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Query: UNIPROT:P06889 (Mol)
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From a liver metastasis of a human pancreatic adenocarcinoma, we have established cell lines for studying the cell biology of this tumor. We obtained two cell lines with different morphological, chromosomal and functional properties. One of them, named PaTu 8988s, revealed a solid growth in nude mouse xenografts with cells exhibiting only occasional polar organisation of the cytoplasm. In general, no apical or basolateral plasma membrane domains could be distinguished and the sparse organelles were randomly distributed throughout the cytoplasm. Secretory products, such as mucin, were weakly stained histochemically or were completely absent. Transglutaminase (TGase) activity used as a marker for cellular differentiation was low in these cells. The other cell line, named PaTu 8988t, grew tumors composed of tubular structures when injected subcutaneously into nude mice. Cells were polarized with distinct apical and basolateral plasma membranes and the cytoplasmatic organelles were arranged with the nucleus in the lower part of the cell, while the apical cytoplasm contained the Golgi complex and numerous secretion granules. A high content of mucin was stained histochemically and transglutaminase activity was ten times higher than in PaTu 8988s. Comparing the chromosome number per metaphase plate, both cell lines showed a major peak, with 45-55 chromosomes per metaphase plate in PaTu 8988s and about 110-120 chromosomes per metaphase plate in PaTu 8988t. When the two cell lines were injected intravenously into the tail vein of nude mice, only PaTu 8988s developed metastases localized exclusively in the lung, whereas PaTu 8988t produced no metastases in any organ. We conclude, that two cell lines exhibiting different grades of differentiation as well as a different potency to metastasize can be established from the same primary tumor, and that these cell lines represent a suitable model for further study of the cell biology of human pancreatic adenocarcinoma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Establishment and characterisation of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma. 134 91

Extrachromosomal circular DNAs ranging in size from submicroscopic molecules of approximately 100 kb to cytogenetically resolvable structures of 1000+ kb called minute and double-minute chromosomes have been shown to harbor amplified genes in primary tumor cells, tumor cell lines, and drug-resistant cells grown in vitro. The presence of these molecules in transformed and malignant cells trends to reflect genetic instability and also suggests that role in tumor progression. Using a colon carcinoma cell line, we developed a technique to detect extrachromosomal circular DNA-specific sequences by Alu-polymerase chain reaction. Circular DNA was enriched by selective alkaline denaturation of genomic DNA. We have successfully performed this procedure with a minimum of 5 x 10(5) cells. The technique does not require any prior knowledge of the sequences located on the covalent circular DNA molecules for their detection. The procedure should be useful as a routine screen of primary tumor cells for the presence of extrachromosomal circular DNA and should permit the preparation of specific probes ot aid in their detailed characterizations.
Mol Carcinog 1992
PMID:Detection of extrachromosomal circular DNA sequences from tumor cells by an alkaline lysis, Alu-polymerase chain reaction technique. 155 8

The DNA ploidy pattern and amplification of ERBB and ERBB2 genes were examined in paraffin-embedded tissue from gastric carcinomas using flow cytometry and a slot-blot hybridization technique. The incidence of aneuploidy in well differentiated adenocarcinomas (56%) was significantly higher (p less than 0.05) than that in poorly differentiated adenocarcinomas (21%). The DNA ploidy pattern was not remarkably different between the primary tumors and metastatic deposits in lymph nodes. Of the nine specimens having an aneuploid stem cell line in the primary tumor and/or in metastases, three showed ERBB2 gene amplification and one showed ERBB gene amplification. The incidence of epidermal growth factor (EGF) immunoreactivity in tumor cells showed no difference between diploid and aneuploid tumors. These findings indicate that aneuploidy is frequently associated with amplification of ERBB and ERBB2 genes.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas. 197 Jun 90

Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease-free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study.
Mol Biother 1990 Sep
PMID:Phase II study of recombinant interferon alpha-C in patients with metastatic renal cell carcinoma. 222 99

In A/J strain mice, the carcinogen urethan induces lung adenomas and adenocarcinomas that contain Ki-ras-activating mutations primarily in codon 61. These mutations affect the middle adenine in codon 61 resulting in the substitution of either arginine (AT----GC transition) or leucine (AT----TA transversion) for the wild-type glutamine. To analyze the expression of the wild-type and mutant Ki-ras mRNAs in primary mouse lung tumors and transformed mouse lung cell lines, we utilized reverse transcription of total mRNA and DNA amplification by the polymerase chain reaction. The wild-type allele of codon 61 was expressed in all normal lung and primary tumor samples and in all transformed cell lines, except one. Significantly, the leucine-substituted allele was expressed primarily in very small lung adenomas, whereas the arginine-substituted allele was expressed in large lung adenocarcinomas and transformed lung cell lines. The relative amounts of expression of the mutant versus wild-type Ki-ras alleles and the total Ki-ras mRNA expression was similar in both lung adenomas and adenocarcinomas. Further, the arginine mutant allele was present in adenocarcinomas having either alveolar or papillary tumor morphologies. These results suggest that the specific activating Ki-ras mutation is more critical to either lung adenoma or adenocarcinoma development than is the tumor's cell of origin or the extent to which the mutant alleles are expressed. A distinct role of the specific activating Ki-ras mutations in affecting lung tumor growth or malignant potential is indicated.
Mol Carcinog 1990
PMID:Specific Ki-ras codon 61 mutations may determine the development of urethan-induced mouse lung adenomas or adenocarcinomas. 224 61

A thyroid tumor cell line has been established from the metastases of a follicular carcinoma in a female patient. Although the primary tumor released thyroglobulin (Tg) into the circulation (greater than 10,000 ng/ml), the uptake of I131 was less than 2%. After 37 replications the doubling time was 4 days and confluency was reached after 7 days from inoculation of 3 x 10(7) cells. This human thyroid tumor cell line has now been growing in culture for several years. An aneuploid chromosomal pattern was observed (62-82 chromosomes). A pair of X chromosomes was present but no Y chromosome was found which is compatible with the female origin of the cell line. EM studies revealed the presence of microvilli. Immunoperoxidase staining using specific anti-human Tg antisera indicated the presence of Tg within the cells. Nude mice developed solid-cystic tumors within 6 months after injection of the cells. The basal release of immunodetectable Tg, as measured in a perifusion system, increased in response to thyroid stimulating hormone (TSH) (P less than 0.025) or TSH combined with theophylline (P less than 0.001). Unusual isoenzyme patterns for galactose-1-phosphate-uridyltransferase (GALT) and phosphoglucomutase1 (PGM1) were detected in the tumor, compared with normal human fibroblasts and blood cells and isoenzyme patterns from the patient's lymphocytes. Because this malignant human thyroid follicular cell line has retained the ability to synthesize Tg it represents a valuable model for the study of human follicular carcinomas.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1). 257 Apr 83

We examined the expression of six proto-oncogenes in (i) whole rat liver and isolated liver cell populations during the course of hepatocarcinogenesis induced by a choline-deficient diet containing 0.1% ethionine and (ii) fetal rat liver at different stages of development. The abundance of c-Ki-ras, c-Ha-ras, and c-myc transcripts in polysomal polyadenylated RNA from liver cells increased by 2 weeks after the start of the carcinogenic diet. c-Ki-ras and c-myc expression remained elevated during the 35 weeks of the diet, whereas c-Ha-ras transcripts increased transiently. A primary tumor sampled at 35 weeks after the carcinogenic diet was started contained high levels of both c-Ki-ras and c-myc RNA. The abundance of c-src transcripts was unchanged throughout carcinogenesis; c-abl and c-mos transcripts were not detected in either preneoplastic or neoplastic livers. To determine which cell types within the liver contained proto-oncogene transcripts, we isolated hepatocytes, oval cells, and bile duct cells from normal and preneoplastic livers. The results indicate that proto-oncogenes are expressed differentially in these cell types during hepatocarcinogenesis and that the expression of c-Ki-ras and c-myc is high in oval cells throughout carcinogenesis. In developing livers, c-Ki-ras, c-Ha-ras, and c-myc transcript levels were high at 17 days of gestation but reached the low values characteristic of adult rat livers between 20 days of gestation and 3 days after birth.
Mol Cell Biol 1985 Apr
PMID:Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis. 258 Nov 26

Several human rhabdomyosarcoma cell lines, cultured primary tumor explants, and biopsies of tumor and normal skeletal muscle tissue expressed a 2.0-kilobase transcript that hybridized to the mouse muscle determination gene MyoD1. This transcript was found in tumor cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines derived from other mesenchymal tumor cell types. Expression of the human homolog of MyoD1 therefore can define a tumor as a rhabdomyosarcoma. Transfection of the mouse MyoD1 gene into the human rhabdomyosarcoma cell line RD increased the ability of the tumor cells to differentiate into multinucleated myotubes and enhanced myosin heavy-chain gene expression but did not decrease tumorigenicity in nude mice.
Mol Cell Biol 1989 Nov
PMID:Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas. 260 95

A long-term culture Epstein-Barr virus (EBV)-negative malignant lymphoid cell line (NAK) was established from a lymph node biopsy of a chronic lymphocytic leukemia patient. This cell line is of particular interest because it grows as an adherent cell line and depends on the presence of autologous conditioned medium for growth. After 6 months of growth in vitro, doubling time and cell cycle parameters were derived. Doubling time was 48 hours with over 45% cycling cells. Cell viability was over 90%. Expression of B-cell markers (CD19 and CD20) and surface immunoglobulin of the original tumor cell biopsy were roughly the same as in passage 14 (3 months in culture), including the expression of the original patient idiotype and IgM-lambda. Furthermore, binding of antiidiotypic antibodies was only slightly decreased at passage 14. Cytogenetic studies of chromosomal abnormalities in the primary tumor tissue and in later passages indicated similar abnormalities, with no translocations t(8;14), t(14;22), or t(2;8). However, frequent trisomies, deletions, and t(1;4) translocations were observed. Negative results for EBV nuclear antigen indicate that this cell line is an EBV-negative cell line.
Mol Biother 1989
PMID:Establishment and characterization of a malignant lymphoid cell line from a chronic lymphocytic leukemia patient. 261 Sep 52

Two cell lines with different in vitro growth characteristics were established from a single mucinous colonic adenocarcinoma. Epithelial cells of the line 5583-E demonstrated anchorage-dependent growth while those of line 5583-S were anchorage-independent and grew as multicellular floating spheroids. Both cell lines shared common characteristics with respect to the expression of differentiation markers (secretory component, carcinoembryonic antigen), mucins and karyotype (trisomy 12 and 14, marker chromosome) but also showed consistent differences. In nude mice 5583-S cells formed moderately differentiated mucinous adenocarcinomas with high carcinoembryonic antigen and mucin production, whereas 5583-E xenografts were poorly differentiated and almost entirely failed to produce carcinoembryonic antigen and mucins. The plating efficiency of 5583-E cells appeared to be greater and doubling time shorter than those of 5583-S cells. Furthermore, 5583-E cells showed an extra isochromosome, 1q. The cell lines were genotypically and phenotypically stable over a period of 2 years. Our results reemphasize that multiple cell lines with heterogeneous phenotypic and genotypic characteristics can be obtained from a single primary tumor.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:The establishment and characterization of two new cell lines derived from a single human colonic adenocarcinoma. 289 Feb 31


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