BACKGROUND: Autologous cultured dermal fibroblasts can be transplanted to the full thickness of skin wounds and this successfully accelerates the early wound healing of epidermis and dermis with less inflammation and scarring than allogeneic transplantations. The wound-healing effect of dermal fibroblasts is thought to be due to their growth factor and extracellular matrix releasing effects. Fibroblasts could therefore help chronic wound healing, where lower concentration of growth factors have been observed. OBJECTIVE: The purpose of this study was to examine the early wound healing effects of the autologous cultured dermal fibroblasts and to confirm that several growth factors and fibroblasts are closely associated in the mechanism of wound healing. METHODS: Suspensions of cultured autologous dermal fibroblasts were transplanted to full thickness wounds in 15 guinea pigs, and the wounds were then covered with transparent membrane. Wound biopsy materials were excised and collected from 9 guinea pigs at 7, 14, 21 and 28 days after wounding. Comparisons of the clinical wound healings between the experimental and control groups at the 3rd, 7th and 14th day after fibroblast transplantations were made in 8 guinea pigs, in which continuous clinical observation was possible in the same guinea pigs. Samples were processed for routine hematoxylin and eosin stains, immunohistochemical stains for fibroblast growth factor (FGF), transforming growth factor beta (TGF-beta), vascular endothelial growth factors (VEGF), and insulin like growth factors (IGF). RESULTS: The experimental groups showed decreased wound surface area at 3 and 7 days after transplantations, and more vascular, granulomatous wounds and fibroplasia responses compared with the control groups. Immunohistochemal stains revealed increased positive staining for FGF, TGF beta, and VEGF at the 1st, 2nd and 3rd weeks, compared with the controls. CONCLUSION: Transplantations of autologous cultured dermal fibroblasts proved to be clinically effective in the early wound healing of full thickness wounds of guinea pigs, and growth factors such as FGF, TGF VEGF must have some role in the mechanism of wound healing by autologous dermal fibroblasts.
Animals ; Biopsy ; Cicatrix ; Coloring Agents ; Dermis ; Eosine Yellowish-(YS) ; Epidermis ; Extracellular Matrix ; Fibroblast Growth Factors ; Fibroblasts* ; Guinea Pigs* ; Guinea* ; Hematoxylin ; Inflammation ; Intercellular Signaling Peptides and Proteins ; Membranes ; Skin ; Somatomedins ; Suspensions ; Transforming Growth Factor beta ; Transplantation ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Wound Healing* ; Wounds and Injuries*

BACKGROUND: Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. METHOD: Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). RESULTS: Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression n stromal cells was significantly associated with p-stage in non-small cell lung cancer (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T-factor, nodal involvement, differentiation. Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with progonosis showed that nodal involvement was the only independent prognostic factor in all patients. CONCLUSION: Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.
Adenocarcinoma ; Breast Neoplasms ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cathepsin D* ; Cathepsins* ; Humans ; Lung Neoplasms ; Multivariate Analysis ; Neoplasm Metastasis ; Paraffin ; Prognosis* ; Stromal Cells ; Survival Rate