ZHAI TIANYUE (サイ テンゲツ)

医学研究院 専門医学系部門 生殖・発達医学分野特任助教
Last Updated :2024/12/06

■研究者基本情報

学位

  • 博士(医学), 北海道大学, 2018年03月

Researchmap個人ページ

研究者番号

  • 50905601

研究キーワード

  • Cancer Stem Cells
  • Preeclampsia
  • Ovarian Cancer

研究分野

  • ライフサイエンス, 産婦人科学

■経歴

学歴

  • 2014年10月 - 2018年03月, 北海道大学, 大学院医学研究科, 生殖発達医学講座 産科・生殖医学分野 博士課程, 日本国

■研究活動情報

受賞

  • 2016年10月, 日本妊娠高血圧学会, 学術奨励賞               
    妊娠高血圧腎症妊婦における尿中ポドサイトの量的ならびに質的変化
    翟 天玥;古田 伊都子;赤石 理奈;石川 聡司;森川 守;山田 崇弘;小山 貴弘;水上 尚典

論文

  • The significance of N6-methyladenosine-modified non-coding RNAs in different disorders
    Soudeh Ghafouri-Fard, Hamed Shoorei, Bashdar Mahmud Hussen, Peixin Dong, Tianyue Zhai, Mohammad Taheri, Mohammad Samadian
    European Journal of Pharmacology, 175644, 175644, Elsevier {BV}, 2023年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer
    Yu Miao, Yosuke Konno, Baojin Wang, Lin Zhu, Tianyue Zhai, Kei Ihira, Noriko Kobayashi, Hidemichi Watari, Xin Jin, Junming Yue, Peixin Dong, Mingyan Fang
    Journal of Translational Medicine, 21, 1, Springer Science and Business Media {LLC}, 2023年02月25日, [査読有り]
    英語, 研究論文(学術雑誌), Abstract
    Background
    Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood.

    Methods
    Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells.

    Results
    We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial–mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel.

    Conclusion
    Our findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.
  • Combination therapy with bevacizumab and a CCR2 inhibitor for human ovarian cancer: An in vivo validation study.
    Tianyue Zhai, Takashi Mitamura, Lei Wang, Shimpei I Kubota, Masaaki Murakami, Shinya Tanaka, Hidemichi Watari
    Cancer medicine, 12, 8, 9697, 9708, 2023年02月22日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Anti-angiogenic therapy with bevacizumab (BEV), an anti-VEGF antibody, plays a critical role in the treatment of ovarian cancer. However, despite an encouraging initial response, most tumors become resistant to BEV over time, and a new strategy that enables sustainable treatment using BEV is therefore needed. METHODS: To overcome the resistance to BEV in patients with ovarian cancer, we performed a validation study of combination therapy with BEV (10 mg/kg) and the CCR2 inhibitor BMS CCR2 22 (20 mg/kg) (BEV/CCR2i) using 3 consecutive patient-derived xenografts (PDXs) of immunodeficient mice. RESULTS: BEV/CCR2i demonstrated a significant effect of growth suppression in the BEV-resistant serous PDX and BEV-sensitive serous PDX compared with BEV (30.4% after the second cycle and 15.5% after the first cycle, respectively), and treatment cessation did not attenuate this effect. Tissue clearing and immunohistochemistry with an anti-α-SMA antibody suggested that BEV/CCR2i suppressed angiogenesis from the host mice more than BEV. In addition, human CD31 immunohistochemistry revealed that BEV/CCR2i decreased microvessels originating from the patients to a significantly greater degree than BEV. Regarding the BEV-resistant clear cell PDX, the effect of BEV/CCR2i was unclear during the first five cycles, but the following two cycles of increased-dose BEV/CCR2i (CCR2i 40 mg/kg) significantly suppressed tumor growth compared with BEV (28.3%) by inhibiting the CCR2B-MAPK pathway. CONCLUSIONS: BEV/CCR2i showed a sustained anticancer immunity-independent effect in human ovarian cancer that was more significant in serous carcinoma than in clear cell carcinoma.
  • Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer
    Takashi Mitamura, Tianyue Zhai, Kanako C Hatanaka, Yutaka Hatanaka, Toraji Amano, Lei Wang, Shinya Tanaka, Hidemichi Watari
    Pharmacogenomics and Personalized Medicine, 15, 977, 984, 2022年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients. PATIENTS AND METHODS: DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III-IV ovarian cancer with no recurrence for 8-23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role. RESULTS: The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the PRDM1 gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group. CONCLUSION: Germline heterozygous rs2185379 in PRDM1 is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.
  • Promotion of Parenting and Mental Health Needs among Chinese Women Living in Japan: A Qualitative Study
    Yunjie Luo, Yoko Sato, Tianyue Zhai, Hiromi Kagamiyama, Yasuhiko Ebina
    International Journal of Environmental Research and Public Health, 19, 20, 2022年10月19日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Chinese women raising children in Japan tend to experience high parenting stress and poor mental well-being. However, their specific parenting and mental health promotion needs remain unknown. This study aimed to explore the parenting and mental health promotion needs of Chinese women living in Japan and provide recommendations to guide interventions. Semi-structured in-depth interviews were conducted. Participants included 15 women aged 28-39 years who were pregnant or rearing a child younger than six years old. Thematic analysis was performed for data analysis. More than half of the participants experienced mental health problems, such as depressive symptoms and child-rearing stress. Four themes relating to their needs were identified: concrete support, information provision, caring and understanding, and social network building. Information provision and social network building should be emphasized as practical social support mechanisms to improve these women's mental health. Furthermore, a mental health promotion intervention should be developed to address this vulnerable population's needs. Healthcare providers and public health workers should help improve the social support systems of Chinese women in Japan to prevent mental health problems. Potential transcultural education can, arguably, help healthcare providers better understand transcultural care.
  • LncRNAs: Novel Biomarkers for Pancreatic Cancer
    Soudeh Ghafouri-Fard, Mohadeseh Fathi, Tianyue Zhai, Mohammad Taheri, Peixin Dong
    Biomolecules, 11, 11, 1665, 1665, {MDPI} {AG}, 2021年11月10日, [査読有り]
    研究論文(学術雑誌), Pancreatic cancer is one of the most deadly neoplasms and the seventh major cause of cancer-related deaths among both males and females. This cancer has a poor prognosis due to the lack of appropriate methods for early detection of cancer. Long non-coding RNAs (lncRNAs) have been recently found to influence the progression and initiation of pancreatic cancer. MACC1-AS1, LINC00976, LINC00462, LINC01559, HOXA-AS2, LINC00152, TP73-AS1, XIST, SNHG12, LUCAT1, and UCA1 are among the oncogenic lncRNAs in pancreatic cancer. On the other hand, LINC01111, LINC01963, DGCR5, MEG3, GAS5, and LINC00261 are among tumor suppressor lncRNAs in this tissue. In the current review, we summarize the roles of these two classes of lncRNAs in pancreatic cancer and discuss their potential as attractive diagnostic and prognostic biomarkers for pancreatic cancer. We also identified that the low expression of MEG3, LINC01963, and LINC00261 and the high expression of MACC1-AS1, LINC00462, LINC01559, and UCA1 were significantly correlated with worse survival in pancreatic cancer patients. Further research on these lncRNAs will provide new clues that could potentially improve the early diagnosis, prognostic prediction, and personalized treatments of patients with pancreatic cancer.
  • 血管新生阻害薬の有効利用               
    三田村 卓, 王 磊, 翟 天玥, 渡利 英道
    BIO Clinica, 34, 10, 1020, 1022, 2019年09月, [査読有り], [国内誌]
    日本語, 研究論文(学術雑誌), 抗Vascular Endothelial Growth Factor(VEGF)抗体Bevacizumab(BEV)による血管新生阻害療法は、卵巣がん、大腸がん、肺がんや乳がんなどのヒト悪性腫瘍の予後改善に寄与しているが、薬剤耐性の出現、他剤との併用効果、および他治療との併用効果については不明な点が多く、これらの解明によりさらに有効に活用できる可能性がある。血管新生阻害薬の最近の知見について、婦人科悪性腫瘍の例を中心にまとめる。(著者抄録)
  • Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies.
    Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Takashi Kojima, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    American journal of physiology. Renal physiology, 312, 6, F1112-F1119, 2017年06月01日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) = -0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.
  • Effect of urine creatinine level during pregnancy on dipstick test.
    Yosuke Baba, Itsuko Furuta, Tianyue Zhai, Akihide Ohkuchi, Takahiro Yamada, Kayo Takahashi, Shigeki Matsubara, Hisanori Minakami
    The journal of obstetrics and gynaecology research, 43, 6, 967, 973, 2017年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), AIM: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). CONCLUSIONS: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.
  • Post-partum podocyturia following pre-eclamptic pregnancy.
    Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Ami Hosokawa, Takashi Kojima, Kentaro Chiba, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    The journal of obstetrics and gynaecology research, 43, 6, 1008, 1013, 2017年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), AIM: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). METHODS: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied. Determination of urine protein and creatinine concentration and quantitative analysis of podocyte-specific podocin and nephrin mRNA expression were carried out using reverse transcription-polymerase chain reaction in pelleted urine samples. Podocyturia was monitored via urine podocin mRNA expression. Podocyturia and proteinuria were normalized by urine creatinine concentration. RESULTS: Podocyturia and urine PNR decreased with decreasing proteinuria as well as with increasing time after delivery in the urine from PE women. In physiological proteinuria (i.e. protein : creatinine ratio [P/Cr] 0.005-0.1 mg/mg), however, both podocyturia and PNR were significantly greater in the urine from PE women compared with NPC women, although P/Cr was similar between the groups (median, 0.037 mg/mg for PE vs 0.029 mg/mg for NCP). CONCLUSIONS: Podocyturia decreases with decreasing proteinuria in PE women after childbirth. In PE women, however, pathological podocyturia consisting of podocytes with decreased nephrin mRNA expression persisted even after proteinuria decreased to a level similar to that in NCP women.
  • Increased podocyturia in pregnant women compared to non-pregnant women.
    Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Rina Akaishi, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    The journal of obstetrics and gynaecology research, 43, 5, 873, 879, 2017年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), AIM: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). METHODS: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied. Determination of protein and creatinine concentrations and number of cells in urine other than blood cells, and quantitative analyses of the mRNA expression of aquaporin 2 (AQP2-mRNA), podocin (Pod-mRNA), and nephrin (Nep-mRNA) were performed using RT-PCR in pelleted urine samples. Podocyturia was monitored with urine Pod- and Nep-mRNA expression levels normalized relative to creatinine. RESULTS: Urine cell density and urine AQP2-, Pod-, and Nep-mRNA expression normalized relative to creatinine were significantly higher in PW than NPW. The number of cells per milligram of creatinine was significantly positively correlated with expression of all three mRNAs with correlation coefficients (R-value) of 0.442, 0.481, and 0.561 for Pod-, Nep-, and AQP2-mRNA, respectively. AQP2-mRNA expression was strongly (R  >  0.8) positively correlated with both Pod- and Nep-mRNA expression. CONCLUSION: Podocyturia monitored by Pod- and Nep-mRNA expression and urine cells expressing AQP2-mRNA were increased in uncomplicated pregnancies compared to healthy non-pregnant women. Urine cells expressing AQP2-mRNA increased with increasing podocyturia in healthy women.
  • Association between nephrinuria, podocyturia, and proteinuria in women with pre-eclampsia.
    Itsuko Furuta, Tianyue Zhai, Satoshi Ishikawa, Takeshi Umazume, Kinuko Nakagawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    The journal of obstetrics and gynaecology research, 43, 1, 34, 41, 2017年01月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), AIM: Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. METHODS: Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. RESULTS: Nephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P <  0.001), Pod-mRNA expression level (R = 0.824, P < 0.001), and Nep-mRNA expression level (R  =  0.724, P <  0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R  =  0.419, P <  0.005) in urine samples from normotensive women. CONCLUSION: Nephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.
  • Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine kinase-1:placental growth factor ratio for prediction of preeclampsia among asymptomatic women.
    Tianyue Zhai, Itsuko Furuta, Kinuko Nakagawa, Takashi Kojima, Takeshi Umazume, Satoshi Ishikawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    Scientific reports, 6, 37442, 37442, 2016年11月22日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), This prospective observational study compare urine nephrin:creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22-27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0-38.6) and 35.3 (27.6-38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6-38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0 (3.82-26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91-13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.
  • Feasibility of nephrinuria as a screening tool for the risk of pre-eclampsia: prospective observational study.
    Tianyue Zhai, Itsuko Furuta, Rina Akaishi, Kosuke Kawabata, Kentaro Chiba, Takeshi Umazume, Satoshi Ishikawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami
    BMJ open, 6, 8, e011229, 2016年08月02日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), OBJECTIVES: To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE). DESIGN: Prospective observational study. SETTING: A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR, ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was diagnosed in women with both SPIP and hypertension. PARTICIPANTS: 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively. RESULTS: PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR≤122 at that time. CONCLUSIONS: Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE.
  • Alteration of podocyte phenotype in the urine of women with preeclampsia.
    Tianyue Zhai, Itsuko Furuta, Rina Akaishi, Satoshi Ishikawa, Mamoru Morikawa, Takahiro Yamada, Takahiro Koyama, Hisanori Minakami
    Scientific reports, 6, 24258, 24258, 2016年04月07日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Podocyte injury has been suggested to induce phenotypic alteration of glomerular podocytes and accelerate the detachment of podocytes from the glomeruli resulting in podocyturia. However, it is not clear whether podocyte phenotypic alteration occurs in the urine of women with preeclampsia (PE). Seventy-seven and 116 pelleted urine samples from 38 and 18 women at various stages of normal and PE pregnancies, respectively underwent quantitative analysis of podocyte-specific or associated protein mRNA expression, including podocin, nephrin, and synaptopodin using RT-PCR. Significant proteinuria in pregnancy (SPIP) is defined as protein:creatinine ratio (P/Cr, mg/mg) ≥ 0.27 in the urine supernatant. All three urine-pellet mRNAs expression levels were significantly positively correlated with P/Cr levels, suggesting that podocyturia increased with proteinuria. The podocin:nephrin mRNA ratio (PNR) and synaptopodin:nephrin mRNA ratio (SNR) increased significantly with increasing P/Cr, while the podocin:synaptopodin mRNA ratio (PSR) did not change significantly according to P/Cr, resulting in significantly higher PNR and SNR, but not PSR levels, in urine from PE women with than without SPIP. The PNR, SNR, and PSR in urine from PE women before onset of SPIP were comparable to those from controls. Thus, nephrin mRNA expression was reduced in the podocytes recovered from PE women.

講演・口頭発表等

  • Combination therapy with bevacizumab and a CCR2 inhibitor for human ovarian cancer: An in vivo validation study               
    Tianyue Zhai, Takashi Mitamura, Daisuke Endo, Hiroyuki Kurosu, Hiroyuki Yamazaki, Hiroko Matsumiya, Kei Ihira, Hiroaki Yoshikawa, Manami Sakurai, Yosuke Konno, Hidemichi Watari
    The 75th Annual Congress of the Japan Society of Obstetrics and Gynecology, 2023年05月12日, 英語, ポスター発表
  • 妊娠高血圧腎症:尿中Podocyte検出の臨床的意義の解析               
    翟 天玥
    第40回日本妊娠高血圧学会学術集会, 2019年09月22日, 日本語, 口頭発表(一般)
    [招待講演]
  • 妊娠女性におけるポドサイト尿ならびにネフリン尿に関する研究               
    翟 天玥
    第39回日本妊娠高血圧学会学術集会, 2018年11月02日, 日本語, 口頭発表(一般)
  • 妊娠高血圧腎症妊婦における尿中ポドサイトの量的ならびに質的変化               
    翟 天玥, 古田 伊都子, 赤石 理奈, 石川 聡司, 森川 守, 山田 崇弘, 小山 貴弘, 水上 尚典
    第37回日本妊娠高血圧学会学術集会, 2016年10月07日, 日本語, 口頭発表(一般)
  • 妊娠高血圧腎症:尿中ポドサイト検出の臨床的意義の解析               
    翟 天玥, 赤石 理奈, 古田 伊都子, 森川 守, 山田 崇弘, 石川 聡司, 小山 貴弘, 水上 尚典
    第36回日本妊娠高血圧学会学術集会, 2015年09月11日, 日本語, 口頭発表(一般)

所属学協会

  • 北海道産婦人科学会               
  • 日本産科婦人科学会               

共同研究・競争的資金等の研究課題

  • PRDM1 機能変化に伴う T リンパ球の抗腫瘍免疫能に関 する基礎的研究               
    2023年度(第55回)倉田奨励金
    2024年03月 - 2025年02月
    公益財団法人 日立財団, 北海道大学, 研究代表者
  • 妊娠高血圧腎症:尿中Podocyte検出の 臨床的意義の解析               
    学術助成 平成28年課題研究
    2016年10月 - 2017年09月
    日本妊娠高血圧学会, 妊婦(産褥婦も含む)の蛋白尿に関する研究, 研究代表者

社会貢献活動

  • 国際誌Frontiers in Pharmacology(査読者)               
    助言・指導