Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elucidating the relevant genomic changes mediating development and evolution of prostate cancer is paramount for effective diagnosis and therapy. A putative dominant-acting nude mouse prostatic carcinoma tumor-inducing gene, PTI-1, has been cloned that is expressed in patient-derived human prostatic carcinomas but not in benign prostatic hypertrophy or normal prostate tissue. PTI-1 was detected by cotransfecting human prostate carcinoma DNA into CREF-Trans 6 cells, inducing tumors in nude mice, and isolating genes displaying increased expression in tumor-derived cells by using differential RNA display (DD). Screening a human prostatic carcinoma (LNCaP) cDNA library with a 214-bp DNA fragment found by DD permitted the cloning of a full-length 2.0-kb PTI-1 cDNA. Sequence analysis indicates that PTI-1 is a gene containing a 630-bp 5' sequence and a 3' sequence homologous to a truncated and mutated form of human elongation factor 1 alpha. In vitro translation demonstrates that the PTI-1 cDNA encodes a predominant approximately 46-kDa protein. Probing Northern blots with a DNA fragment corresponding to the 5' region of PTI-1 identifies multiple PTI-1 transcripts in RNAs from human carcinoma cell lines derived from the prostate, lung, breast, and colon. In contrast, PTI-1 RNA is not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines. By using a pair of primers recognizing a 280-bp region within the 630-bp 5' PTI-1 sequence, reverse transcription-PCR detects PTI-1 expression in patient-derived prostate carcinomas but not in normal prostate or benign hypertrophic prostate tissue. In contrast, reverse transcription-PCR detects prostate-specific antigen expression in all of the prostate tissues. These results indicate that PTI-1 may be a member of a class of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate and other tissues. The approaches used, rapid expression cloning with the CREF-Trans 6 system and the DD strategy, should prove widely applicable for identifying and cloning additional human oncogenes.
 ...
PMID:Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. 754 76

A monoclonal antibody 6DS1 against a human glioblastoma multiforme cell line U-87MG recognizes a tumor-specific, cell surface antigen of human glioblastoma cell lines. Partial cross-reactivity is observed with two human neuroblastoma cell lines, SK-N-SH and SK-N-MC, with little or no reactivity towards a rat glioma cell line C6 or normal human adult and fetal brain tissues. The antibody recognizes an antigen of molecular mass 38 kDa as inferred from Western blot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate. The monoclonal antibody 6DS1 inhibits both the attachment to substratum and growth of U-87MG cells. It strongly cross-reacts with xenotransplants of U-87MG cells and inhibits tumorigenesis (subcutaneous implants of U-87MG cells) in nude mice.
 ...
PMID:Monoclonal antibody against human glioblastoma multiforme (U-87MG) immunoprecipitates a protein of molecular mass 38 kDa and inhibits tumor growth in nude mice. 782 86

The cytotoxic effects of taxol at concentrations of 0.001-1.0 microgram/ml were determined in two human glioblastoma multiforme, two neuroblastoma and two primitive neuroectodermal tumor cell lines. The neuroectodermal cell lines were established from previously treated patients, while the glioblastomas were from untreated patients. At exposure durations of 1, 4 and 24 h there was an inverse taxol concentration-survival relationship for all six cell lines as measured by the MTT method. Significant differences in sensitivity to taxol among these cell lines were observed; the most resistant cell line SK-N-FI is characterized by very high levels of MDR1 expression and the most sensitive SK-N-AS by very low levels. An additional level of complexity concerns a saturation threshold for taxol-induced cytotoxic effects which when reached precludes additional effects of prolonged or additional exposure. Tumors of the brain and peripheral nervous system appear to be sensitive to taxol. However, dosage necessary to maximize cytocidal effects in tumors requires knowledge of at least the range of each tumors constitutive sensitivity to taxol and a way to optimize drug delivery.
 ...
PMID:A saturation threshold for taxol cytotoxicity in human glial and neuroblastoma cells. 810 44

In this paper the results of two coordinated biomedical research projects are presented. The first project involves the determination of the average values of elements in normal human brain (20 individuals, age-group 65-75). 21 brain parts were selected from both hemispheres. Determinations were carried out by ICP-AES and INAA methods. The main (Na, K, Mg, Ca, Fe, P, S) and trace elements (Al, B, Ba, Co, Cr, Mn, Ni, Pb, Sr, Zn) were investigated. Quality control was ensured by using NBS Bovine Liver SRMs. On the basis of our investigations the regional distribution of elements can be given. The second goal was to detect the possible trace element changes in histopathologically selected brain regions from patients with glioblastoma multiforme. The majority of elements displayed no statistically significant differences between the studied groups, except the reduced levels of B and Zn and the increased level of Sr compared to the tissue from control individuals.
 ...
PMID:Concentration of elements in human brain: glioblastoma multiforme. 827 44

The efficacy and cytotoxic properties of immunotoxin conjugates directed against the transferrin receptor were examined in cell lines and operative specimens from pediatric brain tumors. Dose-response relationships were assessed for immunotoxin-mediated inhibition of protein synthesis for two immunotoxins, 454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell line exhibited similar sensitivity to both immunotoxins with IC50s in the 10(-9)-10(-10) M range. The time course of protein synthesis inhibition by the immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain tumors was also examined. The more aggressive and malignant tumor types such as glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), indicating that these tumors were extremely sensitive to transferrin receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and benign tumors was not as greatly affected by immunotoxins. Immunoblots showed expression of transferrin receptors on the cell lines and tumors which correlated with in vitro sensitivity to immunotoxin. The results demonstrate that two immunotoxins targeted to the transferrin receptor are efficacious in killing brain tumor cell lines and primary tumor cultures at very low concentrations and that highly malignant tumors are especially sensitive to this cytotoxic response.
 ...
PMID:Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. 844 15

Telomeric association (tas) is a cytogenetic phenomenon in which chromosome ends fuse to form dicentric, multicentric, and ring chromosomes. We observed clonal tas in six pediatric solid tumors of various types and histological grades studied using short-term in situ culture and G-banding techniques. These tumors included a neurilemoma, an undifferentiated (embryonal) sarcoma of the liver (UESL), two anaplastic astrocytomas (AA), one case of glioblastoma multiforme (GBM), and a neuroblastoma (NB) of the kidney. Cytogenetic data from all six tumors demonstrated multiple numerical and structural aberrations including tas. The tas appeared to be a secondary aberration in these tumors, however, it was possible to follow the progression of the telomeric chromosome aberrations in several cases. In all but one case (UESL) the loss of chromosome segments occurred. Tas of 11p was observed in three of the six tumors, two of which showed the subsequent loss of 11p (AA and AB). In addition, tas of 4p was seen in three tumors, two of which showed clonal tas of 4p with 22q. Tas of 10p, 21p, and 22q were all observed in at least two different tumors. The clonal telomeric fusions of 4p with 22q, recurring tas of 11p, and the subsequent loss of the short arm of 11 demonstrated here, suggests that some chromosome regions are subject to nonrandom instability and sometimes loss.
 ...
PMID:Telomeric associations in the progression of chromosome aberrations in pediatric solid tumors. 878 Jul 39

SV40 T antigen (Tag) coding sequences were detected by PCR amplification followed by Southern blot hybridization in human brain tumors and tumor cell lines, as well as in peripheral blood cells and sperm fluids of healthy donors. SV40 early region sequences were found in 83% of choroid plexus papillomas, 73% of ependymomas, 47% of astrocytomas, 33% of glioblastoma multiforme cases, 14% of meningiomas, 50% of glioblastoma cell lines, and 33% of astrocytoma cell lines and in 23% of peripheral blood cell samples and 45% of sperm fluids from normal individuals. None of the 13 normal brain tissues were positive for SV40 DNA, nor were seven oligodendrogliomas, two spongioblastomas, one neuroblastoma, one meningioma, or four neuroblastoma cell lines. Expression of SV40 early region was found by reverse transcription PCR, and SV40-specific Tag was detected by indirect immunofluorescence in glioblastoma cell lines. DNA sequence analysis, performed in four positive samples, confirmed that the amplified PCR products belong to the SV40 early region. Sixty-one % of the neoplastic patients positive for SV40 sequences had an age excluding exposure to SV40-contaminated polio vaccines, suggesting a contagious transmission of SV40. The possible role of SV40 Tag in the etiopathogenesis of human brain tumors and the spread of SV40 by horizontal infection in the human population are discussed.
 ...
PMID:SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. 924 67

Using the technique of DD-PCR (differential display-polymerase chain reaction) we isolated a novel gene (D2-2) that is overexpressed in glioblastoma multiforme tissue (GMT) as compared to normal brain tissue (NBT). D2-2 is also highly expressed in recurrent glioma, colon tumor metastatic to brain, breast tumors, prostate tumors and a prostate tumor cell line (LNCaP). Northern blot analysis showed that D2-2 is highly expressed in several tumor cell lines (MOLT lymphoblastic leukemia, SW480 colorectal adrenocarcinoma, A549 lung carcinoma, HL-60 promyelocytic leukemia, S3 HeLa cells, K-562 chronic myelogeneous leukemia and G361 melanoma) as compared to NBT. Additionally, D2-2 is very highly expressed in cell lines derived from glioblastomas, grade IV astrocytomas, normal human fetal astrocytes (NHFA) and glioma. D2-2 is moderately expressed in neuroblastoma, neuroectodermal and medulloblastoma tumor cell lines. D2-2 expression is localized to the frontal lobe, occipital lobe and the cerebellum in the normal brain. Normal tissues such as thyroid, stomach, adrenal cortex, small intestine and pancreas show high expression of D2-2. We also show that D2-2 is expressed 28-fold higher in fetal brain (20 weeks) than in adult brain. Sequence analysis of a 2.0-kb fragment for D2-2 shows no homology to known sequences in the data base.
 ...
PMID:Isolation and characterization of a novel gene from human glioblastoma multiforme tumor tissue. 917 9

Using the technique of differential display-polymerase chain reaction (DD-PCR), we isolated a cDNA fragment that is over-expressed in glioblastoma multiforme tissue as compared to normal brain tissue. Sequence analysis indicated that this sequence is identical to the previously isolated human neuron-glia-related cell adhesion molecule hNr-CAM. Gene-specific RT-PCR analysis indicated that hNr-CAM is over-expressed in high-grade astrocytomas, gliomas and glioblastoma tumor tissues as compared to normal brain tissue. High levels of hNr-CAM expression also were observed in cell lines derived from astrocytomas, gliomas and glioblastoma multiforme tumors. Low levels of hNr-CAM expression were observed in neuroblastoma, meningiomas, melanoma, normal breast and prostate tumor tissues. Northern blot analysis showed an alternatively spliced mRNA of 1.4 kb in several tumors as compared to the 7.5 kb transcript found in normal brain tissue. Genomic Southern blot analysis of DNA from 3 brain tumor cell lines showed that over-expression of hNr-CAM in brain tumors was not due to gene amplification. In situ hybridization analysis indicated that 11 of the 20 human brain tumor samples studied showed hNr-CAM over-expression. Our results suggest that hNr-CAM is over-expressed in malignant brain tumors and can serve as a novel marker for brain tumor detection and perhaps therapy.
 ...
PMID:Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. 959 Jan 16

The principle hurdles for gene therapy are selectivity and efficacy. Toward that end, we constructed an adenovirus gene delivery system to enable robust, glial-specific, and repressible ectopic expression. A replication-incompetent (E1-deleted) adenovirus 5 vector was modified by the addition of three tandem repeats of a 300-bp fragment enhancer region of the glial fibrillary acidic protein gene coupled to a minimal promoter sequence from human cytomegalovirus to drive a tetracycline-controlled transactivator. Using beta-galactosidase as a reporter gene, we demonstrated high level expression in cells of glial origin (including cell lines derived from glioblastoma multiforme) but no detectable expression in nonglial cells (neuroblastoma or fibroblasts). Furthermore, expression was tightly regulated by anhydrous tetracycline. To our knowledge, this is the first gene therapy delivery system that is glial specific and which also allows for repression of ectopic gene expression.
 ...
PMID:A glial-specific, repressible, adenovirus vector for brain tumor gene therapy. 972 49


<< Previous 1 2 3 4 5 6 Next >>