Publications by authors named "Shingo Miyamoto"

183 Publications

Comparison between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff.

Palliat Support Care 2021 Mar 5:1-7. Epub 2021 Mar 5.

Section of Liaison Psychiatry and Palliative Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Objectives: The goal of palliative and supportive care is to improve patients' quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff).

Methods: This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs).

Results: One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient-staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and -0.038 (Practical Problems) to 0.830 (Nausea), respectively.

Significance Of Results: The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.
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http://dx.doi.org/10.1017/S1478951521000018DOI Listing
March 2021

Rabdosianone I, a Bitter Diterpene from an Oriental Herb, Suppresses Thymidylate Synthase Expression by Directly Binding to ANT2 and PHB2.

Cancers (Basel) 2021 Feb 26;13(5). Epub 2021 Feb 26.

Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Natural products have numerous bioactivities and are expected to be a resource for potent drugs. However, their direct targets in cells often remain unclear. We found that rabdosianone I, which is a bitter diterpene from an oriental herb for longevity, Hara, markedly inhibited the growth of human colorectal cancer cells by downregulating the expression of thymidylate synthase (TS). Next, using rabdosianone I-immobilized nano-magnetic beads, we identified two mitochondrial inner membrane proteins, adenine nucleotide translocase 2 (ANT2) and prohibitin 2 (PHB2), as direct targets of rabdosianone I. Consistent with the action of rabdosianone I, the depletion of ANT2 or PHB2 reduced TS expression in a different manner. The knockdown of ANT2 or PHB2 promoted proteasomal degradation of TS protein, whereas that of not ANT2 but PHB2 reduced TS mRNA levels. Thus, our study reveals the ANT2- and PHB2-mediated pleiotropic regulation of TS expression and demonstrates the possibility of rabdosianone I as a lead compound of TS suppressor.
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http://dx.doi.org/10.3390/cancers13050982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956614PMC
February 2021

Medical costs of lung cancer care in Japan during the first one or two years after initial diagnosis.

Jpn J Clin Oncol 2021 Jan 28. Epub 2021 Jan 28.

Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.

Objectives: Japan's healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer.

Methods: We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis-Cohort 1: 2008-2010, Cohort 2: 2011-2014 and Cohort 3: 2015-2018-and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis.

Results: Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P < 0.001), with a median incremental cost of Japanese Yen 6 million during the initial two years. The proportion of outpatient costs increased over time, especially for NSCLC patients (P < 0.001). No changes in costs or survival were observed in SCLC patients.

Conclusions: In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.
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http://dx.doi.org/10.1093/jjco/hyaa258DOI Listing
January 2021

Medical costs of Japanese lung cancer patients during end-of-life care.

Jpn J Clin Oncol 2021 Jan 28. Epub 2021 Jan 28.

Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.

Objective: The medical costs associated with cancer treatment have increased rapidly in Japan; however, little data exist on actual costs, especially for end-of-life care. Therefore, this study aimed to examine the medical costs of lung cancer patients during the last 3 months before death and to compare the costs with those of initial anticancer treatment.

Methods: We retrospectively evaluated all patients who died from lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 August 2019. Patients were classified into three cohorts (2008-2011, 2012-2015 and 2016-2019) according to the year of death; the medical costs were evaluated for each cohort. Costs were then divided into outpatient and inpatient costs and calculated per month.

Results: Seventy-nine small cell lung cancer and 213 non-small cell lung cancer patients were included. For small cell lung cancer and non-small cell lung cancer patients, most end-of-life medical costs were inpatient costs across all cohorts. The median monthly medical costs for the last 3 months among both small cell lung cancer and non-small cell lung cancer patients did not differ significantly among the cohorts, but the mean monthly costs for non-small cell lung cancer tended to increase. The monthly medical costs for the last 3 months were significantly higher than those for the first year in SCLC (P = 0.013) and non-small cell lung cancer (P < 0.001) patients and those for the first 3 months in non-small cell lung cancer patients (P = 0.005).

Conclusions: The medical costs during the end-of-life period for lung cancer were high and surpassed those for initial treatment.
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http://dx.doi.org/10.1093/jjco/hyaa259DOI Listing
January 2021

Adipose tissue-derived regenerative cells improve implantation of fertilized eggs in thin endometrium.

Regen Med 2020 07 23;15(7):1891-1904. Epub 2020 Jul 23.

Department of Obstetrics & Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Embryo implantation and subsequent pregnancy depends on endometrial thickness. To investigate potential fertility strategies for women with thin endometrium, we explored the efficacy of adipose tissue-derived regenerative cells (ADRCs) on thin endometrium and embryo implantation in a mouse model. ADRCs isolated from mouse subcutaneous fat were characterized by flow cytometry. Endometrium thickness, endometrial fibrosis, embryo implantation and angiogenesis factors were evaluated in uterine cavities of ethanol-induced thin endometrium mice with ADRC transplantation. ADRCs included adipose-derived stem cells and some blood vessel component cells. ADRCs improved endometrial thickness, endometrial fibrosis and embryo implantation and augmented vascular endothelial growth factor expression in the mouse uterine. ADRCs may be a useful therapeutic strategy to improve fertility of women with thin endometrium.
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http://dx.doi.org/10.2217/rme-2020-0037DOI Listing
July 2020

Low-Dose Erlotinib Treatment in Elderly or Frail Patients With EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Multicenter Phase 2 Trial.

JAMA Oncol 2020 07 9;6(7):e201250. Epub 2020 Jul 9.

Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Importance: Although the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for EGFR gene mutation-positive non-small cell lung cancer is well established, optimal dosing remains to be established, especially in elderly or frail patients.

Objective: To investigate the efficacy and safety of low-dose erlotinib in elderly or frail patients with EGFR mutation-positive non-small cell lung cancer.

Design, Setting, And Participants: Single-arm phase 2 trial with the Southwest Oncology Group (SWOG) 2-stage design that enrolled frail patients from 21 Japanese institutions after meeting the inclusion criteria. Chemotherapy-naive patients with EGFR-activating mutation-positive non-small cell lung cancer who were considered frail based on age, the Charlson Comorbidity Index, and Eastern Cooperative Oncology Group performance status were eligible for the study.

Interventions: Patients were initially administered 50 mg/d erlotinib for 4 weeks, which was modified based on response or adverse events. Dose increase was permitted for patients with stable disease after 4 weeks.

Main Outcomes And Measures: The primary end point was the independent review committee-confirmed objective response rate (ORR) at the dose of 50 mg/d. The study also evaluated the pharmacokinetics of low-dose erlotinib and influence of ABCB1 gene polymorphisms.

Results: Eighty patients were enrolled, with a median (range) age of 80 (49-90) years; 54 (68%) were men. An independent review committee confirmed a significant ORR of 60.0% (90% CI, 50.2%-69.2%). The disease control rate was 90.0% (90% CI, 82.7%-94.9%), median progression-free survival was 9.3 months (95% CI, 7.2-11.4 months), and median overall survival was 26.2 months (95% CI, 21.9-30.4 months). Mild adverse events were observed in some participants, with few patients exhibiting grade 3 or greater adverse events. Low-dose erlotinib treatment was temporarily suspended for 10 patients owing to adverse events. Five of 80 patients (6%) had their erlotinib dose reduced to 25 mg because of oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia. Two patients discontinued treatment because of adverse events (cutaneous ulcer and bone infection, and oral mucositis, respectively). There were no cases of interstitial lung disease or treatment-related deaths. The median (range) erlotinib plasma concentration was measured at 685 (153-1950) ng/mL. Seventy-three patients discontinued study treatment owing to disease progression (n = 60), death (n = 3), AEs (n = 4), and patient requests (n = 6). No clear association was observed between the pharmacokinetics of low-dose erlotinib and the treatment outcome.

Conclusions And Relevance: Low-dose erlotinib appears to be safe and effective in elderly or frail patients with EGFR mutation-positive non-small cell lung cancer and can be a valid treatment option.

Trial Registration: UMIN-CTR Identifier: UMIN000015949.
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http://dx.doi.org/10.1001/jamaoncol.2020.1250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226294PMC
July 2020

Salvage Chemotherapy Following Osimertinib in Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation.

Anticancer Res 2020 Apr;40(4):2239-2246

Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan

Aim: The current study reports the type of salvage chemotherapy following osimertinib and its treatment efficacy in patients with non-small-cell lung carcinoma (NSCLC) who acquire resistance to osimertinib.

Patients And Methods: In this retrospective cohort study, data from the medical charts of 40 patients with NSCLC treated with osimertinib were obtained, primarily focusing on 14 undergoing salvage chemotherapy including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) or cytotoxic agents immediately following osimertinib. The treatment efficacy of salvage chemotherapy was evaluated.

Results: Five and nine patients received EGFR-TKI and cytotoxic agents following osimertinib, respectively. The overall response rate to EGFR-TKI treatment following osimertinib tended to be lower than that for cytotoxic agents (0% vs. 44.4%). The median progression-free-survival was significantly poorer in patients receiving EGFR-TKI treatment than in those receiving cytotoxic agents.

Conclusion: Cytotoxic agent administration should be considered more frequently than EGFR-TKIs for patients with NSCLC resistant to osimertinib.
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http://dx.doi.org/10.21873/anticanres.14186DOI Listing
April 2020

Theracurmin inhibits intestinal polyp development in Apc-mutant mice by inhibiting inflammation-related factors.

Cancer Sci 2020 Apr 22;111(4):1367-1374. Epub 2020 Feb 22.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well-known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc-mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10-20 µM Theracurmin for 24 hours reduced nuclear factor-κB (NF-κB) transcriptional activity in human colon cancer DLD-1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF-κB promoter transcriptional activity. As NF-κB is a regulator of inflammation-related factors, we next investigated the downstream targets of NF-κB: monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP-1 and IL-6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J-CAP-C study).
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http://dx.doi.org/10.1111/cas.14329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156816PMC
April 2020

The Radical Scavenger NZ-419 Suppresses Intestinal Polyp Development in -Mutant Mice.

J Clin Med 2020 Jan 18;9(1). Epub 2020 Jan 18.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.

Colorectal cancer is the fourth leading cause of cancer death worldwide, and it is important to establish effective methods for preventing colorectal cancer. One effective prevention strategy could be the use of antioxidants. However, the role of the direct antioxidative function of antioxidants against carcinogenesis has not been clarified. Thus, we aimed to determine whether the direct removal of reactive oxygen species by a hydroxyl radical scavenger, NZ-419, could inhibit colorectal carcinogenesis. NZ-419 is a creatinine metabolite that has been shown to be safe and to inhibit the progression of chronic kidney disease in rats, and it is now under clinical development. In the present study, we demonstrated that NZ-419 eliminated reactive oxygen species production in HCT116 cells after HO stimulation and suppressed HO-induced Nrf2 promoter transcriptional activity. The administration of 500 ppm NZ-419 to -mutant Min mice for 8 weeks resulted in a decrease in the number of polyps in the middle segment of the small intestine to 62.4% of the value in the untreated control ( < 0.05 vs. control group). As expected, NZ-419 treatment affected the levels of reactive carbonyl species, which are oxidative stress markers in the serum of Min mice. Suppression of the mRNA levels of the proliferation-associated factor was observed in intestinal polyps of Min mice after NZ-419 treatment, with a weak suppression of epithelial cell proliferation assessed by proliferation cell nuclear antigen (PCNA) staining in the intestinal polyps. This study demonstrated that NZ-419 suppress the development of intestinal polyps in Min mice, suggesting the utility of radical scavenger/antioxidants as a cancer chemopreventive agent.
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http://dx.doi.org/10.3390/jcm9010270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019572PMC
January 2020

Treatment effect and safety profile of salvage chemotherapy following immune checkpoint inhibitors in lung cancer.

Lung Cancer Manag 2019 Oct 9;4(6):LMT12. Epub 2019 May 9.

Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.

Aim: To assess the relationship of treatment effects between immune checkpoint inhibitor (ICI) and salvage chemotherapy, with the safety profile of salvage chemotherapy.

Patients & Methods: 18 patients with advanced NSCLC treated using salvage chemotherapy following ICI treatment were retrospectively included. We assessed the overall response rate to and adverse events of salvage chemotherapy.

Results: The overall response rate to salvage chemotherapy was 33.3% and that of ICI responders was significantly higher than that of ICI nonresponders (66.7 vs 16.7%, respectively, p = 0.03). The incidence rate of adverse events to salvage chemotherapy was 55.6%.

Conclusion: The efficacy of salvage chemotherapy was similar to that preceding ICI. Moreover, the safety of salvage chemotherapy was good.
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http://dx.doi.org/10.2217/lmt-2019-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802711PMC
October 2019

High mortality and poor treatment efficacy of immune checkpoint inhibitors in patients with severe grade checkpoint inhibitor pneumonitis in non-small cell lung cancer.

Thorac Cancer 2019 10 3;10(10):2006-2012. Epub 2019 Sep 3.

Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.

Background: The treatment efficacy of immune checkpoint inhibitor (ICI) and clinical outcomes in patients with non-small cell lung cancer (NSCLC) who develop severe grade checkpoint inhibitor pneumonitis (CIP) are unclear. Here, we report on the treatment efficacy of ICI and prognosis in NSCLC patients with severe grade CIP.

Methods: In this retrospective cohort study, CIP severity, CIP-related mortality, and ICI efficacy in 71 patients with advanced NSCLC treated with ICIs were evaluated. Data was obtained from the patients' medical charts.

Results: All grade and severe grade CIP were observed in 22 and 11 patients, respectively. The CIP-related mortality rate was 22.7% (N = 5). An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of ≥2 and pre-existing interstitial lung disease (ILD) were significantly associated with the development of severe grade CIP (P = 0.001 and P = 0.035, respectively). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with severe grade CIP than in those without severe grade CIP (PFS 1.0 month, 95% confidence interval [CI] 0.5-2.0 vs. 3.5 months, 95% CI 2.0-5.0 months, P = 0.003; OS 3.0 months, 95% CI 0.5-13 vs. 12.7 months, 95% CI 8.0-21.0 months, P = 0.011).

Conclusion: CIP is a serious complication with a poor prognosis associated with high mortality. The efficacy of ICI is significantly worse in patients with severe grade CIP than in those without severe grade CIP. Whether ICIs should be administered to patients with CIP risk factors, such as an ECOG PS score of ≥2 or pre-existing ILD, should be carefully assessed.
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http://dx.doi.org/10.1111/1759-7714.13187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775002PMC
October 2019

Clinical Features of Recurrence in Patients Without Residual Tumour in Endometrial Cancer.

Anticancer Res 2019 Aug;39(8):4581-4588

Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

Background/aim: Initial treatment of endometrial cancer with surgery and platinum and taxane-based chemotherapy is often successful, but it remains unclear as to whether certain types of the disease relapse. The aim of this study was to identify the clinical features of recurrence in patients without residual tumour in endometrial cancer.

Patients And Methods: Clinical features, histological type, and time to recurrence were analyzed in 640 endometrial cancer patients without residual tumours.

Results: Of 640 patients, 517 were type I and 123 were type II. For type I, early recurrent (ER) disease and late recurrent (LR) disease were noted in 80 and 8 patients, respectively, and 97.5% of ER occurred within 2 years. After recurrence, 76.2% of ER and 50% of LR patients died. In type II, ER and LR were noted in 41 and 1 patients, respectively, and 97.6% of ER occurred within 2 years, of which 75.6% died after recurrence. One LR case died of disease.

Conclusion: Most patients recurred within 2 years irrespective of clinical stage or type.
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http://dx.doi.org/10.21873/anticanres.13637DOI Listing
August 2019

Spontaneous regression of quiescent gestational trophoblastic disease after pregnancy: a case report.

BMC Womens Health 2019 07 23;19(1):101. Epub 2019 Jul 23.

Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.

Background: A persistent low-level elevation of serum human chorionic gonadotropin (hCG) without clinical or radiological evidence of pregnancy or tumors was recently defined as quiescent gestational trophoblastic disease (Q-GTD). Whether patients with Q-GTD should be treated or allowed to become pregnant remains unclear. We herein report a rare case of Q-GTD in which the hCG level spontaneously returned to normal after a successful pregnancy.

Case Presentation: The patient was a 37-year-old primigravida who presented with a persistent low-level elevation of hCG after uterine evacuation of a hydatidiform mole. There was no evidence of neoplasia in the uterus or distant metastasis. The low-level elevation of hCG persisted for at least 2 years but never exceeded 200 mIU/mL. The patient had a successful pregnancy at the age of 40 years.

Conclusions: Interestingly, her hCG level subsequently normalized without chemotherapy. The present case may imply the safety and therapeutic effect of pregnancy in women with Q-GTD.
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http://dx.doi.org/10.1186/s12905-019-0794-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651975PMC
July 2019

The combination of maternal blood and amniotic fluid biomarkers improves the predictive accuracy of histologic chorioamnionitis.

Placenta 2019 05 23;80:4-7. Epub 2019 Mar 23.

Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Introduction: This study was performed to determine whether the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of histologic chorioamnionitis (HC).

Methods: This retrospective study included 80 singleton pregnant women who were suspected to have intrauterine infection and underwent measurement of two maternal blood biomarkers [maternal white blood cell count (mWBC) and maternal C-reactive protein level (mCRP)] and three amniotic fluid biomarkers [amniotic white blood cell count (aCell), amniotic glucose level (aGlucose), and amniotic lactate dehydrogenase level (aLDH)]. We divided the patients into two groups based on the presence or absence of HC and assessed the predictors of HC using logistic regression models: Model 1, combination of mWBC and mCRP; Model 2, combination of Model 1 and aGlucose; and Model 3, combination of Model 2, aCell, and aLDH.

Results: The multivariable analysis showed that aCell was the only significant predictor of HC [odds ratio, 1.24; 95% confidence interval (CI), 1.06-1.68] independent of mWBC, mCRP, aGlucose, and aLDH. The c-statistics were higher in Model 3 (0.803; 95% CI, 0.701-0.905) than Model 1 (0.634; 95% CI, 0.511-0.758) and Model 2 (0.785; 95% CI, 0.684-0.887).

Discussion: We found that the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of HC. Therefore, our data provide relevant information to support counseling with regard to improving the predictive accuracy of HC in patients with suspected intrauterine infection.
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http://dx.doi.org/10.1016/j.placenta.2019.03.007DOI Listing
May 2019

A partial supernumerary umbilical vein: a case report.

J Med Case Rep 2019 May 18;13(1):149. Epub 2019 May 18.

Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Background: Abnormalities in the number of vessels can be found for both the umbilical artery and vein. We sometimes encounter cases of a decreased number of umbilical cord vessels, such as a single umbilical artery. In contrast, there may be an increase from three to four vessels within the umbilical cord. A supernumerary umbilical vein is particularly very rare, and it is generally found in combination with congenital anomalies. We report a case of a partial supernumerary umbilical vein.

Case Presentation: The previous pregnancy of a 37-year-old healthy Japanese woman (gravida 2, para 1) had been uncomplicated, and the resulting child was alive and well. Prenatal examination at 36 weeks of gestation revealed the coexistence of a four-vessel part and a normal three-vessel part of the umbilical cord. A healthy female neonate weighing 2726 g was born at 38 weeks of gestation. The umbilical cord measured 40 cm in length; the four-vessel part continued to a distance of 18 cm from the surface of the infant's body, and the remaining umbilical cord comprised three vessels. On histological examination, the fetal side of the umbilical cord had two arteries and two veins, and the placental side had two arteries and one vein. Isolated supernumerary umbilical veins tend to be overlooked. We consider that it is important to evaluate the number of umbilical cord vessels in the second trimester using ultrasound combined with color Doppler in at least three sites: the insertion sites on both the fetal abdomen and placenta, and the free loop of the umbilical cord.

Conclusions: Prenatal diagnosis of isolated supernumerary umbilical cord vessels tends to be overlooked. However, supernumerary vessels of the umbilical can be associated with fetal congenital anomalies. The number of vessels within the umbilical cord must be examined because the detection of such abnormalities may lead to the prenatal diagnosis of other congenital anomalies.
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http://dx.doi.org/10.1186/s13256-019-2094-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525366PMC
May 2019

Novel screening system revealed that intracellular cholesterol trafficking can be a good target for colon cancer prevention.

Sci Rep 2019 04 17;9(1):6192. Epub 2019 Apr 17.

Division of Prevention, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

In conventional research methods for cancer prevention, cell proliferation and apoptosis have been intensively targeted rather than the protection of normal or benign tumor cells from malignant transformation. In this study, we aimed to identify candidate colon cancer chemopreventive drugs based on the transcriptional activities of TCF/LEF, NF-κB and NRF2, that play important roles in the process of malignant transformation. We screened a "validated library" consisting of 1280 approved drugs to identify hit compounds that decreased TCF/LEF and NF-κB transcriptional activity and increased NRF2 transcriptional activity. Based on the evaluation of these 3 transcriptional activities, 8 compounds were identified as candidate chemopreventive drugs for colorectal cancer. One of those, itraconazole, is a clinically used anti-fungal drug and was examined in the Min mouse model of familial adenomatous polyposis. Treatment with itraconazole significantly suppressed intestinal polyp formation and the effects of itraconazole on transcriptional activities may be exerted partly through inhibition of intracellular cholesterol trafficking. This screen represents one of the first attempts to identify chemopreventive agents using integrated criteria consisting of the inhibition of TCF/LEF, NF-κB and induction of NRF2 transcriptional activity.
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http://dx.doi.org/10.1038/s41598-019-42363-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470178PMC
April 2019

Inhibition of NF-kappaB transcriptional activity enhances fucoxanthinol-induced apoptosis in colorectal cancer cells.

Genes Environ 2019 22;41. Epub 2019 Jan 22.

1Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan.

Background: Evidence from epidemiological and experimental studies has shown that the etiology of colorectal cancer (CRC) is related to lifestyle, mainly diet. At the same time, there are many foods and beverages that have been shown to provide protection against CRC. We turned our attention to a traditional Japanese food, brown algae, that contains carotenoids and various functional polyphenols, especially fucoxanthin (FX) and fucoxanthinol (FxOH).

Results: Both FX and FxOH treatments induced apoptosis in a dose-dependent and time-dependent manner as detected by annexin V / propidium iodide and the presence of a subG1 population in human colon cancer HCT116 cells. This apoptotic effect of FxOH was stronger than that of FX. We also found that nuclear factor-kappa B (NF-κB) transcriptional activity was significantly increased by treatment with ≥5 μM FxOH. Thus, we cotreated the cells with FxOH plus NF-κB inhibitor, and the results demonstrated that this cotreatment strongly enhanced the induction of apoptosis compared with the effects of FxOH or NF-κB inhibitor treatment alone and resulted in X-linked inhibitor of apoptosis (IAP) downregulation.

Conclusions: This study suggested that FxOH is a more potent apoptosis-inducing agent than FX and that its induction of apoptosis is enhanced by inhibiting NF-κB transcriptional activity via suppression of IAP family genes.
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http://dx.doi.org/10.1186/s41021-018-0116-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341523PMC
January 2019

Validation of the Integrated Palliative care Outcome Scale (IPOS) - Japanese Version.

Jpn J Clin Oncol 2019 Mar;49(3):257-262

Section of Liaison Psychiatry and Palliative Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University.

Background: To improve palliative care practice, the need for patients-reported outcome measures is increasing globally. The Integrated Palliative care Outcome Scale (IPOS) is a streamlined outcome scale developed to comprehensively evaluate patients' distress. The goal of this study is to assess the reliability and validity of IPOS-Japanese version in cancer patients.

Methods: This is a multicenter, cross-sectional observational study. We assessed the missing values, prevalence, test-retest reliability, criterion validity and known-group validity in Japanese adult cancer patients. Patients provided responses to IPOS, European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Functional Assessment of Chronic Illness Therapy- Spiritual 12 (FACIT-Sp12). Our medical staff provided responses to Support Team Assessment Schedule (STAS).

Results: One hundred forty-two patients were enrolled at six palliative care facilities. Missing values accounted for less than 1% of most items, with a maximum of 2.8%. The prevalence of symptoms was 17.7-88.7%. The intra-class correlation coefficient ranged from 0.522 to 0.951. The range of correlation coefficients with EORTC-QLQ-C30, FACIT-Sp12 and STAS as gold standards was 0.013 to 0.864 (absolute values). Total IPOS scores were positively correlated with Eastern Corporative Oncology Group Performance Status (P < 0.001).

Conclusion: IPOS-Japanese version is a valid and reliable tool. The scale is useful in assessing physical, psychological, social and spiritual symptoms and in measuring outcomes of adult cancer patients in Japan.
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http://dx.doi.org/10.1093/jjco/hyy203DOI Listing
March 2019

Nivolumab and stereotactic radiation therapy for the treatment of patients with Stage IV non-small-cell lung cancer.

Jpn J Clin Oncol 2019 Feb;49(2):160-164

Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.

Background: Radiation therapy might modify the cancer immune environment to enhance the antitumor effect of immune checkpoint inhibitors. We performed a feasibility study of nivolumab following stereotactic radiation therapy for chemotherapy pretreated advanced non-small-cell lung cancer.

Patients And Methods: Pretreated advanced/recurrent non-small-cell lung cancer patients received stereotactic radiation therapy to one of the disease sites. Nivolumab at a dose of 3 mg/kg was given within 2 weeks after the completion of stereotactic radiation therapy and continued every 2 weeks thereafter until disease progression or unacceptable toxicities. The primary endpoint was the occurrence rate of Grade 3 pneumonitis (within 12 weeks) or other non-hematological toxicity (within 8 weeks).

Results: From September 2016 to September 2017, six patients were enrolled. Five received stereotactic radiation therapy to their primary lesions. All patients received nivolumab on the following day after stereotactic radiation therapy completion. Grade 3 pneumonitis occurred in one patient, but no other serious adverse events were reported for the other patients. One complete response and two partial responses were achieved. Four patients had measurable lesions outside the irradiated area, of whom three patients responded to the treatment. The initial progression sites were mainly outside the irradiated field, including one brain metastasis.

Conclusions: Nivolumab therapy immediately following stereotactic radiation therapy was well tolerated. This sequential combination warrants further study.
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http://dx.doi.org/10.1093/jjco/hyy171DOI Listing
February 2019

Publisher Correction: Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration.

Sci Rep 2018 Oct 23;8(1):15883. Epub 2018 Oct 23.

Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-34168-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199297PMC
October 2018

Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration.

Sci Rep 2018 07 25;8(1):11205. Epub 2018 Jul 25.

Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.

The discovery of circulating tumour DNA molecules created a paradigm shift in tumour biomarkers as predictors of recurrence. Non-invasive prenatal testing (NIPT) to detect circulating cell-free foetal DNA in maternal plasma is increasingly recognised as a valuable substitute to perceive foetal copy number variation (CNV). This study aimed to determine whether the copy number detection in plasma samples using NIPT platform could be used as a prognostic biomarker in patients with gynaecological cancer. We conducted a prospective study using samples containing preoperative plasma from 100 women with gynaecological cancers. Samples were randomly rearranged and blindly sequenced using a low-coverage whole-genome sequencing plasma DNA, NIPT platform. The NIPT pipeline identified copy number alterations (CNAs) were counted in plasma as a gain or loss if they exceeded 10 Mb from the expected diploid coverage. Progression-free survival (PFS) and overall survival (OS) were analysed according to the presence of CNA in plasma using Kaplan-Meier analyses. The NIPT pipeline detected 19/100 cases of all gynaecological cancers, including 6/36 ovarian cancers, 3/11 cervical cancers, and 10/53 endometrial cancers. Patients with CNA in plasma had a significantly poorer prognosis in all stages concerning PFS and OS. Therefore, low-coverage sequencing NIPT platform could serve as a predictive marker of patient outcome.
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http://dx.doi.org/10.1038/s41598-018-29381-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060170PMC
July 2018

Association of Serum HB-EGF Value and Response to Chemotherapy in Patients with Recurrent Ovarian Cancer.

Anticancer Res 2018 Jul;38(7):4347-4351

Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan

Background/aim: Many anticancer agents including molecularly-targeted drugs have been developed for ovarian cancer. However, the prognosis of recurrent ovarian cancer remains extremely poor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is reported as a rational target for ovarian cancer therapy. Moreover, serum HB-EGF expression is recognized as a biomarker in patients with primary ovarian cancer.

Materials And Methods: We analysed serum samples with recurrent ovarian cancer at the Fukuoka University Hospital from April 2009 to March 2014. To assess the clinical significance of serum HB-EGF in recurrent ovarian cancer, the association between serum HB-EGF levels and prognosis in patients with recurrent ovarian cancer was examined using ELISA.

Results: Patients with high serum HB-EGF expression showed a significantly poor response to second-line chemotherapeutic agents compared with patients with low HB-EGF levels.

Conclusion: HB-EGF expression in serum may be a potential therapeutic indicator for novel HB-EGF-targeted therapy in recurrent ovarian cancer.
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http://dx.doi.org/10.21873/anticanres.12735DOI Listing
July 2018

Activated EphA2 Processing by MT1-MMP Is Involved in Malignant Transformation of Ovarian Tumours .

Anticancer Res 2018 Jul;38(7):4257-4266

Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

Background/aim: Erythropoietin-producing hepatocellular receptor-2 (EphA2) is overexpressed in ovarian cancer. The N-terminals of EphA2 are processed by membrane-type 1 matrix metalloproteinase (MT1-MMP) and can subsequently induce ligand-independent signal activation to promote motility, invasion, and metastasis. The aim of this study was to investigate whether EphA2 processing occurs in benign, borderline, and malignant ovarian tumours.

Materials And Methods: Overall 107 ovarian epithelial carcinomas (OECs; 47 serous, 24 endometrioid, 16 mucinous, and 20 clear cell), 54 ovarian borderline tumours (OBTs; 12 serous, 42 mucinous), and 45 adenomas (15 serous, 17 mucinous, and 13 endometriotic cysts) were evaluated. Expression and processing of EphA2 were semi-quantitatively analyzed. EphA2 processing was also investigated by immunoblotting.

Results: EphA2 and MT1-MMP co-expression were detected. N-terminal EphA2 levels were significantly lower than those of C-terminal EphA2 in OECs and OBTs, but not in adenomas. Immunoblotting revealed processed fragments in OEC and OBTs.

Conclusion: EphA2 processing by MT1-MMP is associated with malignant transformation in ovarian tumours.
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http://dx.doi.org/10.21873/anticanres.12722DOI Listing
July 2018

Drug review: Pazopanib.

Jpn J Clin Oncol 2018 Jun;48(6):503-513

Department of Urology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.

Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma. The importance of pazopanib has been acknowledged, with positive results demonstrated in large-scale clinical trials involving patients with soft-tissue sarcoma and renal cell carcinoma. However, adverse events such as liver dysfunction and hypertension are common, often necessitating treatment discontinuation. These adverse events are generally manageable, and from the perspective of health-related quality of life and cost-effectiveness, pazopanib provides an improvement in quality-adjusted life years and decreases the treatment cost compared with other alternatives. In this review, we present the results of clinical trials and discuss the pharmacological action of pazopanib, with the aim of evaluating its current state by examining various associated issues.
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http://dx.doi.org/10.1093/jjco/hyy053DOI Listing
June 2018

Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome.

J Virol 2018 06 29;92(12). Epub 2018 May 29.

Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan

Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1, = 56; CIN2/3, = 68; ICC, = 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions. HPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.
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http://dx.doi.org/10.1128/JVI.00017-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974501PMC
June 2018

Validation of the Edmonton Symptom Assessment System: Ascites Modification.

J Pain Symptom Manage 2018 06 23;55(6):1557-1563. Epub 2018 Mar 23.

Division of Psycho-Oncology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan. Electronic address:

Context: Few patient-reported outcomes are available to measure the symptoms associated with malignant-related ascites in patient care and clinical research. Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM) is a brief tool to measure symptoms associated with malignant-related ascites, it remains to be fully validated.

Objectives: The objective of the study was to validate the ESAS:AM in Japanese cancer patients.

Methods: We assessed the internal consistency, test-retest reliability, concurrent validity, and construct validity in 292 Japanese adult patients with cancer. They completed Japanese versions of the ESAS:AM, M.D. Anderson Symptom Inventory, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module.

Results: Cronbach's alpha coefficient of the ESAS:AM was 0.89. The intraclass correlation coefficient on test-retest examination of its total score was 0.93 (P < 0.001). Pearson correlation coefficients of the total score of the ESAS:AM with the total score of the M.D. Anderson Symptom Inventory and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module ranged from 0.44 to 0.81 (P < 0.001) and those with global health status/quality of life and functional subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 ranged from -0.40 to -0.61 (P < 0.001). The total scores of the ESAS:AM were significantly higher in 20 patients with symptomatic ascites (34 [SD, 26]) than 267 patients without symptomatic ascites (23 [SD, 19]) (P = 0.018).

Conclusion: The ESAS:AM is a reliable and valid tool for measuring symptoms associated with malignant-related ascites and can be used in daily patient care and future epidemiological studies and clinical trials.
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http://dx.doi.org/10.1016/j.jpainsymman.2018.03.016DOI Listing
June 2018

The Significant Antitumor Activity of Nivolumab in Lung Adenocarcinoma with Choriocarcinomatous Features.

Intern Med 2018 Jun 9;57(12):1773-1777. Epub 2018 Feb 9.

Department of Medical Oncology, Nihon Sekijujisha Iryo Center (Japanese Red Cross Medical Center), Japan.

We report the case of a 60-year-old Japanese man with a metastatic brain tumor that caused ataxia. As a consequence of resection of a cerebellar tumor, the tumor was diagnosed as a poorly differentiated adenocarcinoma with choriocarcinomatous features. The patient underwent bronchoscopy, leading to a diagnosis of the same histology as the brain tumor. After the administration of first-line chemotherapy and maintenance therapy due to progressive disease, he was given nivolumab and obtained a partial response; however, 11-months later, computed tomography showed tumor progression. Our experience suggests that nivolumab has strong activity, even in patients with a rare form of lung cancer.
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http://dx.doi.org/10.2169/internalmedicine.0002-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047983PMC
June 2018

Aberrant alternative splicing of RHOA is associated with loss of its expression and activity in diffuse-type gastric carcinoma cells.

Biochem Biophys Res Commun 2018 01 13;495(2):1942-1947. Epub 2017 Dec 13.

Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, 2-2 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address:

RhoA is a member of Rho family small GTPases that regulates diverse cellular functions. Recent large-scale sequencing studies have identified recurrent somatic mutations of RHOA in diffuse-type gastric carcinoma (DGC), indicating that RHOA is a driver of DGC. In this study, we investigated the possible abnormalities of RHOA in a panel of gastric carcinoma (GC) cell lines. Pulldown assay and immunoblot analysis showed that the activity and expression of RhoA were detectable in all GC cell lines tested, except for two DGC cell lines, HSC-59 and GSU. RHOA coding region sequencing revealed that aberrant alternative splicing of RHOA occurred in these cell lines. Quantitative real-time PCR analysis showed that the expression of wild-type RHOA was nearly undetectable, whereas splicing variants were almost exclusively expressed in HSC-59 and GSU cell lines. However, the expression levels of RHOA splicing variants were very low and the corresponding proteins were not detected by immunoblotting. Moreover, the splicing isoforms of RhoA protein were neither efficiently expressed nor activated even if ectopically expressed in cells. These results indicate that aberrant alternative splicing of RHOA results in the loss of its activity and expression in DGC cells.
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http://dx.doi.org/10.1016/j.bbrc.2017.12.067DOI Listing
January 2018

Ultrasound-based logistic regression model LR2 versus magnetic resonance imaging for discriminating between benign and malignant adnexal masses: a prospective study.

Int J Clin Oncol 2018 Jun 13;23(3):514-521. Epub 2017 Dec 13.

Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.

Background: The diagnostic performances of the International Ovarian Tumor Analysis (IOTA) ultrasound-based logistic regression model (LR2) and magnetic resonance imaging (MRI) in discriminating between benign and malignant adnexal masses have not been directly compared in a single study.

Methods: Using the IOTA LR2 model and subjective interpretation of MRI findings by experienced radiologists, 265 consecutive patients with adnexal masses were preoperatively evaluated in two hospitals between February 2014 and December 2015. Definitive histological diagnosis of excised tissues was used as a gold standard.

Results: From the 265 study subjects, 54 (20.4%) tumors were histologically diagnosed as malignant (including 11 borderline and 3 metastatic tumors). Preoperative diagnoses of malignant tumors showed 91.7% total agreement between IOTA LR2 and MRI, with a kappa value of 0.77 [95% confidence interval (CI), 0.68-0.86]. Sensitivity of IOTA LR2 (0.94, 95% CI, 0.85-0.98) for predicting malignant tumors was similar to that of MRI (0.96, 95% CI, 0.87-0.99; P = 0.99), whereas specificity of IOTA LR2 (0.98, 95% CI, 0.95-0.99) was significantly higher than that of MRI (0.91, 95% CI, 0.87-0.95; P = 0.002). Combined IOTA LR2 and MRI results gave the greatest sensitivity (1.00, 95% CI, 0.93-1.00) and had similar specificity (0.91, 95% CI, 0.86-0.94) to MRI.

Conclusions: The IOTA LR2 model had a similar sensitivity to MRI for discriminating between benign and malignant tumors and a higher specificity compared with MRI. Our findings suggest that the IOTA LR2 model, either alone or in conjunction with MRI, should be included in preoperative evaluation of adnexal masses.
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http://dx.doi.org/10.1007/s10147-017-1222-yDOI Listing
June 2018

CT features for diagnosing acute torsion of uterine subserosal leiomyoma.

Jpn J Radiol 2018 Mar 9;36(3):209-214. Epub 2017 Dec 9.

Department of Radiology, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555, Japan.

Purpose: To evaluate the usefulness of computed tomographic (CT) features for identifying acute torsion of uterine subserosal leiomyoma (USL).

Subjects And Methods: We analyzed contrast-enhanced CT examinations of 7 USLs with torsion and 44 USLs without torsion. Two radiologists evaluated the CT features, which consisted of poor contrast enhancement inside the USL, thin rim enhancement around the USL, calcification within the USL, a beak sign between the uterus and USL, fan-shaped poor contrast enhancement in the uterus area adjacent to the USL (dark fan sign), and ascites. We analyzed the frequencies of these CT features in the USLs with versus without torsion using Fisher's exact test.

Results: The respective frequencies of CT features in USLs with and without torsion were as follows: poor contrast enhancement, 86 and 5% (P = 0.001); thin rim enhancement, 71 and 9% (P = 0.001); calcification, 29 and 18% (P = 0.61); beak sign, 57 and 86% (P = 0.10); dark fan sign, 57 and 0% (P = 0.001); and ascites, 100 and 20% (P = 0.01).

Conclusions: The CT features of poor contrast enhancement, thin rim enhancement, and dark fan sign are valuable for identifying acute torsion of USL.
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http://dx.doi.org/10.1007/s11604-017-0712-1DOI Listing
March 2018