Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A plasmid, designated p72, constructed from human lung carcinoma DNA inserted into the promoterless herpes simplex virus thymidine kinase gene pML-TK-Bgl II vector, hybridizes strongly to human nucleic acids on Southern and Northern blots. The portion of the DNA insert responsible for the strong signal following hybridization to human DNA or RNA is a 167-bp 3' terminal portion of the mitochondrial 16S ribosomal RNA gene. The expression of this gene is constitutive in the several human cell lines that were tested and is unaffected by exposure to cytotoxic chemicals that alter the expression of nuclear genes. This plasmid offers an excellent tool for studies of perturbations of gene expression and for controlling for the variations in sample preparation, loading, and transfer in Southern or Northern analysis of nucleic acids.
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PMID:Mitochondrial nucleic acids as internal standards for blot hybridization analyses. 152 8

To assess whether a fully functional VV ribonucleotide reductase enzyme is required during both in vitro and in vivo replication of VV, three mutant viruses were constructed by marker transfer techniques: M1 lambda, an M1 insertion mutant; TK-, an insertion mutant of the VV thymidine kinase (tk) gene; and M1 lambda/TK-, a double mutant. Extracts of cells infected with the M1 lambda or M1 lambda/TK- mutant viruses were assayed for ribonucleotide reductase activity and it was found that insertional inactivation of the M1 gene abolished the induction of viral enzyme activity in VV-infected cells. Each of the three mutant viruses replicated to levels comparable to the wild-type (WT) virus in BSC40 (monkey), growing A549 (human lung carcinoma) cells, and serum-starved A549 cells, indicating that a functional M1 gene was not required for viral replication in tissue culture. In contrast, in vivo studies indicate that the loss of viral ribonucleotide reductase activity leads to a mild attenuation of VV. By the intracranial route of inoculation, approximately 10-fold more of the M1 lambda recombinant than the WT virus was required to produce the average lethal dose for 50% of the population of injected mice.
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PMID:Insertional inactivation of the large subunit of ribonucleotide reductase encoded by vaccinia virus is associated with reduced virulence in vivo. 215 95

Base propenals arise from DNA by a Fe(II)-bleomycin-mediated reaction which leads to strand scission. These compounds undergo addition-elimination reactions with thiols and other nucleophilic groups under physiological conditions and form an addition product with glutathione. Thymine- and adenine-N1-propenals inhibit DNA synthesis in HeLa cells; both compounds are cytotoxic [50% inhibiting concentration (IC50) = 1 to 2 microM]. A structurally related nucleoside, thymidine-N3-propenal, designed as a metabolic pathway inhibitor, inhibits growth of HeLa, L1210 leukemia, Lewis lung carcinoma, B16 melanoma, and DLD-1 human colon carcinoma cells in culture (IC50 = 1 to 6 microM). A single injection of this compound, administered on the first day following transplant of L1210 leukemia cells, increased the mean survival time of mice by 50% (T/C = 154). Thymidine-N3-propenal selectively blocks DNA synthesis in HeLa cells and inhibits thymidine kinase (Ki = 5.1 microM) and DNA polymerase-alpha. We suggest that base propenals, rather than damaged DNA, account for some of the cytotoxic effects of bleomycin and that nucleoside propenals represent a novel class of site-directed inhibitors.
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PMID:Origin and cytotoxic properties of base propenals derived from DNA. 257 72

Variants of the mouse hepatoma cell clone inducible for aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH) (EC 1. 14. 14.1) activity and deficient in hypoxanthine guanine phosphoribosyl-transferase (EC 2.4.2.8), and human primary lung carcinoma cell clone noninducible for AHH activity and deficient in thymidine kinase (EC 2.7.1.21) were isolated. The variant lines characterized for AHH inducibility and drug resistant phenotype were utilized to study somatic cell hybrids for the expression of AHH induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In two hybrids AHH activity was not expressed. In view of these results we conclude that aryl hydrocarbon hydroxylase activity is suppressed in AHH noninducible human lung carcinoma x AHH inducible mouse hepatoma cell hybrids.
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PMID:Suppression of aryl hydrocarbon hydroxylase activity in human primary lung carcinoma x mouse hepatoma somatic cell hybrids. 281 4

A human primary lung carcinoma cell line (HPL-R1) established from the tumor biopsy of a lung cancer patient, lacking in cytochrome P1-450 [aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH)], was cloned and used to obtain variants deficient in the expression of thymidine-kinase via treatment with 5-bromo-2'-deoxyuridine, and selection for drug resistance phenotype. The variant cell line, precharacterized for thymidine kinase negative phenotype, was transfected with the thymidine kinase gene bearing p R-tk and px1-tk plasmids. Transfections from both the plasmids, demonstrated a frequency of 5.5 X 10(-5). The transfectants showed a 76-100% retention of the transferred phenotype. These data suggest that transfection in variant human cells can approach significant levels of stability observed with rodent cell recipients.
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PMID:Plasmid DNA mediated transfer of the herpes simplex virus thymidine kinase gene to a new bromodeoxyuridine resistant variant of human primary lung carcinoma cells. 283 65

At a nontoxic dose (50 microM), the two potent uridine phosphorylase inhibitors, benzylacyclouridine and benzyloxybenzylacyclouridine (BBAU), potentiated 5-fluoro-2'-deoxyuridine (FdUrd) growth inhibition of human pancreatic carcinoma (DAN) and, to a lesser extent, human lung carcinoma (LX-1) cells in culture. BBAU was more effective than benzylacyclouridine. BBAU (50 microM) enhanced the cytocidal effect of FdUrd (1 microM, 3 hr) on DAN grown on soft agar from 75 to 88%. In antithymocyte serum-immunosuppressed mice bearing DAN, the mean tumor weight in animals treated with FdUrd (50 mg/kg/day for 2 days) was 11% less than that of untreated controls. When BBAU (10 mg/kg/day for 2 days) was coadministered, the mean tumor weight at Day 10 was 78% less than untreated controls, with no apparent host toxicity, clearly demonstrating the potentiation of the antitumor effects of FdUrd by BBAU. The fact that DAN responded better than LX-1 to benzylacyclouridine and BBAU could be due, in part, to the lower relative activity of thymidine phosphorylase to uridine phosphorylase in DAN compared to LX-1. The activities of other enzymes involved in FdUrd metabolism, thymidine kinase, uridine kinase, orotate phosphoribosyltransferase, 5'-nucleotidase, and dihydrouracil dehydrogenase, did not differ between the two cell lines.
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PMID:Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. 623 86

To define the human homolog (or homologs) of transforming sequences (v-fes gene) common to Gardner (GA) and Snyder Theilen (ST) isolates of feline sarcoma virus (FeSV), a representative library of human lung carcinoma DNA in a cosmid vector system was constructed. Three cosmid clones were isolated containing GA/ST FeSV v-fes homologous cellular sequences, within 32- to 42-kilobase cellular inserts representing 56 kilobases of contiguous human cellular DNA. Sequences both homologous to, and colinear with, GA or ST FeSV v-fes are distributed discontinuously over a region of up to 9.5 kilobases and contain a minimum of three regions of nonhomology representing probable introns. A thymidine kinase selection system was used to show that, upon transfection to RAT-2 cells, the human c-fes sequence lacked detectable transforming activity.
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PMID:Isolation of human oncogene sequences (v-fes homolog) from a cosmid library. 628 90

Present study was undertaken to reveal the effects of total parenteral nutrition (TPN) on the immunocompetence associated with nutritional status and on the tumor growth. The 4-nitro-quinoline-1-oxide induced Sato Lung Carcinoma was transplanted subcutaneously on the back of Donryu rats. Rats were controlled by TPN, low calorie infusion or oral feeding for one or two weeks. Each group was subdivided into chemotherapy and non chemotherapy group. Chemotherapy was performed with adriamycin or ACNU. Tumor bulk was bigger in the well nourished TPN rats than in malnourished group, revealing an accelerated tumor growth by TPN. Despite no significant change in polyamine level and phosphorylation activity, thymidine kinase activity and mitotic index in tumor were significantly higher in TPN than in low calorie infusion. Compared to the results of low calorie infusion, higher activity of IgG, IgM plaque forming cells and lymphocytic blastformation by PHA was suggested the good maintenance of both cellular and humoral immunity in well nourished rats. There was no positive evidence to support the facilitated effect of chemotherapeutic agents in TPN. However, TPN decreased an incidence of adverse reactions of chemotherapy such as loss of weight, leukopenia. Survival rate of rats at nine weeks after treatment also showed the favorable effect of TPN on chemotherapy.
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PMID:[Effect of total parenteral nutrition on the nutritional status and immunocompetence in host and on the tumor growth]. 643 77

The delivery of viral vectors to the brain for treatment of intracerebral tumors is most commonly accomplished by stereotaxic inoculation directly into the tumor. However, the small volume of distribution by inoculation may limit the efficacy of viral therapy of large or disseminated tumors. We have investigated mechanisms to increase vector delivery to intracerebral xenografts of human LX-1 small-cell lung carcinoma tumors in the nude rat. The distribution of Escherichia coli lacZ transgene expression from primary viral infection was assessed after delivery of recombinant virus by intratumor inoculation or intracarotid infusion with or without osmotic disruption of the blood-brain barrier (BBB). These studies used replication-compromised herpes simplex virus type 1 (HSV; vector RH105) and replication-defective adenovirus (AdRSVlacZ), which represent two of the most commonly proposed viral vectors for tumor therapy. Transvascular delivery of both viruses to intracerebral tumor was demonstrated when administered intraarterially (i.a.) after osmotic BBB disruption (n = 9 for adenovirus; n = 7 for HSV), while no virus infection was apparent after i.a. administration without BBB modification (n = 8 for adenovirus; n = 4 for HSV). The thymidine kinase-negative HSV vector infected clumps of tumor cells as a result of its ability to replicate selectively in dividing cells. Osmotic BBB disruption in combination with i.a. administration of viral vectors may offer a method of global delivery to treat disseminated brain tumors.
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PMID:Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption. 756 27

We investigated the effects of hypoxia (< 2.5% O2) on rat manganese superoxide dismutase (MnSOD) gene promoter-luciferase reporter constructs in transiently transfected lung epithelial cells (A549, L2, and E1A-T2) and fibroblasts (R9Ab). We cloned MnSOD promoter-luciferase reporter constructs (numbers refer to length in base pairs [bp] in the 5' direction from the transcription initiation site): 2,505, 1,064, 507, 405, and 289 into pGL2-Basic, a promoterless, firefly luciferase vector. Lung cells were transfected with MnSOD promoter-reporter constructs with or without thymidine kinase-driven Renilla luciferase (pRL-TK), and were exposed to air/5% CO2 or hypoxia (2.5% O2/5% CO2/balance N2) for 24 h. Hypoxia caused a significant (by two-way analysis of variance) consistent increase in luciferase in the A549 cell (human lung carcinoma) line. Greatest expression (> 3-fold increase) in hypoxia was associated with the 2,505-bp MnSOD promoter (normalized to cellular protein). Azide (10 microM) did not increase expression of the MnSOD reporter constructs. The 289-bp promoter was sufficient to express the reporter in air and to increase its expression in hypoxia. Promoter activity of the rat MnSOD 5' region, assessed by luciferase reporter constructs in A549 cells, increased in hypoxia. The increase was exclusive to A549 cells and did not occur in other cells.
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PMID:Hypoxic modulation of manganese superoxide dismutase promoter activity and gene expression in lung epithelial cells. 1038


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