Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical studies have indicated that the structurally simple gangliosides, including GD3 and GM3, are major glycolipid components of glioma tissues. In order to clarify the localization of the gangliosides in ethylnitrosourea-induced rat glioma, an immunohistochemical study was performed using antibodies against GM1, GM3, and GD3. The results obtained in normal fetus, newborn, and adult rat brain, and also in human glioma, were compared. In fetal and newborn rat brain, GD3 was present mainly in the neuroepithelial cell surface of the matrix and subependymal layers of the ventricular wall, but GM3 and GM1 were not detected. In adult rat brain, GD3-positive cells were absent, or present in diminished number, and GM1 was found chiefly in the neuropil of the cerebral cortex. Most of the rat glioma cells were positive for GD3, but not for GM1. It was demonstrated that the ganglioside composition of glioma cells was similar to that of immature neuroectodermal cells in fetal and newborn rat brain. Furthermore, the number of GD3-positive oligodendroglioma cells increased with tumor growth. In anaplastic gliomas and gross oligodendrogliomas, most tumor cells expressed not only GD3 but also GM3. These results suggest that GD3 is a marker of proliferating neuroectodermal cells, and that activity of the key enzymes in ganglioside synthesis alters with tumor growth and anaplastic change.
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PMID:Immunohistochemical localization of gangliosides in ENU-induced rat glioma. 144 52

Malignant oligodendrogliomas have been shown to be responsive to chemotherapy. The authors administered systemic chemotherapy to seven patients with oligodendroglioma or anaplastic oligodendroglioma, and to 14 with mixed oligodendroglioma-astrocytoma. Fourteen patients underwent chemotherapy before and seven after irradiation. The PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) chemotherapy was administered every 6 weeks (42-day cycles) for two to five cycles as follows: CCNU, 110 mg/sq m on Day 1; procarbazine, 60 mg/sq m/day on Days 8 to 21; and vincristine, 1.4 mg/sq m/day on Days 8 and 29. Complete or partial (greater than 50% reduction in tumor mass) responses at 20 to 100+ weeks after treatment were noted in 11 (79%) of the 14 patients treated before irradiation, including two with anaplastic oligodendroglioma and nine with mixed tumors. Complete responses were seen in two patients, one with anaplastic oligodendroglioma and one with a mixed tumor. Partial responses were seen in three of seven patients treated after radiotherapy. Stabilization of tumor growth followed PCV chemotherapy in four patients (two treated before and two after radiotherapy). Tumor growth progressed in two patients during therapy despite an initial response and in two patients despite therapy. The authors conclude that mixed oligodendroglial tumors as well as anaplastic oligodendrogliomas are responsive to PCV chemotherapy.
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PMID:The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy. 156 35

A rare glial tumor known as 'minigemistocytic astrocytoma (gliofibrillary oligodendroglioma)' is reported in a 73 year old Japanese male. A low-density area found by computed tomography and thought to be an operative scare remaining after hematoma in the right frontal lobe of the cerebrum had been followed for 10 years. This area, however, had been accompanied by a cyst for 2 years and had developed gradually for 1 year prior to dissection. The tumor was poorly demarcated from the surrounding normal tissue macroscopically at operation. Microscopically, the tumor consisted of small gemistocytic cells in uniform sheets intersected by a small vascular stroma with frequent eosinophilic granular bodies, mitoses and apoptotic bodies. Immunohistochemical examination for glial fibrillary acidic protein (GFAP) revealed remarkable positive reactivity in the perinuclear cytoplasm, but no immunoreactivity for vimentin or Leu 7 was found. Electron microscopically, rich filaments arranged in parallel bundles were found in the neoplastic cells. These histological findings are closely consistent with those of previously reported minigemistocytic astrocytoma cases. The GFAP-rich minigemistocytic astrocytoma with granular bodies and frequent mitoses in the present case is considered to indicate a higher degree of astrocytic differentiation and malignant potential than previous cases. The frequent apoptoses, however, might inhibit tumor growth in this case.
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PMID:Minigemistocytic astrocytoma with frequent apoptoses: analysis of tumor growth. 749 8

In recent years there has been considerable progress in brain tumor neuropathology. Several new diagnostic entities have been recognized, subclassification schemes have been modified, and new concepts on the histogenesis and cell biology of brain tumors have emerged. In 1993, a revised WHO classification of brain tumors was published by an international committee. This article summarizes the pertinent new aspects. As novel tumor entities, the central neurocytoma, the dysembryoplastic neuroepithelial tumor (DNT), desmoplastic infantile ganglioglioma (DIG) and pleomorphic xanthoastrocytoma (PXA) have been included. Several histopathological variants of meningiomas have been added of which only the papillary meningioma and the atypical meningioma are characterized by an increased rate of recurrence. Meningeal hemangiopericytomas and hemangioblastomas are classified as tumors of non-meningothelial origin. The glioblastoma multiforme, which had previously been listed as an embryonal tumor, is now recognized as an astrocytic glioma. Immunohistochemistry has greatly advanced the practical diagnosis and classification of brain tumors. There are specific markers for all normal and neoplastic cell types except for oligodendroglioma cells. The prognosis of and therapeutic approaches to brain tumors greatly depend on histopathological grading. The WHO proposes four tumor grades, i.e., I, II, III, and IV. As a rule, grades I and II tumors are viewed as benign or semi-benign neoplasms and grades III and IV tumors as malignant. There are attempts to use new biological parameters for the grading of brain tumors. Antibodies to proliferation-associated proteins reflect tumor growth. Molecular genetic approaches to tumor-associated genes and gene loci are particularly promising new tools for the future.
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PMID:[Revised WHO classification and new developments in diagnosis of central nervous system tumors]. 766 6

Cytogenetic and molecular analyses such as allelotyping studies have revealed several genetic changes typical for human glial neoplasms. However, most studies to date have involved malignant gliomas and thus are likely to reflect late events of tumor progression. To elucidate the initial events of glial tumor growth, we performed a genome-wide search for genetic alterations in the DNA of 43 low-grade gliomas as compared to the constitutional DNA of the patients' peripheral blood leucocytes using the two-dimensional (2D) DNA fingerprint approach. Reliable results were obtained for 28 blood/tumor sample pairs (13 astrocytomas, 9 pilocytic astrocytomas, 1 oligodendroglioma, 3 oligoastrocytomas, and 2 ependymomas). DNA was digested with the restriction enzyme HaeIII and the resulting fragments were separated on 2D gels according to size and sequence in the first and second dimensions, respectively. Patterns of hundreds of spots were generated by hybridization with four different mini- and microsatellite core probes. A total of 655 to 1,122 spots could be visualized per sample. Comparison of blood and tumor spot patterns revealed two to 11 reproducible changes per patient. Most of the differences were spot losses (77.1%), while the others appeared to be gains or amplifications. Exactly the same changes were found in tumor recurrences which lacked histological signs of progression. When comparing different patients, many of the affected spots tended to cluster in particular areas of the gel as revealed by computer-aided comparison of all spot patterns. Eleven different spot clusters were identified which may correspond to several major deletion targets. This study provides the basis for the future molecular cloning of the candidate tumor suppressor genes affected by the common spot losses and will allow new insights into the genetic mechanisms of glial tumorigenesis.
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PMID:Genomic difference analysis by two-dimensional DNA fingerprinting reveals typical changes in human low-grade gliomas. 960 Mar 81

We report a case of brain surface clear cell ependymoma. A 13-year-old boy presented with complaints of right hypesthesia. Computed tomography and magnetic resonance image showed a left fronto-parietal cystic, calcified mass lesion. He underwent total resection of the tumor including cyst wall. The tumor located on the surface of the parietal lobe was sharply demarcated from the surrounding brain tissue and there was no continuity with the ventricular wall. Histological examination of the surgical specimens showed oligodendroglioma-like cells that had round unclei, clear cytoplasm which formed perivascular pseudorosettes, and immunoreactivity for glial fibrillary acidic protein (GFAP). Electromicroscopically, microvilli were seen. The findings were compatible with clear cell ependymoma. The cyst wall was lined with a layer of single cuboidal cells and, immunohistochemically, had no basal membrane. The inner surface of the cyst was positive for EMA, and the cuboidal cells were positive for GFAP. We discuss possible mechanisms for tumor growth in our case and the histogenesis of its cyst.
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PMID:[Brain surface clear cell ependymoma: case report]. 1047 46

Heme oxygenase (HO-1, HSP32) catalyzes the oxidation of heme to biliverdin and carbon monoxide, a putative neurotransmitter. In the brain, HO-1 expression has been associated with neuroprotection during oxidative stress and hypoxia. However, consecutive downstream mediation is involved in neoangiogenesis and consequent neoplastic outgrowth. We have analyzed HO-1 expression in 69 oligodendroglioma tissue samples, in rat intracranially transplanted C6 gliomas, and neuropathologically unaltered control brains by immunohistochemistry. Double labeling experiments confirmed the nature of HO-1 expressing cells. Reverse transcription-polymerase chain reaction was used to demonstrate HO-1 gene expression. HO-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of HO-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in their matched relapses (P<0.0001) and lower in primary anaplastic oligodendrogliomas than in their relapses (P=0.0006). Prominent accumulation of HO-1 expressing macrophages/microglial cells was observed in perinecrotic areas of both experimental rat and human glioblastoma relapses. HO-1 expressing neurons, macrophages/microglial cells and astrocytes were scattered in areas of infiltrative tumor growth. Surprisingly, HO-1 mRNA was detected in only one glioblastoma multiforme relapse. We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis. However, overall biological function of this phenomenon remains to be determined.
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PMID:Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression. 1105 78

Bis-2-chloroethylnitrosourea (BCNU) or temozolomide (TMZ) were tested alone or in combination with the AGT inhibitors O6-benzyl-2'-deoxyguanosine (dBG) or O6-benzylguanine (BG) against human glial tumor xenografts growing s.c. in athymic mice. Four glioblastoma (SWB77, SWB40, SWB39, and D-54) and one anaplastic oligodendroglioma (SWB61) xenografts having O6-alkylguanine-DNA alkyltransferase (AGT) activities of 75, 45, 10, < 10, and 16 fmol/mg protein, respectively, were used. BCNU at 35 mg/m2 was ineffective against these tumors, although 70 mg/m2 (LD10, 75 mg/m2) produced a marked tumor growth delay (T-C) in D54 but had no effect against SWB40 or SWB77. Coadministration of BG or dBG and BCNU necessitated reduction of the BCNU dose to a maximum of 30 and 35 mg/m2, respectively, because of increased toxicity. Optimized treatment with dBG (250 mg/m2) and BCNU (35 mg/m2) resulted in T-Cs of 30, 29, 11, 16, and 14 days for SWB77, SWB40, SWB39, D-54 and SWB61, respectively. These delays were more pronounced than those induced with optimized, isotoxic treatments with BG (180 mg/m2) and BCNU (30 mg/m2). In comparison to BCNU, TMZ was less toxic, with an LD10 of 400 mg/m2. TMZ (300 mg/m2) was more effective than BCNU against SWB77, SWB40, and SWB61, inducing T-Cs of 23, 53, and 56 days, respectively. BG and dBG enhanced the toxicity of TMZ in athymic mice by decreasing the LD10 from 400 to 200 mg/m2. TMZ (180 mg/m2) with either BG (180 mg/m2) or dBG (250 mg/m2) resulted in T-Cs of 31 and 49 days in SWB77, respectively, as compared with 16 days for TMZ (180 mg/m2) alone. In SWB40, the combination of TMZ with dBG, but not with BG, was significantly more effective than the maximum tolerated dose of TMZ (300 mg/m2) alone. The combination of TMZ with AGT inactivators had no benefit, as compared with TMZ alone, against xenografts with marginal AGT activity. In conclusion, at equimolar doses dBG was less toxic than BG in athymic mice when combined with either BCNU or TMZ. In this regard, BCNU or TMZ can be used at higher doses in combination with dBG than with BG. This study further demonstrates that there is a significant benefit of depleting AGT with nonspecific AGT inhibitors prior to treatment with either BCNU or TMZ in tumors having AGT activity >45 fmol/mg protein.
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PMID:Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide. 1123 99

Adult patients with a magnetic resonance scan suggestive of a supratentorial low-grade glioma should generally undergo at least a stereotactic biopsy to confirm the diagnosis and rule out an anaplastic glioma or a non-neoplastic lesion. Early tumor treatment should be given to patients with newly diagnosed low-grade gliomas who are over age 50 years, those who have headaches or neurologic deficits other than seizures, or those whose neuroimaging studies show tumor growth or mass effect. For younger patients presenting with seizures and no other neurologic symptoms, it is reasonable to defer therapy until there is clinical or radiographic tumor progression. When it is judged that intervention is necessary, patients should undergo the maximal surgical tumor resection, which preserves or improves neurologic function. For younger (<50 years) astrocytoma patients with a good tumor resection, radiation may be deferred until tumor progression. Early radiation should be given to astrocytoma patients who are older than 50 years of age at diagnosis (regardless of the type of surgery) or to younger patients who are judged to require early intervention but who are not candidates for aggressive surgical resection. The radiation dose for low-grade glioma should be 4500 to 5000 cGy, preferably with three-dimensional conformal ports. The same guidelines for management apply to patients with low-grade oligodendroglioma or oligoastrocytoma, except that chemotherapy is a reasonable alternative to radiation when it is judged that treatment other than surgical resection is required.
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PMID:Low-Grade Gliomas in Adults. 1515 4

Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade gliomas by continuous intravenous infusion (2.0 mg/kg/day for 21 days per month). Twenty-one patients entered this trial. Their median age was 46 years (range, 28-68 years), median Karnofsky performance status was 80 (range, 60-100), median tumor volume was 58 cm3 (range, 16-254 cm3), and histology included glioblastoma multiforme (n = 16), anaplastic oligodendroglioma (n = 4), and anaplastic astrocytoma (n = 1). The number of prior chemotherapy regimens included none (n = 3), one (n = 10), and two (n = 8). No tumor responses were observed. Patients on this therapy rapidly developed symptoms of increased intracranial pressure with increased edema, enhancement, and mass effect on neuroimaging. The median time to progression was 36 days, and median survival was 3.4 months. The observed toxicities were mild, reversible, and uncommon (grade 3 thrombocytopenia [n = 3] and grade 4 AST [n = 1]), and no coagulopathy or CNS bleeding resulted from this therapy. Plasma concentrations of aprinocarsen during the infusion exhibited significant interpatient variability (mean = 1.06 mug/ml; range, 0.34-6.08 mug/ml). This is the first study to use an antisense oligonucleotide or a specific PKC-alpha inhibitor in patients with high-grade gliomas. No clinical benefit was seen. The rapid deterioration seen in these patients could result from tumor growth or an effect of aprinocarsen on bloodbrain barrier integrity.
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PMID:Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. 1570 Dec 80


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