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Fujita medical journal 9(3) 200-205 2023年8月OBJECTIVES: Nectin-4 is a cell adhesion molecule with vital functions at adherens and tight junctions. Cumulative evidence now indicates that the NECTIN4 gene is overexpressed in a variety of cancers, and that the nectin-4 protein is both a disease marker and therapeutic target in a subset of these cancers. We previously demonstrated that NECTIN4 is overexpressed in placenta during pre-eclamptic pregnancy, which is one of the most serious obstetric disorders. METHODS: Nectin-4 protein levels were measured in maternal sera from pregnant women with pre-eclampsia and its related disorder, unexplained fetal growth retardation. RESULTS: Maternal serum concentrations of nectin-4 were significantly elevated in pre-eclamptic women compared with those with an uncomplicated normotensive pregnancy. However, no increase was observed in pregnancies with unexplained fetal growth retardation. Serum nectin-4 levels were higher in cases with early-onset pre-eclampsia that generally showed more severe clinical symptoms, but levels were not correlated to other clinical indicators of disease severity. CONCLUSIONS: Nectin-4 is a potential new diagnostic and predictive biomarker for severe pre-eclampsia.
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Journal of clinical medicine 11(15) 2022年8月7日BACKGROUND: FLT1 is one of the significantly overexpressed genes found in a pre-eclamptic placenta and is involved with the etiology of this disease. METHODS: We conducted genome-wide expression profiling by RNA-seq of placentas from women with pre-eclampsia and those with normotensive pregnancy. RESULTS: We identified a lncRNA gene, MG828507, located ~80 kb upstream of the FLT1 gene in a head-to-head orientation, which was overexpressed in the pre-eclamptic placenta. MG828507 and FLT1 are located within the same topologically associated domain in the genome. The MG828507 mRNA level correlated with that of the FLT1 in placentas from pre-eclamptic women as well as in samples from uncomplicated pregnancies. However, neither the overexpression nor knockdown of MG828507 affected the expression of FLT1. Analysis of pre-eclampsia-linking genetic variants at this locus suggested that the placental genotype of one variant was associated with the expression of MG828507. The MG828507 transcript level was not found to be associated with maternal blood pressure, but showed a relationship with birth and placental weights, suggesting that this lncRNA might be one of the pivotal placental factors in pre-eclampsia. CONCLUSION: Further characterization of the MG828507 gene may elucidate the etiological roles of the MG828507 and FLT1 genes in pre-eclampsia in a genomic context.
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Fujita medical journal 8(3) 96-101 2022年8月Objectives: Alterations in the vaginal bacterial flora reflect the status of various obstetric conditions and are associated with mechanisms that underlie certain pregnancy-associated complications. These changes are also a predictive biomarker for clinical outcomes of these adverse events. Methods: We examined the vaginal microbiome in samples from pregnant Japanese women with preterm labor. Results: The microbiota composition in preterm delivery (PD) samples differed from those of control or threatened preterm delivery (TPD) samples in principal component analysis. An increase in Firmicutes and a decrease in Actinobacteria were significantly associated with PD only (both P<0.01). In the Firmicutes phylum, Lactobacillus tended to be abundant, and the abundance of L. iners and L. crispatus was especially high, whereas the L. gasseri population was low in PD samples. Longitudinal analysis showed that the abundance of L. iners decreased after commencing tocolytic treatment in TPD samples compared with before treatment, but it remained high in PD samples. Conclusions: The vaginal microbiome may be a useful prognostic indicator of preterm labor and a monitoring tool for tocolytic treatment to prevent preterm birth.
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Hypertension Research in Pregnancy 9(4) 68-74 2021年11月30日
MISC
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日本産科婦人科學會雜誌 65(2) 831-831 2013年
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PLACENTA 33(11) 919-926 2012年11月 査読有りHigh temperature requirement A (HtrA) family proteins are serine proteases that may serve in the quality control of misfolded or mislocalized proteins. Recently, possible involvements of HtrA1 in the normal development of the placenta and in the pathogenesis of pre-eclampsia were reported. In this study, we characterized HtrA4, a previously uncharacterized HtrA protein family member, in pre-eclampsia. Elevated expression levels of placental HtrA4 in pre-eclampsia patients were observed by qRT-PCR. Western blotting also showed an increased production of HtrA4 at the protein level in pre-eclamptic placentas. In normal chorionic villi, HtrA4 protein was more abundant in the cytoplasm of cytotrophoblasts than in syncytiotrophoblasts. In contrast, the amount of HtrA4 protein in syncytiotrophoblasts was dramatically increased in pre-eclamptic placentas. Circulating HtrA4 was detected at higher levels in sera from women with pre-eclampsia than from those with normotensive pregnancies. Serum HtrA4 levels were higher in patients with early onset and inversely correlated with the weights of the newborn and placenta. Furthermore, serum levels correlated with serum PAPP-A and PAPP-A2 levels, indicating a functional role for HtrA4 in the common pathway. These data suggest that increased HtrA4 may be involved in the onset of pre-eclampsia, and elevated levels in sera imply a potential application as a biomarker for this disorder. (c) 2012 Elsevier Ltd. All rights reserved.
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日本産科婦人科内視鏡学会雑誌 28(1) 346-352 2012年8月 査読有り症例1(31歳、0経妊0経産婦)。症例2(35歳、1経妊1経産婦)。症例3(28歳、1経妊1経産婦)。3症例とも子宮筋腫に対する腹腔鏡下手術目的に受診となった。いずれの症例も術前検査にて子宮は正常形態を保ち、漿膜下および筋層内に筋腫は認められなかった。だが、腫瘤は子宮に近接しており、周囲臓器と強固な癒着を形成していたため臓器圧迫症状があった。以後、腹腔鏡下手術を行なったところ、腫瘤の癒着剥離操作により腫瘤は速やかに虚血性変化を示した。尚、病理検査では中心性壊死が認められ、臨床経過と総合し、PM(骨盤内腫瘤)の自然発生が考えられた。
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European journal of obstetrics, gynecology, and reproductive biology 163(1) 67-70 2012年7月 査読有りOBJECTIVE: Levels of 5-FU metabolic or related enzymes, particularly thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), have been investigated in various cancer types, including uterine cervical cancer. Intratumoral TP levels have been reported to increase in response to several chemotherapeutic agents or irradiation in both xenografts and clinical studies. In cervical cancer, however, only a few studies about changes in TP and DPD expression associated with cancer treatment have been published. We evaluated the effect of chemotherapy and/or irradiation on TP and DPD expression in cervical squamous cell carcinoma. STUDY DESIGN: Of 27 patients in this study, 12 patients underwent neoadjuvant chemotherapy consisting of nedaplatin, ifosfamide, and/or peplomycin followed by radical surgery, and 15 patients underwent radiotherapy (n=8) or chemoradiotherapy with nedaplatin (n=7) as initial treatment. Tumor specimens were obtained from biopsies acquired before treatment and after administration of chemotherapy (2 weeks after the first and second cycles), and after irradiation with 10 Gy, 20 Gy, and 30 Gy. These specimens were used to measure TP and DPD levels by ELISA. RESULTS: In the 12 patients who received neoadjuvant chemotherapy, intratumoral TP and DPD levels did not change. In contrast, in the 15 patients who underwent radiotherapy or chemoradiotherapy with nedaplatin, TP or DPD expression appeared to be slightly increased or decreased, respectively, after irradiation with 20 Gy, and consequently the TP/DPD ratio was significantly higher after irradiation with 20 Gy than before irradiation. CONCLUSIONS: These results suggest a clinical advantage of chemoradiotherapy with capecitabine or doxyfluridine over radiotherapy alone via the elevation of the TP/DPD ratio in cervical squamous cell carcinoma. However, no advantage of combination chemotherapy with these 5-FU derivatives was demonstrated. Therefore, further evaluation with a larger number of patients or with other chemotherapeutic agents is required to confirm these observations.
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東海産科婦人科学会雑誌 48 153-158 2012年3月 査読有り子宮体部G3腺癌は子宮外への進展頻度、再発率が高く予後不良とされている。今回、子宮体部G3腺癌の臨床的特徴をG1およびG2腺癌と比較し、さらにG3腺癌の予後に影響する因子について検討した。対象は2001年〜2010年に当院にて手術を施行した子宮体癌のうち、非類内膜腺癌の混在のない類内膜腺癌のみ172例とし、その内訳はG1腺癌が84例、G2腺癌が64例、G3腺癌が24例であった。G1〜G3腺癌各々の発症年齢、III+IV期の割合、累積生存率(OS)および原病死例の生存期間中央値(MST)を比較した。またG3腺癌の予後因子について以下の11項目に関して解析を行った(60歳以上vs60歳未満、筋層浸潤1/2以上vs未満、脈管侵襲ありvsなし、頸部浸潤ありvsなし、リンパ節転移ありvsなし、傍大動脈リンパ節転移ありvsなし、腹水細胞診陽性vs陰性、I+II期vsIII+IV期、子宮外進展ありvsなし、治療前CA125値>35vs≦35U/ml、完全切除vs不完全手術)。年齢中央値はG1:58歳(32〜85歳)、G2:61歳(32〜80歳)、G3:55歳(44〜81歳)と差は認めなかった。III+IV期の割合はG1:11.9%、G2:23.4%、G3:54.2%と有意にG3腺癌で多く、OSはG1:90.7%、G2:86.7%、G3:76.7%とG3腺癌で予後不良であった。原病死例のMSTはG1:68ヵ月(55〜74ヵ月)、G2:30ヵ月(17〜72ヵ月)、G3:16ヵ月(6〜37ヵ月)と分化度の低下に伴いMSTは短縮した。G3腺癌の予後は、リンパ節転移(p<0.001)、傍大動脈節転移(p<0.0001)、III+IV期(p=0.034)、不完全手術(p<0.0001)の症例で不良であった。G3腺癌は必ずしも高齢者に多いわけではなく、診断時に進行例が多く、リンパ節転移を有し不完全手術となった症例の予後は極めて不良であった。(著者抄録)
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東海産科婦人科学会雑誌 48 165-171 2012年3月 査読有り子宮頸癌FIGO Ib2〜IIb期に対する術前化学療法(NAC:neoadjuvant chemotherapy)の予後改善効果に関しては一定の見解はなく、試験的治療と規定されている。しかしながら実地臨床においては、出血のコントロールや腫瘍の縮小を目的として、あるいは手術までの時間調整のためなど種々の要因でNACが施行されることもある。今回、NACの意義に関して後方視的に検討を行った。1999年から2008年に子宮頸癌FIGO Ib2〜IIb期に対して広汎子宮全摘出術を施行した52例(NAC未施行群:34例、NAC施行群:18例)を対象とし、両群間の臨床病理学的因子(年齢、FIGO stage、腫瘍径、組織型、リンパ節転移、脈管侵襲、子宮傍組織浸潤、切除断端、術後補助療法の方法)および予後(DFS:disease free survivai、OS:overall survival)に関して比較検討した。また、両群間の手術時間、出血量を比較した。その結果、NACの奏効率は72.2%であった。両群間で年齢、FIGO stage、組織型、リンパ節転移、脈管侵襲、子宮傍観織浸潤、切除断端、術後補助療法の方法に差はなかったが、治療前の腫瘍径に有意差が認められた(p=0.016)。5年DFSはNAC未施行群、施行群それぞれ62.3%vs77.8%、5年OSは77.5%vs81.9%であり、両群間に差は認められなかった(各々p=0.604,0.818)。また、出血量中央値はNAC未施行群、施行群で1266g vs 815gとNAC施行群の出血量が有意に減少していた(p=0.044)。両群間の手術時間には差を認めなかった。今回の検討から、NACは予後改善を目的としてではなく、腫瘍縮小により手術の難易度を低下させるため、あるいは時間調整が必要とされる場合には許容されうるオプションと思われた。(著者抄録)
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The journal of obstetrics and gynaecology research 37(11) 1734-8 2011年11月 査読有りWe present three extremely rare cases of spontaneous spinal epidural hematoma occurring in pregnancy. The patients developed progressive paralysis of the upper and lower limbs and the diagnoses were confirmed by magnetic resonance imaging. Urgent decompression is required to prevent neurological sequelae. The pregnancy may either be continued or delivered depending on the gestational age and severity of the disorder. Pregnancy-induced structural changes of the vascular walls and hemodynamic changes may play a role in the pathogenesis of spontaneous spinal epidural hematoma.
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救急・集中治療 23(9-10) 1484-1491 2011年11月 査読有り＜point＞●腹痛、無月経、性器出血の三主徴を認めた場合には、子宮外妊娠を念頭において診察を行う。●既往歴・月経歴を十分に聴取した後、超音波断層法、hCG定性・定量検査(尿、血清)を行う。●hCG値が高く、超音波断層法検査で子宮内に胎嚢を認めない場合に子宮外妊娠を疑い、子宮外に胎嚢およびその中に卵黄嚢、胎児(胎芽)を認めた場合には確定診断となる。●すでに出血性ショックとなっている場合には、バイタルサインをチェックして点滴ラインを確保すると同時に必要な血液検査を実施し、輸液・輸血を行いつつ緊急手術(開腹手術、腹腔鏡手術)の準備を行う。(著者抄録)