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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that pH-sensitive immunoliposomes can mediate a target-specific delivery of plasmid DNA to tumor cells grown in a mouse model [Wang, C.-Y., & Huang, L. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7851-7855]. The efficiency of delivery in terms of the target cell transformation frequency has now been characterized for both short- and long-term gene expression in a tissue culture system. Herpes simplex virus thymidine kinase (TK) gene was used as a reporter gene. It was placed under the control of the promoter for the rat phosphoenolpyruvate carboxykinase gene, which contains a cAMP regulatory element. Therefore, the expression of the exogenous gene in the target cell, mouse Ltk- cells, can be regulated by cAMP drugs. The plasmid DNA was encapsulated in liposomes using a detergent dialysis method. The efficiency of gene delivery was optimized with respect to the time course and dose of liposome-associated DNA. The existence of antibody of the liposomes was essential for the maximal level of DNA delivery. Delivery was also dependent on the lipid composition of the liposome. The pH-sensitive lipid composition gave 8-fold higher efficiency than the corresponding pH-insensitive composition. The transformation efficiency of the target cell also depended on the regulation of gene expression; cells incubated with dibutyryl-cAMP and theophylline showed a much higher level of transformation frequency than cells incubated without the drugs. When all liposome and incubation parameters are optimized, the Ltk- cells showed a 47% efficiency for the short-term transformation, and 2% for the long-term transformation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes. 255 22

Rat2 cells are thymidine kinase-deficient derivatives from the immortalized rat embryo cell line Rat1. They show no phenotypic correlates of malignancy in vitro and produce tumors in syngeneic Fischer rats after long latency periods. We have investigated how transfection with oncogenes would alter the in vitro and in vivo behavior of Rat2 cells. Thus we have manipulated Rat2 cultures in various ways. The cell lines obtained were categorized as parental, in vitro subclones, untransfected in vivo derivatives, non-oncogene (neor and tk) transfectants, oncogene (mutated c-Ha-ras, polyoma middle-T, FBR v-gag-fos-fox) transfectants, and in vivo derivatives of transfectants. They were tested in vitro for morphotype, colony formation in soft agar, growth in organ culture, invasion in organ culture, and in vivo for latency period of tumor formation, tumor growth rate, invasiveness, and metastasis. Differences between the consequences of various manipulations were found in the number of malignancy-related phenotypic alterations. The following trend could be deduced from our data: induction of invasiveness in organ culture by all manipulations; morphotypic transformation and shortening of tumor-latency period by all oncogene transfections and by passage with tumor formation in vivo; growth in organ culture and increased tumor growth rate in vivo by transfection with ras-, or fos-oncogenes and by passage in vivo. Metastatic capability (present in parental Rat2 cell tumors) and colony formation in soft agar (absent in Rat2 cells) were not affected by the present manipulations. We concluded that differences between the oncogene-transfectants and the untransfected in vivo derivatives do not lie in the expression of malignancy-related phenotypes but in the time needed to acquire them.
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PMID:Effect of oncogene transfection or passage in vivo on malignant phenotypes of rat2 cells. 269 82

The C-1300 neuroblastoma tumor which arises spontaneously in the A/J mouse has been maintained in this mouse strain. Two different cell populations have been recognized in cultured C-1300 mouse neuroblastoma (MNB): (1) round, "neuroblast-like" cells, growing in suspension (poorly attached), that have a highly malignant behavior when injected into the A/J mouse (T1 cells); and (2) flat, "epithelioid" cells that attach well to surfaces and show low malignancy towards the inoculated animals (T2 cells). The specific activities of the pyrimidine metabolizing enzymes thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) were examined in both MNB cell lines by a new radiochromatographic method. Enzymatic activities of TP and DPD in the cytosols of T2 (weakly malignant) cells were up to 15 times higher than those of T1 (strongly malignant) cells, whereas the mean TP/DPD activity ratio was 16 in either cell line. TP and DPD activity levels increased with time of growth in culture in T2 cells while no such increase was seen in the T1 cells. Maximal TK activity was similar in both cell lines but dropped more rapidly in the T2 cells as cell densities increased. The enzymatic activity levels of TP and DPD but not of TK correlated inversely with neoplastic expression of MNB cells. The observed patterns of pyrimidine metabolizing enzymes in MNB cells could result in an increased thymidine pool in T1 cells whenever TK activity is suppressed, whereas such conditions would favor the generation of thymine in the T2 cells.
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PMID:Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells. 271 95

A cultured cell line of mouse fibroblasts was transfected with DNA from murine leukemia cells expressing a previously characterized tumor-associated antigen. Antigen-positive cells were used as immunogens in an immunotherapy protocol to determine if they stimulated resistance to the malignant proliferation of the leukemia in susceptible mice. For the experiments, LM(TK-) mouse fibroblasts, a thymidine kinase-deficient mouse cell line, were cotransfected with DNA from ASL-1 murine leukemia cells and the plasmid pSV2neo conferring resistance to Geneticin. Integration of the plasmid into cellular DNA was confirmed by restriction digest blot analysis. A/J mice, highly susceptible to the malignant proliferation of passively transferred ASL-1 leukemia cells, were immunized with the transfected cells. Animals receiving two prior injections of antigen-positive transfected cells and then challenged with an injection of viable ASL-1 cells survived longer than animals in the unprotected control group or in the group receiving immunizations with LM(TK-) cells transfected with plasmid only (p less than 0.01). Some of the mice appeared to have rejected the tumor and lived more than 80 days. One group of protected animals rechallenged with a second injection of ASL-1 cells, 40 days after the first, survived for more than 50 additional days, without evidence of recurrent disease.
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PMID:Immunity to murine leukemia induced in susceptible mice by transfected mouse fibroblasts. 282 15

Macromolecules such as DNA and RNA can be entrapped within liposomes associated with gangliosides by reverse-phase evaporation. When these liposomes are incubated with HVJ2 (Sendai virus), they deliver their contents into cultured cells efficiently. More than 95% cells of a Ltk- cell line (thymidine kinase-deficient cells) transiently expressed thymidine kinase activity by thymidine kinase gene transfer using HVJ liposomes with gangliosides. Stable transformants could be obtained efficiently from various cell lines by use of HVJ liposomes containing the neoR gene. The neo+ transformants were obtained at frequencies of about 0.2-1.0, 0.06-0.25, and 0.06-0.1% in monolayers of L, CHO-Kl, and HeLa-S3 cells, respectively. Moreover, in Ehrlich ascites tumor cells which grow in suspension, the frequency was more than 0.01%. On introduction of plasmid pTK4 into Ltk- cells, about 0.5-1.0% TK+ transformants were obtained. Cosmid DNA containing the neoR gene (about 45 kbp) was also introduced into L cells by this method and neo+ transformants were obtained at a frequency of 0.1%. When rat liver mRNA was introduced into L cells by HVJ liposomes with gangliosides, immunoprecipitation studies showed that the L cells secreted rat albumin and some other proteins into the cultured medium. Moreover, using erythrocyte membrane vesicles containing IgM that had been incubated with HVJ empty liposomes with gangliosides, the IgM could be introduced into all the L cells.
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PMID:The improved efficient method for introducing macromolecules into cells using HVJ (Sendai virus) liposomes with gangliosides. 282 24

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

We analyzed serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and thymidine kinase (TK) levels in 22 patients with small cell lung cancer. Tumor proliferation was expressed as the proportion of S-phase cells (SPF), determined by DNA flow cytometry, from concomitantly taken biopsy samples. A positive correlation between serum NSE (r = 0.41) or LDH (r = 0.65, p = 0.05) levels and tumor SPF was noted, but was not found between serum TK levels and the SPF. The correlation between NSE and SPF was even more pronounced if only patients with extensive disease were considered (r = 0.77). The serum NSE and LDH, but not TK levels, were significantly greater in the patients with extensive disease (NSE 50.4 ng/ml, LDH 621 U/ml) compared to the patients with limited disease (NSE 21.0 ng/ml, LDH 272 U/ml, p = 0.05). Our results suggest that the combined determination of serum LDH and NSE levels gives valuable data on the primary tumor mass and its proliferative activity in small cell lung cancer.
Tumour Biol 1988
PMID:Correlation between serum tumor marker levels and tumor proliferation in small cell lung cancer. 284 99

The potential therapeutic effects of differentiating agents on leukemic and solid tumor cells are being evaluated worldwide. These effects can be followed by morphologic as well as biochemical parameters. The enzymatic profile of four enzymes and the level of carcinoembryonic antigen were studied in 24 human colorectal carcinoma specimens and their adjacent uninvolved mucosa. The enzymes studied were thymidine kinase and 6-phosphogluconate dehydrogenase as markers of proliferation, and alkaline phosphatase and gamma-glutamyl transpeptidase as markers of differentiation. A consistent finding was a marked increase in the activities of thymidine kinase and 6-phosphogluconate dehydrogenase in the tumor cells as compared with the adjacent normal mucosa. The activity of gamma-glutamyl transpeptidase was not significantly different between tumor and uninvolved colon tissue. Alkaline phosphatase activity was markedly reduced in the tumor specimens. A relationship between the degree of differentiation and the degree of penetration and CEA expression was demonstrated in the tumor specimens as well as in their surrounding uninvolved mucosa.
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PMID:Biochemical tissue markers of human colorectal carcinoma. 289 33

The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.
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PMID:Comparison of tumor growth inhibitory and toxic effects of a new fluorouracil--nitrosourea derivative (B-3839). 297 32

Murine mammary carcinoma (FM3A TK-/HSV-1 TK+) cells, which are thymidine kinase (TK)-deficient but have been transformed with the herpes simplex virus type 1 (HSV-1) TK gene are inhibited in their growth by (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC) at 0.5, 0.5 and 0.8 ng/ml, respectively; i.e., a concentration 5000 to 20 000-fold lower than that required to inhibit the growth of the corresponding wild-type FM3A/0 cells. Hence, transformation of tumor cells with the HSV-1 TK gene makes them particularly sensitive to the cytostatic action of BVDU and related compounds.
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PMID:Murine mammary FM3A carcinoma cells transformed with the herpes simplex virus type 1 thymidine kinase gene are highly sensitive to the growth-inhibitory properties of (E)-5-(2-bromovinyl)-2'-deoxyuridine and related compounds. 298 41


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