BACKGROUND To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl‐2, Ki‐67, and CD34, was performed by the standard avidin‐biotin‐peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase–mediated dUTP‐biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl‐2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki‐67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki‐67 LI and MVD (P < 0.001 for both). CONCLUSIONS These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis. Cancer 2001;91:2026–32. © 2001 American Cancer Society.

The aim of this study was to investigate the structural characteristics of podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [S S (Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r ‫؍‬ ؊0.71, P ‫؍‬ 0.001) and directly with AER (r ‫؍‬ 0.66, P ‫؍‬ 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P ‫؍‬ 0.001), normoalbuminuric patients (P ‫؍‬ 0.0002) and microalbuminuric patients (P ‫؍‬ 0.04) and correlated with renal structural and functional parameters, including AER (r ‫؍‬ ؊0.52, P ‫؍‬ 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. S S (Fenestrated/cap) was reduced in normoalbuminuric (P ‫؍‬ 0.03), microalbuminuric (P ‫؍‬ 0.03), and proteinuric (P ‫؍‬ 0.002) patients versus control subjects. S S (Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r ‫؍‬ ؊0.57, P ‫؍‬ 0.01), IFP (r ‫؍‬ 0.61, P ‫؍‬ 0.007), and FPW (r ‫؍‬ ؊0.58, P ‫؍‬ 0.01). These novel studies document that podocyte detachment and diminished endothelial cell fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/endothelial cell functional interactions in diabetic nephropathy. Diabetes 56:2155-2160, 2007 S trong correlations between morphometric measures of mesangial expansion and glomerular basement membrane (GBM) width and functional parameters in diabetic nephropathy have long been known (1-2). More recently, however, interest in the possible role of podocytes in the development and/or progression of diabetic nephropathy has grown (3). Podocytes are important in maintaining glomerular permselectivity, and the development of proteinuria is associated with morphological changes in these cells, including foot process effacement (4). Podocyte detachment and GBM denudation have been documented in diverse renal conditions associated with severe proteinuria, such as idiopathic focal and segmental glomerulosclerosis (FSGS), puromycin nephrosis, amyloidosis, and reflux nephropathy (5-8). Foot process effacement and decreased podocyte number and/or density per glomerulus have been reported in patients with type 1 and type 2 diabetes (9 -14). There is, how...

No abstract

No abstract

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a ؉ TIDCs, and 82 (63.1%) samples contained CD83 ؉ TIDCs. The number of CD83 ؉ TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-␤, whereas the number of CD1a ؉ TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83 ؉ TIDCs with longer relapsefree (p ‫؍‬ 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83 ؉ TIDCs was significantly better than that of patients with fewer CD83 ؉ TIDCs. Multivariate analysis revealed that CD83 ؉ TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.