Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.
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PMID:Effect of selenium on malignant tumor cells of brain. 757 18

Aggressiveness of follicular (FTC) and papillary thyroid cancer (PTC) varies widely. Tumorigenesis is associated with an imbalance of growth-promoting and growth-constraining factors. We investigated the effects of thyrotropin (TSH), epidermal growth factor (EGF) and transforming growth factor beta 1 (TGF-beta 1) on invasion and growth of 3 FTC- and 2 PTC-cell lines. Invasion (penetration through an 8 microns pore membrane, covered by Matrigel) and growth were measured using the MTT-method. EGF (10 ng/ml) and TSH in low concentrations (1 mU/ml) stimulated invasion and growth of FTC and PTC, whereas TGF-beta 1 (10 ng/ml) and TSH in high concentrations (100 mU/ml) were inhibiting. The parental cell line FTC133 was considerably more responsive to all growth factors than the metastatic clones. Invasion of FTC133 was enhanced by 42% (EGF) and 21% (TSH), invasion of FTC236 by 8% (EGF and TSH). Conversely, invasion of FTC133 was inhibited by 32% (TGF-beta 1) and 21% (TSH), invasion of FTC236 by 18% (TGF-beta 1) and 11% (TSH). TSH, EGF and TGF-beta 1 have an important impact on differentiated thyroid cancer cells and metastases may have developed by escaping from the normal control of growth factors.
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PMID:[Growth and invasion in differentiated thyroid carcinoma. Function of different growth factors]. 785 Nov 42

A number of studies have demonstrated that potent anti-tumor immunity can be induced using cytokine gene transfer, a strategy termed transgenic immunotherapy. Our aim is to express cytokine genes in the vicinity of tumor cells, either by transducing tumor cells themselves, or by delivering cytokine-expressing endothelial cells to tumor sites. We compared the ability of cytokine-expressing tumor cells or endothelial cells to inhibit the tumorigenesis of MDA-MB-435 breast cancer cells in athymic nude mice. Retroviral vectors containing either human interleukin 2 (hIL-2) or interleukin 1 (hIL-1 alpha) were used to transduce MDA-MB-435 cells or human umbilical vein endothelial cells (HUVEC). Using a modified MTT bioassay and an ELISA specific for hIL-2, 43 of 70 MDA-MB-435 clones transduced with IL-2 were found to secrete between 100-800 units of IL-2/10(6) cells/24 hr. hIL-2 and hIL-1 alpha-transduced HUVEC secreted 40 ng/IL-2/10(6)/24 hr and 1.8 ng/10(6)/24 hr, respectively. To facilitate in vivo tracking of tumor cells, both nontransduced and IL-2-expressing MDA-MB-435 cells were genetically-marked with the E. coli lacZ gene and selected using flow cytometry. To study in vivo tumorigenicity, cells were injected into the mammary fat pad of athymic nude mice: (1) lacZ/MDA-MB-435 cells injected alone formed tumors in all animals; (2) IL-2-expressing lacZ/MDA-MB-435 cells did not form any tumors; (3) co-inoculation of MDA-MB-435/IL-2, or HUVEC/IL-2, or HUVEC/IL-1 alpha with lacZ/MDA-MB-435 cells prevented or delayed tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breast cancer gene therapy: transgenic immunotherapy. 788 Nov 11

About 90% of human pancreatic cancers carry K-ras point mutation, which may play an important role in tumorigenesis. We investigated the inhibitory effects of anti-sense oligonucleotides targeting K-ras point mutation on the growth of cultured human pancreatic cancer cells. Eight human pancreatic cancer cell lines were screened for K-ras codon 12 point mutations by PCR-RFLP analysis and direct sequencing. Then, 3 cell lines with the major types of K-ras point mutation, i.e.,HuP-T1, HuP-T3 and PANC-1, and 1 without mutation, BxPC-3, were used for the experiments. Seventeen mer anti-sense oligonucleotides were designed, targeting the point mutation of K-ras codon 12, and transfected into the cells by the liposome-mediated method. Cell-growth activities were estimated by MTT assay. Levels of K-ras mRNA expression were determined using quantitative RT-PCR, and K-ras p21 protein synthesis was evaluated with Western blotting. Mutation-matched anti-sense oligonucleotides effectively inhibited the growth of these pancreatic cancer cell lines, except for BxPC-3, by suppressing K-ras mRNA expression and K-ras p21 protein synthesis. Moreover, mutation-matched anti-sense oligonucleotides showed stronger anti-proliferative effects than did mutation-mismatched ones. Our results suggest that anti-sense therapy specific to point mutations of K-ras mRNA is a practical approach to selective suppression of tumor growth, with little effect on normal cells.
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PMID:Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes. 993 56

Apoptosis plays a major role in gastrointestinal epithelial cell turnover, ulcerogenesis and tumorigenesis. We have examined apoptosis induction by non-steroidal anti-inflammatory drugs (NSAIDs) in human gastric (AGS) cancer cells and the role of protein kinase C (PKC) and apoptosis-related oncogenes. After treatment with aspirin or indomethacin, cell growth was quantified by MTT assay, and apoptosis was determined by acridine orange staining, DNA fragmentation and flow cytometry. The mRNA and protein of p53, p21waf1/cip1 and c-myc was detected by Northern and Western blotting respectively. The influence of PKC on indomethacin-induced apoptosis was determined by co-incubation of 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of c-myc was determined using its antisense oligonucleotides. The results showed that both aspirin and indomethacin inhibited cell growth and induced apoptosis of AGS cells in a dose- and time-dependent manner, without altering the cell cycle. Indomethacin increased c-myc mRNA and protein, whereas p53 and p21wafl/cip1 were unchanged. Down-regulation of c-myc by its antisense oligonucleotides reduced apoptosis induction by indomethacin. TPA could inhibit indomethacin-induced apoptosis and accumulate cells in G2/M. Overexpression of c-myc was inhibited by TPA and p21waf1/cip1 mRNA increased. In conclusion, NSAIDs induce apoptosis in gastric cancer cells which may be mediated by up-regulation of c-myc proto-oncogene. PKC activation can abrogate the effects of NSAIDs by decreasing c-myc expression.
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PMID:Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c-myc. 1002 4

In vitro changes of normal human keratinocytes (NHKs) derived from the oral mucosa after treatment with the chemical carcinogen 7,12 dimethylbenz[a]anthracene (DMBA; 5, 50, 200 ng/10 ml) were evaluated. NHKs were also treated with chemopreventive nutrient agents that previously had enhanced growth of epidermal and oral keratinocytes or suppressed growth of oral squamous cell carcinoma. These agents included the carotenoids beta-carotene and canthaxanthin and the retinoid retinyl palmitate (60 microM). Plating efficiency, growth in agarose (independent growth), viability [tetrazolium salt (MTT) assay], and proliferation ([3H]thymidine labeling) defined the growth of NHKs. The number of cornified cells and keratin expression (high-molecular-weight keratin) defined differentiation. gamma-Glutamyl transpeptidase, p53 expression, and tumorigenesis in mice defined oxidation and malignant transformation. Treatment with DMBA (50 ng/10 ml) was detected by autofluorescence; it produced an increase in pleomorphism and multinucleation and enhanced plating efficiency and the number of colonies grown in agarose. Chemopreventive treatment enhanced the number of colonies grown in agarose, but the MTT levels and [3H]thymidine incorporation-proliferation (24 h) were reduced. Chemopreventives also increased differentiation defined by the number of cornified cells and the expression of high-molecular-weight keratin-positive cells. Malignant transformation potential was depressed by reducing gamma-glutamyl transpeptidase and mutant p53 expression, whereas tumor suppressor p53 was enhanced. NHKs treated with DMBA and injected into nude mice (nu/nu: 1 x 10(6) cells/0.25 ml) produced tumor masses (3 of 3 animals), whereas the nutrient and DMBA groups produced smaller tumor masses, some with central ulcers (2 of 3 animals). Mock injection of untreated or nutrient-treated NHKs without DMBA treatment did not produce a tumor mass (0 of 3 animals). beta-Carotene, retinyl palmitate, and canthaxanthin increased differentiation and reduced transformation induced by DMBA in oral NHKs.
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PMID:In vitro growth changes of oral human keratinocytes after treatment with carotenoids, retinoid, and/or DMBA. 1022 45

Human primary hepatocellular carcinoma (HCC)is one of the highly prevalent malignant diseases worldwide, the identification of HCC-associated genes has been a major approach in elucidating the molecular mechanism of tumorigenesis of HCC. In our previous studies, a function-unknown gene, which displayed marked expression difference between the HCC sample and normal liver control has been detected by cDNA microarray. This gene was named after fup1 (function-unknown protein 1), and was cloned according to the data of GenBank. The cDNA of fup1 has an open-reading frame 1233 base pairs in size. Here, the function analysis of FUP1 related to HCC is being reported. The NIH3T3 cells transiently transfected with FLAG-conjugated FUP1 revealed strong nuclear staining in immunofluorescent assay. Furthermore, cell proliferation enhancing activity of fup1 was shown by MTT assay in stable transfectant NIH3T3 cell line with pcDNA3-derived plasmid having fup1 under the regulation of pCMV, while cell proliferation repressing activity of antisense fup1 was observed in BEL7404 stable transfectant cells. Tumorigenicity of the above stable transfectant cells was analyzed in nude mice compared with appropriate controls. The result was in good agreement with MTT assay. Elevated tumorigenicity of fup1 transfected NIH3T3 cell and repressed tumorigenicity of antisense fup1 transfected BEL7404 cell were clearly demonstrated. The results above suggested that fup1 might be a critical gene related to carcinogenesis of HCC. Detailed molecular function of fup1 remains to be elucidated.
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PMID:FUP1, a gene associated with hepatocellular carcinoma, stimulates NIH3T3 cell proliferation and tumor formation in nude mice. 1152 4

To evaluate whether leptin plays a putative role in breast tumorigenesis, we studied the expression of its long and short receptor isoforms in various tumoral breast tissues. We applied semiquantitative RT-PCR method to RNA extracted from 20 breast cancer biopsies and two human breast cancer cell lines (T47-D and MCF-7). Our results showed the expression of both leptin receptor transcripts in all tumoral tissues examined. By in situ hybridization experiments, we localized leptin receptors in proliferating epithelial cells. Study of leptin effects on human breast cancer cells growth was performed by [3H]-thymidine incorporation method and colorimetric MTT assay. We demonstrated that leptin (50-100 ng/ml) significantly stimulates proliferation of the human breast cancer cell line T47-D (P<0.05). Western blot analysis indicated that leptin induces a time-dependent activation of mitogen-activated protein kinases (MAPKinase) 1 and 2 in T47-D cell line. Moreover, the specific MAPK-inhibitor PD 98059 blocked cell proliferation induced by leptin. In conclusion, we demonstrate that leptin receptors are expressed in breast cancer and that leptin induces proliferation in the T47-D cell line via activation of the MAPKinases pathway. These data suggest that leptin and its receptors may be implicated in mammary cell proliferation and in breast cancer pathogenesis.
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PMID:Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. 1191 59

A number of selenium compounds have been found to inhibit tumorigenesis in a variety of animal and cell models. In order to explore the molecular mechanism involved in the anticarcinogenesis activity of selenium, we examined the effects of sodium selenite on cell viabilty, generation of reactive oxygen species (ROS), and mitochondrial transmembrane potential (delta(psi)m) in human colonic carcinoma cells SW480. The result from MTT test showed that sodium selenite reduced cell viability. Morophologic and flow cytometric results indicated that Na2SeO3 induced the apoptosis of SW480 cells. Na2SeO3 increased the generation of intracellular ROS, whereas BAPTA-AM, rotenone, and NaCN completely inhibited the increase of ROS induced by Na2SeO3. Na2SeO3 also caused the disruption of delta(psi)m. The intracellular ROS increase and apoptosis induced by Na2SeO3 were significantly decreased by superoxide dismutase (SOD), catalase. These data suggest that the ROS mediate apoptosis induced by Na2SeO3 and mitochondria may be a major source of Na2SeO3-induced ROS.
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PMID:Reactive oxygen species from mitochondria mediate SW480 cells apoptosis induced by Na2SeO3. 1193 48

Secretion of human chorionic gonadotropin (hCG) during pregnancy induces differentiation of the mammary gland, thereby making breast tissue less susceptible to carcinogenesis. HCG binds to specific hCG receptors on mammary epithelial cells inducing changes in gene expression that can inhibit cell proliferation and, therefore, interfere with tumorigenesis. Since breast cancer cells also contain a relatively high level of the hCG receptor, hCG has potential as a therapeutic agent. We postulated that hCG might also enhance the radiosensitivity of breast cancer cells and, therefore, be useful as an adjunctive therapy. In the present study, MCF-7 breast cancer cells grown in cell culture were treated with hCG (0.2-5 IU/ml) for 24 h prior to exposing the cells to 0 Gy, 3 Gy, 4 Gy, or 5 Gy of radiation. Following irradiation, the MCF-7 cells were incubated either in the presence or absence of hCG. Cell survival was monitored with an MTT assay 1 day, 4 days, and 7 days after irradiation. All of the concentrations of hCG tested enhanced radiosensitivity of MCF-7 cells. The maximum enhancement occurred with MCF-7 cells that had been exposed to 2 IU/ml of hCG for at least 24 h prior to irradiation with 4 Gy. The use of higher concentrations of hCG or a higher dose of radiation did not increase the enhancement effect. Treatment of MCF-7 cells with hCG for only 24 h was sufficient to achieve the maximum effect. However, maintaining the cells in hCG beyond 24 h increased the effectiveness of the lowest hCG concentration. Using a linear-quadratic equation to analyze the data, we determined that the use of hCG would result in an 8-10% reduction in MCF-7 cell survival at a dose of 2 Gy, a typical dose used in conventional cancer therapy.
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PMID:Enhancement of radiosensitivity of the MCF-7 breast cancer cell line with human chorionic gonadotropin. 1200 Feb 19


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