There is considerable need for reliable prognostic markers to guide clinicians in management decisions for the breast cancer. The cell cycle is governed by a family of cyclin-dependent kinases(Cdks), regulated by associated cyclin p27, a cyclin dependent kinase inhibitors, regulates progression from GI into S phase by inhibiting cyclin/cdks complex. This study was performed to evaluate the association between p27 expression, determined by immunohistochemical stain, and various histopathologic features in breast cancer. It was also determined whether p27 expression had the significance as the prognostic factorin the breast cancer patients. 45 patients who got the relatively good preserved paraffin blocks among the 100 patients was chosen for immunohistochemical staining against p27, cyclin E, c-erbB2, cathepsin D and p53 and reexamined their unclear and histological grades from Jan. 1989 through Dec. 1992. As a results, the patients with negative expression of p27 had more metastatic axillary nodes than those with positive expression. (5.87+/-1.87 vs 1.14+/-0.54, p=0.021) p27 negative group got worse nuclear grade than p27 negative group but beyond statistical significance. (48.4% vs 28.6%, p=0.281) On univariate analysis, primary tumor size, status of axillary nodes and the expression of p27 were the significant prognostic factors affecting overall survival rates. In particular, p27 positive group had better outcomes on 5 years survival rate than p27 negative group. (92.31+/-7.39% vs 73.33+/-8.07%, p=0.0441) but didn't affect the disease free survival with statistical significance. On multivariate analysis, the primary tumor size and axillary node were significant prognostic factors on overall and disease free survival. In conclusion, despite relativeiy small size of this study group, considering that p27 negative group got the more metastatic node and worse overall survival, 27 expression might be a novel prognostic indicator in the breast cancer.
Breast Neoplasms* ; Breast* ; Cathepsin D ; Cell Cycle ; Cyclin E* ; Cyclins* ; Disease-Free Survival ; Humans* ; Multivariate Analysis ; Paraffin ; Phosphotransferases ; S Phase ; Survival Rate

OBJECTIVETo study the effect of imbalance between lysosomal enzymes and their inhibitors in blood on disturbance of the local and whole body after trauma.

METHODSThe dynamic changes of lysosomal enzymes and proteinase inhibitors were studied in 12 pigs with femoral comminuted fractures in both hind limbs caused by high velocity missiles. Four normal pigs served as controls.

RESULTSAfter injury, the activity of Cathepsin D in arterial plasma increased gradually and reached the highest level at 8 hours, acid phosphatase in serum began to increase at 12 hours and the value of serum elastase did not change significantly. The level of alpha1-antitrypsin, a proteinase inhibitor in plasma, decreased significantly in the early stage after injury [73.5%+/-6.4% and 81.0%+/-5.1% of the baseline value (1.67 micromol x ml(-1) x min(-1)+/- 0.29 micromol x ml(-1) x min(-1)) at l and 2 hours after injury, respectively, P<0.05], then increased gradually and was higher than the baseline value at 12 hours after injury.

CONCLUSIONSImbalance between lysosomal enzymes and proteinase inhibitors occurs soon after injury, which might result in continuous tissue damage and play an important role in the disturbance of general reaction after injury.

Acid Phosphatase ; blood ; Animals ; Cathepsin D ; blood ; Endopeptidases ; blood ; Female ; Lysosomes ; enzymology ; Male ; Pancreatic Elastase ; blood ; Swine ; Wounds, Gunshot ; blood ; alpha 1-Antitrypsin ; analysis

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

BACKGROUND/AIMS: A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients. METHODS: Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens. RESULTS: Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002). CONCLUSIONS: Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy.
Adenocarcinoma/*pathology ; Adenocarcinoma, Mucinous/pathology ; Adult ; Aged ; Cathepsin D/analysis ; Colorectal Neoplasms/*pathology ; Cyclooxygenase 2/analysis ; Female ; Humans ; Ki-67 Antigen/analysis ; Male ; Middle Aged ; Prognosis ; Receptor, Epidermal Growth Factor/analysis ; Receptor, ErbB-2/analysis ; Survival Analysis ; Tumor Markers, Biological/*analysis ; Tumor Suppressor Protein p53/analysis

OBJECTIVETo investigate the effects of HCMV infection on phenotypes of parotid duct epithelial cells and relative mechanisms.

METHODSThe expressions of immediate early antigen of HCMV, pan cytokeratin and cathepsin D etc. were detected by immunohistochemical staining in tissues of parotid cytomegalic inclusion disease.

RESULTSCytokeratin which acts as an epithelial marker became negative while staining of Cathepsin D was intensified in parotid duct epithelial cells after infected by HCMV.

CONCLUSIONIt demonstrated that cytokeratin was lost through over-expression of Cathepsin D in parotid duct epithelial cells infected by HCMV.

Animals ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Antigens, Viral ; analysis ; Cathepsin D ; analysis ; Cytomegalovirus ; immunology ; physiology ; Cytomegalovirus Infections ; metabolism ; pathology ; virology ; Desmin ; analysis ; Epithelial Cells ; metabolism ; pathology ; virology ; Female ; Glial Fibrillary Acidic Protein ; analysis ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; Infant ; Keratins ; analysis ; Male ; Mice ; Salivary Ducts ; metabolism ; pathology ; virology ; Vimentin ; analysis

BACKGROUNDE-cadherin, beta-catenin, cathepsin D, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 are all invasion-related proteins. The expression patterns of these proteins in invasive ductal breast carcinomas, and their associations with known clinicopathological parameters, tumor recurrence and expressions of estrogen receptor (ER), progesterone receptor (PR), PS2 and c-erbB2 were not well studied in Chinese patients.

METHODSIn a set of 94 invasive ductal breast carcinomas, protein expressions of these molecular markers were investigated by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence and expressions of ER, PR, PS2 and c-erbB2 were also examined. In addition, the interrelationship between the expressions of these proteins were studied.

RESULTSPreserved membrane E-cadherin expression was associated with late tumor stage and tumor recurrence, whereas the reduced junctional beta-catenin associated with positive lymph node status and c-erbB2 overexpression. Positive staining of cathepsin D in tumor stromal cells displayed a significant association with late tumor stage. High expression of MMP-2 in cancer cells was associated with large tumor size and PR positive expression. TIMP-2 expression was positively associated with tumor recurrence. In addition, inter-relationship between the expressions of these biomarkers was also assessed. Cathepsin D staining in cancer cells was inversely correlated with its staining in stromal cells, and also inversely correlated with MMP-2 staining in tumor stromal cells. MMP-2 expression in stromal cells displayed an inverse correlation with TIMP-2 expression. MMP-9 expression displayed parallel associations with TIMP-1 and TIMP-2 expression.

CONCLUSIONEvaluation of E-cadherin, beta-catenin, cathepsin D, MMP-2 and TIMP-2 expression may be of some help in more accurately predicting the prognosis of invasive ductal breast carcinomas.

Adult ; Aged ; Breast Neoplasms ; chemistry ; pathology ; Cadherins ; analysis ; Carcinoma, Ductal, Breast ; chemistry ; pathology ; Cathepsin D ; analysis ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2 ; analysis ; Matrix Metalloproteinase 9 ; analysis ; Middle Aged ; Tissue Inhibitor of Metalloproteinase-1 ; analysis ; Tissue Inhibitor of Metalloproteinase-2 ; analysis ; beta Catenin ; analysis