Introduction of gasless laparoscopic surgery as a minimally invasive procedure for endometrial cancer and its usefulness from the viewpoint of the learning curve.

BACKGROUND: We investigated the usefulness of gasless laparoscopic surgery (GLS) using a subcutaneous abdominal wall lifting method for endometrial cancer. METHODS: We studied 105 patients with early endometrial cancer who underwent GLS (55) or open surgery (50). A uterine manipulator was used in all GLS cases. We compared operative time, blood loss, number of lymph nodes removed, hospital stay, perioperative complications, cases converted to laparotomy, and recurrence and survival rates. We also studied the learning curve and proficiency of GLS. RESULTS: The GLS group had significantly longer operative time (265 vs. 191 min), reduced blood loss (184 vs. 425 mL), shorter hospital stay (9.9 vs. 17.6 days), and fewer postoperative complications (1.8 vs. 12.0%) than the open group. No case was converted to laparotomy. Disease-free and overall survival rates at 4 years postoperatively (GLS vs. open groups) were 98.0 versus 97.8 and 100 versus 95.7%, respectively, and there was no significant difference between the groups. Regarding the learning curve for GLS, two different phases were observed in approximately 10 cases. Operator 2, who was not accustomed to laparoscopic surgery, showed a significant reduction in operative time in the later phase 2. CONCLUSIONS: GLS for endometrial cancer results in less bleeding, shorter hospital stay, and fewer complications than open surgery. Recurrence and survival rates were not significantly different from those of open surgery. This technique may be introduced in a short time for operators who are skilled at open surgery but not used to laparoscopic surgery.

Krüppel-like factor 5 is upregulated and induces cell proliferation in endometrial cancer.

Krüppel-like factor 5 (KLF5) is involved in various cellular processes, such as cell proliferation and survival. KLF5 has been implicated in cancer pathology. The aim of the present study was to investigate the expression levels and function of KLF5 in endometrial cancer. A total of 30 patients, including 12 patients with endometrial cancer and 18 with benign gynecological diseases (controls), were enrolled at Tokyo Medical University (Tokyo, Japan) between March 2017 and May 2018. Endometrial cancer and control endometrium tissues were collected, and the expression levels of KLF5 were determined using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. For the functional analyses of KLF5 in endometrial cancer, the present study employed a loss-of-function strategy in the human endometrial cancer cell lines in vitro. Ishikawa and HEC1 cells were transduced with lentiviral constructs expressing shRNAs targeting KLF5. MTT and TUNEL assays were performed in cells after knockdown to analyze the role of KLF5 in cell proliferation and survival. The results revealed that the mRNA and protein expression levels of KLF5 were increased in endometrial cancer tissues. In vitro analyses demonstrated that depletion of KLF5 inhibited cell proliferation and decreased the expression levels of cyclin E1. However, silencing KLF5 did not induce cell death. Overall, these results indicated that KLF5 may be crucial in the tumorigenesis of endometrial cancer and has potential as a therapeutic target.

The post-progression survival of patients with recurrent or persistent ovarian clear cell carcinoma: results from a randomized phase III study in JGOG3017/GCIG.

OBJECTIVE: In this study we sought to investigate the clinical factors that affect post-progression survival (PPS) in patients with recurrent or persistent clear cell carcinoma (CCC). We utilized the JGOG3017/Gynecological Cancer InterGroup data to compare paclitaxel plus carboplatin (TC) and irinotecan plus cisplatin (CPT-P) in the treatment of stages I to IV CCC. METHODS: We enrolled 166 patients with recurrent or persistent CCC and assessed the impact of variables, including platinum sensitivity, treatment arm, crossover chemotherapy, primary stage, residual tumor at primary surgery, performance status, ethnicity, and tumor reduction surgery at recurrence on the median of PPS in patients with recurrent or persistent CCC. RESULTS: A total of 77 patients received TC, and 89 patients received CPT-P. The median PPS for patients with platinum-resistant disease was 10.9 months, compared with 18.8 months for patients with platinum-sensitive disease (hazard ratio [HR]=1.88; 95% confidence interval [CI]=1.30-2.72; log-rank p<0.001). In the multivariate analysis, the platinum sensitivity (resistant vs. sensitivity; HR=1.60; p=0.027) and primary stage (p=0.009) were identified as independent predictors of prognosis factors for PPS in recurrent or persistent CCC. CONCLUSIONS: Our findings revealed that platinum sensitivity and primary stage are clinical factors that significantly affect PPS in patients with recurrent or persistent CCC as well as other histologic subtypes of ovarian cancer. PPS in patients with recurrent CCC should establish the basis for future clinical trials in this population.

Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial.

PURPOSE: Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC. PATIENTS AND METHODS: Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events. RESULTS: Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. CONCLUSION: No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC.

Profiling analysis of circulating microRNA expression in cervical cancer.

MicroRNA (miRNA) expression is altered in cancer cells and is associated with the development and progression of various types of cancer. Accordingly, miRNAs may serve as diagnostic or prognostic biomarkers in cancer patients. In this study, we attempted to analyze circulating exosomal miRNA in patients with cervical cancer. Total RNA was extracted from the serum of healthy subjects, subjects with cervical intraepithelial neoplasia (CIN) and patients with cervical cancer. We first investigated miRNA expression profiles in 6 serum samples from healthy subjects and patients with cervical cancer using the miRCURY LNA microRNA array. miRNAs with significant differences in expression were validated in a larger sample set by quantitative reverse transcription-polymerase chain reaction, using TaqMan gene expression assays. The results of the miRCURY LNA microRNA array indicated that 6 of 1,223 miRNAs found in serum samples from cervical cancer patients and normal controls exhibited a >3.0-fold change in expression level in subjects with cervical cancer, with a P-value of <0.01. In a validation set (n=131) that investigated the expression of 4 of the 6 miRNAs (miR-483-5p, miR-1246, miR-1275 and miR-1290), miR-1290 was found to have significantly higher expression levels in cervical cancer samples (n=45) compared with control samples (n=31). We also found that the median levels of these miRNAs were significantly higher in subjects with cervical cancer (n=45) compared with those in subjects with CIN (n=55). Circulating miRNAs were not correlated with clinicopathological parameters. However, receiver operating characteristic curve analysis suggested that these serum miRNAs may be useful diagnostic markers in cervical cancer. The expression of circulating miR-1290 was significantly higher in the blood of cervical cancer patients compared with that in controls and may thus serve as a useful biomarker in cervical cancer diagnosis. However, larger studies are required to fully elucidate the role of circulating exosomal miRNAs in cervical cancer.

Hypoxia inducible factor-1 mediates upregulation of urokinase-type plasminogen activator receptor gene transcription during hypoxia in cervical cancer cells.

Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia mediates tumor cells to have more invasive property in a variety of cancers. Urokinase plasminogen activator receptor (uPAR) which mediates invasion is considered to be induced by hypoxia. We sought to determine the regulators of uPAR expression during hypoxia in cervical cancer. We showed that cervical cancer cell lines, CaSki and CA, were more invasive under hypoxic condition (1% O2) than under normoxic condition (20% O2) by invasion assays. Using western blot analysis, hypoxia enhanced the endogenous hypoxia-inducible factor (HIF)-1α and uPAR protein expression. uPAR mRNA level was also upregulated by hypoxia using real-time RT-PCR. Overexpression of HIF-1α which is induced by hypoxia activated the transcriptional activity of the uPAR promoter by luciferase assays. HIF-1 protein bound the putative HIF-1 response element on the uPAR promoter using electrophoretic mobility shift analysis, and additional luciferase assays show that this is essential for uPAR transactivation by HIF-1. HIF-1 overexpression enhanced the endogenous uPAR expression and introduction of siRNA for HIF-1α diminishes uPAR expression during hypoxia. These results indicate the upregulation of uPAR by hypoxia in cervical cancer cells is mediated through HIF-1. In cervical cancer tissues, we also demonstrated that uPAR protein expression was detected in cervical cancer but not in normal cervix or cervical intraepithelial neoplasia (CIN) by immunohistopathological staining. Our results provide evidence that regulation of uPAR expression by HIF-1 represents a mechanism for cervical cancer invasion during hypoxia.

Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study.

Despite exhaustive efforts to detect early-stage ovarian cancers, greater than two-thirds of patients are diagnosed at an advanced stage. Although diaphragmatic metastasis is not rare in advanced ovarian cancer patients and often precludes optimal cytoreductive surgery, little is known about the mechanisms and predictive factors of metastasis to the diaphragm. Thus, as an initial step toward investigating such factors, the present study was conducted to characterize the pathological status of ovarian cancer patients who underwent debulking surgery in combination with diaphragmatic surgery. This is a retrospective and cross-sectional study of patients who underwent debulking surgery in combination with diaphragmatic surgery at our institution between January 2005 and July 2015. Clinicopathological data were reviewed by board-certified gynecologists, pathologists, and cytopathologists. The rates of various pathological findings were investigated and compared by Fisher exact test between 2 groups: 1 group that was pathologically positive for diaphragmatic metastasis (group A) and another group that was pathologically negative for diaphragmatic metastasis (group B). Forty-six patients were included: 41 patients pathologically positive and 5 pathologically negative for diaphragmatic metastasis. The rates of metastasis to the lymph node (95.8% vs 20%, P = 0.001) and metastasis to the peritoneum except for the diaphragm (97.6% vs 60.0%, P = 0.028) were significantly increased in group A compared with group B. However, no significant differences between the 2 groups were found for rates of histological subtypes (high-grade serous or non-high-grade serous), the presence of ascites, the presence of malignant ascites, exposure of cancer cells on the ovarian surface, blood vascular invasion in the primary lesion, and lymphovascular invasion in the primary lesion. Our study demonstrated that metastasis to the lymph node and nondiaphragmatic metastasis to the peritoneum are significantly associated with metastasis to the diaphragmatic peritoneum, indicating that these factors may be pathological predictors of diaphragmatic metastasis in patients with ovarian cancer. However, as the data available are not sufficient to demonstrate the predictive power of these factors, a further comprehensive, large-scale study should be performed.

Pathology-oriented treatment strategy of malignant ovarian tumor in pregnant women: analysis of 41 cases in Japan.

BACKGROUND: The aim of this study was to investigate the impact of the histological findings on the treatment of malignant ovarian tumors in pregnant women. METHODS: This is a retrospective study of 41 patients diagnosed and treated for ovarian malignancy during pregnancy between 1985 and 2010. RESULTS: The median age of the study group was 30 years old, ranging from 20 to 41. Thirty-eight (92 %) patients were diagnosed with stage I, and one (2 %) with each of stages II, III, and IV. Twenty-five (61 %) patients had borderline malignancy, 8 (20 %) were diagnosed with epithelial ovarian cancer, 7 (17 %) with germ cell tumor, and one with sex cord stromal tumor. All patients received primary surgery; 7 (17 %) patients had cystectomy, 32 (78 %) had unilateral salpingo-oophorectomy, and 3 (7 %) underwent hysterectomy with bilateral salpingo-oophorectomy. Thirty-one (76 %) patients delivered live newborns; 21 had borderline tumor (84 %), 2 had ovarian cancers (25 %), and 8 had non-epithelial tumor (100 %). Six cases were terminated in order to perform the standard treatment for ovarian malignancy and 2 cases aborted spontaneously. CONCLUSION: In pregnant women, ovarian cancer is exceptionally less frequent compared with non-pregnant women, i.e. age-matched, statistically-corrected controls based on the Japanese annual report [8/33 (24 %) vs. control (60 %); ovarian cancer/(ovarian cancer + borderline tumor), P = 0.001]. The pregnant women with ovarian cancer chose to prioritize treatment of ovarian cancer at the sacrifice of their babies while those with borderline tumor or non-epithelial tumor were able to successfully deliver live newborns.

A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix.

BACKGROUND: Hypoxia occurs during the development of uterine cervical cancer and is considered to correlate with its invasion. Hypoxia promotes both the invasiveness and the metastasis of cancer cells through urokinase-type plasminogen activator receptor (uPAR) expression. The aim of this study was to evaluate the correlation between uPAR mRNA level and clinical prognostic factors of uterine cervical cancer. METHODS: We performed a retrospective review of 59 patients with cervical cancer and 9 subjects with normal cervical tissues. Total RNA was isolated from tissues of the uterine cervix surgically removed from patients. The mRNA of uPAR could be measured by real time PCR (RT-PCR). Histopathological factors such as histopathological type, cervical stromal, parametrial, lymphovascular, and uterine corpus invasions, metastasis to the pelvic lymph nodes, and pTNM stage were confirmed by two pathologists. The examined prognostic factors alongside the histopathological ones were FIGO clinical stage, hemoglobin level, serum level of SCC, and the effect on clinical outcomes. These factors were statistically evaluated by Fisher's exact test, log-rank test, and ROC analysis. Immunohistochemical staining with anti-uPAR monoclonal antibody was also performed. RESULTS: In uterine cervical cancer, overexpression of uPAR mRNA was significantly related to shorter disease-free survival (p = 0.0396). However, the other clinical prognostic and histopathological factors were not related to uPAR mRNA expression level. Immunohistochemical staining showed that positive staining for uPAR was histologically localized on the membrane of carcinoma cells. However, the staining was not very intense. CONCLUSIONS: Overexpression of uPAR mRNA may be a prognostic factor in cancer of the uterine cervix.

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial.

BACKGROUND: The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival. METHODS: This randomised controlled trial was done at 85 centres in Japan. Patients with stage II-IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m(2) on day 1) or dose-dense treatment (carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratified by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915. FINDINGS: 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9-85·6). Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3-33·8] vs 17·5 months [15·7-21·7]; hazard ratio [HR] 0·76, 95% CI 0·62-0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2-∞) in the dose-dense treatment group and 62·2 months (52·1-82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63-0·99; p=0·039). INTERPRETATION: Dose-dense treatment offers better survival than conventional treatment and is a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer.

Does severe anemia caused by dose-dense paclitaxel-Carboplatin combination therapy have an effect on the survival of patients with epithelial ovarian cancer? Retrospective analysis of the Japanese gynecologic oncology group 3016 trial.

INTRODUCTION: To evaluate the incidence of anemia in patients with epithelial ovarian cancer receiving paclitaxel-carboplatin combination therapy (TC) using data from the Japanese Gynecologic Oncology Group (JGOG) 3016 trial, and to examine the effect of severe anemia on survival during dose-dense TC. METHODS: Retrospective analysis was conducted in patients enrolled in the JGOG 3016 trial who underwent at least one cycle of the protocol therapy (n = 622). Hemoglobin values at enrollment and during each cycle of TC were collected. One-to-one matching was performed between patients with and patients without grade 3/4 anemia during TC (anemia and nonanemia groups) to adjust the baseline characteristics of the patients. The cumulative survival curve and median progression-free survival were estimated using the Kaplan-Meier method. RESULTS: Grades 2 to 4 anemia was observed in 19.8% of patients before first-line TC. The incidence of grade 3/4 anemia rapidly increased to 56.1% after the fourth cycle of dose-dense TC. After matching, the median progression-free survival in the anemia (hemoglobin <8.0 g/dL) and nonanemia (hemoglobin >8.0 g/dL) groups was 777 and 1100 days, respectively (P = 0.3493) for patients receiving dose-dense TC. The median progression-free survival in patients receiving conventional TC was similar between the 2 groups. CONCLUSIONS: The difference in progression-free survival between patients with epithelial ovarian cancer with and those without severe anemia during TC was not statistically significant, but for patients receiving dose-dense TC, severe anemia seems to have prognostic relevance. Prospective trials are needed to investigate whether the optimal management of chemotherapy-induced anemia, including appropriate use of erythropoiesis-stimulating agents, would further improve the survival of patients with ovarian cancer receiving dose-dense TC.

[Strategies for marginally resectable tumor in patients with advanced ovarian cancer].

There are approximately 7, 000 cases of ovarian cancer in Japan every year. The lack of an appropriate examination for ovarian cancer contributes to nearly half the cases being undetected until reaching advanced stages III and IV. By the ovarian cancer treatment guidelines, primary debulking surgery is a standard modality for the initial treatment of ovarian cancer. Many studies have reported that the prognosis is clearly improved once optimal surgery(residual disease<1 cm)is successfully performed for advanced ovarian cancer. Actually, no residual disease group that underwent complete cytoreductive surgery was improved more significantly than the residual disease<1 cm group. For achievement of a complete cytoreductive surgery, there is a need to devise some appropriate strategies for marginally resectable tumors in patients with advanced ovarian cancer.

Incidental events of diaphragmatic surgery in 82 patients with advanced ovarian, primary peritoneal and fallopian tubal cancer.

Surgical resections, such as peritoneal stripping (peritonectomy) are performed for disseminated diaphragmatic lesions of advanced ovarian cancer. This study retrospectively investigated the incidental events of diaphragmatic surgery. The records of patients with advanced mullerian carcinomas, including ovarian, primary peritoneal and fallopian carcinomas, who underwent diaphragmatic surgery were reviewed. Based on our criteria, stripping was performed for surface disease on the diaphragm, and full-thickness resection was performed for bulky disease. In certain cases, both procedures were performed. We analyzed intra- and post-operative incidental events in 82 patients. The χ(2) and Fisher's exact tests were used in the statistical analysis. There were 82 stage III-IV cases of which 56 patients underwent stripping, 12 underwent full-thickness resection and 14 patients underwent both procedures. Unexpected open chest surgery following stripping occurred in 1 out of 63 patients (1.6%) in the primary, 4 out of 13 patients (30.8%) in the interval and 0 out of 6 patients (0.0%) in the secondary debulking surgery groups. The incidence of unexpected open chest surgery was high in the interval debulking surgery group (p<0.001). Regarding post-operative events, accumulation of pleural effusion was identified in 43 patients (52.4%). The incidence of pleural effusions was not significantly different between the two procedures. No complications were encountered, nor was a chest tube required, during unexpected open chest surgery and postoperative pleural effusions. Therefore, it was concluded that special attention should be paid during interval debulking surgery even though it was possible for surgical resections of diaphragmatic lesions to be performed safely.

Prognostic factor on optimal debulking surgery by maximum effort for stage IIIC epithelial ovarian cancer.

OBJECTIVES: The aim of this study was to assess the prognostic factor of radical surgery in patients with stage IIIc ovarian cancer. STUDY DESIGN: Fifty-two patients were subjected to the study. The complete resection or optimal primary cytoreductive surgery (OPCS) was set as the maximum effort, and the accomplishment rate and prognosis were assessed. In addition, the poor prognosis cases among the OPCS-accomplished were evaluated with several factors based on univariate and multivariate analyses. RESULTS: The OPCS accomplishment rate was 84.6%. A worse prognosis was obtained in the more-than-4-weeks-delayed postoperative chemotherapy group, assessing poor-outcome cases in the OPCS group. A case that required more than three colon resections was the significant factor for the delay of postoperative chemotherapy. CONCLUSIONS: OPCS should be performed with maximum effort to improve the prognosis of stage IIIc ovarian cancer. We should avoid any delay in starting postoperative chemotherapy. In cases that require more than three colon resections, it seems that 'perioperative management' should be reconsidered and that priority should be given to postoperative management so that chemotherapy can be started soon after the operation.

A case of advanced ovarian cancer upstaged on the bases of pleural washing cytology.

We encountered a case of ovarian cancer that had positive pleural washing cytology diagnosed by thoracoscopy. A 65-year-old woman was referred to our hospital with a sensation of abdominal fullness. A whole-body examination revealed a solid tumor of the ovary and accumulation of ascites. Neither pleural effusion nor lung metastasis was found at the time. Laparotomy showed extensive dissemination and we classified the stage as IIIc. As the diaphragm was thickened with dissemination, we tried to strip the diaphragm and used thoracoscopy to identify the thoracic area. No tumor or pleural effusion was detected. We performed pleural biopsy and pleural washing cytology. Finally, malignant cells were found in the pleural washing cytology. Pathological findings showed serous papillary adenocarcinoma of the ovary in this stage IV case. We suggest in this report that thoracoscopy is a useful method for making the correct surgical staging.

Pilot study on transdiaphragmatic thoracoscopic-assisted pleural biopsy and intrathoracic washing cytology for Stage IIIc ovarian cancer with diaphragmatic metastases.

PURPOSE: The significance of investigations of thoracic cavities as well as pleural biopsy and intrathoracic washing cytology through transdiaphragmatic thoracoscopy for stage IIIc ovarian cancer with diaphragmatic metastases was assessed as a prospective pilot study. SUBJECTS AND METHODS: Eligibility criteria were established to include patients with stage IIIc ovarian cancer in whom pleural effusions were not detected preoperationally, but prominent diaphragmatic metastases were observed when the abdomen was opened and those who submitted consent. Transdiaphragmatic thoracoscopy was performed after diaphragm stripping. Then, biopsy of the lesion suspected to be disseminated or the plural membrane of the thoracic opening was performed followed by washing cytology using physiological saline. RESULTS: Ten subjects were enrolled. Disseminated lesions were observed on plural membranes, and positive results were obtained in biopsy and washing cytology in 3 subjects. In addition, positive results were seen with biopsy alone in 2 subjects and with washing cytology alone in 2 subjects. Hence, a total of 7 subjects (70.0%) were up-staged to the level of stage IV. Postoperational complications were not observed in any of these cases. CONCLUSIONS: It was suggested that stage IIIc ovarian cancer with prominent diaphragmatic metastasis may advance to the level of stage IV from a clinical point of view even if carcinomatous pleural effusions are not detected pre-operationally. Therefore, it is thought that this operational method is useful in the management of progressive ovarian cancer.

Early growth response-1 mediates downregulation of telomerase in cervical cancer.

Early growth response (Egr)-1 is a transcription factor that triggers transcription of downstream genes within 15-30 min of various stimulations. These genes are expressed rapidly through specific promoter activation and mediate cell growth and angiogenesis. Following the previous computational identification of a site that was thought to be an Egr-1 consensus binding site at -273 to -281 in the human telomerase reverse transcriptase (hTERT) promoter region, the present study was conducted to evaluate the role of Egr-1 in the regulation of hTERT and telomerase in uterine cervical cancer. First, the expression of Egr-1 and hTERT at the mRNA level was examined in cervical cancer tissues. Egr-1 and hTERT were expressed much higher in cervical cancer tissues than in the normal cervix. However, a negative correlation was noted in the expression between Egr-1 and hTERT. By luciferase assay using hTERT promoter constructs, hTERT transcriptional activation was shown to be inhibited when Egr-1 was overexpressed. Furthermore, Egr-1 overexpression decreased hTERT protein production as well as hTERT mRNA as observed by western blotting analysis and real-time reverse transcription-polymerase chain reaction, respectively. The present study suggests that Egr-1 plays an important regulatory role in the transcriptional activation of hTERT.