Eiji Hirata

Alangionosides A and B, ionol glycosides from leaves of Alangium premnifolium

From leaves of Alangium premnifolium harvested on Okinawa island, two new ionol glycosides, named alangionosides A and B, along with dendranthemoside A and benzyl alcohol xyloglucoside, were isolated. Their structures were determined mainly by means of spectroscopic methods. The application of β-d-glucosylation induced shift trends for the determination of the absolute configuration of a carbon atom having a secondary hydroxyl group is also discussed.

Intergender differences in histological architecture of the fascia pelvis parietalis: a cadaveric study.

The fascia pelvis parietalis (FPP) or endopelvic fascia is a well‐known structure, but few studies described the detailed histological architecture, including the composite fiber directions. We hypothesized a gender‐specific fiber architecture corresponding to the functional demand. For the first step to examine this hypothesis, we investigated specimens from 27 adult cadavers (10 males and 17 females) and 11 midterm fetuses (five males and six females) using immunohistochemistry and aldehyde‐fuchsin staining. The adult female FPP was a solid, thick monolayered structure that was reinforced by abundant elastic fibers running across the striated muscle fibers, but it contained little or no smooth muscles (SM). In contrast, the male FPP was multilayered with abundant SM. In midterm fetuses, SM originated from the inferior part of the bladder and extended inferiorly along the gender‐specific courses. Thus, we found a clear intergender difference in FPP architecture. However, the functional significance remained unknown because the basic architecture was common between nulliparous and multiparous women. Rather than for meeting the likely mechanical demands of pregnancy and vaginal delivery, the intergender difference of the FPP seemed to result from differences in the amount and migration course of bladder‐derived SM as well as in hormonal background. Clin. Anat. 24:469–477, 2011.

Comparative histological study of levels 1–3 supportive tissues using pelvic floor semiserial sections from elderly nulliparous and multiparous women

Aim:u2002 The connective tissue located between the uterine cervix and sacrospinous ligament (the uterospinous connective tissue; USCT) has recently been noted as the level 1 supportive tissue instead of the classical uterosacral ligament. We examined whether or not the USCT changes its histological architecture by vaginal delivery in correlation with the levels 2 and 3 supportive tissues.

(+)-Isolarisiresinol 3a-O-sulphate from leaves of Myrsine seguinii.

From leaves of Myrsine seguinii, (+)-isolarisiresinol 3a-O-beta-D-glucopyranoside and 3a-O-sulphate were isolated. Their structures were elucidated by spectroscopic analyses.

Predicting the chemosensitivity of ovarian and uterine cancers with the collagen gel droplet culture drug-sensitivity test

We investigated the utility of the collagen gel droplet culture drug-sensitivity test (CD-DST) for predicting the response of gynecological cancers to chemotherapy. Eighty-three cancer patients were enrolled in this study: 26 ovarian, 29 cervical and 31 endometrial cancers. The CD-DST was performed at various concentrations of drugs. We calculated the T/C ratio, where T is the total volume of the treated culture and C is the total volume of the control culture, and a T/C ratio of 50% or less was defined as sensitive in vitro. The efficacy rate (%) was defined as the number of cultures with a T/C ratio of 50% or less, divided by the total number of evaluable cultures. True-positive cases were defined as clinical responders (complete+partial responses) and true-negative cases were defined as clinical non-responders. The overall tumor evaluation rate was found to be 79.1%. The appropriate drug concentrations were selected as 1.0u2009μg/ml for cisplatin, 20.0u2009μg/ml for carboplatin, 1.0u2009μg/ml for paclitaxel and 0.1u2009μg/ml for docetaxel by the linear regression equations. The in vitro sensitivity for each drug showed a significant correlation with clinical response rates (r=0.592, p=0021). We therefore conclude that the CD-DST can be used to predict the response to anti-cancer drugs, and may also provide important information by contributing to the development of new chemotherapy regimens.

Impact of UGT1A1 genotype upon toxicities of combination with low-dose irinotecan plus platinum

Irinotecan‐induced severe toxicities are possibly related to UGT1A1*6 and *28 genotypes. However, the correlation between UGT1A1 polymorphisms and the risk of toxicities induced by low‐dose irinotecan plus platinum combination therapy still remains controversial. This prospective observational study aimed to examine the correlation between UGT1A1 genotypes and clinical outcomes of low‐dose irinotecan (median 60 mg/m2, range 25–115 mg/m2) plus platinum in Japanese patients with solid tumors.

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial

OBJECTIVEnA multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with weekly cisplatin (CDDP) and paclitaxel (PTX) in patients with locally advanced uterine cervical cancer.nnnMETHODSnPatients with FIGO stage III-IVA uterine cervical cancer without para-aortic lymphadenopathy were enrolled. Patients received definitive radiotherapy (RT) consisting of external beam whole-pelvic RT and high-dose-rate intracavitary brachytherapy. The cumulative linear quadratic equivalent dose was 62-65Gy prescribed at point A. weekly CDDP at 30mg/m(2) and PTX at 50mg/m(2) were administered concurrently with RT for ≥5 courses.nnnRESULTSnSixty-eight of the 70 registered patients were eligible. The complete response rate was 76.5% (95% confidence interval [CI], 66.4-86.6%). With a median follow-up of 27months (range, 7.9-33.5), the 2-year cumulative progression-free survival and the 2-year cumulative overall survival rates were 83.8% (95% CI, 75.1-92.6%) and 92.7% (95% CI, 86.4-98.9%), respectively. The pelvic cumulative disease progression-free and the 2-year cumulative distant metastasis rates were 89.6% (95% CI, 82.3-96.9%) and 13.2% (95% CI, 5.2-21.3%), respectively. The 2-year cumulative late complication rates were 25% for all grades, 13.2% for grade 1, 5.9% for grade 2, 2.9% for grade 3, and 2.9% for grade 4.nnnCONCLUSIONSnFor locally advanced cervical cancer, CCRT with weekly CDDP 30mg/m(2) and PTX at 50mg/m(2) demonstrated favorable antitumor activity, and was feasible and safe with respect to the protocol-specified serious adverse reactions and events. Evaluation of this regimen in phase III trials is warranted.

Regulation of multidrug resistance 1 expression by CDX2 in ovarian mucinous adenocarcinoma

Epithelial ovarian cancer is an aggressive gynecological malignancy with a high mortality rate. Resistance against chemotherapeutic agents often develops in ovarian cancer patients, contributing to high recurrence rates. The multidrug resistance 1 (MDR1/ABCB1) gene encodes P‐glycoprotein, which affects the pharmacokinetic properties of anticancer agents. We previously reported that the Caudal‐related homeobox transcription factor CDX2 transcriptionally regulates MDR1 expression in colorectal cancer. CDX2 is a factor that influences cancer cell differentiation, malignancy, and cancer progression. We hypothesized that profiling of CDX2 and MDR1 expression could be an effective strategy for predicting anticancer drug resistance. We studied the expression of these factors in clinical samples from ovarian cancer patients. We found that endogenous MDR1 expression was positively associated with CDX2 expression in ovarian mucinous adenocarcinoma. Using ovarian mucinous adenocarcinoma cell lines, we also observed decreased MDR1 expression following inhibition of CDX2 by RNA interference. In addition, CDX2 overexpression in MN‐1 cells, which display low endogenous CDX2, resulted in upregulation of MDR1 expression. CDX2 induced MDR1‐dependent resistance to vincristine and paclitaxel, which was reversed by treatment with the MDR1‐specific inhibitor verapamil. Our findings show that CDX2 promotes upregulation of MDR1 expression, leading to drug resistance in ovarian mucinous adenocarcinoma. Therefore, our study demonstrates the potential of novel chemotherapy regimens based on CDX2 status and MDR1 expression in ovarian mucinous adenocarcinoma.

Two Case Reports of Intravenous Leiomyomatosis with Hyaluronan Expression

Intravenous leiomyomatosis (IVL) is a rare benign neoplasm. Herein, we describe two cases of IVL at different levels of progression. The tumor in Case 1 was extensive, invading the right atrium after a hysterectomy for a uterine myoma. The tumor temporarily responded to hormonal treatment; however, tumor regrowth occurred. In contrast, the tumor in Case 2 extended only to the pelvic veins and was revealed preoperatively. Hysterectomy and bilateral salpingo-oophorectomy were performed, resulting in the complete surgical resection of the tumor. In Case 2, no recurrence has been observed. Tumor samples were evaluated for hyaluronan expression using Alcian blue staining (with and without hyaluronidase digestion). The tumor in Case 1 stained strongly positive for hyaluronan while the tumor in Case 2 stained weakly positive for hyaluronan. In contrast, a large non-IVL uterine leiomyoma (control) stained negative for hyaluronan. These results suggest a relationship between tumor hyaluronan expression and IVL progression, similar to that in other cancers.