Time-resolved pair distribution function analysis of disordered materials on beamlines BL04B2 and BL08W at SPring-8.

A dedicated apparatus has been developed for studying structural changes in amorphous and disordered crystalline materials substantially in real time. The apparatus, which can be set up on beamlines BL04B2 and BL08W at SPring-8, mainly consists of a large two-dimensional flat-panel detector and high-energy X-rays, enabling total scattering measurements to be carried out for time-resolved pair distribution function (PDF) analysis in the temperature range from room temperature to 873 K at pressures of up to 20 bar. For successful time-resolved analysis, a newly developed program was used that can monitor and process two-dimensional image data simultaneously with the data collection. The use of time-resolved hardware and software is of great importance for obtaining a detailed understanding of the structural changes in disordered materials, as exemplified by the results of commissioned measurements carried out on both beamlines. Benchmark results obtained using amorphous silica and demonstration results for the observation of sulfide glass crystallization upon annealing are introduced.

Synthesis of Sulfide Solid Electrolytes through the Liquid Phase: Optimization of the Preparation Conditions.

All-solid-state lithium batteries using inorganic sulfide solid electrolytes have good safety properties and high rate capabilities as expected for a next-generation battery. Presently, conventional preparation methods such as mechanical milling and/or solid-phase synthesis need a long time to provide a small amount of the product, and they have difficult in supplying a sufficient amount to meet the demand. Hence, liquid-phase synthesis methods have been developed for large-scale synthesis. However, the ionic conductivity of sulfide solid electrolytes prepared via liquid-phase synthesis is typically lower than that prepared via solid-phase synthesis. In this study, we have controlled three factors: (1) shaking time, (2) annealing temperature, and (3) annealing time. The factors influencing lithium ionic conductivity of Li3PS4 prepared via liquid-phase synthesis were quantitatively evaluated using high-energy X-ray diffraction (XRD) measurement coupled with pair distribution function (PDF) analysis. It was revealed from PDF analysis that the amount of Li2S that cannot be detected by Raman spectroscopy or XRD decreased the ionic conductivity. Furthermore, it was revealed that the ionic conductivity of Li3PS4 is dominated by other parameters, such as remaining solvent in the sample and high crystallinity of the sample.

A diagnostic evaluation of serum human telomerase reverse transcriptase mRNA as a novel tumor marker for gynecologic malignancies.

Human telomerase reverse transcriptase (hTERT) and epidermal growth factor receptor (EGFR) play an important role in many cancers including gynecological cancers. We previously reported the usefulness of a quantitative highly sensitive detection method for hTERT mRNA in the serum of cancer patients. By this method, we attempted to elucidate the diagnostic evaluation of serum hTERT mRNA for gynecologic malignancies. In 174 female patients with gynecological lesions (47 with ovarian lesions, 63 with uterine lesions, 2 with malignancies in other gynecological lesions, and 62 benign lesions) and 20 healthy individuals, we measured serum hTERT mRNA and EGFR mRNA by using the newly developed real-time quantitative RT-PCR. We examined their sensitivity and specificity in cancer diagnosis, clinical significance in comparison with conventional tumor markers, and their correlations with the clinical parameters by using multivariate analyses. Serum hTERT mRNA showed higher values in patients with gynecologic cancers than in those with benign diseases and healthy individuals. The hTERT mRNA level independently correlated with the presence of cancers (P=0.004 for both ovarian and uterine cancer) and clinical stage (P<0.001). The sensitivity and specificity of hTERT mRNA in cancer diagnosis was 74.4% and 74.1%, respectively. The hTERT mRNA level showed a significant correlation with CA125 by Pearson's relative test (P=0.035) and with histological findings in ovarian cancer by the Friedman test (P<0.004). EGFR mRNA did not display any differences between the diseases. hTERT mRNA is useful for diagnosing gynecologic cancer and is superior to conventional tumor markers. Therefore, serum hTERT mRNA is a novel and available biomarker for gynecologic malignancies.

PTEN-positive and phosphorylated-Akt-negative expression is a predictor of survival for patients with advanced endometrial carcinoma.

PTEN and the PI3K/Akt pathway are involved in the development and/or progression of endometrial carcinoma. To clarify the impact of the pathway-related molecules on prognosis, we analyzed PTEN, phosphorylated-Akt (p-Akt), and Ki-67 expression by immunohistochemistry in 99 patients with advanced endometrial carcinoma. PTEN-negative or PTEN-mixed staining was found in 66% of tumors. Positive staining of p-Akt was found in 40% of tumors. Loss of PTEN expression (negative or mixed) was significantly associated with positive p-Akt expression. The patients with PTEN-positive and p-Akt-negative expression clearly showed a higher survival rate than patients in the other groups. Subsequent multivariate analysis revealed that the combination of PTEN/Akt expression was an independent prognostic factor. Examining the relationship between p-Akt expression and Ki-67 labeling index (LI), we found that negative p-Akt was related to a decrease in Ki-67 LI. Additionally, the patients with low Ki-67 LI, as determined by p-Akt-expression status, had a better prognosis. In the present study, we demonstrated that PTEN-positive and p-Akt-negative expression was a predictor of survival for patients with advanced endometrial carcinoma. This study suggests the clinical significance of PTEN and p-Akt expression analysis in treatment decisions for patients with advanced endometrial carcinoma.

Hydrotubation for diagnosing carcinoma in situ of the fallopian tube. A case report.

BACKGROUND: Primary adenocarcinoma of the fallopian tube is rare and not diagnosed until at an advanced stage. We present a case of carcinoma in situ of the fallopian tube in which cytologic examination obtained by hydrotubation facilitated the diagnosis. CASE: A 55-year-old woman presented to Yamaguchi Red Cross Hospital for uterine cancer screening. Endometrial brush cytology revealed adenocarcinoma cells, but endometrial curettage showed no abnormal findings. We performed hydrotubation, collecting abdominal fluid by culdocentesis for cytology. The smear test showed adenocarcinoma with cells similar to those obtained by endometrial brush cytology. Laparotomy showed no abnormalities in the abdominal cavity, and pelvic washing cytology was negative. Based on the positive cytology found by hydrotubation, we performed a hysterectomy and bilateral salpingo-oophorectomy. Postsurgical histology revealed adenocarcinoma in situ of the fallopian tube. CONCLUSION: The present case suggests that cytologic examination obtained by hydrotubation may be useful in diagnosing early tubal cancer.

PTEN is involved in the signal transduction pathway of contact inhibition in endometrial cells.

PTEN is involved in the regulation of normal cellular functions in addition to its well-known role as a tumor suppressor. In the present study, we have shown that stable transfection of the PTEN gene into PTEN-mutated endometrial carcinoma cells leads to contact inhibition accompanied by a decreased level of phosphorylated-Akt (p-Akt) expression, an increase in p27(Kip1), and a decrease in beta-catenin. PTEN-induced cells with contact inhibition exhibit G0-G1 cell-cycle arrest, and the Ki-67 labeling index is reduced. These changes are canceled by transfection of a double-stranded short-interfering RNA against the PTEN gene. Normal endometrial stromal cells increase their PTEN expression when reaching confluence; this is followed by changes in the expression of Akt-related proteins in the same way as in tumor cells. These results indicate that PTEN, p-Akt, p27, and beta-catenin are involved in the signal transduction of contact inhibition and suggest that PTEN may, in part, control the proliferation of endometrial carcinoma cells through the induction of contact inhibition.

Stromal invasion of the cervix can be excluded from the criteria for using adjuvant radiotherapy following radical surgery for patients with cervical cancer.

BACKGROUND: Regarding complications of radiotherapy, the indications for adjuvant radiotherapy should be restricted. We conducted the present study to determine whether deep stromal invasion of the cervix could be excluded from the criteria used to identify patients for this treatment surgery. METHODS: This study included 115 patients with FIGO stage Ib to IIb cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection. Patients had the following tumors: 61 nonkeratinizing squamous cell carcinoma, 21 keratinizing squamous cell carcinoma, 26 adenocarcinoma, and 7 adenosquamous cell carcinoma. Our study criteria for using adjuvant radiotherapy included positive lymph node involvement, a compromised surgical margin, or parametrial extension. Deep stromal invasion of the cervix was excluded from the criteria in this study. RESULTS: Seventy-two of the 115 patients (62.6%) underwent radical surgery only and all were alive. The remaining 43 patients received a complete course of external irradiation following radical surgery. The estimated 5-year survival rate is 100% for patients with stage Ib, 93.3% for stage IIa, and 52.7% for stage IIb. Fifty-five patients (47.8%) had deep stromal invasion. The prognosis for patients with deep stromal invasion was significantly worse than that for patients without deep stromal invasion (5-year survival rate, 69.8% vs. 98.0%). However, 21 patients (18.3%) with deep stromal invasion, but without positive lymph node involvement, compromised surgical margin, or parametrial extension, were alive without recurrence. Multivariate analysis showed that lymph node involvement and parametrial extension were independent prognostic factors, but that deep stromal invasion was not. CONCLUSION: Deep stromal invasion of the cervix can be excluded from the list of criteria for selecting patients with cervical cancer who would benefit from adjuvant radiotherapy following radical surgery.

Mechanisms of cisplatin resistance in clear cell carcinoma of the ovary.

Resistance of clear cell carcinoma (CCC) of the ovary to platinum-based chemotherapy is associated with a poor prognosis. However, the mechanism underlying the resistance of CCC to platinum has not yet been understood. We conducted the present study to clarify the mechanism of cisplatin (CDDP) resistance in CCC cells. Eleven CCC and 5 serous adenocarcinoma (SAC) cell lines were used in this study. The IC(50) to CDDP ranged from 1.3 to 18.0 microM for CCC cells and from 2.2 to 13.0 microM for SAC cells. There was no correlation between multidrug resistance-associated protein expression and the sensitivity to CDDP in CCC cells. In contrast, the doubling time for CCC cells was significantly longer than that for SAC cells (61.4 vs. 29.8 h). A significant reverse correlation between the S-phase fraction and the response to CDDP was observed (r = 0.647, p < 0.05). The present study suggests that the resistance of CCC to CDDP may be caused by low cell proliferation.