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Abstract Background Persistent infection of human papillomavirus (HPV) types 16 and 18 causes cervical cancer. To better understand immune responses to the prophylactic vaccine, HPV 16/18 L1 virus-like particles (HPV-VLPs), we investigated B cell epitopes of HPV16 L1-derived peptides. Methods Sera from mice immunized with HPV-16/18 L1 VLPs were analyzed for their IgG titers against 10 different HPV16 L1-derived peptides (20-mer) that contain human leukocyte antigen (HLA)-class I A-2, A-24 and class II DR. Results One 20-mer peptide at positions 300 to 319 was identified as a common B cell epitope in both Balb/c (H-2d) and C57BL/6 (H-2b) mice. Mapping analysis showed that the 10-amino-acid sequence at positions 304to 313 was an immunogenic portion. It is of note that the binding capability of this 10-mer peptide to the HLA-A2 and HLA-A24 molecules was confirmed by the HLA class I stabilization assay. In addition, one unique 20-mer was determined as a B cell epitope in each strain. Conclusions These results might provide new information for better understanding of immune responses to HPV 16 L1.

N-myc downstream regulated gene-1 (NDRG1) has attracted much attention as a protein associated with angiogenesis. This study investigated the associations of NDRG1 expression, determined by immunohistochemical analysis, with other clinicopathological factors and prognosis in patients with endometrial endometrioid carcinoma (EEC). Surgical specimens were obtained from 113 patients with EEC. High NDRG1 expression was correlated with advanced stage, poor differentiation, lymph node metastasis, and significantly poorer survival compared with patients with low expression. High expression of NDRG1 was also correlated with high levels of angiogenesis and low expression of the estrogen receptor. These results suggest that high expression of NDRG1 is associated with angiogenesis and is an indicator of a poor prognosis in women with EEC.

Since uterine cervical cancer is regarded as a radiosensive tumor, ionizing radiation is the most frequently used treatment modality against the disease. Although the crucial end-point is radiation-induced cell death, the tumors are not equally sensitive to radiation. Determining the criteria that may be used to predict tumor radiosensitivity is of importance; however, little success has been achieved thus far. In radioresistant cases the therapeutic strategy should be changed, thereby avoiding ineffective or unnecessary treatment. Furthermore, identification of the underlying molecular processes leading to radioresistance may lead to novel radiosensitising strategies. Cervical smears were obtained from seven patients with locally advanced cervical cancer following each radiotherapy, and the radiation-induced damage of cancer tissue was examined by routine cytology. Since the formation of DNA double-strand breaks is considered critical for the cytocidal effect of radiation therapy, the molecular changes of the neoplastic cells were also assessed by laser scanning cytometry (LSC). Radiation-induced morphological changes of cancer cells were evident at a dose of 7.2 Gy, whereas increased DNA content (or DNA index) was observed prior to the onset of morphological changes. Molecular change was detected earlier than the morphological change of the irradiated cancer cells, indicating the feasibility of LSC in predicting the radiosensitivity of cervical cancer tissue.

The aim of this study was to identify risk factors to allow us to detect patients at high risk of requiring insulin therapy, among Japanese pregnant women with one abnormal value (OAV) on a 75-g oral glucose tolerance test (75-g OGTT). A total of 118 pregnant women with OAV on a previous 75-g OGTT between 1997 and 2010 were studied. We identified the factors which can predict patients at high risk of requiring insulin therapy among Japanese pregnant women with OAV, by comparing severe abnormal glucose tolerance (insulin treatment; n=17) with mild glucose tolerance patients (diet only; n=101). The following factors were examined; plasma level of glucose (PG) and immunoreactive insulin (IRI) at fasting, 0.5, 1 and 2 hours after loading glucose, insulinogenic index, homeostasis model assessment insulin resistance (HOMA-IR), insulin sensitivity index-composite (ISI composite), and HbA1c at the time of the 75-g OGTT. Univariate analysis showed a positive correlation between insulin therapy and 2-h PG value, 0.5-h and 1-h IRI values, AUC-IRI and insulinogenic index (p<0.05). Multivariate analysis showed that the PG 2-h value and insulinogenic index were independent predictive factors of insulin therapy. A 2-h PG ≥153 mg / dl and an insulinogenic index of <0.42 had a sensitivity of 81.8%, a specificity of 83.8%, a positive predictive value of 60.0% and a negative predictive value of 93.9% for the prediction of patients who required insulin therapy among pregnant women with OAV. These results suggest that a level of 2-h PG ≥153 mg/dl and an insulinogenic index of <0.42 on 75-g OGTT are predictive factors for insulin therapy in Japanese pregnant women with OAV.

Background: The long-term efficacy and safety of docetaxel/cisplatin as first-line chemotherapy in Japanese patients was evaluated in order to find an optional regimen for ovarian cancer., Patients and Methods: Women with surgically resected stage Ic-IV epithelial ovarian cancer were treated with docetaxel 70 mg/m2 and cisplatin 60 mg/m2 every 4 weeks., Results: Ninety women were enrolled of whom 89 (median age, 54 years) received a median of 6 cycles (range 1 to 9). With a median 38 months'follow-up, median progression-free survival was 28 months (95% lower confidence interval, 24 months) in 60 patients with stage III-IV disease. The overall response rate for 20 patients was 45%. Neutropenia was the most common (67%) grade 3/4 toxicity. Major grade 3/4 nonhaematological toxicities were gastrointestinal toxicities (< or = 11%) and fatigue (8%). No grade 3/4 neurotoxicity was observed., Conclusion: The combination of docetaxel/cisplatin is a regimen with favourable progression-free survival for ovarian cancer.

Purpose: We examined the antiproliferative effect of IFN-alphaCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo., Experimental Design: (a) The effects of IFN-alphaCon1 on growth, morphology, cell cycle, and type I IFN-alpha receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors., Results: Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-alphaCon1 were not obvious., Conclusions: IFN-alphaCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-alphaCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-alphaCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.