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)

One of the three human retinoic acid receptors, RAR-beta, maps to a region on the short arm of chromosome 3 frequently deleted in lung cancer. Because retinoic acid is required for normal epithelial cell growth and regulation, and loss of a retinoic acid receptor might be expected to contribute to oncogenesis, we examined RAR-beta RNA and DNA in normal lung, 33 lung cancer cell lines and nine primary lung tumors. Normally, RAR-beta is expressed as two transcripts, of sizes 3.1 kb and 2.8 kb, which are strongly induced by retinoic acid. At least 50% of the cell lines and 30% of the tumor samples show altered RAR-beta expression and/or inducibility, including examples of absence or specific loss of one of the RAR-beta transcripts. Abnormalities in the expression patterns of RAR-alpha and RAR-gamma also are found, but at a lower frequency than RAR-beta abnormalities. Southern analysis reveals alteration of the RAR-beta gene in three of the cell lines. Our data suggest that abnormalities in structure and expression of the RAR-beta gene may be involved in the pathogenesis of lung cancer.
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PMID:High frequency of retinoic acid receptor beta abnormalities in human lung cancer. 171 24

To examine the influence of retinol acetate (retinol, known as an inhibitor of tumor promotion) on 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB)-induced hepatocarcinogenesis, rats were fed with a diet containing 0.06% 3'MeDAB for 4 or 7 weeks and then with a normal diet for 21 or 18 weeks. Rats were given retinol (0, 6.25, 12.5 and 25.0 mg/rat, dissolved in DMSO) i.p. every 5 days from the 10th week to the 20th week. As a control, rats were fed a basal diet and given retinol at the same doses as mentioned above. At the 25th week, the incidence of hepatoma (hepatocellular carcinoma and cholangiocarcinoma) of each group was checked. In rats fed diet containing 3'MeDAB for 7 weeks, significant increases in the incidence of hepatoma were seen in retinol-treated groups at various doses. In rats fed 3'MeDAB diet for 4 weeks, all three doses also moderately, though not significantly, increased the incidence of hepatoma. No liver tumor was found in rats fed normal diet followed by treatment with retinol at any dose. Except for slight but detectable elevation of cellular retinoic acid binding protein levels in tumor tissues obtained from rats treated with retinol, no obvious differences in cellular retinol binding protein and gamma-glutamyl transpeptidase in the tumor tissues were observed between retinol-treated and untreated rats. Phytohemagglutinin-induced lymphocyte blastogenesis of the tumor-bearing rats with or without retinol treatment showed approximately 50% inhibition compared with that of rats fed normal diet without retinol treatment. These results indicated that the administration of retinol in the early stages of hepatocarcinogenesis enhanced the tumor induction, possibly due to the fixation of malignant transformation of the cells.
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PMID:The facilitated effect of retinol on rat hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. 172 Oct 9

We have investigated the effects of retinoic acid (RA), human recombinant gamma interferon (gamma-IFN), and the association of both agents on the growth of human neuroblastoma (NB) cells in [CD1(nu/nu)] nude mice. Two human NB cell lines, namely LAN-5 and GI-LI-N, were previously adapted to grow in syngeneic animals for 7 consecutive passages. At the eighth passage, only animals which developed 10-mm diameter tumors within 40 days from xenograft were admitted to the study. RA and/or gamma-IFN were administered subcutaneously 3-5 days per week for 3 consecutive weeks. The number of days necessary for each tumor mass to grow up to 20 mm diameter (in vivo doubling time, ivDT) was then evaluated. Tumor growth was significantly inhibited in gamma-IFN (P less than 0.005) and RA (P less than 0.05) treated mice grafted with GI-LI-N. The combination of the two agents did not further enhance ivDT. The tumor growth inhibition was not statistically significant in LAN-5 bearing mice treated with RA or gamma-IFN alone, while a synergistic effect between the two drugs was observed (P less than 0.05). We conclude that parenteral combined administration of RA and gamma-IFN may prove to be useful in inhibiting the growth of tumors derived from human NB cells resistant to single inducers.
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PMID:Gamma-interferon and retinoic acid synergize in inhibiting the growth of human neuroblastoma cells in nude mice. 173 46

It is becoming increasingly clear that cutaneous carcinogenesis in murine skin is a stepwise process comprising of initiation, promotion and progression. Most of the papillomas induced by an initiation-promotion protocol regress, while a few of them progress to malignant carcinomas. Progression of benign tumors into malignant cancer is critical since the latter lesions are capable of metastatic spread and eventual death. Inhibitors of the conversion process are therefore likely to be useful as cancer chemopreventive agents. All-trans retinoic acid (RA) is a known regulator of cellular proliferation and differentiation, and a known inhibitor of tumor promotion in murine skin. In this study we assessed the effect of topical application of RA on conversion of benign skin papillomas to malignant carcinomas. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) as tumor initiator followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter. In SKH-1 hairless mice papillomas were induced by thrice weekly exposure to ultraviolet B (UVB) radiation. At 18 (DMBA/TPA group) and 25 (UVB group) weeks papilloma yield stabilized and no new tumors developed. Beginning at the 20th week (DMBA/TPA group) and at the 27th week (UVB group), malignant conversion was achieved by twice weekly topical application of TPA or free radical-generating compounds benzoyl peroxide (BPO), 2,2-azobis(2-amidinopropane) (ABP) and tert-butyl peroxybenzoate (BPB). Application of RA (10 micrograms/animal) 1 h prior to skin application of TPA, BPO, ABP or BPB afforded significant protection (up to 70%) only against malignant conversion mediated by free radical-generating compounds in both chemically induced and UVB-induced benign skin papillomas. On the other hand, preapplication of RA was less effective in the suppression of spontaneous malignant conversion in vehicle-treated animals. These results suggest that, in addition to their anti-tumor promoting effects, retinoids may also act as anti-carcinogens by inhibiting the process of malignant conversion induced by free radical-generating compounds.
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PMID:All-trans retinoic acid protects against conversion of chemically induced and ultraviolet B radiation-induced skin papillomas to carcinomas. 174 35

p34cdc2 is a protein kinase that has an important role in controlling cell cycle progression and may regulate tumor suppressor gene activity. In this work, we show that the arrest of cell growth and induction of differentiation in a tumorigenic neuroblastoma cell line by retinoic acid (RA) is associated with a 75-fold decrease in the level of p34cdc2 protein. The RA induced decrease in p34cdc2 levels does not simply reflect the arrest of cell growth, because p34cdc2 levels are not reduced when neuroblastoma cells are growth arrested by nutrient deprivation. Furthermore, dephosphorylation of the tumor suppressor gene product RB, a substrate for the p34cdc2 kinase activity, is observed only when p34cdc2 levels are decreased in RA treated cells. These studies link regulation of cdc2 level, RB phosphorylation state, and induction of differentiation by RA and suggest that alterations in the cdc2 gene or in genes controlling its regulation contribute to tumorigenesis.
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PMID:Retinoic acid negatively regulates p34cdc2 expression during human neuroblastoma differentiation. 175 5

Ornithine decarboxylase (ODC) activity of C3H/10T1/2 cells reflects their response to conflicting actions of many tumor promoters and tumor suppressors. In cultured C3H/10T1/2 cells, addition of vanadate (50 nM) increased ODC activity. Over the range 0.05-5 microM, vanadate increased ODC levels in a dose dependent manner to 11 times control levels. The presence of retinoic acid (5 microM) or the absence of fetal calf serum blocked the stimulation by vanadate.
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PMID:Vanadate stimulates ornithine decarboxylase activity in C3H/10T1/2 cells. 177 24

Several studies have correlated the excessive production of prostaglandins (PGs) with tumor promotion and the suppression of the immune response. Inhibition of PGs by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. In this study we examined the effect of retinol (I), all-trans-retinoic acid (II), N-(4-Hydroxyphenyl) retinamide (N-4-HPR) (III), canthaxanthin (CTX) (IV), and beta-carotene (beta-CT) (V) on the bioconversion of 14C-arachidonic acid (AA) to PGE2 by squamous carcinoma cells of the tongue, SCC-25. Agents (I), (II), (III), (IV) inhibited while (V) stimulated PGE2 formation in a dose related manner. N-4-HPR was the most potent inhibitor of PGE2 synthesis. The data suggest that certain retinoids and carotenoids have the potential of inhibition of PG synthesis by oral squamous carcinoma cells. Inhibitory effects such as those described here and antioxidant properties might in part contribute to the antiinflammatory and anticarcinogenic activity of retinoids in vivo.
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PMID:Effect of retinoids and carotenoids on prostaglandin formation by oral squamous carcinoma cells. 183 Dec 72

Transforming growth factor-beta (TGF-beta) plays a complex role as a regulator of proliferation and differentiation of many cell types, including cells of epithelial origin. In this study, we examined whether TGF-beta, alone or in combination with retinoic acid, was able to inhibit the transformation of the murine epidermal cell line JB6. When treated with phorbol myristate acetate (PMA) and other tumor promoters, the nontumorigenic and anchorage-dependent JB6 cells acquired a tumor phenotype, as shown by the acquisition of tumorigenicity and anchorage independence. We found that TGB-beta inhibited the PMA-induced transformation of a subclone of JB6 cells. The effect of TGF-beta was due to an anti-transformation promoting activity, rather than to generalized growth inhibition, since TGF-beta neither inhibited the growth of monolayer cultures of JB6 cells, nor affected the colony-forming efficiency in agar of the JB6-derived permanently transformed RT101 cell line. TGF-beta was synergistic with retinoic acid, a known anti-tumor promoter, in inhibiting the PMA-induced transformation of JB6 cells. Examination of TGF-beta receptor expression on JB6 cells, by both binding and affinity labeling, showed that treatment with PMA significantly decreased TGF-beta receptor expression while retinoic acid counteracted this effect of PMA, thus suggesting that the synergy between retinoic acid and TGF-beta may be due, at least in part, to modulation of TGF-beta receptor expression. TGF-beta, therefore, appears to function as an incomplete antipromoter whose action can be permitted and/or complemented by retinoic acid. Our data demonstrating that TGF-beta has anti-transformation promoting activity suggest that TGF-beta plays a role in maintaining homeostasis of epithelial cells, not only by regulating cell proliferation and differentiation, but also by counteracting events that lead to malignant transformation.
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PMID:Synergistic inhibition of phorbol ester-induced transformation of JB6 cells by transforming growth factor-beta and retinoic acid. 184 57

A rare case of Turcot's syndrome is reported in a long-time survivor of glioblastoma multiforme. The patient was treated for his tumor in 1976 with macroscopically complete surgical resection and radiotherapy consisting of 60 Gy to the tumor bed and 40 Gy to the whole brain. Five years later, in 1981, he developed adenocarcinoma of the colon Dukes Stage B which was successfully treated at another hospital by surgery alone. In 1990, he presented with multiple colon polyps and adenocarcinoma Dukes Stage A. For more than 15 years, the patient has been afflicted with cystic and conglobate acne. Possible mechanisms and treatment with 13-cis retinoic acid are discussed.
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PMID:Long-time survival of a patient with glioblastoma and Turcot's syndrome. Case report. 184 56

A 35-year-old man with refractory cutaneous Ki-1 lymphoma was salvaged successfully with oral 13-cis-retinoic acid (1 mg/kg/day). He had a complete remission lasting for 20 months before a single nodule recurred on his skin. Excisional biopsy of the recurrent tumor revealed a distinct morphologic change, suggesting cellular differentiation toward a more benign phenotype. No significant side effects were noted except mild xerostomia, bone pain, and hyperlipidemia. The authors believe that 13-cis-retinoic acid should be considered in the treatment of cutaneous Ki-1 lymphoma.
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PMID:13-cis-retinoic acid induces cellular differentiation and durable remission in refractory cutaneous Ki-1 lymphoma. 184 87


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