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)

Transforming growth factor-beta 1 (TGF-beta 1), a regulator of growth and differentiation of many cell types, has previously been purified from the human placenta, and the messenger (m) RNA is abundantly expressed there. We found that the approximate 2.5-kilobase TGF-beta 1 mRNA is expressed in JEG-3 human choriocarcinoma cells, which have been widely used as a model system for studying the regulation of trophoblast hormone secretion. Cholera toxin (CT) elevates the cellular levels of the second messenger cAMP and increases the secretion of CG and steroids in these cells, thus being a potent inducer of trophoblast-differentiated functions. We show that CT also stimulates TGF-beta 1 mRNA levels in JEG-3 cells in a concentration- and time-dependent manner as studied by Northern and dot blotting. The maximal effect (about 5-fold increase above basal levels) occurs within 12-48 h of induction with a CT concentration of 1.0 ng/ml. The cell-permeable cAMP-analog 8-bromo-cAMP stimulates the accumulation of TGF-beta 1 mRNA in JEG-3 cells as well. Furthermore, this cAMP analog also induces TGF-beta 1 mRNA levels in normal cultured term placental cytotrophoblasts. 12-O-Tetradecanoyl phorbol-13-acetate, an active phorbol ester protein kinase C regulator and inducer of TGF-beta 1 mRNA in many cells, increases TGF-beta 1 mRNA accumulation in JEG-3 cells with a similar time course as cAMP analogs but to a lesser extent. Human HT-1080 fibrosarcoma and A-549 lung carcinoma cells exhibit up-regulation of TGF-beta 1 mRNA in response to TGF-beta 1 itself, but we show that activation of the cAMP-dependent pathway does not affect TGF-beta 1 mRNA levels in these cells. Cycloheximide, an inhibitor of protein synthesis, prevents the effect of CT and 12-O-tetradecanoyl phorbol-13-acetate on TGF-beta 1 mRNA expression in JEG-3 cells, suggesting that a protein mediator may be involved in the transduction of their effects. Our finding of a cAMP-dependent induction pathway for TGF-beta 1 mRNA expression in JEG-3 cells provides a new mechanism for the regulation of the synthesis of this ubiquitous growth and differentiation factor and suggests that TGF-beta 1 may have a role in trophoblast differentiation.
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PMID:Adenosine 3',5'-monophosphate and phorbol ester induce transforming growth factor-beta 1 messenger ribonucleic acid levels in choriocarcinoma cells. 165 96

The influence of different concentrations of a transforming growth factor of type beta (TGF-beta) and of its combinations with the epidermal growth factor (EGF) and insulin exerted on proliferation of different types of cells in the culture medium with semisolid agar was determined. The following cell lines were tested: mouse fibroblasts of NIH-3T3 and Swiss-3T3 lines, fibroblastic line NRK-49F from rat kidney, cells of A-549 line from human lung carcinoma, HT-1080 line from human fibrosarcoma, and PS-103 line (clone 384/5) from sarcoma stimulated by polychlorvinyl plate implantation to mouse. It is detected that TGF-beta alone does not affect the substrate-independent proliferation of pseudonormal lines of fibroblastic cells, but stimulates it significantly in sarcoma and inhibits in carcinoma cells. If EGF and/or insulin are added to the culture medium besides TGF-beta, certain proliferative effect specific of either type of pseudonormal and malignant cells is detected. The results of the action of TGF-beta, and of its combinations with the most important polypeptide growth factors on several types of cells of different origin may be useful for determination of regulatory functions of TGF-beta in cell proliferation in vivo to promote better grounding of its utilization in the practice of medicine.
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PMID:[The effect of the beta-type transforming growth factor and its combination with epidermal growth factor and insulin on substrate-dependent proliferation of normal and tumor cells]. 268 71

The presence of dominant transforming genes in human tumor cell lines has been investigated. High molecular weight DNAs isolated from cell lines established from carcinomas and sarcomas of various organs as well as from a glioblastoma and two melanomas were utilized to transfect NIH/3T3 mouse fibroblasts. The DNAs of T24 and A2182, two cell lines derived from a bladder and a lung carcinoma, respectively, and of HT-1080, a cell line established from a fibrosarcoma, were able to transform recipient NIH/3T3 cells. First-cycle transformants exhibited anchorage-independent growth and were tumorigenic in athymic and immunocompetent mice. Moreover, they contained human DNA sequences and were able to transmit their malignant phenotype in additional cycles of transfection. Southern blot analysis of T24-derived transformants showed that a single fragment of human DNA specifically cosegregated with the malignant phenotype, suggesting that it contained the T24 oncogene. Therefore, these human sequences were molecularly cloned with lambda Charon 9A as the cloning vector. The resulting recombinant DNA molecule, designated lambda T24-15A, was shown to contain a 15-kilobase-pair EcoRI insert of human cellular DNA. lambda T24-15A DNA (either intact or EcoRI digested) transformed NIH/3T3 fibroblasts with a specific activity of 20,000 focus-forming units per pmol of cloned DNA. Our results indicate that we have molecularly cloned a biologically active oncogene present in T24 human bladder carcinoma cells.
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PMID:Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells. 695 33

Photodynamic therapy (PDT) by combination of photofrin II and excimer dye laser was evaluated for its usefulness in experimental tumors. High antitumor effects of PDT on sarcoma 180 solid type were obtained when PDT was performed with laser irradiation at an energy of 50 or 100 J/cm2 (40 or 80 Hz, 4 mJ/pulse) 48 h after i.v. administration of photofrin II at a dose of 25 mg/kg. Under the same conditions, the antitumor effects of PDT on murine Lewis lung carcinoma, human fibrosarcoma HT-1080 and human bladder transitional cell carcinoma KK-47 were also observed. These results suggest that clinical application of PDT with photofrin II and excimer dye laser might be useful.
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PMID:Photodynamic therapy of photofrin II and excimer dye laser on experimental tumors. 773 52

Recently we have shown that in fibroblasts (NIH 3T3 and Rat-1 cells) inhibition of protein geranylgeranylation leads to a G0/G1 arrest, whereas inhibition of protein farnesylation does not affect cell cycle distribution. Here we demonstrate that in human tumor cells the geranylgeranyltransferase-I (GGTase-I) inhibitor GGTI-298 blocked cells in G0/G1, whereas the farnesyltransferase (FTase) inhibitor FTI-277 showed a differential effect depending on the cell line. FTI-277 accumulated Calu-1 and A-549 lung carcinoma and Colo 357 pancreatic carcinoma cells in G2/M, T-24 bladder carcinoma, and HT-1080 fibrosarcoma cells in G0/G1, but had no effect on cell cycle distribution of pancreatic (Panc-1), breast (SKBr 3 and MDAMB-231), and head and neck (A-253) carcinoma cells. Furthermore, treatment of Calu-1, Panc-1, Colo 357, T-24, A-253, SKBr 3, and MDAMB-231 cells with GGTI-298, but not FTI-277, induced the protein expression levels of the cyclin-dependent kinase inhibitor p21WAF. HT-1080 and A-549 cells had a high basal level of p21WAF, and GGTI-298 did not further increase these levels. Furthermore, GGTI-298 also induces the accumulation of large amounts of p21WAF mRNA in Calu-1 cells, a cell line that lacks the tumor suppressor gene p53. There was little effect of GGTI-298 on the cellular levels of another cyclin- dependent kinase inhibitor p27KIP as well as cyclin E and cyclin D1. These results demonstrate that GGTase-I inhibitors arrest cells in G0/G1 and induce accumulation of p21WAF in a p53-independent manner and that FTase inhibitors can interfere with cell cycle events by a mechanism that involves neither p21WAF nor p27KIP. The results also point to the potential of GGTase-I inhibitors as agents capable of restoring growth arrest in cells lacking functional p53.
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PMID:The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21(WAF1/CIP1/SDI1) in a p53-independent manner. 934 Nov 67

The antitumor activity of cinnamamide (CNM), an agent acting on matrix metalloproteinase (MMP), was investigated in the present study. CNM displayed low cytotoxicity. By the MTT assay the IC50 (50% inhibitory concentration) values of CNM on cell proliferation ranged from 1.29 to 1.94 mM in human oral epidermoid carcinoma KB cells, human hepatoma BEL-7402 cells and human fibrosarcoma HT-1080 cells. Moreover, the IC50 for human fetal lung 2BS cells reached 4.33 mM. The administration of CNM in the range of 50-150 mg/kg (i.p. or p.o.) showed moderate antitumor effects in mice. When administered i.p. or p.o., CNM (150 mg/kg) inhibited the growth of transplanted hepatoma 22 by 48.8 or 40.5%, respectively. At the dose of 100 mg/kg, CNM inhibited the growth of colon 26 carcinoma by 39.0% and that of Lewis lung carcinoma by 53.9%. In the Lewis lung carcinoma model, CNM at the dose of 100 mg/kg (i.p.) also reduced the lung metastasis by 59.1%. Gelatine zymography revealed that CNM was able to decrease the level of MMP-2 in conditioned medium of HT-1080 tumor cells in a concentration-dependent manner. These results indicate that CNM is an antitumor agent with low cytotoxicity acting on MMP and may serve as a lead compound in the development of antitumor drugs.
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PMID:Cinnamamide, an antitumor agent with low cytotoxicity acting on matrix metalloproteinase. 1075 63

Cathepsin B and in particular cell-surface and secreted cathepsin B has been implicated in the invasive and metastatic phenotype of numerous types of cancer. We describe here a method to easily survey cancer cell lines for cathepsin B activity using the highly selective substrate Z-Arg-Arg-AMC. Intact human U87 glioma cells hydrolyze Z-Arg-Arg-AMC with a Km of 460 microM at pH 7.0 and 37 degrees C. This is nearly the same as the Km of 430 microM obtained with purified cathepsin B assayed under the same conditions. The pericellular (i.e. both cell-surface and released) cathepsin B activity was inhibited by the cysteine protease inhibitors E-64, leupeptin, Mu-Np2-HphVS-2Np, Mu-Leu-HpHVSPh and the cathepsin B selective inhibitor Mu-Tyr(3,5 I2)-HphVSPh with IC50 values similar to those observed for the inhibition of purified human liver cathepsin B. Other human cancer cell lines with measurable pericellular cathepsin B activity included HT-1080 fibrosarcoma, MiaPaCa pancreatic, PC-3 prostate and HCT-116 colon. Cathepsin B activity correlated with protein levels of cathepsin B as determined by immunoblot analysis. Pericellular cathepsin B activity was also detected in the rat cell lines MatLyLu prostate and Mat B III adenocarcinoma and in the murine lines B16a melanoma and Lewis lung carcinoma. The ability to determine pericellular cathepsin B activity will be useful in selecting appropriate cell lines for use in vivo when analyzing the effects of inhibiting cathepsin B activity on tumor growth and metastasis.
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PMID:Fluorescent microplate assay for cancer cell-associated cathepsin B. 1086 20

On radiograms, glial tumors are usually seen to invade in a finger-like fashion, while non-central nervous system (CNS) tumors expand in a mass-like fashion. We prepared organotypic brain slice cultures from newborn rats to investigate the invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U-373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080 (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area that was centered at a junction between deep cortical layers and the striatum, punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different rhodamine-labeled tumor cells at that site, and observed their invasive behavior under an inverted fluorescent microscope. Over the course of several days, all glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest. Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice cultures, we also investigated the regulatory effect on tumor invasion of forced expression of glial fibrillary acidic protein (GFAP) after gene transfection. The forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our results show that organotypic brain slice cultures are an excellent medium for studying the invasive features of glial and non-CNS tumors.
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PMID:The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats. 1125 Nov 66

Methanol, methanol-water (1:1) and water extracts were prepared from seventy-seven Vietnamese medicinal plants and tested for their antiproliferative activities against human HT-1080 fibrosarcoma cells. Among them, fifteen extracts including seven methanol extracts of Caesalpinia sappan, Catharanthus roseus, Coscinium fenestratum, Eurycoma longifolia, Hydnophytum formicarum and Streptocaulon juventas (collected at two areas), six methanol-water (1:1) extracts of Cae. sappan, Cat. roseus, Co. fenestratum, H. formicarum and S. juventas (at two areas), and two water extracts of Cae. sappan and S. juventas exhibited antiproliferative activities in a concentration-dependent manner. Their antiproliferative activities against human cervix HeLa adenocarcinoma, human lung A549 adenocarcinoma, murine colon 26-L5 carcinoma, murine Lewis lung carcinoma (LLC) and murine B16-BL6 melanoma cells were then examined. Co. fenestratum showed selective activity against lung carcinoma and/or lung metastatic cell lines, A549, LLC and B16-BL6, while H. formicarum and S. juventas showed selective activity against human tumor cell lines, HeLa and A549. Characteristic morphological change and DNA fragmentation indicated the antiproliferative activity to be due to the induction of apoptosis.
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PMID:Antiproliferative activity of Vietnamese medicinal plants. 1208 Nov 42

Our focus was to develop an anti-angiogenic drug possessing the inhibitory activity of urokinase-type plasminogen activator (u-PA) production. During preliminary screening, the effects of 13 ozonides on the inhibition of u-PA production in human fibrosarcoma HT-1080 cells and on the inhibition of angiogenesis on chicken embryonic chorioallantoic membranes were determined. Of the ozonides tested, 9 inhibited in vitro u-PA production of HT-1080 cells and 7 of these 9 exhibited strong anti-angiogenic activity. Interestingly, 6 of the 13 ozonides also inhibited cathepsin B activity. 1-Phenyl-1, 4-epoxy-1H,4H-naphtho[1,8-de][1, 2]dioxepin (ANO-2) potently inhibited cathepsin B (IC(50) = 0.47 microM) as well as u-PA production. Consequently, ANO-2 was selected for further study. ANO-2 inhibited tube formation by human umbilical vein endothelial cells cultured on Matrigel while exhibiting no cytotoxicity. Additionally, in vivo administration of ANO-2 inhibited angiogenesis induced by mouse Sarcoma-180 cells tested using the mouse dorsal air sac assay. Moreover, ANO-2 also suppressed primary tumor growth and reduced the number of pulmonary metastases caused by Lewis lung carcinoma cells in mice. These in vitro and in vivo activities indicate that ANO-2 has considerable potential as a new and potent anti-angiogenic drug that inhibits both u-PA production and enzymatic activity of cathepsins, indicating that ANO-2 may be a multifunctional inhibitor of angiogenesis.
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PMID:Multifunctional anti-angiogenic activity of the cyclic peroxide ANO-2 with antitumor activity. 1211 73


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