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Human Brain Tumors (human + brain_tumor)
Selected AbstractsModeling Human Brain Tumors in MiceBRAIN PATHOLOGY, Issue 1 2009David H. Gutmann First page of article [source] The natural compound n -butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo3JOURNAL OF NEUROCHEMISTRY, Issue 4 2006Nu-Man Tsai Abstract The naturally-occurring compound, n -butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis (AS-C), has been investigated with respect to the treatment of angina. In this study, we have examined the anti-tumor effects of n -butylidenephthalide on glioblastoma multiforme (GBM) brain tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and the effects of proliferation, cell cycle and apoptosis were determined. In vivo, DBTRG-05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. The effects on tumor growth were determined by tumor volumes, magnetic resonance imaging and survival rate. Here, we report on the potency of BP in suppressing growth of malignant brain tumor cells without simultaneous fibroblast cytotocixity. BP up-regulated the expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease phosphorylation of Rb proteins, and down-regulated the cell-cycle regulators, resulting in cell arrest at the G0/G1 phase for DBTRG-05MG and RG2 cells, respectively. The apoptosis-associated proteins were dramatically increased and activated by BP in DBTRG-05MG cells and RG2 cells, but RG2 cells did not express p53 protein. In vitro results showed that BP triggered both p53-dependent and independent pathways for apoptosis. In vivo, BP not only suppressed growth of subcutaneous rat and human brain tumors but also, reduced the volume of GBM tumors in situ, significantly prolonging survival rate. These in vitro and in vivo anti-cancer effects indicate that BP could serve as a new anti-brain tumor drug. [source] MMP-7 (matrilysin) expression in human brain tumorsMOLECULAR CARCINOGENESIS, Issue 6 2007Claire Rome Abstract Matrix metalloproteinases (MMP) which degrades protein components of the extra-cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and protein were clearly identified in human glioma. MMP-7 mRNA expression was highly variable within our glioma population. When analyzing MMP-7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but intra-individual variations were lower than inter-individual differences. With a xenograft model of U87 human tumors in RAG2/,c immune-deficient mice, the strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross-talk occurring between the tumor and the surrounding stroma to regulate MMP-7 expression. © 2007 Wiley-Liss, Inc. [source] Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spreadNEUROPATHOLOGY, Issue 2 2009Julia Snoei Leptomeningeal spread is a casual but conspicuous finding in both low- and high-grade gliomas. We hypothesized a compromised integrity of the glia limitans-basal lamina complex due to glycosylation defects by loss of protein-o-mannosyltransferase-1 (POMT1) activity, also a well-known feature in developmental brain disorders with leptomeningeal heterotopia. Hypothesizing it as analogous in gliomas, we have performed a comprehensive polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of the POMT1 gene in 41 brain tumor specimens. Each specimen was subjected to laser capture microdissection analyses to dissect: (i) subarachnoid tumor components; (ii) deeply localized tumor areas; and (iii) histologically unaffected CNS fragments. In addition, leukocyte DNA of healthy Caucasians served as controls (n = 100). Sequence alterations were found in exons 7, 9, 15 and 18. Exon 7 bore two sequence alterations, one 751C > T transition with amino acid exchange of arginine by tryptophane (Arg251Trp) (n = 12/41 in Tu vs n = 7/82 in Co) and a 752G > A transition with replacement of arginine by glutamine (Arg251Gln) (n = 3/41 in Tu vs n = 0/82 in Co) that were significantly increased in the tumor specimens compared to controls (P < 0.05). A 979G > A transition in exon 9 resulted in a valine to isoleucine switch (Val327Ile) (n = 6/40 in Tu vs n = 4/84 in Co). Individual specimens revealed a 1565G > A (Arg522Lys) transition in exon 15 and a 1922C > T (Ala641Val) transition in exon 18. Two gangliogliomas only revealed sequence alterations in the superficial area but not in intraparenchymal and adjacent control specimens. We conclude that a significant increase of POMT1 missense mutations may indicate a functional role in neoplastic conditions in individual tumors. Future studies will be important to evaluate a functional impact of POMT1 alterations in human brain tumors. [source] Genetic pathways to glioblastomasNEUROPATHOLOGY, Issue 1 2005Hiroko Ohgaki Glioblastomas, the most frequent and malignant human brain tumors, may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). These glioblastoma subtypes constitute distinct disease entities that affect patients of different ages and develop through different genetic pathways. Our recent population-based study in the Canton of Zürich, Switzerland, shows that primary glioblastomas develop in older patients (mean age, 62 years) and typically show LOH on chromosome 10q (69%) and other genetic alterations (EGFR amplification, TP53 mutations, p16INK4a deletion, and PTEN mutations) at frequencies of 24,34%. Secondary glioblastomas develop in younger patients (mean, 45 years) and frequently show TP53 mutations (65%) and LOH 10q (63%). Common to both primary and secondary glioblastoma is LOH on 10q, distal to the PTEN locus; a putative suppressor gene at 10q25-qter may be responsible for the glioblastoma phenotype. Of the TP53 point mutations in secondary glioblastomas, 57% were located in hotspot codons 248 and 273, while in primary glioblastomas, mutations were more widely distributed. Furthermore, G:C,A:T mutations at CpG sites were more frequent in secondary than in primary glioblastomas (56% vs 30%). These data suggest that the TP53 mutations in these glioblastoma subtypes arise through different mechanisms. There is evidence that G:C,A:T transition mutations at CpG sites in the TP53 gene are significantly more frequent in low-grade astrocytomas with promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene than in those without methylation. This suggests that, in addition to deamination of 5-methylcytosine (the best known mechanism of formation of, G:C,A:T, transitions, at, CpG, sites),, involvement of alkylating agents that produce O6 -methylguanine or related adducts recognized by MGMT cannot be excluded in the pathway leading to secondary glioblastomas. [source] Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigationNMR IN BIOMEDICINE, Issue 6 2005Fritz-Georg Lehnhardt Abstract High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p,=,0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p,=,0.0001) and glutamate (Glu)/glutamine (Gln) (p,=,0.004). Meningiomas showed increased Ala (p,=,0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p,=,0.001) relative to astrocytomas, and N -acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p,=,0.029; tCho, p,=,0.034; Glu, p,=,0.015; tCho/tCr, p,=,0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p,=,0.037) and Glu (p,=,0.003) and metabolite ratio tCho/tCr (p,=,0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n,=,11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism. Copyright © 2005 John Wiley & Sons, Ltd. [source] 1H- and 31P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral componentsNMR IN BIOMEDICINE, Issue 5 2001Fritz-Georg Lehnhardt Abstract In vitro NMR spectrocopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. 31P- and 1H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. 31P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the 1H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the 31P- and the 1H-spectra. Based on the total detectable 31P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p,=,0.0003), whereas the level of sphingomyelin was about 45% lower in primary gioblastomas than in primary astrocytomas (p,=,0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p,=,0.0103) and ,23% (p,=,0.0314) change, respectively]. 1H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the 31P-spectra, the 1H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. 1H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution 1H- and 31P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||