Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mouse monoclonal antibody, FKH1, was produced to detect cytoplasmic melanoma-associated antigen. FKH1 was raised using cultured human melanoma cell line KHm-6 as an immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques against cell lines and normal and neoplastic tissues. Positive reactions were seen against 5 human melanoma cell lines. It stained cytoplasm of melanoma cells in a diffuse and granular pattern in indirect immunofluorescence. Immunoelectron microscopy showed diffuse distribution of immunoreactant in the cytoplasm of KHm-1 cells excluding melanosomes and other organelles. Reactivity against frozen and alcohol-fixed, paraffin-embedded melanocytic tumors was also tested with IIF or indirect or avidin biotinylated horseradish peroxidase complex immunoperoxidase techniques. All cases of frozen sections from benign and malignant melanocytic tumors showed positive staining with FKH1. In fixed tissues, however, reactivity was 11 of 14 (79%) in malignant melanoma and 28 of 42 (67%) in other melanocytic tumors. FKH1 did not react against normal melanocytes and nonmelanocytic tumors except APUDoma and 2 glioblastoma cell lines. It failed to stain the B-16 mouse melanoma cell line, neuroblastoma cell line, breast carcinoma cell line, and T-cell lymphoma cell line. Normal human peripheral nerves were nonreactive with FKH1. In immunoelectroblot study, FKH1 bound with proteins having molecular weight of 71,000 and 55,000 extracted from KHm-6 cells. It was suggested that FKH1 is a useful monoclonal antibody in diagnostic study of human malignant melanoma specimens.
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PMID:Mouse monoclonal antibody (FKH1) detecting human melanoma-associated antigens. 375 74

The development of sarcoma within a glioblastoma is a well recognised complication: in the majority of cases it is a fibro-sarcoma originating in the tissues of the proliferating hyperplastic blood vessels. In the case described here the tumour is a rhabdomyosarcoma, apparently derived from abnormal prolific vascular mesenchyme. Only one comparable example has been recorded previously.
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PMID:Gliomyosarcoma. Report of a case of rhabdomyosarcoma arising in a malignant glioma. 396 96

We studied two children who had rhabdomyosarcoma and glioblastoma and who were from a family with a hereditary cancer syndrome that was characterized by sarcoma, breast cancer, brain tumors, lung cancer, laryngeal carcinoma, leukemia, and adrenocortical carcinoma. The deleterious genotype has now been expressed through the fourth generation of this large kindred. The pedigree emphasizes the need for an extended history of several generations to arrive at a hereditary-syndrome diagnosis. A limited pedigree may result in nonappreciation of the genetic component. The pedigree illustrates that, in certain circumstances, the highly specific varieties of cancer may occur in children before it is expressed in the parent who carries the putative gene. Pediatricians, in evaluating the causes of childhood cancer, must be cognizant of cancer among adult relatives, since this recognition may aid in the diagnosis of those hereditary cancer syndromes that are characterized by cancer occurrence in children as well as adults.
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PMID:The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited. Childhood cancer. 397 85

Alpha and beta interferon were tested for antitumor activity and clinical toxicity in 15 children suffering from cancer. The drug was administered IV, IM, IT or intralesionally daily in the majority of cases in total doses of 18 X 10(6) to 9,634 X 10(5) IU. Major toxicities were a flulike syndrome, elevation of transaminase activity and leukopenia. A minor response (less than 50%) was observed in one patient with glioblastoma, treated by intrathecal administration, and an objective local response was noted in one rhabdomyosarcoma patient with multiple subcutaneous metastases, who was treated by intralesional administration. CNS leukemia in two patients improved without hematological response. Further trials are warranted.
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PMID:[Clinical experience with alpha and beta interferon in childhood cancer]. 659 60

Expression of the RCK gene, which is a target gene on 11q23 of the t(11;14) (q23;q32) translocation in the B-cell lymphoma cell line RC-K8, was studied by Northern and Western blot analyses. The RCK gene product is a member of the D-E-A-D box protein/RNA helicase family. With the use of Northern blot analysis, a 7.5-kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against the RCK gene product were raised, and the RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal anti-rck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues, although RCK mRNA is abundantly present in these tissues. It is of interest that malignant transformed human cells arising from tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma, and lung cancer cell lines, produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role in tumorigenesis. In addition, the rck/p54 protein was localized to cytoplasm by immunostaining with the use of laser microscopy and by subcellular fractionation.
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PMID:The rck/p54 candidate proto-oncogene product is a 54-kilodalton D-E-A-D box protein differentially expressed in human and mouse tissues. 761 84

The invasiveness of three medulloblastoma permanent cell lines (D-283, D-341, and DAOY), a human medulloblastoma biopsy, and in addition, a human rhabdomyosarcoma permanent cell line (TE-671), which previously had been regarded as a human medulloblastoma, was studied in an organ co-culture assay. All the four cell lines and the biopsy were co-cultured with normal rat brain cell aggregates for up to six days in vitro. The medulloblastoma biopsy, the D-283 and the D-341 cells invaded the brain tissue by diffuse single cell infiltration. The medulloblastoma cell line (DAOY) showed an invasive pattern similar to that observed earlier for most glioblastoma cell lines. This was characterized by massive cell replacement and destruction of normal brain tissue. The rhabdomyosarcoma cell line (TE-671) presented a solid invasive pattern with a fairly well defined border between normal brain and tumour tissue. Thus, the organ co-culture assay system in vitro seems to mimic several aspects of the in situ invasive behaviour of medulloblastomas. It may, therefore, provide new perspectives for pretreatment investigations with chemotherapy and radiotherapy of these malignancies.
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PMID:Interaction between human medulloblastomas and foetal rat brain aggregates in vitro. 815 16

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.
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PMID:Human astrocytoma cells express a unique chloride current. 874 85

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.
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PMID:Human astrocytoma cells express a unique chloride current. 880 32

Astrocytic tumors occasionally arise in the central nervous system following radiotherapy. It is not clear if these gliomas represent a unique molecular genetic subset. We identified nine cases in which an astrocytoma arose within ports of previous radiation therapy, with total doses ranging from 2400 to 5500 cGy. Irradiated primary lesions included craniopharyngioma, pituitary adenoma, Hodgkin's lymphoma, ependymoma, pineal neoplasm, rhabdomyosarcoma, and three cases of lymphoblastic malignancies. Patients ranged from 9 to 60 years of age and developed secondary tumors 5 to 23 years after radiotherapy. The 9 postradiation neoplasms presented as either anaplastic astrocytoma (3 cases) or glioblastoma multiforme (6 cases). Two of the latter contained malignant mesenchymal components. We performed DNA sequence analysis, differential polymerase chain reaction (PCR), and quantitative PCR on DNA from formalin-fixed, paraffin-embedded tumors to evaluate possible alterations of p53, PTEN, K-ras, EGFR, MTAP, and p16 (MTS1/CDKN2) genes. By quantitative PCR, we found EGFR gene amplification in 2 of 8 tumors. One of these demonstrated strong immunoreactivity for EGFR. Quantitative PCR showed chromosome 9p deletions including p16 tumor suppressor gene (2 of 7 tumors) and MTAP gene (3 of 7). Five of 9 tumors demonstrated diffuse nuclear immunoreactivity for p53 protein. Sequencing of the p53 gene in these 9 cases revealed a mutation in only one of these cases, a G-to-A substitution in codon 285 (exon 8). Somewhat unexpectedly, no mutations were identified in PTEN, a commonly altered tumor suppressor gene in de novo glioblastoma multiformes. Unlike some radiation-induced tumors, no activating point mutations of the K-ras proto-oncogene or base pair deletions of tumor suppressor genes were noted. These radiation-induced tumors are distinctive in their high histological grade at clinical presentation. The spectrum of molecular genetic alterations appears to be similar to that described in spontaneous high grade astrocytomas, especially those of the de novo type.
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PMID:Molecular genetic alterations in radiation-induced astrocytomas. 1032 96

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeated every 21 days over a period of 8 weeks. Doses of topotecan ranged from 0.16 to 1.5 mg/kg to simulate clinically achievable topotecan lactone plasma systemic exposures. Vincristine was administered i.v. every 7 days at a fixed dose of 1 mg/kg. Given as a single agent, vincristine induced complete responses (CRs) in all mice bearing two rhabdomyosarcomas (Rh28 and Rh30) and some CRs in Rh12-bearing mice (57%) but relatively few CRs (<29%) in other tumors. As a single agent, topotecan induced CR in a low proportion of tumor lines. A dose-response model with a logit link function was used to investigate whether the combination of topotecan and vincristine resulted in greater than expected responses compared with the activity of the agents when administered alone. Only CR was used to evaluate tumor responses. The combination resulted in significantly greater than expected CRs than individual agents in nine tumor lines (four neuroblastoma, three brain tumors, and two rhabdomyosarcomas). Similar event-free (failure) distributions were shown in SJ-GBM2 glioblastoma xenografts, whether vincristine was administered on day 1 or day 5 of each topotecan course. To determine whether the increased antitumor activity with the combination was attributable to a change in drug disposition, extensive pharmacokinetic studies were performed. However, little or no interaction between these two agents was determined. Toxicity of the combination was marked by prolonged thrombocytopenia and decreased hemoglobin. However, approximately 75 and 80% of the maximum tolerated dose of each single agent, topotecan (1.5 mg/kg) or vincristine (1 mg/kg), could be given in combination, resulting in a combination toxicity index of approximately 1.5. These results show that the therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors, and toxicity data suggest that this can be administered to mice with only moderate reduction in the dose levels for each agent.
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PMID:Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts. 1058 79


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