10 research outputs found
Expressão de ERCC1, NF-kB e transglutaminase como fatores preditivos de resposta à quimioterapia em pacientes com câncer de testículo
No full textTumores de células germinativas testiculares (TGCT) estão associados com uma alta taxa de cura, e são muito sensíveis às platinas. Diferentes mecanismos são relacionados a resistência à cisplatina. Identificar pacientes platino resistentes poderia permitir uma melhor seleção do tratamento, evitando toxicidade desnecessária. Neste estudo, revisamos na literatura possíveis marcadores de resposta às platinas, bem como avaliamos o risco de recorrência relacionado a expressão de nuclear factor kappa-B (NF-κB), excision repair cross-complementation group 1 (ERCC1) e transglutaminase 2 (TG2), em pacientes com TGCT, tratados com combinações de platina. Foram analisados 76 pacientes com TGCT tratados com quimioterapia à base de platina 2001 a 2011 no Departamento de Oncologia do HSL/PUCRS. A análise imunohistoquímica foi realizada e a expressão correlacionada com dados clínicos e laboratoriais. Cinquenta pacientes foram incluídos, idade média do grupo foi de 28,4 anos (18 a 45), 68% histologia não-seminomatosa. Todos os pacientes foram tratados com bleomicina, etoposide e cisplatina (BEP) ou etoposide e cisplatina (EP). A análise multivariada identificou que as expressões positivas de NF-κB e ERCC1 são fatores de risco independentes para maior recorrência de TGCT após a quimioterapia (RR 3.16 e 2.96). Resultados com transglutaminase 2 não mostraram diferença significativa. A expressão de ERCC1 e NF-κB conferem prognóstico pior para recidiva em pacientes com TGCT tratados com quimioterapia baseada em platina. Estes marcadores podem representar fatores que predizem má evolução clínica e resposta a quimioterapia.Tumors of testicular germ cells (TGCT) are associated with a high cure rate, and are very sensitive to platinum based chemotherapy. Different mechanisms are related to resistance to chemotherapy and higher recurrence. We evaluate the risk of recurrence related to expression of nuclear factor kappa- B (NF-κB), excision repair cross-complementation group 1 (ERCC1) e transglutaminase 2 (TG2), in patients with TGCT treated with platinum combinations. Seventy-six patients were evaluated with TGCT treated with platinum-based chemotherapy 2001 to 2011 in the Department of Oncology of the HSL/PUCRS. Immunohistochemistry analysis was performed and expression correlated with clinical and laboratory data. Fifty patients were included in the group, mean age was 28.4 (18 to 45), 68% non-seminoma histology. All patients were treated with BEP or EP. Multivariate analysis identified that positive expressions of NF-κB and ERCC1 are independent risk factors for higher recurrence TGCT after chemotherapy (RR 3.16 and 2.96). There was no significance in TG2 cases. In conclusion, expression of ERCC1 and NF-κB give much worse prognosis for relapse to patients with TGCT treated with platinumbased chemotherapy. They may represent markers that predict poor clinical outcome and response to chemotherapy
Express?o de ERCC1, NF-kB e transglutaminase como fatores preditivos de resposta ? quimioterapia em pacientes com c?ncer de test?culo
No full textSubmitted by Caroline Xavier ([email protected]) on 2017-03-23T17:01:21Z
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Previous issue date: 2016-12-14Tumors of testicular germ cells (TGCT) are associated with a high cure rate, and are very sensitive to platinum based chemotherapy. Different mechanisms are related to resistance to chemotherapy and higher recurrence. We evaluate the risk of recurrence related to expression of nuclear factor kappa- B (NF-?B), excision repair cross-complementation group 1 (ERCC1) e transglutaminase 2 (TG2), in patients with TGCT treated with platinum
combinations. Seventy-six patients were evaluated with TGCT treated with platinum-based chemotherapy 2001 to 2011 in the Department of Oncology of the HSL/PUCRS. Immunohistochemistry analysis was performed and expression correlated with clinical and laboratory data. Fifty patients were included in the group, mean age was 28.4 (18 to 45), 68% non-seminoma histology. All patients were treated with BEP or EP. Multivariate analysis identified that positive expressions of NF-?B and ERCC1 are independent risk factors for higher recurrence TGCT after chemotherapy (RR 3.16 and 2.96). There was no
significance in TG2 cases. In conclusion, expression of ERCC1 and NF-?B give much worse prognosis for relapse to patients with TGCT treated with platinumbased chemotherapy. They may represent markers that predict poor clinical outcome and response to chemotherapy.Tumores de c?lulas germinativas testiculares (TGCT) est?o associados com uma alta taxa de cura, e s?o muito sens?veis ?s platinas. Diferentes mecanismos s?o relacionados a resist?ncia ? cisplatina. Identificar pacientes platino resistentes poderia permitir uma melhor sele??o do tratamento, evitando toxicidade desnecess?ria. Neste estudo, revisamos na literatura poss?veis marcadores de resposta ?s platinas, bem como avaliamos o risco de recorr?ncia relacionado a express?o de nuclear factor kappa-B (NF-?B), excision repair cross-complementation group 1 (ERCC1) e transglutaminase 2 (TG2), em pacientes com TGCT, tratados com combina??es de platina. Foram analisados 76 pacientes com TGCT tratados com quimioterapia ? base de platina 2001 a 2011 no Departamento de Oncologia do HSL/PUCRS. A an?lise imunohistoqu?mica foi realizada e a express?o correlacionada com dados cl?nicos e laboratoriais. Cinquenta pacientes foram inclu?dos, idade m?dia do grupo foi de 28,4 anos (18 a 45), 68% histologia n?o-seminomatosa. Todos os pacientes foram tratados com bleomicina, etoposide e cisplatina (BEP) ou etoposide e cisplatina (EP). A an?lise multivariada identificou que as express?es positivas de NF-?B e ERCC1 s?o fatores de risco independentes para maior recorr?ncia de TGCT ap?s a quimioterapia (RR 3.16 e 2.96). Resultados com transglutaminase 2 n?o mostraram diferen?a significativa. A express?o de ERCC1 e NF-?B conferem progn?stico pior para recidiva em pacientes com TGCT tratados com quimioterapia baseada em platina. Estes marcadores podem representar fatores que predizem m? evolu??o cl?nica e resposta a quimioterapia
Análise da atividade das ectonucleotidases no soro de pacientes com tumores cerebrais primários e metastáticos
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Association between bisphosphonates and jaw osteonecrosis: a study in Wistar rats
No full textBACKGROUND: This work aimed at determining whether bisphosphonate therapy produces a sufficient condition for jaw osteonecrosis after tooth extraction. METHODS: Rats were allocated into 3 groups: (1) 11 rats treated with alendronate, (2) 10 rats treated with zoledronic acid, and (3) 10 control rats. The animals were subjected to tooth extractions, and at the end of bisphosphonate therapy, they were humanely killed. Histologic sections of the surgical site were processed and analyzed. RESULTS: The zoledronic acid group showed higher incidences of osteonecrosis, inflammatory infiltrate, and microorganisms. There was no significant difference for epithelial or connective tissue, root fragments, vital bone, and positive staining for vascular endothelial growth factor (VEGF) among the groups. CONCLUSION: Zoledronic acid is associated with jaw osteonecrosis, whereas alendronate did not produce a condition sufficient for osteonecrosis after tooth extraction. Neither zoledronic acid nor alendronate was associated with a reduced immunohistochemical expression of VEGF in vital bone at the tooth extraction site
Comparison of effects of clodronate and zoledronic acid on the repair of maxilla surgical wounds - histomorphometric, receptor activator of nuclear factor-kB ligand, osteoprotegerin, von Willebrand factor, and caspase-3 evaluation
No full textBACKGROUND: The aim of this study was to compare clodronate and zoledronic acid regarding their influence on the repair of surgical wounds in maxillae (soft tissue wound and tooth extraction) and their relation to osteonecrosis. MATERIAL AND METHODS: Thirty-four Wistar rats were allocated into three groups according to the treatment received: (i) 12 animals treated with zoledronic acid, (ii) 12 animals treated with clodronate and (iii) 10 animals that were given saline solution. All animals were subjected to tooth extractions and surgically induced soft tissue injury. Histological analysis of the wound sites was performed by means of hematoxylin–eosin (H&E) staining and immunohistochemical staining for receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), von Willebrand factor, and caspase-3. RESULTS: The zoledronic acid group showed higher incidence of non-vital bone than did the clodronate group at the tooth extraction site. At the soft tissue wound site, there were no significant differences in non-vital bone between the test groups. RANKL, OPG, von Willebrand factor, and caspase-3 did not show significant differences between the groups for both sites of surgical procedures. CONCLUSION: Both of the bisphosphonates zoledronic acid and clodronate are capable of inducing maxillary osteonecrosis. Immunohistochemical analysis suggests that the involvement of soft tissues as the initiator of osteonecrosis development is less probable than has been pointed out
Effect of hyperbaric oxygen therapy on tooth extraction sites in rats subjected to bisphosphonate therapy—histomorphometric and immunohistochemical analysis
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Brazilian cohort results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer
No full textPRECONNECT is a multicenter study demonstrating the efficacy and tolerability of trifluridine/tipiracil in adult patients with histologically confirmed adenocarcinoma of the colon or rectum and pretreated metastatic lesions. The current article describes the characteristics and outcomes of the Brazilian cohort of patients who underwent trifluridine/tipiracil therapy within PRECONNECT. Brazilian patients (n=55) received oral trifluridine/tipiracil 35mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety including time to ECOG (Eastern Cooperative Oncology Group) PS (performance status) deterioration, and the secondary endpoints included progression-free survival (PFS) and quality of life (QoL). Baseline characteristics showed only 34.5% of patients underwent ≥3 lines of treatment, 29.1% presented ≥3 metastatic sites and 52.7% showed an ECOG PS of 0. The disease control rate (DCR) was 32.0% and 28.6% in patients with one and two metastatic sites, respectively, the median PFS was 3.0 months (95%CI: 2.5-3.4), and the time to ECOG PS deterioration (≥2) was 5.4 months. Drug-related treatment-emergent adverse events (TEAE) were observed at least once in 87.3% of patients, and the most common (≥40% of patients) hematological TEAEs were neutropenia and anemia; there was no febrile neutropenia case. The shorter time to ECOG PS deterioration showed in the Brazilian subset of patients is likely due to late diagnosis setting compared to the global population, despite that trifluridine/tipiracil showed good DCR results, including patients with two metastatic sites. In conclusion, safety and efficacy results provide confidence in routine practice use and are in line with the PRECONNECT stud
Sunitinib Improves Some Clinical Aspects and Reverts DMBA-Induced Hyperplasic Lesions in Hamster Buccal Pouch
No full textRESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer
No full textPURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m(2) every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m(2) daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade >= 3 related treatment-emergent adverse events (TEAEs). The most common grade >= 3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged
