Navegando por Palavras-chave "Neoadjuvant therapy"

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    Desdiferenciação do câncer da próstata após terapia antiandrogênica
    (Associação Médica Brasileira, 2005-04-01) Moritz, Rogério [UNIFESP]; Srougi, Miguel [UNIFESP]; Ortiz, Valdemar [UNIFESP]; Leite, Kátia Ramos Moreira [UNIFESP]; Nesrallah, Luciano [UNIFESP]; Dall'oglio, Marcos [UNIFESP]; Sant'anna, Alexandre Crippa [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: Neoadjuvant androgen deprivation in prostate cancer induces tumor volume regression but does not improve outcome of the patient. A possible explanation for this phenomenon could be an increase of the residual tumor aggressiveness brought about by antiandrogen therapy. The purpose of the present study was to evaluate the frequency of tumor dedifferentiation following androgen blockade in prostate cancer and to determine if the remaining tumor shows signs of increased aggressiveness. METHODS: Thirty patients bearing locally advanced prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic therapy during four months followed by radical prostatectomy. Gleason scores from biopsy and surgical specimens were compared. Furthermore, the cell proliferation index was evaluated by immunohistochemistry assay for PCNA, tests with strong nuclear staining were considered positive. The percentage of positive nuclei, counted in 500 cells, was determined in several categories of the Gleason score from surgical specimens. RESULTS: In 11(37%) surgical specimens the Gleason score was equal or lower than that found in the biopsy and in 19 (63%) the total score was higher in the surgical specimens (p<0.05). The median of PCNA expression was 4.5%, 10%, 12% and 14% in Gleason scores 2-4, 5-6,7 and 8-10, respectively (p>0.05). The median of cell proliferation indexes was 9% for glandular or specimen confined tumors and was 17% for extraprostatic tumors (p<0.05). CONCLUSION: The lower Gleason score was found in almost 2/3 of patients submitted to antiandrogen therapy. However, the cell proliferation index measured by PCNA was the same for tumors with lower or higher Gleason scores. It seems that cell dedifferentiation seen after neoadjuvant androgen deprivation represents a mere morphologic phenomenon and not a real increase in tumor aggressiveness.
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    Endostatin neoadjuvant gene therapy extends survival in an orthotopic metastatic mouse model of renal cell carcinoma
    (Elsevier B.V., 2012-06-01) Braga, Marina de Souza [UNIFESP]; Chaves, Karen Barbosa [UNIFESP]; Chammas, Roger [UNIFESP]; Schor, Nestor [UNIFESP]; Bellini, Maria Helena [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Dept Biotechnol
    Despite recent advances in targeted therapy, renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies. Approximately 30% of patients with localised RCC will develop metastases after curative surgery. Presurgical therapy has been explored for treatment of localised RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. in this study, we examined the potential use of an antiangiogenic agent as a neoadjuvant therapy in an orthotopic metastatic mouse model of RCC. BALB/c mice bearing Renca cells were treated before nephrectomy with NIH/3T3-LendSN cells. At the end of the experiment, ES serum levels were measured. Primary and metastatic tumour area and microvascular area were determined. in the survival studies, mice were monitored daily until they died. ES serum levels in treated mice were higher in the control group (P < 0.05). the median primary tumour area and the mean microvascular area were significantly lower in the ES-treated group compared to control group (P < 0.05). the proliferation of Renca cells in the ES-treated group was significantly reduced compared with the control group (P < 0.01). ES therapy led to a significant reduction in the number of pulmonary metastatic nodules compared with the control group (P < 0.01). Kaplan-Meier survival curves showed that the probability of survival was significantly higher in mice receiving ES therapy (P = 0.0243, Log-Rank test). Our results indicated that neoadjuvant ES gene therapy has the potential to decrease tumour burden, extend survival, and may have clinical benefit in the management of RCC. (C) 2011 Elsevier Masson SAS. All rights reserved.
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    Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness-a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer
    (Biomed Central Ltd, 2013-09-18) Madeira, Marcelo [UNIFESP]; Mattar, Andre [UNIFESP]; Logullo, Angela Flavia [UNIFESP]; Soares, Fernando Augusto; Gebrim, Luiz Henrique [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Albert Einstein Hosp; Perola Byington Hosp; AC Camargo Hosp
    Background: the role of estrogen receptor beta (ER-beta) in breast cancer (BC) remains unclear. Some studies have suggested that ER-beta may oppose the actions of estrogen receptor alpha (ER-alpha), and clinical evidence has indicated that the loss of ER-beta expression is associated with a poor prognosis and resistance to endocrine therapy. the objective of the present study was to determine the role of ER-beta and the ER-alpha/ER-beta ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-beta expression levels.Methods: Ninety postmenopausal patients with primary BC were recruited for a short-term double-blinded randomized prospective controlled study. To determine tumor cell proliferation, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of treatment with anastrozole 1 mg/day (N = 25), tamoxifen 20 mg/day (N = 24) or placebo (N = 29) of 78 participants. the pre-and post-samples were placed in tissue microarray blocks and submitted for immunohistochemical assay. Biomarker statuses (ER-beta, ER-alpha and Ki67) were obtained by comparing each immunohistochemical evaluation of the pre- and post-surgery samples using the semi-quantitative Allred's method. Statistical analyses were performed using an ANOVA and Spearman's correlation coefficient tests, with significance at p <= 0.05.Results: the frequency of ER-beta expression did not change after treatment (p = 0.33). There were no significant changes in Ki67 levels in ER-beta-negative cases (p = 0.45), but in the ER-beta-positive cases, the anastrozole (p = 0.01) and tamoxifen groups (p = 0.04) presented a significant reduction in post-treatment Ki67 scores. There was a weak but positive correlation between the ER-alpha and ER-beta expression levels. Only patients with an ER-alpha/ER-beta expression ratio between 1 and 1.5 demonstrated significant differences in Ki67 levels after treatment with anastrozole (p = 0.005) and tamoxifen (p = 0.026).Conclusions: Our results provide additional data that indicate that the measurement of ER-beta in BC patients may help predict tamoxifen and anastrozole responsiveness in the neoadjuvant setting. These effects of hormonal treatment appear to be dependent on the ratio of ER-alpha/ER-beta expression.