Histologic grade and peritoneal cytology as prognostic factors in type 1 endometrial cancer.

BACKGROUND: Prognostic clinicopathological factors for type 1 endometrial cancer are unknown and the purpose of the current study was to determine the independent prognostic variables for type 1 endometrial cancer. METHODS: We performed a retrospective study of 168 patients with type 1 endometrial cancer primarily treated with comprehensive staging surgery. The median follow-up time was 68 (12-100) months. Independent risk factors for disease-free survival (DFS) and overall survival (OS) were determined using multivariate Cox regression models. Sub-group analysis of stage I was also performed. We also assessed the patterns of failure among patients with recurrences and investigated the associations with the prognostic variables determined by multivariate analysis. RESULTS: Twenty patients (11.9%) had recurrence and 13 patients (7.7%) died of the disease overall. Multivariate analysis revealed that grade 2 (G2) histology (p = 0.008) and positive peritoneal cytology (p = 0.001) predicted the recurrent event in type 1 endometrial cancer. G2 histology (p = 0.007) and positive peritoneal cytology (p = 0.003) were also found to be independent risk factors for tumor-related deaths. Among stage I patients, G2 histology and positive peritoneal cytology were also independent prognostic variables for DFS and OS. Patients with G2 histology and/or positive peritoneal cytology were more likely to have recurrence at distant sites. CONCLUSIONS: G2 histology and positive peritoneal cytology were independent prognostic factors for DFS and OS in type 1 endometrial cancer.

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/µm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/µm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/µm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation.

Improved transformation of the halo-tolerant yeast Zygosaccharomyces rouxii by electroporation.

To improve the transformation efficiency of Zygosaccharomyces rouxii by electroporation, glycerol was added to the electroporation buffer and the cells were frozen at -80 degrees C. These alterations drastically increased transformation efficiency, and we found that competent cells can be preserved at -80 degrees C without decreasing their transformation efficiency for at least 30 d.

Endometrial adenosquamous carcinoma with osteoclast-like giant cells: immunohistochemistry and histogenesis.

Primary extraskeletal epithelial neoplasms containing osteoclast-like giant cells (OGCs) are rare. We herein describe a case of adenosquamous carcinoma that developed in the endometrium together with non-neoplastic OGCs. The patient was a 72-year-old woman who underwent radical hysterectomy with salpingo-oophorectomy and lymph node dissection after being diagnosed with uterine cancer. Histologically, the tumor was found to be an adenosquamous carcinoma containing a large number of OGCs and mononuclear cells (MNCs) that had infiltrated into the stroma. Immunohistochemically, the OGCs and MNCs stained strongly positive for KP-1 and alpha-1-antichymotrypsin, and negative for the epithelial markers epithelial membrane antigen (EMA) and cytokeratins. These findings suggest that the OGCs and MNCs in this patient's tumor originated from monocytes/histiocytes, and most likely developed as part of the stromal reaction to the neoplasm.

Loss of Aspergillus oryzae amyR function indirectly affects hemicellulolytic and cellulolytic enzyme production.

Aspergillus oryzae AB390, a derivative of A. oryzae OR101, was found to be suitable for soy sauce production, yielding a product light brown in color. Compared to the parent strain, hemicellulase and cellulase activities in the mutant were higher; however, its amylase activity was found to be much lower. To determine the cause of these differences, the enzymatic profile change, as a function of the carbon source in submerged cultures, was examined. Amylase activity in AB390 was hardly detectable and not affected by the carbon source utilized. In the absence of starch where glucose could not be generated, hemicellulase and cellulase activities in both the parent and mutant were the same. A nonsense mutation was found in the upstream region of the putative transactivation domain of the transcriptional activator of the amylolytic genes, amyR in AB390. Complementation of AB390 with the wild-type amyR reduced hemicellulase and cellulase activities and increased amylase activity in soy sauce koji, the mold responsible for giving soy sauce. Northern analysis and two-dimensional (2-D) electrophoresis indicated that the unique enzymatic profile of AB390 was regulated transcriptionally. The results suggested that the loss of amyR function indirectly affected the production of hemicellulolytic and cellulolytic enzymes, likely through a carbon catabolite repression-mediated control.

Characterization of Aspergillus oryzae aspartyl aminopeptidase expressed in Escherichia coli.

To characterize aspartyl aminopeptidase from Aspergillus oryzae, the recombinant enzyme was expressed in Escherichia coli. The enzyme cleaves N-terminal acidic amino acids. About 30% activity was retained in 20% NaCl. Digestion of defatted soybean by the enzyme resulted in an increase in the glutamic acid content, suggesting that the enzyme is potentially responsible for the release of glutamic acid in soy sauce mash.

A study of abnormal cervical cytology in pregnant women.

During the 4-year routing study of smears in 2,919 pregnant women, 33 cases of abnormalities of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy, and in case of need, sometimes punch biopsies were performed. As a result of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa and 7 cases were class IIIb. All cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, punch biopsies were performed. The results of histologic examination were wide: 5 chronic cervicitis, 1 condyloma, 1 mild dysplasia, 3 moderate dysplasia, 3 severe dysplasia, 3 carcinoma in situ, and 1 microinvasive carcinoma. Only two cases were treated during pregnancy, condyloma underwent Laser vaporization and microinvasive carcinoma underwent Loop electrosurgical excision procedure (LEEP) conization. Other cases were conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the other cases with regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.

A study of abnormal cervical cytology in pregnant women.

During the 4 year routine study of smears in 2,919 pregnant women, 33 cases of abnormals of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy and in case of need, sometimes punch biopsies were performed. The results of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa, 7 cases were class IIIb. All the cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, and punch biopsies were performed. The results of histologic examination were wide variety, five chronic cervicitis, one condyloma, one mild dysplasia, three moderate dysplasia, three severe dysplasia, three carcinoma in situ, and one microinvasive carcinoma. Only two cases were treated during pregnancy; one with condyloma underwent Laser vaporization and another with microinvasive carcinoma underwent LEEP conization. Other cases were given conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the cases showed regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.

P16-immunostaining pattern as a predictive marker of lymph node metastasis and recurrence in early uterine cervical cancer.

OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor.

Inhibitory effects of herbal drugs on the growth of human ovarian cancer cell lines through the induction of apoptosis.

OBJECTIVE: In order to develop and search for more effective and safe treatments for early and advanced stages of ovarian cancer, we examined the direct effects of four extracts of Chinese herbal drugs on ovarian cancer cells in vitro. METHODS: The growth inhibition of four herbal drugs on a total of six cell lines of human ovarian cancer cells was determined by a Cell Counting Kit-8 by counting viable cells. Apoptotic cells induced by herbal drugs were detected by using MEBCYTO Apoptosis Kit. All experiments were performed in triplicate. The significance of the difference was analyzed with a two-sided Student's t test. A P value less than 0.05 was accepted as statistically significant. RESULTS: The MN, A2780, and KF cell lines exhibited significant growth inhibition in the presence of Sho-saiko-to concentrations of 150 microg/ml, 300 microg/ml, and 500 microg/ml, respectively, and at the concentration of 1000 microg/ml, Sho-saiko-to demonstrated a significant apoptotic induction effect on all six kinds of ovarian cancer cell lines. This concentration is the same as the blood concentration attained when 7.5 g of Sho-saiko-to per day is orally administered and all absorbed. CONCLUSIONS: Sho-saiko-to exhibited significant growth inhibition of ovarian cancer cell lines, and the mechanisms of the inhibitory effects can be attributed, in part, to apoptosis induced by Sho-saiko-to.

Effect of amlodipine on vascular responses after coronary stenting compared with an angiotensin-converting enzyme inhibitor.

BACKGROUND: Prevention of restenosis after coronary stenting is clinically important. We compared amlodipine and quinapril to determine which is more effective in preventing restenosis after stenting. METHODS AND RESULTS: Immediately after successful coronary stenting of 101 lesions in 63 consecutive patients, the patients were randomly divided into 2 groups: 32 patients with 48 lesions were administered amlodipine 5 mg/day (group A), and 31 patients with 53 lesions were administered quinapril 10 mg/day (group Q). Lesions were assessed by quantitative coronary angiography (QCA) before and immediately after stenting and in the follow-up phase. Intravascular ultrasound (IVUS) could only be performed on 20 lesions in group A and 16 lesions in group Q throughout the follow-up period. We analyzed each lesion at 5 sites. In the follow-up phase, the minimal lumen diameter in group A was significantly larger than that in group Q (1.88 +/- 0.64 mm vs 1.52 +/- 0.53 mm, p<0.01). In the follow-up phase, the neointimal area (stent area-lumen area) in group A was significantly smaller than that in group Q (1.9 +/- 0.5 mm2 vs 2.7 +/- 0.8 mm2 at the middle portion of stent, p<0.01). CONCLUSION: These QCA and IVUS findings suggest that amlodipine has beneficial effects in inhibiting neointimal hyperplasia in stented lesions compared with quinapril.

U-shaped effect of drinking and linear effect of smoking on risk for stomach cancer in Japan.

A case-control study was conducted to evaluate the relationship between smoking or drinking doses and risk for stomach cancer, and to clarify whether the relationship is dose-dependent or U-shaped. Smoking dose was categorized as 0, 1 - 399, 400 - 799, or 800 + cigarette-years, and drinking dose as 0, occasional/0.1 - 134.9, 135 - 1349.9, or 1350 + alcohol-years (ml of pure alcohol intake per day multiplied by years of drinking). Helicobacter pylori status was determined by serology for adjustment. Using logistic regression, the adjusted effects of smoking and drinking doses on risk for stomach cancer were calculated for both genders. Among male subjects, the odds ratios (95% confidence intervals (CIs)) were 1.29 (0.76, 2.18) for 1 - 399, 1.71 (1.05, 2.80) for 400 - 799 and 2.46 (1.49, 4.07) for 800 + cigarette-years compared with never-smokers, and 1.89 (0.97, 3.69) for never-drinkers, 2.82 (1.63, 4.86) for 135 - 1349.9 and 2.84 (1.97, 4.83) for 1350.0 +, compared with occasional/0.1 - 134.9 alcohol-years. Among female subjects, they were 0.44 (0.20, 1.00) for 1 - 399 and 2.471 (0.91, 6.68) for 400 + cigarette-years compared with never-smokers, and 1.54 (0.90, 2.63) for never-drinkers and 1.39 (0.66, 2.93) for 135.0 + alcohol-years. Smoking seems to exert a linear effect and drinking, a J- or U-shaped effect on risk for stomach cancer, although there might be a dip of risk in light smokers among female subjects.