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)

Several studies have shown that expression of exogenous wild-type p53 is detrimental to the growth of cell lines with absent or mutant p53. In this study, wild-type p53 cDNA expression plasmids were transfected into A549 lung carcinoma cells which had previously been shown by sequencing to contain wild-type p53. When a constitutively expressed wild-type p53 plasmid containing the neomycin resistance gene was transfected into these cells, no G418-resistant colonies contained the exogenous p53 cDNA even though the neomycin resistance gene was integrated. When cells were transfected with a dexamethasone-inducible wild-type p53 cDNA expression plasmid, induction of p53 expression resulted in a decreased growth rate and a decreased proportion of S-phase cells. Continuous treatment with dexamethasone resulted in continued p53 expression for 16 days, but beyond that time expression ceased and could not be reinduced. These data indicated that although the A549 cell line could proliferate in the presence of endogenous wild-type p53 there was a strong selection pressure against continued expression of additional exogenous wild-type p53.
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PMID:Effects of exogenous wild-type p53 on a human lung carcinoma cell line with endogenous wild-type p53. 145 95

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld-negative, and two Neor clones were selected by means of a 125I-protein A binding assay using an anti-H-2Ld monoclonal antibody. The antigenic expression of the H-2Ld gene products was only 20-40% on the Ld-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 X 10(6) in the Ld-positive clones, but only 1.3 X 10(5) in the 3LL/3 parent clone, 1.2 X 10(5) in the Neor clones, and 2.2 X 10(5) in the Ld-negative clones. The tumorigenicity of the Ld-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the Ld-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable Ld-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between Ld-positive, Ld-negative, Neor, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity.
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PMID:Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogeneic class I major histocompatibility complex gene (H-2Ld). 310 4

Gene therapy with cytokine cDNA will provide a new tool for cancer treatment. We have already reported that immunization with interleukin-2 (IL2) cDNA transfected Lewis lung carcinoma (LLC) cells induced anti-tumor immunity, which, however, was not strong enough to eradicate an established tumor. In an attempt to develop more effective gene therapy methods, we have used tumor cells co-transfected with IL-2 and tumor necrosis factor (TNF) cDNAs. These cDNAs were introduced into pBMG-Neo and pcDV-X819 vectors, respectively, and then co-transfected into LLC cells. The co-transfectants were selected by incubating them in a medium containing G418 followed by the limiting dilution method twice to obtain IL2 and TNF cDNA co-transfected LLC (LLC-TNF-IL2) cells. When 5 x 10(5)/ml LLC-TNF-IL2 cells were incubated for 48 h, they secreted 7.56 U/ml TNF and 527.0 U/ml IL2 into the culture supernatant. When C57BL/6 mice were transplanted with 1 x 10(6) LLC-TNF-IL2 cells, all the tumors were rejected. The growth of transplanted LLC, but not B16F10 melanoma cells, was retarded in mice inoculated with LLC-TNF-IL2 on their contralateral sides, which suggests specific immunity was induced. The immunization effect by the co-transfectant was superior to that of the IL2- and TNF-transfectants alone.
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PMID:Gene therapy for Lewis lung carcinoma with tumor necrosis factor and interleukin 2 cDNAs co-transfected subline. 758 91

Multiple genetic alterations, including inactivation of the RB gene, occur commonly in small-cell lung carcinoma (SCLC). To assess a functional role of RB inactivation in the development of SCLC, an RB expression plasmid was introduced by stable transfection into SCLC cell lines, Lu-135 and N417, in which the RB gene was inactivated. Lu-135 and N417 cells transfected with the wild-type RB gene formed G418-resistant colonies twofold less efficiently than those with a mutated RB gene or with the control vector. Intact exogenous wild-type RB genes were detected only in approximately 20% of G418-resistant clones; three of 14 in Lu-135 and three of 16 in N417, respectively. Transcripts from the transfected RB gene were also detected in two of these three clones from Lu-135 and two of three from N417 but the amount of RB mRNA and protein was less than one fifth of that in normal fibroblast cells WI-38. Furthermore, clones with exogenous wild-type RB expression showed either reduced growth rates in culture or suppressed tumorigenicity in nude mice. These findings suggest that functional correction of the RB gene is sufficient to suppress the growth of SCLC cells, even though several other genetic alterations in the cells remain uncorrected.
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PMID:Reconstitution of the RB gene suppresses the growth of small-cell lung carcinoma cells carrying multiple genetic alterations. 839 62

The lung carcinoma cell line Calu3, which overexpresses the c-erbB-2 oncogene, was stably transfected with antisense (AS) cDNA constructs encompassing different regions of the c-erbB-2 gene. Transfected cells were analyzed for their tumorigenic properties in vitro and in nude mice. Two independent clones, AS F1 (low erbB-2 expressor) and AS B12 (high erbB-2 expressor), as well as the polyclonal Calu3/AS 5', were selected for these analyses. In Calu3/AS 5' transfected cells and in the AS F1 clone, c-erbB-2 RNA and protein levels were lower than those detected in the parental cell line and the AS B12 clone. Anchorage-independent growth and tumor take were also significantly reduced. Furthermore, cells derived from primary tumors of Calu3/AS 5', AS F1 and AS B12 lost the AS c-erbB-2 DNA insert but retained the gene for G418 resistance. Our results suggest that a correlation between c-erbB-2 overexpression and tumorigenicity may exist in the Calu3 lung carcinoma cell line.
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PMID:Inhibition of tumorigenicity in lung adenocarcinoma cells by c-erbB-2 antisense expression. 925 3

Sleeping Beauty (SB) is a gene-insertion system reconstructed from transposon sequences found in teleost fish and is capable of mediating the transposition of DNA sequences from transfected plasmids into the chromosomes of vertebrate cell populations. The SB system consists of a transposon, made up of a gene of interest flanked by transposon inverted repeats, and a source of transposase. Here we carried out a series of studies to further characterize SB-mediated transposition as a tool for gene transfer to chromosomes and ultimately for human gene therapy. Transfection of mouse 3T3 cells, HeLa cells, and human A549 lung carcinoma cells with a transposon containing the neomycin phosphotransferase (NEO) gene resulted in a several-fold increase in drug-resistant colony formation when co-transfected with a plasmid expressing the SB transposase. A transposon containing a methotrexate-resistant dihydrofolate reductase gene was also found to confer an increased frequency of methotrexate-resistant colony formation when co-transfected with SB transposase-encoding plasmid. A plasmid containing a herpes simplex virus thymidine kinase gene as well as a transposon containing a NEO gene was used for counterselection against random recombinants (NEO+TK+) in medium containing G418 plus ganciclovir. Effective counterselection required a recovery period of 5 days after transfection before shifting into medium containing ganciclovir to allow time for transiently expressed thymidine kinase activity to subside in cells not stably transfected. Southern analysis of clonal isolates indicated a shift from random recombination events toward transposition events when clones were isolated in medium containing ganciclovir as well as G418. We found that including both transposon and transposase functions on the same plasmid substantially increased the stable gene transfer frequency in Huh7 human hepatoma cells. The results from these experiments contribute technical and conceptual insight into the process of transposition in mammalian cells, and into the optimal provision of transposon and transposase functions that may be applicable to gene therapy studies.
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PMID:Counterselection and co-delivery of transposon and transposase functions for Sleeping Beauty-mediated transposition in cultured mammalian cells. 1615 96

This study was designed to establish an interleukin-12 (IL-12)-expressing murine Lewis lung carcinoma (LLC) cell vaccine (LLC/murine IL-12 [mIL-12]) and assess its antitumor efficacy and mechanism in vivo. The recombinant IL-12 plasmid was transfected into LLC cells and screened by G418, and positive clones were obtained. C57BL/6 tumor-bearing mouse model was established and tumor-bearing mice were randomly divided into three groups (n = 20), that is, treated with an intratumoral injection of phosphate-buffered solution, blank plasmid, or LLC/mIL-12 vaccine, respectively, at days 0, 7, and 14. Tumor size was measured before and after treatment. Tumor growth curve was plotted, cytolytic T lymphocyte (CTL) activity assay and natural killer (NK) cell activity assay were performed, CD4(+) and CD8(+) T lymphocyte were quantitated using flow cytometry, and the expression of interferon-gamma (IFN-gamma), IL-12, and interferon-inducible protein-10 (IP-10) in serum was detected by ELISA. Microvessel density was determined by immunohistochemistry after all mice were euthanized at day 21. The study revealed suppressed tumor growth, elevated levels of IFN-gamma, IP-10, and IL-12, augmented NK and CTL cell activities, and decreased microvessel density of tumor tissues. There were abundant CD4(+) and CD8(+) T lymphocyte infiltration in the vaccine group. This study demonstrated that the antitumor mechanism of LLC/mIL-12 vaccine was to promote IFN-gamma and IL-12 secretion, augment the NK and CTL cell activities, and decrease the microvessel density of tumors.
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PMID:Antitumor mechanism of recombinant murine interleukin-12 vaccine. 2057 31

Lung cancer is the leading cause of cancer-related death worldwide, mainly due to its highly metastatic properties. Previously, we reported an inverse correlation between Rho-kinase inhibitor and the progression of the lung cancer cells. The purpose of this study was to investigate the effects of RhoA on the proliferation, adhesion, invasion, and migration of SPCA1 lung carcinoma cells and to explore the underlying molecular mechanisms. RNA interference was used to downregulate RhoA expression in these cells. Through G418 screening, we generated SPCA1 lung cancer cell lines with stable RhoA silencing. We then observed the cell behaviour, and used matrix metalloproteinase (MMP) activity and western blot assays to evaluate the underlying molecular mechanisms. The proliferation, adhesion, migration, and invasion of SPCA1 lung cancer cells were decreased after knockdown of RhoA. At the molecular level, the total amounts of active MMP2 and MMP9 were decreased by about 17.21% (P<0.05) and 45.32% (P<0.01), respectively. Myosin phosphatase targeting subunit 1 phosphorylation (P-MYPT1) was reduced by 36.16% (P<0.05). Taken together, our findings show that the knockdown of RhoA prevents proliferation and metastasis in SPCA1 lung cancer cells. Changes in MMP2, MMP9, and P-MYPT1 levels and activity might be some of the molecular mechanisms underlying these effects.
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PMID:Loss of RhoA expression prevents proliferation and metastasis of SPCA1 lung cancer cells in vitro. 2566 83