Matrix metalloproteinases (MMP) play a role in a wide range of tumorigenesis, including early carcinogenesis events, tumor growth and tumor invasion and metastasis. Given that the ability of tumor cells to infiltrate and disseminate widely is what makes the tumors malignant, a role of MMP in cell migration during this invasive and metastatic process is important. There are two types of cancer cell migration: single cell locomotion and cohort migration (cell movement en mass keeping cell-cell contact, which is frequently seen in better differentiated carcinomas). Cell surface localization and activation of MMP is essential for cells to migrate, through rearrangement of extracellular matrix (ECM) to suit cell migration. Certain MMP, such as gelatinases and membrane -type 1 MMP, have special mechanisms to localize at leading edges in both types of cell migration. Moreover, in cohort migration, expression of these MMP is regulated via cell-cell contact within migrating cell sheets and confined to the foremost pathfinder cells of the migrating cell sheets. New roles of cell surface MMP, such as cleavage of cell surface receptors or cofactors involved in cell-ECM interactions during cell migration, are also discussed.

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As the numbers of aging patients with manifestations of renal disease increase, the elderly must frequently undergo renal biopsies. This study examined the characteristics of clinicopathological correlations in elderly patients. Medical and clinical records from renal biopsies registered in two hospitals between January 2000 and December 2004 were reviewed. Among 406 patients (female: male 224/182; age 43.9 +/- 18.8 years, mean +/- SD) who underwent renal biopsies, 61 (15.1%) who were aged 65 years and older (female: male, 29/32; age 72.8 +/- 5.2 years) were selected. The elderly usually underwent percutaneous renal biopsies for renal diseases such as nephrotic syndrome (43%) and acute or rapidly progressive renal failure (A/RPRF, 39%). Focal/segmental glomerulosclerosis (23%), minimal change disease (19%), and membranous nephropathy (15%) are frequently diagnosed based on biopsy specimens from patients with nephrotic syndrome. Among patients presenting with A/RPRF, 17 (71%) and 4 (17%) had pauci-immune, MPO-ANCA positive, crescentic glomerulonephritis and interstitial nephritis, respectively, and benefited from therapeutic intervention. Histopathological and pre-biopsy clinical diagnoses differed in nine (15%) patients. The complication rate after biopsy was low (3%). Primary glomerular diseases presenting with nephrotic syndrome and primary crescentic glomerulonephritis associated with rapidly progressive renal failure were the most frequently diagnosed among the elderly who underwent renal biopsy. Percutaneous renal biopsy provides clinically useful information about the elderly because clinical presentation and the predicted diagnosis sometimes vary.

This evidence suggests that c-Met expression in the brain could be associated with astrocytoma progression and also reactive process. Immunohistochemical determination of c-Met-expressing cell types helps to understand possible roles of c-Met in tumour tissues.

BackgroundA new histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was recently proposed. We evaluated the predictive value of this classification for renal outcome in Japanese patients.MethodsWe enrolled 122 patients with ANCA-associated glomerulonephritis diagnosed at several institutions in Japan between January 2000 and March 2010. Twenty patients were excluded because of observation durations of <1 year, and/or because their biopsy specimens contained <10 glomeruli. Renal biopsy specimens were categorized into four classes according to the proposed classification. We evaluated the predictive value of immunohistochemical staining for α-smooth muscle actin (SMA), Wilm’s tumor 1 (WT1), CD68, and cytokeratin for end-stage renal disease (ESRD).ResultsThe study population included 54 men and 48 women. Age, estimated glomerular filtration rate (eGFR), and proteinuria were 66.3 ± 11.3 years, 21.6 ml/min. and 1.10 g/24 h, respectively. Eighty-six patients were positive for myeloperoxidase-ANCA, five were positive for proteinase 3-ANCA, and 11 were negative for both antibodies. Median follow-up time was 41.0 months. Twenty-three patients (22.5%) developed ESRD during the follow-up period. Twelve patients died during follow up; 7/12 patients developed ESRD before death, and 5/12 patients died without ESRD. The incidence of ESRD increased with sequential categories: focal, 2/46 (4.3%); crescentic, 9/32 (28%); mixed, 8/18 (44%); and sclerotic, 4/6 (67%). The focal class had the best renal survival and the sclerotic class had the worst renal survival (p < 0.001). Kaplan-Meier renal survival analysis was similar to that of the new classification system proposal. In the multivariate analysis, the classification system tended to be a prognostic factor for ESRD (p = 0.0686, crescentic, mixed and sclerotic vs. focal, hazard ratio (HR) [95% confidence interval, CI]; 2.99 [0.61–22.7], 5.04 [1.11–36.4] and 9.93 [1.53–85.7], respectively). α-SMA-positivity also tended to be associated with ESRD (p = 0.1074).ConclusionThe new histopathological classification was associated with eGFR at 1 year and tended to be associated with ESRD in our Japanese cohort with ANCA-associated glomerulonephritis. α-SMA positivity might be an additional prognostic factor for ESRD.