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1.  The angiogenesis regulator vasohibin-1 inhibits ovarian cancer growth and peritoneal dissemination and prolongs host survival 
International Journal of Oncology  2015;47(6):2057-2063.
Vasohibin-1 (VASH1) is expressed in vascular endothelial cells stimulated by several angiogenic growth factors and displays autocrine activity to regulate angiogenesis via a negative feedback mechanism. In this study, we investigated the effect of VASH1 on ovarian cancer progression using VASH1-expressing ovarian cancer cells in vitro and in vivo. The growth ability of ovarian cancer cells engineered to express the VASH1 gene remained unchanged in vitro. However, we showed that VASH1 secretion by tumor cells inhibited the growth of human umbilical vein endothelial cells. Further, animal experiments showed that VASH1 expression inhibited tumor angiogenesis and growth. In a murine model of peritoneal dissemination of ovarian cancer cells, VASH1 inhibited peritoneal dissemination and ascites, resulting in significantly prolonged survival in mice. This indicates that VASH1 exerts an antitumor effect on ovarian cancer by inhibiting angiogenesis in the tumor environment. These findings suggest that a novel therapy based on VASH1 could be a useful therapeutic strategy for ovarian cancer.
PMCID: PMC4665704  PMID: 26460696
angiogenesis; ovarian cancer; peritoneal dissemination; SKOV-3; vasohibin-1
2.  Effect of providing risk information on undergoing cervical cancer screening: a randomized controlled trial 
In Japan, the cervical cancer screening rate is extremely low. Towards improving the cervical cancer screening rate, encouraging eligible people to make an informed choice, which is a decision-making process that relies on beliefs informed by adequate information about the possible benefits and risks of screening, has attracted increased attention in the public health domain. However, there is concern that providing information on possible risks of screening might prevent deter from participating.
In total, 1,912 women aged 20–39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 3 groups. Group A received a printed reminder with information about the possible benefits of screening, group B received a printed reminder with information about possible benefits and risks, and group C received a printed reminder with simple information only (control group).
Out of 1,912 participants, 169 (8.8%) participated in cervical cancer screening. In the intervention groups, 137 (10.9%) participated in cervical cancer screening, compared to only 32 (4.9%) of the control group (p < 0.001). In addition, logistic regression analysis revealed that there was no significant difference in screening rate between group A and group B (p = 0.372).
Providing information on the possible risks of screening may not prevent people from taking part in cervical cancer screening among a Japanese non-adherent population.
PMCID: PMC4340285  PMID: 25717376
Cervical cancer screening; Informed choice; Risk information; Printed client reminder; Organized screening
3.  Successful management of severe intrahepatic cholestasis of pregnancy: report of a first Japanese case 
BMC Gastroenterology  2014;14:160.
Intrahepatic cholestasis of pregnancy (ICP) is a cholestasis condition caused by elevated levels of serum bile acids that mainly occurs in the third trimester of pregnancy. Maternal symptoms include pruritus; elevation of transaminases, biliary enzymes, and bilirubin levels; and abnormal liver function tests. Fetal symptoms include spontaneous preterm labor, fetal distress, and intrauterine death. It is more prevalent in the Caucasians and is rarely found in Asian countries, including Japan. The etiology of ICP has been reported as involving various factors such as, environmental factors, hormone balance, and genetic components. The genetic factors include single-nucleotide polymorphisms (SNPs) in the genes of canalicular transporters, including ABCB4 and ABCB11. It has also been reported that the combination of these SNPs induces severe cholestasis and liver dysfunction.
Case presentation
Here, we report for the first time a 24-year Japanese case of severe ICP diagnosed by typical symptoms, serum biochemical analysis, and treated with the administration of ursodeoxycholic acid which improved cholestasis and liver injury and prevented fetal death. The sequence analysis showed SNPs reported their association with ICP in the ABCB11 (rs2287622, V444A) and ABCB4 (rs1202283, N168N) loci.
The risk of ICP has been reported to be population-specific, and it is rare in the Japanese population. Our case was successfully treated with ursodeoxycholic acid and the genetic sequence analysis has supported the diagnosis. Because genetic variation in ABCB4 and ABCB11 has also been reported in the Japanese population, we need to be aware of potential ICP cases in pregnant Japanese women although further studies are necessary.
PMCID: PMC4175624  PMID: 25218883
Intrahepatic cholestasis of pregnancy; Bile acid; Ursodeoxycholic acid; Single-nucleotide polymorphism; ABCB11; ABCB4
4.  Downregulation of vasohibin-2, a novel angiogenesis regulator, suppresses tumor growth by inhibiting angiogenesis in endometrial cancer cells 
Oncology Letters  2013;5(3):1058-1062.
The vasohibin-2 (VASH2) gene was originally found to be expressed in infiltrating mononuclear cells of a mouse model of hypoxia-induced subcutaneous angiogenesis. These cells are mobilized from bone marrow to promote angiogenesis. Recently, VASH2 has been demonstrated to be expressed in several types of cancer in which it promotes tumor development through angiogenesis. However, its role in endometrial cancer remains unknown. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), we found that VASH2 was overexpressed in several human endometrial cancer cell lines, including the HEC50B cell line, which we used to further examine the role of VASH2. Although knockdown of VASH2 with stable transfection of shRNA had little effect on the proliferation of HEC50B cells in vitro, knockdown in an in vivo murine xenograft model inhibited tumor growth by decreasing tumor angiogenesis. In addition, the supernatant from HEC50B cells that expressed VASH2 significantly promoted the proliferation of human umbilical vein endothelial cells. By contrast, knockdown of VASH2 significantly attenuated the proliferative effect. These results indicate that VASH2 contributes to the development of endometrial cancer by promoting angiogenesis through a paracrine mode of action. Consequently, VASH2 may be considered to be a novel molecular target for endometrial cancer therapy.
PMCID: PMC3576280  PMID: 23426782
endometrial cancer; vasohibin-2; tumor angiogenesis; molecular-targeted therapy; endothelial cells
5.  Fertility-sparing treatment using medroxyprogesterone acetate for endometrial carcinoma 
Oncology Letters  2012;3(5):1002-1006.
The purpose of this study was to present the results of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC), and to clarify patient characteristics by investigating patient background factors. A total of 59 patients with EC, who received MPA as fertility-sparing therapy at two institutions over a 21-year period between 1987 and 2008, were studied retrospectively. Patients were administered oral MPA at 400–600 mg/day for 16–24 weeks as long as they responded. Endometrial tissue was assessed twice, at 8–12 weeks (during treatment) and shortly after treatment. The overall complete response (CR) rate was 71%. A total of 22 (52%) of 42 responders later developed relapse. A total of 19 cases became pregnant, and 25 infants were born. Eighty percent of recurrences occurred within 2 years. For stages I a and I b- II a (FIGO, 1988), initial CR rates were 80.0 and 42.9%, respectively (p<0.01), demonstrating a significant difference. Total hysterectomy was performed for 26 patients (44%) due to recurrence or failure to respond to the initial treatment. Among these 26 patients, postoperative stages were more advanced in 10 patients (38%). The grade advanced (became more poorly differentiated) postoperatively in 2 patients (8%). Premenopausal females with EC can be treated successfully with MPA, however patients should be informed of the risks and limitations of this conservative treatment.
PMCID: PMC3389624  PMID: 22783380
endometrial carcinoma; fertility-sparing treatment; medroxyprogesterone acetate
6.  Detection of Large Interaural Delays and Its Implication for Models of Binaural Interaction  
The interaural time difference (ITD) is a major cue to sound localization along the horizontal plane. The maximum natural ITD occurs when a sound source is positioned opposite to one ear. We examined the ability of owls and humans to detect large ITDs in sounds presented through headphones. Stimuli consisted of either broad or narrow bands of Gaussian noise, 100 ms in duration. Using headphones allowed presentation of ITDs that are greater than the maximum natural ITD. Owls were able to discriminate a sound leading to the left ear from one leading to the right ear, for ITDs that are 5 times the maximum natural delay. Neural recordings from optic-tectum neurons, however, show that best ITDs are usually well within the natural range and are never as large as ITDs that are behaviorally discriminable. A model of binaural cross-correlation with short delay lines is shown to explain behavioral detection of large ITDs. The model uses curved trajectories of a cross-correlation pattern as the basis for detection. These trajectories represent side peaks of neural ITD-tuning curves and successfully predict localization reversals by both owls and human subjects.
PMCID: PMC3202365  PMID: 12083726
interaural; binaural; owl; ITD

Results 1-6 (6)