Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UV-TDTx cells are cloned from foci arising after C3H10T1/2 cells are sequentially exposed to u.v. irradiation followed by tetradecanoylphorbol acetate (TPA). When grown in pure culture, UV-TDTx cells appear transformed. Co-culture with C3H10T1/2 cells suppresses focus formation by the UV-TDTx cells. In the presence of TPA, however, focus formation by UV-TDTx cells occurs in C3H10T1/2 co-cultures. We now demonstrate that only tumor promoters that activate protein kinase C (TPA, teleocidin) can reverse C3H10T1/2 suppression of UV-TDTx focus formation in co-culture; other promoters (diethyl stilbestrol, dioxin, saccharin, cadmium) are inactive. Retinoic acid, a potent inhibitor of many biological effects of TPA, blocks the action of TPA in UV-TDTx:C3H10T1/2 co-cultures. Focus formation by UV-TDTx cells in co-culture is dependent on the size of the UV-TDTx colony at confluence; if the UV-TDTx colony is below a minimal size when the co-cultures reach density-dependent growth arrest, suppression of focus formation by C3H10T1/2 cells occurs even in the presence of TPA. Finally, TPA must be present prior to confluence to relieve suppression of focus formation. If TPA is added to co-cultures after density arrest, UV-TDTx cells will not subsequently form foci.
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PMID:Colony size, cell density and nature of the tumor promoter are critical variables in expression of a transformed phenotype (focus formation) in co-cultures of UV-TDTx and C3H10T1/2 cells. 359 32

Retinoic acid is a potent inhibitor of mouse skin tumor promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). We have further evaluated the effect of retinoic acid on the stages of tumor promotion and also analyzed the effect of duration of retinoic acid treatment on mouse skin tumor promotion by TPA. In a number of independent experiments, either with female CD-1 or SENCAR mice, we failed to observe a specificity of inhibition by retinoic acid of either Stage I or Stage II tumor promotion. In a typical experiment with SENCAR mice, application of 34 nmol of retinoic acid concurrently with each application of either TPA (3.2 nmol) or mezerein (3.2 nmol) to initiated (with 10 nmol 7,12-dimethylbenz(a)anthracene) skin equally inhibited promotion of skin papilloma formation. Furthermore, sustained inhibition of tumor promotion by retinoic acid required a continuous application of retinoic acid in conjunction with each promotional treatment with TPA; if retinoic acid treatment was discontinued, TPA treatment elicited tumor formation. These results indicate: (a) retinoic acid inhibits both Stage I and Stage II of tumor promotion; and (b) inhibition of tumor promotion exhibits retinoic acid dependency.
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PMID:Inhibition of both stage I and stage II mouse skin tumour promotion by retinoic acid and the dependence of inhibition of tumor promotion on the duration of retinoic acid treatment. 362 Nov 94

N-homocysteine thiolactonyl retinamide was synthesized from trans retinoic acid and the free base of homocysteine thiolactone. In doses of 90-1800 mg/kg given i.p. in mixed lipid vehicle over nine weeks, the compound decreased to 60% of controls the number of lung tumors which was induced in A/J mice by 20 mg of ethyl carbamate. The highest dose also decreased the mean volume of lung tumors to 50% of controls, resulting in a total tumor volume of 30% of controls. Retinoic acid itself at 450 mg/kg was toxic, and no chemopreventive activity was observed. The free base and the lipophilic perchlorate salt of homocysteine thiolactone both increased the number of lung tumors to 114-117% of controls, indicating a co-carcinogenic effect. In C57BL/6N mice with transplanted MUO4 rhabdomyosarcoma, N-homocysteine thiolactonyl retinamide in a dose of 1000 mg/kg given over 11-21 days decreased the weight of the tumors to 30-70% of controls. These results show that N-homocysteine thiolactonyl retinamide has chemopreventive activity against chemical carcinogenesis and antineoplastic activity against a transplanted neoplasm.
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PMID:Chemopreventive and antineoplastic activity of N-homocysteine thiolactonyl retinamide. 365 91

Retinoic acid can alter the differentiation of a variety of cell types, including chondrocytes. This action may explain the high incidence of craniofacial and limb defects resulting from exposure to retinoic acid during development, and may be the basis for the compound's inhibition of a chondrosarcoma tumor in vivo. In order to understand the mechanism of action of retinoic acid, we studied the expression of chondrocyte-specific proteins as well as other proteins that indicate a shift in the differentiated phenotype of the cell following exposure to retinoic acid. After 48 hr of exposure to retinoic acid chondrocytes stopped synthesizing the chondrocyte-specific pro alpha 1 (II) chain of collagen II and a 370-kDa precursor protein of a cartilage-specific proteoglycan. Instead, the cells synthesized increased amounts of fibronectin and the pro alpha 1 chain of collagen III. These changes could be detected as early as 12 hr after treatment. In addition, the steady-state levels of specific mRNA transcripts coding for these differentiation markers correlated with their protein synthesis levels. Also, nuclear runoff experiments indicated that retinoic acid down regulated transcription of the collagen II gene, while stimulating collagen III gene transcription. These observations suggest that retinoic acid may alter the expression of the chondrocyte phenotype by selectively changing the normal pattern of gene expression.
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PMID:Retinoic acid rapidly reduces cartilage matrix synthesis by altering gene transcription in chondrocytes. 365 21

Calcium, phospholipid-dependent protein kinase (C-kinase) was partially purified from skin of hairless mice. This enzyme activity was stimulated 6- to 15-fold in the presence of calcium and either diolein (DO), phosphatidyl serine (PS), or a mixture of the two. Tumor promoter, phorbol 12-myristate 13-acetate (PMA), also activated the enzyme either in the presence or in the absence of PS. beta-Carotene, retinol, retinal, retinoic acid, etretinate (trimethyl methoxyphenyl analog of retinoic acid), and isotretinoin (13-cis-retinoic acid) were tested for their effects on enzyme activity. Retinoic acid, etretinate, and isotretinoin stimulated enzyme activity in the absence of PS-DO, but inhibited PS-DO stimulated activity. The remaining compounds had no significant effect of C-kinase. In the presence of PS alone, these 3 retinoids had no effect on enzyme activity whereas retinoic acid and isotretinoin exhibited a dual effect of C-kinase in the presence of DO alone. Although the active retinoids seem to compete for binding sites on the enzyme with DO, the overall interaction among retinoids, DO, PS, and PMA appears to be more complex.
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PMID:Retinoid effect on calcium, phospholipid-dependent protein kinase from mouse skin. 374 56

Treatment of mouse fibroblast BALB/c 3T6 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate or the antipromoter retinoic acid affects the release of several glycoproteins into the medium. The phorbol ester decreases the secretion of a 180-kd and 160-kd glycoprotein and increases the release of a 38-kd glycoprotein. In contrast, retinoic acid affects these glycoproteins in the opposite way. Moreover, retinoic acid enhances the level of a 55-kd and 60-kd glycoprotein. The 180-kd and 160-kd glycoproteins appear sensitive to collagenase and after pepsin treatment are converted to bands which comigrate with collagen alpha 1 (I) and alpha 2 (I). These glycoproteins are tentatively identified as being pro alpha 1 (I) and pro alpha 2 (I). The 38-kd glycoprotein appears to comigrate with the major excreted protein. Retinoic acid appears to reduce significantly the incorporation of mannose into secreted glycoproteins whereas treatment with the phorbol ester induces an enhancement in mannose incorporation. Our results indicate that both phorbol esters and retinoids alter the release of several glycoproteins from 3T6 mouse fibroblasts. These changes appear to relate to the influence of these compounds on the expression of the transformed phenotype of these cells.
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PMID:Retinoic acid and 12-O-tetradecanoylphorbol-13-acetate alter release of glycoproteins from mouse fibroblast BALB/C 3T6 cells. 391 54

Tumour-promoting phorbol diesters are mitogenic for lymphocytes and induce differentiation of B and T cell lines as well as promyelocytic leukaemia cells. This paper demonstrates that 12-O-tetradecanoyl-13-acetate (PMA), when cocultured with normal murine bone marrow cells (BMC), significantly augments an antigenic cell-surface determinant called 14D10. This antigen is present constitutively in the majority of bone-marrow lymphocytes of autoimmune lpr mice. PMA has little enhancing effect when cocultured with lpr BMC. In addition, Ia antigenic determinants are increased by PMA in normal but not lpr BMC. Retinoic acid (RA) and PMA act synergistically both to increase 14D10 and to enhance the stimulatory ability of target lymphocytes as measured by proliferation in an autologous mixed lymphocyte reaction (AMLR). We suggest that lpr mice have persistent expression of gene products like 14D10 that are usually repressed in normal adult mice. These gene products can be activated in normal mouse bone marrow by PMA which acts through a Ca2+-dependent phospholipid-dependent C protein kinase. The in vivo enhanced expression of 14D10 in lpr mice suggests activation by some mechanism or factors yet to be described.
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PMID:Phorbol ester induction of Ia and a shared B-cell/T-cell phenotype in normal but not autoimmune (lpr) mice. 393 28

Chondrosarcoma is a malignant cartilage-forming tumor that affects predominently the middle-aged population. There are three histologic grades, but differentiation of Grade I tumors from enchondromas can be difficult. The measurement of polypoidy (augmented chromosomal content per cell) appears to offer a method of segregation of benign from low-grade from high-grade tumors. With the exception of the high-grade spindle elements, current chemotherapy does not appear to affect chondrosarcomas. Retinoic acid, however, by enhancing lysosomal enzyme release, may be a potential efficacious therapeutic agent. Enhanced tumor staging as provided by the computed tomographic (CT) scan has demonstrated the boundaries for wide surgical excisions, most notably internal hemipelvectomies for low- and moderate-grade pelvic chondrosarcomas. Currently, low-grade chondrosarcomas have an overall five-year survival of 65%--85% in contradistinction to 15% for the highest grade chondrosarcomas.
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PMID:Chondrosarcoma. 395 3

Inhibition of intercellular junctional communication by 12-O-tetradecanoylphorbol-13-acetate (TPA) and retinoids was investigated using a citrulline incorporation assay. This new assay uses metabolic co-operation between argininosuccinate lyase-deficient human fibroblasts and arginosuccinate synthetase-deficient cells as a measure of junctional communication. Short-term exposure to TPA resulted in virtually complete inhibition of metabolic co-operation when V79 cells were used as the synthetase-deficient type. When synthetase-deficient human fibroblasts were used, inhibition by TPA was only partial. Exposure to high concentrations of TPA for prolonged periods resulted in partial reversal of communication inhibition and a refractory state in which cells were unresponsive to TPA. Retinoic acid and other retinoids also inhibited metabolic co-operation, but did not cause desensitisation of the type seen with TPA after prolonged exposure. Cultures which had been made refractory to TPA remained sensitive to inhibition by retinoic acid and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, indicating that these latter compounds inhibit junctional communication by a mechanism different from TPA. Simultaneous exposure of cultures to TPA and retinoic acid showed that the inhibitory effects on metabolic co-operation of these compounds were additive. Fluocinolone acetonide did not antagonise the effect of TPA. These results suggest that retinoic acid and fluocinolone acetonide exert their anti-tumor-promoting action by mechanisms which are not mediated by intercellular junctional communication.
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PMID:Effects of 12-O-tetradecanoylphorbol-13-acetate and retinoids on intercellular junctional communication measured with a citrulline incorporation assay. 398 68

The effect of different retinoids on morphological transformation and anchorage independent growth of Syrian hamster embryo cells has been studied. Retinoic acid and its derivatives were found to induce morphological transformation of hamster embryo cells, and to synergistically increase the transformation frequency when exposed in combination with benzo[a]pyrene. The increase was maintained when the cells were sequentially exposed to benzo[a]pyrene and retinoids in a similar way as observed for tumor promoting phorbol esters. At the same time retinoids were found to strongly decrease anchorage independent growth of a hamster embryo cell line. The present results support previous findings indicating that retinoids may have an enhancing effect on the early stages in carcinogenesis, and an inhibitory effect on the later stages.
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PMID:Retinoids have different effects on morphological transformation and anchorage independent growth of Syrian hamster embryo cells. 401 75


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