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)

Chemotherapeutic response of two squamous cell carcinoma xenograft lines (established from the primary and metastatic lesion of a tongue carcinoma) was studied using SC and SRC assays (as well as immunocompetent and -suppressed recipients in the latter assay). The two assays provided similar ranking of drugs, in the sense that in each instances two of the three (cyclophosphamide, 5-fluorouracil, vinblastine) most active agents were identical. The host response in immunocompetent recipients supports the need for histology to prove the proper quality of the implanted tumor tissue in order to be used for drug evaluation.
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PMID:Chemotherapeutic response of squamous cell carcinoma xenografts (subcutaneous and subrenal capsule assay). 367 Jul 98

This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)-labeled anti-CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT-6 was used as a control. Tumor CEA levels (ng/g of tumor +/- standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT-6, 0; WiDr, 105 +/- 5.7; LS174T, 2052 +/- 198; SW403, 17,575 +/- 1,785. The 111In-labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue +/- SEM. The non-CEA-producing tumor, EMT-6, showed the lowest tumor uptake (1.4 +/- 0.3). WiDr, an intermediate CEA-producing tumor, showed some tumor uptake (16.4 +/- 1.5). The high CEA-producing tumors, SW403 and LS174T, had high tumor uptake (29.5 +/- 5.0 and 51.1 +/- 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor-to-blood (T/B), tumor-to-liver (T/L), and liver-to-blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = -0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.
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PMID:The effect of tumor CEA content and tumor size on tissue uptake of indium 111-labeled anti-CEA monoclonal antibody. 394 92

Previously, we reported that high concentrations of eosinophils in human colonic carcinomas are associated with better prognoses, that sections taken 1 cm remote from (deep to) the margin of tumor (SRM) and sections contiguous to the margin (SCM) of tumor and adjacent uninvolved colon contain significantly different concentrations of eosinophils, and that concentrations of eosinophils in SCM and SRM are both useful and complementary for the prediction of prognosis. As a first step towards studying the ecology of the eosinophil in colonic carcinoma and with the goal of identifying other kinds of cells that might be useful for the prediction of prognosis, we counted cells in SCM and SRM that expressed histochemically demonstrable acid phosphatase, alpha-naphthylbutyrate esterase, and peroxidase. The tumors of patients with and without metastases at the time of resection of the primary tumor contained different (P = 0.0314) concentrations of cells with histochemically demonstrable alpha-naphthylbutyrate esterase in SCM but not in SRM. In contiguous 1- to 2-micron sections, morphologically macrophage-like cells with histochemically demonstrable acid phosphatase and cells with histochemically demonstrable alpha-naphthylbutyrate esterase were found to be present in different concentrations both in SCM (P less than 0.01) and in SRM (P less than 0.01); i.e., these phenotypic markers appear to identify different subpopulations of macrophages in tumors. In contrast to our previous study of human pulmonary alveolar macrophages, examination of sections stained sequentially for these phenotypic markers that are commonly used for the identification of macrophages in tumors revealed numerous cells in the same sections that expressed histochemically demonstrable acid phosphatase (red) but not alpha-naphthyl butyrate esterase (brown) and vice versa. Several of these markers promise to be useful and complementary for the prediction of prognosis.
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PMID:Heterogeneity and prognostic significance of macrophages in human colonic carcinomas. 402 96

The bioreductive alkylating agent mitomycin C (mitomycin) has been shown to have greater activity under hypoxic than oxic conditions on murine cell lines such as the EMT-6 fibrosarcoma cell line. Solid tumors are known to contain hypoxic cells and are relatively resistant to ionizing radiation and some chemotherapeutic agents. We tested the cytotoxicity of mitomycin against fresh biopsies of human carcinomas under both hypoxic and oxic conditions in the human tumor clonogenic assay (HTCA). Additionally, we examined the metabolism of mitomycin by sonicates of the murine EMT-6 cells and the human WiDR colon carcinoma cells. We confirmed that under our clonogenic assay conditions the EMT-6 cell line was more sensitive to mitomycin under hypoxic than oxic conditions. Additionally, we established that EMT-6 cells also metabolize mitomycin at a more rapid rate under hypoxic than oxic conditions. However, these effects of hypoxia on mitomycin activity were not demonstrable for the human WiDR colon cancer cell line. In addition to these findings, the cytotoxicity of mitomycin was either unchanged or reduced under hypoxic conditions for ten fresh human tumors tested for mitomycin sensitivity in HTCA. Based on these observations, we conclude that the potentiating effect of hypoxia on mitomycin metabolism and biological activity may be peculiar to the murine EMT-6 and S-180 cell lines and that mitomycin C is not likely to have differential efficacy against hypoxic human carcinoma cells.
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PMID:Cytotoxicity of mitomycin C on clonogenic human carcinoma cells is not enhanced by hypoxia. 642 4

The growth of 29 different human tumor lines under the renal capsule of immunocompetent mice was investigated. The tumors, previously established in athymic mice, included malignant melanomas, colon carcinomas, soft-tissue sarcomas, lung cancers and a mammary carcinoma. The growth rates of 17 tumors, measured repeatedly over a period of several years, were highly reproducible. The different grafts exhibited distinctly different and individual growth rates for up to 6 days. In animals pretreated with an immunosuppressive dose of cyclophosphamide, the growth rate was the same as in non-pretreated animals, but the growth continued for several more days. In the case of 9 different grafts, the subrenal growth rates were compared with those observed when the same tumors were growing subcutaneously in athymic, nude mice. The relative growth rates of the different tumors were practically the same in the two systems. The results indicate that the growth conditions under the renal capsule permit the grafts to express their inherent growth potentials and that the subrenal grafts do not represent a selected sub-population of the tumor cells. The extent of infiltration of the grafts by mouse inflammatory cells was measured by flow cytometry on single-cell suspension as well as by quantitative analysis of serial histological sections. In most cases the mouse cells occupied 15-25% of the total graft volume on day 6. The results indicate that the effect of mouse cell infiltration on the growth of established tumor lines is slight and that it is unnecessary to use athymic mice as host animals when testing new investigational drugs by the SRC assay. The use of established tumor lines in the SRC assay in immunocompetent mice may be useful also in the study of factors influencing the anti-cancer activity of current drugs.
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PMID:Human tumor xenografts transplanted under the renal capsule of conventional mice. Growth rates and host immune response. 650 Jul 47

Seventy-one patients with symptoms of colorectal disease were evaluated with the rigid 25-cm sigmoidoscope and an inexpensive 35-cm flexible proctosigmoidoscope (American Optical FPS-2) to determine if the latter is a diagnostically reliable alternative for routine sigmoidoscopy. Examination time was comparable, 3.6 min for the rigid and 4.2 min for the flexible sigmoidoscope. Average insertion length was 21 cm for the rigid and 29.5 cm for the flexible instrument. Forty-two patients had more discomfort during the rigid versus nine during the flexible examination. Significant lesions were documented in eight patients with the rigid and 13 with the flexible sigmoidoscope. One rectal carcinoma and seven polyps were detected with both instruments, while an additional nine polyps were documented only with the flexible instrument. The 35-cm flexible proctosigmoidoscope may be a feasible alternative for routine sigmoidoscopy.
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PMID:Flexible versus rigid sigmoidoscopy: a comparison using an inexpensive 35-cm flexible proctosigmoidoscope. 661 70

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

Radiation therapy of cervix carcinoma is applied in this Institute by means of a modified Stockholm method in combination with external beam irradiation. In 1968, parametrial portals were replaced by large planparallel opposed fields extending cranially to LIII/LIV with central shielding in order to avoid overdosage in the area of intracavitary treatment. This resulted in a marked increased incidence of severe sigmoid-colon radiation lesions from 0.25% to 4%; predominantly in Stage I and II patients. Therefore two measures have been introduced: beginning in 1972 measures were taken to prevent the cranial displacement of the uterus during intracavitary treatment in order to avoid shortening the distance between the radioactive sources and the sigmoid-colon; from 1972 stereo X ray photogrammetry (SMR) was applied for dose determinations at points of the sigmoid-colon, which were seen to be located close to the applicator. When SRM data indicated that a high dose at the sigmoid-colon might occur, treatment modifications enabled prevention of radiation damage. Change of position of the applicator was the first to be considered. In the last seven years no surgical intervention had to be performed because of a sigmoid-colon lesion resulting from an unexpected high radiation dose delivered by intrauterine sources. The local recurrence rate was not increased following treatment modifications for prevention of sigmoid-colon radiation damage.
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PMID:Stereo X ray photogrammetry applied for prevention of sigmoid-colon damage caused by radiation from intrauterine sources. 710 31

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.
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PMID:Involvement of pp60c-src with two major signaling pathways in human breast cancer. 750 22

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


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