RODRIGO OLIVA PEREZ
Índice h a partir de 2011
25
Projetos de Pesquisa
Unidades Organizacionais
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Consolidation chemotherapy during neoadjuvant chemoradiation (CRT) for distal rectal cancer leads to sustained decrease in tumor metabolism when compared to standard CRT regimen(2016) HABR-GAMA, Angelita; PEREZ, Rodrigo O.; JULIAO, Guilherme P. Sao; PROSCURSHIM, Igor; FERNANDEZ, Laura M.; FIGUEIREDO, Marleny N.; GAMA-RODRIGUES, Joaquim; BUCHPIGUEL, Carlos A.Background: Neoadjuvant CRT may lead to significant tumor regression in patients with rectal cancer. Different CRT regimens with consolidation chemotherapy may lead to increased rates of complete tumor regression. The purpose of this study was to understand tumor metabolic activity following two different neoadjuvant CRT regimens using sequential PET/CT imaging in two different intervals following RT. Methods: Patients with cT2-4 N0-2 M0 rectal cancer treated by standard CRT (54Gy and 2 cycles of 5FU-based chemotherapy) or extended CRT (54Gy and 6 cycles of 5FU-based chemotherapy) underwent sequential PET/CT imaging at baseline, 6 weeks and 12 weeks from radiation completion. Results: 99 patients undergoing standard CRT were compared to 12 patients undergoing CRT with consolidation chemotherapy. Patients treated with consolidation CRT had increased rates of complete clinical or pathological response (66 % vs. 23 %; p < 0.001). SUVmax variation between baseline and 6 weeks (88 % vs. 63 %; p < 0.001) and between baseline and 12 weeks (90 % vs. 57 %; p < 0.001) were significantly more pronounced among patients undergoing extended CRT with consolidation chemotherapy. An increase in SUVmax between 6 and 12 weeks was observed in 51 % of patients undergoing standard and 18 % of patients undergoing consolidation CRT (p = 0.04). Conclusions: Most of the reduction in tumor metabolism after neoadjuvant CRT occurs within the first 6 weeks from RT completion. In patients undergoing CRT with consolidation chemotherapy, tumors are less likely to regain metabolic activity between 6 and 12 weeks. Therefore, assessment of tumor response may be safely postponed to 12 weeks in patients undergoing extended CRT with consolidation chemotherapy.
- E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer(2017) LOPES-RAMOS, Camila M.; BARROS, Bruna P.; KOYAMA, Fernanda C.; CARPINETTI, Paola A.; PEZUK, Julia; DOIMO, Nayara T. S.; HABR-GAMA, Angelita; PEREZ, Rodrigo O.; PARMIGIANI, Raphael B.Background Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. Methods We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. Results We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. Conclusions We demonstrated that somatic mutation within E2F1: MIR136-5p target site impairs miRNAmediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.
- Effect of Akt activation and experimental pharmacological inhibition on responses to neoadjuvant chemoradiotherapy in rectal cancer(2018) KOYAMA, F. C.; RAMOS, C. M. Lopes; LEDESMA, F.; ALVES, V. A. F.; FERNANDES, J. M.; VAILATI, B. B.; JULIAO, G. P. Sao; HABR-GAMA, A.; GAMA-RODRIGUES, J.; PEREZ, R. O.; CAMARGO, A. A.Background: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT.& para;& para;Methods: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 NO-2 rectal cancer within 7 cm of the anal verge. Downstream Akt activation was assessed in an independent set of pretreatment biopsies and in colorectal cancer cell lines using immunohistochemistry and western blot respectively. The radiosensitizing effects of the Akt inhibitor MK2206 were assessed using clonogenic assays and xenografts in immunodeficient mice.& para;& para;Results: A total of 350 differentially expressed genes were identified, of which 123 were upregulated and 199 downregulated in tumours from poor responders. Mitochondrial oxidative phosphorylation (P <0.001) and phosphatidylinositol signalling pathways (P <0.050) were identified as significantly enriched pathways among the set of differentially expressed genes. Deregulation of both pathways is known to result in Akt activation, and high immunoexpression of phosphorylated Akt S473 was observed among patients with a poor histological response (tumour regression grade 0-2) to CRT (75 per cent versus 48 per cent in those with a good or complete response; P = 0.016). Akt activation was also confirmed in the radioresistant cell line SW480, and a 50 per cent improvement in sensitivity to CRT was observed in vitro and in vivo when SW480 cells were exposed to the Akt inhibitor MK2206 in combination with radiation and 5-fluorouracil.& para;& para;Conclusion: Akt activation is a key event in the response to CRT. Pharmacological inhibition of Akt activation may enhance the effects of CRT.
- Tumour response to neoadjuvant chemoradiation within lateral pelvic nodes: another step towards precision surgery(2018) PEREZ, R. O.; DANERI, M. D.; VAILATI, B.; JULIAO, G. P. Sao
- Continence changes following transanal endoscopic microsurgery result from the impact on rectal capacity: clinical and functional evaluation before and after surgical treatment(2018) MENDES, Carlos Ramon Silveira; ARAUJO, Sergio Eduardo Alonso; PEREZ, Rodrigo; CECCONELLO, Ivan; DÁLBUQUERQUE, Luiz Augusto CarneiroABSTRACT Introduction: Described in 1983 and with a stable clinical application, the impact of Transanal Endoscopic Microsurgery on anorectal function remains unknown. The objectives of the present study were to evaluate the impact of Transanal Endoscopic Microsurgery on anorectal function according to clinical (Wexner score) and functional (anorectal manometry) evaluations before and after surgery. Method: Prospectively, 23 consecutive patients with rectal lesions were operated using TEO® equipment (Karl Storz, Tuttlingen, Germany). For all patients, the value of Wexner score was obtained before and after surgery (7, 30 and 90 days) and anorectal electromanometry was performed before surgery, and also postoperatively (30 and 90 days). Results: Fourteen patients were men. The mean age was 53.7 (24-81) years. The mean distance from the lesion to the pectineal line was 7 (2-15) cm. The histopathologic analysis revealed adenoma in 14 (61%); neuroendocrine tumor in 5 (21.7%); invasive carcinoma in 3 (13%); and hyperplastic polyp in 1 (4.3%) case. The mean duration of postoperative follow-up was 5 (3-7) months. Wexner score was significantly lower at 30 days compared to 7 days (Wilcoxon; p = 0.03). Rectal capacity was significantly lower 30 days after surgery and recovered at 90 days of surgery (ANOVA; p = 0.04). Conclusions: After Transanal Endoscopic Microsurgery, a modest impact on anorectal function can be observed. The transient impairment results from loss of rectal capacity and not from impairment of the anal sphincters, being completely resolved 90 days after surgery.