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)

Radiofrequency electromagnetic fields at 13.56 MHz were used to heat locally EMT-6 sarcomas and KHJJ carcinomas in BALB/cKa mice. Temperature profiles obtained in tumors during treatment showed uniform temperature distribution throughout the tumor volume with no systemic hyperthermia. Temperature could be maintained at a stable level throughout treatment by adjustment of power. Tumors were treated at 43 degrees, 43-5 degrees, and 44 degrees, for 5, 10, 20, 30, and 40 min. The EMT-6 tumor was highly sensitive to cure by radiofrequency heating: a 5-min exposure at 44 degrees resulted in cure of almost 50% of the tumors. Cure rate was a function of temperature and of duration of exposure. The KHJJ carcinoma was somewhat more resistant to cure by radiofrequency heating, although most of the animals treated at 43.5 degrees or above were cured of their tumors. In an effort to explain the remarkable effectiveness of radiofrequency heating, tumor cell survival studies were done on EMT-6 tumors treated in situ. Cell inactivation by radiofrequency heating was similar to that for hot water bath heating. However, direct cell killing cannot account for the observed cures, and an additional mechanism must be responsible for tumor eradication.
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PMID:Tumor cure and cell survival after localized radiofrequency heating. 83 83

The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.
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PMID:BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma. 141 May 89

One hundred heterosexual women presenting at our clinic in 1979 with anogenital warts, were reviewed 10 years later. Median duration of warts following initial clinic attendance was 2 months (range 0-120 months). In 1979 cervical PAP smear results were available for 76 patients; cervical intraepithelial neoplasia (CIN) was seen in 15/76 (19.7%) women; 3 (4%) women had low grade CIN, 12 (15.7%) women had high grade CIN. Nineteen women had had treatment for CIN between 1979 and 1989, 7 laser ablation, 9 cone biopsy, 2 laser ablation and cone biopsy, and one woman laser ablation, cauterization and cone biopsy. At 10-year follow-up in 1989 4/100 women had anogenital warts, 12/100 women had cytological evidence of CIN (7 low grade, 5 high grade), and 37/100 women had CIN detected on colposcopic biopsy (31 low grade, 6 high grade). No women developed invasive cervical carcinoma during the study period. CIN lesions, detected in 1979, regressed without any treatment in 2 women. Colposcopic biopsy was 3.1 times more sensitive than single cervical PAP smear at detecting CIN (4.4 times as sensitive in detecting low grade CIN; 1.2 times as sensitive in detecting high grade CIN). In 1989 CIN was detected in 7/19 (36.8%) of women who had undergone cervical treatment between 1979 and 1989, and in 35/81 (43.2%) of women having no cervical treatment within this period (chi squared P greater than 0.5). These findings suggest that cervical laser ablative therapy and cone biopsy do not in the long term influence the natural history of cervical human papilloma virus-associated disease (CIN) in women with anogenital warts.(ABSTRACT TRUNCATED AT 250 WORDS)
Int J STD AIDS
PMID:Ten year follow-up study of women presenting to a genitourinary medicine clinic with anogenital warts. 154 64

Monoclonal antibody TEC-02, raised against mouse embryonal carcinoma cells, has been shown to react with murine preimplantation embryos and with a very limited number of adult mouse tissues. The target epitope, TEC-2, is a carbohydrate carried in mouse embryonal carcinoma cells by large glycoprotein-bound glycan. We report here the expression of TEC-2 epitope on human carcinoma-derived cell lines, HeLa and HS, and the properties of its carbohydrate carriers. Immunolabeling of Nonidet P-40 lysates of HeLa cells separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that TEC-2 antigens are polydispersed glycoconjugates of high molecular weight (mostly above 100,000). TEC-2 antigens detected by the two-site sandwich assay, in which the antigen is immobilized and detected with the same antibody, had a slightly higher molecular weight than those detected by the solid-phase assay. This suggests heterogeneity in the number of TEC-2 epitopes per carrier molecule. When the cells were lysed by Triton X-114 and the detergent and aqueous phases were separated by warming and centrifugation, most of the TEC-2 antigenic activity was found in the aqueous phase. TEC-2 antigens isolated by indirect precipitation from [3H]galactose-labeled HeLa cells were degraded by extensive pronase digestion or mild alkaline treatment to glycopeptides or oligosaccharides of low molecular weight. Thus, TEC-2 epitope in human HeLa cells is carried by carbohydrates of only several monosaccharide units. TEC-02 antibody was also found to bind to Tamm-Horsfall glycoprotein isolated from human urine and its binding was enhanced by desialylation. Combined data indicate that TEC-02 antibody recognizes the GalNAc beta 1----4Gal beta 1----4 structure which may be carried on different types of molecule, according to the site of their synthesis.
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PMID:Expression of mouse embryonic epitope TEC-2 on human carcinoma-derived cell lines and characterization of its glycoprotein carriers. 244 11

Two distinct mechanisms by which bladder carcinoma cells of the NBT-II cell line dissociate and migrate away from an in vitro reconstituted epithelial sheet were examined as regards intercellular adhesion and cell locomotion. Scattering of NBT-II bladder carcinoma cell line was promoted by 2 distinct culture protocols: (i) deposition of some components of the extracellular matrix onto the culture substratum (glass or plastic) induced cell dispersion of the epithelial sheet of carcinoma cells, and (ii) addition of Ultroser G, a serum substitute, to the culture medium induced scattering and acquisition of motility of NBT-II cells. Under both culture conditions, NBT-II cells dissociated, lost their epithelial morphology, acquired fibroblastic shape and migrated actively. We show that, among different extracellular matrix proteins, only collagens were able to promote the transition towards fibroblastic phenotype (referred as epithelium-to-mesenchyme transition or EMT). Furthermore, the native 3-dimensional helical structure of collagens was required for their function. During induction of EMT of NBT-II cells with Ultroser G, the junctions between epithelial cells were split, polarized epithelial cell organization was lost, and the resulting individual cells became motile and assumed a spindle-like fibroblastoid appearance. Using immunofluorescence microscopy techniques, we demonstrate that this change is accompanied by redistribution of desmosomal plaque proteins (desmoplakins, desmoglein, plakoglobin) and by reorganization of the cytokeratin and the actin-fodrin filament systems. Intermediate-sized filaments of the vimentin type were formed de novo in the fibroblastoid cell form. The observed transition towards fibroblastic phenotype (epithelium-to-mesenchyme transition or EMT) was fully reversed by removing the inducing factors from the culture medium, as shown by the disappearance of vimentin filaments and the reappearance of desmosomes in the newly formed epithelial cells.
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PMID:Reversible transition towards a fibroblastic phenotype in a rat carcinoma cell line. 250 87

Female genital organs infected with human papillomavirus (HPV) have drawn attention as STD and in connection with the mechanism of carcinogenesis. Recently, we used a simplified HPV detection kit, Vira Pap method in clinical tests. To estimate the usefulness of the Vira Pap method in clinical application, a comparison was made between the results of the Vira Pap method and those of the conventional method. Furthermore, an investigation was made of the relationship between uterine-cervical lesions and the types of HPV. The following findings were obtained: 1. It was demonstrated that the Vira Pap method was superior to the conventional methods and was almost equal to the Southern blot method. 2. The cases in which HPV infection were confirmed by the Vira Pap method were further analyzed and HPV typed by the Southern blot method. And, types 6, 11, 18, 31, 33, 35 and unclassifiable types were found. 3. HPV 16, 18, and 33, which are said to be closely related to carcinoma, were detected in cases of chronic cervicitis as well. In these cases, further investigation seems to be required.
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PMID:[Fundamental and clinical studies on human papillomavirus infection in the uterine cervix especially by Vira Pap (dot blot) method]. 254 33

The environment of cells within solid tumors is known to be acidic relative to that in normal tissue, and the viability of tumor cells may depend on mechanisms which maintain intracellular pH (pHi) above the extracellular pH (pHe). We have assessed therefore the toxicity in vitro of the proton ionophore carbonylcyanide-3-chlorophenylhydrazone (CCCP), since this agent has been reported to be capable of transporting H+ equivalent through artificial lipid bilayers and mitochondrial membranes. CCCP was toxic to the human bladder carcinoma cell line MGHU1 and to the murine mammary sarcoma cell line EMT-6 only at pH, less than 6.5. CCCP transported H+ equivalents through cell membranes at physiological (7.35) and low pHc (6.20). Cell lines were found to have steady-state pHi values approximately 0.1 to 0.2 pH units above pHc at pHc less than 6.50. Addition of CCCP led to a decrease in steady-state pHi values as compared to untreated cells at pHc less than 6.50, whereas there was no apparent effect of CCCP on steady-state pHi values at pHc greater than 6.50. The CCCP-induced reduction in steady-state pHi combined with the uncoupling of oxidative phosphorylation by CCCP appeared to be the major mechanisms leading to cell death at pHc less than 6.50. The toxicity of CCCP under acidic conditions was enhanced by amiloride and 4,4'-diisothiocyanostilbene-2,2-disulfonic acid, agents which are known to inhibit membrane-based ion exchange mechanisms which regulate pHi under acidic conditions. When both agents were combined with CCCP, cell killing was observed at pHc less than 7.30. Our results suggest that mechanisms which regulate pHi under acidic conditions which occur in solid tumors may represent targets for new forms of tumor-specific therapy.
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PMID:Reduction of intracellular pH as a possible mechanism for killing cells in acidic regions of solid tumors: effects of carbonylcyanide-3-chlorophenylhydrazone. 274 36

Human papillomaviruses (HPV) 16 and 18 are closely linked with human genital cancer. In most cervical carcinomas, viral sequences are integrated into the host genome. HeLa, a cervical carcinoma cell line, has multiple copies of integrated HPV 18 DNA. In this study, in situ chromosome hybridization was used to assign the integration sites of HPV 18 DNA sequences on HeLa cell chromosomes. Four sites of hybridization were identified at 8q23----q24, 9q31----q34, p11----p13 on an abnormal chromosome 5, and q12----q13 on an abnormal 22. Three of these sites correspond with the locations of MYC, ABL, and SIS protooncogenes, and are at or in close proximity to fragile sites. The chromosomal localization of HPV 18 DNA may be useful in assessing the role of viral integration in the development of this malignancy.
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PMID:Integration sites of human papillomavirus 18 DNA sequences on HeLa cell chromosomes. 302 16

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

In vivo and in vitro chemosensitivity testing has been applied to kidney carcinoma tumor lines. Serially transplantable tumors were implanted subcutaneously in nude mice and the animals were treated with cytostatic drugs. The results of this in vivo assay were compared with the results obtained with the subrenal capsule assay, the DNA precursor assay (3H-thymidine), and the colony-formation assay, utilizing the same tumor line in each case. Higher rates of resistant tumors were found in the in vivo assays than in the in vitro assays. The SRC assay and the DNA assay had the highest predictive value, as judged from comparison with the results obtained with the source tumor (human kidney carcinoma tumor line).
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PMID:In vivo and in vitro chemotherapy sensitivity testing for human kidney tumor lines: a comparative study. 339 74


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