This study suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy.
We studied the effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing in genetically diabetic mice. Wound closure after full-thickness excision of skin was markedly delayed in diabetic mice compared to normoglycemic mice. A single application of bFGF caused a marked acceleration of wound healing in a dose-dependent manner. There were no hypertrophic scars or unlimited granulation tissue formation in regenerated tissues treated with any doses of bFGF under histological examination. The repeated application of bFGF for 7 d showed a bell-shaped dose-response in the rate of wound closure, and the optimal dose was as small as 0.2-2 mu g per wound. Reduced angiogenesis and granulation tissue formation were observed in diabetic mice compared to normal mice, and bFGF treatment restored both responses to significant levels. The beneficial effect of bFGF on wound healing would be largely explained by enhanced angiogenesis and granulation tissue formation.
Background. During the last two decades, a rising incidence of adenocarcinoma of the esophagus has been observed in the Western world. The prognostic relevance of tumor‐biological factors, such as DNA ploidy or c‐erbB‐2 overexpression, for overall survival following complete resection is still unknown.
Methods. In a retrospective study of 80 patients with adenocarcinoma of Barrett's esophagus, the prognostic significance of flow cytometric DNA ploidy determination was investigated. Overexpression of c‐erbB‐2 oncoprotein was studied by immunohistochemical alkaline phosphatase‐antialkaline phosphatase staining of formalin fixed, paraffin embedded tissue sections of the primary tumor.
Results. The rate of aneuploidy was 86%. Aneuploidy was significantly correlated with lymph node metastases only. c‐erbB‐2 oncoprotein overexpression of the primary tumor was detected in 15 patients (19%). A significant correlation was seen between c‐erbB‐2 overexpression and depth of tumor invasion, lymph node involvement, distant metastases, and status of residual tumor after resection (R category, International Union Against Cancer [UICC], 1987). All primary tumors with c‐erbB‐2 oncoprotein overexpression were aneuploid. In a multivariate Cox regression analysis for overall survival of those 62 patients (78%) whose tumor resection was macroscopically and microscopically complete (RO‐UICC), depth of invasion, distant metastases, and c‐erbB‐2 over‐expression were independent prognostic factors. The relative risk of death due to recurrence was nearly identical for patients with either c‐erbB‐2 oncoprotein overexpression or distant metastases: 4.06 (1.4–11.8) and 3.94 (1.6–9.5). In a multivariate Cox regression analysis of the subgroup of lymph node‐negative patients (n = 26), the ploidy status of the primary tumor (defined as neardiploid plus tetraploid versus aneuploid plus multiploid) was the only independent prognostic factor for overall survival.
Conclusions. These findings demonstrate that DNA ploidy as well as c‐erbB‐2 oncoprotein overexpression are valuable prognostic factors in patients with adenocarcinoma of Barrett's esophagus after complete tumor resection.
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