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Introduction Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model. Materials and Methods Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5 mg/kg/day, p.âo.), anastrozole (0.004 mg/day, p.âo.), or normal saline (0.1 mL, i.âp.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax. Results Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment. Conclusion Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.
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OBJECTIVE: Prostate cancer is among the most common cancers in males. Prostate cancer is androgen dependent in the beginning, but as time progresses, it becomes refractory to androgen deprivation treatment. At this stage, docetaxel has been used as standard treatment for years. Cabazitaxel has become the first chemotherapeutic agent which has been shown to increase survival for patients with metastatic Castrate Resistant Prostate Cancer (mCRPC) that progresses after docetaxel. Phase 3 TROPIC study demonstrated that cabazitaxel prolongs survival. PATIENTS AND METHODS: In this study, we evaluated a total of 103 patients who took cabazitaxel chemotherapy for mCRPC diagnosis in 21 centers of Turkey, retrospectively. This study included patients who progressed despite docetaxel treatments, had ECOG performance score between 0-2, and used cabazitaxel treatment. Patients received cabazitaxel 25 mg/m2 at every 3 weeks, and prednisolone 5 mg twice a day. RESULTS: Median number of cabazitaxel cures was 5.03 (range: 1-17). Cabazitaxel response evaluation detected that 34% of the patients had a partial response, 22.3% had stable disease and 32% had a progressive disease. Grade 3-4 hematological toxicities were neutropenia (28.2%), neutropenic fever (14.5%), anemia (6.7%), and thrombocytopenia (3.8%). In our study, median progression-free survival (PFS) was 7.7 months and overall survival (OS) was 10.6 months. CONCLUSIONS: This study reflects toxicity profile of Turkish patients as a Caucasian race. We suggest that cabazitaxel is a safe and effective treatment option for mCRPC patients who progress after docetaxel. Moreover, ethnicity may play important roles both in treatment response and in toxicity profile.
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Antineoplásicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Taxoides/efectos adversos , Resultado del Tratamiento , Turquía/epidemiologíaRESUMEN
BACKGROUND: Angiogenesis is a very essential process in tumor biology. Vascular endothelial growth factor (VEGF), angiopoietin and its receptor (TIE-2) are very important mediators for angiogenesis. In this trial, we aimed to analyze the role of these mediators on chemotherapy response and survival. PATIENTS AND METHODS: Forty four cancer patients and 22 healthy controls were included in the study. Baseline serum samples were obtained from all participants and post-chemotherapy serum samples were obtained from the cancer patients. Serum vascular endothelial growth factor and TIE-2 levels were measured with quantitative enzyme-linked immunosorbent assay techniques. RESULTS: The baseline serum vascular endothelial growth factor level was 187.5 and 120.2 pg/ml in cancer patients and the control group (p = 0.006). The baseline serum TIE-2 level was 615.9 and 242.5 pg/ml in the patients and control group (p < 0.001). There was a significant difference between patients' baseline and post-chemotherapy VEGF levels (111.9 pg/ml; p < 0.001) and patients' baseline and post-chemotherapy TIE-2 levels (344.5 pg/ml; p < 0.001). The overall survival rate was better in patients who had lower baseline VEGF and TIE-2 levels and whose TIE-2 level had decreased with chemotherapy. CONCLUSIONS: Higher baseline TIE-2 and VEGF levels are related and worsen survival. Decreasing levels of TIE-2, but not VEGF, which, with chemotherapy, may be predictive for survival.