System (INIS)

    Leon Cabana, Alba

    1994-01-01

    For obtain good brain scintillation images in nuclear medicine must be used several radiopharmaceuticals. Cerebral studies give a tumors visual image as well as brain anomalities detection and are helpful in the diagnostic diseases . Are described in this work: a cerebrum radiopharmaceuticals classification,labelled compounds proceeding and Tc 99m good properties in for your fast caption, post administration and blood purification for renal way

  12. Plasticidad cerebral y lenguaje

    OpenAIRE

    Moreno-Torres Sánchez, Ignacio; Berthier-Torres, Marcelo Luis

    2012-01-01

    Hace pocos años se daba por sentado que la recuperación del lenguaje tras una lesión cerebral era imposible, al igual que adquirir la lengua materna más allá de los tres primeros años de vida. Sin embargo, las últimas indagaciones muestran que nuestra capacidad de aprender es mucho mayor.

  13. Cerebral malformations without antenatal diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Girard, Nadine J. [Diagnostic Neuroradiology, Hopital Timone, Marseille (France)

    2010-06-15

    Cerebral malformations are usually described following the different steps in development. Disorders of neurulation (dysraphisms), or diverticulation (holoprosencephalies and posterior fossa cysts), and total commissural agenesis are usually diagnosed in utero. In contrast, disorders of histogenesis (proliferation-differentiation, migration, organization) are usually discovered in infants and children. The principal clinical symptoms that may be a clue to cerebral malformation include congenital hemiparesis, epilepsy and mental or psychomotor retardation. MRI is the imaging method of choice to assess cerebral malformations. (orig.)

  14. Cerebral malformations without antenatal diagnosis

    International Nuclear Information System (INIS)

    Girard, Nadine J.

    2010-01-01

    Cerebral malformations are usually described following the different steps in development. Disorders of neurulation (dysraphisms), or diverticulation (holoprosencephalies and posterior fossa cysts), and total commissural agenesis are usually diagnosed in utero. In contrast, disorders of histogenesis (proliferation-differentiation, migration, organization) are usually discovered in infants and children. The principal clinical symptoms that may be a clue to cerebral malformation include congenital hemiparesis, epilepsy and mental or psychomotor retardation. MRI is the imaging method of choice to assess cerebral malformations. (orig.)

  15. PARPi-FL - a Fluorescent PARP1 Inhibitor for Glioblastoma Imaging

    Directory of Open Access Journals (Sweden)

    Christopher P. Irwin

    2014-05-01

    Full Text Available New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.

  16. Postoperative extracranial metastasis from glioblastoma: a case report and review of the literature.

    Science.gov (United States)

    Wu, Wenjiao; Zhong, Dequan; Zhao, Zhan; Wang, Wentao; Li, Jun; Zhang, Wei

    2017-12-29

    Glioblastoma is the most common primary malignant brain tumor. Extraneural metastases are rarely reported in the literature. We report a case of a 38-year-old patient who was diagnosed with glioblastoma in 2015. Four months after surgery, local relapse was found and the patient received a second surgery. After another 4 months, we found a hard mass in the right posterior neck when she admitted to our department for fourth cycle of adjuvant chemotherapy. Immunohistochemical investigation supported the diagnosis of glioblastoma metastases to the neck after resection of the right neck mass. A few days later, spinal vertebral magnetic resonance imaging (MRI) confirmed multiple metastases in the thoracic, lumbar, sacral, and bilateral iliac bones. Glioblastoma is the most common primary malignant brain tumor. Whole tumor resection and early radiotherapy and chemotherapy can delay recurrence and prolong survival. Extracranial metastases are extremely rare. We report this case with the aim of bringing attention to extracranial metastasis of brain glioma.

  17. A 4-miRNA signature to predict survival in glioblastomas

    DEFF Research Database (Denmark)

    Hermansen, Simon K; Sørensen, Mia D; Hansen, Anker

    2017-01-01

    Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control...... multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups. Samples from 40 glioblastoma patients were included...... that expression patterns of miRNAs; particularly the four miRNAs: hsa-miR-107_st, hsa-miR-548x_st, hsa-miR-3125_st and hsa-miR-331-3p_st could determine short- and long-term survival with a predicted accuracy of 78%. Heatmap dendrograms dichotomized glioblastomas into prognostic subgroups with a significant...

  18. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

    DEFF Research Database (Denmark)

    Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

    2014-01-01

    Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic...

  19. Testicular teratoma, mimicking a simple testicular cyst, in an infant.

    Science.gov (United States)

    Di Renzo, Dacia; Persico, Antonello; Sindici, Giulia; Lelli Chiesa, Pierluigi

    2013-09-01

    Prepubertal testicular tumors are rare, and teratoma is the second most frequent histologic type. Its typical features are those of a hard and painless scrotal mass at clinical examination, and nonhomogeneous, echoic, often with calcifications at ultrasonography. Rare but reported is the atypical presentation as a transilluminating scrotal mass, due to the presence of some internal cystic areas, detectable at ultrasonography. We report the case of an infant with a transilluminating scrotal mass, mimicking at ultrasonography and surgery a simple, fully liquid cyst, which the pathologic examination revealed to be mature cystic testicular teratoma. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Report of ischemic stroke mimicking isolated ulnar nerve paralysis

    Directory of Open Access Journals (Sweden)

    Çetin Kürşad Akpınar

    2016-12-01

    Full Text Available The cortical motor hand area is the precentral gyrus. Small cortical infarcts of this area can caused isolated hand weakness. Weakness can consist of either all fingers or ulnar-sided fingers. A 71-year-old man admitted to the emergency department with sudden weakness of the right fourth and fifth fingers Diffusion-weighted brain imaging of a magnetic resonance imaging scan revealed acute infarction of right precentral gyrus. Cardioembolus is the determined ischemic stroke subtype. This report presented a case of ischemic stroke mimicking isolated ulnar nerve paralysis.

  1. Dual anaplastic large cell lymphoma mimicking meningioma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keun Ho; Kim, Ki Hwan; Lee, Ghi Jai; Lee, Hye Kyung; Shim, Jae Chan; Lee, Kyoung Eun; Suh, Jung Ho [Seoul Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Lee, Chae Heuck [Dept. of Neurosurgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of)

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare T cell lymphoma composed of CD30-positive lymphoid cells. Most ALCLs present as nodal disease, with skin, bone, soft tissue, lung, and liver as common extranodal sites. ALCL rarely occurs in the central nervous system and is even more infrequent in the dura of the brain. We report a case of dural-based ALCL secondary to systemic disease in a 17-year-old male that mimicked meningioma on magnetic resonance imaging and angiography.

  2. Pancreatitis with Electrocardiographic Changes Mimicking Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Paul Khairy

    2001-01-01

    Full Text Available A 64-year-old woman with mild acute pancreatitis presented with epigastric pain, nausea and vomiting while undergoing hemodialysis for chronic renal insufficiency. Serial electrocardiograms revealed new onset ST segment elevations in leads V2 to V4 mimicking an anterior myocardial infarction, followed by diffusely inverted deep T waves. No cardiac pathology was demonstrated by echocardiography or coronary angiography. A review of the literature and possible pathophysiological mechanisms of electrocardiographic changes in acute pancreatitis, such as metabolic abnormalities, hemodynamic instability, vasopressors, pericarditis, myocarditis, a cardiobiliary reflex, exacerbation of underlying cardiac pathology, coagulopathy and coronary vasospasm, are discussed.

  3. Paracoccidioidomycosis Mimicking Sarcoidosis: A Review of 8 Cases.

    Science.gov (United States)

    Coelho, Mariana Guimarães; Severo, Cecília Bittencourt; de Mattos Oliveira, Flávio; Hochhegger, Bruno; Severo, Luiz Carlos

    2016-02-01

    Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with this disease. The diagnosis is based on exhaustive exclusion of differential diagnoses, particularly granulomatous infections. We report data on eight patients with paracoccidioidomycosis mimicking sarcoidosis. Five patients presented with a chronic pulmonary type infection and three had a disseminated form after immunosuppressive treatment. The mycological diagnosis in noncaseating granulomas is emphasized and reviewed.

  4. Epithelioid sarcoma mimicking abscess: review of the MRI appearances

    International Nuclear Information System (INIS)

    Dion, E.; Forest, M.; Brasseur, J.L.; Grenier, P.; Amoura, Z.

    2001-01-01

    A case of epithelioid sarcoma involving the soft tissue of the ankle is presented. The tumor was a hemorrhagic, fluid-filled, multiloculated lesion with inflammatory changes in the surrounding planes. Tuberculous abscess was diagnosed on the basis of the clinical picture, ultrasound and MRI findings. Surgical exploration of the ankle mass was carried out because of lack of local healing while the patient's general and pulmonary status improved on antituberculosis treatment. This was an unusual case of epithelioid sarcoma mimicking a multilocular abscess. (orig.)

  5. Cartilage Delamination Flap Mimicking a Torn Medial Meniscus

    Directory of Open Access Journals (Sweden)

    Gan Zhi-Wei Jonathan

    2016-01-01

    Full Text Available We report a case of a chondral delamination lesion due to medial parapatellar plica friction syndrome involving the medial femoral condyle. This mimicked a torn medial meniscus in clinical and radiological presentation. Arthroscopy revealed a chondral delamination flap, which was debrided. Diagnosis of chondral lesions in the knee can be challenging. Clinical examination and MRI have good accuracy for diagnosis and should be used in tandem. Early diagnosis and treatment of chondral lesions are important to prevent progression to early osteoarthritis.

  6. Hızma Induced Papul of Nose Mimicking Pyogenic Granuloma

    Directory of Open Access Journals (Sweden)

    Mualla Polat

    2014-09-01

    Full Text Available The application of body piercing is popular among young people, who consider it as a sign of marginality, beauty, or group identity. Piercing procedure is observed to cause a large number of complications such as infections, pain, inflammatory reactions, bleeding, dental fractures or fissures, and gingival damage, etc., mostly in young individuals. Hizma is a traditional body ornament worn by Anatolian women via a piercing procedure. Herein, we describe a papule of nose mimicking pyogenic granuloma as an uncommon complication of Hızma.

  7. Subcutaneous phaeohyphomycosis due to Pyrenochaeta romeroi mimicking a synovial cyst

    Directory of Open Access Journals (Sweden)

    Aurelien Dinh

    2016-08-01

    Full Text Available Opportunistic subcutaneous fungal infections are increasing nowadays due to the growing number of medical conditions causing immunosuppression, especially organ transplant. The incidence rate of subcutaneous phaeohyphomycosis is very low. Most studies found are case reports. They showed a wide variation of clinical presentations. Pyrenochaeta romeroi, a fungus from the Dematiaceae group is a saprophyte found in soil and plants and a possible causative agent of phaeohyphomycosis. We present a rare case of subcutaneous phaeohyphomycosis caused by P. romeroi mimicking a synovial cyst in a diabetic patient.

  8. Cystic fibrous dysplasia mimicking giant cell tumor: MRI appearance

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Kyoji; Yoshida, Sumiko [Department of Orthopaedics, Akita University School of Medicine, Akita (Japan); Okane, Kumiko [Department of Radiology, Akita University School of Medicine, Akita (Japan); Sageshima, Masato [Division of Clinical Pathology, Akita University Hospital, Akita (Japan)

    2000-01-01

    We report the case of a 43-year-old man who presented with an osteolytic and expansive lesion in the left distal femur mimicking a giant cell tumor. Magnetic resonance imaging (MRI) showed that most of the lesion was cystic, and histological examination revealed fibrous dysplasia with marked cystic degeneration. Radiographic findings of cystic fibrous dysplasia in the end of a long bone may be similar to those of a giant cell tumor, and a biopsy is essential for the final diagnosis. (orig.)

  9. Mental foramen mimicking as periapical pathology - A case report

    Directory of Open Access Journals (Sweden)

    Anusha Rangare Lakshman

    2014-09-01

    Full Text Available The radiographic recognition of any disease requires a thorough knowledge of the radiographic appearance of normal structure. Intelligent diagnosis mandates an appreciation of the wide range of variation in the appearance of normal anatomical structures. The mental foramen is usually the anterior limit of the inferior dental canal that is apparent on radiographs. It opens on the facial aspect of the mandible in the region of the premolars. It can pose diagnostic dilemma radiographically because of its anatomical variation which can mimic as a periapical pathosis. Hereby we are reporting a rare case of superimposed mental foramen over the apex of right mandibular second premolar mimicking as periapical pathology.

  10. Femoroacetabular impingement mimicking avascular osteonecrosis on bone scintigraphy

    International Nuclear Information System (INIS)

    Suarez, Juan Pablo; Domínguez, María Luz; Nogareda, Zulema; Gómez, María Asunción; Muñoz, Jose

    2016-01-01

    Femoroacetabular impingement (FAI) is a structural abnormality of proximal femur and/or acetabulum. It has been recently described, and there are limited reports in nuclear medicine literature because bone scintigraphy is not listed in its diagnostic protocol, but it should be included on differential diagnosis when evaluating patients, with hip-related symptoms because it may be misinterpreted as degenerative changes or avascular necrosis, and its early treatment avoid progression to osteoarthritis. We describe the case of a male who suffered from hip pain. Bone planar scintigraphic appearance mimicked avascular necrosis, but single photon emission computed tomography (CT) imaging and CT examination confirmed the diagnosis of FAI

  11. Embolized prostatic brachytherapy seeds mimicking acute chest pain syndromes

    Directory of Open Access Journals (Sweden)

    Nirmal Guragai

    2017-01-01

    Full Text Available A 59-year-old male with a history of nonobstructive coronary artery disease, diabetes mellitus, hypertension, and prostate cancer presented to the hospital with 1-day history of pleuritic chest pain. Initial workup for acute coronary event was unremarkable. Chest X-ray revealed multiple small radial densities which were linear and hyperdense, consistent with embolization of metallic seeds to the pulmonary circulation. The patient was noted to have had radioactive metallic seeds implanted for prostate cancer 6 months ago. Diagnosis of pulmonary embolization of prostatic seeds is challenging as they frequently present with chest pain mimicking acute coronary syndromes.

  12. Mondor Disease Of Penis; A Rare Entity Mimicking Peyronie's Disease

    Directory of Open Access Journals (Sweden)

    Türker Acar

    2015-11-01

    Full Text Available Mondor’s disease of the penis is a rare entity characterized by thrombosis in the dorsal penile vein. Unlike anxiety resulting from this condition which is conservatively treated, recognizing this disease is quite easy with Doppler ultrasonography. Peyronie’s disease and sclerosing lymphangitis are considered in the differential diagnosis of Mondor’s disease. In this present case report we aimed to present ultrasonography findings and briefly review the literature in a male patient diagnosed with Mondor's disease who admitted with rope like stiffness on the dorsal side of penis mimicking Peyronie's disease.

  13. Endometriosis mimicking the perianal fistula tract: Case report

    Directory of Open Access Journals (Sweden)

    Gül Türkcü

    2014-09-01

    Full Text Available Endometriosis is the presence of endometrial glands and stroma outside the uterine cavity. Nowadays, in many cases, although routine use of episiotomy perineal endo metriosis is extremely rare. A 36 year old female patient was referred to our hospital with complaints of pain in the perianal region for five months. On physical examination, stiffness was palpated and then magnetic resonance im aging (MRI was performed. MRI is compatible with fistula tract. The lesion was excised and the histopathological appearance correspond to endometriosis. Perianal endo metriosis is rare in the perianal region and in the clinic mimicking perianal fistulas and malignancy should be kept in mind in the differential diagnosis

  14. Hyperventilation, cerebral perfusion, and syncope

    DEFF Research Database (Denmark)

    Immink, R V; Pott, F C; Secher, N H

    2014-01-01

    the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced...... dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2...

  15. Molecular pathophysiology of cerebral edema.

    Science.gov (United States)

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. © The Author(s) 2015.

  16. What You Should Know about Cerebral Aneurysms

    Science.gov (United States)

    ... Month Infographic Stroke Hero F.A.S.T. Quiz What You Should Know About Cerebral Aneurysms Updated:Nov ... About Cerebral Aneurysms Diagnosis and Symptoms Damage Treatments What is a cerebral aneurysm? An aneurysm is a ...

  17. Cerebral Autoregulation in Normal Pregnancy and Preeclampsia

    NARCIS (Netherlands)

    van Veen, Teelkien R.; Panerai, Ronney B.; Haeri, Sina; Griffioen, Annemiek C.; Zeeman, Gerda; Belfort, Michael A.

    2013-01-01

    OBJECTIVE: To test the hypothesis that preeclampsia is associated with impaired dynamic cerebral autoregulation. METHODS: In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (determined by noninvasive

  18. CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of patients.

    Science.gov (United States)

    Wang, Hong-Xiang; Qin, Rong; Mao, Jian; Huang, Qi-Lin; Hong, Fan; Li, Feng; Gong, Zhen-Yu; Xu, Tao; Yan, Yong; Chao, Shao-Hui; Zhang, Shi-Kun; Chen, Ju-Xiang

    2018-04-03

    Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma. We determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation. In our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls. Our study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    OpenAIRE

    Goffart, Nicolas; KROONEN, Jérôme

    2013-01-01

    Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays sti...

  20. Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma.

    Science.gov (United States)

    Gramatzki, Dorothee; Kickingereder, Philipp; Hentschel, Bettina; Felsberg, Jörg; Herrlinger, Ulrich; Schackert, Gabriele; Tonn, Jörg-Christian; Westphal, Manfred; Sabel, Michael; Schlegel, Uwe; Wick, Wolfgang; Pietsch, Torsten; Reifenberger, Guido; Loeffler, Markus; Bendszus, Martin; Weller, Michael

    2017-04-11

    To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O 6 -methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase ( IDH ) mutation status. These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS. © 2017 American Academy of Neurology.

  1. Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Takuya; Hirata, Kenji; Kobayashi, Kentaro; Manabe, Osamu; Watanabe, Shiro; Hattori, Naoya; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Yamaguchi, Shigeru [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Tanaka, Shinya [Hokkaido University Graduate School of Medicine, Department of Cancer Pathology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University Graduate School of Medicine, Department of Biostatistics, Sapporo (Japan)

    2017-04-15

    Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV

  2. Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity.

    Science.gov (United States)

    Angelova, Assia L; Barf, Milena; Geletneky, Karsten; Unterberg, Andreas; Rommelaere, Jean

    2017-12-15

    Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood-brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

  3. Epilepsy in Adults with Supratentorial Glioblastoma: Incidence and Influence Factors and Prophylaxis in 184 Patients.

    Science.gov (United States)

    Liang, Shuli; Zhang, Junchen; Zhang, Shaohui; Fu, Xiangping

    2016-01-01

    To analyze the incidence of epilepsy in adult patients with supratentorial glioblastoma, assess the factors influencing the development of epilepsy in these cases, and evaluate patients' response to antiepileptic drugs (AEDs) in a series of 184 patients. We retrospectively analyzed the 184 adult patients diagnosed with supratentorial glioblastoma. All subjects were treated within our hospital and subsequently died between 2003 and 2013. The incidence of epilepsy was assessed before and after initial resection and reexamined every 2 months thereafter. We evaluated the efficacy of prophylactic AEDs in this patient population based on the gathered incidence data. Of 184 patients, 43 (23.37%) were diagnosed with epilepsy before their initial resection. The total incidence of epilepsy (both pre- and postoperative) was 68.48%. The prevalence of active epilepsy reached over 80% in patients with epilepsy and survival of greater than 13 months postoperatively. Patients with glioblastoma in the frontal and/or temporal lobes had a higher prevalence of epilepsy. In the 43 patients with preoperative epilepsy, total resection of glioblastoma resulted in significantly lower seizure frequency. Patients who received epilepsy prophylaxis with AEDs for at least 6 months had significantly fewer seizures and higher Karnofsky scores than those receiving AEDs for less than one month or not at all. The incidence of epilepsy in adult patients with glioblastoma was high and responded poorly to AEDs in the short term. However, when taken for longer periods, AEDs can reduce the frequency of seizures in patients with glioblastoma.

  4. Autophagy suppression potentiates the anti-glioblastoma effect of asparaginase in vitro and in vivo

    Science.gov (United States)

    Chen, Qicheng; Ye, Li; Fan, Jiajun; Zhang, Xuyao; Wang, Huan; Liao, Siyang; Song, Ping; Wang, Ziyu; Wang, Shaofei; Li, Yubin; Luan, Jingyun; Wang, Yichen; Chen, Wei; Zai, Wenjing; Yang, Ping; Cao, Zhonglian; Ju, Dianwen

    2017-01-01

    Asparaginase has been reported to be effective in the treatment of various leukemia and several malignant solid cancers. However, the anti-tumor effect of asparaginase is always restricted due to complicated mechanisms. Herein, we investigated the mechanisms of how glioblastoma resisted asparaginase treatment and reported a novel approach to enhance the anti-glioblastoma effect of asparaginase. We found that asparaginase could induce growth inhibition and caspase-dependent apoptosis in U87MG/U251MG glioblastoma cells. Meanwhile, autophagy was activated as indicated by autophagosomes formation and upregulated expression of LC3-II. Importantly, abolishing autophagy using chloroquine (CQ) and LY294002 enhanced the cytotoxicity and apoptosis induced by asparaginase in U87MG/U251MG cells. Further study proved that Akt/mTOR and Erk signaling pathways participated in autophagy induction, while reactive oxygen species (ROS) served as an intracellular regulator for both cytotoxicity and autophagy in asparaginase-treated U87MG/U251MG cells. Moreover, combination treatment with autophagy inhibitor CQ significantly enhanced anti-glioblastoma efficacy of asparaginase in U87MG cell xenograft model. Taken together, our results demonstrated that inhibition of autophagy potentiated the anti-tumor effect of asparagine depletion on glioblastoma, indicating that targeting autophagy and asparagine could be a potential approach for glioblastoma treatment. PMID:29207624

  5. Bee venom induces apoptosis and suppresses matrix metaloprotease-2 expression in human glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Mohsen Sisakht

    Full Text Available Abstract Glioblastoma is the most common malignant brain tumor representing with poor prognosis, therapy resistance and high metastasis rate. Increased expression and activity of matrix metalloproteinase-2, a member of matrix metalloproteinase family proteins, has been reported in many cancers including glioblastoma. Inhibition of matrix metalloproteinase-2 expression has resulted in reduced aggression of glioblastoma tumors in several reports. In the present study, we evaluated effect of bee venom on expression and activity of matrix metalloproteinase-2 as well as potential toxicity and apoptogenic properties of bee venom on glioblastoma cells. Human A172 glioblastoma cells were treated with increasing concentrations of bee venom. Then, cell viability, apoptosis, matrix metalloproteinase-2 expression, and matrix metalloproteinase-2 activity were measured using MMT assay, propidium iodide staining, real time-PCR, and zymography, respectively. The IC50 value of bee venom was 28.5 µg/ml in which it leads to decrease of cell viability and induction of apoptosis. Incubation with bee venom also decreased the expression of matrix metalloproteinase-2 in this cell line (p < 0.05. In zymography, there was a reverse correlation between bee venom concentration and total matrix metalloproteinase-2 activity. Induction of apoptosis as well as inhibition of matrix metalloproteinase-2 activity and expression can be suggested as molecular mechanisms involved in cytotoxic and antimetastatic effects of bee venom against glioblastoma cells.

  6. Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

    KAUST Repository

    Vasaikar, Suhas

    2018-02-06

    BackgroundGlioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.ResultsBy bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.ConclusionsETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.

  7. IDH1-associated primary glioblastoma in young adults displays differential patterns of tumour and vascular morphology.

    Directory of Open Access Journals (Sweden)

    Sergey Popov

    Full Text Available Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous, and assessed for specific tumour (cellularity, necrosis, palisades and vascular features (glomeruloid structures, arcades, pericyte proliferation. IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

  8. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

    Science.gov (United States)

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-04-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

  9. Spontaneous motor entrainment to music in multiple vocal mimicking species.

    Science.gov (United States)

    Schachner, Adena; Brady, Timothy F; Pepperberg, Irene M; Hauser, Marc D

    2009-05-26

    The human capacity for music consists of certain core phenomena, including the tendency to entrain, or align movement, to an external auditory pulse [1-3]. This ability, fundamental both for music production and for coordinated dance, has been repeatedly highlighted as uniquely human [4-11]. However, it has recently been hypothesized that entrainment evolved as a by-product of vocal mimicry, generating the strong prediction that only vocal mimicking animals may be able to entrain [12, 13]. Here we provide comparative data demonstrating the existence of two proficient vocal mimicking nonhuman animals (parrots) that entrain to music, spontaneously producing synchronized movements resembling human dance. We also provide an extensive comparative data set from a global video database systematically analyzed for evidence of entrainment in hundreds of species both capable and incapable of vocal mimicry. Despite the higher representation of vocal nonmimics in the database and comparable exposure of mimics and nonmimics to humans and music, only vocal mimics showed evidence of entrainment. We conclude that entrainment is not unique to humans and that the distribution of entrainment across species supports the hypothesis that entrainment evolved as a by-product of selection for vocal mimicry.

  10. Tension pneumocephalus mimicking septic shock: a case report

    Directory of Open Access Journals (Sweden)

    Caroline Miranda, MD

    2018-02-01

    Full Text Available Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

  11. Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging

    Science.gov (United States)

    Cook, Jason R.; Bouchard, Richard R.; Emelianov, Stanislav Y.

    2011-01-01

    In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid® 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies. PMID:22076278

  12. In vitro catheter and sorbent-based method for clearance of radiocontrast material during cerebral interventions

    Energy Technology Data Exchange (ETDEWEB)

    Angheloiu, George O., E-mail: goangheloiu@drmc.org [Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Department of Cardiology, Dubois Regional Medical Center, Dubois, PA (United States); Hänscheid, Heribert; Reiners, Christoph [Department of Nuclear Medicine, University of Würzburg, Würzburg (Germany); Anderson, William D. [Cardiology Department, Exempla Healthcare, Denver, CO (United States); Kellum, John A. [CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2013-07-15

    Background: Contrast-induced acute kidney injury is a severe condition resulting from the use of radiology contrast in patients with predisposing factors. Hypothesis: We hypothesized that a novel system including a device containing polymer resin sorbent beads and a custom-made suctioning catheter could efficiently remove contrast from an in vitro novel model of circulatory system (MOCS) mimicking the cerebral circulation. Methods: A custom-made catheter was built and optimized for cerebral venous approach. The efficiency of a system made of a polymer resin sorbent beads column (CST 401, Cytosorbents) and this particular catheter was tested in the MOCS running a solution composed of 0.9% saline and radio-contrast. During two series of 18 cycles of first-pass experiments we assessed the catheter's suctioning efficiency and the system's ability to clear radio-contrast injected into the MOCS's cerebral arterial segment. We also assessed the functioning and reliability of the MOCS. Results: Mean suctioning efficiency of the catheter was 84% ± 24%. The polymer sorbent column contrast removal rate was initially 96% and gradually decreased with subsequent cycles in a linear fashion during an experiment lasting approximately 90 minutes. The MOCS had a reliability of 0.9946×min{sup −1} where 1 × min{sup −1} was the optimum value. Conclusion: A system including a polymer resin sorbent beads column and a custom-made suctioning catheter had an excellent initial efficiency in quickly removing contrast from an artificial MOCS mimicking the cerebral circulation. MOCS is an inexpensive and relatively reliable custom-made system that can be used for training or testing purposes.

  13. In vitro catheter and sorbent-based method for clearance of radiocontrast material during cerebral interventions

    International Nuclear Information System (INIS)

    Angheloiu, George O.; Hänscheid, Heribert; Reiners, Christoph; Anderson, William D.; Kellum, John A.

    2013-01-01

    Background: Contrast-induced acute kidney injury is a severe condition resulting from the use of radiology contrast in patients with predisposing factors. Hypothesis: We hypothesized that a novel system including a device containing polymer resin sorbent beads and a custom-made suctioning catheter could efficiently remove contrast from an in vitro novel model of circulatory system (MOCS) mimicking the cerebral circulation. Methods: A custom-made catheter was built and optimized for cerebral venous approach. The efficiency of a system made of a polymer resin sorbent beads column (CST 401, Cytosorbents) and this particular catheter was tested in the MOCS running a solution composed of 0.9% saline and radio-contrast. During two series of 18 cycles of first-pass experiments we assessed the catheter's suctioning efficiency and the system's ability to clear radio-contrast injected into the MOCS's cerebral arterial segment. We also assessed the functioning and reliability of the MOCS. Results: Mean suctioning efficiency of the catheter was 84% ± 24%. The polymer sorbent column contrast removal rate was initially 96% and gradually decreased with subsequent cycles in a linear fashion during an experiment lasting approximately 90 minutes. The MOCS had a reliability of 0.9946×min −1 where 1 × min −1 was the optimum value. Conclusion: A system including a polymer resin sorbent beads column and a custom-made suctioning catheter had an excellent initial efficiency in quickly removing contrast from an artificial MOCS mimicking the cerebral circulation. MOCS is an inexpensive and relatively reliable custom-made system that can be used for training or testing purposes

  14. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    International Nuclear Information System (INIS)

    Oka, Naoki; Soeda, Akio; Inagaki, Akihito; Onodera, Masafumi; Maruyama, Hidekazu; Hara, Akira; Kunisada, Takahiro; Mori, Hideki; Iwama, Toru

    2007-01-01

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche

  15. Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Wenchao; Bao, Shideng, E-mail: baos@ccf.org [Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States)

    2014-03-26

    Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described.

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

    International Nuclear Information System (INIS)

    Facchino, Sabrina; Abdouh, Mohamed; Bernier, Gilbert

    2011-01-01

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

  17. Dapsone induced methemoglobinemia in a patient with glioblastoma

    Science.gov (United States)

    Walker, Julie G.; Kadia, Tapan; Brown, Latrondria; Juneja, Harinder S.; de Groot, John F.

    2015-01-01

    Primary brain tumor patients have multiple risk factors for Pneumocystis jiroveci and may require prophylaxis with TMP-SMZ or dapsone. Although dapsone is generally safe and efficacious, we present a case of a patient diagnosed with a brain stem glioblastoma who developed methemoglobinemia and haemolytic anemia after presenting with worsening confusion and cardiopulmonary system dysfunction. This case highlights one of the potentially severe complications associated with dapsone therapy. Although this illustrates an unusual toxicity of dapsone, a high index of suspicion should be given to high-risk patients due to ethnic heritage, anemia, or advanced age. Furthermore, given the toxicities of TMP-SMZ and dapsone, further work is needed to determine the threshold CD4+ count at which empiric prophylaxis should be initiated. PMID:19219404

  18. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  19. Overview of Cellular Immunotherapy for Patients with Glioblastoma

    Directory of Open Access Journals (Sweden)

    Elodie Vauleon

    2010-01-01

    Full Text Available High grade gliomas (HGG including glioblastomas (GBM are the most common and devastating primary brain tumours. Despite important progresses in GBM treatment that currently includes surgery combined to radio- and chemotherapy, GBM patients' prognosis remains very poor. Immunotherapy is one of the new promising therapeutic approaches that can specifically target tumour cells. Such an approach could also maintain long term antitumour responses without inducing neurologic defects. Since the past 25 years, adoptive and active immunotherapies using lymphokine-activated killer cells, cytotoxic T cells, tumour-infiltrating lymphocytes, autologous tumour cells, and dendritic cells have been tested in phase I/II clinical trials with HGG patients. This paper inventories these cellular immunotherapeutic strategies and discusses their efficacy, limits, and future perspectives for optimizing the treatment to achieve clinical benefits for GBM patients.

  20. Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations

    Energy Technology Data Exchange (ETDEWEB)

    Chanana, A.D.; Coderre, J.A.; Joel, D.D.; Slatkin, D.N.

    1996-12-31

    In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH.

  1. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

    Science.gov (United States)

    Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

    2014-06-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

  2. Different angiogenic phenotypes in primary and secondary glioblastomas.

    Science.gov (United States)

    Karcher, Sibylle; Steiner, Hans-Herbert; Ahmadi, Rezvan; Zoubaa, Saida; Vasvari, Gergely; Bauer, Harry; Unterberg, Andreas; Herold-Mende, Christel

    2006-05-01

    Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve through different genetic pathways, including EGF receptor and PDGF and its receptor and thus genes that are involved in tumor-induced angiogenesis. However, whether other angiogenic cytokines are also differentially expressed in these glioblastoma subtypes is not known so far, but this knowledge might be important to optimize an antiangiogenic therapy. Therefore, we studied the expression of several angiogenic cytokines, including VEGF-A, HGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in pGBMs and sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In tumor tissues, expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 30 tissue-corresponding glioma cultures revealed a predominant expression of VEGF-A in pGBMs and significantly higher expression levels of PDGF-AB in sGBMs. HGF and bFGF were determined in nearly all tumor cultures but with no GBM subtype or malignancy-related differences. Interestingly, GM-CSF and especially G-CSF were produced less frequently by tumor cells. However, GM-CSF secretion occurred together with an increased number of simultaneously secreted cytokines and correlated with a worse patient prognosis and may thus represent a more aggressive angiogenic phenotype. Finally, we confirmed an independent contribution of each tumor-derived cytokine analyzed to tumor-induced vascularization. Our data indicate that an optimal antiangiogenic therapy may require targeting of multiple angiogenic pathways that seem to differ markedly in pGBMs and sGBMs. 2005 Wiley-Liss, Inc.

  3. Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

    International Nuclear Information System (INIS)

    Niewald, Marcus; Berdel, Christian; Fleckenstein, Jochen; Licht, Norbert; Ketter, Ralf; Rübe, Christian

    2011-01-01

    Retrospective evaluation of toxicity and results after radiochemotherapy for glioblastoma. 46 patients with histopathologically proven glioblastoma received simultaneous radiochemotherapy (RCT). The mean age at the beginning of therapy was 59 years, the mean Karnofsky performance index 80%. 44 patients had been operated on before radiotherapy, two had not. A total dose of 60 Gy was applied in daily single fractions of 2.0 Gy within six weeks, 75 mg/m 2 /day Temozolomide were given orally during the whole radiotherapy period. A local progression could be diagnosed in 34/46 patients (70%). The median survival time amounted to 13.6 months resulting in one-year and two-year survival probabilities of 48% and 8%, respectively. Radiotherapy could be applied completely in 89% of the patients. Chemotherapy could be completed according to schedule only in 56.5%, the main reason being blood toxicity (50% of the interruptions). Most of those patients suffered from leucopenia and/or thrombopenia grade III and IV CTC (Common toxicity criteria). Further reasons were an unfavourable general health status or a rise of liver enzymes. The mean duration of thrombopenia and leucopenia amounted to 64 and 20 days. In two patients, blood cell counts remained abnormal until death. In two patients we noticed a rise of liver enzymes. In one of these in the healing phase of hepatitis a rise of ASAT and ALAT CTC grade IV was diagnosed. These values normalized after termination of temozolomide medication. One patient died of pneumonia during therapy. Our survival data were well within the range taken from the literature. However, we noticed a considerable frequency and intensity of side effects to bone marrow and liver. These lead to the recommendations that regular examinations of blood cell count and liver enzymes should be performed during therapy and temozolomide should not be applied or application should be terminated according to the criteria given by the manufacturer

  4. Cerebral oxygenation after birth

    DEFF Research Database (Denmark)

    Hessel, Trine W; Hyttel-Sorensen, Simon; Greisen, Gorm

    2014-01-01

    AIM: To compare absolute values of regional cerebral tissue oxygenation (cStO2 ) during haemodynamic transition after birth and repeatability during steady state for two commercial near-infrared spectroscopy (NIRS) devices. METHODS: In a prospective observational study, the INVOS 5100C and FORE......: The INVOS and FORE-SIGHT cStO2 estimates showed oxygenation-level-dependent difference during birth transition. The better repeatability of FORE-SIGHT could be due to the lower response to change in saturation....

  5. Cerebral venous thrombosis.

    Science.gov (United States)

    Ameri, A; Bousser, M G

    1992-02-01

    Neuroimagining facilities allow early recognition of cerebral venous thrombosis (CVT), which now appears far more common than previously assumed. The diagnosis remains difficult because of a wide spectrum of clinical presentation and a highly variable mode of onset. Numerous conditions (presently mostly noninfectious) can cause or predispose to CVT, which therefore requires an extensive etiologic work-up. The functional and vital prognosis is much better than classically thought with, in noninfectious CVT, a fatality rate of less than 10% and a complete recovery in over 70%. Although spontaneous recovery is possible, the efficacy of heparin is now well established.

  6. Cerebral aneurysms – an audit

    African Journals Online (AJOL)

    Enrique

    Abstract. We performed an audit to determine the profile of cerebral aneurysms at the Universitas Hospital Bloem- fontein, the only government hospital with a vascular suite in the Free State and Northern Cape area. Two hun- dred and twenty-three government patients, diagnosed with cerebral aneurysms during the period.

  7. Syncope, cerebral perfusion, and oxygenation

    NARCIS (Netherlands)

    van Lieshout, Johannes J.; Wieling, Wouter; Karemaker, John M.; Secher, Niels H.

    2003-01-01

    During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes

  8. Therapeutic interventions in cerebral palsy.

    Science.gov (United States)

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

  9. Classifying Glioblastoma Multiforme Follow-Up Progressive vs. Responsive Forms Using Multi-Parametric MRI Features.

    Science.gov (United States)

    Ion-Mărgineanu, Adrian; Van Cauter, Sofie; Sima, Diana M; Maes, Frederik; Sunaert, Stefan; Himmelreich, Uwe; Van Huffel, Sabine

    2016-01-01

    Purpose: The purpose of this paper is discriminating between tumor progression and response to treatment based on follow-up multi-parametric magnetic resonance imaging (MRI) data retrieved from glioblastoma multiforme (GBM) patients. Materials and Methods: Multi-parametric MRI data consisting of conventional MRI (cMRI) and advanced MRI [i.e., perfusion weighted MRI (PWI) and diffusion kurtosis MRI (DKI)] were acquired from 29 GBM patients treated with adjuvant therapy after surgery. We propose an automatic pipeline for processing advanced MRI data and extracting intensity-based histogram features and 3-D texture features using manually and semi-manually delineated regions of interest (ROIs). Classifiers are trained using a leave-one-patient-out cross validation scheme on complete MRI data. Balanced accuracy rate (BAR)-values are computed and compared between different ROIs, MR modalities, and classifiers, using non-parametric multiple comparison tests. Results: Maximum BAR-values using manual delineations are 0.956, 0.85, 0.879, and 0.932, for cMRI, PWI, DKI, and all three MRI modalities combined, respectively. Maximum BAR-values using semi-manual delineations are 0.932, 0.894, 0.885, and 0.947, for cMRI, PWI, DKI, and all three MR modalities combined, respectively. After statistical testing using Kruskal-Wallis and post-hoc Dunn-Šidák analysis we conclude that training a RUSBoost classifier on features extracted using semi-manual delineations on cMRI or on all MRI modalities combined performs best. Conclusions: We present two main conclusions: (1) using T1 post-contrast (T1pc) features extracted from manual total delineations, AdaBoost achieves the highest BAR-value, 0.956; (2) using T1pc-average, T1pc-90th percentile, and Cerebral Blood Volume (CBV) 90th percentile extracted from semi-manually delineated contrast enhancing ROIs, SVM-rbf, and RUSBoost achieve BAR-values of 0.947 and 0.932, respectively. Our findings show that AdaBoost, SVM-rbf, and RUSBoost

  10. Tax mimicking and yardstick competition among local governments in the Netherlands

    NARCIS (Netherlands)

    Allers, MA; Elhorst, JP

    This paper provides a spatial-econometric analysis of the setting of property tax rates by Dutch municipalities. We find evidence of tax mimicking: a ten percent higher property tax rate in neighboring municipalities leads to a 3.5 percent higher tax rate. Mimicking is less pronounced in

  11. Cerebral sinus venous thrombosis

    Directory of Open Access Journals (Sweden)

    Hernando Raphael Alvis-Miranda

    2013-01-01

    Full Text Available Cerebral sinus venous thrombosis (CSVT is a rare phenomenon that can be seen with some frequency in young patients. CSVT is a multifactorial condition with gender-related specific causes, with a wide clinical presentation, the leading causes differ between developed and developing countries, converting CSVT in a condition characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis that requires fine medical skills and a high suspicious index. Patients who presents with CSVT should underwent to CT-scan venography (CVT and to the proper inquiry of the generating cause. This disease can affect the cerebral venous drainage and related anatomical structure. The symptoms may appear in relation to increased intracranial pressure imitating a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the cause, generally the complications can be prevented. Mortality trends have diminished, and with the new technologies, surely it will continue. This work aims to review current knowledge about CSVT including its pathogenesis, etiology, clinical manifestations, diagnosis, and treatment.

  12. Cerebral imaging in pediatrics

    International Nuclear Information System (INIS)

    Gordon, I.

    1998-01-01

    Radioisotope brain imaging has focused mainly on regional cerebral blood flow (rCBF). However the use of ligand which go to specific receptor sites is being introduced in pediatrics, mainly psychiatry. rCBF is potentially available in many institutions, especially with the availability of multi-headed gamma cameras. The use of this technique in pediatrics requires special attention to detail in the manner of data acquisition and handling the child. The interpretation of the rCBF study in a child requires knowledge of normal brain maturation. The major clinical use in pediatrics is epilepsy because of the advances in surgery and the frequency of complex partial seizures. Other indications in pediatric neurology include brain death, acute neurological loss including stroke, language disorders, cerebral palsy, hypertension due to renovascular disease, traumatic brain injury and migraine. There are pediatric physiological conditions in which rCBF has been undertaken, these include anorexia nervosa, autism, Gilles de la Tourette syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD). Research using different ligands to specific receptor sites will also be reviewed in pediatrics

  13. Cerebral imaging in pediatrics

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, I. [London, Great Ormond Street Hospital for Children (United Kingdom)

    1998-06-01

    Radioisotope brain imaging has focused mainly on regional cerebral blood flow (rCBF). However the use of ligand which go to specific receptor sites is being introduced in pediatrics, mainly psychiatry. rCBF is potentially available in many institutions, especially with the availability of multi-headed gamma cameras. The use of this technique in pediatrics requires special attention to detail in the manner of data acquisition and handling the child. The interpretation of the rCBF study in a child requires knowledge of normal brain maturation. The major clinical use in pediatrics is epilepsy because of the advances in surgery and the frequency of complex partial seizures. Other indications in pediatric neurology include brain death, acute neurological loss including stroke, language disorders, cerebral palsy, hypertension due to renovascular disease, traumatic brain injury and migraine. There are pediatric physiological conditions in which rCBF has been undertaken, these include anorexia nervosa, autism, Gilles de la Tourette syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD). Research using different ligands to specific receptor sites will also be reviewed in pediatrics.

  14. Cerebral cartography and connectomics.

    Science.gov (United States)

    Sporns, Olaf

    2015-05-19

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  15. MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma

    Directory of Open Access Journals (Sweden)

    Skiriute Daina

    2012-06-01

    Full Text Available Abstract Background Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome. Methods The methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis. Results The overwhelming majority (97.3% of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p CASP8 with older (p MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p CASP8 was more frequent in patients who survived shorter than 36 months (p MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p MGMT and GATA6 were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy. Conclusions High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome.

  16. Glioblastoma stem cell differentiation into endothelial cells evidenced through live-cell imaging.

    Science.gov (United States)

    Mei, Xin; Chen, Yin-Sheng; Chen, Fu-Rong; Xi, Shao-Yan; Chen, Zhong-Ping

    2017-08-01

    Glioblastoma cell-initiated vascularization is an alternative angiogenesis called vasculogenic mimicry. However, current knowledge on the mechanism of de novo vessel formation from glioblastoma stem cells (GSCs) is limited. Sixty-four glioblastoma samples from patients and 10 fluorescent glioma xenograft samples were examined by immunofluorescence staining for endothelial marker (CD34 and CD31) and glial cell marker (glial fibrillary acidic protein [GFAP]) expression. GSCs were then isolated from human glioblastoma tissue and CD133+/Sox2+ red fluorescent protein-containing (RFP)-GSC-1 cells were established. The ability of these cells to form vascular structures was examined by live-cell imaging of 3D cultures. CD34-GFAP or CD31-GFAP coexpressing glioblastoma-derived endothelial cells (GDEC) were found in 30 of 64 (46.9%) of clinical glioblastoma samples. In those 30 samples, GDEC were found to form vessel structures in 21 (70%) samples. Among 21 samples with GDEC vessels, the CD34+ GDEC vessels and CD31+ GDEC vessels accounted for about 14.16% and 18.08% of total vessels, respectively. In the xenograft samples, CD34+ GDEC were found in 7 out of 10 mice, and 4 out of 7 mice had CD34+ GDEC vessels. CD31+ GDEC were also found in 7 mice, and 4 mice had CD31+ GDEC vessels (10 mice in total). Through live-cell imaging, we observed gradual CD34 expression when cultured with vascular endothelial growth factor in some glioma cells, and a dynamic increase in endothelial marker expression in RFP-GSC-1 in vitro was recorded. Cells expressed CD34 (9.46%) after 6 hours in culture. The results demonstrated that GSCs may differentiate into endothelial cells and promote angiogenesis in glioblastomas. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  17. Noninvasive absolute cerebral oximetry with frequency-domain near-infrared spectroscopy

    Science.gov (United States)

    Hallacoglu, Bertan

    Near-infrared spectroscopy (NIRS) measurements of absolute concentrations of oxy-hemoglobin and deoxy-hemoglobin in the human brain can provide critical information about cerebral physiology in terms of cerebral blood volume, blood flow, oxygen delivery, and metabolic rate of oxygen. We developed several frequency domain NIRS data acquisition and analysis methods aimed at absolute measurements of hemoglobin concentration and saturation in cerebral tissue of adult human subjects. Extensive experimental investigations were carried out in various homogenous and two-layered tissue-mimicking phantoms, and biological tissues. The advantages and limitations of commonly used homogenous models and inversion strategies were thoroughly investigated. Prior to human subjects, extensive studies were carried out in in vivo animal models. In rabbits, absolute hemoglobin oxygen desaturation was shown to depend strongly on surgically induced testicular torsion. Methods developed in this study were then adapted for measurements in the rat brain. Absolute values were demonstrated to discern cerebrovascular impairment in a rat model of diet-induced vascular cognitive impairment. These results facilitated the development of clinically useful optical measures of cerebrovascular health. In a large group of human subjects, employing a homogeneous model for absolute measurements was shown to be reliable and robust. However, it was also shown to be limited due to the relatively thick extracerebral tissue. The procedure we develop in this work and the thesis thereof performs a nonlinear inversion procedure with six unknown parameters with no other prior knowledge for the retrieval of the optical coefficients and top layer thickness with high accuracy on two-layered media. Our absolute measurements of cerebral hemoglobin concentration and saturation are based on the discrimination of extracerebral and cerebral tissue layers, and they can enhance the impact of NIRS for cerebral hemodynamics and

  18. An Adolescent Patient with Scabies Mimicking Gottron Papules

    Directory of Open Access Journals (Sweden)

    Eiji Yoshinaga

    2009-01-01

    Full Text Available Atypical features of scabies occur in infants and children and patients with prolonged use of corticosteroids or immunosuppression. We report a non-immunosuppressed 15-year-old female case of scabies showing scaly reddish papules over the proximal interphalangeal joints mimicking Gottron papules in classic dermatomyositis. Periungal erythema was also seen. Four months’ topical corticosteroids from previous clinics had been used. Dermoscopic findings were consistent with typical pictures of scabies. Scraping of hand crusts demonstrated scabies mites and ova. Skin lesions of the patient were cured with oral ivermectin and topical 10% crotamiton. This case suggests that a lesion resembling Gottron papules may be added to the panel of unusual presentations of scabies.

  19. Nephropathic Cystinosis Mimicking Bartter Syndrome: a Novel Mutation.

    Science.gov (United States)

    Bastug, Funda; Nalcacioglu, Hulya; Ozaltin, Fatih; Korkmaz, Emine; Yel, Sibel

    2018-01-01

    Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. The clinical phenotype of nephropathic cystinosis is characterized by renal tubular Fanconi syndrome and development of end-stage renal disease during the first decade. Although metabolic acidosis is the classically prominent finding of the disease, a few cases may present with hypokalemic metabolic alkalosis mimicking Bartter syndrome. Bartter-like presentation may lead to delay in diagnosis and initiation of specific treatment for cystinosis. We report a case of a 6-year-old girl initially presenting with the features of Bartter syndrome that was diagnosed 2 years later with nephropathic cystinosis and a novel CTNS mutation.

  20. Methicillin-resistant Staphylococcus Aureus Lip Infection Mimicking Angioedema.

    Science.gov (United States)

    Lucerna, Alan R; Espinosa, James; Darlington, Anne M

    2015-07-01

    It is rare for angioedema to be misidentified by the experienced clinician or for it to mimic another disease process. As an Emergency Physician, it is important to recognize and treat angioedema immediately. Of equal importance is the recognition and initiation of treatment of facial cellulitis. A case report follows that illustrates methicillin-resistant Staphylococcus aureus (MRSA) lip infection mimicking angioedema. Here, we describe a case of a 21-year-old man who presented with a swollen lower lip, initially diagnosed as angioedema. Further investigation revealed the cause of his lip swelling was actually a MRSA abscess and surrounding cellulitis, an unusual presentation for lip infection, which we discuss below. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Misidentifying MRSA lip infection for angioedema, with a delay in proper treatment, could result in serious morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A case of giant nodular posterior scleritis mimicking choroidal malignancy.

    Science.gov (United States)

    Liu, Andrea T; Luk, Fiona O; Chan, Carmen K

    2015-12-01

    To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biopsy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure.

  2. Enterobiasis in Ectopic Locations Mimicking Tumor-Like Lesions

    Directory of Open Access Journals (Sweden)

    Silvio Pampiglione

    2009-01-01

    Full Text Available Both the clinical and the histopathological diagnostic difficulties of oxyuriasis in unusual sites and their importance from a clinical point of view are pointed out. The authors report two ectoptic cases of enterobiasis observed in Northern Italy, one located in a fallopian tube of a 57-year-old woman and the other in a perianal subcutaneous tissue of a 59-year-old man, mimicking tumor-like lesions. The authors take advantage of the occasion to focus the attention of the medical world on this subject, lamenting the scarce importance given to this parasitosis in university courses of medical schools and in medical textbooks as it is incorrectly considered “out-of-fashion.”

  3. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS....../AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients treated...

  4. A case of giant nodular posterior scleritis mimicking choroidal malignancy

    Directory of Open Access Journals (Sweden)

    Andrea T Liu

    2015-01-01

    Full Text Available To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biospy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure.

  5. Dilated Virchow–Robin spaces mimicking a brainstem arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Thomas J Buell

    2017-01-01

    Full Text Available Virchow–Robin spaces (VRS are ubiquitous and commonly observed as the resolution of magnetic resonance imaging (MRI continues to improve. The function of VRS and the etiology of their dilation is still a subject of research. Diagnosing dilated VRS (dVRS can be challenging because they may appear similar to other pathologies such as cystic neoplasms, infectious cysts, and even arteriovenous malformations (AVMs on certain MRI pulse sequences. We reported a unique case of brainstem dVRS mimicking an AVM. Furthermore, the extensive pontine involvement of our patient's lesion is rarely described in neurosurgical literature. Understanding the imaging characteristics of dVRS is critical to accurately diagnose these lesions and avoid unnecessary tests and procedures.

  6. Acute dystonic reaction leading to lingual hematoma mimicking angioedema

    Science.gov (United States)

    Sezer, Özgür; Aydin, Ali Attila; Bilge, Sedat; Arslan, Fatih; Arslan, Hasan

    2017-01-01

    Lingual hematoma is a severe situation, which is rare and endangers the airway. It can develop due to trauma, vascular abnormalities, and coagulopathy. Due to its sudden development, it can be clinically confused with angioedema. In patients who applied to the doctor with complaints of a swollen tongue, lingual hematoma can be confused with angioedema, in particular, at the beginning if the symptoms occurred after drug use. It should especially be considered that dystonia in the jaw can present as drug-induced hyperkinetic movement disorder. Early recognition of this rare clinical condition and taking precautions for providing airway patency are essential. In this case report, we will discuss mimicking angioedema and caused by a bite due to dystonia and separation of the tongue from the base of the mouth developing concurrently with lingual hematoma. PMID:29326495

  7. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Białek

    2016-12-01

    Full Text Available Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  8. Basaloid Carcinoma of the Breast Mimicking Cutaneous Basaloid Neoplasms.

    Science.gov (United States)

    Solus, Jason F; Goyal, Amrita; Duncan, Lyn M; Nazarian, Rosalynn M

    2015-09-01

    Basaloid carcinoma of the breast (BCB) is a rare, triple-negative aggressive primary breast tumor that can closely mimic cutaneous basal cell carcinoma (BCC), neuroendocrine tumors, adnexal neoplasms, and other primary breast tumors. Accurate diagnosis of this tumor is critical for appropriate clinical management. We add to the literature 2 female patients with BCB presenting with a nipple mass. Histopathologic findings from both patients showed dermal nests and cords of atypical basaloid cells with epidermal involvement, closely resembling cutaneous BCC. A panel of immunohistochemical stains, including the novel use of CK17, is essential for differentiating BCB from mimickers. BCB is a rare primary breast tumor that follows an aggressive clinical course and closely mimics many basaloid neoplasms, including cutaneous BCC clinicopathologically. Increased awareness of BCB among dermatologists and dermatopathologists is critical for accurate diagnosis and patient care.

  9. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  10. Postpartum Unilateral Sacral Stress Fracture Mimicking Lumbar Radiculopathy: Case Report

    Directory of Open Access Journals (Sweden)

    Sinan Bağçacı

    2018-01-01

    Full Text Available Postpartum sacral stress fracture is a very rare clinical entity. Because of the ambiguous clinical and radiological findings, it is often diagnosed late. A case of a postpartal 25-year-old female patient presented with acute onset of low back pain radiating to the right extremity, mimicking lumbar radiculopathy. Magnetic resonance imaging of sacrum revealed a non-displaced stress fracture of the right sacral ala. The 25-hydroxy vitamine D level of the patient was very low; dual energy X-ray absorptiometry measurements were in the normal range. The patient is completely cured as a result of conservative treatment. As a result, sacrum stress fracture should be kept in mind in the presence of back pain during pregnancy and postpartum period.

  11. A Case of Myopericarditis Mimicking Acute Myocardial Infarction in Childhood

    Directory of Open Access Journals (Sweden)

    Rahmi Özdemir

    2015-11-01

    Full Text Available Myopericarditis is an inflammatory disease of the both myocardial and pericardial tissues, and resulting from different etiologies. Viral agents such as coxsackie virus type B, adenovirus, and echovirus are the most common leading cause of this disease and it usually occurs following viral upper respiratory tract infections. Although there are different clinical features according to ages groups, some common findings such as tachycardia incompatible with fever, deeply heared heart sounds, and heart failure can be seen. Clinical findings often mimics a myocardial infarction. Diagnosis of this disease is made by the evaluation of the clinical condition, electrocardiography, echocardiography and elevation of the cardiac enzymes. Because it is mortality, discrimination of myopericarditis from myocardial infarction is very important. Herein, we report a 13 year-old-girl with the diagnosis of myopericarditis presenting with chest pain, electrocardiographic changes mimicking myocardial infarction and elevated cardiac enzymes and also aimed to emphasize the importance of accurate diagnosis of this disease.

  12. Cerebral metastases from malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, G. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Radiation Oncology Royal Prince Alfred Hospital, Sydney (Australia). Sydney Melanoma Unit); Firth, I. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Medical Oncology); Coates, A. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Radiation Oncology Royal Prince Alfred Hospital, Sydney (Australia). Sydney Melanoma Unit)

    1993-03-01

    A retrospective study was undertaken of factors affecting survival in 129 patients with cerebral metastases from malignant melanoma referred to the Department of Radiation Oncology from June '82-January '90. Their ages ranged from 19-83 years and the time interval form diagnosis of the primary tumour to development of cerebral metastases ranged from 1 month-17 years. Cerebral metastases were apparently solitary in 59 (46%) and multiple in 70 (54%) patients. Craniotomy with resection of tumour was performed in 49 patients, of whom 24 had a solitary cerebral metastasis as the only evidence of disease Most patients (94%) received radiotherapy-course. Median survival of the whole group after detection of cerebral metastases was 5 months (range <1-87+). Univariate analysis indicated that a solitary cerebral metastasis, absence of extracranial disease and tumour resection predicted improved survival, but only surgical intervention was of independent prognostic significance in a multivariate analysis. The effect of cranial irradiation on survival could not be assessed, but the dose of radiation did not influence survival. Of the 10 patients who survived for more than 2 years, 8 had total resection of a solitary cerebral metastasis. (author). 25 refs., 3 figs., 3 tabs.

  13. [Disseminated histoplamosis in adolescent mimicking granulomatosis with polyangiitis].

    Science.gov (United States)

    van Weelden, Marlon; Viola, Gabriela R; Kozu, Katia T; Aikawa, Nadia E; Ivo, Claudia M; Silva, Clovis A

    2015-03-04

    Systemic histoplasmosis is an invasive fungal infection that may mimic primary vasculitis, particularly granulomatosis with polyangiitis (GPA), and was rarely described in adult patients. We reported an immunocompetent patient with disseminated histoplasmosis mimicking GPA who fulfilled European League Against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organisation (PRINTO)/Pediatric Rheumatology European Society (PRES) validated classification criteria. A 6-year old boy presented acute migratory polyarthritis with spontaneous improvement, sinus inflammation, fever, headache and abdominal pain. Serologic test for hepatitis, cytomegalovirus, human immunodeficiency virus, Epstein-Barr virus, toxoplasmosis, dengue virus and antistreptolysin O were all negative. Magnetic resonance imaging (MRI) showed moderate ascites in pelvis and pansinusitis. Antineutrophil cytoplasmic antibodies (c-ANCA) were positive. He had spontaneous remission of the symptoms including fever. At the age of 11 years and 11 months, he had sinusitis, pneumonia and epididymitis. A month later, he was hospitalized and MRI showed left eye proptosis. Cerebrospinal fluid was normal and indirect tests of fungi were negative. Two months later, he had lumbar pain and computer tomography showed a mass in the right kidney and pulmonary nodule in the right lung. He fulfilled EULAR/PRINTO/PRES criteria for GPA, however the renal biopsy showed a focal granulomatous interstitial nephritis with yeast fungal cells compatible with Histoplasma sp. He was treated with liposomal amphotericin B and itraconazole with improvement of signs and symptoms. We reported a progressive disseminated histoplasmosis case mimicking GPA. Histoplasmosis infection should be considered in immunocompetent subjects with uncommon clinical manifestations, such as arthritis, nephritis and epididymitis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  14. A natural biomimetic porous medium mimicking hypomineralized enamel.

    Science.gov (United States)

    Vennat, E; Denis, M; David, B; Attal, J-P

    2015-03-01

    In order to evaluate the clinical impact of low viscosity resin infiltration in hypomineralized enamel, it is necessary to obtain a biomimetic porous substrate capable of mimicking enamel. The specifications for the biomimetic porous medium are defined using the literature data on hypomineralized enamel. Based on these specifications, we propose to use deproteinized dentin, the latter being deproteinized by heat treatment. Thermogravimetry analysis (TGA), field emission scanning electron microscopy (FESEM) observations, mercury intrusion porosimetry (MIP) tests and nanoindentation are performed on the deproteinized dentin tissue. Heat treatment is shown to be an effective and reproducible method for removing organic fluids and protein residues in dentin. Deproteinizing dentin also enables forming nanovoids by eliminating its organic matrix. The interconnected open nanoporosities (porosities of less than 100 nm) created at 600°C are distributed between 14 nm and 32 nm and the total porosity is 39% (including 36% due to nanoporosities). At 800°C, they are distributed between 60 nm and 100 nm and total porosity is 37% (including 33% arising from the nanoporosities). The hydroxyapatite crystal structure is transformed less at 600°C, so this temperature should be preferred. Besides providing new understanding of the dentin tissue itself, this study led to characterizing a porous medium made of natural apatite, and proposing and validating its use as a porous medium mimicking hypomineralized enamel. The next logical step of this study is the characterization of resin infiltration in this medium and its mechanical reinforcement. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  15. Teflon granulomas mimicking cerebellopontine angle tumors following microvascular decompression.

    Science.gov (United States)

    Deep, Nicholas L; Graffeo, Christopher S; Copeland, William R; Link, Michael J; Atkinson, John L; Neff, Brian A; Raghunathan, Aditya; Carlson, Matthew L

    2017-03-01

    To report two patients with a history of microvascular decompression (MVD) for hemifacial spasm who presented with Teflon granulomas (TG) mimicking cerebellopontine angle (CPA) tumors and to perform a systematic review of the English-language literature. Case series at a single tertiary academic referral center and systematic review. Retrospective chart review with analysis of clinical, radiological, and histopathological findings. Systematic review using PubMed, Embase, MEDLINE, and Web of Science databases. Two patients with large skull base TGs mimicking CPA tumors clinically and radiographically were managed at the authors' institution. The first presented 4 years after MVD with asymmetrical sensorineural hearing loss, multiple progressive cranial neuropathies, and brainstem edema due to a growing TG. Reoperation with resection of the granuloma confirmed a foreign-body reaction consisting of multinucleated giant cells containing intracytoplasmic Teflon particles. The second patient presented 11 years after MVD with asymmetrical sensorineural hearing loss and recurrent hemifacial spasm. No growth was noted over 2 years, and the patient has been managed expectantly. Only one prior case of TG after MVD for hemifacial spasm has been reported in the English literature. TG is a rare complication of MVD for hemifacial spasm. The diagnosis should be suspected in patients presenting with a new-onset enhancing mass of the CPA after MVD, even when performed decades earlier. A thorough clinical and surgical history is critical toward establishing an accurate diagnosis to guide management and prevent unnecessary morbidity. Surgical intervention is not required unless progressive neurologic complications ensue. 4 Laryngoscope, 127:715-719, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Radiation induced sarcoma after treatment of glioblastoma: case report; Sarcoma radioinduzido pós-tratamento de glioblastoma: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, Victor Domingos Lisita; Anjos, Caroline Souza dos; Candido, Priscila Barile Marchi; Dias Junior, Antonio Soares; Santos, Evandro Airton Sordi dos; Godoy, Antonio Carlos Cavalcante; Saggioro, Fabiano P.; Carlotti Junior, Carlos Gilberto; Oliveira, Harley Francisco de; Peria, Fernanda Maris, E-mail: fernandaperia@fmrp.usp.br, E-mail: victor_lisita@yahoo.com.br, E-mail: carolinesanjos@gmail.com, E-mail: priscilabarile@yahoo.com.br [Universidade de Sao Paulo (USP), Ribeirão Preto, SP (Brazil). Hospital das Clinicas

    2016-07-01

    Introduction: Glioblastoma multiform is the most lethal central nervous system neoplasm, with a median survival of around 13 months and the worst prognosis among all gliomas. The therapeutic approach of glioblastoma consists in neurosurgery with maximum possible resection of tumor volume, followed by radiotherapy and chemotherapy. Radiotherapy reduces the risk of tumor recurrence through direct and indirect damage to tumor deoxyribonucleic acid. The long-term effects of radiation therapy include tissue necrosis, vasculopathy, and radiation-induced neoplasia. The most reported secondary intracranial malignant tumors include meningiomas, gliomas, and sarcomas. The latency period between skull radiotherapy and the appearance of radioinduced lesions varies in the literature from six months to 47 years, with an average of 18.7 years. Case report: The present report describes the appearance of high-grade spindle cell sarcoma after ten months in a patient who received glioblastoma treatment at Hospital das Clínicas of Ribeirão Preto of the University of São Paulo. Conclusion: The rarity of this association is probably due to the poor survival of patients with glioblastoma, thus limiting the time to development of secondary neoplasia.

  17. Natriuretic peptides and cerebral hemodynamics

    DEFF Research Database (Denmark)

    Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth

    2014-01-01

    in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases...... where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response...

  18. Cerebral Vasculitis Complicating Pneumococcal Meningitis

    Directory of Open Access Journals (Sweden)

    Ahmed Khedher

    2018-03-01

    Full Text Available Introduction: Cerebral vasculitis is an uncommon life-threatening complication of community-acquired bacterial meningitis. Patient and methods: We report the case of a 64-year-old woman with pneumococcal meningitis who developed parainfectious vasculitis causing ischaemic brain damage. Cerebral magnetic resonance imaging (MRI confirmed the diagnosis. Clinical and radiological recovery after delayed addition of corticosteroid was achieved. Discussion: This report shows that the onset of neurological deficits following pneumococcal meningitis can be caused by cerebral vasculitis. Underdosing with antibiotics and delayed adjunctive dexamethasone seem to favour this complication. There are no guidelines for treatment but high doses of steroids led to resolution in this case.

  19. 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...

  20. Cerebral white matter hypoplasia

    International Nuclear Information System (INIS)

    Dietrich, R.B.; Shields, W.D.; Sankar, R.

    1990-01-01

    This paper demonstrates the MR imaging findings in children with cerebral white matter hypoplasia (CWMH). The MR studies of four children, aged 3-7 y (mean age, 2.3 y) with a diagnosis of CWMH were reviewed. In all cases multiplanar T1-weighted and T2-weighted spin-echo images were obtained. All children had similar histories of severe developmental delay and nonprogressive neurologic deficits despite normal gestational and birth histories. In two cases there was a history of maternal cocaine abuse. Autopsy correlation was available in one child. The MR images of all four children demonstrated diffuse lack of white matter and enlarged ventricles but normal-appearing gray matter. The corpus callosum, although completely formed, was severely thinned. There was no evidence of gliosis or porencephaly, and the distribution of myelin deposition was normal for age in all cases. Autopsy finding in one child correlated exactly with the MR finding

  1. Cerebral toxoplasmosis in AIDS

    International Nuclear Information System (INIS)

    Christ, F.; Steudel, H.; Klotz, D.; Bonn Univ.; Bonn Univ.

    1986-01-01

    Since 1982 (Hauser and co-workers), literature has reported focal cerebral tissue charges in AIDS patients whose diagnosis was unclear at first but which could be identified finally as florid toxoplasmosis encephalitis by biopsy and autopsy. It was found that the value of otherwise reliable serological tests (KBR, Sabin-Feldmann tests, etc.) is questionable in patients with severely impaired or incompetent immune systems, and, in particular, that a negative or uncharacteristic test result may not preclude any opportunistic infection process. Furthermore, isolation of Toxoplasma gondii or specific antibodies from the cerebrospinal fluid will be successful in exceptional cases only. In patients with AIDS or lymphadenopathy syndrome, the differential diagnosis will have to include - first and foremost - reactivated toxoplasma infection (not newly acquired, as a rule) if central neurological symptoms occur. (orig.) [de

  2. Temozolomide during radiotherapy of glioblastoma multiforme. Daily administration improves survival

    Energy Technology Data Exchange (ETDEWEB)

    Nachbichler, Silke Birgit; Schupp, Gabi; Ballhausen, Hendrik; Niyazi, Maximilian; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany)

    2017-11-15

    Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m{sup 2}) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1-year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration. (orig.) [German] Eine Temozolomid-(TMZ-)basierte Radiochemotherapie ist der gegenwaertige Goldstandard in der Behandlung von neu diagnostizierten Glioblastomen. Daten bezueglich des Einflusses der TMZ-Dosisdichte waehrend der Radiochemotherapie sind derzeit nicht vorhanden. Wir haben retrospektiv die Ergebnisse von Patienten verglichen, die entweder kein TMZ, TMZ zur Strahlentherapie nur an Bestrahlungstagen oder TMZ konstant 7 Tage/Woche erhalten hatten. Von 2002-2012 bekamen insgesamt 432 Patienten mit

  3. Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy.

    Science.gov (United States)

    Natsumeda, Manabu; Motohashi, Kunio; Igarashi, Hironaka; Nozawa, Takanori; Abe, Hideaki; Tsukamoto, Yoshihiro; Ogura, Ryosuke; Okada, Masayasu; Kobayashi, Tsutomu; Aoki, Hiroshi; Takahashi, Hitoshi; Kakita, Akiyoshi; Okamoto, Kouichirou; Nakada, Tsutomu; Fujii, Yukihiko

    2017-09-27

    We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

  4. The prognostic IDH1( R132 ) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma

    NARCIS (Netherlands)

    Bleeker, Fonnet E.; Atai, Nadia A.; Lamba, Simona; Jonker, Ard; Rijkeboer, Denise; Bosch, Klazien S.; Tigchelaar, Wikky; Troost, Dirk; Vandertop, W. Peter; Bardelli, Alberto; van Noorden, Cornelis J. F.

    2010-01-01

    Somatic mutations in the isocitrate dehydrogenase 1 gene (IDH1) occur at high frequency in gliomas and seem to be a prognostic factor for survival in glioblastoma patients. In our set of 98 glioblastoma patients, IDH1 ( R132 ) mutations were associated with improved survival of 1 year on average,

  5. Diamond, graphite, and graphene oxide nanoparticles decrease migration and invasiveness in glioblastoma cell lines by impairing extracellular adhesion

    DEFF Research Database (Denmark)

    Wierzbicki, Mateusz; Jaworski, Slawomir; Kutwin, Marta

    2017-01-01

    The highly invasive nature of glioblastoma is one of the most significant problems regarding the treatment of this tumor. Diamond nanoparticles (ND), graphite nanoparticles (NG), and graphene oxide nanoplatelets (nGO) have been explored for their biomedical applications, especially for drug...... that nanoparticles could be used in biomedical applications as a low toxicity active compound for glioblastoma treatment....

  6. Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness.

    Science.gov (United States)

    Bogeas, Alexandra; Morvan-Dubois, Ghislaine; El-Habr, Elias A; Lejeune, François-Xavier; Defrance, Matthieu; Narayanan, Ashwin; Kuranda, Klaudia; Burel-Vandenbos, Fanny; Sayd, Salwa; Delaunay, Virgile; Dubois, Luiz G; Parrinello, Hugues; Rialle, Stéphanie; Fabrega, Sylvie; Idbaih, Ahmed; Haiech, Jacques; Bièche, Ivan; Virolle, Thierry; Goodhardt, Michele; Chneiweiss, Hervé; Junier, Marie-Pierre

    2018-02-01

    Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity. Immunohistochemistry confirmed ARNT2 expression in cell sub-populations within proliferative zones of patients' glioblastoma. Decreased ARNT2 expression was consistently observed in non-tumorigenic glioblastoma cells, compared to tumorigenic cells. Moreover, ARNT2 expression correlated with a tumorigenic molecular signature at both the tissue level within the tumor core and at the single cell level in the patients' tumors. We found that ARNT2 knockdown decreased the expression of SOX9, POU3F2 and OLIG2, transcription factors implicated in glioblastoma cell tumorigenicity, and repressed glioblastoma stem-like cell tumorigenic properties in vivo. Our results reveal ARNT2 as a pivotal component of the glioblastoma cell tumorigenic signature, located at a node of a transcription factor network controlling glioblastoma cell aggressiveness.

  7. Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas

    International Nuclear Information System (INIS)

    Kaaijk, P.; Academic Medical Center, Amsterdam; Troost, D.; Leenstra, S.; Bosch, D.A.; Sminia, P.; Hulshof, M.C.C.M..; Kracht, A.H.W. van der

    1997-01-01

    The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastomas patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas. (author)

  8. The role of IDH1 mutated tumour cells in secondary glioblastomas: an evolutionary game theoretical view

    Science.gov (United States)

    Basanta, David; Scott, Jacob G.; Rockne, Russ; Swanson, Kristin R.; Anderson, Alexander R. A.

    2011-02-01

    Recent advances in clinical medicine have elucidated two significantly different subtypes of glioblastoma which carry very different prognoses, both defined by mutations in isocitrate dehydrogenase-1 (IDH-1). The mechanistic consequences of this mutation have not yet been fully clarified, with conflicting opinions existing in the literature; however, IDH-1 mutation may be used as a surrogate marker to distinguish between primary and secondary glioblastoma multiforme (sGBM) from malignant progression of a lower grade glioma. We develop a mathematical model of IDH-1 mutated secondary glioblastoma using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolytic cells. Our model recapitulates glioblastoma behavior well and is able to reproduce two recent experimental findings, as well as make novel predictions concerning the rate of invasive growth as a function of vascularity, and fluctuations in the proportions of phenotypic populations that a glioblastoma will experience under different microenvironmental constraints.

  9. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Science.gov (United States)

    Nitta, Masayuki; Kozono, David; Kennedy, Richard; Stommel, Jayne; Ng, Kimberly; Zinn, Pascal O; Kushwaha, Deepa; Kesari, Santosh; Inda, Maria-del-Mar; Wykosky, Jill; Furnari, Frank; Hoadley, Katherine A; Chin, Lynda; DePinho, Ronald A; Cavenee, Webster K; D'Andrea, Alan; Chen, Clark C

    2010-05-24

    Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  10. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Directory of Open Access Journals (Sweden)

    Masayuki Nitta

    Full Text Available Despite the critical role of Epidermal Growth Factor Receptor (EGFR in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER genes required for the repair of Reactive Oxygen Species (ROS-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1. Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  11. Molecular Mechanisms of Fenofibrate-Induced Metabolic Catastrophe and Glioblastoma Cell Death

    Science.gov (United States)

    Wilk, Anna; Wyczechowska, Dorota; Zapata, Adriana; Dean, Matthew; Mullinax, Jennifer; Marrero, Luis; Parsons, Christopher; Peruzzi, Francesca; Culicchia, Frank; Ochoa, Augusto; Grabacka, Maja

    2014-01-01

    Fenofibrate (FF) is a common lipid-lowering drug and a potent agonist of the peroxisome proliferator-activated receptor alpha (PPARα). FF and several other agonists of PPARα have interesting anticancer properties, and our recent studies demonstrate that FF is very effective against tumor cells of neuroectodermal origin. In spite of these promising anticancer effects, the molecular mechanism(s) of FF-induced tumor cell toxicity remains to be elucidated. Here we report a novel PPARα-independent mechanism explaining FF's cytotoxicity in vitro and in an intracranial mouse model of glioblastoma. The mechanism involves accumulation of FF in the mitochondrial fraction, followed by immediate impairment of mitochondrial respiration at the level of complex I of the electron transport chain. This mitochondrial action sensitizes tested glioblastoma cells to the PPARα-dependent metabolic switch from glycolysis to fatty acid β-oxidation. As a consequence, prolonged exposure to FF depletes intracellular ATP, activates the AMP-activated protein kinase–mammalian target of rapamycin–autophagy pathway, and results in extensive tumor cell death. Interestingly, autophagy activators attenuate and autophagy inhibitors enhance FF-induced glioblastoma cytotoxicity. Our results explain the molecular basis of FF-induced glioblastoma cytotoxicity and reveal a new supplemental therapeutic approach in which intracranial infusion of FF could selectively trigger metabolic catastrophe in glioblastoma cells. PMID:25332241

  12. The role of IDH1 mutated tumour cells in secondary glioblastomas: an evolutionary game theoretical view

    International Nuclear Information System (INIS)

    Basanta, David; Scott, Jacob G; Anderson, Alexander R A; Rockne, Russ; Swanson, Kristin R

    2011-01-01

    Recent advances in clinical medicine have elucidated two significantly different subtypes of glioblastoma which carry very different prognoses, both defined by mutations in isocitrate dehydrogenase-1 (IDH-1). The mechanistic consequences of this mutation have not yet been fully clarified, with conflicting opinions existing in the literature; however, IDH-1 mutation may be used as a surrogate marker to distinguish between primary and secondary glioblastoma multiforme (sGBM) from malignant progression of a lower grade glioma. We develop a mathematical model of IDH-1 mutated secondary glioblastoma using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolytic cells. Our model recapitulates glioblastoma behavior well and is able to reproduce two recent experimental findings, as well as make novel predictions concerning the rate of invasive growth as a function of vascularity, and fluctuations in the proportions of phenotypic populations that a glioblastoma will experience under different microenvironmental constraints

  13. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  14. Identification of a novel fusion gene HMGA2-EGFR in glioblastoma.

    Science.gov (United States)

    Komuro, Akiyoshi; Raja, Erna; Iwata, Caname; Soda, Manabu; Isogaya, Kazunobu; Yuki, Keiko; Ino, Yasushi; Morikawa, Masato; Todo, Tomoki; Aburatani, Hiroyuki; Suzuki, Hiromichi; Ranjit, Melissa; Natsume, Atsushi; Mukasa, Akitake; Saito, Nobuhito; Okada, Hitoshi; Mano, Hiroyuki; Miyazono, Kohei; Koinuma, Daizo

    2018-04-15

    Glioblastoma is one of the most malignant forms of cancer, for which no effective targeted therapy has been found. Although The Cancer Genome Atlas has provided a list of fusion genes in glioblastoma, their role in progression of glioblastoma remains largely unknown. To search for novel fusion genes, we obtained RNA-seq data from TGS-01 human glioma-initiating cells, and identified a novel fusion gene (HMGA2-EGFR), encoding a protein comprising the N-terminal region of the high-mobility group AT-hook protein 2 (HMGA2) fused to the C-terminal region of epidermal growth factor receptor (EGFR), which retained the transmembrane and kinase domains of the EGFR. This fusion gene product showed transforming potential and a high tumor-forming capacity in cell culture and in vivo. Mechanistically, HMGA2-EGFR constitutively induced a higher level of phosphorylated STAT5B than EGFRvIII, an in-frame exon deletion product of the EGFR gene that is commonly found in primary glioblastoma. Forced expression of HMGA2-EGFR enhanced orthotopic tumor formation of the U87MG human glioma cell line. Furthermore, the EGFR kinase inhibitor erlotinib blocked sphere formation of TGS-01 cells in culture and inhibited tumor formation in vivo. These findings suggest that, in addition to gene amplification and in-frame exon deletion, EGFR signaling can also be activated by gene fusion, suggesting a possible avenue for treatment of glioblastoma. © 2017 UICC.

  15. Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship

    Science.gov (United States)

    Kim, Hyunsoo; Huang, Wei; Jiang, Xiuli; Pennicooke, Brenton; Park, Peter J.; Johnson, Mark D.

    2010-01-01

    Using a multidimensional genomic data set on glioblastoma from The Cancer Genome Atlas, we identified hsa-miR-26a as a cooperating component of a frequently occurring amplicon that also contains CDK4 and CENTG1, two oncogenes that regulate the RB1 and PI3 kinase/AKT pathways, respectively. By integrating DNA copy number, mRNA, microRNA, and DNA methylation data, we identified functionally relevant targets of miR-26a in glioblastoma, including PTEN, RB1, and MAP3K2/MEKK2. We demonstrate that miR-26a alone can transform cells and it promotes glioblastoma cell growth in vitro and in the mouse brain by decreasing PTEN, RB1, and MAP3K2/MEKK2 protein expression, thereby increasing AKT activation, promoting proliferation, and decreasing c-JUN N-terminal kinase-dependent apoptosis. Overexpression of miR-26a in PTEN-competent and PTEN-deficient glioblastoma cells promoted tumor growth in vivo, and it further increased growth in cells overexpressing CDK4 or CENTG1. Importantly, glioblastoma patients harboring this amplification displayed markedly decreased survival. Thus, hsa-miR-26a, CDK4, and CENTG1 comprise a functionally integrated oncomir/oncogene DNA cluster that promotes aggressiveness in human cancers by cooperatively targeting the RB1, PI3K/AKT, and JNK pathways. PMID:20080666

  16. Antiproliferative effects of Tubi-bee propolis in glioblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Kleiton Silva Borges

    2011-01-01

    Full Text Available Propolis is a resin formed by a complex chemical composition of substances that bees collect from plants. Since ancient times, propolis has been used in folk medicine, due to its biological properties, that include antimicrobial, anti-inflammatory, antitumoral and immunomodulatory activities. Glioblastoma is the most common human brain tumor. Despite the improvements in GBM standard treatment, patients' prognosis is still very poor. The aim of this work was to evaluate in vitro the Tubi-bee propolis effects on human glioblastoma (U251 and U343 and fibroblast (MRC-5 cell lines. Proliferation, clonogenic capacity and apoptosis were analyzed after treatment with 1 mg/mL and 2 mg/mL propolis concentrations for different time periods. Additionally, glioblastoma cell lines were submitted to treatment with propolis combined with temozolomide (TMZ. Data showed an antiproliferative effect of tubi-bee propolis against glioblastoma and fibroblast cell lines. Combination of propolis with TMZ had a synergic antiproliferative effect. Moreover, propolis caused decrease in colony formation in glioblastoma cell lines. Propolis treatment had no effects on apoptosis, demonstrating a cytostatic action. Further investigations are needed to elucidate the molecular mechanism of the antitumor effect of propolis, and the study of its individual components may reveal specific molecules with antiproliferative capacity.

  17. Targeting Oncogenic ALK and MET: A Promising Therapeutic Strategy for Glioblastoma

    Science.gov (United States)

    Wallace, Gerald C; Dixon-Mah, Yaenette N; Vandergrift, W Alex; Ray, Swapan K; Haar, Catherine P; Mittendorf, Amber M; Patel, Sunil J; Banik, Naren L; Giglio, Pierre; Das, Arabinda

    2015-01-01

    Glioblastoma is the most common aggressive, highly glycolytic, and lethal brain tumor. In fact, it is among the most commonly diagnosed lethal malignancies, with thousands of new cases reported in the United States each year. Glioblastoma's lethality is derived from a number of factors including highly active pro-mitotic and pro-metastatic pathways. Two factors increasingly associated with the intracellular signaling and transcriptional machinery required for such changes are anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor (HGFR or, more commonly MET). Both receptors are members of the receptor tyrosine kinase (RTK) family, which has itself gained much attention for its role in modulating mitosis, migration, and survival in cancer cells. ALK was first described as a vital oncogene in lymphoma studies, but it has since been connected to many carcinomas, including non-small cell lung cancer and glioblastoma. As the receptor for HGF, MET has also been highly characterized and regulates numerous developmental and wound healing events which, when upregulated in cancer, can promote tumor progression. The wealth of information gathered over the last 30 years regarding these RTKs suggests three downstream cascades that depend upon activation of STAT3, Ras, and AKT. This review outlines the significance of ALK and MET as they relate to glioblastoma, explores the significance of STAT3, Ras, and AKT downstream of ALK/MET, and touches on the potential for new chemotherapeutics targeting ALK and MET to improve glioblastoma patient prognosis. PMID:23543207

  18. Pseudoprogression as an adverse event of glioblastoma therapy.

    Science.gov (United States)

    Balaña, Carmen; Capellades, Jaume; Pineda, Estela; Estival, Anna; Puig, Josep; Domenech, Sira; Verger, Eugenia; Pujol, Teresa; Martinez-García, Maria; Oleaga, Laura; Velarde, JoseMaria; Mesia, Carlos; Fuentes, Rafael; Marruecos, Jordi; Del Barco, Sonia; Villà, Salvador; Carrato, Cristina; Gallego, Oscar; Gil-Gil, Miguel; Craven-Bartle, Jordi; Alameda, Francesc

    2017-12-01

    We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5-fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606-7.564; P = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; P = 0.0001) but was similar for PsP and nP patients (P = 0.91). OS was shorter-though not significantly so-for PsP than nP patients (OS: 19.5 vs. 27.9 months; P = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P = 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.

    Science.gov (United States)

    Skardelly, Marco; Dangel, Elena; Gohde, Julia; Noell, Susan; Behling, Felix; Lepski, Guilherme; Borchers, Christian; Koch, Marilin; Schittenhelm, Jens; Bisdas, Sotirios; Naumann, Aline; Paulsen, Frank; Zips, Daniel; von Hehn, Ulrike; Ritz, Rainer; Tatagiba, Marcos Soares; Tabatabai, Ghazaleh

    2017-05-01

    The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p  = .46). Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in

  20. Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

    International Nuclear Information System (INIS)

    Iliadis, Georgios; Kotoula, Vassiliki; Chatzisotiriou, Athanasios; Televantou, Despina; Eleftheraki, Anastasia G; Lambaki, Sofia; Misailidou, Despina; Selviaridis, Panagiotis; Fountzilas, George

    2012-01-01

    In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O 6 -methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore

  1. Unsupervised deep learning reveals prognostically relevant subtypes of glioblastoma.

    Science.gov (United States)

    Young, Jonathan D; Cai, Chunhui; Lu, Xinghua

    2017-10-03

    One approach to improving the personalized treatment of cancer is to understand the cellular signaling transduction pathways that cause cancer at the level of the individual patient. In this study, we used unsupervised deep learning to learn the hierarchical structure within cancer gene expression data. Deep learning is a group of machine learning algorithms that use multiple layers of hidden units to capture hierarchically related, alternative representations of the input data. We hypothesize that this hierarchical structure learned by deep learning will be related to the cellular signaling system. Robust deep learning model selection identified a network architecture that is biologically plausible. Our model selection results indicated that the 1st hidden layer of our deep learning model should contain about 1300 hidden units to most effectively capture the covariance structure of the input data. This agrees with the estimated number of human transcription factors, which is approximately 1400. This result lends support to our hypothesis that the 1st hidden layer of a deep learning model trained on gene expression data may represent signals related to transcription factor activation. Using the 3rd hidden layer representation of each tumor as learned by our unsupervised deep learning model, we performed consensus clustering on all tumor samples-leading to the discovery of clusters of glioblastoma multiforme with differential survival. One of these clusters contained all of the glioblastoma samples with G-CIMP, a known methylation phenotype driven by the IDH1 mutation and associated with favorable prognosis, suggesting that the hidden units in the 3rd hidden layer representations captured a methylation signal without explicitly using methylation data as input. We also found differentially expressed genes and well-known mutations (NF1, IDH1, EGFR) that were uniquely correlated with each of these clusters. Exploring these unique genes and mutations will allow us to

  2. Treatment options and outcomes for glioblastoma in the elderly patient

    Directory of Open Access Journals (Sweden)

    Arvold ND

    2014-02-01

    Full Text Available Nils D Arvold,1 David A Reardon2 1Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA; 2Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA Abstract: Age remains the most powerful prognostic factor among glioblastoma (GBM patients. Half of all patients with GBM are aged 65 years or older at the time of diagnosis, and the incidence rate of GBM in patients aged over 65 years is increasing rapidly. Median survival for elderly GBM patients is less than 6 months and reflects less favorable tumor biologic factors, receipt of less aggressive care, and comorbid disease. The standard of care for elderly GBM patients remains controversial. Based on limited data, extensive resection appears to be more beneficial than biopsy. For patients with favorable Karnofsky performance status (KPS, adjuvant radiotherapy (RT has a demonstrated survival benefit with no observed decrement in quality of life. Concurrent and adjuvant temozolomide (TMZ along with RT to 60 Gy have not been prospectively studied among patients aged over 70 years but should be considered for patients aged 65–70 years with excellent KPS. Based on the recent NOA-08 and Nordic randomized trials, testing for O6-methylguanine-DNA-methyltransferase (MGMT promoter methylation should be performed routinely immediately after surgery to aid in adjuvant treatment decisions. Patients aged over 70 years with favorable KPS, or patients aged 60–70 years with borderline KPS, should be considered for monotherapy utilizing standard TMZ dosing for patients with MGMT-methylated tumors, and hypofractionated RT (34 Gy in ten fractions or 40 Gy in 15 fractions for patients with MGMT-unmethylated tumors. The ongoing European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial will help clarify the role for concurrent TMZ with hypofractionated RT. For elderly patients with poor KPS, reasonable

  3. Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

    Directory of Open Access Journals (Sweden)

    Iliadis Georgios

    2012-01-01

    Full Text Available Abstract Background In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. Methods We prospectively analyzed 65 patients suffering from glioblastoma (GBM who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy. The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA, for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. Results In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS (p = 0.023 and for preoperative necrosis on progression-free survival (PFS (p = 0.030. Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5% evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei was inversely associated with pre-operative tumor necrosis (p = 0.021. Conclusions Our findings implicate that volumetric parameters may have a significant role in

  4. Glioblastoma: a pathogenic crosstalk between tumor cells and pericytes.

    Directory of Open Access Journals (Sweden)

    Elisabetta M Caspani

    Full Text Available Cancers likely originate in progenitor zones containing stem cells and perivascular stromal cells. Much evidence suggests stromal cells play a central role in tumor initiation and progression. Brain perivascular cells (pericytes are contractile and function normally to regulate vessel tone and morphology, have stem cell properties, are interconvertible with macrophages and are involved in new vessel formation during angiogenesis. Nevertheless, how pericytes contribute to brain tumor infiltration is not known. In this study we have investigated the underlying mechanism by which the most lethal brain cancer, Glioblastoma Multiforme (GBM interacts with pre-existing blood vessels (co-option to promote tumor initiation and progression. Here, using mouse xenografts and laminin-coated silicone substrates, we show that GBM malignancy proceeds via specific and previously unknown interactions of tumor cells with brain pericytes. Two-photon and confocal live imaging revealed that GBM cells employ novel, Cdc42-dependent and actin-based cytoplasmic extensions, that we call flectopodia, to modify the normal contractile activity of pericytes. This results in the co-option of modified pre-existing blood vessels that support the expansion of the tumor margin. Furthermore, our data provide evidence for GBM cell/pericyte fusion-hybrids, some of which are located on abnormally constricted vessels ahead of the tumor and linked to tumor-promoting hypoxia. Remarkably, inhibiting Cdc42 function impairs vessel co-option and converts pericytes to a phagocytic/macrophage-like phenotype, thus favoring an innate immune response against the tumor. Our work, therefore, identifies for the first time a key GBM contact-dependent interaction that switches pericyte function from tumor-suppressor to tumor-promoter, indicating that GBM may harbor the seeds of its own destruction. These data support the development of therapeutic strategies directed against co-option (preventing

  5. New perspective for GdNCT. Gd-DTPA reaches the nucleus of glioblastoma cells in culture and in vivo

    International Nuclear Information System (INIS)

    Stasio, G. de; Gilbert, B.; Frazer, B.H.

    2000-01-01

    We investigated the prospects of gadolinium as a neutron capture therapy agent by combining three independent techniques to study the uptake of Gd-DTPA in vitro, in cultured glioblastoma cells, and in vivo, in the glioblastoma tissue sections after injection of Gd-DTPA and tumor extraction. We show that gadolinium not only penetrates the plasma membrane of glioblastoma cells grown in culture, but we also observe a statistically significant higher concentration of Gd in the nucleus relative to the cytoplasm. For the in vivo experiments, Gd-DTPA was administered to 6 glioblastoma patients before neurosurgery. The extracted bioptic tissue was then analyzed with spectromictroscopy, showing Gd localized in the nuclei of glioblastoma cells in 5 patients out of the 6 analyzed. (author)

  6. Learn More About Cerebral Palsy

    Centers for Disease Control (CDC) Podcasts

    2008-03-30

    This podcast describes the causes, preventions, types, and signs and symptoms of cerebral palsy.  Created: 3/30/2008 by National Center on Birth Defects and Developmental Disabilities.   Date Released: 3/21/2008.

  7. Cerebral spinal fluid (CSF) collection

    Science.gov (United States)

    ... ency/article/003428.htm Cerebral spinal fluid (CSF) collection To use the sharing features on this page, please enable JavaScript. Cerebrospinal fluid (CSF) collection is a test to look at the fluid ...

  8. Cerebral Cavernous Malformation and Hemorrhage

    Science.gov (United States)

    ... Text Size: SMALL • LARGE Cerebral Cavernous Angioma and Hemorrhage By Jack Hoch; Reviewed by Dr. Issam Awad ... for years, the mechanism by which these lesions hemorrhage remains poorly understood. Hemorrhage Types Since cavernous angiomas ...

  9. Hydrocephalus in cerebral venous thrombosis

    NARCIS (Netherlands)

    Zuurbier, Susanna M.; van den Berg, René; Troost, Dirk; Majoie, Charles B.; Stam, Jan; Coutinho, Jonathan M.

    2015-01-01

    Increased intracranial pressure is common in cerebral venous thrombosis (CVT), but hydrocephalus is rarely reported in these patients. We examined the frequency, pathophysiology and associated clinical manifestations of hydrocephalus in patients with CVT admitted to our hospital between 2000 and

  10. Influência do gene PTEN na expressão de RAD51 e suas parálogas, RAD51C e RAD51B, em linhagens de glioblastoma multiforme tratadas com etoposídeo

    OpenAIRE

    Ana Clara Oliveira

    2016-01-01

    O Glioblastoma Multiforme (GBM) é o tipo de tumor cerebral maligno com maior incidência na população. A perda do gene PTEN (fosfatase e tensina homóloga) é uma alteração comum associada ao GBM (até 60%) e esse gene codifica uma enzima que antagoniza a ação de PI3K, inibindo a fosforilação de AKT e, desse modo, regulando vias de sinalização relativas à sobrevivência celular e proliferação. Mutações em PTEN têm sido associadas à instabilidade genômica e ao aumento no número de quebras de fita d...

  11. Cerebral candidiasis. Computed tomography appearance

    International Nuclear Information System (INIS)

    Chaabane, M.; Ladeb, M.F.; Bouhaouala, M.H.; Ben Hammouda, M.; Ataalah, R.; Gannouni, A.; Krifa, H.

    1989-01-01

    A three year old child who had been suffering from oral candidiasis since the age of 1 year presented with osteitis of the clavicle, 2 cerebral frontal abscesses and an occipital abscess which extended across the calvaria and was associated with osteolysis. Histological and microbiological studies following surgery confirmed the diagnosis of candidiasis in this girl who was found to have IgA immunodefinciency. The authors report the computed tomographic appearance of the cerebral lesions and review the literature. (orig.)

  12. Cerebral candidiasis. Computed tomography appearance

    Energy Technology Data Exchange (ETDEWEB)

    Chaabane, M.; Ladeb, M.F.; Bouhaouala, M.H.; Ben Hammouda, M.; Ataalah, R.; Gannouni, A.; Krifa, H.

    1989-07-01

    A three year old child who had been suffering from oral candidiasis since the age of 1 year presented with osteitis of the clavicle, 2 cerebral frontal abscesses and an occipital abscess which extended across the calvaria and was associated with osteolysis. Histological and microbiological studies following surgery confirmed the diagnosis of candidiasis in this girl who was found to have IgA immunodefinciency. The authors report the computed tomographic appearance of the cerebral lesions and review the literature. (orig.).

  13. Parálisis cerebral :

    OpenAIRE

    Giral Lamenca, Mónica

    2015-01-01

    Se aborda el tema de la parálisis cerebral definiendo qué es, clasificando los tipos de parálisis dependiendo de la afectación y las características principales. Se explican algunos de sus tratamientos, se dan sistemas alternativos y/o aumentativos de comunicación para un alumno con PC (parálisis cerebral).

  14. Response Assessment in Neuro-Oncology criteria, contrast enhancement and perfusion MRI for assessing progression in glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tensaouti, Fatima [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); Khalifa, Jonathan [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Lusque, Amelie [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Biostatistics, Toulouse (France); Plas, Benjamin [CHU Toulouse, Department of Neurosurgery, Toulouse (France); Lotterie, Jean Albert; Berry, Isabelle [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); CHU Toulouse, Department of Nuclear Medicine, Toulouse (France); Laprie, Anne [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Cohen-Jonathan Moyal, Elizabeth [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Toulouse Center for Cancer Research (U1037), Inserm, Toulouse (France); Lubrano, Vincent [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); CHU Toulouse, Department of Neurosurgery, Toulouse (France)

    2017-10-15

    The purpose of the study was to evaluate Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma multiforme (GBM), with respect to the Macdonald criteria and changes in contrast-enhancement (CE) volume. Related variations in relative cerebral blood volume (rCBV) were investigated. Forty-three patients diagnosed between 2006 and 2010 were included. All underwent surgical resection, followed by temozolomide-based chemoradiation. MR images were retrospectively reviewed. Times to progression (TTPs) according to RANO criteria, Macdonald criteria and increased CE volume (CE-3D) were compared, and the percentage change in the 75th percentile of rCBV (rCBV75) was evaluated. After a median follow-up of 22.7 months, a total of 39 patients had progressed according to RANO criteria, 32 according to CE-3D, and 42 according to Macdonald. Median TTPs were 6.4, 9.3, and 6.6 months, respectively. Overall agreement was 79.07% between RANO and CE-3D and 93.02% between RANO and Macdonald. The mean percentage change in rCBV75 at RANO progression onset was over 73% in 87.5% of patients. In conclusion, our findings suggest that CE-3D criterion is not yet suitable to assess progression in routine clinical practice. Indeed, the accurate threshold is still not well defined. To date, in our opinion, early detection of disease progression by RANO combined with advanced MRI imaging techniques like MRI perfusion and diffusion remains the best way to assess disease progression. Further investigations that would examine the impact of treatment modifications after progression determined by different criteria on overall survival would be of great value. (orig.)

  15. Differentiation of solitary brain metastasis from glioblastoma multiforme: a predictive multiparametric approach using combined MR diffusion and perfusion

    International Nuclear Information System (INIS)

    Bauer, Adam Herman; Moser, Franklin G.; Maya, Marcel; Erly, William; Nael, Kambiz

    2015-01-01

    Solitary brain metastasis (MET) and glioblastoma multiforme (GBM) can appear similar on conventional MRI. The purpose of this study was to identify magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can differentiate MET from GBM. In this retrospective study, patients were included if they met the following criteria: underwent resection of a solitary enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) perfusion. Using co-registered images, voxel-based fractional anisotropy (FA), mean diffusivity (MD), K trans , and relative cerebral blood volume (rCBV) values were obtained in the enhancing tumor and non-enhancing peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting of GBM vs. MET. Twenty-three patients (14 M, age 32-78 years old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the enhancing tumor, rCBV, K trans , and FA were higher in GBM, whereas MD was lower, neither without statistical significance. In the NET2, rCBV was significantly higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA and K trans were higher in GBM, though not reaching significance. The best discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD, resulting in an area under the curve (AUC) of 0.98. The combination of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over solitary MET with diagnostic accuracy of 98 %. (orig.)

  16. Role of Redox Status in Development of Glioblastoma

    Science.gov (United States)

    Salazar-Ramiro, Aleli; Ramírez-Ortega, Daniela; Pérez de la Cruz, Verónica; Hérnandez-Pedro, Norma Y.; González-Esquivel, Dinora Fabiola; Sotelo, Julio; Pineda, Benjamín

    2016-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described. PMID:27199982

  17. Role of redox status in development of glioblastoma

    Directory of Open Access Journals (Sweden)

    Aleli eSalazar-Ramiro

    2016-04-01

    Full Text Available Glioblastoma (GBM is a highly aggressive neoplasia, prognosis remains dismal and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of ROS play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and pro-inflammatory environment involved in tumor cell proliferation, resistance and immune scape. In addition, are described some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM.

  18. A New Investigational Perspective for Purines Against Glioblastoma Invasiveness.

    Science.gov (United States)

    Giuliani, Patricia; Zuccarini, Mariachiara; Carluccio, Marzia; Ziberi, Sihana; Di Iorio, Patrizia; Caciagli, Francesco; Ciccarelli, Renata

    2018-02-26

    Glioblastoma multiforme (GBM) is the most common and lethal brain malignancy. Recent evidence suggests that the presence of stem-like cells (GSCs) inside the tumor with high self-renewal, resistance to chemotherapy and invasiveness/migration potential is associated with poor GBM prognosis. GSC aggressiveness seems to be linked to an important process involved in tumorigenesis and cancer metastasis called epithelial-to-mesenchymal transition (EMT), which is responsible for several biochemical changes and the acquisition of a more mesenchymal phenotype by GSCs, that enhance their migration, invasiveness and resistance to apoptosis. Since previous reports demonstrated that purines, interacting with their own receptors, exerted anti-tumor effects in GBM and derived cells, we tried to investigate the ability of these compounds to reduce tumor cell migration/invasion acting on EMT-associated genes/activators and/or signal pathways. Search in literature of relevant articles related to the objective. Papers examining the activity of purines on EMT signaling pathways/markers in GSCs are still few whereas literature is more abundant as for other kinds of tumors. Considering the significance of EMT in GBM aggressiveness and the promising involvement of purines in this process, we think that further research in this regard may open the way towards a new therapeutic approach for the control of GBM invasiveness/recurrence. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Recurrent glioblastoma: Current patterns of care in an Australian population.

    Science.gov (United States)

    Parakh, Sagun; Thursfield, Vicky; Cher, Lawrence; Dally, Michael; Drummond, Katharine; Murphy, Michael; Rosenthal, Mark A; Gan, Hui K

    2016-02-01

    This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, pera where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Investigation of platinum nanoparticle properties against U87 glioblastoma multiforme

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Slawomir

    2017-01-01

    and morphology of tumor tissue, but they also upregulated p53 and caspase-3 mRNA expression. Conclusions: The comparison between the effectiveness of glioblastoma treatment by NP-Pt vs cisplatin showed promising results for future studies. The results indicate that the properties of NP-Pt might be utilized......-Pt and cisplatin were compared through the morphology, viability, mortality, genotoxicity and the type of cell death of U87 glioma cells, the morphology and ultrastructure of glioma tumor, and expression of caspase-3, p53 and PCNA mRNA. Results: NP-Pt at concentrations of 0.14 μM/ml, 0.29 μM/ml and 0.65 μM/ml had...... of platinum nanoparticles and cisplatin and their anticancer properties in examination with a U87 glioma cell line and tumor. Material and methods: Nanoparticles of platinum (NP-Pt) and cisplatin were incubated with U87 glioma cells or injected directly into tumor tissue. The biological properties of NP...

  1. Altered expression of polycomb group genes in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available The Polycomb group (PcG proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM. By systematically interrogating The Cancer Genome Atlas (TCGA, we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.

  2. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Directory of Open Access Journals (Sweden)

    Maria-del-Mar Inda

    2014-01-01

    Full Text Available Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM, the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  3. Glioblastoma multiforme: a look inside its heterogeneous nature.

    Science.gov (United States)

    Inda, Maria-Del-Mar; Bonavia, Rudy; Seoane, Joan

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  4. Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

    Energy Technology Data Exchange (ETDEWEB)

    Inda, Maria-del-Mar, E-mail: mminda@vhio.net; Bonavia, Rudy [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Seoane, Joan [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Catalan Institution of Research and Advanced Studies (ICREA), Barcelona 08035 (Spain)

    2014-01-27

    Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

  5. Methionine Uptake and Required Radiation Dose to Control Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-cc.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo [Division of Radiation Oncology, Tokyo Bay Advanced Imaging and Radiation Oncology Clinic, Makuhari, Chiba (Japan); Uchino, Yoshio [Division of Nuclear Medicine, Chiba Ryogo Center, Chiba (Japan); Itami, Makiko [Division of Surgical Pathology, Chiba Cancer Center, Chiba (Japan); Hasegawa, Yuzo; Kawasaki, Koichiro; Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2015-09-01

    Purpose: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. Methods and Materials: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. Results: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P=.005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P<.0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. Conclusions: Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

  6. Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Jhanwar-Uniyal, Meena, E-mail: meena_jhanwar@nymc.edu; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj [Department of Neurosurgery, New York Medical College, Valhalla, NY 10595 (United States)

    2015-03-25

    Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM.

  7. Association of collagen architecture with glioblastoma patient survival.

    Science.gov (United States)

    Pointer, Kelli B; Clark, Paul A; Schroeder, Alexandra B; Salamat, M Shahriar; Eliceiri, Kevin W; Kuo, John S

    2017-06-01

    OBJECTIVE Glioblastoma (GBM) is the most malignant primary brain tumor. Collagen is present in low amounts in normal brain, but in GBMs, collagen gene expression is reportedly upregulated. However, to the authors' knowledge, direct visualization of collagen architecture has not been reported. The authors sought to perform the first direct visualization of GBM collagen architecture, identify clinically relevant collagen signatures, and link them to differential patient survival. METHODS Second-harmonic generation microscopy was used to detect collagen in a GBM patient tissue microarray. Focal and invasive GBM mouse xenografts were stained with Picrosirius red. Quantitation of collagen fibers was performed using custom software. Multivariate survival analysis was done to determine if collagen is a survival marker for patients. RESULTS In focal xenografts, collagen was observed at tumor brain boundaries. For invasive xenografts, collagen was intercalated with tumor cells. Quantitative analysis showed significant differences in collagen fibers for focal and invasive xenografts. The authors also found that GBM patients with more organized collagen had a longer median survival than those with less organized collagen. CONCLUSIONS Collagen architecture can be directly visualized and is different in focal versus invasive GBMs. The authors also demonstrate that collagen signature is associated with patient survival. These findings suggest that there are collagen differences in focal versus invasive GBMs and that collagen is a survival marker for GBM.

  8. Tumor cells and neovasculature dual targeting delivery for glioblastoma treatment.

    Science.gov (United States)

    Gao, Huile; Yang, Zhi; Cao, Shijie; Xiong, Yang; Zhang, Shuang; Pang, Zhiqing; Jiang, Xinguo

    2014-02-01

    Glioblastoma multiforme (GBM), one of the most common primary malignant brain tumors, was characterized by angiogenesis and tumor cells proliferation. Antiangiogenesis and antitumor combination treatment gained much attention because of the potency in dual inhibition of both the tumor proliferation and the tumor invasion. In this study, a neovasculature and tumor cell dual targeting delivery system was developed through modification of nanoparticles with interleukin-13 peptide and RGD (IRNPs), in which interleukin-13 peptide was targeting GBM cells and RGD was targeting neovasculature. To evaluate the potency in GBM treatment, docetaxel was loaded into IRNPs. In vitro, interleukin-13 peptide and RGD could enhance the corresponding cells (C6 and human umbilical vein endothelial cells) uptake and cytotoxicity. In combination, IRNPs showed high uptake in both cells and increased the cytotoxicity on both cells. In vivo, IRNPs could effectively deliver cargoes to GBM with higher intensity than mono-modified nanoparticles. Correspondingly, docetaxel-IRNPs displayed best anti-tumor effect with a median survival time of 35 days, which was significantly longer than that of mono-modified and unmodified nanoparticles. Importantly, treatment with docetaxel-IRNPs could avoid the accumulation of HIF1α in GBM site, which was crucial for the tumor invasion. After the treatment, there was no obvious change in normal organs of mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma

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    Dinesh K. Singh

    2017-01-01

    Full Text Available Efforts to identify and target glioblastoma (GBM drivers have primarily focused on receptor tyrosine kinases (RTKs. Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2 transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2 and zinc-finger E-box binding homeobox 1 (ZEB1, which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  10. A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme.

    Science.gov (United States)

    Vidone, Michele; Clima, Rosanna; Santorsola, Mariangela; Calabrese, Claudia; Girolimetti, Giulia; Kurelac, Ivana; Amato, Laura Benedetta; Iommarini, Luisa; Trevisan, Elisa; Leone, Marco; Soffietti, Riccardo; Morra, Isabella; Faccani, Giuliano; Attimonelli, Marcella; Porcelli, Anna Maria; Gasparre, Giuseppe

    2015-06-01

    Glioblastoma multiforme (GBM) is the most malignant brain cancer in adults, with a poor prognosis, whose molecular stratification still represents a challenge in pathology and clinics. On the other hand, mitochondrial DNA (mtDNA) mutations have been found in most tumors as modifiers of the bioenergetics state, albeit in GBM a characterization of the mtDNA status is lacking to date. Here, a characterization of the burden of mtDNA mutations in GBM samples was performed. First, investigation of tumor-specific vs. non tumor-specific mutations was carried out with the MToolBox bioinformatics pipeline by analyzing 45 matched tumor/blood samples, from whole genome or whole exome sequencing datasets obtained from The Cancer Genome Atlas (TCGA) consortium. Additionally, the entire mtDNA sequence was obtained in a dataset of 104 fresh-frozen GBM samples. Mitochondrial mutations with potential pathogenic interest were prioritized based on heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. A preliminary biochemical analysis of the activity of mitochondrial respiratory complexes was also performed on fresh-frozen GBM samples. Although a high number of mutations was detected, we report that the large majority of them does not pass the prioritization filters. Therefore, a relatively limited burden of pathogenic mutations is indeed carried by GBM, which did not appear to determine a general impairment of the respiratory chain. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Exosome Proteome of U-87MG Glioblastoma Cells

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    Sohyun Chun

    2016-12-01

    Full Text Available Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus. Cell culture medium was collected, and exosomes were isolated by continuous centrifugation eliminating cell debris, nucleic acids, and other particles. The morphology of exosomes was observed by cryo-tunneling electron microscopy. According to 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, certain proteins including collagen type VI alpha 1, putative RNA-binding protein 15B chain A, substrate induced remodeling of the active site regulates HTRA1, coatomer protein complex-subunit beta 2, myosin-heavy chain 1, and keratin-type I cytoskeletal 9 showed differences between the control proteome and the low temperature-exposed proteome.

  12. Phase I trial of dovitinib (TKI258) in recurrent glioblastoma.

    Science.gov (United States)

    Schäfer, Niklas; Gielen, Gerrit H; Kebir, Sied; Wieland, Anja; Till, Andreas; Mack, Frederic; Schaub, Christina; Tzaridis, Theophilos; Reinartz, Roman; Niessen, Michael; Fimmers, Rolf; Simon, Matthias; Coch, Christoph; Fuhrmann, Christine; Herrlinger, Ulrich; Scheffler, Björn; Glas, Martin

    2016-07-01

    Dovitinib (TKI258) is an oral multi-tyrosine kinase inhibitor of FGFR, VEGFR, PDGFR β, and c-Kit. Since dovitinib is able to cross the blood-brain barrier and targets brain tumor-relevant pathways, we conducted a phase I trial to demonstrate its safety in recurrent glioblastoma (GBM). Patients with first or second GBM recurrence started treatment with the maximal tolerated dose (MTD) previously established in systemic cancer patients (500 mg/d, 5 days on/2 days off). A modified 3 + 3 design in three cohorts (500, 400, 300 mg) was used. Twelve patients were enrolled. Seventy-two adverse events (AEs) occurred and 16.7 % of AEs were classified as ≥CTC grade 3 toxicity, mainly including hepatotoxicity and hematotoxicity. Only one out of six patients of the 300-mg cohort showed grade 3 toxicity. The PFS-6 rate was 16.7 %, and it was not associated with detection of the FGFR-TACC gene fusion in the tumor. Dovitinib is safe in patients with recurrent GBM and showed efficacy in only some patients unselected for target expression. The recommended phase II dose of 300 mg would be substantially lower than the recently established MTD in systemic cancer patients. Further personalized trials are recommended.

  13. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma.

    Science.gov (United States)

    Singh, Dinesh K; Kollipara, Rahul K; Vemireddy, Vamsidara; Yang, Xiao-Li; Sun, Yuxiao; Regmi, Nanda; Klingler, Stefan; Hatanpaa, Kimmo J; Raisanen, Jack; Cho, Steve K; Sirasanagandla, Shyam; Nannepaga, Suraj; Piccirillo, Sara; Mashimo, Tomoyuki; Wang, Shan; Humphries, Caroline G; Mickey, Bruce; Maher, Elizabeth A; Zheng, Hongwu; Kim, Ryung S; Kittler, Ralf; Bachoo, Robert M

    2017-01-24

    Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Data Analysis and Tissue Type Assignment for Glioblastoma Multiforme

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    Yuqian Li

    2014-01-01

    Full Text Available Glioblastoma multiforme (GBM is characterized by high infiltration. The interpretation of MRSI data, especially for GBMs, is still challenging. Unsupervised methods based on NMF by Li et al. (2013, NMR in Biomedicine and Li et al. (2013, IEEE Transactions on Biomedical Engineering have been proposed for glioma recognition, but the tissue types is still not well interpreted. As an extension of the previous work, a tissue type assignment method is proposed for GBMs based on the analysis of MRSI data and tissue distribution information. The tissue type assignment method uses the values from the distribution maps of all three tissue types to interpret all the information in one new map and color encodes each voxel to indicate the tissue type. Experiments carried out on in vivo MRSI data show the feasibility of the proposed method. This method provides an efficient way for GBM tissue type assignment and helps to display information of MRSI data in a way that is easy to interpret.

  15. Post progression survival in glioblastoma: where are we?

    Science.gov (United States)

    Franceschi, Enrico; Ermani, Mario; Bartolini, Stefania; Bartolotti, Marco; Poggi, Rosalba; Tallini, Giovanni; Marucci, Gianluca; Fioravanti, Antonio; Tosoni, Alicia; Agati, Raffaele; Bacci, Antonella; Pozzati, Eugenio; Morandi, Luca; Balestrini, Damiano; Ghimenton, Claudio; Crisi, Girolamo; Brandes, Alba A

    2015-01-01

    The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥ 18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

  16. Differential Connexin Function Enhances Self-Renewal in Glioblastoma

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    Masahiro Hitomi

    2015-05-01

    Full Text Available The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43, but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

  17. Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience

    International Nuclear Information System (INIS)

    Ciammella, Patrizia; Podgornii, Ala; Galeandro, Maria; D’Abbiero, Nunziata; Pisanello, Anna; Botti, Andrea; Cagni, Elisabetta; Iori, Mauro; Iotti, Cinzia

    2013-01-01

    Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient

  18. Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme

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    Liu Yang

    2015-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional treatment (surgery, chemotherapy, and radiation. Dendritic cells (DCs are the most powerful antigen presenting cells and DC-based vaccination has the potential to target and eliminate GBM cells and enhance the responses of these cells to the existing therapies with minimal damage to the healthy tissues around them. It can enhance recognition of GBM cells by the patients’ immune system and activate vast, potent, and long-lasting immune reactions to eliminate them. Therefore, this therapy can prolong the survival of GBM patients and has wide and bright future in the treatment of GBM. Also, the efficacy of this therapy can be strengthened in several ways at some degree: the manipulation of immune regulatory components or costimulatory molecules on DCs; the appropriate choices of antigens for loading to enhance the effectiveness of the therapy; regulation of positive regulators or negative regulators in GBM microenvironment.

  19. [Foundation of preoperative prognosis estimation model for glioblastoma multiforme].

    Science.gov (United States)

    Jiang, H H; Feng, G Y; Liu, D; Ren, X H; Cui, Y; Lin, S

    2017-08-15

    Objective: This study explored the preoperative prognostic factors of patients with glioblastoma multiforme (GBM) in order to propose a preoperative prognosis estimation model. Methods: The clinical data of 416 patients diagnosed with GBM in Beijing Tiantan Hospital affiliated to Capital Medical University from 2008 to 2015 were retrospectively reviewed.A total of nine factors: gender, age, duration of symptoms, preoperative epilepsy, preoperative muscle weakness, preoperative headache, preoperative KPS score, tumor location and tumor diameter were enrolled in the survival analysis.The significant factors identified by Kaplan-Meier plot were further collected in the multivariate Cox regression analysis.On the basis of multivariate analysis results, a preoperative prognosis estimation model was founded. Results: Univariate analysis showed that Age ≥50 years, without preoperative epilepsy, tumor located in non-frontotemporal lobe, tumor diameter ≥6 cm and preoperative KPS score preoperative epilepsy, tumor located in non-frontotemporal lobe were independent risk factors ( P <0.05). The prognostic estimation model based on the independent risk factors divided the whole cohort into three subgroups with different survival ( P <0.001). Conclusions: The more risk factors, the higher score but poorer prognosis. Patients in the high-risk group had lower gross total resection degree but higher rate of postoperative complications, which suggested that aggressive resection was not suitable for high-risk patients.

  20. Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

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    Grodzik M

    2011-11-01

    Full Text Available Marta Grodzik1, Ewa Sawosz1, Mateusz Wierzbicki1, Piotr Orlowski1, Anna Hotowy2, Tomasz Niemiec1, Maciej Szmidt3, Katarzyna Mitura4, André Chwalibog21Division of Biotechnology and Biochemistry of Nutrition, Warsaw University of Life Sciences, Warsaw, Poland; 2Department of Basic Animal and Veterinary Science, University of Copenhagen, Copenhagen, Denmark; 3Division of Histology and Embryology, Warsaw University of Life Sciences, Warsaw, Poland; 4Department of Biomedical Engineering, Koszalin University of Technology, Koszalin, PolandAbstract: The objective of the study was to determine the effect of carbon nanoparticles produced by different methods on the growth of brain tumor and the development of blood vessels. Glioblastoma multiforme cells were cultured on the chorioallantoic membrane of chicken embryo and after 7 days of incubation, were treated with carbon nanoparticles administered in ovo to the tumor. Both types of nanoparticles significantly decreased tumor mass and volume, and vessel area. Quantitative real-time polymerase chain reaction analysis showed downregulated fibroblast growth factor-2 and vascular endothelial growth factor expression at the messenger ribonucleic acid level. The present results demonstrate antiangiogenic activity of carbon nanoparticles, making them potential factors for anticancer therapy.Keywords: cancer, nanoparticle, embryo, angiogenesis, FGF-2, VEGF

  1. CD133 is essential for glioblastoma stem cell maintenance.

    Science.gov (United States)

    Brescia, Paola; Ortensi, Barbara; Fornasari, Lorenzo; Levi, Daniel; Broggi, Giovanni; Pelicci, Giuliana

    2013-05-01

    The role of the cell surface CD133 as a cancer stem cell marker in glioblastoma (GBM) has been widely investigated, since it identifies cells that are able to initiate neurosphere growth and form heterogeneous tumors when transplanted in immune-compromised mice. However, evidences of CD133-negative cells exhibiting similar properties have also been reported. Moreover, the functional role of CD133 in cancer stem/progenitor cells remains poorly understood. We studied the biological effects of CD133 downregulation in GBM patient-derived neurospheres. Our results indicate that there is not a hierarchical relation between CD133-positive and CD133-negative cells composing the neurospheres. Indeed, CD133 appears in an interconvertible state, changing its subcellular localization between the cytoplasm and the plasmamembrane of neurosphere cells. Silencing of CD133 in human GBM neurospheres using lentivirus-mediated short hairpin RNA impairs the self-renewal and tumorigenic capacity of neurosphere cells. These results imply that CD133 could be used as a therapeutic target in GBMs. Copyright © 2013 AlphaMed Press.

  2. Current Trends in Targeted Therapies for Glioblastoma Multiforme

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    Fumiharu Ohka

    2012-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most frequently occurring tumors in the central nervous system and the most malignant tumor among gliomas. Despite aggressive treatment including surgery, adjuvant TMZ-based chemotherapy, and radiotherapy, GBM still has a dismal prognosis: the median survival is 14.6 months from diagnosis. To date, many studies report several determinants of resistance to this aggressive therapy: (1 O6-methylguanine-DNA methyltransferase (MGMT, (2 the complexity of several altered signaling pathways in GBM, (3 the existence of glioma stem-like cells (GSCs, and (4 the blood-brain barrier. Many studies aim to overcome these determinants of resistance to conventional therapy by using various approaches to improve the dismal prognosis of GBM such as modifying TMZ administration and combining TMZ with other agents, developing novel molecular-targeting agents, and novel strategies targeting GSCs. In this paper, we review up-to-date clinical trials of GBM treatments in order to overcome these 4 hurdles and to aim at more therapeutical effect than conventional therapies that are ongoing or are about to launch in clinical settings and discuss future perspectives.

  3. Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness.

    Science.gov (United States)

    Richichi, Cristina; Osti, Daniela; Del Bene, Massimiliano; Fornasari, Lorenzo; Patanè, Monica; Pollo, Bianca; DiMeco, Francesco; Pelicci, Giuliana

    2016-11-01

    Glioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture.All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content.Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumor-bearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers.

  4. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation.

    Science.gov (United States)

    Takano, Shingo

    2012-04-01

    Glioblastomas are highly vascular tumors. Recent preclinical and clinical investigations have revealed that agents targeting angiogenesis may have efficacy against this type of tumor. Antibodies to vascular endothelial growth factor are being studied in this patient population. Unfortunately, treatment inevitably fails. This review provides an update on recent research on the mechanisms by which tumor cells acquire resistance, and discusses recent preclinical and experimental development of novel new-generation anti-angiogenic agents that overcome this problem, especially those based on the molecular mechanisms of tumor vessel formation. The tumor vasculature not only nourishes glioblastomas, but also provides a specialized microenvironment for tumor stem-like cells and for the brain tumor. The factors, pathways, and interactions described in this review provide information about the cell biology of glioblastomas which may ultimately result in new modes of treatment.

  5. Acute hypoxia induces upregulation of microRNA-210 expression in glioblastoma spheroids

    DEFF Research Database (Denmark)

    Rosenberg, Tine Agerbo; Thomassen, Mads; Jensen, Stine Skov

    2015-01-01

    AIM: Tumor hypoxia and presence of tumor stem cells are related to therapeutic resistance and tumorigenicity in glioblastomas. The aim of the present study was therefore to identify microRNAs deregulated in acute hypoxia and to identify possible associated changes in stem cell markers. MATERIALS...... & METHODS: Glioblastoma spheroid cultures were grown in either 2 or 21% oxygen. Subsequently, miRNA profiling was performed and expression of ten stem cell markers was examined. RESULTS: MiRNA-210 was significantly upregulated in hypoxia in patient-derived spheroids. The stem cell markers displayed...... a complex regulatory pattern. CONCLUSION: MiRNA-210 appears to be upregulated in hypoxia in immature glioblastoma cells. This miRNA may represent a therapeutic target although it is not clear from the results whether this miRNA may be related to specific cancer stem cell functions....

  6. Tumor treating fields therapy device for glioblastoma: physics and clinical practice considerations.

    Science.gov (United States)

    Lok, Edwin; Swanson, Kenneth D; Wong, Eric T

    2015-01-01

    Alternating electric fields therapy, as delivered by the tumor treating fields device, is a new modality of cancer treatment that has been approved by the US FDA for recurrent glioblastoma. At a frequency of 200 kHz, these fields emanate from transducer arrays on the surface of the patient's scalp into the brain and perturb processes necessary for cytokinesis during tumor cell mitosis. In the registration Phase III trial for recurrent glioblastoma patients, the efficacy of the tumor treating fields as monotherapy was equivalent to chemotherapy, while scalp irritation was its major adverse event compared with systemic toxicities that were associated with cytotoxic chemotherapies. Alternating electric fields therapy is, therefore, an essential option for the treatment of recurrent glioblastoma. Here, we summarize our current knowledge of the physics, cell biology and clinical data supporting the use of the tumor treating fields therapy.

  7. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2016-01-01

    Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano.......0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive...

  8. Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment.

    Science.gov (United States)

    Bruna, Jordi; Miró, Júlia; Velasco, Roser

    2013-05-01

    Glioblastoma-related epilepsy requires paying careful attention to a combination of factors with an integrated approach. Major interrelated issues must be considered in the seizure care of glioblastoma patients. Seizure control frequently requires the administration of antiepileptic drugs simultaneously with other treatments, including surgery, radiotherapy and chemotherapy, with complete seizure relief often being difficult to achieve. The pharmacological interactions between antiepileptic drugs and antineoplastic agents can modify the activity of both treatments, compromising their efficacy and increasing the probability of developing adverse events related to both therapies. This review summarizes the new pathophysiological pathways involved in the epileptogenesis of glioblastoma-related seizures and the interactions between antiepileptic drugs and oncological treatment, paying special attention to its impact on survival and the current evidence of the antiepileptic treatment efficacy, including the potential usefulness of new third-generation compounds.

  9. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions.

    Science.gov (United States)

    Agnihotri, Sameer; Zadeh, Gelareh

    2016-02-01

    A defining hallmark of glioblastoma is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. Altered metabolic enzymes and their metabolites are oncogenic and not simply a product of tumor proliferation. Here we highlight the advantages of why tumor cells, including glioblastoma cells, require metabolic reprogramming and how tumor metabolism can converge on tumor epigenetics and unanswered questions in the field. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Therapeutic implications of melatonin in cerebral edema.

    Science.gov (United States)

    Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit

    2014-12-01

    Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema.

  11. Glioblastoma Inhibition by Cell Surface Immunoglobulin Protein EWI-2, In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Tatiana V. Kolesnikova

    2009-01-01

    Full Text Available EWI-2, a cell surface IgSF protein, is highly expressed in normal human brain but is considerably diminished in glioblastoma tumors and cell lines. Moreover, loss of EWI-2 expression correlated with a shorter survival time in human glioma patients, suggesting that EWI-2 might be a natural inhibitor of glioblastoma. In support of this idea, EWI-2 expression significantly impaired both ectopic and orthotopic tumor growth in nude mice in vivo. In vitro assays provided clues regarding EWI-2 functions. Expression of EWI-2 in T98G and/or U87-MG malignant glioblastoma cell lines failed to alter two-dimensional cell proliferation but inhibited glioblastoma colony formation in soft agar and caused diminished cell motility and invasion. At the biochemical level, EWI-2 markedly affects the organization of four molecules (tetraspanin proteins CD9 and CD81 and matrix metalloproteinases MMP-2 and MT1-MMP, which play key roles in the biology of astrocytes and gliomas. EWI-2 causes CD9 and CD81 to become more associated with each other, whereas CD81 and other tetraspanins become less associated with MMP-2 and MT1-MMP. We propose that EWI-2 inhibition of glioblastoma growth in vivo is at least partly explained by the capability of EWI-2 to inhibit growth and/or invasion in vitro. Underlying these functional effects, EWI-2 causes a substantial molecular reorganization of multiple molecules (CD81, CD9, MMP-2, and MT1-MMP known to affect proliferation and/or invasion of astrocytes and/or glioblastomas.

  12. Quantitative susceptibility mapping differentiates between blood depositions and calcifications in patients with glioblastoma.

    Directory of Open Access Journals (Sweden)

    Andreas Deistung

    Full Text Available OBJECTIVES: The application of susceptibility weighted imaging (SWI in brain tumor imaging is mainly used to assess tumor-related "susceptibility based signals" (SBS. The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM, is able to distinguish between both entities reliably. MATERIALS AND METHODS: SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication. Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. RESULTS: 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. CONCLUSIONS: QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of

  13. Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

    Science.gov (United States)

    Uno, Miyuki; Oba-Shinjo, Sueli Mieko; Camargo, Anamaria Aranha; Moura, Ricardo Pereira; de Aguiar, Paulo Henrique; Cabrera, Hector Navarro; Begnami, Marcos; Rosemberg, Sérgio; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

    2011-01-01

    OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue. PMID:22012047

  14. Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

    Directory of Open Access Journals (Sweden)

    Miyuki Uno

    2011-01-01

    Full Text Available OBJECTIVES: 1 To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT promoter to its gene and protein expression levels in glioblastoma and 2 to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001. However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297. The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing, and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

  15. Over-expression of CHAF1A promotes cell proliferation and apoptosis resistance in glioblastoma cells via AKT/FOXO3a/Bim pathway

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Honghai; Du, Bin [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Jiang, Huili [Friendship Nephrology and Blood Purification Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Gao, Jun, E-mail: gaoj1666@126.com [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China)

    2016-01-22

    Chromatinassembly factor 1 subunit A (CHAF1A) has been reported to be involved in several human diseases including cancer. However, the biological and clinical significance of CHAF1A in glioblastoma progression remains largely unknown. In this study, we found that up-regulation of CHAF1A happens frequently in glioblastoma tissues and is associated with glioblastoma prognosis. Knockout of CHAF1A by CRISPR/CAS9 technology induce G1 phase arrest and apoptosis in glioblastoma cell U251 and U87. In addition, inhibition of CHAF1A influenced the signal transduction of the AKT/FOXO3a/Bim axis, which is required for glioblastoma cell proliferation. Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma.

  16. Over-expression of CHAF1A promotes cell proliferation and apoptosis resistance in glioblastoma cells via AKT/FOXO3a/Bim pathway

    International Nuclear Information System (INIS)

    Peng, Honghai; Du, Bin; Jiang, Huili; Gao, Jun

    2016-01-01

    Chromatinassembly factor 1 subunit A (CHAF1A) has been reported to be involved in several human diseases including cancer. However, the biological and clinical significance of CHAF1A in glioblastoma progression remains largely unknown. In this study, we found that up-regulation of CHAF1A happens frequently in glioblastoma tissues and is associated with glioblastoma prognosis. Knockout of CHAF1A by CRISPR/CAS9 technology induce G1 phase arrest and apoptosis in glioblastoma cell U251 and U87. In addition, inhibition of CHAF1A influenced the signal transduction of the AKT/FOXO3a/Bim axis, which is required for glioblastoma cell proliferation. Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma.

  17. Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

    DEFF Research Database (Denmark)

    Sehested, Astrid Marie

    2016-01-01

    fusions activated mitogen-activated protein kinase (MAPK) signaling and, in cooperation with lesions compromising cell cycle regulation, induced aggressive glial tumors in vivo. MET inhibitors suppressed MET tumor growth in xenograft models. Finally, we treated a pediatric patient bearing a MET-fusion......Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET...

  18. Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

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    Salacz ME

    2016-04-01

    Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

  19. Evaluation of the impact of tumour hypoxia on the response of glioblastoma to radiotherapy

    International Nuclear Information System (INIS)

    Deviers, A.; Moyal, E.; Laprie, A.; Ken, S.; Franceries, X.; Lotterie, J.A.; Celsis, P.; Berry, I.; Mboup, A.K.; Mogicato, G.

    2011-01-01

    The study aimed at characterizing hypoxic areas of a glioblastoma by spectroscopic magnetic resonance imagery (MRI), and at correlating the presence of metabolites of interest in these areas with the glioblastoma response to radiotherapy, and with survival. The analysis is based on 68 MRI and spectroscopic MRI examinations made on 17 patients. Lactate metabolite maps have been established. It appears that studying these lactates by spectroscopic MRI is a promising method for the definition of predictive factors of local evolution and of survival. Short communication

  20. Aplastic anemia as a cause of death in a patient with glioblastoma multiforme treated with temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Kopecky, Jindrich; Priester, Peter; Slovacek, Ladislav; Petera, Jiri; Macingova, Zuzana [Dept. of Clinical Oncology and Radiotherapy, Charles Univ. Hospital and Faculty of Medicine in Hradec Kralove (Czech Republic); Kopecky, Otakar [Clinical Oncology, Regional Hospital Nachod (Czech Republic)

    2010-08-15

    Background: Standard treatment of glioblastoma multiforme consists of postoperative radiochemotherapy with temozolomide, followed by a 6-month chemotherapy. Serious hematologic complications are rarely reported. Case Report and Results: The authors present the case of a 61-year-old female patient with glioblastoma multiforme treated with external-beam radiation therapy and concomitant temozolomide. After completion of treatment, the patient developed symptoms of serious aplastic anemia that eventually led to death due to prolonged neutro- and thrombocytopenia followed by infectious complications. Conclusion: Lethal complications following temozolomide are, per se, extremely rare, however, a total of four other cases of aplastic anemia have been reported in the literature so far. (orig.)

  1. Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma

    OpenAIRE

    Lou, Emil; Peters, Katherine B; Sumrall, Ashley L; Desjardins, Annick; Reardon, David A; Lipp, Eric S; Herndon, James E; Coan, April; Bailey, Leighann; Turner, Scott; Friedman, Henry S; Vredenburgh, James J

    2013-01-01

    Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6?10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m2 on days 1?5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tum...

  2. Cerebral trypanosomiasis and AIDS

    Directory of Open Access Journals (Sweden)

    Antunes Apio Claudio Martins

    2002-01-01

    Full Text Available A 36 year-old black female, complaining of headache of one month's duration presented with nausea, vomiting, somnolence, short memory problems, loss of weight, and no fever history. Smoker, intravenous drugs abuser, promiscuous lifestyle. Physical examination: left homonimous hemianopsia, left hemiparesis, no papilledema, diffuse hyperreflexia, slowness of movements. Brain CT scan: tumor-like lesion in the splenium of the corpus calosum, measuring 3.5 x 1.4 cm, with heterogeneous enhancing pattern, sugesting a primary CNS tumor. Due to the possibility of CNS infection, a lumbar puncture disclosed an opening pressure of 380 mmH(20; 11 white cells (lymphocytes; glucose 18 mg/dl (serum glucose 73 mg/dl; proteins 139 mg/dl; presence of Trypanosoma parasites. Serum Elisa-HIV tests turned out to be positive. Treatment with benznidazole dramatically improved clinical and radiographic picture, but the patient died 6 weeks later because of respiratory failure. T. cruzi infection of the CNS is a rare disease, but we have an increasing number of cases in HIV immunecompromised patients. Diagnosis by direct observation of CSF is uncommon, and most of the cases are diagnosed by pathological examination. It is a highly lethal disease, even when properly diagnosed and treated. This article intends to include cerebral trypanosomiasis in the differential diagnosis of intracranial space-occupying lesions, especially in immunecompromised patients from endemic regions.

  3. Monitoring Cerebral Oxygenation in Neonates: An Update

    Science.gov (United States)

    Dix, Laura Marie Louise; van Bel, Frank; Lemmers, Petra Maria Anna

    2017-01-01

    Cerebral oxygenation is not always reflected by systemic arterial oxygenation. Therefore, regional cerebral oxygen saturation (rScO2) monitoring with near-infrared spectroscopy (NIRS) is of added value in neonatal intensive care. rScO2 represents oxygen supply to the brain, while cerebral fractional tissue oxygen extraction, which is the ratio between rScO2 and systemic arterial oxygen saturation, reflects cerebral oxygen utilization. The balance between oxygen supply and utilization provides insight in neonatal cerebral (patho-)physiology. This review highlights the potential and limitations of cerebral oxygenation monitoring with NIRS in the neonatal intensive care unit. PMID:28352624

  4. Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Despoina N. Maritsi

    2013-01-01

    Full Text Available We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata, chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256 against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent.

  5. Abdominal wall desmoid tumor mimicking a subserosal uterine leiomyoma

    Directory of Open Access Journals (Sweden)

    Al-Jefout M

    2011-06-01

    Full Text Available Moamar Al-Jefout1,2, Alabed Walid2, Abomayale Esam2, Alqaisi Amin2, Hawa Nather1,2, Nawayse Sultan2, Khadra Maysa31Department of Obstetrics and Gynaecology, Mutah Medical Faculty, Mutah University, Karak; 2Karak Hospital, Ministry of Health, Karak; 3University of Jordan, Amman, JordanAbstract: Desmoid tumors are cytologically bland fibrous neoplasms originating from musculoaponeurotic structures throughout the body. The cause of desmoid tumors is uncertain, but may be related to trauma or hormonal factors, or may have a genetic association. These tumors can be found in some young women during pregnancy or just after giving birth. We report herein a case of desmoid tumor on the inner aspect of the abdominal wall that mimicked a large subserosal uterine leiomyoma. Initial clinical examination of the patient suggested a large abdominal wall tumor, while the imaging techniques including transabdominal ultrasound and magnetic resonance imaging suggested a large subserosal uterine leiomyoma as the initial diagnosis. This case emphasizes the importance of clinical examination during the diagnostic process.Keywords: diagnosis, lesion, ultrasound

  6. Ant-Mimicking Spiders: Strategies for Living with Social Insects

    Directory of Open Access Journals (Sweden)

    Fadia Sara Ceccarelli

    2013-01-01

    Full Text Available Mimicry is a fascinating topic, in particular when viewed in terms of selective forces and evolutionary strategies. Mimicry is a system involving a signaller, a signal receiver, and a model and has evolved independently many times in plants and animals. There are several ways of classifying mimicry based on the interactions and cost-benefit scenarios of the parties involved. In this review, I briefly outline the dynamics of the most common types of mimicry to then apply it to some of the spider-ant associative systems known to date. In addition, this review expands on the strategies that ant-associating (in particular ant-mimicking spiders have developed to minimise the costs of living close to colonies of potentially dangerous models. The main strategy that has been noted to date is either chemical mimicry or actively avoiding contact with ants. If these strategies warrant protection for the spider (living close to potentially dangerous models, then the benefits of ant associations would outweigh the costs, and the association will prevail.

  7. Follicular thyroid carcinoma mimicking meningioma: A case report

    Directory of Open Access Journals (Sweden)

    Krishnalatha Buandasan

    2012-02-01

    Full Text Available Follicular thyroid carcinoma (FTC is a well-differentiated tumor which resembles the normal microscopic pattern of the thyroid. Although intracranial metastasis to the brain is frequent in adults, metastasis from FTC is very rare. Dural metastases mimicking meningioma have been documented in the literature now and then. However, cases arising from a FTC are again very rare. We report the case of a middle-aged lady who presented with progressive, painless left eye proptosis. She was noted to have a non-axial proptosis with dystopia, compressive optic neuropathy and exposure keratitis. She also had a painless swelling over the occipital region. She was initially misdiagnosed to have multiple foci of meningioma based on magnetic resonance imaging findings. Subsequent histopathological examination revealed presence of FTC. She was euthyroid but was found to have multiple small thyroid nodules by ultrasonography. Hence, the definite diagnosis of all dural masses must be histological wherever possible and thyroid carcinoma should be considered as a potential primary tumour in such presentations.

  8. Toxicology Analysis of Tissue-Mimicking Phantom Made From Gelatin

    Science.gov (United States)

    Dolbashid, A. S.; Hamzah, N.; Zaman, W. S. W. K.; Mokhtar, M. S.

    2017-06-01

    Skin phantom mimics the biological skin tissues as it have the ability to respond to changes in its environment. The development of tissue-mimicking phantom could contributes towards the reduce usage of animal in cosmetics and pharmacokinetics. In this study, the skin phantoms made from gelatin were tested with four different commonly available cosmetic products to determine the toxicity of each substance. The four substances used were; mercury-based whitening face cream, carcinogenic liquid make-up foundation, paraben-based acne cleanser, and organic lip balm. Toxicity test were performed on all of the phantoms. For toxicity testing, topographical and electrophysiological changes of the phantoms were evaluated. The ability of each respective phantom to react with mild toxic substances and its electrical resistance were analysed in to determine the toxicity of all the phantom models. Four-electrode method along with custom made electrical impedance analyser was used to differentiate electrical resistance between intoxicated phantom and non-intoxicated phantom in this study. Electrical resistance values obtained from the phantom models were significantly higher than the control group. The result obtained suggests the phantom as a promising candidate to be used as alternative for toxicology testing in the future.

  9. Mimicking biochar-albedo feedback in complex Mediterranean agricultural landscapes

    International Nuclear Information System (INIS)

    Bozzi, E; Genesio, L; Miglietta, F; Toscano, P; Pieri, M

    2015-01-01

    Incorporation of charcoal produced by biomass pyrolysis (biochar) in agricultural soils is a potentially sustainable strategy for climate change mitigation. However, some side effects of large-scale biochar application need to be investigated. In particular a massive use of a low-reflecting material on large cropland areas may impact the climate via changes in surface albedo. Twelve years of MODIS-derived albedo data were analysed for three pairs of selected agricultural sites in central Italy. In each pair bright and dark coloured soil were identified, mimicking the effect of biochar application on the land surface albedo of complex agricultural landscapes. Over this period vegetation canopies never completely masked differences in background soil colour. This soil signal, expressed as an albedo difference, induced a local instantaneous radiative forcing of up to 4.7 W m −2 during periods of high solar irradiance. Biochar mitigation potential might therefore be reduced up to ∼30%. This study proves the importance of accounting for crop phenology and crop management when assessing biochar mitigation potential and provides more insights into the analysis of its environmental feedback. (letter)

  10. Synchrony and motor mimicking in chimpanzee observational learning.

    Science.gov (United States)

    Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

    2014-06-13

    Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function.

  11. Extramedullary Plasmacytoma Mimicking Pancreatic Cancer: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Daniela Sciancalepore

    2016-01-01

    Full Text Available Multiple myeloma is a plasma cell tumor that homes to and expands in the bone marrow and that, despite the new available drugs, remains incurable. Extramedullary plasmacytoma is a not frequent manifestation during the natural history of multiple myeloma and is frequently associated with plasma cell bone marrow infiltration. The most common locations for an EMP include the gastrointestinal tract, pleura, testis, skin, peritoneum, liver, endocrine glands, and lymph nodes. Primary involvement of the gallbladder fossa is exceedingly rare. In this report, we describe a patient with multiple myeloma who achieved a clinical and serological remission after autologous transplant but progressed rapidly at extramedullary site mimicking a second cancer (i.e., pancreatic or biliary cancer. In this case, the extramedullary localization was refractory to standard therapy, differently from bone marrow localization, but responded to lymphoma-like therapy. In this patient (i the particular site of developing plasmacytoma is the gallbladder fossa, (ii the timing of onset of this neoplasm is immediately after autologous transplant, and (iii its disjunction from primary myeloma is that it appears in clinical and serological remission phase which may be confounding during the diagnostic approach simulating a different tumor (solid tumor.

  12. Trastuzumab-Induced Myocardiotoxicity Mimicking Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    K.B. Ribeiro

    2012-03-01

    Full Text Available Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6–4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high-risk patients.

  13. Mimicking the magnetic properties of rare earth elements using superatoms.

    Science.gov (United States)

    Cheng, Shi-Bo; Berkdemir, Cuneyt; Castleman, A W

    2015-04-21

    Rare earth elements (REs) consist of a very important group in the periodic table that is vital to many modern technologies. The mining process, however, is extremely damaging to the environment, making them low yield and very expensive. Therefore, mimicking the properties of REs in a superatom framework is especially valuable but at the same time, technically challenging and requiring advanced concepts about manipulating properties of atom/molecular complexes. Herein, by using photoelectron imaging spectroscopy, we provide original idea and direct experimental evidence that chosen boron-doped clusters could mimic the magnetic characteristics of REs. Specifically, the neutral LaB and NdB clusters are found to have similar unpaired electrons and magnetic moments as their isovalent REs (namely Nd and Eu, respectively), opening up the great possibility in accomplishing rare earth mimicry. Extension of the superatom concept into the rare earth group not only further shows the power and advance of this concept but also, will stimulate more efforts to explore new superatomic clusters to mimic the chemistry of these heavy atoms, which will be of great importance in designing novel building blocks in the application of cluster-assembled nanomaterials. Additionally, based on these experimental findings, a novel "magic boron" counting rule is proposed to estimate the numbers of unpaired electrons in diatomic LnB clusters.

  14. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry.

    Directory of Open Access Journals (Sweden)

    Qingqing Lin

    Full Text Available Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM and/or phosphatidylcholine (PC outside/phosphatidylethanolamine (PE and phosphatidylserine (PS inside, and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes "artificial plasma membrane mimicking" ("PMm" vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

  15. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry.

    Science.gov (United States)

    Lin, Qingqing; London, Erwin

    2014-01-01

    Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes "artificial plasma membrane mimicking" ("PMm") vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

  16. Visual Loss from Choroidal Melanoma Mimicking Neurological Syndromes

    Directory of Open Access Journals (Sweden)

    Karim Hammamji

    2017-03-01

    Full Text Available Melanoma of the eye is rare, but can mimic a range of disorders. This report highlights 2 cases of choroidal melanoma with vision loss mimicking neurological diagnoses. The first patient is a 41-year-old white male with a known history of multiple sclerosis and a previous episode of optic neuritis in the right eye, who presented with a 6-month history of decreased vision in the same eye, and occasional photopsiae. He was treated with 2 courses of oral steroids for presumed recurrent optic neuritis. After a temporary improvement in his symptoms, his vision worsened, following which he had a head MRI, which revealed a solid intraocular mass. He was subsequently diagnosed with a choroidal melanoma for which he was treated successfully with ruthenium-106 plaque brachytherapy. The second patient is a 57-year-old female, who presented with a progressive cerebellar syndrome under investigation by the neurology service, as well as decreased vision in the right eye. Her visual acuity gradually deteriorated and her neurological assessment, which included a PET-CT, revealed uptake in the right eye. The diagnosis of a choroidal melanoma was made, and following conservative treatment with proton beam radiotherapy, she had an enucleation of the eye. Intraocular tumours can masquerade as many different entities. Unexplained unilateral visual loss, especially if it is atypical for a neurological syndrome, should prompt dilated fundoscopy and referral to an ophthalmologist.

  17. Wernicke's Encephalopathy Mimicking Acute Onset Stroke Diagnosed by CT Perfusion

    Directory of Open Access Journals (Sweden)

    Alok Bhan

    2014-01-01

    Full Text Available Background. Metabolic syndromes such as Wernicke’s encephalopathy may present with a sudden neurological deficit, thus mimicking acute onset stroke. Due to current emphasis on rapid admission and treatment of acute stroke patients, there is a significant risk that these stroke mimics may end up being treated with thrombolysis. Rigorous clinical and radiological skills are necessary to correctly identify such metabolic stroke mimics, in order to avoid doing any harm to these patients due to the unnecessary use of thrombolysis. Patient. A 51-year-old Caucasian male was admitted to our hospital with suspicion of an acute stroke due to sudden onset dysarthria and unilateral facial nerve paresis. Clinical examination revealed confusion and dysconjugate gaze. Computed tomography (CT including a CT perfusion (CTP scan revealed bilateral thalamic hyperperfusion. The use of both clinical and radiological findings led to correctly diagnosing Wernicke’s encephalopathy. Conclusion. The application of CTP as a standard diagnostic tool in acute stroke patients can improve the detection of stroke mimics caused by metabolic syndromes as shown in our case report.

  18. Synchrony and motor mimicking in chimpanzee observational learning

    Science.gov (United States)

    Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

    2014-01-01

    Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function. PMID:24923651

  19. Regional Pericarditis Mimicking Inferior Myocardial Infarction following Abdominal Surgery

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    Ahmad T. Alhammouri

    2014-01-01

    Full Text Available Acute pericarditis is common but illusive, often mimicking acute coronary syndrome in its clinical and electrocardiographic presentation. Regional pericarditis, though rare, presents further challenge with a paucity of published diagnostic criteria. We present a case of postoperative regional pericarditis and discuss helpful electrocardiographic findings. A 66-year-old male with history of open drainage of a liver abscess presented with abdominal pain and tenderness. CT of the abdomen was concerning for pneumatosis intestinalis of the distal descending colon. He underwent lysis of liver adhesions; exploration revealed only severe colonic impaction, for which he had manual disimpaction and peritoneal irrigation. Postoperatively, he developed sharp chest pain. Electrocardiogram revealed inferior ST elevation. Echocardiogram revealed normal left and right ventricular dimensions and systolic function without wall motion abnormalities. Emergent coronary angiography did not identify a culprit lesion, and left ventriculogram showed normal systolic function without wall motion abnormalities. He received no intervention, and the diagnosis of regional pericarditis was entertained. His cardiac troponin was 0.04 ng/dL and remained unchanged, with resolution of the ECG abnormalities in the following morning. Review of his preangiography ECG revealed PR depression, downsloping baseline between QRS complexes, and reciprocal changes in the anterior leads, suggestive of regional pericarditis.

  20. Orbital compressed air and petroleum injury mimicking necrotizing fasciitis.

    Science.gov (United States)

    Mellington, Faye E; Bacon, Annette S; Abu-Bakra, Mohammed A J; Martinez-Devesa, Pablo; Norris, Jonathan H

    2014-09-01

    Orbital injury secondary to petroleum-based products is rare. We report the first case, to our knowledge, of a combined compressed air and chemical orbital injury, which mimicked necrotizing fasciitis. A 58-year-old man was repairing his motorcycle engine when a piston inadvertently fired, discharging compressed air and petroleum-based carburetor cleaner into his left eye. He developed surgical emphysema, skin necrosis, and a chemical cellulitis, causing an orbital compartment syndrome. He was treated initially with antibiotics and subsequently with intravenous steroid and orbital decompression surgery. There was almost complete recovery by 4 weeks postsurgery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Petroleum-based products can cause severe skin irritation and necrosis. Compressed air injury can cause surgical emphysema. When these two mechanisms of injury are combined, the resulting orbitopathy and skin necrosis can mimic necrotizing fasciitis and cause diagnostic confusion. A favorable outcome is achievable with aggressive timely management. Copyright © 2014 Elsevier Inc. All rights reserved.