The cyclooxygenase-2/prostaglandin E2 pathway and its role in the pathogenesis of human and dog hematological malignancies.

The overexpression of cyclooxygenase-2 (COX-2) has been documented in many types of cancer occurring in humans and animals. Increasing evidences have shown that the overexpression of COX-2 and increased production of prostaglandin E2 (PGE2) correlate with poor prognosis in human solid tumours and hematological malignancies. Both, in vitro and in vivo studies have demonstrated that increased proliferation of cancer cells as well as an impairment of anti-tumour immunity are influenced by the overexpression of this enzyme. In leukemia and lymphoma, an increased activity of COX-2 and subsequent increase in prostaglandins (PGs) concentration allow cancer cells to evade immune response and contribute to metastases. Cancer stem cells (CSCs) in tumour microenvironment, suppression of innate and adaptive immunity depends on COX-2/PGE22 axis activity which increases in hematological malignancies. Cyclooxygenases inhibitors block the formation of PGs, consequently inhibiting angiogenesis, and in some malignancies they decrease cancer cells proliferation and tumour invasiveness. They also increase apoptosis of CSCs and cancer cells, decrease their drug resistance as well as enhance the host immune response. Therefore COX-2/PGE2 axis suppressors: selective COX-2 inhibitors or PG receptors antagonists have been considered as promising anticancer drugs. In comparative oncology dogs are increasingly used as a large animal model because they share the same environmental conditions with people and are exposed to the same environmental factors and also due to their relatively short life span. In dogs, spontaneously occurring non-Hodgkin lymphomas and leukemias have a large number of genetic and morphological features that are similar to those of humans' corresponding cancers. This, additionally makes the species a useful model for the study of new therapeutic strategies in human oncology. While the influence of COX-2 activity and PGE2 receptors have been evaluated extensively in human cancer, their role in veterinary oncology still needs to be elucidated.

[Effectiveness of Gn-RH application through the nasal mucosa]. / Efektywnosc dzialania Gn-RH poprzez blone sluzowa nosa

PIP: 218 women with secondary ovarian deficiency, of the Stein-Leventhal or the Sheehan syndromes, were administered 400 mug of gonadotropin-releasing hormone for 5 consecutive days in the 2nd half of the cycle. Radioimmunological examinations of the follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were made 1 hour before and 1 hour after the nasal spray application. A statistically significant increase in the level of LH and a 1.5-fold increase (statistically not significant) of FSH were observed in women with hypothalamic hypofunction of the ovaries. This increase was not observed in the other cases. Cytohormonal smears, performed on the 4th and 5th days of the experiment, showed a normalization of the hormonal pattern in 4 out of 5 women with secondary ovarian deficiency. Results suggested that the applied dose was effective and that the method of application was efficient and to be recommended for the treatment of this illness.^ieng