Soft tissue metastasis of an immature teratoma of the ovary.

In patients with immature teratoma of the ovary, blood-borne metastasis to organ parenchyma, such as the lungs, liver, or brain, are uncommon. Moreover, soft tissue metastasis is extremely rare. We describe a 31-year-old woman with an immature teratoma of the left ovary, which metastasized to soft tissue of the right thigh after surgery. Because of the rarity of this condition, we report the results of treatment and review the literature.

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix.

OBJECTIVE: To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. METHODS: We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m(2) cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m(2)/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. RESULTS: Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. CONCLUSION: CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated.

Validation of a nomogram for predicting outcome of vulvar cancer patients, primarily treated by surgery, in Korean population: multicenter retrospective study through Korean Gynecologic Oncology Group (KGOG-1010).

OBJECTIVE: Regarding vulvar cancer, a nomogram has been suggested for the prediction of relapse-free survival (RFS). While the nomogram has been developed and validated in a Western study, there was no validation in Korean population. Thus, we have undertaken the study to assess the applicability of nomogram for predicting RFS in Korean patients with vulvar cancer. METHODS: A total of 204 cases newly diagnosed as vulvar cancer between 1982 and 2006 were identified. Among them 70 cases were not eligible due to inappropriate cell type (40 cases) and radiation as primary therapy (30 cases). Forty-four cases were not evaluable due to inadequate data and persistent disease. Finally a total of 90 patients primarily treated by surgery were included for analysis. Variables including age and the characteristics of primary tumor, nodal status, and surgical margin were collected for predicting RFS based on nomogram, which was compared with actual RFS. A calibration plot was drawn showing the actual versus predicted probability for 6 groups of patients segregated according to their predicted probabilities. In addition, discrimination of the nomogram was quantified with the concordance index. RESULTS: Patients' mean age was 58 years and mean follow-up period was 47.9 months. Observed 2y- and 5y-RFS rates were 81% and 68%, respectively, corresponding to 79% and 72% in the original cohort. The trend line in calibration plot showed comparable concordance with an ideal line, having a slope of 1.04 for 2y-RFS (R(2)=.35) and 0.98 for 5y-RFS (R(2)=.80), respectively. The concordance index was 0.79 in the KGOG data set, which was improved to 0.82 with the data set limited to squamous cell carcinoma. CONCLUSION: The nomogram provides the predictive capacity for relapse-free survival in Korean patients with vulvar cancer.

Benzo[a]pyrene induces apoptosis in RL95-2 human endometrial cancer cells by cytochrome P450 1A1 activation.

Benzo[a]pyrene (B[a]P) has been shown to be an inducer of apoptosis in some cell types. To date, due to the lack of an appropriate model system, studies of the cellular and biochemical mechanism(s) by which B[a]P induces apoptosis have been focused on Hepa1c1c7 cells. Moreover, the precise relationship between the bioactivation of B[a]P by CYP1A1 or CYP1B1 and the occurrence of cytotoxicity-mediated apoptosis requires further elucidation. In the present study, we showed that B[a]P-induced apoptosis in RL95-2 cells is accompanied by the activation of caspases. In addition, the mitochondrial changes, including the decrease of mitochondrial potential and the release of mitochondrial cytochrome c and second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein binding protein with low PI (Smac/DIABLO) into the cytosol, support the suggestion that the mitochondrial pathway is robustly associated with B[a]P-evoked apoptosis. This study showed the involvement of the nuclear translocation of mitochondrial apoptosis-inducing factor in B[a]P-induced apoptosis of RL95-2 cells. Exposure to B[a]P up-regulates aryl hydrocarbon receptor, heat-shock protein 90, cytochrome P450 1A1 (CYP1A1), cytochrome P450 1B1 (CYP1B1), and epoxide hydrolase significantly, which might be prerequisites for the conversion of B[a]P to B[a]P-7,8-dihydroxy-9,10-epoxide. Although both CYP1A1 and CYP1B1 proteins were up-regulated significantly by B[a]P, only CYP1A1 exhibited activity. Thus, CYP1A1 is believed to be a central oxidative enzyme that is ultimately required for formation of B[a]P-7,8-dihydroxy-9,10-epoxide from B[a]P in RL95-2 cells. Altogether, our data showed that RL95-2 cells are susceptible to apoptosis by exposure to B[a]P and that B[a]P-evoked apoptosis is mediated predominantly by the activation of CYP1A1. Here we suggest that RL95-2 cells are an excellent model for the investigation of xenobiotic mechanisms associated with CYP1A1 as well as CYP1B1.

Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas.

PURPOSE: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal transduction. Activation of MAPK is regulated by upstream kinases including KRAS and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma. This study evaluates the expression of active MAPK in ovarian serous carcinomas, with response to treatment and survival. EXPERIMENTAL DESIGN: Expression of active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous tumors. Immunoreactivity was correlated with tumor grade, mutational status of KRAS and BRAF, in vitro drug resistance, and clinical outcome. RESULT: There was a lower frequency of expression of active MAPK in high-grade ovarian serous carcinomas as compared with low-grade serous tumors, including borderline tumors and low-grade serous carcinoma (P < 0.001). Active MAPK was present in all of the 19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of 34 tumors with wild-type KRAS and BRAF in both low- and high-grade carcinomas. Expression of active MAPK alone served as a good survival indicator in the 2-year follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a combination of expression of active MAPK and in vitro sensitivity of paclitaxel significantly correlated with a better prognosis in 5-year survival rate (P = 0.048) in patients with advanced-stage high-grade serous carcinoma. CONCLUSIONS: Active MAPK is more frequently expressed in low-grade than in high-grade ovarian serous carcinoma. Active MAPK serves as a good prognostic marker in patients with high-grade serous carcinomas.

Sphingosine 1-phosphate in amniotic fluid modulates cyclooxygenase-2 expression in human amnion-derived WISH cells.

The metabolism of arachidonic acid, in particular the generation of prostaglandins (PGs), has been proposed to play a key role in the regulation of labor. Moreover, several extracellular proteins have been reported to modulate PG synthesis in amnion cells. In this study, we found that lipid components dissolved in the amniotic fluid modulate PG synthesis in WISH human amnion cells and identified one of these components as a sphingosine 1-phosphate (S1P). WISH cells express several S1P receptors including S1P1, S1P2, and S1P3. When WISH cells were stimulated with S1P, PGE2 synthesis increased in a concentration-dependent manner, showing maximal activity at around 100 nM. S1P treatment also caused the up-regulation of cyclooxygenase-2 (COX-2) mRNA and protein, which was apparent within 3-12 h of stimulation. In terms of the intracellular signaling pathway of S1P-induced WISH cell activation, we found that S1P stimulated two kinds of MAPK, ERK, and p38 kinase. We examined the roles of these two MAPKs in S1P-induced COX-2 expression. S1P-induced COX-2 expression was blocked completely by PD-98059 but not by SB-203580, suggesting that ERK has a critical role in the process. Transfection of S1P1 or S1P3 but not of S1P2 antisense oligonucleotide inhibited S1P-induced COX-2 expression and PGE2 production in WISH cells, indicating the involvements of S1P1 and S1P3 in the processes. This study demonstrates the physiological role of S1P in amniotic fluid and its effect on the modulation of COX-2 expression and PGs synthesis in WISH cells.