Navegando por Palavras-chave "Renal cell carcinoma"
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- ItemSomente MetadadadosBest practice for PTEN gene and protein assessment in anatomic pathology(Elsevier B.V., 2014-01-01) Carvalho, Katia C.; Maia, Beatriz M.; Omae, Samantha V.; Rocha, Antonio A. [UNIFESP]; Covizzi, Luiz P.; Vassallo, Jose; Rocha, Rafael M.; Soares, Fernando A.; Universidade de São Paulo (USP); Hosp AC Camargo Fund Antonio Prudente; Universidade Federal de São Paulo (UNIFESP)There is a lack of standardization of a best practice protocol for Phosphatase and Tensin Homolog (PTEN) assessment by immunohistochemistry in anatomic pathology routine practice. We performed immunohistochemistry for 19 antibodies against PTEN, eleven of which were excluded during the standardization step. Immunohistochemistry of the remaining eight antibodies was performed on a Tissue Microarray containing 55 prostate and 40 renal carcinoma samples. Fluorescent in situ hybridization (FISH) was used as reference standard for immunohistochemistry specificity evaluation. Concerning nuclear staining, polyclonal (Cat#22034-1-AP); 6H2.1 mMAb (Cat#ABM-2052), Y184 RabMAb (Cat#NB110-57441) and 217702 mMAb antibodies presented the highest agreement with fluorescent in situ hybridization (p<0.001 for all) and with regard to cytoplasmic staining, Y184 RabMAb (Cat#NB110-57441); polyclonal (Cat#22034-1-AP) and 217702 mMAb presented the highest agreement (p < 0.001 for all). Our results indicate that several commercially available antibodies do not show reliability of sensitivity and specificity for PTEN evaluation and we propose 6H2.1 mMAb (Cat#ABM-2052) as the antibody of choice for laboratory standardization and best practice in clinical routine, which demonstrated excellent sensitivity for both nuclear and cytoplasmic staining, specificity for PTEN by Western blot and good correlation with PTEN status by FISH with regard to nuclear staining. (C) 2013 Elsevier GmbH. All rights reserved.
- ItemAcesso aberto (Open Access)Carcinoma renal sarcomatóide: achados de imagem e anatomopatológicos. A propósito de um caso(Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2003-08-01) Figueirêdo, Sizenildo Da Silva [UNIFESP]; Argollo, Renato Santos; Costa, Marlos Augusto Bittencourt; Ribeiro, Flávia Aparecida De Souza; Nóbrega, Bruno Barcelos Da [UNIFESP]; Pinto, Sebastião Alves; Lôbo, Leonardo Valadares Barbosa; Rebolças, Marise Amaral Moreira; Teixeira, Kim-ir-sen Santos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Goiás Faculdade de Medicina Hospital das Clínicas; Universidade Federal de Goiás Faculdade de Medicina Serviço de Anatomia PatológicaSarcomatoid renal carcinoma is an aggressive neoplasm with clinical and radiological features similar to those of clear cell renal sarcomas. The tumor is formed by layers of malignant spindle cells that show immunohistochemical and ultrastructural characteristics of both stromal and epithelial cells, and may also contain mixoid areas of osteoclast-like giant cells, rhabdomyoblast-like pleomorphic cells as well as other rare sarcomatoid components. The authors report a case of sarcomatoid renal carcinoma in a 54-year-old male patient presenting with the classic clinical triad seen on patients with renal cell carcinomas. The typical macroscopic and microscopic features, imaging findings and differential diagnosis with true renal sarcomas are discussed.
- ItemAcesso aberto (Open Access)Endostatin gene therapy inhibits intratumoral macrophage M2 polarization(Elsevier France-Editions Scientifiques Medicales Elsevier, 2016) Foguer, Karen [UNIFESP]; Braga, Marina de Souza [UNIFESP]; Schatzmann Peron, Jean Pierre; Bortoluci, Karina Ramalho [UNIFESP]; Bellini, Maria Helena [UNIFESP]Background: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated the impact of ES gene therapy on the polarization of tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice. Methods: BALB/c mice divided into three groups: Normal, Control and ES-treated. Tumor-bearing mice were treated with ES-transduced cells or control cells over ten days. At the end of the study, plasma was collected, and pulmonary macrophages were isolated and used for FACS or RT-PCR. ELISA tests were used to analyze plasma and cell culture supernatant cytokines. Results: ES treatment significantly reduced the levels of anti-inflammatory and pro-angiogenic cytokines, including IL4, IL-10, IL-13 and VEGF. Gene expression of M2 markers, such as IL-10, Arg-1, VEGF and YM-1, declined significantly. Flow cytometry showed a reduction in the number of M2 F4/80 + CD36 + CD206 + CD209+ macrophages and in IL-10 secretion by these cells. Reduced levels of IL-10 were also found in the culture supernatants of the ES-treated group. Conclusions: Our research corroborates previous observations that ES has an important anti-tumoral role. However, aside from promoting interferon-g secretion and an effective T cell response, we show here that this switch is extended to TAMs, complicating the maintenance of pro-tumorigenic M2 macrophages and thus favoring tumor elimination. (C) 2016 Elsevier Masson SAS. All rights reserved.
- ItemAcesso aberto (Open Access)Estudo da modulação das células mielóides supressoras no adenocarcinoma metastático após terapia antiangiogênica(Universidade Federal de São Paulo (UNIFESP), 2016-08-31) Chaves, Karen Cristina Barbosa [UNIFESP]; Bellini, Maria Helena [UNIFESP]; http://lattes.cnpq.br/4219112551635779; http://lattes.cnpq.br/1190409748118272; Universidade Federal de São Paulo (UNIFESP)Renal cell carcinoma (RCC), the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and resistant to radiotherapy and chemotherapy. Antiangiogenic drugs are promising and widely used in clinical, on the other hand, mechanism of evasive resistance has been seen to treatment with anti-VEGF antibody. Recent reports suggest that treatment resistance of patients with cancer is related to the presence of myeloid-derived suppressor cells. Endostatin (ES) is a fragment of collagen XVIII that mediates antiangiogenic activity, however, its mechanisms of action are unclear. In this study, we tracked Gr-1+ cells in different organs, evaluated the role of CD11b+Gr-1+ cells and their subsets during tumoral progression and examined the therapeutic potential of ES in modulating CD11b+Gr-1+ cells and their subsets as well as their immunosuppressive activities in lung metastasis. Healthy Balb/c mice were used to detect Gr-1+ cells. CCRm-bearing mice were nephrectomized on day 7 and collected metastatic lung, spleen and bone marrow after 3, 7 and 10 days. Quantification of CD11b+Gr-1+ cells and their monocytic and granulocytic subsets was performed by flow cytometry and microscopic analysis were viewed in HE staining. CCRm-bearing mice were treated with NIH/3T3-LendSN-clone 5 or with NIH/3T3-LXSN cells as a control. ES and G-CSF levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b+Gr-1+ cells and their subsets was performed by flow cytometry. Gr-1+ cells magnetically separated were evaluated in vitro the nitrite levels in supernatant and arginase activity in cells by colorimetric assays. ROS production was measured in CD11b+Gr-1+ cells using the DCFDA marker by flow cytometry. Our data showed the presence of CD11b+Gr-1+ cells in the bone marrow as well as in the kidney, lung and spleen, confirming the monocytic and granulocytic morphologies In metastatic progression, saw the expansion of CD11b+Gr-1+ cells and, preferably, the granulocytic subtype in the bone marrow. Our data demonstrate the progressive accumulation of splenic CD11b+Gr-1+ cells and the opposite was seen in metastatic lungs.Gene therapy with ES reduced the number of pulmonary metastatic lesions, the number of CD11b+Gr-1+ cells and the number of granulocytic cells. G-CSF levels were also reduced and ROS production by granulocytic cells was affected after the treatment with ES. Here, we demonstrate that the metastatic progression is inversely proportional to the number of CD11b+Gr-1+ cells present in the tumor microenvironment, showing that the granulocytic subtype is involved in advanced metastasis. Treatment with ES induced relevant antitumor immune response abrogating the reduction of ROS-producing myeloid-derived suppressor cells in the metastatic local.
- ItemSomente MetadadadosInvolvement of the NF-kappa B/p50/Bcl-3 complex in response to antiangiogenic therapy in a mouse model of metastatic renal cell carcinoma(Elsevier B.V., 2014-09-01) Braga, Marina de Souza [UNIFESP]; Silva Paiva, Katiucia Batista da; Foguer, Karen [UNIFESP]; Barbosa Chaves, Karen Cristina [UNIFESP]; Lima, Larissa de Sa; Scavone, Cristoforo; Bellini, Maria Helena [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); IPEN CNENRenal cell carcinoma (RCC) represents approximately 2-3% of human malignancies. Nuclear transcription factor kappa B (NF-kappa B) is composed of a family of transcription factors that have been associated with the development and progression of RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. in this study, we evaluated the expression of NF-kappa B in metastatic tumor cells from animals treated with ES. Balb/c-bearing Renca-EGFP cells were treated with NIH/3T3-LendSN or NIH/3T3-LXSN cells as a control. At the end of the in vivo experiment, plasma Renca-EGFP-sorted cells and tissue lung samples were collected. A real-time PCR array for NF-kappa B target genes revealed that ES therapy led to down regulation of Bcl-3 (P < 0.031), NF-kappa B1 (P < 0.001) and c-Rel (P < 0.004) in the ES-treated group. Using an electrophoretic mobility shift assay (EMSA), we observed a reduction in NF-kappa B binding activity in ES-treated Renca-EGP cells. Furthermore, a supershift assay showed a clear shift of the NF-kappa B DNA band in samples incubated with a p50 antibody. By immunohistochemistry analysis, ES treatment resulted in a significant reduction in expression of p50. (ES vs. control P < 0.05). the immunoprecipitation experiments confirmed the presence of a p50/Bcl-3 complex in nuclear extracts from cells of metastatic lung tissues. Our findings indicate that p50 and Bcl-3 plays a regulatory role in gene transcription in RCC. (C) 2014 Elsevier Masson SAS. All rights reserved.
- ItemAcesso aberto (Open Access)Nefrectomia parcial minimamente invasiva versus crioablação renal para pequenas massas renais(Universidade Federal de São Paulo (UNIFESP), 2016-01-08) Juncal, Samuel Ribeiro [UNIFESP]; Ribeiro, Cassio Andreoni [UNIFESP]; http://lattes.cnpq.br/2915020488175752; http://lattes.cnpq.br/5883446756740287; Universidade Federal de São Paulo (UNIFESP)Introduction and Objectives: Minimally invasive partial nephrectomy (MIPN) is the first-line option for the management of small renal masses (SMRs). Renal cryoablation (RC) is being increasingly offered to patients with SRMs due to encouraging outcomes and increasing experience with this treatment modality. We compared the perioperative, functional, and oncologic outcomes of MIPN and RC in the treatment of patients with SRMs. Methods: We retrospectively reviewed the medical records of 264 patients who underwent minimally invasive nephron-sparaing approach (percutaneous renal cryoablation, laparoscopic renal cryoablation, laparoscopic partial nephrectomy, and robotic partial nephrectomy) as a primary treatment for renal mass at our institution from January 2003 to March 2013. The tumors were divided into two groups according to the procedure performed: renal cryoablation (percutaneous and laparoscopic renal cryoablation) and minimally invasive partial nephrectomy (laparoscopic and robotic partial nephrectomy). Results: A total of 271 SRMs were identified in 264 patients (RC, n=123; MIPN, n=148). Patients undergoing MIPN were significantly younger (mean age: 60.6 years vs 65.8 years; P<0.0001). The two groups were similar in gender, body mass index, ethnicity, and American Society of Anesthesiologists score. Patients treated under RC had more baseline comorbidities, presenting a significantly higher percentage of solitary kidney and previous surgery in ipsilateral kidney (P=0.003 and P=0.013,respectively), and a trend to a higher age-adjusted Charlson comorbidity index (P=0.063). Median renal mass size (cm) was larger in the MIPN group (3.0 vs 2.4; P<0.0001). The incidence of perioperative complications had a lower trend in favor of RC (14.6% vs 23.6%;P=0.062). RC was associated with a shorter mean operative and anesthesia time (P<0.001 and P<0.0001, respectively), decreased median estimated blood loss (P<0.0001), shorter mean hospital stay (P<0.0001). Patients who underwent RC had a significantly higherimmediate and delayed treatment failure rate (8.9% vs 2.0%;P=0.01). The 3-,5-, and 10-year recurrence-free survival rate was 94.9%, 86.3% and 86.3% and 97.4%, 97.4% and 91.3% for the RC and MIPN groups, respectively (p=0.123). The 10-year disease-free survival probability was 95.5% for patients in the RC group and 98.5% for patients in the MIPN group (P=0.930). When comparing exclusively the eGFR postoperative day 1 value between both groups, the MIPN group had a significantly lower value compared to the RC group (P=0.019) and a significantly reclassification to a higher CKD stage (P=0.033). CONCLUSION : Renal cryoablation and minimally invasive partial nephrectomy remain viable treatment options in the management of SRMs. Patients undergoing RC had a lower incidence of perioperative complications and better preservation of renal function on immediate postoperative. Although MIPN had a lower local recurrence rate, there was an equivalent treatment effect when patients initially treated under RC were salvaged. A well-designed prospective comparative study with long-term follow is expected to validate our findings.