Leptomeningeal Metastasis of Primary Central Nervous System (CNS) Neoplasms

Engelhard, Herbert H.; Corsten, Luke A.

doi:10.1007/0-387-24199-x_5

Cited by 30 publications

(16 citation statements)

References 74 publications

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“…Altogether, our findings indicate that high MYC levels drive BMP7 overexpression, promoting cell survival in MB cells. This observation suggests the potential relevance ofIntroduction Medulloblastoma (MB) represents >20% of all pediatric tumors of the central nervous system (Gurney and Kadan-Lottick, 2001), and is characterized by aggressive clinical behavior and high risk of leptomeningeal dissemination (Engelhard and Corsten, 2005). Multimodal therapy (surgery, radiotherapy and chemotherapy) has improved the overall survival rate.…”

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confidence: 99%

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

et al. 2011

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Medulloblastoma (MB) is the most common malignant brain tumor in children. It is known that overexpression and/or amplification of the MYC oncogene is associated with poor clinical outcome, but the molecular mechanisms and the MYC downstream effectors in MB remain still elusive. Besides contributing to elucidate how progression of MB takes place, most importantly, the identification of novel MYC-target genes will suggest novel candidates for targeted therapy in MB. A group of 209 MYC-responsive genes was obtained from a complementary DNA microarray analysis of a MB-derived cell line, following MYC overexpression and silencing. Among the MYC-responsive genes, we identified the members of the bone morphogenetic protein (BMP) signaling pathway, which have a crucial role during the development of the cerebellum. In particular, the gene BMP7 was identified as a direct target of MYC. A positive correlation between MYC and BMP7 expression was documented by analyzing two distinct sets of primary MB samples. Functional studies in vitro using a small-molecule inhibitor of the BMP/SMAD signaling pathway reproduced the effect of the small interfering RNA-mediated silencing of BMP7. Both approaches led to a block of proliferation in a panel of MB cells and to inhibition of SMAD phosphorylation. Altogether, our findings indicate that high MYC levels drive BMP7 overexpression, promoting cell survival in MB cells. This observation suggests the potential relevance of targeting the BMP/SMAD pathway as a novel therapeutic approach for the treatment of childhood MB.

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confidence: 99%

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

et al. 2011

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“…Thirty of 87 patients (34.5%) developed dissemination, which is higher than the 7–27% that has been reported elsewhere [10]. Patients with high-grade gliomas who received high-dose radiation therapy had a higher rate of CSFD than those who had received lower doses [27].…”

Section: Discussionmentioning

confidence: 99%

“…Although CSF dissemination may be more common [7, 8, 9] than generally realized [10], it is unusual following current standard therapy for high-grade gliomas. Mandel et al [11] have reported that in a series of 595 GBM patients treated in clinical trials at the Baylor College of Medicine, 36 (4%) developed dissemination.…”

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confidence: 99%

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

et al. 2017

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We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

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“…The incidence of leptomeningeal metastasis of primary central nervous system (CNS) tumors has been reported to range from 7% to 27%, but extra-CNS GCT metastasis is rare (Engelhard et al 2005). There has been only one report in the last 10 years (Miranda et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Leptomeningeal Metastases in a Patient with an Extragonadal Germ Cell Tumor

Kinebuchi

Ishikawa

Ishizuka

et al. 2008

Clinical medicine. Oncology

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Abstract:We present a case of leptomeningeal metastases in a 30-year-old man with an extragonadal germ cell tumor. The patient was referred to our hospital for treatment of an occipital brain metastasis. This lesion was resected, followed by whole brain radiotherapy and further chemotherapy, and a temporary complete remission was achieved. However, leptomeningeal recurrence developed, and despite salvage chemotherapy, the patient died of disease. Although multidisciplinary treatment is given to treat brain metastases of germ cell tumors, the patients' prognosis has been unsatisfactory. The identifi cation of a standard/effective treatment is required.

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Leptomeningeal Metastasis of Primary Central Nervous System (CNS) Neoplasms

Cited by 30 publications

References 74 publications

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

Leptomeningeal Metastases in a Patient with an Extragonadal Germ Cell Tumor

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