Neurofibromatosis

Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in an autosomal dominant fashion, this phacomatosis is classified into two genetically distinct subtypes characterized by multiple cutaneous lesions and tumors of the peripheral and central nervous system. Neurofibromatosis type 1 (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500 individuals and presents with a variety of characteristic abnormalities of the skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2), previously termed central neurofibromatosis, is much more rare occurring in less than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent in the late teens with a sudden loss of hearing due to the development of bi-or unilateral vestibular schwannomas. In addition NF2 patients may suffer from further nervous tissue tumors such as meningiomas or gliomas. This review summarizes the characteristic features of the two forms of NF and outlines commonalities and distinctions between NF1 and NF2

The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis

<p>Abstract</p> <p>Background</p> <p><it>SOX2 </it>is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. <it>SOX2 </it>appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of <it>SOX2 </it>in GBM has not yet been defined.</p> <p>Results</p> <p>We show that knockdown of the <it>SOX2 </it>gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the <it>SOX2 </it>response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 <it>SOX2 </it>binding regions in the GBM cancer genome. <it>SOX2 </it>binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 <it>SOX2 </it>binding regions. Microarray analysis identified 489 genes whose expression altered in response to <it>SOX2 </it>knockdown. Interesting findings include that <it>SOX2 </it>regulates the expression of SOX family proteins <it>SOX1 </it>and <it>SOX18</it>, and that <it>SOX2 </it>down regulates <it>BEX1 </it>(brain expressed X-linked 1) and <it>BEX2 </it>(brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by <it>SOX2</it>, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and <it>SOX2 </it>form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.</p> <p>Conclusions</p> <p>We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the <it>SOX2 </it>response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of <it>SOX2 </it>in carcinogenesis and serves as a useful resource for the research community.</p

Association of mast cell-derived VEGF and proteases in dengue shock syndrome

Background: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls. Methodology/Principal Findings: The study was performed at Children\u27s Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. Conclusions: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity

Brain tumors in the mesial temporal lobe: long-term oncological outcome

Object. Surgical treatment of brain tumors in the mesial temporal lobe (MTL) is a highly demanding procedure. Only a few studies describing the surgery of MTL tumors have been reported, and they have been focused on the operative techniques and immediate results of the surgery. The authors have analyzed the long-term oncological outcome in patients with MTL tumors. Methods. Thirty-six patients with an MTL tumor were studied. The mean patient age at surgery was 32 years (range 13-62 years). The tumors were confined to the MTL (Schramm Type A) in 25 patients (69%). Extension of the tumor into the fusiform gyrus (Schramm Type C) and temporal stem (Schramm Type D) was observed in 4 and 7 patients (11 and 19%),respectively. There was a significant difference in the tumor size according to Schramm types (p = 0.001). Complete tumor resection was achieved in 26 patients (72%). All tumors were low-grade lesions except for 1 anaplastic astrocytoma. Results. After a median follow-up period of 50.5 months, 7 patients showed progression of the disease. The actuarial progression-free survival rates were 97% in the 1st year, 84% in the 2nd year, and 80% in the 5th year. The degree of tumor resection was significantly related to the tumor control failure (p = 50 years (p = 0.007, RR 8.312); and 4) short duration of epilepsy (< 6 months; p = 0.001, RR 21.54). Conclusions. Surgery is the principal treatment for MTL tumors, despite its technical difficulty. Complete tumor resection is strongly recommended for long-term tumor control. The MTL tumors are heterogeneous in their prognosis. Older age, short duration of epilepsy, and tumor size are all associated with poor outcome. Patients with these characteristics may have a more aggressive form of the disease than those with MTL tumors associated with chronic epilepsy. (DOI: 10.3171/2009.5.FOCUS09106)Uribe JS, 2009, J NEUROSURG, V110, P137, DOI 10.3171/2008.4.17508PHI JH, 2009, CANCER IN PRESSPichlmeier U, 2008, NEURO-ONCOLOGY, V10, P1025, DOI 10.1215/15228517-2008-052McGirt MJ, 2008, NEUROSURGERY, V63, P700, DOI 10.1227/01.NEU.0000325729.41085.73Schramm J, 2008, ACTA NEUROCHIR, V150, P857, DOI 10.1007/s00701-008-0013-7Smith JS, 2008, J CLIN ONCOL, V26, P1338, DOI 10.1200/JCO.2007.13.9337van Breemen MSM, 2007, LANCET NEUROL, V6, P421Schramm J, 2007, NEUROSURGERY, V60, P285, DOI 10.1227/01.NEU.0000249281.69384.D7Cataltepe O, 2005, J NEUROSURG, V102, P280Clusmann H, 2004, J NEUROL NEUROSUR PS, V75, P1589, DOI 10.1136/jnnp.2003.024208Schramm J, 2004, NEUROSURGERY, V55, P340, DOI 10.1227/01.NEU.0000129546.38675.1BDoetsch F, 2003, NAT NEUROSCI, V6, P1127, DOI 10.1038/nn1144Luyken C, 2003, EPILEPSIA, V44, P822Bauman G, 1999, INT J RADIAT ONCOL, V45, P923Lote K, 1997, J CLIN ONCOL, V15, P3129Piepmeier J, 1996, NEUROSURGERY, V38, P872Duffner PK, 1996, J NEURO-ONCOL, V28, P245Campbell JW, 1996, NEUROSURGERY, V38, P258PRAYSON RA, 1993, EPILEPSIA, V34, P609YASARGIL MG, 1992, ACTA NEUROCHIR, V118, P40YASARGIL MG, 1992, ACTA NEUROCHIR, V116, P147