OBJECTIVES: The TGF-Beta1 (transforming growth factor-Beta1 ), which has been shown to inhibit cellular proliferation in vitro as a growth regulator, has been demonstrated to enhance tumori-genicity in vivo. The proteolytic processes of cancer are thought to be the crucial point in tumor invasion and metastasis, mainly by matrix metalloproteinases.(MMPs) We investigated the serum TGF-Beta1 and MMP-2 levels in patients with cervical cancer in contrast to those of normal, patients with benign myoma, and cervical intraepithelial neoplasia (CIN). And we questioned whether these serum levels are different according to the therapy of cancer or not. METHODS: We measured serum TGF-Beta1, MMP-2 concentrations by ELISA in 34 patients with cervical cancer, as well as 5 normal volunteers, 14 patients with benign myoma and 23 patients with CIN. Especially in 7 patients with cervical cancer, we measured serum TGF-Beta1, MMP-2 levels before and after therapy. RESULTS: The serum TGF-Beta1 levels in patients with cervical lancer(37.8 +/-15.4pg/ml) were significantly lower than those of the patients with CIN(46.2+/-9.2pg/ml)(p<0.05). But there is no differences among the serum MMP-2 levels in the patients with cervical cancers(680.30+/-116.6pg/ml), CIN(715.2+/-150.0pg/ml), and benign myoma(682.4+/-112.5pg/ml)(p>0.05). Patients undergoing cancer therapy did not have different values of serum TCF-Beta1 and MMP-2 levels as those without cancer therapy.(p>0.05) CONCLUSION: So we suggest that serum TGF-Beta1 may be helpful in differential diagnosing cervical cancers from CIN.
Cell Proliferation ; Cervical Intraepithelial Neoplasia* ; Enzyme-Linked Immunosorbent Assay ; Healthy Volunteers ; Humans ; Myoma ; Neoplasm Metastasis ; Transforming Growth Factor beta1* ; Uterine Cervical Neoplasms*

OBJECTIVES: Angiogenesis is a critical factor in the growth, progression, and metastatic spread of solid tumors. Angiogenic factors are soluble molecules released by the tumor itself and are able to induce an angiogenic response. Vascular endothelial growth factor(VEGF) is a multifunctional cytokine that has been shown to be an important regulator of tumor angiogenesis. The aim of this study was to determine the value of serum VEGF levels in the diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. And we questioned whether the serum VEGF levels are related to cancer stages and prognosis of patients. METHODS: Serum samples were taken from 85 patients; healthy women(n=15), the patients with benign ovarian cyst(n=36), and the patients with ovarian cancer(n=34). The concentration of VEGF, CA-125, and CA 19-9 were determined in the serum of each patients before and after treatment with an enzyme linked immunoassay(EIA), RESULTS: There are statistical differences among the serum VEGF levels in patients with ovarian cancer(491.5+/-335.6 pg/ml), and benign ovarian cyst (247.7+/-183.6 pg/ml)(p<0.05). The patients undergoing cancer therapy had lower values than those without cancer therapy(p<0.05). The serum VEGF levels were not correlated with the cancer stages and histologic types(p>0.05) CONCLUSION: The serum VEGF level appears to be a helpful tool in the differential diagnosis of ovarian cancer and may help in predicting the therapeutic effects of patients with ovarian cancer.
Angiogenesis Inducing Agents ; Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Ovarian Cysts ; Ovarian Neoplasms* ; Prognosis ; Vascular Endothelial Growth Factor A*

In comparison with normal cervix, mitosis occur more frequently in cervical intraepithelial neoplasia(CIN) and are seen at high levels, suggesting that CIN may be associated with a progressive dysfunction in proliferative activity of cervical cells. This study aims that expression of proliferative cell nuclear antigen(PCNA) was examined to determine proliferative activity at the cell of CIN. Sixty four colposcopic biopsies from patients with cytologically and/or colposcopically dtagnosed condyloma and CIN. The cases were classified as follows ; 19 as normal cervix and condyloma, 15 as CIN I, 16 as CIN II and 14 as CIN III. Immunohistochemical detection of PCNA was performed on paraffin sections by the streptavidin-biotin peroxidase method using the monoclonal antibody PC10. There was a statisically significant correlation between the CIN grade and the PCNA grade(p<0.05). In addition, the PCNA grade showed significant correlation with mitotic grade(p<0.05) and the CIN grade was also observed(p<0.05). This study suggests that the cell proliferation index as detected immunohistochemically using PCNA may be a useful adjunct to histopathological diagnosis of various grades of CIN.
Biopsy ; Cell Proliferation ; Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Diagnosis ; Female ; Humans ; Mitosis ; Paraffin ; Peroxidase ; Proliferating Cell Nuclear Antigen*

BACKGROUND: EGF and TGF-a are ligands for the EGF-receptor and act as mitogens for a variety of tissues. TGF-a, in particular, has been implicated as an autocrine growth factor for several cancer cell lines. TGF-B exerts an inhibitory effect on the growth of most epithelial cell types, and the loss of responsiveness to this growth inhibition has been implicated in the development of a variety of human cancers. In the present study, we evaluate whether EGF, TGF-a and TGF-B modulate apoptosis and cell cycle progression in cervical cancer cell lines. MATERIALS & METHODS: The effect of EGF, TGF-a and TGF-B on apoptosis and cell cycle such as CaSki and HeLa cell lines was analysed by flow cytometry RESULTS: 1. TGF-B did not induce apoptosis in CaSki and HeLa cell lines. 2. TGF-B as well as EGF, TGF-a, did not affect the process of apoptosis significantly. 3. The time to occur apoptosis was different between CaSki and HeLa cells treated by growth factots. 4. G1 phase was the checkpoint in CaSki and HeLa cells treated with TGF-B. CONCLUSION: These results suggest that TGF-B as well as EGF, TGF-a does not induce apoptosis and cell growth inhibition.
Apoptosis* ; Cell Cycle Checkpoints* ; Cell Cycle* ; Cell Line* ; Epidermal Growth Factor* ; Epithelial Cells ; Flow Cytometry ; G1 Phase ; HeLa Cells ; Humans ; Ligands ; Mitogens ; Uterine Cervical Neoplasms*

The technique of plssma exchange has been applied to a number of immune disorders in which c4eulating antibodies are present. We observed a patient with bullous pemphigoid and serious side effects of longterm use of steroid therspy. We applied ten times of plasmapheresis to him over six months period. After the plasmapheresis, clinical symptoms have greatly improved and steroid maintenance doses have been decreased. We have not observed any side effect of plasmapheresis such as thrambotopenia or hypogarnrnaglobulinemia during the whole therapeutic period.
Antibodies ; Humans ; Immune System Diseases ; Pemphigoid, Bullous* ; Plasmapheresis*

OBJECTIVE: SCC-Ag(Squamous Cell Carcinoma Antigen) is a tumor marker for patients with squamous cell carcinoma of the uterine cervix. It has shown that the SCC-Ag was well related with the response of cancer therapy and course of cervical cancer. The aim of this study is to investigate whether the presence of pelvic lymph node metstasis can be predicted by the measurement of the preoperative SCC-Ag levels in the patients with early staged squamous cell carcinoma of cervix. METHODS: The preoperative serum SCC-Ag levels were measured in 45 patients with stage I-II squamous cell carcinoma of cervix undergoing radical hysterectomy from September 1995 to December 1997. The serum SCC-Ag levels were analyzed for the clinicopathologic characteristics and other prognostic factors using univariate and multivariate analysis. RESULTS: The serum SCC-Ag levels of the patients exhibited pelvic lymph node metastasis were above 4.8ng/ml. An elevated preoperative serum SCC-Ag level, and tumor size were independent predictors for the presence of lymph node metastasis(p<0.01). CONCLUSION: The determination of the preoperative serum SCC-Ag levels provides a new prognostic factor in early staged cervical cancer.
Carcinoma, Squamous Cell* ; Cervix Uteri ; Female ; Humans ; Hysterectomy ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis* ; Uterine Cervical Neoplasms

Interferons(IFNs) exhibit an antiproliferative effect on many normal and transformed cells and have in vivo antitumor activity in a variety of cancers. Recent clinical studies have suggested major activity with IFNs, especially in advanced squamous cell carcinoma of the skin and cervix. With the objective of exploring how the IFNs might work in squamous carcinoma cell line, we studied the effect of IFN-a on cervical cancer cell lines. The effect of IFNs on apoptosis and cell cycle of cervical cancer cell lines(C33A, CaSki, SiHa, HeLa, ME-180) was analysed by flow cytometry in time dependent manner. Results were as follows: (1) According to cell count of studied cancer cell lines treated with 2,000 IU/ml IFN-a for 7 days exposure, IFN-a had the antiproliferative effect on all five tested cervical cancer cell lines. Also this antiproliferative effect was confirmed by WST-1 assay. (2) The effect of IFN-a on apoptosis of each cultute was analysed by flow cytometry after 3 days and 7 days exposure with 2,000 IU/ml IFN-a, Apoptosis was not induced by IFN-a treatment. (3) The effect of IFN-a on the cell cycle of each culture was analysed by flow cytometry after 3 days exposure with 2,000 IU/ml IFN-a. As compared to control cells, treatment with IFN-a resulted in a higher proportion of cells in S phase with lower portion of cells with G2/M phase. (4) Time course of IFN-a effect on HPV 16 and HPV 18 E6 mRNA levels was evaluated by northern blot analysis. In CaSki cell line, HPV 16 E6 mRNA expression induced by IFN-a was not inhibited. But in HeLa cell line, HPV 18 E6 inRNA expression was inhibited. IFN-a appears to have the antiproliferative effect on all five tested cervical cancer cell lines and the antiproliferative effect of IFN-a seemed to be induced not by apoptosis but by disruption on specific cell cycle. Also regulation of HPV E6 mRNA expression induced by IFN-a is not directly related to the mechanisms of the antiproliferative effect of IFN-a in cancer cell lines.
Apoptosis ; Blotting, Northern ; Carcinoma, Squamous Cell ; Cell Count ; Cell Cycle ; Cell Line* ; Cervix Uteri ; Female ; Flow Cytometry ; HeLa Cells ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; RNA, Messenger ; S Phase ; Skin ; Uterine Cervical Neoplasms*

Purpose: Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies. Materials and Methods: Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity. Results: Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein–Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability–high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1. Conclusions These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.

Purpose: Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies. Materials and Methods: Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity. Results: Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein–Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability–high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1. Conclusions These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.

Purpose: Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies. Materials and Methods: Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity. Results: Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein–Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability–high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1. Conclusions These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.