MedWorm: Brain Tumor

Patient Sensitivity To Important Drug Target In Deadly Brain Cancer Predicted

Health News from Medical News Today — Wed, 08 Feb 2012 08:00:00 +0100

A recent discovery by Van Andel Research Institute (VARI) scientists enables the prediction of patient sensitivity to proposed drug therapies for glioblastoma - the most common and most aggressive malignant brain tumor in humans. The study, published in the Proceedings of the National Academy of Science, investigated glioblastoma models characterized by cell signaling activation and gene amplification for their susceptibility to inhibitors of both the human MET oncogene and the epidermal growth factor receptor (EFGR). An oncogene is a gene with the potential to cause cancer... (Source: Health News from Medical News Today)

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CT-based quantitative SPECT for the radionuclide (201)Tl: experimental validation and a standardized uptake value for brain tumour patients.

Cancer Imaging — Wed, 08 Feb 2012 00:30:02 +0100

Authors: Willowson K, Bailey D, Schembri G, Baldock C Abstract We have previously reported on a method for reconstructing quantitative data from (99m)Tc single photon emission computed tomography (SPECT) images based on corrections derived from X-ray computed tomography, producing accurate results in both experimental and clinical studies. This has been extended for use with the radionuclide (201)Tl. Accuracy was evaluated with experimental phantom studies, including corrections for partial volume effects where necessary. The quantitative technique was used to derive standardized uptake values (SUVs) for (201)Tl evaluation of brain tumours. A preliminary study was performed on 26 patients using (201)Tl SPECT scans to assess residual tumour after surgery and then to monitor response...

Pilot study on evaluation of any correlation between MR perfusion (K(trans)) and diffusion (apparent diffusion coefficient) parameters in brain tumors at 3 Tesla.

Cancer Imaging — Wed, 08 Feb 2012 00:30:02 +0100

Conclusion: We found that irrespective of brain tumor type, there is an inverse correlation between ADC and K(trans). Our findings highlight an intricate relationship between vascular permeability and the tumor microenvironment, probably modulating and/or interacting with changes such as increased cellularity, ischemic insult and varying extracellular matrix composition. PMID: 22275724 [PubMed - in process] (Source: Cancer Imaging)

CD97 gene expression and function correlate with WT1 protein expression and glioma invasiveness

EurekAlert! - Medicine and Health — Tue, 07 Feb 2012 05:00:00 +0100

(Journal of Neurosurgery Publishing Group) Researchers at Virginia Commonwealth University and Old Dominion University have discovered that suppression of Wilms tumor 1 protein (WT1) results in downregulation of CD97 gene expression in three glioblastoma cell lines and reduces the characteristic invasiveness exhibited by glial tumor cells. This finding is published online Feb. 7 in the Journal of Neurosurgery. Although further studies must be performed, the authors propose that CD97 may prove to be a new target for anti-glioma therapies. (Source: EurekAlert! - Medicine and Health)

Gene-Gene Interactions Between Interleukin-12A and Interleukin-12B with the Risk of Brain Tumor

DNA and Cell Biology — Mon, 06 Feb 2012 21:03:55 +0100

DNA and Cell Biology Feb 2012, Vol. 31, No. 2: 219-223. (Source: DNA and Cell Biology)

Namibia: Mother Distances Herself From Financial Appeal

AllAfrica News: Health and Medicine — Mon, 06 Feb 2012 13:15:06 +0100

[New Era] Windhoek - The mother of 13-year-old Jade Sinead Abrahams who has a cancerous brain tumour, has distanced herself from a newspaper report in which the teenager's father requested the public for financial assistance for an operation. (Source: AllAfrica News: Health and Medicine)

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Brain Tumor Eradication And Prolonged Survival

Health News from Medical News Today — Mon, 06 Feb 2012 09:00:00 +0100

Tocagen Inc. has announced the publication of data showing the company's investigational treatment for high grade glioma eradicates brain tumors and provides a dramatic survival benefit in mouse models of glioblastoma. Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43. The article was published in the February issue of the Neuro-Oncology journal... (Source: Health News from Medical News Today)

New Hope For Patients With Deadly Brain Tumor

Health News from Medical News Today — Mon, 06 Feb 2012 08:00:00 +0100

Jim Black is fighting the meanest, most aggressive, most common kind of brain tumor in the United States: recurrent glioblastoma multiforme (GBM). In the United States, each year, approximately 10,000 patients are affected by GBM. Now, a novel investigational device - available only at clinical trial sites - is offering new hope to these patients. The non-invasive procedure - called Tumor Treating Fields (TTF) - is delivered using a portable device - called the NovoTTF-100A System made by Novocure... (Source: Health News from Medical News Today)

Discovery predicts patient sensitivity to important drug target in deadly brain cancer

EurekAlert! - Medicine and Health — Mon, 06 Feb 2012 05:00:00 +0100

(Van Andel Research Institute) A recent discovery by Van Andel Research Institute scientists enables the prediction of patient sensitivity to proposed drug therapies for glioblastoma - the most common and most aggressive malignant brain tumor in humans. (Source: EurekAlert! - Medicine and Health)

Development and piloting of a brain tumour‐specific question prompt list

European Journal of Cancer Care — Mon, 06 Feb 2012 05:00:00 +0100

The objective of this research was to develop a question prompt list aimed at increasing question asking and reducing the unmet information needs of adults with primary brain tumours, and to pilot the question prompt list to determine its suitability for the intended population. Thematic analysis of existing resources was used to create a draft which was refined via interviews with 12 brain tumour patients and six relatives, readability testing and review by health professionals. A non‐randomised before–after pilot study with 20 brain tumour patients was used to assess the acceptability and usefulness of the question prompt list, compared with a ‘standard brochure’, and the feasibility of evaluation strategies. The question prompt list developed covered seven main topics (diagnosis...

Scientists target cholesterol to treat brain tumors

Cancer — Sun, 05 Feb 2012 12:56:15 +0100

(Source: Cancer)

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W5: Life or death - who gets to decide?

CTV Health — Sun, 05 Feb 2012 00:02:59 +0100

Hassan Rasouli, an electrical engineer, brought his family to Toronto from Iran, in the spring of 2010. Five months later, what was supposed to be routine surgery for a benign brain tumor, left Hassan unconscious. Bacterial meningitis had infected his brain. (Source: CTV Health)

CCND1 G870A Polymorphism with Altered Cyclin D1 Transcripts Expression Is Associated with the Risk of Glioma in a Chinese Population

DNA and Cell Biology — Sat, 04 Feb 2012 04:05:10 +0100

DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)

'Cycling gave me my freedom back'

BBC News | Health | UK Edition — Sat, 04 Feb 2012 01:28:41 +0100

'How cycling helped me fight my brain tumours' (Source: BBC News | Health | UK Edition)

New hope for patients with brain tumors

ScienceDaily Headlines — Fri, 03 Feb 2012 19:11:11 +0100

In the United States, each year, approximately 10,000 patients are affected by recurrent glioblastoma multiforme. Now, a novel investigational device – available only at clinical trial sites – is offering new hope to these patients. (Source: ScienceDaily Headlines)

Heparan sulfate sulfatase SULF2 regulates PDGFR{alpha} signaling and growth in human and mouse malignant glioma

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2–/– tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in a...

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Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma

Cell and Tissue Research — Fri, 03 Feb 2012 17:53:17 +0100

Abstract In human glioblastoma, the blood–brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metallopr...

For Brain Cancer - A Thought-Provoking New Therapeutic Target?

Health News from Medical News Today — Fri, 03 Feb 2012 08:00:00 +0100

Glioblastoma multiforme (GBM) is the most common of all malignant brain tumors that originate in the brain. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant to current therapies. New therapeutic approaches are therefore much needed. Joanna Phillips, Zena Werb, and colleagues, at the University of California, San Francisco, have now identified a potential new therapeutic target for the treatment of GBM... (Source: Health News from Medical News Today)

Study published in Neuro-Oncology shows brain tumor eradication and prolonged survival

EurekAlert! - Biology — Fri, 03 Feb 2012 05:00:00 +0100

(Canale Communications) Tocagen Inc. today announced the publication of data showing the company's investigational treatment for high grade glioma eradicates brain tumors and provides a dramatic survival benefit in mouse models of glioblastoma. Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43. The article was published today in the February issue of the Neuro-Oncology journal. (Source: EurekAlert! - Biology)

UC San Diego Moores Cancer Center offers new hope for deadly brain tumor

EurekAlert! - Medicine and Health — Fri, 03 Feb 2012 05:00:00 +0100

(University of California - San Diego) In the United States, each year, approximately 10,000 patients are affected by recurrant glioblastoma multiforme. Now, a novel investigational device - available only at clinical trial sites - is offering new hope to these patients. (Source: EurekAlert! - Medicine and Health)

Multiple eruptive pilomatricomas in a 9‐year‐old boy with glioblastoma

Pediatric Dermatology — Fri, 03 Feb 2012 05:00:00 +0100

Abstract: A 9‐year‐old male presented to our dermatology clinic with a recent history of developing numerous cutaneous pilomatricomas, and was subsequently discovered to have sustained a recurrence of his glioblastoma multiforme. Immunohistochemical staining of a representative pilomatricoma and his original brain tumor revealed upregulation and nuclear localization of beta‐catenin, a sign associated with poor prognosis in glioblastoma. We hypothesize that the development of multiple pilomatricomas may have been a hallmark of this patient's tumor recurrence and provide support for a recent report of an association between multiple pilomatricomas and gliomatosis cerebri. (Source: Pediatric Dermatology)

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Sodium-dependent Migration and Proliferation in Glioma Cells [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

In this study, we have investigated the role of a glioma-specific cation channel assembled from subunits of the Deg/epithelial sodium channel (ENaC) superfamily, in the regulation of migration and cell cycle progression in glioma cells. Channel inhibition by psalmotoxin-1 (PcTX-1) significantly inhibited migration and proliferation of D54-MG glioma cells. Both PcTX-1 and benzamil, an amiloride analog, caused cell cycle arrest of D54-MG cells in G0/G1 phases (by 30 and 40%, respectively) and reduced cell accumulation in S and G2/M phases after 24 h of incubation. Both PcTX-1 and benzamil up-regulated expression of cyclin-dependent kinase inhibitor proteins p21Cip1 and p27Kip1. Similar results were obtained in U87MG and primary glioblastoma multiforme cells maintained in primary culture and ...

An essential role for p38 MAPK in cerebellar granule neuron precursor proliferation

Acta Neuropathologica — Thu, 02 Feb 2012 18:15:33 +0100

Abstract Development of the cerebellum occurs postnatally and is marked by a rapid proliferation of cerebellar granule neuron precursors (CGNPs). CGNPs are the cells of origin for SHH-driven medulloblastoma, the most common malignant brain tumor in children. Here, we investigated the role of ERK, JNK, and p38 mitogen-activated protein kinases in CGNP proliferation. We found high levels of p38α in proliferating CGNPs. Concomitantly, members of the p38 pathway, such as ASK1, MKK3 and ATF-2, were also elevated. Inhibition of the Shh pathway or CGNP proliferation blunts p38α levels, irrespective of Shh treatment. Strikingly, p38α levels were high in vivo in the external granule layer of the postnatal cerebellum, Shh-dependent mouse medulloblastomas and human medulloblastoma...

A meningioma with peripheral rim enhancement on MRI

Brain Tumor Pathology — Thu, 02 Feb 2012 18:12:00 +0100

Abstract Meningiomas are common, typically benign intracranial neoplasms with well-demarcated borders. Meningiomas with indistinct boundaries have been reported. These can invade surrounding structures, and present surgical and diagnostic challenges. We present the case of an unusual meningioma in a 53-year-old male in which preoperative magnetic resonance imaging (MRI) revealed an irregular lesion with clear boundaries and peripheral rim enhancement. Intraoperatively, however, no cleavage plane was apparent. Histological examination showed an increase of fibroconnective tissue with proliferation of dilated vessels in the periphery of the tumor concordant with the rim. Immunohistochemical staining of the tumor was positive for EMA and CD34, but negative for CEA, Ki67, and ...

Noninvasive imaging technique may replace risky brain tumor biopsies

HemOncToday.com — Thu, 02 Feb 2012 13:24:51 +0100

(Source: HemOncToday.com)

Del Mar Pharmaceuticals Granted U.S. Orphan Drug Designation For VAL-083 For The Treatment Of Glioma

Pharmaceutical Online News — Thu, 02 Feb 2012 10:36:00 +0100

DelMar Pharma today announced that the United States FDA Office of Orphan Products Development has granted orphan drug designation for VAL-083 for the treatment of glioma, including glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. (Source: Pharmaceutical Online News)

Early prediction of response to Vorinostat in an orthotopic rat glioma model

NMR in Biomedicine — Thu, 02 Feb 2012 05:00:00 +0100

Glioblastoma is the most common primary brain tumor and is uniformly fatal despite aggressive surgical and adjuvant therapy. As survival is short, it is critical to determine the value of therapy early on in treatment. Improved early predictive assessment would allow neuro‐oncologists to personalize and adjust or change treatment sooner to maximize the use of efficacious therapy. During carcinogenesis, tumor suppressor genes can be silenced by aberrant histone deacetylation. This epigenetic modification has become an important target for tumor therapy. Suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) is an orally active, potent inhibitor of histone deacetylase (HDAC) activity. A major shortcoming of the use of HDAC inhibitors in the treatment of patients with brain tumors is t...

In silico Experimentation of Glioma Microenvironment Development and Anti-tumor Therapy

PLoS Computational Biology — Thu, 02 Feb 2012 05:00:00 +0100

by Yu Wu, Yao Lu, Weiqiang Chen, Jianping Fu, Rong Fan Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but striki...

Deletion of the SPARC acidic domain or EGF-like module reduces SPARC-induced migration and signaling through p38 MAPK/HSP27 in glioma

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

In conclusion, deletions of the acidic domain and EGF-like module have differential effects on cell surface binding and HSP27 protein stability; however, both regions regulate SPARC-induced migration and signaling through HSP27. Our data link the domains of SPARC with different functions and suggest one or both of the constructs as potential therapeutic agents to inhibit SPARC-induced migration. (Source: Carcinogenesis)

A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

This study has uncovered a mechanism by which glioma cells exploit microglia for increased invasiveness. Specifically, glioma-derived CCL2 acts upon CCR2-bearing microglia, which then produces IL-6 to stimulate gliomas. The CCL2/CCR2/IL-6 loop is a potential therapeutic target for the currently incurable malignant gliomas. (Source: Carcinogenesis)

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5-Aminolevulinic acid-induced protoporphyrin IX fluorescence as immediate intraoperative indicator to improve the safety of malignant or high-grade brain tumor diagnosis in frameless stereotactic biopsies

Acta Neurochirurgica — Wed, 01 Feb 2012 17:14:11 +0100

Conclusion 5-ALA fluorescence in stereotactic biopsies can increase the safety and accuracy of these procedures by reducing sampling errors and eliminating the need for multiple samples and/or frozen section verification, creating a more accurate, faster and safer procedure for cases of suspected malignant or high-grade brain tumors situated in deep or eloquent areas. Content Type Journal ArticleCategory Clinical ArticlePages 1-4DOI 10.1007/s00701-012-1290-8Authors Gord von Campe, Universitätsklinik für Neurochirurgie, Medizinische Universität Graz, Graz, AustriaMichael Moschopulos, Department of Neuropathology, Kantonsspital Aarau, Aarau, SwitzerlandMartin Hefti, Neurochirurgisches Zentrum, Klinik Am Rosenberg, Hasenbühlstrasse 11, 9410 Heiden, Switzerland ...

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas

Investigational New Drugs — Wed, 01 Feb 2012 17:10:49 +0100

Summary L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase (hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma. We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals w...

Secrets of the inner voice unlocked

NHS News Feed — Wed, 01 Feb 2012 10:19:00 +0100

Conclusion This study of 15 people undergoing brain surgery has demonstrated a method of reconstructing the sound of a heard word using only the signals obtained from the brain. This study represents an important progression in the field of speech reconstruction, which has the potential to improve the lives of many who suffer from speech difficulties in the future. But the words, when reconstructed, were not of good enough quality to be recognised by a human listener when played. The words could only be identified when the original and reconstructed sound patterns were compared visually. The researchers suggest that improving the brain sensors detecting the STG brain activity may, in the future, improve the reconstructed sound to a level that could be understood by a person listening. The ...

Defects In The Packaging Of DNA In Malignant Brain Tumors

Health News from Medical News Today — Wed, 01 Feb 2012 08:00:00 +0100

Glioblastomas grow extremely aggressively into healthy brain tissue and, moreover, are highly resistant to radiation therapy and chemotherapy. Therefore, they are regarded as the most malignant type of brain tumor. Currently available treatment methods are frequently not very effective against this type of cancer. Glioblastoma can affect people of all ages, but is less common in children than in adults... (Source: Health News from Medical News Today)

Inhibition of sphingosine kinase 1 suppresses proliferation of glioma cells under hypoxia by attenuating activity of extracellular signal‐regulated kinase

Cell Proliferation — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: SphK1 and SphK2 are involved in proliferation of glioma cells in hypoxic conditions through distinct signalling pathways. SphK1, but not SphK2, promotes cell population expansion in hypoxic conditions by activating ERK. (Source: Cell Proliferation)

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A thought-provoking new therapeutic target for brain cancer?

EurekAlert! - Cancer — Wed, 01 Feb 2012 05:00:00 +0100

(Journal of Clinical Investigation) Glioblastoma multiforme (GBM) is the most common of all malignant brain tumors that originate in the brain. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant to current therapies. As reported in the Journal of Clinical Investigation, researchers have now identified the protein SULF2 as a potential new therapeutic target for the treatment of GBM. (Source: EurekAlert! - Cancer)

[News] Qiagen acquires new rights for personalised cancer care

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

As the push towards personalised healthcare in many developed and emerging economies continues, the race to develop quick and accurate companion diagnostic tests is hotting up, with cancer diagnostics at the forefront. In the past week Qiagen (Hilden, Germany) announced its acquisition of worldwide exclusive rights to develop a genetic test for the anaplastic lymphoma kinase (ALK) biomarker, which would potentially be used in conjunction with a new class of lung-cancer drugs, and similar rights to develop a test for mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), which have been implicated in low-grade gliomas, anaplastic gliomas, secondary glioblastoma, and acute myeloid leukaemia. (Source: The Lancet Oncology)

[Cancer and Society] Medikidz explain cancer

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

The Medikidz are a gang of superheroes with a mission—to explain medical information to children in plain language. In a series that includes titles such as What's up with Lyndon? Medikidz explain osteosarcoma, these five superheroes help kids understand brain tumours, melanoma, and several other types of cancer that affect children and families. Each 32-page book is designed as a graphic novel with vibrant illustrations and recurring themes and characters to keep kids engaged with the medical content. (Source: The Lancet Oncology)

Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria‐related appendicitis

Histopathology — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: Our data demonstrate that bacteria‐related active inflammation results in a sharp increase of DMBT1 levels in enterocytes. These findings substantiate the view that DMBT1 is of functional relevance for host defence and modulation of the course of intestinal bacteria‐related inflammatory responses. (Source: Histopathology)

Pseudotumoral form of neuroschistosomiasis: report of three cases in ganzi, china.

The American Journal of Tropical Medicine and Hygiene — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Wan H, Masataka H, Zhang LP, Zheng DF Abstract Abstract. The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnose...

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[Treatment of neuropathic pain with lacosamide].

Revista de Neurologia — Wed, 01 Feb 2012 05:00:00 +0100

CONCLUSION. Lacosamide can be an effective and well-tolerated alternative in the treatment of neuropathic pain and, moreover, its intravenous use can achieve pain control faster or be suitable when it is not tolerated orally. PMID: 22278893 [PubMed - in process] (Source: Revista de Neurologia)

Childhood Brain Tumors Linked To Newly Discovered Mutations

Health News from Medical News Today — Tue, 31 Jan 2012 17:00:00 +0100

A recent study published in the online edition of the scientific journal Nature Genetics of rare, lethal childhood tumors of the brainstem has revealed that almost 80% of tumors contain gene mutations that have previously not been associated with cancer. According to early evidence, gene alterations also implicate other aggressive pediatric brain tumors. The results provide a significant insight into a poorly understood tumor that has a mortality rate of over 90% in patients within two years... (Source: Health News from Medical News Today)

Brain Tumors in Children- Current Therapies and Newer Directions

Indian Journal of Pediatrics — Tue, 31 Jan 2012 16:47:55 +0100

Abstract Brain tumors are the second most common malignancy and the major cause of cancer related mortality in children. Though significant advances in neuroimaging, neurosurgery, radiation therapy and chemotherapy have evolved over the years, overall survival rate remains less than 75%. Malignant gliomas, high risk medulloblastoma with recurrence and infant brain tumors continue to be a major cause of therapeutic frustration. Even today diffuse pontine gliomas are universally fatal. Though tumors like low grade glioma have an overall excellent survival, recurrences and progression in eloquent areas pose therapeutic challenges. As research continues to unravel the biology including key molecules and signaling pathways responsible for the oncogenesis of different childhood ...

Central nervous system lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease)

Neurological Sciences — Tue, 31 Jan 2012 16:44:48 +0100

We report a case of CNS primitive lymphoma in an adult patient who resulted positive for NF1 at genetic testing. At present, only one case of CNS lymphoma in an adult patient displaying clinical criteria for NF1 diagnosis has been reported. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s10072-011-0886-8Authors Marica Eoli, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Unit of Molecular Neuro-Oncology, Milan, ItalyDonata Bianchessi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyAnna Luisa Di Stefano, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Prodi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Anghileri, Fondazione I.R.C.C.S. Istituto Neurologic...

Monoallelic Expression Determines Oncogenic Progression and Outcome in Benign and Malignant Brain Tumors

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Although monoallelic expression (MAE) is a frequent genomic event in normal tissues, its role in tumorigenesis remains unclear. Here we carried out single-nucleotide polymorphism arrays on DNA and RNA from a large cohort of pediatric and adult brain tumor tissues to determine the genome-wide rate of MAE, its role in specific cancer-related genes, and the clinical consequences of MAE in brain tumors. We also used targeted genotyping to examine the role of tumor-related genes in brain tumor development and specifically examined the clinical consequences of MAE at TP53 and IDH1. The genome-wide rate of tumor MAE was higher than in previously described normal tissue and increased with specific tumor grade. Oncogenes, but not tumor suppressors, exhibited significantly higher MAE in high-grade c...

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Classifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here, we illustrate how gliomas can be rapidly classified by desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was carried out on 36 human glioma samples, including oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Gray and white matter from glial tumors were readily discriminated and detailed diagnostic information could ...

A Pharmacologic Inhibitor of the Protease Taspase1 Effectively Inhibits Breast and Brain Tumor Growth

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

In this study, we developed and evaluated small molecule inhibitors of Taspase1 as a new candidate class of therapeutic modalities. Genetic deletion of Taspase1 in the mouse produced no overt deficiencies, suggesting the possibility of a wide therapeutic index for use of Taspase1 inhibitors in cancers. We defined the peptidyl motifs recognized by Taspase1 and conducted a cell-based dual-fluorescent proteolytic screen of the National Cancer Institute diversity library to identify Taspase1 inhibitors (TASPIN). On the basis of secondary and tertiary screens the 4-[(4-arsonophenyl)methyl]phenyl] arsonic acid NSC48300 was determined to be the most specific active compound. Structure–activity relationship studies indicated a crucial role for the arsenic acid moiety in mediating Taspase1 inhibi...

A unified impulse response model for DCE‐MRI

Magnetic Resonance in Medicine — Tue, 31 Jan 2012 05:00:00 +0100

We describe the gamma capillary transit time model, a generalized impulse response model for DCE‐MRI that mathematically unifies the Tofts‐Kety, extended Tofts‐Kety, adiabatic tissue homogeneity, and two‐compartment exchange models. By including a parameter (α−1) representing the width of the distribution of capillary transit times within a tissue voxel, the GCTT model discriminates tissues having relatively monodisperse transit time distributions from those having a large degree of heterogeneity. All five models were compared using in vivo data acquired in three brain tumors (one glioblastoma multiforme, one pleomorphic xanthoastrocytoma, and one anaplastic meningioma) and Monte Carlo simulations. Our principal findings are : (1) The four most commonly used models for dynamic c...

Stunning 7-Year Survival Difference in Brain Tumor TrialStunning 7-Year Survival Difference in Brain Tumor Trial

Medscape Today Headlines — Mon, 30 Jan 2012 17:23:42 +0100

A study of patients with oligodendrogliomas has a practice-changing result. Medscape Medical News (Source: Medscape Today Headlines)

New MRI Technique Helps Diagnose Gliomas

Diagnostic Imaging — Mon, 30 Jan 2012 09:30:01 +0100

A new magnetic resonance spectroscopy (MRS) technique provides a definitive diagnosis of brain cancer based on imaging of a protein associated with a mutated gene found in 80 percent of low- and intermediate-grade gliomas, according to a new study published January 26 in Nature Medicine. (Source: Diagnostic Imaging)

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Mutations Tied To Aggressive Childhood Brain Tumors Revealed By Cancer Sequencing Initiative

Health News from Medical News Today — Mon, 30 Jan 2012 09:00:00 +0100

Researchers studying a rare, lethal childhood tumor of the brainstem discovered that nearly 80 percent of the tumors have mutations in genes not previously tied to cancer. Early evidence suggests the alterations play a unique role in other aggressive pediatric brain tumors as well. The findings from the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project (PCGP) offer important insight into a poorly understood tumor that kills more than 90 percent of patients within two years... (Source: Health News from Medical News Today)

Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model.

Cell Cycle — Mon, 30 Jan 2012 08:36:30 +0100

In this study, we demonstrated that the Salmonella typhimurium A1-R tumor-targeting strain can inhibit and eradicate human glioma in an orthotopic nude-mouse model. S. typhimurium A1-R was administered by injection through a craniotomy open-window or intravenously in nude mice. To establish the model, 2 x 105 U87-RFP human glioma cells were injected stereotactically into the mouse brain through the craniotomy open window. Two weeks after glioma-cell implantation, mice were treated with S. typhimurium A1-R [2 x 10 ( 7) CFU/200 μl intravenous injection (i.v.) or 1 x 10 ( 6) CFU/1 μl intracranial injection (i.c.)] once a week for 3 weeks. Brain tumors were observed by fluorescence imaging through the craniotomy open window over time. S. typhimurium A1-R, administered i.c., inhibited brain t...

Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma and is a potential chemotherapeutic target in gliomas.

Cell Cycle — Mon, 30 Jan 2012 08:36:21 +0100

Authors: Lehman NL, O'Donnell JP, Whiteley LJ, Stapp RT, Lehman TD, Roszka KM, Schultz LR, Williams CJ, Mikkelsen T, Brown SL, Ecsedy JA, Poisson LM Abstract Aurora A is critical for mitosis and is overexpressed in several neoplasms. Its overexpression transforms cultured cells, and both its overexpression and knockdown cause genomic instability. In transgenic mice, Aurora A haploinsufficiency, not overexpression, leads to increased malignant tumor formation. Aurora A thus appears to have both tumor-promoting and tumor-suppressor functions. Here, we report that Aurora A protein, measured by quantitative protein gel blotting, is differentially expressed in major glioma types in lineage-specific patterns. Aurora A protein levels in WHO grade II oligodendrogliomas (n = 16) and grade I...

Patient Care Could Be Revolutionized By Diagnostic Brain Tumor Test

Health News from Medical News Today — Mon, 30 Jan 2012 08:00:00 +0100

Researchers at UT Southwestern Medical Center have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. The unique test could preclude the need for surgery in patients whose tumors are located in areas of the brain too dangerous to biopsy. This new magnetic resonance spectroscopy (MRS) technique provides a definitive diagnosis of cancer based on imaging of a protein associated with a mutated gene found in 80 percent of low- and intermediate-grade gliomas. Presence of the mutation also means a better prognosis... (Source: Health News from Medical News Today)

Care and support needs of patients and carers early post-discharge following treatment for non-malignant brain tumour: establishing a new reality

Supportive Care in Cancer — Mon, 30 Jan 2012 06:32:03 +0100

Conclusion Participants had a tendency to rely on informal support networks but identified unmet information and support needs particularly for carers. These findings highlight the need for more efficient and effective discharge preparation, referral to services and supports, provision of timely information and support for family caregivers of those with brain tumour. Content Type Journal ArticleCategory Original ArticlePages 1-16DOI 10.1007/s00520-012-1383-1Authors Petrea Cornwell, Metro North Health Service District, Queensland Health, Chermside, AustraliaBronwyn Dicks, School of Health and Rehabilitation Sciences, The University of Queensland, St. Lucia, AustraliaJennifer Fleming, School of Health and Rehabilitation Sciences, The University of Queensland, St. Luc...

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A case of primary diffuse leptomeningeal gliomatosis predominantly involving the cervical spinal cord and mimicking chronic meningitis.

Turkish Neurosurgery — Mon, 30 Jan 2012 05:00:02 +0100

Authors: Heijink DS, Urgun K, Sav A, Seker A, Konya D Abstract Gliomas may rarely arise in the leptomeninges without any evidence of intraaxial involvement. A case of primary diffuse leptomeningeal gliomatosis (PDLG) histologically diagnosed as oligoastrocytoma is presented. A 50-year-old woman presented with nausea, vomiting and headache. Magnetic resonance imaging (MRI) of cranium and cervical region revealed dural thickening starting from the craniocervical junction to the level of C4 without any parenchymal lesions. CSF examination showed an increase in protein and decrease in glucose levels. There were neither any kind of atypical cells nor any kind of growth in bacterial cultures. The patient underwent biopsy at the level of C1 for diagnosis. The specimen wa...

Defects in the packaging of DNA in malignant brain tumors

EurekAlert! - Medicine and Health — Mon, 30 Jan 2012 05:00:00 +0100

(Helmholtz Association of German Research Centres) In children with glioblastoma, a particularly aggressive brain tumor, scientists have discovered mutations that affect the function of proteins known as histones. Histones serve as coils around which the DNA wraps. At the same time, histones regulate gene activity. Mutations in histone genes have never before been tied to a disease. Scientists of the German Cancer Research Center, Heidelberg University Hospitals and McGill University in Canada have now reported their findings in Nature. (Source: EurekAlert! - Medicine and Health)

Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the anti‐angiogenic effects of cediranib (AZD2171) in rat C6 gliomas

International Journal of Cancer — Mon, 30 Jan 2012 05:00:00 +0100

This study aimed to evaluate CUSPIO biomarkers for the assessment of tumour response to anti‐angiogenic therapy. CUSPIO imaging was performed in subcutaneous rat C6 gliomas before and 2 days after treatment with the potent VEGF signalling inhibitor cediranib (n=12), or vehicle (n=12). Histological validation of Hoechst 33342 uptake (perfusion), smooth muscle actin staining (maturation), pimonidazole adduct formation (hypoxia) and necrosis were sought. Following treatment, there was a significant decrease in fractional blood volume (‐43%, p<0.01) and a significant increase in haemodynamic vascular functionality (treatment altered ΔR2*carbogen from 1.2 to ‐0.2 s‐1, p<0.05). CUSPIO imaging revealed an overall significant decrease in plasma perfusion (‐27%, p<0.05) followin...

Cancer sequencing initiative discovers mutations tied to aggressive childhood brain tumors

ScienceDaily Headlines — Sun, 29 Jan 2012 20:10:10 +0100

A cancer sequencing initiative has discovered mutations tied to aggressive childhood brain tumors. Early evidence suggests the alterations play a unique role in other aggressive pediatric brain tumors as well. (Source: ScienceDaily Headlines)

Experts recommend genetic counseling for young sarcoma patients

Thrive, Children's Hospital Boston — Sun, 29 Jan 2012 13:41:39 +0100

Genetic testing may help sarcoma patients and their famlies know their risk of other cancers later in life If your child is diagnosed with a sarcoma—a tumor in connective tissue like muscles or bones—it’s natural to become totally focused on his immediate recovery. But what if beating sarcoma wasn’t the only time your child might face cancer? Data shows that there is a link between sarcomas and Li-Fraumeni syndrome, a rare condition that raises a person’s risk of developing one or more cancers to as high as 85 percent. Cancers typically diagnosed in patients with Li-Fraumeni syndrome include breast cancer, sarcomas, brain tumors, acute leukemia and adrenal cortical carcinoma. Recently, the list has been expanded to include colon cancer and stomach cancer. Li-Fraumeni syndrome m...

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Cancer sequencing initiative discovers mutations tied to aggressive childhood brain tumors

EurekAlert! - Medicine and Health — Sun, 29 Jan 2012 05:00:00 +0100

(St. Jude Children's Research Hospital) Researchers studying a rare, lethal childhood tumor of the brainstem discovered that nearly 80 percent of the tumors have mutations in genes not previously tied to cancer. Early evidence suggests the alterations play a unique role in other aggressive pediatric brain tumors as well. (Source: EurekAlert! - Medicine and Health)

Evaluation of biocompatibility and anti-glioma efficacy of doxorubicin and irinotecan drug-eluting bead suspensions in alginate

Clinical and Translational Oncology — Sat, 28 Jan 2012 16:53:16 +0100

Discussion We conclude that the alginate suspension of irinotecan DEBs can be considered safe and effective in a clinical setting. Content Type Journal ArticleCategory Research ArticlesPages 50-59DOI 10.1007/s12094-012-0761-yAuthors Silke Glage, Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyAndrew L. Lewis, Biocompatibles UK Ltd., Farnham Business Park Weydon Lane, Farnham, Surrey, GU9 8QL UKPatricia Mertens, International Neuroscience Institute, Rudolf-Pichlmayrstr. 4, 30625 Hannover, GermanySteffen Baltes, International Neuroscience Institute, Rudolf-Pichlmayrstr. 4, 30625 Hannover, GermanyPeter Geigle, CellMed AG, Industriestrasse 19, 63755 Alzenau, GermanyThomas Brinker, Inte...

Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis

Clinical and Translational Oncology — Sat, 28 Jan 2012 16:53:10 +0100

Conclusions NSCLC patients with brain metastasis treated by brain surgery followed by radiotherapy may have a higher chance of relapse when the tumour has methylation of the MGMT promoter region. Content Type Journal ArticleCategory Research ArticlesPages 31-35DOI 10.1007/s12094-012-0758-6Authors Kenji Hashimoto, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYoshitaka Narita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYuko Matsushita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYasuji Miyakita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanMakoto...

Diagnostic brain tumor test could revolutionize care of patients with low-grade gliomas

UT Southwestern Medical Center News — Sat, 28 Jan 2012 10:53:06 +0100

Researchers have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. (Source: UT Southwestern Medical Center News)

Semantic memory is impaired in patients with unilateral anterior temporal lobe resection for temporal lobe epilepsy

Brain — Sat, 28 Jan 2012 05:00:00 +0100

In this study, therefore, we investigated the semantic performance of 20 patients with resection for chronic temporal lobe epilepsy with a full battery of semantic assessments, including more sensitive measures of semantic processing. The results provide a bridge between the current clinical observations about resection for temporal lobe epilepsy and the expectations from semantic dementia and other neuroscience findings. Specifically, we found that on simple semantic tasks, the patients’ accuracy fell in the normal range, with the exception that some patients with left resection for temporal lobe epilepsy had measurable anomia. Once the semantic assessments were made more challenging, by probing specific-level concepts, lower frequency/more abstract items or measuring reaction times...

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Balancing self‐renewal and differentiation by asymmetric division: Insights from brain tumor suppressors in Drosophila neural stem cells

BioEssays — Fri, 27 Jan 2012 21:40:09 +0100

AbstractBalancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular mechanisms of asymmetric cell division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the...

MGMT promoter hypermethylation and its associations with genetic alterations in a series of 350 brain tumors

Journal of Neuro-Oncology — Fri, 27 Jan 2012 17:56:38 +0100

The objective of this study was to retrospectively investigate MGMT promoter hypermethylation status for a series of 350 human brain tumors, including 275 gliomas of different malignancy grade, 21 glioblastoma multiforme (GBM) cell lines, and 75 non-glial tumors. The analysis was performed by methylation-specific PCR and capillary electrophoresis. MGMT expression at the protein level was also evaluated by both immunohistochemistry (IHC) and western blotting analysis. Associations of MGMT hypermethylation with IDH1/IDH2 mutations, EGFR amplification, TP53 mutations, and 1p/19q co-deletion, and the prognostic significance of these, were investigated for the gliomas. MGMT promoter hypermethylation was identified in 37.8% of gliomas, but was not present in non-glial tumors, with the excepti...

Hematogenous extraneural metastasis of the germinomatous component of a pineal mixed germ cell tumor

Brain Tumor Pathology — Fri, 27 Jan 2012 17:56:01 +0100

Abstract A 23-year-old man presented with a mass in the pineal region and obstructive hydrocephalus. A neuroendoscopic biopsy for the lesion, ventriculoperitoneal (VP) shunting, and focal irradiation were conducted as initial treatment. Histological diagnosis of the biopsy specimen was germinoma. He underwent further irradiation and two tumor resections. Histological diagnosis was mature teratoma without a germinomatous component. After serial treatments, the intracranial lesion was controlled. However, 14 months after presentation, extraneural lesions were confirmed in the posterior mediastinum and retroperitoneal space. The biopsy specimen of the retroperitoneal space lesion was histologically diagnosed as germinoma. Although chemotherapy with cisplatin and etoposid...

Intra-operative 3-T MRI for paediatric brain tumours: challenges and perspectives

Pediatric Radiology — Fri, 27 Jan 2012 17:54:47 +0100

Abstract MRI is the ideal modality for imaging intracranial tumours. Intraoperative MRI (ioMRI) makes it possible to obtain scans during a neurosurgical operation that can aid complete macroscopic tumour resection — a major prognostic factor in the majority of brain tumours in children. Intra-operative MRI can also help limit damage to normal brain tissue. It therefore has the potential to improve the survival of children with brain tumours and to minimise morbidity, including neurological deficits. The use of ioMRI is also likely to reduce the need for second look surgery, and may reduce the need for chemotherapy and radiotherapy. High-field MRI systems provide better anatomical information and also enable effective utilisation of advanced MRI techniques such as perfusi...

Study: MRS may provide diagnostic, prognostic biomarker for brain tumors

Health Imaging News — Fri, 27 Jan 2012 13:14:01 +0100

A new magnetic resonance spectroscopy (MRS) technique may offer a method to detect and track a protein associated with a genetic mutation in brain tumor cancer cells. The method could inform diagnosis of glioma and provide prognostic information, according to a study published online Jan. 26 in Nature Medicine. (Source: Health Imaging News)

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Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Nature AOP — Fri, 27 Jan 2012 09:37:24 +0100

Authors: Jeremy Schwartzentruber, Andrey Korshunov, Xiao-Yang Liu, David T. W. Jones, Elke Pfaff, Karine Jacob, Dominik Sturm, Adam M. Fontebasso, Dong-Anh Khuong Quang, Martje Tönjes, Volker Hovestadt, Steffen Albrecht, Marcel Kool, Andre Nantel, Carolin Konermann, Anders Lindroth, Natalie Jäger, Tobias Rausch, Marina Ryzhova, Jan O. Korbel, Thomas Hielscher, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Martin Ebinger, Martin U. Schuhmann, Wolfram Scheurlen, Arnulf Pekrun, Michael C. Frühwald, Wolfgang Roggendorf, Christoph Kramm, Matthias Dürken, Jeffrey Atkinson, Pierre Lepage, Alexandre Montpetit, Magdalena Zakrzewska, Krzystof Zakrzewski, Pawel P. Liberski, Zhifeng Dong, Peter Siegel, Andreas E. Kulozik, Marc Zapatka, Abhijit Guha, David Malkin, J...

Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases [Neurooncology]

Journal of Clinical Oncology — Fri, 27 Jan 2012 05:00:00 +0100

Conclusion Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases. (Source: Journal of Clinical Oncology)

Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: Toxicity and efficacy trends

Pediatric Blood and Cancer — Fri, 27 Jan 2012 05:00:00 +0100

ConclusionBevacizumab‐related acute toxicity appears to be low in children, even in combination with irinotecan. Further prospective trials are required to confirm the hypothetical efficacy of bevacizumab and to assess the risk of long‐term toxicity especially in the youngest children. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Targeting the enhancer of zeste homologue 2 in medulloblastoma

International Journal of Cancer — Fri, 27 Jan 2012 05:00:00 +0100

AbstractEnhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 that catalyzes the trimethylation of histone H3 on Lys 27, and represses gene transcription. EZH2 enhances cancer‐cell proliferation and regulates stem cell maintenance and differentiation. Here, we demonstrate that EZH2 is highly expressed in medulloblastoma, a highly malignant brain tumor of childhood, and this altered expression is correlated with genomic gain of chromosome 7 in a subset of medulloblastoma. Inhibition of EZH2 by RNAi suppresses medulloblastoma tumor cell growth. We show that 3‐deazaneplanocin A, a chemical inhibitor of EZH2, can suppress medulloblastoma cell growth partially by inducing apoptosis. Suppression of EZH2 expression diminishes the ability of tumor cells...

The regulation of cysteine cathepsins and cystatins in human gliomas

International Journal of Cancer — Fri, 27 Jan 2012 05:00:00 +0100

AbstractCysteine cathepsins play an important role in shaping the highly infiltrative growth pattern of human gliomas. We have previously demonstrated that the activity of cysteine cathepsins is elevated in invasive GBM cells in vitro, in part due to attenuation of their endogenous inhibitors, the cystatins. To investigate this relationship in vivo, we established U87‐MG xenografts in NOD/SCID‐eGFP mice. Here, tumour growth correlated with an elevated enzymatic activity of CatB both in the tumour core and at the periphery, whereas CatS and CatL levels were higher at the xenograft edge compared to the core. Reversely, StefB expression was detected in the tumour core, but it was generally absent in the tumour periphery, suggesting that down‐regulation of this inhibitor correlates with ...

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In vivo intraoperative confocal microscopy for real-time histopathological imaging of brain tumors.

Journal of Neurosurgery — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions Further study will be necessary for better definition of the role of intraoperative confocal microscopy as a routine adjunct for intraoperative brain tumor diagnosis. PMID: 22283191 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

The expression and effects the CABYR-c transcript of CABYR gene in hepatocellular carcinoma.

Bulletin du Cancer — Fri, 27 Jan 2012 05:00:00 +0100

Conclusion. CABYR-c is highly expressed in hepatocellular carcinoma tissues and may play an oncogenic role in heptocarcinogenesis as well as its progression. PMID: 22285430 [PubMed - as supplied by publisher] (Source: Bulletin du Cancer)

Efficacy of vincristine administered via convection-enhanced delivery in a rodent brainstem tumor model documented by bioluminescence imaging

Child's Nervous System — Thu, 26 Jan 2012 16:44:15 +0100

Conclusions VCR administered by CED was effective in reducing tumors and prolonging survival time. Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s00381-012-1690-3Authors Guifa Xi, Division of Pediatric Neurosurgery, Falk Brain Tumor Center, Children’s Memorial Hospital, Northwestern University, Feinberg School of Medicine, 2300 Children’s Plaza, 2430N Halsted St, Box # 28, Chicago, IL 60614, USAVeena Rajaram, Division of Anatomic Pathology, Children’s Memorial Hospital, 2300 Children’s Plaza, Box # 28, Chicago, IL 60614, USABabara Mania-Farnell, Department of Biological Sciences, Purdue University Calumet, 2200 169th Street, Hammond, IN 46323, USAChandra S. Mayanil, Department of Development Biology, Children’s Memorial Research Cent...

Are the psychological needs of adolescent survivors of pediatric cancer adequately identified and treated?

Psycho-Oncology — Thu, 26 Jan 2012 13:19:03 +0100

ConclusionsMany adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long‐term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors' needs, particularly for lower‐income survivors and those treated with cranial radiation therapy. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Psycho-Oncology)

The challenge to remove diffuse low-grade gliomas while preserving brain functions

Acta Neurochirurgica — Thu, 26 Jan 2012 06:43:52 +0100

Abstract WHO grade II glioma, i.e. diffuse low-grade glioma, is a pre-malignant tumour, usually revealed by seizures in young patients with a normal life. This tumour has a constant growth, and will inescapably become anaplastic. Surgical resection significantly increases the overall survival by delaying the malignant transformation. Thus, the dilemma is to perform early surgery in order to optimise the extent of resection (and thus the median survival) by removing smaller tumours while preserving the quality of life. To this end, the new concept proposed in this review is to achieve surgical resection according to functional and not to oncological boundaries. In other words, the principle is to first understand the cerebral anatomo-functional organisation at the individua...

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[Image-guided radiation therapy : Paradigm change in radiation therapy.]

Der Radiologe — Thu, 26 Jan 2012 05:00:00 +0100

[Image-guided radiation therapy : Paradigm change in radiation therapy.] Radiologe. 2012 Jan 26; Authors: Wenz F, Belka C, Reiser M, Schönberg SO Abstract CLINICAL ISSUE: The introduction of image-guided radiotherapy (IGRT) has changed the workflow in radiation oncology more dramatically than any other innovation in the last decades. STANDARD TREATMENT: Imaging for treatment planning before the initiation of the radiotherapy series does not take alterations in patient anatomy and organ movement into account. TREATMENT INNOVATIONS: The principle of IGRT is the temporal and spatial connection of imaging in the treatment position immediately before radiation treatment. DIAGNOSTIC ASSE...

Comparison between intensity normalization techniques for dynamic susceptibility contrast (DSC)‐MRI estimates of cerebral blood volume (CBV) in human gliomas

Journal of Magnetic Resonance Imaging — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion:The results suggest Gaussian normalization of leakage‐corrected CBV maps may be the best choice for image intensity correction for use in large‐scale, multicenter clinical trials where MR scanners and protocols vary widely due to ease of implementation, lowest variability, and highest tumor to normal tissue contrast. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc. (Source: Journal of Magnetic Resonance Imaging)

Is T2* Enough to Assess Oxygenation? Quantitative Blood Oxygen Level-Dependent Analysis in Brain Tumor [Experimental Studies]

Radiology — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion: Additional measurements, such as BVf, T2, and B0, are needed to obtain reliable information on oxygenation with BOLD MR imaging. The proposed quantitative BOLD approach, which includes these measurements, appears to be a promising tool with which to map tumor oxygenation. © RSNA, 2011 (Source: Radiology)

Diagnostic brain tumor test could revolutionize care of patients

EurekAlert! - Medicine and Health — Thu, 26 Jan 2012 05:00:00 +0100

(UT Southwestern Medical Center) Researchers have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. The unique test could preclude the need for surgery in patients whose tumors are located in areas of the brain too dangerous to biopsy. (Source: EurekAlert! - Medicine and Health)

Pyruvate Protects the Brain Against Ischemia-Reperfusion Injury by Activating the Erythropoietin Signaling Pathway.

Stroke — Thu, 26 Jan 2012 05:00:00 +0100

CONCLUSIONS: Pyruvate activation of the hypoxia-inducible factor-1α-EPO signaling cascade in neurons and glia could protect the brain from ischemia-reperfusion injury. PMID: 22282883 [PubMed - as supplied by publisher] (Source: Stroke)

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Prognostic significance of MRP5 immunohistochemical expression in glioblastoma

Cancer Chemotherapy and Pharmacology — Wed, 25 Jan 2012 18:14:31 +0100

Conclusion The present results imply that MRP5 index may hold a prognostic role in patients with GBM. Content Type Journal ArticleCategory Short CommunicationPages 1-5DOI 10.1007/s00280-012-1832-zAuthors George A. Alexiou, Department of Neurosurgery, University Hospital of Ioannina, Ioannina, GreeceAnna Goussia, Department of Pathology, University Hospital of Ioannina, Ioannina, GreeceSpyridon Voulgaris, Department of Neurosurgery, University Hospital of Ioannina, Ioannina, GreeceAndreas D. Fotopoulos, Department of Nuclear Medicine, University Hospital of Ioannina, Ioannina, GreeceGeorge Fotakopoulos, Department of Neurosurgery, University Hospital of Ioannina, Ioannina, GreeceAntigoni Ntoulia, Department of Pathology, University Hospital of Ioannina, Ioannina, GreeceA...

Intracranial Masson tumor: case report and literature review

Journal of Neuro-Oncology — Wed, 25 Jan 2012 18:04:09 +0100

We report a third case of a neonate who presented with the appearance of a metastatic brain tumor involving the orbit, sella, and cerebellum that was ultimately proven to be IPEH. A thorough literature review of IPEH is presented and we discuss this clinical entity and its management. Content Type Journal ArticleCategory Case ReportPages 1-7DOI 10.1007/s11060-012-0799-2Authors Chie-Schin Shih, Section of Pediatric Hematology/Oncology, Department of Pediatrics, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 4340, Indianapolis, IN 46202, USARichard Burgett, Department of Ophthalmology, Indiana University, Indianapolis and Midwest Eye Institute, 200 West 103rd Street, Indianapolis, IN 46290, USAJose Bonnin, Department of Pathology and Laboratory Medicine, India...

Potential New Pathway Can Overcome Glioblastoma Resistance

Health News from Medical News Today — Wed, 25 Jan 2012 17:00:00 +0100

Glioblastoma is the most prevalent and most aggressive malignant brain tumor in humans, and is one of the most resistant to current treatments. Individuals with the disease typically survive around 15 months. Earlier research concentrated on activating the (apoptosis) cell death pathway through therapeutic agents like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Most of these experiments were however impeded by resistance. Chunhai "Charlie" Hao, M.D., Ph.D... (Source: Health News from Medical News Today)

New Way Discovered To Image Brain Tumors And Predict Recurrence

Health News from Medical News Today — Wed, 25 Jan 2012 08:00:00 +0100

After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival - depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment... (Source: Health News from Medical News Today)

Protein and phosphoprotein levels in glioma and adenocarcinoma cell lines grown in normoxia and hypoxia in monolayer and three-dimensional cultures

Proteome Science — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: We identified subsets of proteins with clearly concordant/discordant behavior between gliomas and adenocarcinomas. In general, monolayer to 3D culture differences are clearer than normoxia to hypoxia differences, with anti-apoptotic, cytoskeletal rearrangement and cell survival pathways emphasized in the former and mTOR pathway, transcription, cell-cycle arrest modulation, and increased cell motility in the latter. (Source: Proteome Science)

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“Donut’s Shape” Radiosurgical Treatment Planning for Large Cystic Metastatic Brain Tumors

min - Minimally Invasive Neurosurgery — Wed, 25 Jan 2012 05:00:00 +0100

Minim Invasive Neurosurg 2011; 54: 286-289DOI: 10.1055/s-0031-1297987Radiosurgical management of large cystic metastatic brain tumors represents a significant challenge. Nevertheless, modified dose planning has shown beneficial results in such cases.“Donut’s shape” radiosurgical treatment planning is based on the chain-like application of multiple, small-sized isocenters for selective coverage of the contrast-enhancing tumor capsule and minimal irradiation of the central cystic area. Such an approach was used for the management of large cystic intracranial metastases, which were not accompanied by a significant mass effect and did not require immediate volume reduction. Treatment was done using Leksell Gamma Knife model C with automatic positioning system. The majority of treated les...

A proteome comparison between physiological angiogenesis and angiogenesis in glioblastoma.

Molecular and Cellular Proteomics : MCP — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Mustafa DA, Dekker LJ, Stingl C, Kremer A, Stoop M, Sillevis Smitt PA, Kros JM, Luider TM Abstract The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made....

Morphofunctional aspects of the blood-brain barrier.

Current Drug Metabolism — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Nico B, Ribatti D Abstract The blood-brain barrier (BBB) selectively controls the homeostasis of the Central Nervous System (CNS) environment by the specific structural and biochemical features of the endothelial cells, pericytes and glial endfeet, which represent the cellular components of the mature BBB. Endothelial tight junctions (TJs) are the most important structural component of the BBB, and molecular alteration in the phosphorylation state of some TJs proteins, like ZO-1 or occludin, are crucial in determining alterations in the control of BBB vascular permeability. Astrocytes endfeet enveloping the vessels wall, are considered important in the induction and maintenance of the BBB, through secretion of soluble factors, which modulate the expression of enzymatic com...

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

Journal of Clinical Investigation — Tue, 24 Jan 2012 19:12:02 +0100

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor...

Recent advances in the molecular understanding of glioblastoma

Journal of Neuro-Oncology — Tue, 24 Jan 2012 07:32:31 +0100

Abstract Glioblastoma is the most common and most aggressive primary brain tumor. Despite maximum treatment, patients only have a median survival time of 15 months, because of the tumor’s resistance to current therapeutic approaches. Thus far, methylation of the O 6-methylguanine-DNA methyltransferase (MGMT) promoter has been the only confirmed molecular predictive factor in glioblastoma. Novel “genome-wide” techniques have identified additional important molecular alterations as mutations in isocitrate dehydrogenase 1 (IDH1) and its prognostic importance. This review summarizes findings and techniques of genetic, epigenetic, transcriptional, and proteomic studies of glioblastoma. It provides the clinician with an up-to-date overview of current identified molecu...

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Lexical access speed is significantly correlated with the return to professional activities after awake surgery for low-grade gliomas

Journal of Neuro-Oncology — Tue, 24 Jan 2012 07:32:29 +0100

Abstract Awake surgery with intraoperative brain mapping is highly recommended for patients with diffuse low-grade gliomas in language areas, to maximise the extent of resection while preserving the integrity of functional networks and thus quality of life. The picture-naming test “DO.80” is the gold standard for language assessment before, during, and after surgery. Cognitive functioning is correlated with quality of life, itself linked with return to work. Our objective was to evaluate the significance of measuring naming speed, and its correlation with the return to professional activities. Two complementary studies are reported. In the first retrospective study, eleven patients were examined post-operatively. Five patients were selected because they were not able t...

The translocator protein ligand [18F]DPA-714 images glioma and activated microglia in vivo

European Journal of Nuclear Medicine and Molecular Imaging — Tue, 24 Jan 2012 07:19:32 +0100

Conclusion The TSPO radioligand [18F]DPA-714 can be used for PET imaging of intracranial 9L glioma in different rat strains. This preclinical study demonstrates the feasibility of employing [18F]DPA-714 as an alternative radiotracer to image human glioma. Content Type Journal ArticleCategory Original ArticlePages 1-13DOI 10.1007/s00259-011-2041-4Authors Alexandra Winkeler, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceRaphael Boisgard, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceAli R. Awde, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceAlbertine Dubois, Inserm, U1023, Laboratoire d’Imager...

Kinase activation of ClC-3 accelerates cytoplasmic condensation during mitotic cell rounding

AJP: Cell Physiology — Tue, 24 Jan 2012 05:00:00 +0100

"Mitotic cell rounding" describes the rounding of mammalian cells before dividing into two daughter cells. This shape change requires coordinated cytoskeletal contraction and changes in osmotic pressure. While considerable research has been devoted to understanding mechanisms underlying cytoskeletal contraction, little is known about how osmotic gradients are involved in cell division. Here we describe cytoplasmic condensation preceding cell division, termed "premitotic condensation" (PMC), which involves cells extruding osmotically active Cl– via ClC-3, a voltage-gated channel/transporter. This leads to a decrease in cytoplasmic volume during mitotic cell rounding and cell division. Using a combination of time-lapse microscopy and biophysical measurements, we demonstrate that PMC in...

Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience

Annals of Oncology — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen. (Source: Annals of Oncology)

Epigenetically mediated down‐regulation of the differentiation‐promoting chaperon protein CRABP2 in astrocytic gliomas

International Journal of Cancer — Tue, 24 Jan 2012 05:00:00 +0100

AbstractImpairment of endogenous differentiation pathways like retinoic acid (RA) signaling seems to be a central pathogenetic event in astrocytic gliomas. Among others, expression of the differentiation‐promoting RA chaperon protein cellular retinoic acid binding protein 2 (CRABP2) is extenuated in high‐grade gliomas. Against this background, we aimed at identifying potential pathomechanisms underlying reduced CRABP2 expression in these tumors. Employing MassARRAY methylation analysis we detected extensive CpG methylation upstream of the CRABP2 gene locus in a study sample comprising 100 astrocytic gliomas of WHO grade II to IV. Compared to non‐tumorous control samples tumors revealed increased CpG methylation and methylation levels were inversely correlated to CRABP2 mRNA expressio...

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Non-Cytotoxic Radiosensitizers in Brain Radiotherapy: Journey till the First Decade of this Millennium.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

This article reviews the evolution of evidence with use of non-cytotoxic radiosensitizers in brain radiotherapy and their status at the end of the first decade of this millennium. Considering, the era of development and mechanism of action, these agents are classified as first, second and third-generation non-cytotoxic radiosensitizers. The last millennium involved elaboration of first-generation compounds including halogenated pyrimidines, hypoxic cell sensitizers (e.g. imidazoles) and glycolytic inhibitors (e.g. lonidamine). The first decade of this millennium has highlighted redox modulators like motexafin gadolinium and newer hypoxic cell sensitizers like efaproxiral, which have shown promise. However, phase III trials and meta-analyses have not identified a clear winner though the sec...

Targeted Therapy for Brain Tumours: Role of PARP Inhibitors.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Leonetti C, Biroccio A, Graziani G, Tentori L Abstract The prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the d...

Nanotech Revolution for the Anti-Cancer Drug Delivery through Blood-Brain-Barrier.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Caraglia M, De Rosa G, Salzano G, Santini D, Lamberti M, Sperlongano P, Lombardi A, Abbruzzese A, Addeo R Abstract Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the blood-brain-barrier (BBB) that protects brain from toxicological injuries but, at the same...

Target therapy in brain tumours and metastases.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Caraglia M, Addeo R PMID: 22268383 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)

The Malignant Divorce: Has NASA Gone Postal?

Psychology Today Personality Center — Tue, 24 Jan 2012 03:01:06 +0100

Heaven has no rage like love betrayed read more (Source: Psychology Today Personality Center)

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Team Finds New Way to Image Brain Tumors and Predict Recurrence

UCSF Medical Center — Mon, 23 Jan 2012 08:00:00 +0100

After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival, depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment. (Source: UCSF Medical Center)

Team finds new way to image brain tumors and predict recurrence

EurekAlert! - Medicine and Health — Mon, 23 Jan 2012 05:00:00 +0100

(University of California - San Francisco) After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival -- depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment. (Source: EurekAlert! - Medicine and Health)

Isolation and Cytotoxic Activity of Selaginellin Derivatives and Biflavonoids from Selaginella tamariscina

Planta Medica — Mon, 23 Jan 2012 05:00:00 +0100

Planta MedDOI: 10.1055/s-0031-1298175AbstractFive selaginellin derivatives, including two new selaginellins termed selaginellins M (1) and N (2), and three previously identified compounds, selaginellin (3), selaginellin A (4), and selaginellin C (5), were isolated from the Selaginella tamariscina (Beauv.) Spring plant. In addition, four known biflavonoids, namely neocryptomerin (6), hinokiflavone (7), pulvinatabiflavone (8), and 7′′-O-methylamentoflavone (9), were also isolated. The structures of new compounds 1 and 2 were elucidated by spectroscopic analysis. The cytotoxic activity of compounds 1-9 was evaluated against a small panel of human cancer cell lines, including U251 (human glioma cells), HeLa (human cervical carcinoma cells), and MCF-7 (human breast cancer cells). The two ne...

Therapy can add years to certain brain tumor patients' lives

USATODAY.com Health — Sun, 22 Jan 2012 23:25:32 +0100

In a victory for personalized medicine, new treatment doubles survival for brain tumor patients with genetic mutation. (Source: USATODAY.com Health)

In Patients With Rare Brain Tumor, Abnormal Chromosome Indicator Of Treatment And Outcome

Health News from Medical News Today — Sun, 22 Jan 2012 08:00:00 +0100

A recent analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrate that a chromosomal abnormality - specifically, the absence (co-deletion) of chromosomes 1p and 19q - have definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas... (Source: Health News from Medical News Today)

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Fourier transform infrared microspectroscopy identifies protein propionylation in histone deacetylase inhibitor treated glioma cells

Journal of Biophotonics — Sun, 22 Jan 2012 01:20:28 +0100

AbstractHistone deacetylase inhibitors (HDIs) have attracted considerable attention as potential drug molecules in tumour biology. In order to optimise chemotherapy, it is important to understand the mechanisms of regulation of histone deacetylase (HDAC) enzymes and modifications brought by various HDIs. In the present study, we have employed Fourier transform infrared microspectroscopy (FT‐IRMS) to evaluate modifications in cellular macromolecules subsequent to treatment with various HDIs. In addition to CH3 (methyl) stretching bands at 2872 and 2960 cm–1, which arises due to acetylation, we also found major changes in bands at 2851 and 2922 cm–1, which originates from stretching vibrations of CH2 (methylene) groups, in valproic acid treated cells. We further demonstrate that the ch...

A brain tumour left Whistles fashion guru Lucille Lewin unable to smile but a new facial massage gadget is offering hope

the Mail online | Health — Sat, 21 Jan 2012 22:03:49 +0100

Lucille believes the sale of Whistles in 2002 may have been a trigger for the acoustic neuromas. An MRI scan discovered a tumour. (Source: the Mail online | Health)

Charlie Williams shares his battle with cancer to help others

the Mail online | Health — Sat, 21 Jan 2012 13:24:21 +0100

Charlie Williams, from Boxford in Suffolk, was just five when he was diagnosed with medulloblastoma. The killer brain tumour strikes down about 50 children in the UK a year. (Source: the Mail online | Health)

Reduced growth hormone secretion after cranial irradiation contributes to neurocognitive dysfunction.

Growth Hormone and IGF Research — Sat, 21 Jan 2012 05:00:00 +0100

In this study only 21% (4/19) of the patients who received fractionated radiotherapy for a non-endocrine brain tumor were diagnosed with GHD. GHD in these patients was associated with impaired interference control, attentional shifting, and visual long-term memory. The results for interference control and attentional shifting suggest an additional effect of the radiation history. PMID: 22269954 [PubMed - as supplied by publisher] (Source: Growth Hormone and IGF Research)

RTOG reveals “practice-changing” marker for brain tumor treatment

Health Imaging News — Fri, 20 Jan 2012 10:12:47 +0100

An analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrated that a chromosomal abnormality has definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas. "These are exciting and practice-changing results," said Walter J. Curran, Jr., MD, RTOG group chair and executive director of the Winship Cancer Institute of Emory University in Atlanta, in a statement. (Source: Health Imaging News)

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Oxygen Starvation Reverses Radiation-Induced Damage To Brain Tissue In Mouse Model

Health News from Medical News Today — Fri, 20 Jan 2012 08:00:00 +0100

Treating brain tumors with whole brain radiation therapy can damage healthy brain tissue, but a new study in mice reveals that limiting the oxygen supply, or hypoxia, can alleviate some of the cognitive impairment caused by the radiation. The results are reported in the online journal PLoS ONE. The researchers, led by William Sonntag of University of Oklahoma, exposed the mice to a clinically relevant regimen of radiation, which caused progressive deterioration of spatial learning starting about two months post-radiation... (Source: Health News from Medical News Today)

Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas

Diagnostic Pathology — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: This study has provided further evidence that the histological transformation and progression of gliomas may be associated with the inactivation of the EGFR and MGMT genes. It seems that EGFR and MGMT promoter hypermethylations are early events in the clonal evolution of gliomas and this gene inactivation has proved to be stable even in tumour recurrence. However, the DNMT hypermethylation is a late part of glioma progression.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1935054011612460 (Source: Diagnostic Pathology)

Brain tumor formation better understood

Health News - UPI.com — Thu, 19 Jan 2012 22:56:04 +0100

SAN ANTONIO, Jan. 19 (UPI) -- The connection between two RNA-binding proteins may affect glioblastoma, the brain cancer that killed the late Sen. Edward Kennedy, U.S. researchers say. (Source: Health News - UPI.com)

Genetic abnormality predicts benefit from treatment for a rare brain tumor

National Institutes of Health (NIH) News Releases — Thu, 19 Jan 2012 21:06:00 +0100

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

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Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells

Cancer Chemotherapy and Pharmacology — Thu, 19 Jan 2012 06:53:40 +0100

Conclusion These findings indicate that TAp73 silencing is hallmark of GSC to maintain their chemoresistance phenotype. Thus, targeting TAp73 may provide a novel strategy to eradicating GSCs. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s00280-012-1823-0Authors Xiaogang Hu, Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaNan Wu, Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaPeiyuan Xia, Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaSicang Yu, Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaFengjun Sun, Department of Ph...

Quantitative volumetric analysis of gliomas with sequential MRI and 11C-methionine PET assessment: patterns of integration in therapy planning

European Journal of Nuclear Medicine and Molecular Imaging — Thu, 19 Jan 2012 06:51:13 +0100

Conclusion The metabolically active tumour volume observed in 11C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in 11C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s00259-011-2049-9Authors Javier Arbizu, Department of Nuclear Medicine, Clinica Universidad de Navarra, Avenida Pio XII, 36, 31008 Pamplona, SpainS. Tejada, Department of Neurosurgery, Clinica Universidad de Navarra, Avenida Pio XII, 36, 31008 Pamplona, SpainJ. M. Marti-Climent, Department of Nucl...

Rigged to explode?

EurekAlert! - Medicine and Health — Thu, 19 Jan 2012 05:00:00 +0100

(European Molecular Biology Laboratory) An inherited mutation is likely the link between exploding chromosomes and the pediatric brain tumor which is the second most common cause of childhood mortality in developed countries, scientists at EMBL, DKFZ and the University Hospital, all in Heidelberg, Germany, have discovered. (Source: EurekAlert! - Medicine and Health)

Abnormal chromosome indicator of treatment and outcome in patients with rare brain tumor

EurekAlert! - Cancer — Thu, 19 Jan 2012 05:00:00 +0100

(American College of Radiology) A Radiation Therapy Oncology Group trial shows that, in adults with an oligodendroglioma brain tumor, a chromosomal abnormality is associated with a near-doubling of median survival time and better prognosis when patients are treated with combined chemotherapy and radiation therapy compared to radiation therapy alone. (Source: EurekAlert! - Cancer)

Cellular phones: To talk or not to talk

Journal of Cancer Research and Therapeutics — Thu, 19 Jan 2012 05:00:00 +0100

This article gives a summary view of the possible effects related to cellular phone use. It further discusses if we need to observe precautions while using these devices. (Source: Journal of Cancer Research and Therapeutics)

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Communication process in consultation of patients with incurable disease: a prospective study.

Bulletin du Cancer — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Marcoux I Abstract Patients wish to be fully informed about their health, but some information and its disclosure may pose special challenges depending on the severity of the illness. This prospective observational study investigates the content of information about the disease and treatment, as well as the process by which information is disclosed as part of 51 consultations with people with malignant gliomas. Patients and their relatives were fully informed of the diagnosis and treatments (types, risks, practical details), but disease progression with and without treatment, like the prognosis, was rarely addressed. Relatives were more likely than patients to ask questions related to the severity of the illness and the prognosis, leaving doctors in the difficult position...

Radiation-induced damage to brain tissue reversed by oxygen starvation in mice

EurekAlert! - Cancer — Wed, 18 Jan 2012 05:00:00 +0100

(Public Library of Science) Treating brain tumors with whole brain radiation therapy can damage healthy brain tissue, but a new study in mice reveals that limiting the oxygen supply, or hypoxia, can alleviate some of the cognitive impairment caused by the radiation (Source: EurekAlert! - Cancer)

Rapid Radiographic and Clinical Improvement After Treatment of a MET-Amplified Recurrent Glioblastoma With a Mesenchymal-Epithelial Transition Inhibitor [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Wed, 18 Jan 2012 05:00:00 +0100

(Source: Journal of Clinical Oncology)

Dose to craniofacial region through portal imaging of pediatric brain tumors.

Journal of Applied Clinical Medical Physics — Tue, 17 Jan 2012 11:30:03 +0100

Authors: Hitchen CJ, Osa EO, Dewyngaert K, Chang J, Narayana A Abstract The purpose of this study was to determine dose to the planning target volume (PTV) and organs at risk (OARs) from portal imaging (PI) of the craniofacial region in pediatric brain tumor patients treated with intensity-modulated radiation therapy (IMRT). Twenty pediatric brain tumor patients were retrospectively studied. Each received portal imaging of treatment fields and orthogonal setup fields in the craniofacial region. The number of PI and monitor units used for PI were documented for each patient. Dose distributions and dose-volume histograms were generated to quantify the maximum, minimum, and mean dose to the PTV, and the mean dose to OARs through PI acquisition. The doses resulting from PI are reported...

Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway

Journal of Neuro-Oncology — Tue, 17 Jan 2012 07:19:32 +0100

Abstract Glioma stem-like cells (GSCs) may be the initiating cells in glioblastoma (GBM) and contribute to the resistance of these tumors to conventional therapies. Development of novel chemotherapeutic agents and treatment approaches against GBM, especially those specifically targeting GSCs are thus necessary. In the present study, we found that a novel Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor (WP1193) significantly decreased the proliferation of established glioma cell lines in vitro and inhibit the growth of glioma in vivo. To test the efficacy of WP1193 against GSCs, we then administrated WP1193 to GSCs isolated and expanded from multiple human GBM tumors. We revealed that WP1193 suppressed phosphorylation of JAK2...

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Risk of ischemia in glioma surgery: comparison of first and repeat procedures

Journal of Neuro-Oncology — Tue, 17 Jan 2012 07:19:31 +0100

Abstract The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. For...

The “go or grow” potential of gliomas is linked to the neuropeptide processing enzyme carboxypeptidase E and mediated by metabolic stress

Acta Neuropathologica — Tue, 17 Jan 2012 07:11:19 +0100

Abstract Glioblastoma (GBM), the most common malignant brain tumor, is among the most lethal neoplasms, with a median survival of approximately 1 year. Prognosis is poor since GBMs possess a strong migratory and highly invasive potential, making complete surgical resection impossible. Reduced expression of carboxypeptidase E (CPE), a neuropeptide-processing enzyme, in a cell death-resistant glioma cell line and lower CPE expression levels in the cohort of GBM samples of The Cancer Genome Atlas compared to normal brain control specimens prompted us to analyze the function of CPE as a putative tumor suppressor gene. In our samples, CPE was also reduced in GBM compared to normal brain with the strongest loss in cells surrounding hypoxic tumor areas as well as in most gli...

Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells

Child's Nervous System — Tue, 17 Jan 2012 07:08:49 +0100

Abstract Introduction CD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved. Materials and methods In the present study, we isolated CD133+ cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133− cells. Bioinformatics analysis suggested tha...

Temozolomide for Pediatric High-Grade Gliomas

Current Neurology and Neuroscience Reports — Tue, 17 Jan 2012 07:06:32 +0100

Content Type Journal ArticleCategory Clinical Trial ReportPages 1-3DOI 10.1007/s11910-012-0250-2Authors Roger J. Packer, Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Gilbert Neurofibromatosis Institute, Brain Tumor Institute, 111 Michigan Avenue, NW, Washington, DC 20010, USA Journal Current Neurology and Neuroscience ReportsOnline ISSN 1534-6293Print ISSN 1528-4042 (Source: Current Neurology and Neuroscience Reports)

A call to researchers: The Cancer Genome Atlas

National Brain Tumor Society — Tue, 17 Jan 2012 06:00:00 +0100

TCGA is asking for researchers to help them collect low-grade glioma samples. (Source: National Brain Tumor Society)

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Attention Researchers: Help TCGA With Low-Grade Gliomas

National Brain Tumor Society — Tue, 17 Jan 2012 06:00:00 +0100

TCGA is asking for researchers to help them collect low-grade glioma samples. (Source: National Brain Tumor Society)

Eosinophils in glioblastoma biology

Journal of Neuroinflammation — Tue, 17 Jan 2012 05:00:00 +0100

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 e...

Characterization of 3'-untranslated region of the mouse GDNF gene

BMC Molecular Biology - Latest articles — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions: Our study is the first characterization of the possible role of AREs and other suppressive regions in the 3'-UTR in regulating the amounts of GDNF mRNA in C6 cells. (Source: BMC Molecular Biology - Latest articles)

SUMO fusion system facilitates soluble expression and high production of bioactive human fibroblast growth factor 23 (FGF23).

Applied Microbiology and Biotechnology — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Liu X, Chen Y, Wu X, Li H, Jiang C, Tian H, Tang L, Wang D, Yu T, Li X Abstract As a key humoral regulator of phosphate homeostasis and its involvement in the pathogenesis of human disease, human fibroblast growth factor 23 (hFGF23) has become a particularly attractive therapeutic target. To prepare soluble and bioactive recombinant human FGF23 to meet the increasing demand in its pharmacological application, small ubiquitin-related modifier (SUMO)-FGF23 fusion gene and FGF23 non-fusion gene were amplified by standard PCR methods and cloned into vector pET-22b and pET-3c, then transformed into Escherichia coli Rosetta (DE3) and BL21 (DE3). The best combination of plasmid and host strain was screened, and only Rosetta (DE3)/pET-SUMO-FGF23 was screened for rhFGF23 protein ex...

Spheres without Influence: Dissociating In Vitro Self-Renewal from Tumorigenic Potential in Glioma

Cancer Cell — Tue, 17 Jan 2012 00:00:00 +0100

Tracy-Ann Read, Robert J. Wechsler-Reya. The capacity for self-renewal is thought to be a critical property of tumor-initiating cells. This capacity is often associated with the ability to generate spheres in vitro. In this issue of C.... (Source: Cancer Cell)

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Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma

Cancer Cell — Tue, 17 Jan 2012 00:00:00 +0100

Lindy E. Barrett, Zvi Granot, Courtney Coker, Antonio Iavarone, Dolores Hambardzumyan, Eric C. Holland, Hyung-song Nam, Robert Benezra. Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain.... (Source: Cancer Cell)

Imaging Technology For Looking Inside Brain May Help Test New Brain Cancer Drugs

Health News from Medical News Today — Mon, 16 Jan 2012 20:00:00 +0100

Using imaging technology that reveals whether brain tumors have a particular genetic mutation known as IDH, a team of academic and pharmaceutical company researchers has developed a way to help doctors select the right treatment, and developers to make new drugs that target the mutation. The researchers, from MIT, Harvard University, Massachusetts General Hospital (MGH) and Agios Pharmaceuticals, write about their findings in the 11 January online issue of Science Translational Medicine. Some of the deadliest cancers are those that affect the brain... (Source: Health News from Medical News Today)

Targeting EGFR for Treatment of Glioblastoma: Molecular Basis to Overcome Resistance.

Current Cancer Drug Targets — Mon, 16 Jan 2012 05:00:00 +0100

Authors: Taylor TE, Furnari FB, Cavenee WK Abstract Glioblastoma (glioblastoma multiforme; GBM; WHO Grade IV) accounts for the majority of primary malignant brain tumors in adults. Amplification and mutation of the epidermal growth factor receptor (EGFR) gene represent signature genetic abnormalities encountered in GBM. A range of potential therapies that target EGFR or its mutant constitutively active form, ΔEGFR, including tyrosine kinase inhibitors (TKIs), monoclonal antibodies, vaccines, and RNA-based agents, are currently in development or in clinical trials for the treatment of GBM. Data from experimental studies evaluating these therapies have been very promising; however, their efficacy in the clinic has so far been limited by both upfront and acquired drug resistance. Thi...

Treatment strategies for initially disseminated intracranial germinomas

Child's Nervous System — Fri, 13 Jan 2012 17:18:42 +0100

Conclusions IDIG patients did not show reduced survival compared to non-dissemination patients if optimal radiotherapy and chemotherapy were used together. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00381-012-1683-2Authors Yi-Wei Chen, Division of Radiation Oncology, Cancer Center, Neurological Institute, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112 TaiwanPin-I Huang, Division of Radiation Oncology, Cancer Center, Neurological Institute, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112 TaiwanYu-Wen Hu, Division of Radiation Oncology, Cancer Center, Neurological Institute, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112 TaiwanDonald Ming-Tak Ho, Depar...

Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor survivors: A pilot study

Pediatric Blood and Cancer — Fri, 13 Jan 2012 12:55:45 +0100

ConclusionsDonepezil was well tolerated among childhood BT survivors who had received substantial prior therapy. Based on improved executive function and memory performance in this pilot trial, a randomized placebo controlled trial of this pharmacologic agent is warranted to fully evaluate its efficacy in remediating neurocognitive dysfunction. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Complications of chemotherapy in neuro-oncology.

Herpes — Fri, 13 Jan 2012 11:30:16 +0100

Authors: Marosi C Abstract The persisting reservation against the use of chemotherapy in patients with malignant glioma was finally overcome by the breakthrough achieved with the use of the oral alkylating agent temozolomide (TMZ) as concomitant and adjuvant chemotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). The basic condition for an effective systemic drug therapy against malignant glioma is that the drug be able to cross the blood-brain barrier (BBB) and the brain-tumor barrier. Drugs crossing the BBB have to be nonpolar, small molecules with a molecular weight of less than 500Da, to bear no electrical charge, or to be able to use active transport mechanisms, as the BBB is functional in the peripheral growing areas of GBM. The prerequisite of liposolubi...

Gene therapy.

Herpes — Fri, 13 Jan 2012 11:30:16 +0100

Authors: Gomez-Manzano C, Jiang H, Alonso M, Yung WK, Fueyo J Abstract During the last 10 years, gene therapy for brain tumors has known peaks and valleys. The first attempts to induce therapeutic effect, using retrovirus to transduce the HSV-TK gene and adenovirus to transfer wild-type p53 cDNA, failed significantly to improve the survival of the patients. In both cases, the failure was attributed to vector deficiencies, also termed the 'vector gap'. To address the problem of delivery, investigators have moved from replication-deficient vectors to replication-competent, tumor-selective viruses. These viruses are currently being tested in the clinical setting. In this review, we discuss the progress made with herpes simplex viruses (G207), reoviruses that naturally target Ras pathw...

Brain Tumors Sensitized To Chemotherapy By Selectively Stopping Glutathione

Health News from Medical News Today — Fri, 13 Jan 2012 09:00:00 +0100

Brain cancer cells are particularly resistant to chemotherapy - toxins enter the cells, but before the toxins can kill, cancer cells quickly pump them back outside. In fact, brain cancer cells are even better than healthy cells at cleaning themselves. This means that when hit with chemotherapy, healthy cells tend to die before brain cancer cells. Especially in the brain, killing healthy cells is bad. Researchers at the University of Colorado Cancer Center have discovered a way to turn off the pumps - only in brain cancer cells and not in their healthy neighbors... (Source: Health News from Medical News Today)

Sh3rf2/POSHER Antagonizes POSH-mediated JNK Signaling [Protein Synthesis and Degradation]

Journal of Biological Chemistry — Fri, 13 Jan 2012 05:00:00 +0100

We report that Sh3rf2, a homologue of the pro-apoptotic scaffold POSH (Plenty of SH3s), acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway. siRNA-mediated knockdown of Sh3rf2 promotes apoptosis of neuronal PC12 cells, cultured cortical neurons, and C6 glioma cells. This death appears to result from activation of JNK signaling. Loss of Sh3rf2 triggers activation of JNK and its target c-Jun. Also, apoptosis promoted by Sh3rf2 knockdown is inhibited by dominant-negative c-Jun as well as by a JNK inhibitor. Investigation of the mechanism by which Sh3rf2 regulates cell survival implicates POSH, a scaffold required for activation of pro-apoptotic JNK/c-Jun signaling. In cells lacking POSH, Sh3rf2 knockdown is unable to activate JNK. We further find that Sh3rf2 bind...