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)

Studies from this laboratory, employing a hairless mouse model, have indicated that a polyunsaturated fatty acid source rich in omega-3 (n-3) fatty acid (FA) inhibits ultraviolet (UV)-carcinogenic expression, when compared to that of diets containing predominantly n-6 fatty acids. Omega-3 FA is a poor substrate for cyclooxygenase, the rate-limiting step in prostaglandin (PG) synthesis--the latter, particularly PGE2, are known to influence tumor biology. Based upon this rationale, plasma and cutaneous PGE2 levels were determined from hairless mice fed diets containing either 4% or 12% corn or menhaden oil. After two weeks on the respective diets, plasma PGE2 levels of corn oil-fed animals were approximately 6-fold greater than those of the menhaden oil-fed groups. A similar response was found in the dermis. Although the relationship to carcinogenic expression is unknown, dietary n-3 FA content can have a pronounced effect upon PGE2 levels and possesses the potential for influencing other immunomodulators.
 ...
PMID:Influence of omega-3 and omega-6 fatty acid sources on prostaglandin levels in mice. 277 Apr 27

Some postulates of a hypothesis concerned with the deregulation of muscle turnover by the hypoketonemia of cachectic tumor-bearing rats were examined. Plasma concentrations of ketone bodies (D-(3)-hydroxybutyrate + acetoacetate) in rats bearing the Walker 256 carcinosarcoma were reduced by 45% (P less than 0.001) whereas the concentrations of triglyceride and free fatty acids were elevated by 223% (P less than 0.001) and 335% (P less than 0.001), respectively. Parallel with the changes in plasma, the livers of tumor-bearing animals showed decreased concentrations of KB by 35% (P less than 0.05) and increased concentrations of TG and FFA by 49% (NS) and 15% (NS), respectively. In comparison with values for the control liver (fed ad libitum), the perfused liver of animals bearing the Walker 256 tumor formed 42% (P less than 0.05) and 75% (P less than 0.05) less ketone bodies and CO2, respectively, from oleate, while TG formation was enhanced by 33% (P less than 0.001). There was two- to threefold (P less than 0.001) enhancement of [1-14C]leucine oxidation in vivo by the tumor-bearing animals. The activities of branched-chain amino acid aminotransferase and branched-chain keto acid dehydrogenase were elevated by 70% (P less than 0.001) and 560% (P less than 0.001) respectively in the gastrocnemius muscle of the tumor-bearing animals. The results of the investigation supported a second proposal of the hypothesis, namely, that cancer-induced cachexia resulted in the notable elevation in the concentration of arginine vasopressin that was accompanied by parallel increases in the plasma, urine, and muscle concentrations of prostaglandin E2. The proposals of the original hypothesis have been augmented to include roles for PGE2 and the cytokine cachectin/tumor necrosis factor which may engineer all of the events depicted in the original hypothesis.
 ...
PMID:The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats: a proposed role for a cytokine, eicosanoid, and hormone trilogy. 277 64

Prostaglandins (PGs) have been shown to be increased in several tumor tissues. PGE2 and PGF1-alpha Radioimmunoassays (RIAs) have been widely used for quantitative PG-measurements in cancer patients. Our results indicate that optimal processing of plasma samples for the determination of bicyclo-PGE2 is of the highest importance in order to get reproducible results. Therefore it is necessary to fulfill the following requirements: 1. 30 minutes rest before sampling; 2. Avoid venous occlusion; 3. Use constant needle diameter; 4. Precooled anticoagulant; 5. Addition of a cyclooxygenase inhibitor is necessary; 6. Control of processing temperature; 7. Storage at -70 degrees C less than -20 degrees C; 8. Control of storage time; 9. The samples have to be examined after thawing once; 10. Only blood samples processed under the above discovered optimal conditions are of clinical relevance; 11. An international standardization for the processing of plasma samples seems to be necessary considering all these requirements; 12. In 41 patients with maxillo-facial carcinomas the PG-value was significantly higher than in the controls; 13. A RIA-evaluation methodologically properly done may be used as an additional aid for clinical monitoring of the patients.
 ...
PMID:The optimal processing of plasma samples for the determination of bicyclo-PGE in patients with malignant maxillofacial tumors. 278 Jul 59

Macrophages (Mphi) and Mphi-depleted (nonadherent) nonparenchymal cells (NPC) of the liver were examined for their cytotoxic potential against tumor cells, production of tumor necrosis factor (TNF), and release of prostaglandins (PG) following stimulation by lipopolysaccharide (LPS), interferon-gamma (IFN gamma), and zymosan. Resident murine liver macrophages had no natural cytotoxicity for the TNF-resistant target cell line P815. Activation of these cells was only obtained by a combination of IFN gamma and LPS. Inflammatory murine macrophages were in a primed stage and could be activated by LPS alone in the absence of IFN gamma. Rat resident macrophages resembled functionally the inflammatory macrophages of the mouse liver rather than the resident macrophages. They displayed natural cytotoxicity against all targets tested and were further activated by LPS in the absence of IFN gamma. Similar results were obtained with respect to macrophage-depleted nonadherent NPC: Mouse NPC had a low level of NK activity against Yac-1 cells. Treatment with pyran copolymer resulted in a strong increase of cytotoxicity against Yac-1; furthermore, a TNF-dependent killing of Wehi 164 and TNF-independent cytotoxicity against P815 cells were now acquired. In the rat NPC prepared from unstimulated animals expressed high levels of natural cytotoxicity against all targets. No major differences could be observed between inflammatory Mphi and Kupffer cells of rat and mouse liver with regard to TNF production and TNF-dependent killing of Wehi 164 tumor cells. The same was true for the spectrum of secreted prostanoids. Upon activation of all cell populations a marked shift toward the production of PGE2 occurred. Experiments involving the cyclooxygenase inhibitor indomethacin showed enhanced TNF-dependent tumor cell killing by nonactivated Mphi in the absence of prostanoid production.
 ...
PMID:Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages. 278 25

We have recently reported on the effect of PGE2 on T cell activation and suggested that their immunosuppressive effect may involve the PKC activation pathway. In the present study, we further investigated the potential interference of PGE2 with PHA induced signaling in T lymphocytes. We demonstrate that the PHA mediated increase in IP3, the putative mobilizer of intracellular Ca2+, is slightly affected following cell incubation with PGE2. Treatment of cell culture with the tumor promoter TPA abrogates the suppressive activity of PGE2 whereas exogenous diacylglycerol (1,2-diolein) has only a marginal effect. This suggests that PGE2 affect PKC activity at sites distal to IP3 and DG generation. We also demonstrate that the PGE2 suppressive effect on T lymphocyte activation is not related to an inhibition of PKC translocation.
 ...
PMID:The inhibitory effect of PGE2 on T cell activation is not associated with inhibition of PKC translocation. 278 52

The antitumor activity of indomethacin (IND) was investigated in mice bearing advanced colon 26 adenocarcinoma compared with its early transplants. Treatment with 0.001% IND in drinking water retarded the growth of tumor when commenced at Day 1 after the tumor inoculation. The suppression of the tumor growth by IND continued up to 4 to 5 weeks as long as the size of the tumor remained small. On the other hand, IND given to mice bearing a large burden of the tumor at 2 weeks after the inoculation had facilitated the tumor growth. IND reduced tumor-associated PGE2 production in mice bearing either small or large burdens of the tumors. These results indicate that the antitumor activity of IND depends on tumor size and therefore is not simply associated with the reduction of PGE2 levels. We found that colon 26 caused changes in parameters reported for tumor cachexia, such as weight loss, wasting of muscle and adipose tissues and hypoglycemia, when it grew to around 1 g at 2-3 weeks after the tumor inoculation. IND given to the mice with large burdens of colon 26 alleviated the cachexia of the mice, resulting in the increase of the survival time even though the growth of the tumor had been facilitated. It is possible that IND affects the tumor growth and survival by reversing tumor-induced disorders in homeostasis.
 ...
PMID:Antitumor activity of indomethacin in mice bearing advanced colon 26 carcinoma compared with those with early transplants. 279 Aug 9

AOM was administered subcutaneously once a week for 11 consecutive weeks to the rat. On the 15th and 30th week after starting of AOM injection, PGE2 content of the colonic mucosa, tumor and blood of portal vein and NK activity of the spleen and mesenteric lymph node (MLN) were evaluated. On the 15th week, a significant high value of the PGE2 content of colonic mucosa was shown when compared with that of the AOM non-administered group (control group). However, no significant difference was observed in the PGE2 content of blood of portal vein and NK activity of the spleen and MLN. On the 30th week, significant high values of the PGE2 content of AOM-induced tumor and blood of portal vein and low values of NK activity of the spleen and MLN were shown when compared with that of the control group. When indomethacin (IND) was administered intrarectally twice a week for 19 consecutive weeks after completion of AOM injection, induced-colon tumors was significantly suppressed. For this reason, it is important to administer IND at the point when the PGE2 content of colonic mucosa begins to augment.
 ...
PMID:[Effects of indomethacin and prostaglandin E2 administered intrarectally on colon carcinogenesis induced by azoxymethane (AOM) in rats]. 281 Aug 50

Arachidonic acid inhibits the cell shrinkage observed in Ehrlich ascites tumor cells during regulatory volume decrease (RVD) or after addition of the Ca ionophore A23187 plus Ca. In Na-containing media, arachidonic acid increases cellular Na uptake under isotonic as well as under hypotonic conditions. Arachidonic acid also inhibits KCl and water loss following swelling in Na-free, hypotonic media even when a high K conductance has been ensured by addition of gramicidin. In isotonic, Na-free medium arachidonic acid inhibits A23187 + Ca-induced cell shrinkage in the absence but not in the presence of gramicidin. It is proposed that inhibition of RVD in hypotonic media by arachidonic acid is caused by reduction in the volume-induced Cl and K permeabilities as well as by an increase in Na permeability and that reduction in A23187 + Ca-induced cell shrinkage is due to a reduction in K permeability and an increase in Na permeability. The A23187 + Ca-activated Cl permeability in unaffected by arachidonic acid. PGE2 inhibits RVD in Na-containing, hypotonic media but not in Na-free, hypotonic media, indicating a PGE2-induced Na uptake. PGE2 has no effect on the volume-activated K and Cl permeabilities. LTB4, LTC4 and LTE4 inhibit RVD insignificantly in hypotonically swollen cells. LTD4, moreover, induces cell shrinkage in steady-state cells and accelerates the RVD following hypotonic exposure. The effect of LTD4 even reflects a stimulating effect on K and Cl transport pathways. Thus none of the leukotrienes show the inhibitory effect found for arachidonic acid on the K and Cl permeabilities. The RVD response in hypotonic, Na-free media is, on the other hand, also inhibited by addition of the unsaturated oleic, linoleic, linolenic and palmitoleic acid, even in the presence of the cationophor gramicidin. The saturated arachidic and stearic acid had no effect on RVD. It is, therefore, suggested that a minor part of the inhibitory effect of arachidonic acid on RVD in Na-containing media is via an increased synthesis of prostaglandins and that the major part of the arachidonic acid effect on RVD in Na-free media, and most probably also in Na-containing media, is due to the inhibition of the volume-induced K and Cl transport pathways, caused by a nonspecific detergent effect of an unsaturated fatty acid.
 ...
PMID:Effect of arachidonic acid, fatty acids, prostaglandins, and leukotrienes on volume regulation in Ehrlich ascites tumor cells. 282 79

The M1-A5 cell line, isolated from the spleen of a tumor bearing mouse, has been shown to secrete a suppressor cell-inducing factor (SIF) which activates suppressor cells from the spleen cells of unprimed mice. In an earlier publication we demonstrated that prostaglandins of the E series (PGE) regulate the release of SIF from M1-A5 cells. In the present study we provide evidence that cyclic adenosine 3',5'-monophosphate (cyclic AMP) is the second messenger for PGE in regulating the release of SIF from M1-A5 cells. Our data show that PGE1 and PGE2 stimulate cyclic AMP production by M1-A5 cells. Furthermore, we show that drugs which: (1) elevate cyclic AMP levels (dibutyryl (db) cyclic AMP), (2) inhibit the breakdown of cyclic AMP (theophylline), or (3) stimulate adenylate cyclase (isoproterenol and histamine) all restored suppressor cell activation by M1-A5 cells in which PG synthesis had been blocked by acetylsalicylic acid (ASA). Thus, these results are consistent with the hypothesis that cyclic AMP is the second messenger for PGE in modulating the release of SIF from M1-A5 cells.
 ...
PMID:Cyclic AMP as the second messenger for prostaglandin E in modulating suppressor cell-activation by natural suppressor/cytotoxic cells. 282 50

Two omega-3 fatty acids present in fish oil are effective inhibitors of some models of mammary and colon tumorigenesis in rodents. The present studies were conducted to determine if eicosapentaenoic and docosahexaenoic acids can modify the growth of DU-145 human prostatic tumor cells in nude mice. Two experimental diets tested contained either 23.52% corn oil or 20.52% fish oil, plus 3% corn oil (w/w). In the fish oil-fed group of mice: (a) tumor growth was significantly inhibited; (b) tumor cells in histological sections were smaller but more connective tissue was present; (c) immunochemical staining for human prostatic acid phosphatase was less intense, and (d) tumor content of PGE2 was smaller than in the 23.52% corn oil-fed group. Fatty acid composition of phosphoglyceride and neutral lipid fractions of liver, prostate, and tumor tissue reflect the dietary intake of omega-3 and omega-6 fatty acids. These results are consistent with a role for omega-3 fatty acids in the inhibition of growth of human prostatic tumor cells in nude mice by dietary modification.
 ...
PMID:The effects of dietary omega-3 fatty acids on the DU-145 transplantable human prostatic tumor. 283 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>