The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation

Higgs, G. A.; Eakins, Kenneth E.; Mugridge, Kenneth G.; Moncada, Salvador; Vane, John R.

doi:10.1016/0014-2999(80)90297-6

Cited by 231 publications

(81 citation statements)

References 10 publications

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“…However, we must take care before coming to a firm conclusion. PGs in vivo can, unlike in vitro, cause bone formation (Ueda et al, 1980), and cyclo-oxygenase inhibitors may increase the metabolism of PG precursors into lipoxygenase products (Higgs et al, 1980), some of which potently resorb bone in vitro (Meghji et al, 1988). Furthermore, skeletal scans are not always reliable indicators of bone metastases (Coombes et al, 1983), and this might explain why a few of our scanpositive patients were negative on subsequent retesting.…”

Section: Resultsmentioning

confidence: 92%

Breast cancer, prostaglandins and patient survival

Bennett

Stamford²,

Berstock³

et al. 1989

Br J Cancer

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Summary Prostaglandins may have both undesirable and desirable effects in malignant disease. Their possible roles in breast cancer were studied by examining the relationships between different variables and the amounts of prostaglandin-like material (PG-LM) extracted from 141 breast carcinomas. Univariate analysis indicates a direct correlation with patient age and menopausal status, with a greater yield from cancers of post-compared with pre-menopausal women. Tumours up to 2cm diameter yielded more PG-LM than those measuring >2-5cm. Although there was also a direct correlation with bone metastasis near to the time of surgery, this was because no positive bone scans occurred in patients whose tumours yielded little total PG-LM (<16ng PGE2 equivalents per g tissue). Since tumour PG-LM did not predict later spread to bone, and yields of > 16 ng g -' were similar in the positive and negative bone scan groups, tumour PG-LM appears to be unimportant for skeletal metastasis. There was no obvious relationship of tumour PG-LM to the grade of malignancy, tumour type, amounts of fibrous tissue (and therefore malignant cells), invasion of blood vessels and lymphatics or presence of plasma cells. Multivariate analysis indicates that disease-free survival is longest with an intermediate production of tumour total PG-LM. Of the 82 patients now dead, the cause was attributed to metastatic disease in 69 cases. No relationship of PG-LM to the length of survival was seen with univariate or multivariate analysis. However, when just the post-menopausal patients who died within the first 3 postoperative years were analysed, there was a highly significant inverse correlation between the tumour total PG-LM and the time to death. The reason(s) for these different findings on overall survival compared with just the patients who died are not understood, but the results may indicate that one or more other variables must co-exist with a high tumour PG-LM to hasten death.Many tumours can produce more prostaglandins (PGs) than the normal tissues in which they arise (Bennett, 1979(Bennett, , 1982(Bennett, , 1988. Similarly, more prostglandin-like material (PG-LM), assayed on rat gastric fundus which is most sensitive to PGE2, was extracted from homogenates of human mammary carcinomas than from benign tumours or macroscopically normal breast tissue (Bennet et al., 1977). Various PGs and related substances extracted from breast carcinomas were identified by Stamford et al. (1983) using gas chromatography-mass spectrometry; the products were arachidonate, 12-hydroxy-eicosatetraenoate (12-HETE), thromboxane B2, 15-keto-l 3,14-dihydro-TXB2, 6-keto-PGFJ,, 6,15-diketo-PGF1,,, 615-diketo-1 3,14-dihydro-PGF1,,, PGD2, PGE2 and PGF21,. Quantitative gas chromatography-mass spectrometry showed substantial amounts of 6-keto-PGF, . and some PGD2, PGE2 and PGF20,, with much higher yields of arachidonate (Stamford et al., 1986). It might be expected that these potent substances contribute to breast cancer, but the problem is complex because PGs have numerou...

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Section: Resultsmentioning

confidence: 92%

Breast cancer, prostaglandins and patient survival

Bennett

Stamford²,

Berstock³

et al. 1989

Br J Cancer

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“…Perhaps the reduced leukocyte migration observed at high doses of the nonsteroidal antiinflammatory agents is due to dual inhibition of cyclooxygenase and lipoxygenase. 16,19 Whether the relationship of these metabolic pathways and their differential inhibition by glucocorticosteroids, indomethacin, ibuprofen and aspirin are responsible for their different effects on scar formation after myocardial infarction is not known.…”

Section: Discussionmentioning

confidence: 99%

“…Mongrel dogs of either sex that weighed [9][10][11][12][13][14][15][16][17][18][19][20][21][22] After lidocaine, 1.5 mg/kg i. v., was administered, the left anterior descending coronary artery was permanently occluded with a silk ligature. A second, similar dose of lidocaine was administered 5 minutes after occlusion in all dogs.…”

Section: Methods Experimental Preparationmentioning

confidence: 99%

Indomethacin-induced scar thinning after experimental myocardial infarction.

Hammerman¹,

Kloner²,

Schoen³

et al. 1983

Circulation

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SUMMARY We investigated the effect of indomethacin, a widely used nonsteroidal antiinflammatory drug, on the healing of myocardial infarction (MI). Experimental MI was produced in anesthetized, openchest dogs by occluding the left anterior descending coronary artery. Ten dogs received indomethacin, 10 mg/kg i.v., and 11 received saline, 15 minutes and 3 hours after occlusion. After 6 weeks, the dogs were killed and their hearts were subjected to morphologic and biochemical analysis. The After lidocaine, 1.5 mg/kg i. v., was administered, the left anterior descending coronary artery was permanently occluded with a silk ligature. A second, similar dose of lidocaine was administered 5 minutes after occlusion in all dogs. The first seven dogs served as controls and received saline. (These dogs also served as controls in another study. 8) The rest of the dogs were randomized by drawing lots into two groups, six saline and 13 indomethacin, and the investigators were blinded as to which agent the dog received until all scar measurements had been completed. The control dogs received 50 ml of saline infused over 5 minutes. The other 13 dogs received indomethacin (Sigma Chemical Company) (10 mg/kg i.v.) in 50 ml of normal saline infused over 5 minutes, at 15 minutes and 3 hours after occlusion (total dose of 20 mg/kg). This dose of indomethacin was used because it was similar to that used by other investigators to ensure complete inhibition of prostaglandin synthesis in the cardiac vascular bed.9' '°All agents were infused through a peripheral vein. The chest was closed, the air was evacuated from the thoracic cavity and the dogs were returned to the kennel. One dose of benzanthine penicillin, 1.2 million units, was given intramuscularly to each dog.After 6 weeks, the dogs were reanesthetized with pentobarbital, 30 mg/kg i.v., killed with an overdose

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“…Furthermore, PGS inhibitors can divert metabolism of prostaglandin precursors into lipoxygenase products (Higgs et al, 1980) whose actions in cancer are not known. However, most in vivo studies of laboratory animals indicate that PGS inhibitors are beneficial in cancer, and contrary claims by 1 group (Favalli et al, 1980;Hofer et al, 1980) are open to substantial criticism (see Bennett, 1982).…”

Section: Discussionmentioning

confidence: 99%

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy

Bennett¹,

Berstock²,

Carroll³

1982

Br J Cancer

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Summary.-In mice with a transplantable mammary carcinoma, treatment with the prostaglandin-synthesis inhibitors flurbiprofen or indomethacin produced various beneficial effects. Survival time after excision of the transplanted tumour was increased, particularly when the drugs were given with the chemotherapeutic agents methrotrexate and melphalan, and there were more disease-free survivors. The combined treatment with flurbiprofen also gave less tumour recurrence at the excision site. Flurbiprofen did not seem to alter the bioavailability of the chemotherapeutic agents.

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The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation

Cited by 231 publications

References 10 publications

Breast cancer, prostaglandins and patient survival

Breast cancer, prostaglandins and patient survival

Indomethacin-induced scar thinning after experimental myocardial infarction.

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy

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