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ABSTRACT: Ecchordosis physaliphora (EP) is a benign notochordal remnant that is usually asymptomatic; symptomatic cases are extremely rare. Most of the reported symptomatic cases were managed by resection via craniotomy.
We report a case of a 20-year-old male presenting with abducens nerve palsy. Magnetic resonance imaging performed on admission demonstrated a mass in the retroclival prepontine location. The patient was treated successfully by endoscopic endonasal trans-sphenoidal surgery (ETSS), his postoperative course was uneventful, and the abducens nerve palsy disappeared.
ETSS has advantages not only for treatment but also for differentiation between EP and intradural chordoma. This is the first case of symptomatic EP successfully treated solely by ETSS.
Surgical neurology international. 01/2013; 4:13.
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ABSTRACT: Pituitary apoplexy is a rare clinical syndrome attributable to hemorrhage or hemorrhagic infarction of pituitary tumors or pituitary glands. The features of pituitary apoplexy associated with the endocrine stimulation test remain to be elucidated and the importance of surgical treatment has not been discussed enough. We report two rare patients who were treated successfully by endoscopic endonasal transsphenoidal surgery within several hours after onset of pituitary apoplexy associated with the endocrine stimulation test. Their postoperative course was uneventful. We reviewed earlier reports on this clinical entity, document its features especially as related to the endocrine stimulation test, discuss the significance of immediate surgical treatment, and present our treatment outcomes. Performing only conservative treatment is not recommended. We suggest that the necessity of endocrine stimulation test should be assessed on a case-by-case basis and in patients subjected to the test, and neurosurgical support should be sought.
Case reports in endocrinology. 01/2012; 2012:826901.
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ABSTRACT: Perivascular spaces (PVSs) or Virchow-Robin spaces in the brain are pial-lined interstitial fluid (ISF)-filled structures surrounding the penetrating arteries and arterioles. These spaces appear as 1- to 2-mm in diameter, round, oval, or curvilinear smooth-walled structures on magnetic resonance imaging (MRI). Typical PVSs are asymptomatic. Occasionally, they become enlarged and cause specific clinical manifestations that depend on location and the degree of tissue compression. In this case, they are referred to as giant tumefactive PVSs. To our knowledge, there have been no reported cases in which giant PVSs increased remarkably in number and size during both the natural course and postoperative course. We describe a rare progression of giant tumefactive PVSs 14 years after initial surgery.
On first admission at age 17, endoscopic ventriculocystostomy and third ventriculostomy were performed to relieve hydrocephalus caused by cysts compressing the cerebral aqueduct. Fourteen years later, the multicystic lesion reappeared with an increase in both cyst number and size. The patient showed no hydrocephalus but presented with oculomotor and trochlear nerve palsies, which were caused by a mass effect on the midbrain. Endoscopic ventriculocystostomy was performed and symptoms improved.
This is the first case report in which giant PVSs increased significantly in number and size.
Surgical neurology international. 01/2012; 3:127.
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ABSTRACT: Recent findings have demonstrated that malignant tumors, including glioblastoma multiforme, contain cancer-initiating cells (also known as cancer stem cells), which self-renew and are malignant, with features of tissue-specific stem cells. As these cells are resistant to irradiation and anti-cancer drugs, it is important to characterize them and find targeting therapies. In this study, we established two primary human glioma cell lines from anaplastic oligodendroglioma and glioblastoma multiforme. These lines were enriched in glioma-initiating cells, as just 10 cells formed malignant glioma when injected into mouse brain. We used these cell lines to examine the roles of the Notch, Hedgehog and Wnt signaling pathways, which are involved in stem-cell maintenance and tumorigenesis, to determine which of these pathways are crucial to glioma-initiating cells and their regulation. Here we show that the Hedgehog pathway is indispensable for glioma-initiating cell proliferation and tumorigenesis; the Hedgehog signaling inhibitors prevented glioma-initiating cell proliferation, while signaling inhibitors for Notch or Wnt did not. Overexpression of Gli2ΔC, a C-terminal-truncated form of Gli2 that antagonizes Gli transcription factor functions, blocked glioma-initiating cell proliferation in culture and tumorigenesis in vivo. Knockdown of the Gli downstream factor Cdc2 also prevented glioma-initiating cell proliferation. Taken together, these results show that the Hedgehog→ Gli→Cdc2 signaling cascade plays a role in the proliferation and malignancy of glioma-initiating cells.
Cancer Science 03/2011; 102(7):1306-12. · 3.33 Impact Factor
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ABSTRACT: Recent findings have demonstrated that malignant tumors, including glioblastoma multiforme (GBM), contain cancer-initiating cells (CICs; also known as cancer stem cells), which self-renew and are malignant. However, it remains controversial whether such CICs arise from tissue-specific stem cells, committed precursor cells, or differentiated cells. Here, we sought to examine the origin of the CICs in GBM. We first showed that the overexpression of oncogenic HRas(L61) transformed p53-deficient oligodendrocyte precursor cells (OPCs) and neural stem cells (NSCs) into glioma-initiating cell (GIC)-like cells in mice. When as few as 10 of these GIC-like cells were transplanted in vivo, they formed a transplantable GBM with features of human GBM, suggesting that these GIC-like cells were enriched in CICs. DNA microarray analysis showed that widespread genetic reprogramming occurred during the OPCs' transformation: they largely lost their OPC characteristics and acquired NSC ones, including the expression of prominin1, hmga2, ptgs2, and epiregulin. In addition, the combination of a Ptgs2 inhibitor and an epidermal growth factor receptor (EGFR)-signaling inhibitor prevented the tumorigenesis of transformed OPCs and human GICs (hGICs) obtained from anaplastic oligodendroglioma, but not of transformed NSCs or hGICs obtained from GBM. Together, these findings suggest that GBM can arise from either OPCs or NSCs and that the therapeutic targets for GBM might be different, depending on each GIC's cell-of-origin.
Stem Cells 02/2011; 29(4):590-9. · 7.78 Impact Factor
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ABSTRACT: Recent findings have shown that malignant tumors contain cancer-initiating cells (CIC), which self-renew and are tumorigenic. However, CICs have not been characterized properly due to lack of specific markers. We recently established a mouse glioma cell line, NSCL61, by overexpressing an oncogenic HRas(L61) in p53-deficient neural stem cells. Using limiting dilution assays, we show that only 2 of 24 NSCL61 clones retained their tumorigenicity in vivo, although the others also expressed oncogenic HRas(L61) and could proliferate in culture. A comparison of the gene expression profiles of tumorigenic and nontumorigenic clones showed that the tumorigenic clones had lost Sox11 expression. We show that overexpression of sox11 prevented tumorigenesis of NSCL61s by inducing their neuronal differentiation accompanied with decreased levels of plagl1. We also show that overexpression of plagl1 abolished neuronal commitment of nontumorigenic cells and induced them to become tumorigenic. Moreover, we show that human glioma-initiating cells lost sox11 expression, and overexpression of sox11 prevented their tumorigenesis in vivo. Together with the clinical evidence showing that downregulation of sox11 mRNA correlates with a significant decrease in survival, these findings suggest that Sox11 prevents gliomagenesis by blocking the expression of oncogenic plagl1.
Cancer Research 10/2009; 69(20):7953-9. · 7.86 Impact Factor
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ABSTRACT: The study of cancer stem cells (CSCs) is on the cutting edge of cancer research. Following the discovery of neural stem cells (NSCs), extensive studies on their characteristics led to the discovery of cancer stem cells (CSCs) in brain tumors: these cells are termed brain tumor stem cells (BTSCs). The study of NSCs provided insights into mechanisms underlying the maintenance of NSCs, and more recently, BTSCs. Adult NSCs exist in the subventricular zone (SVZ) of the lateral ventricle and in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Specific genes referred to as "stemness genes," combined with a specific microenvironment called the "stem cell niche" are important in maintaining NSC characteristics. Glioblastoma multiforme (GBM) is one of the most malignant forms of human cancer. Regardless of intensive treatment regimens, the mean survival time for GBM patients is approximately 12 months. Early cancer therapies for GBM primarily targeted the rapidly-dividing cells and not the slowly-dividing cells, which were minor populations of cells containing BTSCs. Identification of BTSCs yielded new insights regarding the chemo- and radio-resistant properties that facilitate their selective survival and ability to initiate tumor recurrence. Recent studies have focused on BTSCs as treatment targets for GBM. These investigations showed that inhibiting the pathway for stemness genes decreased the number of BTSCs in vitro and improved survival times of xenografted mice. Moreover, treatment with drugs that affect the stem cell niche in brain tumor-bearing mice prolonged their survival. We expect that the continued study of BTSCs, combined with the findings of past studies, will contribute to breakthroughs that will lead to novel treatments to cure GBM patients. In this review, we discuss recent progress in basic research on BTSCs as treatment targets.
Brain and nerve = Shinkei kenkyū no shinpo 08/2009; 61(7):781-9.
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Mareina Kudo,
Hirofumi Jono,
Satoru Shinriki,
Shigetoshi Yano,
Hideo Nakamura,
Keishi Makino, Takuichiro Hide,
Daisuke Muta,
Mitsuharu Ueda,
Kazutoshi Ota,
Yukio Ando,
Jun-Ichi Kuratsu
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ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial. The aim of this study was to evaluate the involvement of IL-6 signaling in glioma and the inhibitory effect of IL-6 signaling on glioma tumor proliferation.
The expression of IL-6 receptors (IL-6Rs) was evaluated in glioma tissues by means of immunohistochemical analysis, and the involvement of IL-6 signaling in glioblastoma multiforme (GBM) U87MG cell proliferation was also determined. In addition, to examine the inhibitory effect of IL-6 signaling on glioma cell proliferation, the authors investigated the effects of tocilizumab, the humanized anti-human IL-6R antibody in U87MG cells.
Increased immunoreactivity for IL-6R was predominantly found in the cytoplasm of endothelial cells in all GBM samples. Inhibition of IL-6 signaling by both IL-6- and IL-6R-specific small interfering RNA and AG490, a specific inhibitor of JAK2 phosphorylation, suppressed glioma cell proliferation. Furthermore, tocilizumab, a clinically developed humanized anti-human IL-6R antibody, exerted an antiproliferative effect on cells from the GBM cell line U87MG via the IL-6R-dependent JAK-STAT3 pathway.
The IL-6 signaling pathway plays an important role in glioma cell proliferation, and tocilizumab exerts an antitumor effect in U87MG glioma cells. These results may bring new insight into the molecular pathogenesis of glioma and may lead to a new therapeutic intervention.
Journal of Neurosurgery 04/2009; 111(2):219-25. · 2.96 Impact Factor
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ABSTRACT: Glioblastoma multiforme (GBM) is one of the most malignant forms of human cancer. Despite intensive treatment, the mean survival of GBM patients remains about 1 year. Recent cancer studies revealed that cancer tissues are pathologically heterogeneous and only a small population of cells has the specific ability to reinitiate cancer. This small cell population is called cancer stem cells (CSCs); in brain tumors these are known as brain tumor stem cells (BTSCs). The identification of BTSCs yielded new insights into chemo-and radioresistance, by which BTSCs can survive selectively and initiate recurrence. Research focused on BTSCs as treatment targets may contribute to the discovery of new therapeutic strategies.
Brain Tumor Pathology 02/2008; 25(2):67-72. · 1.19 Impact Factor
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ABSTRACT: The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
Nature 12/2004; 432(7015):396-401. · 36.28 Impact Factor
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ABSTRACT: Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and more recently in solid tumors such as breast cancer suggests that the tumor cell population is heterogeneous with respect to proliferation and differentiation. Recently, several groups have described the existence of a cancer stem cell population in human brain tumors of different phenotypes from both children and adults. The finding of brain tumor stem cells (BTSCs) has been made by applying the principles for cell culture and analysis of normal neural stem cells (NSCs) to brain tumor cell populations and by identification of cell surface markers that allow for isolation of distinct tumor cell populations that can then be studied in vitro and in vivo. A population of brain tumor cells can be enriched for BTSCs by cell sorting of dissociated suspensions of tumor cells for the NSC marker CD133. These CD133+ cells, which also expressed the NSC marker nestin, but not differentiated neural lineage markers, represent a minority fraction of the entire brain tumor cell population, and exclusively generate clonal tumor spheres in suspension culture and exhibit increased self-renewal capacity. BTSCs can be induced to differentiate in vitro into tumor cells that phenotypically resembled the tumor from the patient. Here, we discuss the evidence for and implications of the discovery of a cancer stem cell in human brain tumors. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC. Specific genetic and molecular analyses of the BTSC will further our understanding of the mechanisms of brain tumor growth, reinforcing parallels between normal neurogenesis and brain tumorigenesis.
Oncogene 10/2004; 23(43):7267-73. · 6.37 Impact Factor
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ABSTRACT: Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of CBA and B6 strains, backcrossed with B6 females display reduction or loss of mandible, whereas those backcrossed with CBA females do not show noticeable phenotype at birth. The availability of phenotypically disparate strains renders identification of Otx2 modifier loci possible. In this study, a backcross of chimera with B6 was generated and genome-wide scans were conducted with polymorphic markers for non-mendelian distribution of alleles in Otx2 heterozygous mutant mice displaying abnormalities in the lower jaw. We identified one significant locus, Otmf18, between D18Mit68 and D18Mit120 on chromosomes 18, linked to the mandibular phenotype (LOD score 3.33). A similar replication experiment using a second backcross (N3) mouse demonstrated the presence of another significant locus, Otmf2 between D2Mit164 and D2Mit282 on chromosome 2, linked to the mandibular phenotype (LOD score 3.93). These two modifiers account for the distribution of the craniofacial malformations by the genetic effect between B6 and CBA strains. Moreover, Otmf2 contain a candidate gene for several diseases in mice and humans. These genetic studies involving an otocephalic mouse model appear to provide new insights into mechanistic pathways of craniofacial development. Furthermore, these experiments offer a powerful approach with respect to identification and characterization of candidate genes that may contribute to human agnathia-holoprosencephaly complex diseases.
Development 10/2002; 129(18):4347-57. · 6.60 Impact Factor
