Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our purpose is to describe the incidence and clinical features of leptomeningeal dissemination (LM) in children with progressive low-grade neuroepithelial tumor (LGN). We have continuously tracked all patients with primary CNS tumors since 1986. Satisfactorily followed data were obtained on 427 of the 588 patients with localized LGN at diagnosis between 1986 and 1998, 177 (42%) of whom developed progressive or recurrent disease. LM was identified in 13/177 (7%). The median age at initial diagnosis was 5 years and at LM diagnosis was 8.5 years. The primary tumor sites were diencephalon (6), brainstem (3), cerebellum (2), cerebrum (1), and spinal cord (1). The histologies were pilocytic astrocytoma (4), ganglioglioma (4), fibrillary astrocytoma (3), mixed glioma (1), and glioneurofibroma (1). Management included chemotherapy (2) or radiotherapy (3) or both (7); 1 patient received only radical resections of symptomatic lesions. The 5-year progression-free survival rates for patients with localized versus LM disease at recurrence were 22% (95% confidence interval [CI], 13%-25%) versus 15% (95% CI, 0.1%-36%), respectively ( P = 0.28). The 5- and 10-year overall survival rates for patients with localized disease versus LM were 87% (95% CI, 82%-92%) and 83% (95% CI, 77%-89%) versus 68% (95% CI, 39%-91%) and 68% (95% CI, 39%-91%), respectively ( P = 0.05). The 7% incidence of LM is a low estimate because patients were not routinely staged at recurrence. Tumors arising from the diencephalon appeared to predispose to LM; no other predisposing features were identified. We strongly urge that for optimum treatment planning all patients with recurrent LGN be staged with an enhanced spine and brain MRI before adjuvant therapy is initiated. The good survival of patients with LGN and LM reflects a more indolent disease than malignant CNS tumors with LM.
 ...
PMID:Leptomeningeal dissemination in children with progressive low-grade neuroepithelial tumors. 1235 55

Previous studies demonstrated that the Ras suppressor, RSU-1, localizes to human chromosome 10p13, a region frequently deleted in high grade gliomas, and that RSU-1 expression inhibited the tumorigenesis of a glioblastoma cell line. We have now examined RNA from human glial tumors for RSU-1 expression by RT-PCR using primers for the 5' and 3' ends of the RSU-1 open reading frame. Analysis of the amplified RSU-1 cDNA demonstrated that in addition to the entire 858 bp RSU-1 open reading frame, a shorter 725 bp RSU-1 fragment was amplified as well. Sequencing of this product revealed that it encoded a RSU-1 cDNA product which was missing a single 133 bp internal exon. This exon-deleted product was found in 30% of the high grade gliomas studied and 2/3 oligodendrogliomas, but not in other CNS tumors, bladder or colon tumors or normal tissue. The exon-deleted RSU-1 product was infrequently detected in RNA from human tumor cell lines. Expression of an HA-tagged form of the deleted RSU-1 protein in transfected Cos 1 cells revealed that the protein was unstable, with a half life of less than 1 h, in contrast to the full length HA-tagged Rsu-1 protein which was stable for more than 4 h. These results suggest that the alternative splicing of the RSU-1 RNA to produce the exon-deleted form constitutes a mechanism for reduction or loss of functional Rsu-1. Because the expression of Rsu-1 can inhibit malignant growth of glioblastoma cells, the depletion of Rsu-1, via the production of the alternatively spliced form of RSU-1, may inhibit growth regulation in tumors.
 ...
PMID:Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas. 1251 Jul 72

Stereotactic radiosurgery by means of interstitial application of either radionuclides or radiation devices has been used extensively in primary and secondary brain tumors. A few centers have gained sufficient expertise and clinical data to scientifically evaluate this treatment modality. Interstitial stereotactic radiosurgery is limited to circumscribed lesions with a diameter of 3.5 cm or less. The radiobiology of interstitial radiosurgery is quite well elaborated as to doses, dose rates and effects on vascular physiology. Efficacy in low grade gliomas is well documented by several European centers using 125-J sources. Different modes of implantation have been used and evaluated including single fraction treatment using a miniature linear accelerator (Photoelectron). In malignant gliomas interstitial radiosurgery has been investigated in a prospective, randomised, controlled trial and not shown to be effective. Steretactic interstitial radiosurgery is a powerful treatment option in circumscribed CNS tumors like some low grade gliomas and metastasis but does play no major role in the treatment of malignant glioma.
 ...
PMID:Interstitial stereotactic radiosurgery. 1453 60

Effective therapies for primary brain tumors continue to be elusive. Successful adjuvant therapies for CNS tumors will require a better understanding of their basic biology. Hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) is a serine proteinase inhibitor that has a broad inhibitory spectra against various serine proteinases. HAI-2/PB has anti-invasive effects thought to be mediated primarily by the inhibitory activity against serine proteinase-dependent matrix degradation. It has been previously demonstrated that the expression of HAI-2/PB is inversely related to degree of malignancy and possibly involved in the progression and invasion of human gliomas. Aberrant methylation patterns are an early change in glioma tumorigenesis, earlier than genetic changes. Methylation within 5' regulatory CpG islands by DNA methyltransferase is one of the most common epigenetic modifications. 5-Aza-2'-deoxycytidine (azacytidine) inhibits DNA methyltransferase and has been used in vitro to induce the expression of genes silenced by methylation. We have utilized azacytidine treatment and a micro-array system to investigate methylation influenced gene expression across several tumor cell lines of different lineage (brain, breast, prostate, liver). Using this system we have demonstrated that the expression of HAI-2/PB is under methylation control to a variable extent in glioma cell lines, in comparison to the other tested cell lines. Because the expression of HAI-2/B is inversely related to glioma invasiveness and degree of malignancy, this finding may provide insight into glioma initiation and progression as well as potentially providing new therapeutic targets.
 ...
PMID:Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment. 1455 97

Idarubicin (IDA), the 4-demethoxy analog of daunomycin, has had significant cytotoxicity in many malignancies. In previous reports, the alcohol metabolite of IDA, 4-demethoxydaunorubicinol (idarubicinol, or IDOL), had cytotoxic activity and the ability to penetrate the blood-brain barrier. For this reason, the Pediatric Oncology Group conducted a Phase 2 trial of IDA for children with recurrent or progressive brain tumors. Ninety-one eligible children were entered on this study, with ages ranging from 3 months to 19 years. Patients were stratified by tumor types into 6 categories: stratum 1, low-grade astrocytoma; stratum 2, malignant glioma (glioblastoma multiforme and anaplastic astrocytoma); stratum 3, medulloblastoma; stratum 4, brainstem glioma; stratum 5, ependymoma; and stratum 6, miscellaneous malignant tumors not included in the previous diagnoses. IDA(18 mg/m2) was infused over 4 h and followed by granulocyte colony-stimulating factor (G-CSF) beginning day 5 after infusion of IDA. G-CSF was continued until blood cell count recovery. Cycles were repeated at approximately 21-day intervals until patients developed progressive disease or had completed 6 cycles with stable or improved disease. Pharmacokinetic plasma and cerebrospinal fluid (CSF) samples were collected from a subset of these patients. Response was poor in all strata. Most patients developed progressive disease; however, in 21 patients with medulloblastoma there was 1 partial response, and 6 patients had stable disease (SD) that in 4 patients lasted more than 20 weeks. Grades 3/4 hematopoietic toxicities were the most common toxic events, and 14 infection-related events resulted in hospitalization of patients. Only 1 patient developed reduced cardiac function. The systemic clearance data for IDA and IDOL were nearly identical to those published on patients with leukemia, and the plasma elimination of the IDOL metabolite was substantially longer than that of the parent drug IDA. The peak CSF:plasma ratios of IDA and IDOL were very low. The overall response rates to IDA were disappointing despite periods of prolonged SD in nearly a fourth of the patients. We conclude from this data and from that in nonhuman primates that it is unlikely that IDA, daunomycin, or other related anthracyclines will be useful for treating primary CNS tumors.
 ...
PMID:Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG 9237. 1456 63

Since the appearance in 2000 of the World Health Organization (WHO) classification for central nervous system (CNS) neoplasms, numerous descriptions of new entities or variants have appeared in the literature. In the group of neuronal and mixed glioneuronal neoplasms are lesions with distinctive morphological features that are still not included in a precise classification, including extraventricular neurocytoma, papillary glioneuronal tumor, rosette-forming glioneuronal of the fourth ventricle, glioneuronal with neuropil-like rosette, and DNT-like tumor of the septum pellucidum. The glioneuronal tumor with neuropil-like rosette and oligodendroglioma with neurocytic differentiation represent morphological variants of genetically proven diffuse gliomas. The lipoastrocytoma and the pilomixoid astrocytoma enlarge the group of astrocytic lesions. Rare, low-grade gliomas of the spinal cord with extensive leptomeningeal dissemination associated with unusual neuroimaging are described. The chordoid glioma of the third ventricle and the papillary tumor of the pineal region seem to be correlated by a common histogenesis from the specialized ependyma of the subcommissural organ. An embryonal tumor with neuropil and true rosettes combining features of neuroblastoma and ependymoblastoma is discussed. These new, recently described lesions indicate that the complex morphologic spectrum of CNS tumors is far from being completely delineated.
 ...
PMID:Emerging tumor entities and variants of CNS neoplasms. 1505 42

Neurofibromatosis (NF) is the most common of the phakomatoses, with a prevalence of 1 in 3-4,000. Many organ systems can be affected. In addition to multiple peripheral neurofibromas, NF I predisposed to CNS tumors including optic glioma, astrocytoma and plexiform neurofibroma. The purpose of this pictorial review is to illustrate characteristic brain MR imaging lesions in children with NF I and to give some recommendations about diagnostic imaging procedures in children suffering from NF I. Typical findings in brain MRI are hyperintense lesion on T2-weighted images, so-called unknown bright objects, which may be useful as an additional imaging criterion for NF I. Contrast administration is necessary in MR studies to maximize tumor detection and characterization, to add confidence to the diagnosis of benign probable myelin vacuolization, and to document stability of neoplasm on follow-up examinations. We recommend to perform serial MR imaging in children every 12 months. The frequency of follow-up in children with known brain tumors will vary with the tumor grade, biological activity and treatment.
 ...
PMID:Pediatric brain MRI in neurofibromatosis type I. 1529 66

Hemangioblastomas (HBs) are low-grade (World Health Organization grade I/IV) central nervous system (CNS) tumors that frequently contain VHL (3p26) mutations. They occur sporadically and in von Hippel Lindau (VHL) disease. Encoded pVHL aids degradation of hypoxia-inducible factors (HIFs) in the presence of normal oxygen levels. HBs provide an in vivo view of HIF effects within a CNS tumor. Typically, HBs are cystic tumors containing a mural nodule formed by noninvasive, vacuolated stromal cells that are embedded in a network of capillaries. Nine HBs, consecutively resected from 8 patients at our institution during a recent 2-year time span, were evaluated for additional losses of tumor suppressor genes. Non-VHL microsatellites studied for loss of heterozygosity (LOH) are near tumor suppressor genes lost in gliomas, pituitary adenomas, several CNS tumors on 22q, neurofibromatosis 1, and colon carcinomas (13, 2, 2, 1, and 2 markers for each, respectively). LOH in the region of 3p21.3-3p26.3 occurred in 3 of 8 HBs informative for at least 1 marker (D3S1539, D3S2303, or D3S2373). By using 2 markers (D22S417 and D22S532) for 22q13.2, LOH was found in 5 of 8 informative HBs. All 3 HBs with allelic losses near VHL also showed LOH at 22q13.2. No consistent losses were found with markers for 1p34, LMYC, 5q21, 5q32, 9p21, 10q23, 17p13, and 19q13. LOH for the 22q13.2 region in HBs suggests that the loss of another tumor suppressor gene is involved in the pathogenesis of HBs in addition to VHL. Absence of LOH for glioma markers is consistent with the low-grade behavior of HBs.
 ...
PMID:Loss of heterozygosity reveals non-VHL allelic loss in hemangioblastomas at 22q13. 1534 13

Primary central nervous system (CNS) tumors constitute a small fraction of the overall incidence of human cancer, but they represent a major source of cancer-related morbidity and mortality. The most common CNS tumor subtype in adults, high-grade astrocytoma, confers a dismal prognosis with a median survival of only 1 to 2 years. Other common adult CNS tumors, ie, low-grade astrocytomas and oligodendrogliomas, carry a less ominous, yet still poor prognosis. Unfortunately, there has been little progress in extending the survival or quality of life for glioma patients, despite nearly four decades of extensive research. This research has, however, greatly increased our understanding of the underlying molecular biology of these tumors, examples of which include the determination of elevated epidermal growth factor receptor (EGFR) as well as platelet-derived growth factor receptor (PDGF) signaling, and the inactivation of p53 , p16 , and PTEN tumor-suppressor genes (TSGs) that negatively regulate specific enzymatic activities in normal glial cells. Such observations have greatly improved our understanding of the pathogenesis of these tumors and have potential diagnostic as well as therapeutic relevance. With respect to the latter of these two issues, the identification of aberrant enzymatic activities in gliomas has promoted the development of novel therapeutic agents that target specific signaling effectors, and whose inhibition should, in theory, prove to be cytostatic, if not cytotoxic, to tumor cells. Several clinical trials are currently underway for testing these therapeutic agents in patients with primary brain tumors, and it is hoped that the targeting of pro-tumorigenic enzymatic activities will lead to better patient outcomes. In this review, we will describe the most pertinent genetic and signaling pathway alterations that are clinically relevant to the management of glial tumors.
 ...
PMID:Altered molecular pathways in gliomas: an overview of clinically relevant issues. 1549 13

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic protein originally identified as a gene product upregulated in prostate tumor cells undergoing apoptosis. Down-regulation of Par-4 has been linked to several cancers. Since Par-4 also plays a crucial role in neuronal apoptosis, we investigated the expression of Par-4 in tumor cell lines derived from representative tumor types of the CNS, including primitive neuroectodermal tumor (PNET), medulloblastoma, neuroblastoma and glioma of human, rat and murine origin. We show that Par-4 is frequently down-regulated, either transcriptionally or post-transcriptionally in the CNS tumor cell lines. Moreover, we demonstrate that ectopic expression of Par-4 is sufficient to directly induce apoptosis in these CNS tumor cells, in contrast to other cancer cells where replenishment of Par-4 levels only sensitizes the cells to apoptotic stimuli. Induction of apoptosis by Par-4 in the neural tumor cell lines is independent of endogenous Bcl-2 levels and PKCzeta activity, although it has been proposed that Par-4 can exert its pro-apoptotic function by down-modulation of Bcl2 expression and inhibition of PKCzeta. Co-expression of Par-4 and a dominant-negative mutant of FADD resulted in a slight reduction of apoptosis in some tumor cell lines, indicating that Par-4 may partially induce apoptosis via the Fas death pathway. Furthermore, these data suggested that the pro-apoptotic function of Par-4 involves (an)other yet unidentified apoptotic pathway(s) in the CNS tumor cell lines. Since Par-4 by itself is not sufficient to induce apoptosis in non-tumor cells, reintroduction of Par-4 into primary CNS tumors or reactivation of the pathways of Par-4-mediated apoptosis represent promising targets in anti-tumor therapy.
 ...
PMID:Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines. 1558 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>