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We report a 34-year-old woman with recurrent gestational trophoblastic neoplasia (GTN) who showed hypersensitivity to etoposide. Computed tomography (CT) revealed a 32-mm solid mass in the right lung and a 101-mm cystic mass with solid components in the left side of the liver. The patient's serum human chorionic gonadotropin (HCG) level was 689 439 mIU/mL. After eight cycles of combined paclitaxel 175 mg/m2 on day 1, ifosfamide 1 g/m2 on days 2-5, and cisplatin 20 mg/m2 on days 2-5 (TIP) every 3 weeks, the serum HCG level decreased to 2.4 mIU/mL. CT scan revealed disappearance of the lung tumor and significant reduction in the solid components of the liver tumor. Then, left hemihepatectomy was performed. After 3 months, there was no evidence of the disease, and the serum HCG level normalized. Thus, TIP chemotherapy, followed by residual mass resection, might be effective for methotrexate-resistant GTN.

Aim The aim of this study was to compare the efficacy and safety of enoxaparin and intermittent pneumatic compression (IPC) for venous thromboembolism (VTE) prevention in Japanese surgical patients with gynecologic malignancy. Material and Methods Patients ≥40 years old undergoing major surgery for gynecologic malignancy without preoperative VTE were included. Written informed consent was obtained. Enrolled patients received IPC immediately before surgery. After surgery, they were randomly assigned to either an enoxaparin group or an IPC-alone group. The enoxaparin group received enoxaparin injection (20 mg, subcutaneous, every 12 h) from postoperative day 2 to 8. IPC was discontinued after the first injection. In the IPC-alone group, IPC was continued until full ambulation. The primary end-point was incidence of VTE, including pulmonary embolism and deep vein thrombosis, regardless of symptoms. An interim analysis was to be conducted when the first 30 patients had completed the study protocol. A Data and Safety Monitoring Board was established for making recommendation on the continuation or termination of the study based on the interim results. Results At the time of the interim analysis, six cases of VTE were found: five in the IPC-alone group and one in the enoxaparin group (Fisher's exact test, P = 0.08). Three patients in the IPC-alone group developed pulmonary embolism, but none in the enoxaparin group did so (Fisher's exact test, P = 0.10). The study was terminated following the Data and Safety Monitoring Board's recommendation. Conclusion Enoxaparin might have lowered the risk of VTE among surgical patients with gynecologic malignancy. Further studies are necessary to confirm this.

Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics that include chemoresistance resulting in poor prognosis. It was shown that CCC recently was characterized by specific upregulation of the IL-6/IL-6R-signal transducer and activator of transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify whether IL-6/IL-6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and we found that high IL-6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

Aim: Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC. Material and Methods: We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004. Results: The median follow-up period was 91 months. The estimated 8-year overall survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21 stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%, respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was 87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate analysis using the log–rank test revealed that Eastern Cooperative Oncology Group performance-status 1, pT3 stage, and presence of residual disease (stage II-IV) were significantly correlated with shortened patient survival. Multiple regression analysis revealed that pT3 predicted worse OS in patients with CCC than pT1 (P

Aim: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients. Material and Methods: Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis. Results: CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade. Conclusions: These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer.

The PTEN/MMAC1/TEP1 tumor-suppressor gene, which maps to chromosome 10q23.3, is mutated and homozygously deleted in a variety of human tumors, including endometrioid-type ovarian tumors. We examined 33 primary ovarian cancers and 3 ovarian borderline tumors for allelic imbalance (AI) of the 10q23.3 region using 5 polymorphic markers, including an insertion/deletion-type polymorphic marker identified in intron 4 of the PTEN gene. AI at one or more loci was detected in 12 of 31 (39%) informative ovarian cancers and none of 3 ovarian borderline tumors. The commonly deleted region was mapped between the D10S215 and D10S541 loci, including the PTEN locus. Moreover, the incidence of AI at the PTEN locus (38%) was the highest among the 5 loci examined. Therefore, we searched for mutations in the entire coding region of the PTEN gene by PCR-SSCP and sequencing analyses in these tumors and 7 ovarian cancer cell lines. Mutations were detected in 3 of the 33 (9%) ovarian cancers: 2 cases with double mutations and 1 case with a mutation on 1 allele accompanied by deletions on both alleles in the poly T tract preceding the splice acceptor site in intron 7. An intragenic deletion was detected in 1 of the 7 (14%) ovarian cancer cell lines. PTEN mutations were detected not only in the endometrioid type but also in the serous and mucinous types of ovarian cancer. However, PTEN was not mutated in the 12 tumors that showed AI of the PTEN locus. Our results suggest that the PTEN gene plays an important role in the development of a subset but diverse histological types of ovarian tumors. However, it is possible that another tumor-suppressor gene in the close vicinity of the PTEN gene is also inactivated by AI of the 10q23.3 region.

Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMAD4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined allelic imbalance (AI) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. AI at one or more loci was detected in 15 of 37 (41%) informative ovarian cancers and in none of the four borderline tumors. Frequent AI was detected at the D18S46 (31%) and D18S474 (36%) loci, which were adjacent to the SMAD4 gene, and at the D18S69 (33%) locus, which was telomeric to the DCC gene. Therefore, we searched for mutations of the SMAD4 gene in 42 primary tumors and eight cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, whereas silent mutation was detected in a primary ovarian cancer. These results suggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis.

Microsatellite instability (MSI) represents a defect in the DNA mismatch repair system and has been shown to take part in the genesis and/or progression of several human malignancies. In hematological malignancies, the relevance of MSI has been a matter of controversy. Therefore, 29 microsatellite loci were examined for MSI in 57 leukemia and lymphoma cell lines by PCR analysis. Ladder formation of bands representing MSI was observed at multiple loci in 6 of 24 lymphoid leukemia/lymphoma cell lines and in 0 of 33 myeloid leukemia cell lines. Analysis for the BAT-26 and BAT-25 loci confirmed the presence of MSI in five of six lymphoid cell lines exhibiting ladder formation of bands. Thus, at least 5 out of 24 (21%) lymphoid leukemia/lymphoma cell lines were considered as being MSI-positive. These results indicate that MSI contributes to the development of lymphoid but not to myeloid malignancies.