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*

OBJECTIVE: Some growth factors may promote tumor growth by affecting tumor angiogenesis. Midkine(MK) are polypeptides that belong to a new family of heparin-binding growth/differentiation factor and has also been reported to be angiogenic. In various tumor tissues, MK was highly expressed between tumor and normal tissues; however, the pattern of MK expression in normal cervix and cervical cancer has not been established. The aim of this study was to determine the MK mRNA expression in cervical cancer. And we questioned whether its expression is related to cancer stages and prognostic factors. METHODS: The cervical and cervical cancer tissues were taken from patients; healthy women(n=15), and the patients with cervical cancer(n=29). The MK mRNA expression was examined by quantative competitive PCR after polymerase chain reaction amplification of reverse transcriptase copies of RNA transcripts(RT-PCR). RESULTS: The cervical cancer expressed higher levels of MK mRNA than normal cervix(p<0.05). The MK mRNA expression was not correlated with the cervical cancer stage and histopathologic type(p>0.05). CONCLUSION: These results suggested that increased MK mRNA expression is associated with the development of cervical cancer.
Cervix Uteri ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; Peptides ; Polymerase Chain Reaction ; RNA ; RNA, Messenger* ; RNA-Directed DNA Polymerase ; Uterine Cervical Neoplasms*

OBJECTIVES: Cadherin/catenin adhesion complex is fundamentally involved in epithelial cancer invasion and metastasis. E-cadherin and EGFR colocalize on the basolateral membrane of epithelial cell and EGF down-regulate E-cadherin expression. In the invasion and metastasis of cancer, E-cadherin expression is decreased and growth factors receptor is overexpressed. The present study was aimed to find the role of E-cadherin, beta-and gamma-catenin, growth factors and its receptors in cervical cancer cell lines. METHODS: The cervical cancer cell cultures were treated with different time duration of EGF 30 ng/ml and TGF-a 10 ng/ml(0, 10 min, 20 min, 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 24 hr). The change in cancer cell morphology and the changes in E-cadherin, beta- and gamma-catenin, EGFR and activated EGFR expression were studied with a western blot analysis and an immunoprecipitation. RESULTS: Through a western blot analysis, E-cadherin 120 kDa band and EGFR 170 kDa band were expressed in CaSki, HT-3 and ME-180 cell line, which showed epithelial contact growth. 1n these 3 cell lines, expression of E-cadherin did not decrease with time dependent manner. after the treatment of EGF and TGF- alpha. The expression of EGFR decreased and activated EGFR expression increased in 30 minutes to 1 hour but decreased subsequently. When the cells treated with EGF, there were no change in beta-and gamma-catenin expression with there dependent manner. The tyrosine phosphorylation of beta-and gamma-catenin increased in 30 minutes to 1 hour but decreased subsequently with activated EGFR. CONCLUSION: This study showed that an activated EGFR which has involved with tyrosine phosphorylation of beta- and gamma-catenin influenced by growth factors rather than expression of E-cadherin, has a role in the invasion and metastasis of the cervical cancer.
Blotting, Western ; Cadherins* ; Cell Culture Techniques ; Cell Line* ; Epidermal Growth Factor* ; Epithelial Cells ; gamma Catenin* ; Immunoprecipitation ; Intercellular Signaling Peptides and Proteins ; Membranes ; Neoplasm Metastasis ; Phosphorylation* ; Transforming Growth Factor alpha* ; Tyrosine* ; Uterine Cervical Neoplasms*

Angiogenesis is an essential requirement for development, progression, and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) is one of the important angiogenic factors. Recently the role of angiogenesis has been known in premalignant lesions. This study was performed to determine whether the angiogenesis and VEGF expression were increased in association with histological grade of cervical intraepithelial neoplasia (CIN) and to see the relationship between the angiogenesis and VEGF. Immunostainings for factor VIII and VEGF were performed on 52 cases of cervical neoplasia (12 cases of CIN I, 11 cases of CIN II, 15 cases of CIN III, 7 cases of microinvasive squamous cell carcinoma, and 7 cases of invasive carcinoma) and 5 cases of normal cervix. The results showed a significant increase of microvessel count from normal cervix through CIN grades to invasive squamous cell cacinoma. VEGF expression was increased in proportion to the CIN grades. There was no significant correlation between microvessel count and VEGF expression. In conclusion, the tumor angiogenesis is an early event in tumorigenesis of uterine cervix. In addition, no significant relationship between the microvessel count and VEGF expression in CIN suggests the possibility of other growth factors affecting mainly angiogenesis of premalignant lesion of uterine cervix.
Angiogenesis Inducing Agents ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Factor VIII ; Female ; Intercellular Signaling Peptides and Proteins ; Microvessels ; Neoplasm Metastasis ; 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*

OBJECTIVE: In this study, we evaluated the expression of FAS-associated factor 1 (FAF1) and heat shock protein 70 (HSP70) in normal ovary and ovarian cancer, and also analyzed the correlation between FAF1 and HSP70 in ovarian cancer. METHODS: The patient group consisted of 29 unrelated Korean women diagnosed as ovarian cancers and control samples were obtained from 7 patients who underwent oophorectomy for benign disease of uterus, and normal ovary was confirmed histologically from biopsy. We examined FAF1 and HSP70 expression by western blot analysis and immunohistochemical staining in normal ovary and ovarian cancer. Furthermore, we examined a correlation between FAF1 and HSP70 in ovarian cancer. RESULTS: The expression of FAF1 was lower in ovarian cancer than that in normal ovary (P=0.02), and the expression of HSP70 was increased in ovarian cancer in comparison to that in normal ovary (P=0.03). The expression of FAF1 was decreased in advanced stages (stage III or stage IV) as compared with early stages (stage I or stage II) (P=0.01). The expression of HSP70 was not significantly related with ovarian cancer histology (P=0.10), but the expression of HSP70 was most increased with papillary serous carcinomas and undifferentiated ovarian cancer. The expression of FAF1 was inversely correlated with the expression of HSP70 in ovarian cancer (Spearman correlation coefficience=-0.47). CONCLUSION: We concluded that the expression of FAF1 or HSP70 each seems to have a meaning as a biomarker for early detection of ovarian cancer. The expressions of FAF1 and HSP70 seem to be more valuable in predicting ovarian cancer when used together because of their inverse correlation. This is the first study about the expression of FAF1 in ovarian cancer and the correlation between FAF1 and HSP70 expression in ovarian cancer.
Biopsy ; Blotting, Western ; Female ; HSP70 Heat-Shock Proteins* ; Humans ; Ovarian Neoplasms* ; Ovariectomy ; Ovary ; Uterus

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*

OBJECTIVE: We investigated the expression of TSP-1 and -2 in eutopic endometrium of advanced endometriosis and control patients. METHODS: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29-44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage III and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression from eutopic endometrium for TSP-1 and -2 were analyzed by RT-QC PCR. RESULTS: The mRNAs of TSP-1 and -2 were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. There were no significant differences in expression of TSP-1 and TSP-2 in eutopic endometrium between controls and endometriosis patients. CONCLUSION: Our results indicated that TSP-1 and -2 had no crucial role compared to other molecules in the regulation of angiogenesis. These findings also suggest that dysregulation of other angiogenic regulators would be concerned in pathophysiologic role in endometriosis development.
Endometriosis* ; Endometrium ; Female ; Humans ; Hysterectomy ; Laparoscopy ; Menstrual Cycle ; Polymerase Chain Reaction ; RNA, Messenger* ; Thrombospondin 1 ; Thrombospondins

OBJECTIVE: We investigated the expression of uPA and uPAR in eutopic endometrium of advanced stage endometriosis and control patients. METHODS: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29~44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage III and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression of uPA and uPAR from eutopic endometrium were analyzed by RT-QC PCR. RESULTS: The mRNAs of uPA and uPAR were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. Uterine endometrium from women with endometriosis expresses significantly (p<0.05) higher levels of u-PA mRNA than endometrium from normal women without endometriosis in the proliferative phase. There were no significant differences in expression of uPAR in eutopic endometrium between controls and endometriosis patients. CONCLUSION: These results suggest that eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater u-PA mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one etiology for the invasive properties of the endometrium resulting in the development of endometriosis.
Endometriosis* ; Endometrium* ; Female ; Humans ; Hysterectomy ; Laparoscopy ; Menstrual Cycle ; Polymerase Chain Reaction ; Proteolysis ; RNA, Messenger* ; Urokinase-Type Plasminogen Activator