The concentration of 6-keto-PGF1α and TXB2 in plasma samples from patients with benign and malignant tumours of the breast

Nigam, Santosh; Becker, Rolf; Rosendahl, Ulrich; Hammerstein, J.; Benedetto, Chiara; Barbero, Maggiorino; Slater, T. F.

doi:10.1016/0090-6980(85)90076-0

Cited by 32 publications

(12 citation statements)

References 11 publications

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“…They are consistent with our finding that the thromboxane synthetase inhibitor dazmegrel reduced mouse serum TXB2 and increased the 6-keto-PGF1,, but had no effect on the survival of mice bearing NC tumours (Stamford et al, 1986). Similarly, recent work in breast cancer patients demonstrated that the TXB2:6-keto-PGF1, ratio in the systemic circulation is not an indicator of malignancy or metastasis (Nigam et al, 1985).…”

Section: Discussionsupporting

confidence: 80%

Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs

Bennett¹,

Melhuish²,

Patel³

et al. 1987

Br J Cancer

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Summary WHT/Ht mice were transplanted s.c. with NC carcinoma, and the tumours were excised after 2 weeks. The mice were treated orally throughout the experiments with prednisolone 500pgkg-' or mepacrine 3.6mg kg-1, starting the day after tumour transplantation or, with prednisolone, the day after tumour excision. In some experiments the mice were also treated with the cytotoxic drugs methotrexate 2mg kg 1 and melphalan 1.4mgkg-1. The excised tumours were weighed; some of them, and samples of serum, were extracted for prostanoids which were measured by radioimmunoassay. The chemotherapy lengthened the survival of the mice, but prednisolone or mepacrine had little or no effect on survival, metastasis, the response to chemotherapy, tumour size or the formation of tumour prostanoids.Prostaglandin synthesis inhibitors have been extensively investigated in various murine cancers, and they usually show a beneficial effect (Bennett, 1982;1986). In the NC tumour model the prostaglandin synthesis inhibitors indomethacin or flurbiprofen increase mouse survival and usually reduce tumour size. Survival is even longer when these nonsteroidal anti-inflammatory drugs are used with the cytotoxic drugs methotrexate and melphalan . The effects of the anti-inflammatory drugs seems likely to result from inhibition of prostaglandin synthesis rather than from other properties that the drugs may have (Flower, 1974), since administration of a PGE2 analogue counteracted the effect of indomethacin (Bennett et al., (1985). A similar effect might therefore be expected with other drugs that reduce prostaglandin formation, such as corticosteroids and mepacrine which can inhibit phospholipase activity and so depress the release of prostaglandin precursors (Vane et al., 1982). This action may be particularly relevant to human cancers since prednisolone is frequently used in chemotherapy regimens. We have therefore studied the effects of prednisolone and mepacrine, alone and in combination with the cytotoxic drugs methotrexate and melphalan, in mice with NC tumours. Measurements were made of tumour weight and prostanoid content, the occurrence of metastases, and mouse survival. Materials and methodsThe original NC tumour arose spontaneously in the mammary region of a WHT/Ht mouse (Hewitt et al., 1976) and has since been passaged only in this strain. It has a high incidence of local lymphatic spread, recurrence in the scar following tumour excision, and metastasis mainly to the lungs and mediastinum.On day 0, male or female WHT/Ht mice were injected s.c. into the left flank with -106 NC carcinoma cells in a singlecell suspension from passaged tumours as described previously (Bennett et al., 1979. All tumours were excised at 2 weeks and weighed. The study consisted of 6 separate experiments, each with 9-15 WHT/Ht mice/group. Drugs were given orally in 0.1 ml 50% syrup BP for 5 days (Monday to Friday) each week, and treatment with prednisolone or mepacrine was continued until death or the end of the experiment (day 121). The doses chosen are approx...

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Section: Discussionsupporting

confidence: 80%

Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs

Bennett¹,

Melhuish²,

Patel³

et al. 1987

Br J Cancer

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“…Moreover, it has been found that LOX metabolism as well as arachidonic acid metabolites play an important role in tumor progression and survival [40] and are implicated in the etiology of mammary carcinogenesis [41]. Studies have demonstrated that levels of several eicosanoids are increased in breast cancer in comparison to benign breast tumours [42,43]. Thus, LOX inhibitors may have chemopreventive activity in lung carcinogenesis [44,45].…”

Section: Biological Assaysmentioning

confidence: 99%

Novel Cinnamic Acid Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Modeling Studies

et al. 2014

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Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenylsubstituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC 50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC 50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.

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“…Free catecholamines in plasma and urine were determined by HPLC using a kit from Biorad, Richmond, CA, USA. To assay PGE2, prostanoids were separated by HPLC (Nigan et al, 1985). TNF was determined either by an ELISA test (Genzyme, Cambridge, MA, USA) or with the L929 cell toxicity assay (Flick & Gifford, 1984); one unit of activity was defined as the reciprocal dilution required to produce a 50% decrease in absorbance relative to control cells exposed to actinomycin D alone.…”

Section: Assaysmentioning

confidence: 99%

Humoral mediation for cachexia in tumour-bearing rats

Tessitore

Costelli²,

Baccino³

1993

Br J Cancer

109

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Summary Early and severe loss of body weight associated with pronounced tissue changes developed in rats transplanted with a fast-growing ascites hepatoma (Yoshida AH-130). The protein content showed an early and marked fall in the skeletal muscle, while in the liver it transiently increased 4 days after implantation then declined to values lower than in control animals. Protein loss in gastrocnemius muscle and liver resulted mainly from enhancement of protein catabolism (Tessitore L. et al., Biochem. J., 241: 153-158, 1987). In contrast to the tumour-bearing rats, in the pair-fed animals the initial body weight was maintained, while the protein mass decreased sharply in the liver and moderately in the grastrocnemius muscle. In host animals total plasma protein decreased during the period of tumour growth, while both triglycerides and total cholesterol markedly increased. Glucose remained unchanged even when overt cachexia had developed. The total free amino acid concentration in the plasma of tumour-bearing rats decreased slightly by day 4 and returned to values close to those of controls in the late stages of tumour growth. By contrast, in the pair-fed controls the plasma levels of triglycerides and particularly of total free amino acids and glucose decreased over the whole experimental period, whereas total protein and cholesterol were unchanged. Marked perturbations in the hormonal homeostasis developed early after tumour transplantation. The plasma levels of glucagon, corticosterone and catecholamines rose sharply, while those of insulin and thyroid hormones decreased. Furthermore, high plasma concentrations of prostaglandin E2 (PGE2) and tumour necrosis factor (TNF) were observed over the whole experimental period. IL-I-like activity, TNF and PGE2 were released in vitro from AH-130 cells. These data suggest that the systemic effects of AH-130 tumour on the host rat reflected the interplay of a complex network of factors, including classical hormones and cytokines, all of which likely concur in enhancing tissue protein catabolism.

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The concentration of 6-keto-PGF1α and TXB2 in plasma samples from patients with benign and malignant tumours of the breast

Cited by 32 publications

References 11 publications

Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs

Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs

Novel Cinnamic Acid Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Modeling Studies

Humoral mediation for cachexia in tumour-bearing rats

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