Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer

Baxevanis, Constantin N.; Reclos, George J.; Gritzapis, Angelos D.; Dedousis, G.; Missitzis, Ioannis; Papamichail, Michael

doi:10.1002/1097-0142(19930715)72:2<491::aid-cncr2820720227>3.0.co;2-1

Cited by 109 publications

(52 citation statements)

References 29 publications

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“…Prostaglandins were able to make macrophages and/or lymphocytes less sensitive to various stimuli (Pelus and Strausser, 1977;Schultz et al, 1978). Moreover, prostaglandin E 2 suppressed NK cells and lymphokine-activated killer (LAK) cells (Ohnishi et al, 1991;Roth and Golub, 1993;Baxevanis et al, 1993). The present studies showed that hepatic PGF 2R and PGE 2 concentrations were significantly increased in FB 1 -induced promotion of rat hepatocarcinogenesis (Tables 3 and 4), and in the female rats fed purified FB 1 , liver-associated antitumor response was decreased (Figure 1).…”

Section: Discussionmentioning

confidence: 50%

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Dantzer

Hopmans

et al. 1997

J. Agric. Food Chem.

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Fumonisin B1 (FB1) was reacted with fructose in an attempt to detoxify this mycotoxin. Fischer 344/N rats were initiated with diethylnitrosamine (15 mg/kg body weight) and then fed 69.3 μmol FB1/kg diet or 69.3 μmol FB1 reacted with fructose (FB1−fructose)/kg diet for 4 weeks. In comparison with the rats fed basal diet or FB1−fructose, the FB1-fed rats had significantly increased plasma cholesterol (P < 0.01), plasma alanine aminotransferase activity (P < 0.05), and endogenous hepatic prostaglandin production (P < 0.05). Placental glutathione S-transferase-positive and γ-glutamyl transferase-positive altered hepatic foci occurred only in the FB1-fed rats. Liver-associated natural killer (NK) cell activity was significantly decreased in the FB1-fed rats and increased in the group fed FB1-fructose, as compared with the basal group (P < 0.03). Therefore, modifying FB1 with fructose seems to prevent FB1-induced hepatotoxicity and promotion of hepatocarcinogenesis while stimulating liver-associated NK cell activity in rats. Fumonisin B 1 (FB 1 ) was reacted with fructose in an attempt to detoxify this mycotoxin. Fischer 344/N rats were initiated with diethylnitrosamine (15 mg/kg body weight) and then fed 69.3 µmol FB 1 /kg diet or 69.3 µmol FB 1 reacted with fructose (FB 1 -fructose)/kg diet for 4 weeks. In comparison with the rats fed basal diet or FB 1 -fructose, the FB 1 -fed rats had significantly increased plasma cholesterol (P < 0.01), plasma alanine aminotransferase activity (P < 0.05), and endogenous hepatic prostaglandin production (P < 0.05). Placental glutathione S-transferase-positive and γ-glutamyl transferase-positive altered hepatic foci occurred only in the FB 1 -fed rats. Liver-associated natural killer (NK) cell activity was significantly decreased in the FB 1 -fed rats and increased in the group fed FB 1 -fructose, as compared with the basal group (P < 0.03). Therefore, modifying FB 1 with fructose seems to prevent FB 1 -induced hepatotoxicity and promotion of hepatocarcinogenesis while stimulating liver-associated NK cell activity in rats.

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Section: Discussionmentioning

confidence: 50%

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Dantzer

Hopmans

et al. 1997

J. Agric. Food Chem.

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“…8 -10 A large body of evidence has shown PGs to have immune suppressive roles in cancer indicating host-related mechanisms responsible for tumor progression. 15,17,25,28 However, studies that investigated the direct role of PGs in tumorrelated mechanisms, i.e., tumor cell functions that are required for tumor progression, have been limited. 29 -31 The present study in our murine mammary tumor model revealed that tumor-derived PGs owing to COX-2 expression by tumor cells stimulated their migration and invasiveness as well as tumorinduced angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis

2001

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Tumor-derived prostaglandins (PGs) have been implicated in the progression of murine and human breast cancer. Chronic treatment with a non-selective PG inhibitor indomethacin was shown in this laboratory to retard the development and metastasis of spontaneous mammary tumors in C3H/HeJ female retired breeder mice. The present study examined the role of endogenous prostaglandins in the proliferation/survival, the migratory and invasive behavior and angiogenic ability of a highly metastatic murine mammary tumor cell line, C3L5, originally derived from a C3H/HeJ spontaneous mammary tumor. This cell line was shown to express high levels of cyclooxygenase (COX) -2 mRNA and protein as detected by Northern and Western blotting as well as immunostaining. PGE 2 production by C3L5 cells was primarily owing to COX-2, since this was blocked similarly with non-selective COX inhibitor indomethacin and selective COX-2 inhibitor NS-398, but unaffected with the selective COX-1 inhibitor valeryl salicylate. C3L5 cell proliferation/survival in vitro was not influenced by PGs, since their cellularity remained unaffected in the presence of PGE 2 or NS-398 or PG-receptor (EP1/EP2) antagonist AH6809; a marginal decline was noted only at high doses of indomethacin, which was not abrogated by addition of exogenous PGE 2 . Migratory and invasive abilities of C3L5 cells, as quantitated with in vitro transwell migration/invasion assays, were inhibited with indomethacin or NS-398 or AH6809 in a dose-dependent manner; the indomethacin and NS-398-mediated inhibition was partially reversed upon addition of exogenous PGE 2 . An in vivo angiogenesis assay that used subcutaneous implants of growth factor-reduced matrigel inclusive of tumor cells showed a significant inhibition of blood vessel formation in these implants in animals treated with indomethacin compared with animals receiving vehicle alone. These studies show that selective and nonselective COX-2 inhibitors retarded tumor progression in this COX-2-expressing murine mammary tumor model by inhibiting tumor cell migration, invasiveness and tumor-induced angiogenesis. The inhibitory effects were not entirely PG dependent; some PG-independent effects were also noted. Prostaglandins (PGs) produced by tumor cells or tumor-associated host cells (macrophages, endothelial cells and stromal cells) have long been considered to play a stimulating role in the progression and metastases of a variety of animal and human tumors including mammary tumors. Malignant breast tumors produce more PGs than normal breast tissue, and tumors with greater PG production were shown to have greater association with metastasis. 1,2 Also, patients with higher PG levels in breast tumor showed lower rates of survival after surgery. 3 The cyclooxygenase enzymes, COX -1 and -2, synthesize PGs from arachidonic acid, an unsaturated fatty acid found in cell membrane lipids. COX-1 is constitutively expressed in most tissues leading to relatively low levels of PG production. COX-2 expression is induced in a variety of cells, e....

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“…44,47,48 PGE 2 inhibits T cell activation, suppresses NK cell activity, downregulates HLA class II expression and induces upregulation of FoxP3 and production of IL-10 in non-T reg cells, steering immune cell composition towards a T reg phenotype. [49][50][51] TGF- inhibits T cell proliferation, activation and the function of cytotoxic molecules like perforin or granzymes. 51 In addition, TGF- impedes DC maturation and antigen presentation, working synergistically with IL-10 in preventing T cell activation and IL-2-induced proliferation.…”

Section: Tumor Evasion and Immunosuppressionmentioning

confidence: 99%

Immunological challenges for peptide-based immunotherapy in glioblastoma

Mohme

Neidert

Regli

et al. 2014

Cancer Treatment Reviews

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Glioblastoma is the most aggressive primary tumor of the central nervous system with a medium overall survival of 7-15months after diagnosis. Since tumor cells penetrate the surrounding brain tissue, complete surgical resection is impossible and tumor recurrence is almost a certainty. New treatment modalities are therefore needed, and these should be able to trace, identify, and kill dispersed tumor cells with great accuracy. Immunological approaches in principle meet these needs. Unfortunately, due to profound tumor-associated mechanisms of immunosuppression and -evasion, immunotherapeutic strategies like peptide vaccination have so far not been translated into clinical success. If future, peptidebased vaccination approaches shall be successful in glioblastoma therapy, multiple questions need to be solved including identification of suitable antigens, route and mode of vaccination, preparation of the tumor-bearing "host" and antagonizing, as much as this is possible, glioblastoma-associated mechanisms of immune evasion and poor vaccination response. In this review we will address the immunological challenges of glioblastoma and discuss key aspects that have rendered successful immunotherapy difficult in the past. preparation of the tumor-bearing "host" and antagonizing, as much as this is possible, glioblastoma-associated mechanisms of immune evasion and poor vaccination response. In this review we will address the immunological challenges of glioblastoma and discuss key aspects that have rendered successful immunotherapy difficult in the past.

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Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer

Cited by 109 publications

References 29 publications

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis

Immunological challenges for peptide-based immunotherapy in glioblastoma

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Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer

Cited by 109 publications

References 29 publications

Reaction with Fructose Detoxifies Fumonisin B1 while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Reaction with Fructose Detoxifies Fumonisin B1 while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis

Immunological challenges for peptide-based immunotherapy in glioblastoma

Contact Info

Product

Resources

About

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats

Reaction with Fructose Detoxifies Fumonisin B₁ while Stimulating Liver-Associated Natural Killer Cell Activity in Rats