RESUMO
BACKGROUND: Expression profiles of some microRNAs (miRNAs) were associated with clinicopathological findings in human prostate cancer (PC), but the relative expression of miRNAs among Gleason patterns (GPs) remains unclear. In this study, we investigated the expression of several known microRNAs in each GP of PC. METHODS: Formalin-fixed, paraffin embedded (FFPE) tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n = 43, including (GP 3) n = 22, (GP 4) n = 35, and (GP 5) n = 12) and needle biopsy (patient set 2, n = 10, (GP 4) n = 10). Cancer tissues from each GP and adjacent normal counterparts were separately collected using laser-captured microdissection (LCM). Real-time RT-PCR was performed to determine the relative expression of miRNAs, including miR-31-5p, -34c-5p, -96-5p, -182-5p, -183-5p, -205-5p, -221-3p, and -222-3p, which were currently reported to be involved in PC progression. RESULTS: In radical prostatectomy samples, relative expression of miR-31-5p, miR-34c-5p, and miR-205-5p in any GP was significantly decreased compared to normal counterpart. However, no significant difference was detected among GP 3, GP 4, and GP 5. Meanwhile, in the same GP4, expression of miR-31-5p miR-182-5p, and miR-205-5p in cancer tissues obtained from high grade cancer was significantly higher than those obtained from intermediate grade cancer. Validation study using biopsy samples revealed that the relative expression of miR-182-5p was statistically higher in high grade cancer even in same GP4. CONCLUSIONS: We confirmed the expression of miR-182-5p depended on the cancer grade even in same GP 4. Expression of miRNA associated with Gleason grading system may contribute to more accurate preoperative cancer risk evaluation.
Assuntos
MicroRNAs/biossíntese , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , RNA Neoplásico/química , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Treatment with anti-TNF-alpha MAb has been accepted as a successful maintenance therapy for patients with inflammatory bowel diseases (IBD). Moreover, it has been recently reported that blockade of TNF receptor (TNFR) 1 signaling in infiltrating hematopoietic cells may prevent the development of colitis-associated cancer (CAC). However, it remains unclear whether the TNF-alpha signaling in epithelial cells is involved in the development of CAC. To investigate this, we studied the effects of anti-TNF-alpha MAb in an animal model of CAC by administration of azoxymethane (AOM) followed by sequential dextran sodium sulfate (DSS) ingestion. We observed that the NF-kappaB pathway is activated in colonic epithelia from DSS-administered mice in association with upregulation of TNFR2 rather than TNFR1. Immunoblot analysis also revealed that the TNFR2 upregulation accompanied by the NF-kappaB activation is further complicated in CAC tissues induced in AOM/DSS-administered mice compared with the nontumor area. Such NF-kappaB activity in the epithelial cells is significantly suppressed by the treatment of MP6-XT22, an anti-TNF-alpha MAb. Despite inability to reduce the severity of colitis, sequential administration of MP6-XT22 reduced the numbers and size of tumors in association with the NF-kappaB inactivation. Taken together, present studies suggest that the TNFR2 signaling in intestinal epithelial cells may be directly involved in the development of CAC with persistent colitis and imply that the maintenance therapy with anti-TNF-alpha MAb may prevent the development of CAC in patients with long-standing IBD.
Assuntos
Colite/complicações , Neoplasias do Colo/complicações , Células Epiteliais/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos Monoclonais , Carcinoma , Linhagem Celular , Colite/induzido quimicamente , Sulfato de Dextrana/toxicidade , Feminino , Regulação da Expressão Gênica/fisiologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
A case of a small renal oncocytoma with central cystic degeneration, 15 mm in diameter, is reported. Contrast-enhanced computed tomography showed the tumor contained a central hypoattenuating region and had an irregular, heterogeneously enhanced wall. Magnetic resonance images showed a well-circumscribed lesion and the T(1)-weighted image indicated medium signal intensity, whereas the T(2)-weighted image indicated slight hypointensity. Both T(1)- and T(2)-weighted images showed central hyperintensity. Our preoperative diagnosis was renal cell carcinoma originating in a renal cyst wall or cystic renal cell carcinoma. Nephrectomy was performed because frozen-section examination did not completely rule out malignancy. The final pathological diagnosis of the entire surgical specimen was renal oncocytoma with cystic degeneration. To our knowledge, this is the 14th case of renal oncocytoma with central cystic degeneration reported in the published works. We discuss herein the variant forms of oncocytoma and difficulties with their preoperative diagnosis, especially when the tumor is small.