ABSTRACT
PURPOSE: Vascular endothelial growth factor (VEGF) known as an angiogenic factor is a potent inducer of pathologic neovascularization. The purpose of this study is identifying the relationship between serum PSA, invasiveness and VEGF expression in prostatic cancer. MATERIALS AND METHODS: Ex-vivo study with immunohistochemical stain analysis for VEGF expression was performed on 18 paraffin embedded specimens of prostatic cancer patients who were treated with radical prostatectomy. VEGF expressions were classified by three groups (1+ , 2+ , 3+ ) according to the degree of staining of cancer cell. Biochemical failure and recurrence were determined by Takayama's IMx PSA assay criterion (>0.1ng/ml) following radical prostatectomy. RESULTS: Immunohistochemical studies demonstrated that each group contained 1, 2, 8 patients in advanced disease (n=11), and 3, 2, 2 patients in localized disease (n=7), respectively. All cases in strong positive (3+ ) group had Gleason sum higher than 7 and nadir PSA values were lower than 0.1ng/ml except one case. We found no correlation between initial PSA and VEGF expression (p=0.361). Three biochemical recurrent patients were identified as strong positive VEGF expression. CONCLUSIONS: Our study indicates that patients with advanced stage and higher Gleason sum have a trend with more VEGF expression than patients with localized disease. Identifying the angiogenesis factors especially, VEGF involved in prostatic cancer growth and understanding their regulation will lead to the developement of anti-angiogenic strategies useful for diagnostic studies and therapeutic interventions.
Subject(s)
Humans , Angiogenesis Inducing Agents , Neovascularization, Pathologic , Paraffin , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Recurrence , Vascular Endothelial Growth Factor AABSTRACT
Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues. Apoptotic cell death plays an important role in the proliferation and turnover of cells in various tumors. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. Flowcytometric analysis of the cellular DNA content appears to be a useful clinical prognostic indicator in colorectal cancer. The relationship of apoptotic index(AI) and proliferative indices have being investigated. We analyzed the tumor DNA content and AI in 84 patients who underwent resection for colorectal cancer between January 1989 and December 1994 in order to evaluate the prognostic significance of apoptosis, DNA ploidy and index using in situ apoptosis detection method and flowcytometry. The mean value of AI was 32.4, and median value 21. In the cellular DNA, forty-two percent of the tumors were diploidy, fifty-eight percent aneuploidy. The mean value of DNA index(DI) was 1.38, G0/G1 72%, S phase fraction 21.7%, G2/M 6.3%, and proliferative fraction 28%. There was no significant difference between AI and tumor invasion, LN metastasis, DNA ploidy, DI.(p>0.05) There was no significance between overall survival and AI, DNA ploidy, DI. But patients who had tumors with low DNA index had a significantly longer disease free survival than high DNA index.(p<0.05) As a result, this study shows that AI is a less useful as prognostic factor and DNA index is a more important prognostic factor in patients undergoing surgery for colorectal cancer.
Subject(s)
Humans , Aneuploidy , Apoptosis , Cell Death , Colorectal Neoplasms , Diploidy , Disease-Free Survival , DNA , Drug Therapy , Heating , Hot Temperature , Neoplasm Metastasis , Ploidies , S PhaseABSTRACT
Excimer laser PRK (photorefractive keratectomy) for myopic correction provides an accurate correction in the cases of moderate myopia with a little side effect, but in high myopia it frequently causes corneal opacity and myopic regression. To determine the etiology of the corneal opacity, the author studied on the immunohistochemical stain for heat shock protein 72/73 after myopic excimer laser PRK. Thirty Newzealand white rabbits (60 eyes) were divided into four groups: A, B, C, and control group. Myopic PRK was carried out on the cornea to correct the amounts of -6D myopia(group A), -9D(group B), and -15D(group C) with multizone technique using Excimer laser(VisX 20/20, Sunnyvale, USA). The corneal status was examined using a slit lamp. The eyes were enucleated at 6, 24, 48hours, 1 week and 8 weeks after operation. The corneas were obtained and sectioned for immunohistochemical stains. Corneal opacity was found with the mean density of 0.83(A group), 1(B group), and 1.67(C group) 8 weeks after the operation. Hsp 72 immunoreactive staining was noted in corneal epithelium in the C group at 24 hours after operation and maximal expression was found at 48 hours after operation. Hsp 73 was seen in corneal epithelium and stroma of all group. But maximal expression was observed in B and C groups 48 hours after operation. Consquently, the author believes that hsp 72/73 might be an important role of corneal haziness following PRK.
Subject(s)
Rabbits , Coloring Agents , Cornea , Corneal Opacity , Epithelium, Corneal , Heat-Shock Proteins , Hot Temperature , Lasers, Excimer , Myopia , Photorefractive KeratectomyABSTRACT
The bcl-2 proto-oncogene was first described as a result of the chromosomal translocation t(14:18) seen in a large number of follicular B-cell lines. Bcl-2 is so far unique a proto-oncogene in that it codes for an inner mitochondrial membrane protein. This protein regulates the programmed cell death called apoptosis. This study was designed to investigate expression of bcl-2 protein in 81 human breast cancer by using immunohistochemical staining with the monoclonal antibody of bcl-2 protein. Also this factor was compared with established clinicopathological prognostic factors and hormone receptors. The bcl-2 protein expression was positive in 38(47%) cases and was negative in 43(53%) cases. There was significant correlation between bcl-2 protein expression and histologic grade(p=0.014). Positive expression of bcl-2 protein was correlated with positive estrogen(p=0.051) and progesterone(p=0.059) receptors, but this correlation was not significant. Bcl-2 expression failed to show its prognostic role for overall(p=0.115) and disease free(p=0.214) survival. In conclusion, the bcl-2 protein is often expressed in half of breast cancer, and its expression is associated with histologic grade and hormone receptor status, but the overall and disease free survival of breast cancer patient do not appear to be influenced by bcl-2 protein expression.
Subject(s)
Humans , Apoptosis , B-Lymphocytes , Breast Neoplasms , Breast , Cell Death , Disease-Free Survival , Mitochondrial Membranes , Proto-Oncogenes , Translocation, GeneticABSTRACT
Mortality associated with human breast carcinoma is almost entirely due to subsequent cancer metastasis, but the molecular basis of this metastasis is not well established. The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in chromosome 17q22. This gene has been known to be involved in the metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. Tumor angiogenesis, the process leading to the formation of new vessels, plays a central role in tumor progression and distant metastasis. It is implicated in the phenomenon of dormant micrometastasis. This study was designed to determine the prognostic value of expression of the nm23 protein and tumor angiogenesis in breast cancer. Also, these two factors were compared with established clinicopathological prognostic factors and hormone receptors. 118 paraffin embedded surgical specimens of breast cancer were obtained from March, 1988 to February, 1994 and were selected for study. The expression of nm23 protein was studied by using immunohistochemical staining with anti-nm23/nuclear diphosphate kinase A. Tumor angiogenesis was quantified under light microscope by counting of the tumor microvessels(MVC) which were highlighted with anti-CD31 antibodies. The patient were allocated into two groups by mean number of MVC, one group was less 42 and the other was over 42. All the patients were female. The nm23 protein expression was positive in 74(63%) cases and was negative in 44(37%) cases. There was a significant correlation between nm23 protein expression and histologic grade(p=0.023). Positive expression of nm23 protein was correlated with positive estrogen(p=0.031) and progesterone receptors(p=0.001). Also Positive expression of nm23 protein was correlated with longer disease free survival(p=0.0026) and overall survival(p=0.0048). The group of MVC42. But the MVC and established clinicopathological prognostic factors did not show any correlation, neither with hormone status. When the nm23 protein and angiogenesis were considered together, 50 cases of negative nm23 protein and MVC<42 showed the best survival in overall(p=0.0111) and disease free survival(p=0.0114) among the four groups of each combination. In conclusion, the expression of nm23 protein and tumor angiogenesis can be used as new prognostic factors in conjunction with established other prognostic factors.