Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to define the functions of human adenovirus type 12 (Ad12) early region 1 (E1) products in lytic infection and oncogenic transformation we have isolated and phenotypically characterized a set of host-range (hr) mutants of this serotype. These mutants grow efficiently upon HER3 cells, which contain and express type 12 E1 genes, but are restricted for growth upon A549 carcinoma and HeLa cells. Inter- and intratypic complementation analysis, marker-rescue mapping, and DNA sequence analysis have assigned some of the mutations to E1A sequence, and some to the reading frame encoding the E1B 54-kDa (482R) protein. Phenotypic analysis of the E1B mutants in particular has revealed some interesting, and in some cases surprising, findings relating to the roles of that protein in virus-cell interactions. This Ad12 gene product is required, either directly or indirectly, for efficient viral DNA replication in A549 and HeLa cells, unlike its counterpart in type 5 virus. Surprisingly, however, despite the severe defect in viral DNA replication, the synthesis of a few species of viral late proteins continues in cells infected by some of the E1B mutants. In contrast, none of these mutants brings about the inhibition of host-cell protein synthesis characteristic of wild-type virus infection, and with some E1B mutants no viral late proteins are made. Further, in a separate study reported elsewhere, we have demonstrated that the E1B 54-kDa product may also be involved, either directly or indirectly, in positive regulation of both E1A and E1B 19-kDa (163R) gene expression. The molecular and/or physiological bases for these various effects remain to be determined, but our initial results suggest that the E1B 54-kDa protein may carry out multiple regulatory functions during the viral life cycle.
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PMID:Isolation and characterization of adenovirus type 12 E1 host-range mutants defective for growth in nontransformed human cells. 336 87

Oncogene amplification has been observed in various primary tumors and tumor-derived cell lines. In several types of cancer, amplification of specific oncogenes is correlated with the stage of tumor progression. To estimate the frequency of gene amplification in other tumor types and to determine whether the ability to grow in vivo is associated with gene amplification in tumor cell lines, we have developed a modified version of the in-gel renaturation assay that detects human DNA sequences of unknown nature amplified as little as 7- to 8-fold. This assay was used to screen 16 cell lines derived from various solid tumors and leukemias. Amplified DNA sequences were detected in only one cell line, Calu-3 lung adenocarcinoma. This cell line was found to contain coamplified NGL (formerly termed neu) and ERBA1 oncogenes. However, when one of the amplification-negative cell lines, PC-3 prostatic carcinoma, was selected for in vivo growth in nude mice, amplified DNA sequences became detectable in these cells. The amplified sequences included the MYC oncogene, which showed no amplification in the parental cell line but was amplified 10- to 12-fold in the in vivo-selected cells. MYC amplification may, therefore, provide tumor cells with a selective advantage specific for in vivo growth.
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PMID:Analysis of gene amplification in human tumor cell lines. 341 26

The parent R3230 AC rat mammary carcinoma cell line and the two variant cell lines, R3230 AC MET and R3230 AC LR, differ with respect to their abilities to invade bony matrices and to form lung colonies (experimental metastases). Both the R3230 AC and the R3230 AC MET, a cell line selected in vivo for enhanced metastatic capability, express high potentials for invasiveness and lung colony formation, while the Con A- and WGA-resistant R3230 AC LR cell line grows expansively at the periosseus implantation site and is unable to form lung colonies after intravenous inoculation. The abilities to invade bone and to metastasize to the lung are well correlated with the fibrinolytic activity and the production of urokinase-type plasminogen activators. The contribution of plasminogen activators to invasiveness and metastasis has been ascribed to its role in the fibrinolytic and collagenolytic (i.e., activation of latent collagenase) cascades.
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PMID:Correlation of fibrinolytic activity with invasion and metastasis of R3230 AC rat mammary carcinoma cell lines. 359 83

The effect of histamine (H) and H1-, H2-receptor blocking agents was studied on natural (NCMC) and lectin-dependent cell-mediated cytotoxicity (LDCC) of peripheral blood lymphocytes (PBL) from eight healthy subjects on HEP-2 adherent human epipharynx carcinoma target cells. Cytotoxicity was measured by detachment from the monolayer of 3H-TdR-prelabelled HEp-2 cells. LDCC was evaluated in a 24 h assay with a Concanavalin A (Con A) dose of 25 micrograms/ml at 50:1 effector-target cell ratio. Under these conditions, but without Con A, considerable NCMC was not elicited by normal lymphocytes. The presence of histamine and the H2-receptor blocker cimetidine resulted in a significant NCMC to HEp-2 cells. On the contrary, histamine and cimetidine reduced LDCC. The H1-receptor blocker clemastine had no significant effect on either NCMC or LDCC to HEp-2 targets. The possible involvement of H2-receptor bearing cells in the regulation of cytotoxicity to HEp-2 cells is suggested.
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PMID:Effect of histamine-receptor blocking on human natural and lectin-dependent cell-mediated cytotoxicity against adherent HEP-2 cells. 401 22

Thirty-eight patients with small-cell carcinoma were treated with cyclophosphamide, Adriamycin, and VP16-213 + or - MER. Response and survival of the six patients who received radiotherapy prior to entering the study were inferior compared with patients who received chemotherapy alone. Of 32 previously untreated patients, 13 had limited and 19 had extensive disease. Ninety-seven percent of these 32 responded and 63% achieved complete remission (CR). All patients with limited disease had a response and 77% achieved CR. Patients with extensive and limited disease had 91/2 months (range 1-26 months) and 14 months (range 31/2 -42 + months) median survival, respectively. The median survival for all complete responders irrespective of extent of disease was 16 months (range 6 - 42 + months). Three patients with limited disease are disease free more than 34 + months and off all therapy 10 + to 18 + months. Eighteen of 38 patients required antibiotics for fever during neutropenia. Eight patients had MER fevers and nine had serious infections. There were four drug-related deaths. MER therapy did not influence response rate, drug toxicity, or survival, but did add morbidity. This combination chemotherapy alone is an effective treatment for previously untreated small-cell lung cancer patients regardless of extent of disease.
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PMID:Chemotherapy versus chemoimmunotherapy for small-cell undifferentiated carcinoma of the lung. 625 48

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.
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PMID:Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association. 626 42

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).
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PMID:A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. 636 33

A total of 754 persons statistically selected from the age group 54-64 years were asked by letter to provide faecal samples for screening of occult blood during dietary restrictions. A total of 413 persons (55%) returned an average of 5.8 (range, 1-6) faecal samples each. All the faecal specimens were analysed with Hemoccult II slides and the 3,3',5,5'-tetramethylbenzidine (TMB) test 0.10%. For technical reasons, however, the Hemoccult test could not be evaluated. The TMB test showed faecal blood in 50 persons. A case history was obtained in 49 persons, of whom 47 agreed to further clinical, radiological, and endoscopic investigations. The most important findings in these examinations were resectable colonic carcinoma (Dukes's stage B) in 1 subject, a gastric ulcer in 1, haemorrhagic gastritis in 1, duodenal ulcers in 2, and colorectal polyps in 11 persons. The cost of the study was estimated to be NOK 114,000 (about USD 16,000).
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PMID:Screening for occult faecal blood loss in a community by means of Hemoccult II slides and a tetramethylbenzidine test. 674 Feb 9

During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.
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PMID:Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen. 675 25

The early forms of cervical carcinoma are meant to include in situ carcinoma of the portio and early-invasive squamous epithelium carcinoma with 5 mm in maximum depth of invasion. Thirty-six pregnant women were admitted to the authors' department, between January 1st, 1970 and December 31st, 1978, who were between the forth and 20th weeks of pregnancy and had produced positive response to portio cell swab tests. The average age of the patients was 28 years. All cytological findings had been histologically verified by conisation. Cerclage, according to Shirodkar, was applied prior to conisation to avoid excessive gestational bleeding from the conus bed, with attempts being made to obtain compression of the descending branch of the uterine vessels. The sections obtained from conisation gave the following histological results: moderate dysplasia in ten patients, severe dysplasia of the Cervix of eight patients, in situ carcinoma in 16 patients, and beginning stroma invasion in terms of Ia collum carcinoma in two patients. No abortion at all occurred to any of the patients with such conisation in early pregnancy. Thirty-four patients had no-complication vaginal deliveries. Caesarean section had to be applied to two women for EPH gestosis or imminent intra-uterine asphyxia. Conisation did not cause the occurrence of any major injury to the uterine cervix at the time of vaginal delivery.
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PMID:[Diagnosis and therapy of 36 alleged early forms of cervical carcinoma in pregnancy (author's transl)]. 744 27


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