The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of ‘hot’ spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.
The metastasis occurrence, an important prognostic factor, depends on peculiarities such as cellular invasiveness and cell migration, mechanisms controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). An increased expression of this protein promotes tumor growth and metastasis, a mechanism which can be restricted by the use of the effector's inhibitors. Melatonin, a hormone secreted by the pineal gland, has shown oncostatic action and anti-metastatic effects and can modulate the ROCK-1expression. The objective of this study was to investigate the anti-metastatic response mediated by ROCK-1 and through the action of melatonin and its specific inhibitor (Y27632) in vitro and in vivobreast cancer models. Cells from metastatic (MDA-MB-231) and non-metastatic (MCF-7) breast cancer lines were treated with melatonin and Y27632. Cell viability was verified by MTT assay, cell migration/invasion assays in Boyden chamber, ROCK-1 protein and gene expression by western blot and quantitative real time PCR, respectively. In addition, the in vivometastasis study was performed using female athymic nude mice induced by injection of 2x105 MDA-MB-231 viable cells by tail veinfor lung metastasis and byintracardiac for bone metastasis, during 3 weeks. The animals were treated with melatonin and Y27632 for 2 weeks. The metastasis developments were evaluated by single photon emission computed tomography (SPECT). Treatment with melatonin reduced cell viability and migration of both cell lines (p<0.05). The use of melatonin and Y27632, in association or not, decreased the ROCK-1 protein expression in metastatic cells, not significantly altering its expression in the non-metastatic line (p>0.05). An statistically significant reduction of ROCK-1 gene expression was observed in all treatment groups (p<0.05). ROCK-1 downexpression was more efficient in the group with associated treatments for both lines (p < 0.05). In vivoSPECT images showed multiple foci in the lungs (on Tc-99-tetrofomin images) and in the vertebrae (on Tc-99-MDP images). The numbers of "hot" spots were significantly higher in lung metastasis of control animals compared to treated groups. Semi quantitative analysis showed significantly lower activity in animal lungs that received treatment (p<0.05). The bone metastasis did not show difference between control and treatment groups. Melatonin and Y27632 are effective drugs of metastatic breast cancerin vitro treatment, confirming their effects in decreasing cell viability, invasion, migration and protein expression of ROCK-1 in these cells. In vivo, melatonin and Y27632 treatments seem to be effective reducing lung metastasis but not bone metastasis. Melatonin, in particular, appears to be more effective when combined to ROCK-1 inhibitor. Support: FAPESP. Citation Format: Debora C Zuccari, Thaiz F Borin, Ali S Arbab, Lívia C Ferreira, Marina G Moschetta, Gustavo R Martins, Larissa B Maschio, Vanessa A Fabri, Verena B Coimbra. Melatonin's inhibitory effect on breast cancer metastasis mediated by ROCK-1 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-20.
Conflito de interesses: Não AbstractIntroduction: Liver injuries occur in 16% of all poly-trauma patients. The American Association of Surgery of Trauma uses computer tomography findings to classify them into grades I through VI. Grade I, II and III lesions have better prognosis, and may be successfully treated with conservative clinical approaches. Grade IV through VI typically require surgical intervention. The present article presents the efficacy of endovascular treatment of Grade V liver injury in the medium and long terms, describing the clinical stabilization in acute phases and maintenance of hepatic function during a 6-month follow-up. Case Report: A 26-year-old male victim of blunt abdominal trauma and grade V liver injury had a successful hemodynamical stabilization after being subjected to arteriographic selective embolization. A surgical approach was necessary later on to remove intraabdominal clots, with adequate post-surgical evolution. The patient kept under follow up at the outpatient clinic for six months after the traumatic event, with full recovery of liver function and enzymes. Conclusion: Non-surgical treatment of grade V hepatic lesion may be used in selected cases in centers with hemodynamic and intensive care units.
Cobertura de lesões em pé e terço inferior da perna com retalho fasciocutâneo reverso da panturrilha (Carriquiry)
Introdução: Plastrão apendicular é uma condição que ocorre em 2 a 6% dos casos de apendicite aguda. Pode ser classificado em fleimão ou abscesso, sendo este drenado assim que possível. A abordagem terapêutica desses casos permanece controversa. Relato de Caso: Apresenta-se o caso clínico de uma paciente de 52 anos, com dor abdominal na fossa ilíaca direita por duas semanas, sem sinais de peritonite. Foi feito o diagnóstico de plastrão apendicular, e a terapêutica iniciada com antibioticoterapia e analgesia, tendo evoluído com melhora clinica e laboratorial durante a internação, recebendo alta hospitalar com acompanhamento ambulatorial, para posterior programação de colonoscopia para melhor esclarecimento diagnóstico. Conclusão: O tratamento clínico do plastrão apendicular foi seguro e eficaz, evitando as desvantagens cirúrgicas iniciais.
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