Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemosensitivity of liver cell carcinoma was studied by subrenal capsule assay. The method of assay was based on Bogden's one, but the antitumor activity was evaluated by tumor growth inhibition rate (TG-IR). The anticancer agent with more than 50% TG-IR was judged as positive in the chemosensitivity test. Of 3 human hepatoma cell lines transplanted in the subcutaneous space of nude mice, all of 3 were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 66.7%, 100%, 66.7%, 100% and 0%, respectively. Of 24 patients who provided fresh tumor specimens for the assay, 12 (50%) were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 25%, 16.7%, 16.7%, 33.3% and 8.3%, respectively. Our study suggested that 5-FU, MMC and ADR were comparatively active against the hepatoma cell, CDDP was less active than these 3 agents, CPA was inactive. These results seem to justify the use of current anticancer agents against hepatic cell carcinoma and indicate the usefulness of SRC assay for selecting chemotherapeutic agents against liver cell carcinoma.
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PMID:[Study on the chemosensitivity of liver cell carcinoma by subrenal capsule assay]. 334 29

The binding rate of 14C-Misonidazole was determined for freshly isolated mouse hepatocytes, mouse hepatoma cells, EMT-6 tumor cells, and V79 Chinese hamster lung fibroblasts. At 10 microM drug concentration, the four different cell lines bound 14C-Misonidazole at rates of 12.4, 29.9, 51.6, and 13.5 pmoles/10(6) cells/hr, respectively. This relative order of binding was observed over a drug concentration range of 10-100 microM. These data indicate that in extreme hypoxia, mouse hepatocytes do not bind 14C-Misonidazole at a uniquely high rate in vitro, compared to other normal and tumor cell lines. This observation suggests that the increased binding to liver in vivo observed by other investigators is due to the liver existing at a reduced oxygen tension, compared to other normal tissues.
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PMID:In vitro binding of 14C-misonidazole to hepatocytes and hepatoma cells. 374 47

A new embolic material has been devised to improve the therapeutic effect of ferromagnetic embolization upon tumors. Iron sponge microspheres (diameter 10-30 mu) were suspended in viscous, aqueous polysaccharide solution, dextran 40, and sodium carboxymethyl cellulose (Ferro-polysaccharide, FPS). Transcatheter embolization with FPS was performed under external magnetic control (2,800 gauss) in dog kidneys and VX2 carcinomas of rabbits, causing widespread, intraparenchymal vascular occlusion of target vessels. Neither recanalization nor collateral circulation was found to the infarcted areas, and the embolized tumors had extensive necrosis with resultant tumor regression. No significant untoward reaction or other undesirable embolization was noted serologically or histologically, even after intravenous administration of FPS. Clinical application to two patients, one with a hepatoma and the other with a renal cell carcinoma, resulted in excellent tumor infarction with no significant side effects.
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PMID:Transcatheter microembolization with ferropolysaccharide. A new approach to ferromagnetic embolization of tumors: preliminary report. 618 53

Uptake [3H] thymidine was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in nine dogs with spontaneous neoplasms: four lymphomas, two osteosarcomas, two soft-tissue sarcomas, and a thyroid carcinoma. High tumor-to-tissue ratios were observed for all tumor types assayed, and absolute uptakes, when computed as percent dose per gram tumor normalized for body weight, were similar for transplanted and spontaneous tumors. In the rodent tumors, radiothymidine was retained for at least 3 hr in the tumor without appreciable loss. In canine neoplasms, although the highest uptakes were observed in cellular tumors with many mitotic figures, tumor uptake showed significant variability that did not correlate with any obvious histologic change, and thus may reflect true biologic differences in metabolism among tumors at different sites in the same animal. These studies provide additional experimental evidence that the ratios of neoplastic to normal tissue and the kinetics of thymidine uptake by tumors are suitable for positron emission tomography of neoplasms in small and large animals, including both transplanted and spontaneous tumors.
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PMID:Positron imaging feasibility studies. I: Characteristics of [3H]thymidine uptake in rodent and canine neoplasms: concise communication. 697 67

Uptake of [3H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studied. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both between individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic processes of tumors, including glycolysis.
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PMID:Positron imaging feasibility studies. II: Characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms: concise communication. 697 68

We report the cloning of a novel tyrosine kinase (TyK)-encoding gene (TYK) from the human hepatoma cell line Hep3B. Using the polymerase chain reaction (PCR) and oligodeoxyribonucleotide primers based on conserved TYK motifs, a 180-bp fragment was cloned and used to obtain full-length cDNA clones of 2.9 kb, with an open reading frame of 505 amino acids (aa). Restricted expression was detected by Northern blotting or reverse-transcribed PCR in a broad range of cell lines. The predicted aa sequence contains characteristic TyK motifs without a transmembrane region, suggesting an intracellular localization. There was 49% aa sequence identity with human FYN product and 47% with human SRC product; however, several structural differences distinguish this clone from other SRC subfamily members. This clone, FYN-related kinase or FRK, is a novel member of the intracellular TYK gene family.
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PMID:Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-encoding gene. 751 Feb 61

Using an automated cell analyzer system, the effect of hepatocyte growth factor/scatter factor (HGF/SF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), endothelial acidic fibroblast growth factor (a-FGF), platelet derived growth factor (PDGF), and recombinant human insulinlike growth factor (IGF) on the motility and morphology of Madin-Darby canine kidney (MDCK), rat hepatomas, C2, and H5-6 and murine mammary carcinoma (EMT-6) cells was investigated. Treatment of MDCK cells with HGF/SF, bFGF, EGF, and a-FGF resulted in an increase in average cell velocity and in the fraction of moving cells. Cells treated with the PDGF and IGF did not show significant alterations in velocity. MDCK cells treated with each growth factor were classified into groups of "fast" and "slow" moving cells based on their average velocities, and the average morphologic features of the two groups were quantitated. Fast-moving cells had larger average area, circularity, and flatness as compared to slow-moving cells. Factors that stimulated cell movement also induced alterations in cell morphologic parameters including spreading, flatness, area, and circularity. HGF/SF also scattered and stimulated motility of C2 and H5-6 hepatoma cells. In contrast to MDCK cells, there was no significant difference between the morphology of the fast moving and slow moving C2 and H5-6 cells. These studies suggest that growth factor cytokines have specific effects on motility of normal and tumor cells.
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PMID:Effect of hepatocyte growth factor/scatter factor and other growth factors on motility and morphology of non-tumorigenic and tumor cells. 751 97

Antisense oligonucleotide to the translation initiation sequence of human c-mpI reduced the proliferation of human CD34+ bone marrow cells in response to interleukin-3 (IL-3) alone or to the combination of IL-3 and thrombopoietin (TPO). To investigate the molecular basis for these cytokine interactions, we analyzed the relationship between the receptor subunits for IL-3 and TPO and determined whether both receptors activate identical signal transduction pathways. The function of the receptor subunits was characterized in transiently transfected hepatoma cells and fibroblasts by the activation of gene expression via specific regulatory elements and by the stimulation of DNA-binding activity of STAT proteins. Although c-mpl and IL-3 receptor (IL-3R) reconstituted a qualitatively comparable gene regulatory response, there was no detectable functional interaction between their respective receptor subunits. By comparing the receptor action in different cell lines, we observed that in human hepatoma cells the signaling of c-mpI was 100-fold less sensitive to TPO than in rat hepatoma cells. However, IL-3R signaling was comparable between the two cell types, suggesting that c-mpI and IL-3R do not use identical signal transducing mechanisms. The cytoplasmic domains necessary for c-mpI signaling were determined by testing deletion mutants. The membrane-proximal box 1 sequence motif was critical for gene regulation and for STAT protein activation that seemed to involve the Janus kinase 2 (JAK2). Because IL-3R was less dependent on JAK2 than c-mpI, different levels of JAK2 expression may account, in part, for the quantitative difference in IL-3 and TPO response among various cell lines.
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PMID:Signal transduction by the receptors for thrombopoietin (c-mpL) and interleukin-3 in hematopoietic and nonhematopoietic cells. 760 89

The gene regulatory functions of the human IL-2 receptor (IL-2R) were reconstituted in transiently transfected hepatoma cells. The combination of IL-2R beta and -gamma mediated a strong stimulation via the cytokine response element of the alpha 1-acid glycoprotein gene and the hematopoietin receptor response element, but none via the IL-6 response element or the sis-inducible element. IL-2R alpha enhanced 10-fold the sensitivity of the IL-2R beta.gamma complex to respond to IL-2 or IL-15, but did not modify the specificity or the magnitude of maximal gene regulation. A homodimerizing chimeric receptor G-CSFR-IL-2R beta could mimic the IL-2R action. The IL-2R-mediated gene regulation was similar to that seen with receptors for IL-4 and IL-7, but differed from that for IL-6 type cytokines, thrombopoietin, erythropoietin, and growth hormone. The activation of STAT proteins by the IL-2R was assessed in transfected L-cells and COS-1 cells. Although IL-2R subunits were highly expressed in these cells, no STAT protein activation was detectable. Transient overexpression of JAK3 was unable to change the signaling specificity of the hematopoietin receptors in rat hepatoma, L-, and COS cells, but established a prominent activation of the IL-6 response elements by the IL-2R and IL-4R in HepG2 cells. The data support the model that the IL-2R and related hematopoietin receptors produce at least two separate signals which control gene expression.
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PMID:The action of interleukin-2 receptor subunits defines a new type of signaling mechanism for hematopoietin receptors in hepatic cells and fibroblasts. 771 38

The cytoplasmic receptor sequences required for the transcriptional control via the IL-6 response element (IL-6RE) and the hematopoietin receptor response element (HRRE) in hepatoma cells were defined by transient expression of wild-type and mutant granulocyte-colony stimulating factor receptor-gp130 chimeric receptors. gp130 generated two separate transcriptional signals, one of which was directed to IL-6RE and required an intact box 3 motif, and another, which was directed to HRRE and was box 3-independent. The activation of DNA-binding of STAT3 required the same gp130 domains as the IL-6RE response. A box 3-independent activation of STAT proteins was achieved by overexpression of the kinases JAK2 or TYK2. The increase in the DNA-binding activity of STAT proteins, however, did not result in a corresponding increase in transcription via either IL-6RE or HRRE. The data indicate that activation of the DNA-binding potential of STAT proteins via gp130 is not sufficient to achieve transcriptional up-regulation of specific target genes.
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PMID:Separate signaling mechanisms are involved in the control of STAT protein activation and gene regulation via the interleukin 6 response element by the box 3 motif of gp130. 779 60


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