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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoid synthesis by alveolar macrophages (AM), harvested from tumor bearing animals, was measured after tumor inoculation in rats treated with or without carrageenan (carra), an immunomodulating agent. After incubation of the cells with [14]C-arachidonic acid and the Ca-ionophore A23187, samples were measured by high pressure liquid chromatography (HPLC). From the HPLC profiles the lypoxygenase products, 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, and leukotriene-B4 (LTB4) were determined as well as the cyclooxygenase products, prostaglandin (PG)E2, PGF2 alpha and TXB2. After tumor inoculation AM-synthesis of lipoxygenase products tended to increase to values twice those of the base line values, whereas cyclooxygenase products showed subnormal values. In the non treated animals, 10 days after tumor inoculation, statistically significant increases in 12- and 15-HETE, LTB4 and PGE2 were observed when compared with carra treated animals. Later measurements did not show these differences in AM metabolism. AM metabolism was (negatively) correlated with the number of macrophages, which was particularly evident in the correlation with 12-HETE synthesis.
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PMID:Eicosanoid synthesis by alveolar macrophages in rats with malignant mammary tumors: differences in rats treated with and without carrageenan implants. 255 Sep 68

The effect of prostaglandin E1, E2, and F2 alpha on gamma-radiation, benzo(a)pyrene and diphenylhydantoin-induced cytotoxicity in vivo and genotoxicity in vitro was investigated. Prostaglandin E1 prevented both cytotoxic and genotoxic actions of all the three agents, where as both PGE2 and PGF2 alpha were ineffective. In fact, it was seen that both PGE2 and PGF2 alpha are genotoxic by themselves. Gamma-linolenic acid and dihomogamma-linolenic acid, the precursor of PGE1 were also as protective as that of PGE1, where as arachidonic acid, the precursor of 2 series PGs, has genotoxic actions to human lymphocytes in vitro. These results suggest that prostaglandins and their precursors can determine the susceptibility of cells to cytotoxic and genotoxic actions of chemicals and radiation. This study is particularly interesting since, it is known that some tumor cells contain excess of PGE2 and PGF2 alpha and many carcinogens can augment the synthesis of 2 series of PGs.
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PMID:Prostaglandins can modify gamma-radiation and chemical induced cytotoxicity and genetic damage in vitro and in vivo. 263 11

Hypercalcemia is one of well-recognized paraneoplastic syndromes and occurs occasionally in patients with oral cancers. Because bone is the richest source of calcium in the body, it has been proposed that humoral bone resorbing factors which are released by tumors are responsible for the pathogenesis of hypercalcemia. In the present study, partial purification and identification of bone resorbing humoral factors were carried out employing VX2 squamous cell carcinoma which has been known to induce hypercalcemia in rabbits. In addition, extra- and intra-cellular mechanisms which are operating to confer autonomous growth on VX2 cancer cells were also studied. VX2 carcinoma induced marked hypercalcemia not only in rabbits but also in nude mice in parallel with tumor enlargement. Administration of indomethacin (INDO), a prostaglandin (PG) synthesis inhibitor, before onset of the hypercalcemia prevented an elevation of serum calcium levels and growth of the tumor. INDO, however, failed to decrease serum calcium levels and tumor growth when administered after development of the hypercalcemia and tumor enlargement. These results indicate that not only PGs but other humoral factors are involved in the pathogenesis of the hypercalcemia seen in VX2 cancer-bearing animals. VX2 cancer cells in culture retained their cancerous phenotypic properties, synthesized PGE2, PGF2 alpha and 6-keto PGF1 alpha and secreted highly levels of PGE2, a powerful bone resorber, into the culture medium in a time- and cell density-dependent manner. The culture supernatants also contained a trypsin- and heat-sensitive bone risorbing factor (BRF) with a molecular weight of approximately 20kD. BRF was presumed to be similar to parathyroid hormone related protein (PTHrP) from its biological and biochemical behaviors. Both PGE2 and PTHrP promoted VX2 cell growth, thus suggesting that these two substances are autocrine growth factors for VX2 cells. Calcium stimulated VX2 cell growth and secretion of PGE2 and BRF (PTHrP) in a concentration-dependent fashion. Stimulation of VX2 cell proliferation by PGE2 and PTHrP was closely correlated with a transient elevation of intracellular free calcium ion ([Ca2+]i). [Ca2+]i elevated transiently in response to PGE2 and PTHrP was shown to be supplied by influx of extracellular free calcium ion ([Ca2+]e) through calcium channel present in plasma membrane. Involvement of protein kinase C in autocrine growth stimulation of VX2 cells by PGE2 and PTHrP was unclear. These results demonstrate that PGE2 and PTHrP secreted by VX2 cancer cells not only induce hypercalcemia but promote VX2 cell growth as autocrine growth factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Mechanism of hypercalcemia associated with malignancy: interactions between induction of hypercalcemia and autonomous growth in VX2 cancer cells]. 263 47

Immunomodulation is interpreted as a temporary alert in a certain part of the immune system. The activation of immune competent cells is presented as a possible basic mechanism of this phenomenon. In the absence of a primary stimulus, immunomodulation remains physiologically silent, but it results in a modified immune response if the corresponding targets are being stimulated. For practical reasons it is suggested that distinctions be made between preventive and regulative immunomodulation. The PWM-induced IgG production of PBMCs was used as a model for the demonstration of the modulatory effect of thymopentin in vitro. Depending on the concentration of thymopentin used in the cultures, this pentapeptide can either stimulate or inhibit the induced IgG production. It also influences PGE2 production and catabolism in the cultures stimulated with PWM. Indomethacin abolishes the modulatory effect of thymopentin on IgG production in this model. It is suggested that the possibility of interactions between an immune modulator and therapeutic approaches which can influence the proportions or functions of the corresponding target cells be considered.
Med Oncol Tumor Pharmacother 1989
PMID:Immunomodulation with thymopentin: in vitro studies. 265 46

LF 1695, a synthetic immunomodulator with a low mol. wt, has been shown to exert its activity on T-lymphocytes and macrophages. It induced T-cell differentiation of bone marrow precursor cells which acquired the expression of CD3, CD4 and/or CD8. It increased lymphocyte proliferative responses to mitogens, antigens and allogeneic cells. IL-2 production was increased in Con A-activated but not in resting lymphocytes. Added to macrophages, LF 1695 augmented IL-1 production and LTB4 synthesis but it decreased PGE2 secretion. Hematological reconstitution of animals, following bone marrow alteration by irradiation or chemotherapy, was accelerated. Many of the effects of this compound may result from the enhancement of interleukin production, by macrophages especially. After investigations of LF 1695 effect on HIV-infected cells, clinical trials have been initiated in AIDS and ARC patients.
Med Oncol Tumor Pharmacother 1989
PMID:Effect of the immunomodulator LF 1695 on T-lymphocytes and macrophages. Activity in HIV infection. 265 51

It has been recently observed that arachidonic acid (AA) metabolites may modulate many of the mechanisms involved in tumor growth and metastasis. In order to clarify the role played in human brain tumors, authors have determined AA metabolic profiles in 63 surgical specimen of human intracranial tumors (mostly neuroepithelial tumors and meningiomas). The five metabolites via the cyclooxygenase pathway (PGD2, PGE2, TxB2, PGF2a, 6-Keto-PGF1a) were measured by high resolution gas chromatography-mass spectrometry after "ex vivo" metabolism of endogenous AA by tumor homogenates. The overall synthesis capacity of AA metabolites widely varied among different oncotypes, and, except in two cases of dermoid cysts, was higher than in normal brain tissue. AA metabolism seems more active in neuroepithelial tumors with the highest grade of anaplasia; some changes in the percentage of each metabolite is evident when anaplastic features changed. Thromboxane B2 was the most represented and 6-Keto-PGF1a the less abundant metabolite. Meningiomas and neuroepithelial tumors showed different relative proportion of AA metabolites which have in some cases reported to positively or negatively affect tumor growth. In histological subgroups of meningiomas AA metabolites synthesis capacity did not show any statistical difference. In the six cases of brain metastasis there is a wide range of overall synthesis capacity, with predominant synthesis of thromboxane B2 and prostaglandin E2, while the percentage of prostaglandin D2, reported as antimetastatic, is very low.
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PMID:Prostaglandins in human brain tumors. 267 60

We investigated the effects of host inflammatory cells on the progression of QR (C57BL/6 mouse) and ER (SHR rat) regressor tumor cells which spontaneously regress in normal syngeneic hosts. We noted an enhanced tumorigenicity of regressor tumor cells after s.c. implantation with attachment to plastic plate, a situation which induces inflammation in normal hosts accompanied by the development of tumors as compared to normal mice injected with regressor tumor cells in suspension in PBS- which spontaneously regressed. We also observed enhanced tumorigenicity of regressor tumor cells injected into the site of the plastic plate which had been previously implanted into the normal host. Regarding these phenomena, we suggest that tumor progression may be induced by host induced inflammatory cells or their products. We also found enhanced tumor progression of QR regressor tumor cells after co-inoculation with inflammatory cells produced by the implantation of hemostatic spongel into the peritoneal cavity of mice. The mechanisms involved in the progression of regressor tumor cells by co-existence with inflammatory cells are thought to be associated with the production of oxygen radicals, tumor cell chemotactic factors, soft agar colony promoting factors and PGE2.
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PMID:[Experimental approach to the investigation of tumor progression]. 273 20

Resistance of hypoxic cells to radiation and chemotherapy remains a major limitation to effective therapy of solid tumors. Misonidazole, a 2-nitroimidazole analogue, has been studied extensively as a radiosensitizer of hypoxic cells and has been shown to undergo bioreductive metabolism to exert preferential cytotoxicity against hypoxic cells. We have investigated the effects of misonidazole on the biosynthesis of prostaglandins (PGs) in a murine mammary adenocarcinoma cell line (No. 4526) under aerobic and hypoxic conditions in attempts to exploit modulation of PG levels under hypoxia as a means of improving therapeutic approaches for the treatment of solid tumors. We report a time-dependent inhibition of PG biosynthesis by the suspended cells under hypoxia induced by flushing sealed vials with N2 (1.5 liters/min). After 30 min of hypoxia, PG formation was inhibited by 50%. Indomethacin was able to further inhibit the PG formation in a concentration-dependent manner under hypoxia. Misonidazole, however, selectively increased the PGE2 biosynthesis under hypoxia by 49% at 100 microM. This increase was concentration dependent over the range of 25 to 100 microM and was blocked by indomethacin (0.1 microM). Imidazole, the heterocyclic moiety in misonidazole without the nitro function, had no effect on PG biosynthesis at these concentrations. These data suggest that arachidonic acid metabolism is sensitive to the differential oxygen levels which exist within solid tumors and that PG levels may be modulated by electron-affinic agents in hypoxic tumor cells.
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PMID:Modulation of prostaglandin biosynthesis in hypoxic murine mammary adenocarcinoma cells by misonidazole. 273 27

Tissue levels of prostaglandins PGE1, PGE2, PGF1 alpha and PGF2 alpha were determined in muscle tissues of pregnant, and in tumor tissue of pregnant tumor-bearing female syngeneic Balb/c mice bearing a transplanted methylcholanthrene-induced fibrosarcoma. Tests were done on the 7th, 10th, and 15th days of tumor growth/pregnancy using a thin-layer chromatography method. The results showed significantly increased levels of prostaglandins in tumor-bearing animals as well as in pregnant tumor-bearing hosts when compared to controls. Changes in the levels of PGE1 in pregnant mice were the most prominent among all prostaglandins tested. In these animals, the mutual relations between prostaglandin subclasses were not affected. In tumor-bearing mice, especially those which were pregnant, the inversion of prostaglandins of the E series was observed. Tumor changed the levels of the E series prostaglandins in favour of PGE2. However, it did not change the relation between those of the F series. The levels of PGE2 were more expressed in pregnant tumor-bearing hosts than in their non-pregnant counterparts. This has led us to the conclusion that, besides the malignant tumor, the pregnancy itself also potentiates immunosuppression. Blocking of PGE2 production in tumor-bearing animals might have potential therapeutic implications.
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PMID:The levels and relations of prostaglandins in pregnant and non-pregnant tumor-bearing mice. 276 Jan 3

Two rat tumors, Morris hepatoma 7777 (MH) and Yoshida ascites hepatoma AH130 (YAH) were compared, and the influence of systemic inhibition of prostaglandin (PG) synthesis on muscle protein metabolism was evaluated. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats were also treated with naproxen, an inhibitor of PG synthesis. Tumors caused progressive anorexia and weight loss and resulted in decreased weight and/or protein content of the soleus, extensor digitorum longus, and epitrochlearis muscles. The extent of this wasting varied with muscle and tumor type. Muscle wasting induced by the tumors appeared to result from increased protein degradation and/or decreased protein synthesis, as determined in isolated epitrochlearis muscle. In YAH, reduced feed intake did not appear to be responsible for muscle wasting; however, in MH, it accounted for a significant proportion of the muscle loss. YAH produced large amounts of PGE2. Treatment of rats with naproxen inhibited tumor PGE2 production and muscle protein loss in rats bearing YAH. Naproxen had no effect on muscle weight or protein degradation in rats bearing MH. These results would appear to implicate PGE2 in the development of cachexia in the laboratory rat.
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PMID:Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats. 239 72


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