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C Fitzsimons

Publications and source records attributed to C Fitzsimons.

11 recordsLinked to original sources
PubMed2002

Inhibition of human primary melanoma cell proliferation by histamine is enhanced by interleukin-6.

BACKGROUND: Interleukin-6 (IL-6) is a bifunctional growth factor in malignant melanoma; its expression increases during the malignant progression of the disease. Histamine, detected in large amounts in normal and pathological proliferating tissues, is an important paracrine and autocrine regulator of normal and tumour cell proliferation as well. MATERIALS AND METHODS: We investigated the presence and function of IL-6 and histamine in the WM35 primary human melanoma cell line with respect to their direct role in cell proliferation and their regulatory interactions. RESULTS: IL-6 inhibited the proliferation of WM35 melanoma cells and increased significantly the expression of histidine decarboxylase as well as histamine production. It had dose-dependent effects on the proliferation: high concentration (10-5 M) was inhibitory through H1 histamine receptors while low histamine concentration acting on H2 receptors, with a simultaneous increase of cAMP, enhanced colony formation in the monolayer. Furthermore, IL-6 increased the H1- but decreased the H2-histamine receptor expression of the melanoma cells. On the other hand, histamine was locally synthesized by the WM35 melanoma cells. CONCLUSION: We suggest that the growth arrest induced by IL-6 is in part mediated by its dual action on histamine: a shift toward H1 receptor predominance and an elevation of locally produced histamine with prevalent action on the inhibitory response triggered through the H1 receptor. These findings suggest a local cross-talk between histamine and IL-6 in the regulation of melanoma growth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

An experimental model of diabetes and cancer in rats.

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.

Animals↗
PubMed1997

Atypical association of H1 and H2 histamine receptors with signal transduction pathways during multistage mouse skin carcinogenesis.

OBJECTIVE: In the present work we studied the association of histamine receptors with second messengers during multistage carcinogenesis in Sencar mice skin. METHODS: 96 Sencar female mouse, divided into six groups were used. Tumors appeared only in the 7, 12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted group. Control groups received only TPA, or acetone or no treatment at all. Periodically during the promotion period, cAMP and inositol phosphate production were measured after stimulation with H1 or H2 agonists in samples from all groups. RESULTS: In non-treated skin, H1 receptors were coupled to phosphatidylinositol hydrolysis and H2 receptors mediated cAMP production. Conversely, in tumors H2 receptors were associated with phosphatidylinositol hydrolysis and H1 mediated a rise in cAMP levels. The skin among tumors and the skin from all control groups maintained the same coupling as non-treated skin. An increase in mast cell number, with a homogeneous subepithelial distribution and marked phenotypic changes, was also observed in promoted skin. CONCLUSIONS: These findings indicate an atypical association of histamine receptors with second messengers that could be a critical feature for the postulated action of histamine in tumor growth.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.

Administration, Oral↗
PubMed1983

Labetalol disposition and concentration-effect relationships during pregnancy.

1 Labetalol pharmacokinetics and concentration-effect relationships following intravenous administration have been studied in 10 women during the last trimester of pregnancies complicated by hypertension, in seven of these women postpartum (when normotensive) and in 10 normotensive female volunteers. 2 The clearance and volume of distribution of labetalol were the same in all three groups. Clearance values (1 min-1) were: pregnant, 2.16 (range 1.54-3.14); postpartum 2.35 (1.56-3.85); controls 1.96 (0.98-2.61). Volumes of distribution (1) were: pregnant 274 (250-547); postpartum 407 (248-701); controls 234 (186-415). 3 A linear model relating labetalol concentration to effect successfully described the antihypertensive action of labetalol in the pregnant patients. Supine systolic blood pressure fell by 0.38 (0.14-0.91) mm Hg per ng ml-1 of labetalol and diastolic by 0.36 (0.21-1.14) mm Hg per ng ml-1 of labetalol. In the other two groups labetalol did not lower pressure sufficiently to allow modelling to be performed. 4 We conclude that pregnancy does not alter the clearance or volume of distribution of labetalol. Modelling techniques can be applied successfully to drug induced blood pressure changes during pregnancy.

Adolescent↗