Yong-Tark Jeon

Genistein Inhibits Cell Growth by Modulating Various Mitogen-Activated Protein Kinases and AKT in Cervical Cancer Cells

Genistein, a soy‐derived isoflavone, inhibits growth of tumor cells from various malignancies. Here we investigated the effect of genistein on the growth of cervical cancer cells (HeLa and CaSki) and its possible mechanism. Genistein significantly suppressed cell growth of HeLa and CaSki cells at concentrations of 20 and 60 μmol/L, respectively, for 24 h. Western blotting analysis showed that genistein reduced phosphorylation of AKT and extracellular signal–regulated kinase (ERK)‐1/2 and induced phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase (JNK). Moreover, inhibition of ERK1/2 activity enhanced cell growth inhibition by genistein, whereas inhibition of p38 MAPK activity rescued from genistein‐mediated growth inhibition. Interestingly, inhibition of AKT activity recovered genistein‐induced growth inhibition in CaSki cells but did not in HeLa cells. However, inhibition of JNK activity seemed to have little effect on cell growth inhibition by genistein. Taken together, these results suggest that genistein could inhibit cell growth by inhibiting ERK1/2 activity and activating p38 MAPK.

Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer

OBJECTIVE Activation of the mammalian target of rapamycin (mTOR) pathway enhances cell survival and growth by regulating the efficiency of protein translation. This study was conducted to evaluate the association of activated mTOR signaling molecules with the clinicopathologic characteristics in epithelial ovarian cancer. METHODS Immunohistochemical staining with antibodies against p-4EBP1, p-mTOR, and p-p70S6K were performed on specimens of 103 patients with ovarian cancer. Tumors were classified as chemoresistant in cases where time to recurrence after the end of chemotherapy was shorter than 6months. RESULTS Expressions of p-mTOR, p-4EBP1, and p-p70S6K were detected in 47.6%, 85.4%, and 64.1% of all patients, respectively. p-4EBP1 overexpression was associated with advanced stage (p=0.04), histologic grade (p<0.01), residual mass (p<0.01), shorter disease-free survival rate (p=0.01) and chemoresistance (p=0.02). p-p70S6K was associated with residual mass with marginal significance (p=0.06). p-4EBP1 expression was correlated with p-p70S6K expression (r=0.42, p<0.01), whereas p-mTOR was not associated with expression of its downstream effectors or prognostic factors. CONCLUSIONS Our findings suggest that p-4EBP1 expression was associated with poor prognostic factors of ovarian cancer and that p-4EBP1 overexpression may be a prognostic biomarker of ovarian cancer.

Human papillomavirus vaccine: Widening the scope for cancer prevention

Human papillomavirus (HPV) is the necessary cause of cervical cancer. The HPV oncoproteins E6 and E7 have crucial roles in various steps of carcinogenesis, inducing degradation of p53 and destabilization of pRb. Several clinical trials show that recombinant HPV vaccines are safe and effective in preventing persistent infection of HPV and associated anogenital lesions. Although most clinical studies to date have investigated the effectiveness of HPV vaccines in young female subjects, elderly females and males may also be candidates for HPV vaccines. Prophylactic HPV vaccination may be an ideal preventive method for other HPV‐associated cancers in addition to cervical carcinoma. Carcinogenesis by HPV, efficacy trials of currently available HPV vaccines, and the possible roles of HPV vaccines in the prevention of HPV‐associated cancers are reviewed in this article.

CA19-9 elevation in ovarian mature cystic teratoma: Discrimination from ovarian cancer – CA19-9 level in teratoma

Background We aimed to identify clinical characteristics of ovarian mature cystic teratoma (MCT) in association with CA19-9 elevation, and to determine if CA19-9 is a useful marker in discrimination of MCT from ovarian cancer (OC). Material/Methods Medical records of 322 women with pathologically-confirmed MCT or OC (stage 1 or 2) were reviewed retrospectively. The relationships between the characteristics of MCT (mean diameter, bilaterality, and pathologic components) and elevated CA19-9 were evaluated. Tumor markers in MCT were compared to those in OC. Results MCTs with CA19-9 elevation were correlated with a larger diameter (8.53±3.84 cm vs. 6.95±3.97 cm, p=0.002) and presence of fat component (67.1% vs. 32.9%, p<0.001), compared to those with normal CA 19-9. Although the incidence of CA19-9 elevation was not different between patients with MCT and OC (p=0.700), the mean value of CA19-9 was higher in those with OC (114.66±20.66 U/mL vs. 508.58±261.63 U/mL, p=0.013). In addition, simultaneous elevation of CA125 and CA19-9 was associated with a higher probability of malignant neoplasm (p<0.001; odds ratio: 23.7; 95% confidence interval: 8.863–63.576) than single elevation of CA 19-9. Conclusions CA19-9 could be an important tool in the diagnosis of ovarian mature cystic teratoma. CA19-9, in combination with CA125, might be a useful marker in discrimination of MCT from cancer.

Cyclooxygenase-2 is an independent predictor of poor prognosis in uterine leiomyosarcomas.

Introduction: Cyclooxygenase-2 (COX-2) is a well-known enzyme that promotes tumor growth and metastasis. Cyclooxygenase-2 is upregulated in a number of human epithelial tumors, but data about the significance of COX-2 in mesenchymal tumors are lacking. The purpose of this study was to determine COX-2 expression in uterine sarcomas and whether a relationship exists between COX-2 expression and clinicopathologic outcomes. Methods: Immunohistochemical staining for COX-2 was performed on paraffin-embedded tissue blocks of 49 uterine sarcomas (30 leiomyosarcomas, 14 endometrial stromal sarcomas, and 5 carcinosarcomas). Positive staining was defined as moderate or strong staining in 5% or more of tumor cells. Results: Four of 30 leiomyosarcomas, 1 of 14 endometrial stromal sarcomas, and 2 of 5 carcinosarcomas were positive for COX-2 expression. In leiomyosarcomas, COX-2 expression correlated with tumor stage with marginal significance (P = 0.058). Patients with leiomyosarcoma positive for COX-2 expression had a lower overall survival rate than those without COX-2 expression (P = 0.025). In the multivariate Cox proportional hazards regression model, COX-2 expression, tumor stage, and mitotic count were independently associated with overall survival in leiomyosarcomas. Conclusions: Our data suggest that immunohistochemically determined COX-2 expression is an independent prognostic factor in uterine leiomyosarcomas. Assessment of COX-2 status might be useful for determining the prognosis in patients with uterine leiomyosarcomas.

Association of cyclin D1 G870A polymorphism with uterine leiomyoma in women whose body mass index values are above 25 kg/m2

BACKGROUND Many studies have shown that a polymorphism (G870A) in cyclin D1 (CCND1) is associated with carcinogenesis in a variety of cancers. Our aim was to determine if an association exists between the CCND1 G870A polymorphism and uterine leiomyoma in Korean women. METHODS Blood samples of 331 cases and 204 controls aged 47.4 +/- 7.6 and 46.8 +/- 10.4 years (mean +/- SD), respectively, were collected. CCND1 genotyping was determined by PCR and restriction fragment length polymorphism. RESULTS Allelic frequencies of cases (A, 0.53; G, 0.47) were not significantly different from those of controls (A, 0.49; G, 0.51) (P = 0.22). After adjustment for menarche age and BMI, multivariate logistic regression analysis showed that the AA genotype was not associated with increased risk for uterine leiomyoma [odds ratio (OR) = 1.38, 95% confidence interval (CI); 0.85-2.26, P = 0.19]. However, in stratification analysis of cases and controls with BMI >25 kg/m(2), allelic frequencies of cases (A, 0.56; G, 0.44) were significantly different from controls (A, 0.36; G, 0.64) (P = 0.005), and the AA genotype was associated with increased risk for uterine leiomyoma (OR = 3.61, 95% CI; 1.02-12.73, P = 0.046). Furthermore, the OR for AA compared with combined GG and AG genotypes was 3.16 (95% CI 1.01-9.92, P = 0.048). CONCLUSIONS The A allele and AA genotype of CCND1 G870A polymorphism have a significant association with an increased risk of the uterine leiomyoma in obese Korean women.

Cyclooxygenase-2 Expression in Cervical Intraepithelial Neoplasia

To evaluate the role of cyclooxygenase (COX)‐2 during cervical carcinogenesis, we investigated COX‐2 expression in the dysplastic epithelium and stromal cells of cervical intraepithelial neoplasia (CIN). Immunohistochemical analysis with COX‐2 antibody was performed on 148 paraffin‐embedded tissue specimens of patients who were diagnosed as CIN in our institute. COX‐2 expression was evaluated separately in the dysplastic epithelium and stromal cells of CIN. The relationships between COX‐2 expression and clinicopathologic variables were examined. For the dysplastic epithelium, COX‐2 expression was negative in 137 (92.6%) and positive in 11 (7.4%) specimens. For the stromal cells, COX‐2 expression was negative in all specimens. The COX‐2 expression in dysplastic epithelium was higher in older (P= 0.038) or postmenopausal (P= 0.025) women. In conclusion, COX‐2 expression was observed only in the dysplastic epithelium but not in the stromal cells of CIN. The COX‐2 expression in dysplastic epithelium was associated with age and menopausal status.

Quantitative Detection of Serum Survivin and Its Relationship with Prognostic Factors in Ovarian Cancer

Objective: This study was conducted to determine the clinical significance of serum survivin in ovarian cancer. Methods: A total of 65 patients with ovarian tumors including 21 epithelial ovarian cancer, 22 benign epithelial ovarian tumor, 13 dermoid cyst and 9 endometrioma cases were investigated. All histologic types of cancer were serous carcinoma except for 1 case of undifferentiated carcinoma. ELISA was employed to evaluate the serum survivin levels. For statistical analysis, we used Fisher’s exact test, Spearman’s correlation coefficient test, the Mann-Whitney U test, the log-rank test and Cox regression analysis. Results: The survivin level was higher in serous ovarian cancer than in benign epithelial tumors with marginal significance. In ovarian cancer, serum survivin was positively correlated with age, advanced stage and poor disease-free survival. Interestingly, high survivin level positivity was associated with positive peritoneal cytology and omental metastasis of ovarian cancer. Conclusions: Our data collectively suggest that serum survivin reflects the peritoneal metastasis of serous ovarian cancer and may thus be useful as a prognostic biomarker.

A randomized prospective trial of the postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy for the treatment of symptomatic uterine fibroids: clinical trial design.

BackgroundLaparoscopy-assisted vaginal hysterectomy is one of the definite methods for the treatment of symptomatic uterine fibroids with lesser intraoperative bleeding and shorter hospitalization compared with abdominal hysterectomy. However, laparoscopy-assisted vaginal hysterectomy cannot preserve uterus and can show postoperative complications by the change of pelvic structure. Thus, laparoscopic uterine artery ligation has been introduced for relieving the symptoms caused by uterine fibroids in place of hysterectomy. The current study was designed to compare postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy, and to evaluate the efficacy of laparoscopic uterine artery ligation which can treat symptomatic uterine fibroids with the preservation of uterus.Methods and designPatients enrolled the current study are randomized to laparoscopic uterine artery ligation or laparoscopy-assisted vaginal hysterectomy. The primary outcome is to compare postoperative quality of life between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients version 3.0. Secondary outcomes are to evaluate the volume reduction of uterus, uterine fibroids and ovaries by the 2 treatments, to compare the improvement of subjective symptoms using 11-point symptom score and postoperative clinical outcomes between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy, and to investigate the improvement of postoperative vaginal bleeding by laparoscopic uterine artery ligation.DiscussionAmong treatment methods for symptomatic uterine fibroids with the preservation of uterus, laparoscopic uterine artery ligation is expected to have the efficacy like uterine artery embolization, which appeared to be safe for routine use with symptomatic relief. The current study fully recruited in June 2008 and the results will be available in June 2009. If there is no difference of postoperative QOL between laparoscopic uterine artery ligation and laparoscopy-assisted vaginal hysterectomy for the treatment of symptomatic uterine fibroids, the comparison of quality of life between laparoscopic uterine artery ligation and uterine artery embolization will be also needed as a surgical treatment for preserving uterus.Trial registrationCurrent Controlled Trials ISRCTN76790866

Aromatase Expression Was Not Detected by Immunohistochemistry in Endometrial Cancer

Abstract:  Several studies suggested that aromatase could play an important role in tumor progression and prognosis in endometrial cancer because androstenedione is converted to estrogen by the enzyme. For better understanding of the aromatase expression in endometrial cancer and its relation to diverse clinicopathological parameters, we conducted this study. This study was carried out with 141 endometrial cancer patients, all of whom had undergone operations in our institution from 1993 to 2002. Paraffin‐embedded tissue blocks were sectioned and immunostained with monoclonal antiaromatase antibody using human placental tissue as positive control. Clinicopathological variables of all patients were also reviewed. Despite quite a high aromatase expression in positive control, there was no endometrial cancer specimen showing the enzyme expression. Our result, although needs further investigation on the cause of the difference from other studies, suggested that aromatase might not have an important role in endometrial cancer.