Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined whether the single radial complement fixation (SRC-fix) test is applicable to serological diagnosis of viruses. The viruses used for the examination were influenza A and herpes simplex viruses. SRC-fix test was shown to be a very simple method, that is, serum samples were added to agarose plate A containing complement and CF antigen, and agarose plate B, containing antibody-coated erythrocytes, was layered on top of the plate A to form zone areas of unlysed cells. CF titres of the samples were determined from the square of the zone diameter of unlysed cells. Thus SRC-fix test is suggested as a new method for diagnosis of viral diseases.
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PMID:Study on the single radial complement fixation (SRC-fix) test. 626 49

The clinical response to chemotherapy of a series of female patients with advanced pelvic malignancies was compared to the response of their tumors to the same agents in the murine subrenal capsule implant assay. A total of 194 different patients were studied in 242 different assays; 89.3% of the assays were evaluable. There were 83 prospective assays (assays performed before the patient received the chemotherapy) of 66 different patients for which clinical correlations were available. In these assays the sensitivity (frequency of positive test results in responding patients) was 85.0%, the specificity (frequency of negative test results in nonresponding patients) was 57.1%, and the efficiency (percentage correctly classified) was 63.9%. There were 100 retrospective assays (assays performed after the patient had been treated with the chemotherapy) of 69 different patients for which clinical correlations were available. In these assays the sensitivity was 66.7%, the specificity 70.7%, and the efficiency 70.0%. Thirty-one of the patients had both prospective and retrospective assays. There were 59 patients for whom the clinical response to chemotherapy could not be determined. It is believed that the clinical utility of the SRC assay has been validated by the good prospective sensitivity of the assay.
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PMID:The subrenal capsule tumor implant assay as a predictor of clinical response to chemotherapy: 3 years of experience. 650 Mar 76

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

Nematospiroides dubius, Nippostrongylus brasiliensis and Trichuris muris infections in C57BL mice increased background IgM titres to SRC but not to erythrocytes from other species. However, no cross-reaction between parasite extracts and SRC could be demonstrated and the enhancement was not evident in other strains of mice. There were no comparable rises in total IgM levels, but declining IgM responses to ovalbumin were boosted by N. dubius, so the rise was probably caused by selective expansion of activated clones of cells. N. dubius also increased responses to low doses of SRC given intraperitoneally (i.p.) a few days after infection, whilst optimal SRC doses induced normal responses. In contrast, N. brasiliensis and T. muris often depressed responses to SRC though the effect was variable and the timing of challenge was critical. Thus, whereas the enhancement of natural titres occurs in C57BL mice infected with any of the parasites tested here or in previous studies, the effects on responses to injected SRC depend on the species of parasite.
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PMID:Immunological consequences of intestinal helminth infections in C57BL mice. Natural and induced responses to sheep erythrocytes. 665 44

High-boiling coal liquids from the solvent-refined coal-I and -II (SRC-I, -II) processes, respectively, were fractionally distilled. In the case of SRC-I process solvent (PS), 50 degrees F distillation cuts were obtained between 550 and 850 degrees F, while for the SRC-II material, the 50 degrees F cuts were only obtained between 700 and 850 degrees F. These cuts, as well as the parent material, were tested for their ability to initiate skin tumors by applying a single dose (25 mg) to the shaved backs of Charles River female CD-1 mice. After 2 weeks, the mice received twice weekly applications of 5 micrograms of the promoter, phorbol myristate acetate. Only a few tumors were found for SRC-I fractions boiling below 700 degrees F; tumor-initiating activity increased as the boiling point increased. A similar increase in response with increasing boiling point was seen for the SRC-II cuts. The initiating activities for the parent materials were similar to those observed for their respective 800 to 850 degrees F cuts.
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PMID:Skin-tumor initiation activity of coal liquids with different boiling-point ranges. 666

The potential clinical activity of the new phase I drugs N-methylformamide (N-MF) and Echinomycin (ECH) was examined while still undergoing clinical toxicology trials by testing against fresh surgical explants of human tumors in the 6-day in vivo SRC Assay. Sixty-nine tumors representing different histologic types including breast, lung, colon, ovarian, and cervical, as well as neoplasms of undiagnosed origin, were screened against N-MF (NSC-3051) and ECH (NSC-526417) simultaneously with five standard chemotherapeutic agents used clinically for treatment of the specific type of cancer. Thus, activity of N-MF and ECH could be compared directly with that of standard agents tested in the same assay. Treatment schedule was QD1-5, and the criterion for drug activity was tumor graft regression greater than 20%. N-MF was active against 15/69 tumors with a response rate of 22%. ECH was also active against 15/69 tumors, yielding the same response rate. Although the response rates for N-MF and ECH were the same, indicating a similar degree of general anti-tumor activity as evaluated by the assay, N-MF showed greatest activity against lung tumors whereas ECH was more active against ovarian tumors. Twenty-six of 69 tumors (38%) were unresponsive to all drugs tested, only one tumor was responsive to both N-MF and ECH and no tumors were responsive to either N-MF or ECH alone. Cytoxan, one of the standard agents tested concurrently with both phase I drugs yielded a response rate of 35%, one and one-half times greater. Cervical and renal cancers and lymphomas were relatively unresponsive to both drugs.
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PMID:Activity of two phase I drugs N-methylformamide (NSC-3051) and Echinomycin (NSC-526417) against fresh surgical explants of human tumors in the 6-day subrenal capsule (SRC) assay. 667 56

Heavy distillate (HD), the highest-boiling coal liquid from the solvent-refined coal-II process (SRC-II), was administered by intragastric (IG) intubation to pregnant rats. Five dose levels of HD (0.09, 0.14, 0.18, 0.36 and 0.74 g kg-1), were given daily from 12 to 16 days of gestation and the rats were killed at 20 days of gestation. Maternal body weights and weights of the liver, kidneys, spleen, adrenals, thymus, ovaries and the gravid uterus were obtained. Gravid uteri were evaluated for prenatal mortality. Live fetuses were examined for malformations and weighed; fetal lungs were excised and weighed. Maternal (extragestational) weight gains and thymic weights diminished in all groups that received the SRC material. Adrenal weights were increased in all treated animals, except for those in the lowest-dose group (0.9 g kg-1). There was significant maternal mortality at 0.74 g kg-1 and increased intrauterine mortality at doses of 0.37 and 0.74 g kg-1. Placental weight was depressed, and the incidence of fetal anomalies was increased at 0.14 g kg-1 and all higher dose levels.
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PMID:Developmental toxicity following oral administration of a high-boiling coal liquid to pregnant rats. 671 82

Studies with a variety of chemically purified substances have suggested that induction of the enzyme ornithine decarboxylase (ODC) in mouse epidermal cells may be a reliable indicator of neoplastic transformation. In an effort to extend these observations on ODC to chemically complex materials, we examined ODC induction by carcinogenic and non-carcinogenic mixtures and compared these results with tumorigenicity data for these materials. For these studies several boiling range fractions and several solvent-derived subfractions from two solvent-refined coal processes (SRC-I and SRC-II) were evaluated for their ability to induce ODC. Single applications of heavy distillate (HD), the SRC-II high-boiling fraction and a potent mouse skin carcinogen, produced ODC induction kinetics which were similar to that for 12-O-tetradecanoylphorbol-13-acetate (TPA). Both HD and TPA stimulated maximal ODC activity 3-5 h after application, with epidermal ODC levels returning to basal levels within 12 h. The magnitude of ODC induction after multiple applications of HD was not as great as that observed for TPA. Single skin applications of TPA and HD also transiently elevated hepatic ODC levels 27- and 7-fold, respectively; however, liver ODC activity did not increase following multiple applications of either chemical. Further, ODC induction by HD was also dose-dependent. Relative to controls, single applications of HD and process solvent (boiling range greater than 250 degrees C) elevated ODC levels 145- to 205-fold, light distillate and light oil (boiling range less than 180 degrees C) increased ODC levels 23- to 32-fold, and middle distillate and wash solvent (boiling range 180-250 degrees C) stimulated less than 2- to 8-fold increases in ODC. Single applications of three solvent-derived subfractions of HD, which are complete carcinogens, induced 3- to 7-fold ODC elevations over background levels; multiple applications of two of these subfractions elevated ODC levels 10- to 22-fold. Of the complex mixtures evaluated during this study, all complete carcinogens induced ODC; however, the magnitude and temporal pattern of induction varied with the material tested.
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PMID:Ornithine decarboxylase induction by chemically complex liquids from two solvent refined coal processes. 687 35

Fluorescein (FITC)-haptenated mouse spleen cells are capable of inducing a B cell immune response characterized by the production of antibodies directed against hapten-altered self structures. The induction of this response is thymus-independent and strictly dependent on the hapten concentration used for labeling the cells. Pretreatment of mice with immunogenic, labeled spleen cells strongly suppressed the plaque-forming cell response to a subsequent challenge with FITC-labeled spleen cells, sheep (SRC) or horse (HRC) red cells labeled with the same hapten and native FITC-dextran. Mice primed with lightly haptenated (nonimmunogenic) cells 7 days before challenge were completely unresponsive to the immunogenic dose of labeled cells and displayed a significantly reduced response to FITC-SRC or FITC-HRC. However, the response to FITC-dextran was enhanced, as compared to unprimed animals. The concept of immunogenic vs. nonimmunogenic requirements of an antigen to induce unresponsiveness, and the specificity of the B cell clones affected by suppression is discussed.
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PMID:Suppression of the immune response to altered self induced by immunogenic and nonimmunogenic altered self structures. 698 16

Collagen-induced polyarthritis in rats is a new experimental model that shares clinical and histologic features with adjuvant arthritis. To determine whether collagen-induced arthritis is a form of adjuvant disease and to further exclude contamination of collagen with an adjuvant substance, native type II collagen was studied for adjuvant properties. IgM and IgG PFC activity and PBMC [3H]TdR incorporation were studied in rats after injection with TNP-OA combined with IFA, IFA and CII, or CFA. In general, humoral and CMI responses to TNP-OA were lower in rats injected with IFA/CII compared with those with IFA; the presence of CII during primary immunization failed to significantly enhance PFC activity to TNP after a boost. CFA-injected rats gave maximal values in both studies. Mice pretreated with BII in the absence of oil gave PFC responses below control after sensitization with SRC. Furthermore, CII was unable to replace mycobacteria in the induction of EAE in rats and was devoid of mitogenic or polyclonal stimulatory properties. It is concluded that collagen-induced arthritis is a distinct entity from adjuvant arthritis and is dependent upon the unique immunogenicity of type II collagen in rats rather than upon an adjuvant effect.
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PMID:Collagen-induced polyarthritis in rats: a study of native type II collagen for adjuvant activity. 698 10


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