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

The concept of chemoprevention is generating increasing attention among oncologists. This article discusses the issue of dose of chemopreventive agents in relation to the stages of tumor development. Vitamin A-deficient animals have an increased susceptibility to cancer development, and epidemiologic studies have shown an inverse relationship between intake of food rich in vitamin A and/or beta-carotene and cancer risk. These data suggest that physiologic levels of these natural substances exert a protective effect against cancer development. In the presence of precursor lesions, however, this protective effect has been overwhelmed and pharmacologic doses of chemopreventive agents are required to induce regression or to arrest the progression of these lesions. Phase I pharmacologic and toxicologic studies, and Phase II dose-intensity investigation of chemopreventive agents in patients having precancerous lesions need to be carried out. Such studies would enable to select the least toxic effective chemopreventive dose for intervention trials in high-risk populations, which could then be undertaken based on evidence of activity.
 ...
PMID:Retinoid chemoprevention timing and dose intensity. 267 88

Fluorimetric method was used to measure preoperative blood plasma-vitamin A level in 100 gastric cancer patients and 64 healthy controls. The data obtained were analyzed versus site, stage and anatomic growth pattern of tumor. Vitamin A level was found to significantly decrease in 66% of gastric cancer patients, these changes being the most apparent in stage III tumor involvement of two segments of the stomach and endophytic type of growth. It is recommended that measures to correct blood plasma-vitamin A deficiency be taken in stomach cancer patients throughout treatment period.
 ...
PMID:[Blood vitamin A contents in patients with stomach cancer]. 280 Apr 44

Collagenases and other neutral proteases in tumors may facilitate tumor extension, invasion, and subsequent metastasis. We report the effects of vitamin A and dexamethasone, known inhibitors of collagenase production in vitro, on the collagen metabolism of mouse mammary adenocarcinoma and its capsule, borne by C3H/HeJ mice. The weight of the capsule was about 4% of the tumor, yet the total collagen content of the capsule was about 10-fold greater than that of the tumor tissue; tumor cells had no detectable collagen. With tumor growth, the collagenase and other neutral protease activities were increased in the tumor tissue; a negative correlation existed between collagenase activity and collagen content of the capsule. The protease activities of the tumor borne by vitamin A-treated hosts were about 50% lower than those of the controls; this coincided with a slight increase in the collagen content of the capsule. In contrast, the collagen content of the capsule borne by dexamethasone-treated hosts was 50% less than that of the controls; the protease activities were similar to the controls and occurred with tumor invasion and metastasis. Results suggest that the collagen metabolism of the capsule may be an indicator of proteolytic events within the tumor and the metastatic potential of the tumor that, in turn, suggests the possibility of preventing metastasis by inhibiting the production of collagenases and other neutral proteases, thereby localizing the tumor cells within the capsule. Vitamin A could be used for that purpose.
 ...
PMID:Effects of vitamin A and dexamethasone on collagen degradation in mouse mammary adenocarcinoma. 298 67

Different levels of beta-carotene (0, 5, 25, 125, and 250 mg/kg diet) were tested for their chemoprevention effects using 9,10-dimethyl-1,2-benzanthracene-induced salivary gland tumor model in rats. Tumor incidence and tumor weights were slightly lower in rats fed diets supplemented with 25 mg or more beta-carotene/kg diet. Hepatic vitamin A and beta-carotene levels were increased in a dose-dependent fashion, reaching a plateau at 125 mg beta-carotene/kg diet. In plasma, beta-carotene concentrations were also increased with an increase in dietary beta-carotene. Vitamin A levels in plasma were not affected. The normal salivary glands had higher concentrations of beta-carotene than did the tumors. The results suggest that the decreases in tumor incidence and tumor weight may be related to the increase in plasma and tissue levels of beta-carotene as a result of feeding high levels of beta-carotene.
 ...
PMID:The effect of different levels of dietary beta-carotene on DMBA-induced salivary gland tumors. 310 89

Retinol esterification by microsomal acyl coenzyme A:retinol acyltransferase was quantified in rat mammary tumor and liver tissue. Acyltransferase activity in the livers of mammary tumor-bearing rats was 40% of that in normal animals. In response to daily oral doses of 2 mg retinyl acetate for 18-19 days, activity increased 2.8-fold in transplanted rat mammary tumors, 4.1-fold in the livers of tumor-bearing rats, and 1.5-fold in the livers of normal rats. The in vitro esterification of retinol was competitively inhibited by all-trans-N-(4-hydroxyphenyl) retinamide (Ki = 154 microM).
 ...
PMID:Enhancement of acyl coenzyme A:retinol acyltransferase in rat liver and mammary tumor tissue by retinyl acetate and its competitive inhibition by N-(4-hydroxyphenyl) retinamide. 315 81

Protein kinase C (PKC) is a ubiquitous enzyme linked to transmembrane signal transduction. It regulates agonist-mediated activation of intracellular events that result in growth and differentiation in a variety of cells and tissues. PKC is the cellular receptor for phorbol ester tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), that bind to, and directly activate, this enzyme. Vitamin A analogs (retinoids) have been known to antagonize biologic effects of phorbol esters, e.g., promotion of skin tumor formation; however, the extract mechanism(s) of this action is not clear. To analyze the effects of retinoids on T-cell-derived PKC, we partially purified the enzyme from human leukemic T cells (Jurkat) and examined the effects of different vitamin A analogs on its activity. Furthermore, the regulatory effects of retinoids on PKC activity were compared with those of common membrane phospholipids. Retinal inhibited PKC activation induced by TPA, as well as by diacylglycerol, the physiologic activator of PKC. The observed inhibition resulted from competition with phospholipid (phosphatidylserine) and was selective for the phospholipid-dependent C kinase; cAMP-dependent protein kinase, which is phospholipid-independent, was not affected by retinal. The inhibitory effect of retinal on PKC activity was similar to that of phosphatidylcholine. Retinoic acid, in contrast to retinal, induced a Ca2+-dependent activation of PKC, thus substituting for phosphatidylserine. Furthermore, PKC activation by retinoic acid was similar to that by phosphatidylserine, the natural phospholipid cofactor, in that both could be inhibited by phosphatidylcholine and augmented by phosphatidylinositol. The inhibition or activation of PKC by retinal or retinoic acid, respectively, was independent of whether the terminal aldehyde (retinal) or carboxyl (retinoic acid) groups were in the trans or cis configuration. Other vitamin A analogs tested did not affect PKC activity. The results demonstrate that different retinoids and phospholipids may have positive or negative cooperativity in PKC activation, thereby regulating its enzymatic activity and affecting the resulting intracellular activation events. These findings suggest that at least part of the biologic effects of retinoids in general, and their modulation of T-cell function in particular, may be mediated via the influence of their intracellular metabolites on PKC, and that this mechanism may account for some of the antagonistic effects of retinoids on TPA-mediated responses in cells.
 ...
PMID:Regulation of T-cell-derived protein kinase C activity by vitamin A derivatives. 326 37

Epidemiological studies have suggested that the intake of green-yellow vegetables decrease the risk of cancer. Vitamin A, which is abundantly present in green-yellow vegetables in the form of provitamin A, was demonstrated to inhibit chemical and viral-carcinogenesis in experimental animals. However, little is known about the mechanism of anti-carcinogenic effect of vitamin A. Our data seem to support a hypothesis that vitamin A may contribute to the prevention of cancer by augmenting an immunosurveillance system. We found that vitamin A and provitamin A, beta-carotene, enhanced tumor immunity using a syngeneic murine tumor system.
 ...
PMID:[The immunological role of carotenoids in the prevention of cancer]. 348 10

Retinoids have been shown to inhibit the growth and development of neoplastic cells in many systems. One mechanism of action may be through activation of the immune system, specifically natural killer (NK) cell activity. The effect of retinol on NK cell cytotoxicity was examined in three groups of mice: BALB/c (wild-type), BALB/c nu/nu (athymic), and BALB/c nu/nu previously injected with human tumor cells. In untreated mice, NK activity was highest in athymic mice without tumors and lowest in wild-type mice, although serum and liver retinol concentrations were identical in all three groups. In mice fed graded, nontoxic doses of retinol daily for 3 weeks, serum retinol levels in all three groups exhibited a sharp peak and decline following daily bolus retinol administration. Retinol stores in the livers showed a dose-dependent increase in all treated animals. However, NK cell activity, differed for each group. Athymic mice without tumors exhibited no change in NK activity as a result of retinol treatment. Athymic mice with tumors had NK levels that tended to increase with increasing retinol doses, but these changes were not statistically significant. Wild-type mice, on the other hand, demonstrated significantly higher NK levels after treatment with retinol doses of 300 and 600 micrograms/day. In subsequent time course experiments, there was a peak in NK activity 1 h following bolus retinol administration similar to the peak seen in serum retinol concentrations, suggesting either an acute activation or recruitment of cytotoxic cells. Retinol thus appears to increase NK activity in wild-type BALB/c mice, and this activity may be an important component of its antineoplastic activity.
 ...
PMID:Effects of orally administered retinol on natural killer cell activity in wild type BALB/c and congenitally athymic BALB/c mice. 363 13

To test the possible role of protein kinase C (C-kinase) in regulating germinal vesicle breakdown (GVBD) in Spisula oocytes, we studied the effects of phorbol esters and antagonists of C-kinase on GVBD and protein phosphorylation. Responses to these agents were compared to those elicited by fertilization or increased extracellular K+. The tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent agonist of C-kinase, elicited GVBD with half-maximal stimulation at 20 nM. By contrast, 4 alpha-phorbol-12,13-didecanoate, a phorbol ester which does not stimulate C-kinase, did not trigger GVBD. TPA accelerated GVBD when induced by excess K+, but it did not affect the time course of the process when initiated by fertilization. Three structurally different antagonists of C-kinase (W-7, H-7, and retinol) all blocked GVBD when induced by fertilization or TPA. When oocytes were preincubated with [32P]orthophosphate and then stimulated to undergo GVBD by fertilization, TPA, or 45 mM K+, protein phosphorylation was greatly increased, especially for a polypeptide(s) of about 45 kDa. Phosphorylation increased prior to GVBD. Retinol inhibited phosphorylation in activated eggs. C-kinase activity was demonstrated in oocyte extracts. These results strongly suggest that protein phosphorylation by C-kinase is involved in the pathway that regulates GVBD in Spisula oocytes.
 ...
PMID:Protein kinase C activity, protein phosphorylation and germinal vesicle breakdown in Spisula oocytes. 366 13

During a state of pure vitamin A deficiency, without any clinical manifestations, in colonic mucosa: ornithine decarboxylase activity is already stimulated, in deficient animals, by instillation of NaCl 9%. Sodium deoxycholate further enhances and markedly protracts the enzyme activity, as compared to normal rats. These results lead to the conclusion that vitamin A deficiency is a state of special sensibility to the promoter action. Retinol is hence physiologically necessary for natural resistance of intestinal cells against chemically induced tumor promotion.
 ...
PMID:[Experimental cancerogenesis. Stimulation of ornithine decarboxylase of the colonic mucosa in vitamin A-deficient rats by sodium desoxycholate]. 375 61


<< Previous 1 2 3 4 5 6 7 8 9 Next >>