RESUMO
Uterine leiomyomas, or fibroids, are the most frequent gynecological tumors in premenopausal women with as many as 65% of women becoming clinically symptomatic. Uterine fibroids are benign myometrial tumors that produce large quantities of extracellular matrix proteins. Despite its high morbidity, the molecular basis underlying the development of uterine leiomyomas is not well understood. Domestic hens of Gallus gallus domesticus develop oviductal leiomyomas similar to those found in humans. We investigated the natural history of chicken leiomyomas, in vivo expression of protein biomarkers, and in vitro expression of ovarian steroid receptors. Based on the analysis of 263 hens, tumor prevalence, tumor number per hen, and tumor size increased as the hens aged. Immunohistochemistry for alpha-smooth muscle actin (SMA) and desmin confirmed the smooth muscle phenotype of the chicken leiomyomas. Intense collagen expression was detected in these oviductal leiomyomas by Mason's trichrome, and the tumors also showed increased expression of TGFB3 and collagen type I mRNAs. Consistent with human leiomyomas, chicken fibroids displayed increased BCL2 and estrogen (E) and progesterone (P) receptor expression. Chicken leiomyomas were dissociated for in vitro culture. Cells from explants were positive for SMA, desmin, and E and P receptors until the fourth passage. These cells also displayed a response similar to human cells when challenged with halofuginone, an antifibrotic agent. Our findings indicate that the chicken is an excellent complementary model for studies involving the pathophysiology of human uterine leiomyomas.
Assuntos
Envelhecimento/fisiologia , Galinhas , Modelos Animais de Doenças , Leiomioma/patologia , Neoplasias Uterinas/patologia , Envelhecimento/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Leiomioma/tratamento farmacológico , Leiomioma/epidemiologia , Leiomioma/veterinária , Oviductos/patologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/etiologia , Doenças das Aves Domésticas/patologia , Prevalência , Cultura Primária de Células , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico , Células Tumorais Cultivadas , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/veterináriaRESUMO
Epidemiologic studies suggest that zinc deficiency may be associated with increased risk of cancer. We investigated the effects of zinc picolinate supplementation on the development of leiomyomas, malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and heat shock protein 70 (Hsp70) expression in Japanese quails. One hundred fifty quails (6 months old) were assigned to three treatment groups consisting of 50 birds in each group. Birds were fed either a basal diet or the basal diet supplemented with 30 mg or 60 mg of zinc/kg of diet. The animals were sacrificed after 350 days, and the tumors were identified. Zinc picolinate supplementation did not affect the number of leiomyomas compared to control birds (P > .05). However, the tumors in zinc-fed birds were smaller than those found in control birds (P = .01) Serum MDA, 8-isoprostane, and HAE levels were lower in the treatment groups than in the control group: MDA, 1.95 versus 0.93 micromol/L; 8-isoprostane, 108 versus 85 pg/mL; HAE, 1.55 versus 0.96 micromol/L (P = .01 for all three parameters). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were 28.5, 23.6, and 20.1 ng/mL, respectively (P = .01). Hsp70 expression was significantly decreased in zinc-treated birds (P < .01). The results indicate that dietary zinc picolinate supplementation reduces the growth of spontaneously occurring leiomyomas of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of zinc supplementation in the prevention and treatment of uterine leiomyoma in humans.
Assuntos
Doenças das Aves/prevenção & controle , Coturnix , Leiomioma/veterinária , Ácidos Picolínicos/administração & dosagem , 8-Hidroxi-2'-Desoxiguanosina , Animais , Doenças das Aves/tratamento farmacológico , Doenças das Aves/genética , Doenças das Aves/metabolismo , Coturnix/genética , Coturnix/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Leiomioma/tratamento farmacológico , Leiomioma/metabolismo , Leiomioma/prevenção & controle , Distribuição AleatóriaRESUMO
A 12-year-old entire male Maltese terrier was presented with a 1 month history of vomiting and haematemesis. Microcytic hypochromic anaemia was detected. Abdominal radiography, ultrasonography and gastric endoscopy identified a discrete intramural mass in the pyloric antrum. An ulcerated leiomyoma was removed by a partial-thickness intraluminal resection of the gastric wall. The dog recovered well and is free from clinical signs 20 months after surgery.