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1.
Nucleic Acids Res ; 52(3): 1498-1511, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38180813

ABSTRACT

A 'genomically' humanized animal stably maintains and functionally expresses the genes on human chromosome fragment (hCF; <24 Mb) loaded onto mouse artificial chromosome (MAC); however, cloning of hCF onto the MAC (hCF-MAC) requires a complex process that involves multiple steps of chromosome engineering through various cells via chromosome transfer and Cre-loxP chromosome translocation. Here, we aimed to develop a strategy to rapidly construct the hCF-MAC by employing three alternative techniques: (i) application of human induced pluripotent stem cells (hiPSCs) as chromosome donors for microcell-mediated chromosome transfer (MMCT), (ii) combination of paclitaxel (PTX) and reversine (Rev) as micronucleation inducers and (iii) CRISPR/Cas9 genome editing for site-specific translocations. We achieved a direct transfer of human chromosome 6 or 21 as a model from hiPSCs as alternative human chromosome donors into CHO cells containing MAC. MMCT was performed with less toxicity through induction of micronucleation by PTX and Rev. Furthermore, chromosome translocation was induced by simultaneous cleavage between human chromosome and MAC by using CRISPR/Cas9, resulting in the generation of hCF-MAC containing CHO clones without Cre-loxP recombination and drug selection. Our strategy facilitates rapid chromosome cloning and also contributes to the functional genomic analyses of human chromosomes.


Subject(s)
Cloning, Molecular , Animals , Cricetinae , Humans , Mice , Chromosomes, Artificial , Cloning, Molecular/methods , Cricetulus , CRISPR-Cas Systems , DNA , Gene Editing , Induced Pluripotent Stem Cells , Translocation, Genetic
2.
Ann Surg Oncol ; 31(5): 2951-2958, 2024 May.
Article in English | MEDLINE | ID: mdl-38376711

ABSTRACT

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NAC) is a well-established standard practice in invasive bladder cancer (BCa), however patient selection remains challenging. High expression of vasohibin-1 (VASH1), an endogenous regulator of angiogenesis, has been reported in high-grade and advanced BCa; however, its prognostic value for chemotherapy outcomes remains unexplored. In this study, we sought to identify biomarkers of chemotherapy response focusing on the relationship between angiogenesis and tissue hypoxia. METHODS: Forty Japanese patients with BCa who underwent NAC and radical cystectomy were included in the present analysis. We compared the immunohistochemical expression of CD34, VASH1, and carbonic anhydrase 9 (CA9) between patients who achieved tumor clearance at operation (ypT0) and those with residual disease after cystectomy. RESULTS: There were 19 patients in the ypT0 group, while the remaining 21 patients had residual tumors at operation. Patients in the ypT0 group had high microvessel density (p = 0.031), high VASH1 density (p < 0.001), and stronger CA9 staining (p = 0.046) than their counterparts. Multivariate analysis identified microvessel and VASH1 density as independent predictive factors for pathological ypT0 disease (p = 0.043 and 0.002, respectively). The 5-year recurrence-free survival rate was higher in the high VASH1 density group than in the low VASH1 density group (66.3% vs. 33.3%, p = 0.036). CONCLUSION: VASH1 density is a potential therapeutic biomarker for chemotherapy response in BCa.


Subject(s)
Neoadjuvant Therapy , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Prognosis , Pathologic Complete Response , Cystectomy , Retrospective Studies , Cell Cycle Proteins/metabolism
3.
Environ Res ; 243: 117744, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38092240

ABSTRACT

Microbial fuel cells (MFCs) hold considerable promise for harnessing the substantial energy resources present in wastewater. However, their practical application in wastewater treatment is limited by inadequate removal of organic matter and inefficient power recovery. Previous studies have investigated aeration as a method to enhance the removal of organic matter, but this method is energy-intensive. To address this issue, this study proposed using MFC-recovered bioelectricity for aeration, thereby mitigating the associated expenses. An air-cathode MFC with multi-anode was constructed and optimized to maximize electricity supply for aeration. Carbon-felt anodes were chosen as the most effective anode configuration, due to the high abundance of electroactive bacteria and genes observed in the biofilm generated on their surface. By incorporating six carbon felt anodes, the MFC achieved a 1.7 and 1.1 fold enhancement in the maximum power and current density, respectively. The optimized MFC unit achieved a stable current density of 0.32 A/m2 and achieved COD removal of 60% in the long-term operation of 140 days in a 50 L reactor. In a reactor scaled up to 1600 L, 72 MFCs successfully powered a mini air pump work for 10 s after an 81-s charging period. The intermittent aeration resulted in partial increases in DO concentrations to 0.03-3.5 mg/L, which is expected to promote the removal of nitrogen compounds by the nitrification-anammox process. These groundbreaking results lay the foundation for self-sustaining wastewater treatment technologies.


Subject(s)
Bioelectric Energy Sources , Water Purification , Wastewater , Electricity , Carbon , Electrodes
4.
Int J Gynecol Cancer ; 34(4): 510-518, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38316444

ABSTRACT

OBJECTIVE: To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. METHODS: This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. RESULTS: Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). CONCLUSION: This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.


Subject(s)
Endometrial Neoplasms , Laparoscopy , Female , Humans , Retrospective Studies , Prospective Studies , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Hysterectomy/adverse effects , Laparoscopy/adverse effects , Neoplasm Staging
5.
Clin Exp Nephrol ; 28(5): 457-464, 2024 May.
Article in English | MEDLINE | ID: mdl-38238500

ABSTRACT

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.


Subject(s)
Biomarkers , Hospitalization , Kidney Failure, Chronic , Myocardial Ischemia , Natriuretic Peptide, Brain , Peptide Fragments , Renal Dialysis , Humans , Male , Natriuretic Peptide, Brain/blood , Biomarkers/blood , Peptide Fragments/blood , Myocardial Ischemia/blood , Myocardial Ischemia/epidemiology , Myocardial Ischemia/diagnosis , Middle Aged , Aged , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Heart Failure/blood , Heart Failure/therapy , Heart Failure/epidemiology , Prognosis , Incidence , Stroke/blood , Stroke/epidemiology , Predictive Value of Tests , ROC Curve , Proportional Hazards Models , Japan/epidemiology
6.
J Obstet Gynaecol Res ; 50(6): 1061-1066, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38561215

ABSTRACT

Invasive group A streptococcal (iGAS) infection is a leading cause of maternal death. The increase in the number of patients with iGAS in Japan is markedly greater than before the coronavirus pandemic. We encountered a case of iGAS infection, on a remote island with restricted medical resources, in a third-trimester pregnant woman, resulting in both maternal and fetal death. A 34-year-old woman was admitted via a local general hospital with a high fever. Intrauterine fetal death disseminated intravascular coagulation, and septic shock were confirmed. Broad-spectrum antibiotics were started, and the patient was returned to the local general hospital. Eight hours after arrival, the patient died of circulatory and respiratory dysfunction complications. iGAS infections in remote areas may directly lead to life-threatening conditions and should be treated as an emergency, comparable to the serious conditions of placental abruption or placenta previa.


Subject(s)
COVID-19 , Pandemics , Pregnancy Complications, Infectious , Streptococcal Infections , Humans , Female , Pregnancy , Adult , COVID-19/complications , COVID-19/mortality , Fatal Outcome , Japan/epidemiology , Streptococcus pyogenes/isolation & purification , SARS-CoV-2 , Coronavirus Infections/complications , Pneumonia, Viral/mortality , Fetal Death , Betacoronavirus , Pregnancy Trimester, Third
7.
Folia Phoniatr Logop ; : 1-15, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697051

ABSTRACT

INTRODUCTION: Many epidemiological studies of the disorder of stuttering have been conducted during the 20th century, continuing during the current one. Unfortunately, only a few were carried out in Japan. This study aimed at assessing (1) the incidence and prevalence of stuttering in 3-year-old children in multiple Japanese communities and (2) factors associated with the onset of stuttering among these children. METHODS: A questionnaire aimed at screening for the presence of stuttering was employed for 2,055 children aged 3 years, who underwent a standard nationwide health checkup. Positive responses were confirmed in several ways: (1) direct interviews and assessment of the child's speech, (2) confirmatory questionnaire, or (3) telephone interviews by licensed Speech Language Hearing Therapists. RESULTS: Approximately 6.5% of the children were found to exhibit stuttering at the time of their health checkup. This figure rose to 8.9% after including individuals who previously, but not currently, were reported to have exhibited stuttering. Among the putative risk factors, higher stuttering odds (odds ratio, OR = 3.27) were detected in those with a family history of stuttering, those whose guardians had concerns about their child's development (OR = 1.75), and those with diagnosed diseases or disabilities (OR = 2.13). DISCUSSION/CONCLUSIONS: It was concluded that, in Japan, both the risk of stuttering incidence (8.9%) in children up to, and including, the age of 3 years, as well as its prevalence (6.5%) in this population, was similar to those reported by recent studies in other countries. Additionally, our findings also confirmed that an increased risk for stuttering at age 3 is associated with a family history of stuttering.

8.
J Magn Reson Imaging ; 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37886909

ABSTRACT

BACKGROUND: Oscillating gradient diffusion-weighted imaging (DWI) enables elucidation of microstructural characteristics in cancers; however, there are limited data to evaluate its utility in patients with endometrial cancer. PURPOSE: To investigate the utility of oscillating gradient DWI for risk stratification in patients with uterine endometrial cancer compared with conventional pulsed gradient DWI. STUDY TYPE: Retrospective. SUBJECTS: Sixty-three women (mean age: 58 [range: 32-85] years) with endometrial cancer. FIELD STRENGTH/SEQUENCE: 3 T MRI including DWI using oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) research sequences. ASSESSMENT: Mean value of the apparent diffusion coefficient (ADC) values for OGSE (ADCOGSE ) and PGSE (ADCPGSE ) as well as the ADC ratio (ADCOGSE /ADCPGSE ) within endometrial cancer were measured using regions of interest. Prognostic factors (histological grade, deep myometrial invasion, lymphovascular invasion, International Federation of Gynecology and Obstetrics [FIGO] stage, and prognostic risk classification) were tabulated. STATISTICAL TESTS: Interobserver agreement was analyzed by calculating the intraclass correlation coefficient. The associations of ADCOGSE , ADCPGSE , and ADCOGSE /ADCPGSE with prognostic factors were examined using the Kendall rank correlation coefficient, Mann-Whitney U test, and receiver operating characteristic (ROC) curve. A P value of <0.05 was statistically significant. RESULTS: Compared with ADCOGSE and ADCPGSE , ADCOGSE /ADCPGSE was significantly and strongly correlated with histological grade (observer 1, τ = 0.563; observer 2, τ = 0.456), FIGO stage (observer 1, τ = 0.354; observer 2, τ = 0.324), and prognostic risk classification (observer 1, τ = 0.456; observer 2, τ = 0.385). The area under the ROC curves of ADCOGSE /ADCPGSE for histological grade (observer 1, 0.92, 95% confidence intervals [CIs]: 0.83-0.98; observer 2, 0.84, 95% CI: 0.73-0.92) and prognostic risk (observer 1, 0.80, 95% CI: 0.68-0.89; observer 2, 0.76, 95% CI: 0.63-0.86) were significantly higher than that of ADCOGSE and ADCPGSE . DATA CONCLUSION: The ADC ratio obtained via oscillating gradient and pulsed gradient DWIs might be useful imaging biomarkers for risk stratification in patients with endometrial cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

9.
Gynecol Oncol ; 170: 70-76, 2023 03.
Article in English | MEDLINE | ID: mdl-36638744

ABSTRACT

OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.


Subject(s)
Breast Neoplasms , Endometrial Neoplasms , Nucleic Acids , Humans , Female , Lymphatic Metastasis/pathology , Prospective Studies , Nucleic Acid Amplification Techniques/methods , Endometrial Neoplasms/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Keratin-19/genetics , Breast Neoplasms/pathology
10.
Inorg Chem ; 62(16): 6306-6313, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37053521

ABSTRACT

We report the synthesis, characterization, and electronic properties of the quinoid-based three-dimensional metal-organic framework [Fe2(dhbq)3]. The MOF was synthesized without using cations as a template, unlike other reported X2dhbq3-based coordination polymers, and the crystal structure was determined by using single-crystal X-ray diffraction. The crystal structure was entirely different from the other reported [Fe2(X2dhbq3)]2-; three independent 3D polymers were interpenetrated to give the overall structure. The absence of cations led to a microporous structure, investigated by N2 adsorption isotherms. Temperature dependence of electrical conductivity data revealed that it exhibited a relatively high electrical conductivity of 1.2 × 10-2 S cm-1 (Ea = 212 meV) due to extended d-π conjugation in a three-dimensional network. Thermoelectromotive force measurement revealed that it is an n-type semiconductor with electrons as the majority of charge carriers. Structural characterization and spectroscopic analyses, including SXRD, Mössbauer, UV-vis-NIR, IR, and XANES measurements, evidenced the occurrence of no mixed valency based on the metal and the ligand. [Fe2(dhbq)3] upon incorporating as a cathode material for lithium-ion batteries engendered an initial discharge capacity of 322 mAh/g.

11.
Jpn J Clin Oncol ; 53(11): 1034-1037, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37595992

ABSTRACT

OBJECTIVE: This study aimed to report the first surgery for gynecological diseases using a new robotic platform, the hinotori™, and validate its feasibility in clinical settings. METHODS: The world's first robot-assisted total hysterectomy for a gynecological ailment was carried out at Kagoshima University Hospital in December 2022 utilizing the hinotori™ surgical robot system. Eleven other patients then underwent comparable procedures. The surgical team was certified to execute the procedure and had undergone official hinotori™ training. RESULTS: Preoperative diagnoses indicated five cases of endometrial cancer, four cases of uterine myoma and one case each of atypical endometrial hyperplasia, uterine adenosarcoma and high-grade cervical intraepithelial neoplasia. Median age and body mass index were 51 (range: 38-70) years and 26.9 (range: 17.3-33.3) kg/m2, respectively. Median roll-in, cockpit and operation times were 15 (range: 10-18), 161 (range: 110-225) and 214 (range: 154-287) min, respectively. The median blood loss was 22 (range: 7-83) mL and conversion to laparotomy was not allowed. Only one patient had postoperative pelvic region infection. The median length of hospital stay was 6 (range: 4-10) days. CONCLUSION: Based on our experience with presented 12 cases, robotic surgery with the hinotori™ is a feasible technique of minimally invasive surgery for gynecological diseases.


Subject(s)
Endometrial Neoplasms , Laparoscopy , Robotic Surgical Procedures , Robotics , Uterine Neoplasms , Female , Humans , Robotics/methods , Robotic Surgical Procedures/methods , Endometrial Neoplasms/surgery , Hysterectomy/methods , Postoperative Complications , Laparoscopy/methods
12.
Int J Gynecol Cancer ; 33(5): 692-700, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36997229

ABSTRACT

OBJECTIVE: To assess the efficacy of dose-dense weekly paclitaxel plus carboplatin in metastatic or recurrent cervical carcinoma, we conducted a phase II/III randomized controlled study comparing dose-dense paclitaxel and carboplatin with or without bevacizumab to conventional paclitaxel and carboplatin with or without bevacizumab. However, at the primary analysis of the phase II part, the response rate in the dose-dense arm was not higher than in the conventional arm and the study was terminated early before starting phase III. After a further 2 years of follow-up, we conducted this final analysis. METHODS: 122 patients were enrolled and randomly assigned to either the conventional or dose-dense arm. After bevacizumab was approved in Japan, patients in both arms received bevacizumab if not contraindicated. In the final analysis, overall survival, progression-free survival, and adverse events were updated. RESULTS: The median follow-up of surviving patients was 34.8 months (range 19.2-64.8). Median overall survival in the conventional arm was 17.7 months and in the dose-dense arm 18.5 months (p=0.71). Median progression-free survival in the conventional arm was 7.9 months and in the dose-dense arm 7.2 months (p=0.64). A platinum-free interval within 24 weeks and treatment without bevacizumab were identified as prognostic factors for overall and progression-free survival. Grade 3 to 4 non-hematologic toxicity occurred in 46.7% of patients who received the conventional regimen and in 43.3% of patients who received the dose-dense regimen. Adverse events related to bevacizumab in 82 patients included fistula in five (6.1%) and gastrointestinal perforation in three (3.7%). CONCLUSIONS: It was confirmed that dose-dense paclitaxel plus carboplatin for metastatic or recurrent cervical carcinoma is not superior to conventional paclitaxel and carboplatin. Patients who had early refractory disease after prior chemoradiotherapy had the poorest prognosis. The development of treatments that improve the prognosis of such patients remains an important issue. CLINICAL TRIAL INFORMATION: jRCTs031180007.


Subject(s)
Carcinoma , Uterine Cervical Neoplasms , Female , Humans , Carboplatin , Bevacizumab , Paclitaxel , Neoplasm Recurrence, Local/pathology , Uterine Cervical Neoplasms/pathology , Carcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
13.
Cytopathology ; 34(3): 211-218, 2023 05.
Article in English | MEDLINE | ID: mdl-36727290

ABSTRACT

OBJECTIVE: For patients with endometrial cancer, the POLE (polymerase epsilon) mutation (POLEmut)-subtype, one of four molecular-analysis-based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLEmut-subtype: (1) the presence of tumour giant cells, (2) numerous tumour-infiltrating lymphocytes (TILs) and/or peri-tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown. METHODS: DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues was subjected to next-generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types. RESULTS: Seven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLEmut-subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLEmut-subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings. CONCLUSIONS: Preoperative endometrial cytology highlighted the characteristics of the POLEmut-subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Cytodiagnosis , Uterus/pathology , Mutation/genetics , Biomarkers, Tumor/genetics
14.
J Obstet Gynaecol Res ; 49(11): 2766-2770, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37604499

ABSTRACT

The diagnosis of synchronous endometrial and ovarian cancer or metastatic cancer of the same histological type is difficult. In this study, molecular biology analysis was performed to determine ovarian metastasis from endometrial cancer. A 38-year-old woman had pathological evidence of endometrial cancer (endometrioid carcinoma, grade 1) and ovarian cancer (endometrioid carcinoma, grade 3); a disseminated nodule in the serosa uteri was also diagnosed as endometrioid carcinoma (grade 3). Customized panel sequencing revealed a common mutation pattern in ovarian cancer and disseminated nodules. Furthermore, endometrial cancer showed the same mutation patterns for FGFR3 and PTEN as ovarian cancer and disseminated nodules. All tumors were microsatellite instability high. Clinicopathological and molecular biology analyses suggested that the patient had ovarian metastasis from endometrial cancer. The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, with no recurrence. Molecular biology techniques may enable appropriate treatment based on clinically accurate diagnosis.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Neoplasms, Multiple Primary , Ovarian Neoplasms , Humans , Female , Adult , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Mutation
15.
Int J Mol Sci ; 24(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36901788

ABSTRACT

Curli fimbriae are amyloids-found in bacteria (Escherichia coli)-that are involved in solid-surface adhesion and bacterial aggregation during biofilm formation. The curli protein CsgA is coded by a csgBAC operon gene, and the transcription factor CsgD is essential to induce its curli protein expression. However, the complete mechanism underlying curli fimbriae formation requires elucidation. Herein, we noted that curli fimbriae formation was inhibited by yccT-i.e., a gene that encodes a periplasmic protein of unknown function regulated by CsgD. Furthermore, curli fimbriae formation was strongly repressed by CsgD overexpression caused by a multicopy plasmid in BW25113-the non-cellulose-producing strain. YccT deficiency prevented these CsgD effects. YccT overexpression led to intracellular YccT accumulation and reduced CsgA expression. These effects were addressed by deleting the N-terminal signal peptide of YccT. Localization, gene expression, and phenotypic analyses revealed that YccT-dependent inhibition of curli fimbriae formation and curli protein expression was mediated by the two-component regulatory system EnvZ/OmpR. Purified YccT inhibited CsgA polymerization; however, no intracytoplasmic interaction between YccT and CsgA was detected. Thus, YccT-renamed CsgI (curli synthesis inhibitor)-is a novel inhibitor of curli fimbriae formation and has a dual role as an OmpR phosphorylation modulator and CsgA polymerization inhibitor.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Bacterial Proteins/metabolism , Biofilms , Bacterial Adhesion/genetics , Polymerization , Trans-Activators/metabolism , Gene Expression , Gene Expression Regulation, Bacterial
16.
Rinsho Ketsueki ; 64(2): 102-106, 2023.
Article in Japanese | MEDLINE | ID: mdl-36990728

ABSTRACT

A tyrosine kinase inhibitor (TKI) was used to treat the patient, a 35-year-old woman who was diagnosed with chronic myeloid leukemia at the age of 22 years. Since a four-year deep molecular response (DMR) was obtained, spontaneous pregnancy was planned under TKI withdrawal. Even though her disease had advanced to MR2.0 at the time of pregnancy confirmation, 2 months from TKI cessation, interferon α therapy was initiated in light of the patient's history. Later, the patient reached MR3.0, gave birth to a healthy baby, and maintained MR3.0-4.0. TKI was resumed after about 6 months of breastfeeding. Treatment-free remission (TFR) is required for natural conception despite the teratogenicity and miscarriage risks associated with BCR::ABL1 TKIs. When planning a pregnancy, it is also necessary to take the patients' backgrounds, disease states, and medical history into account.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Pregnancy , Female , Young Adult , Adult , Interferon-alpha/therapeutic use , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/therapeutic use , Recurrence , Treatment Outcome
17.
Small ; 18(29): e2202277, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35726082

ABSTRACT

Increasing mass loadings of battery electrodes critically enhances the energy density of an overall battery by eliminating much of the inactive components, while compacting the battery size and lowering the costs of the ingredients. A hard carbon microlattice, digitally designed and fabricated by stereolithography 3D-printing and pyrolysis, offers enormous potential for high-mass-loading electrodes. In this work, sodium-ion batteries using hard carbon microlattices produced by an inexpensive 3D printer are demonstrated. Controlled periodic carbon microlattices are created with enhanced ion transport through microchannels. Carbon microlattices with a beam width of 32.8 µm reach a record-high areal capacity of 21.3 mAh cm-2 at a loading of 98 mg cm-2 without degrading performance, which is much higher than the conventional monolithic electrodes (≈5.2 mAh cm-2 at 92 mg cm-2 ). Furthermore, binder-free, pure-carbon elements of microlattices enable the tracking of structural changes in hard carbon that support the hypothesized intercalation of ions at plateau regions by temporal ex situ X-ray diffraction measurements. These results will advance the development of high-performance and low-cost anodes for sodium-ion batteries as well as help with understanding the mechanisms of ion intercalations in hard carbon, expanding the utilities of 3D-printed carbon architectures in both applications and fundamental studies.

18.
Gynecol Oncol ; 165(1): 149-154, 2022 04.
Article in English | MEDLINE | ID: mdl-35151491

ABSTRACT

OBJECTIVE: Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. METHODS: We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. RESULTS: The median age of the patients was 34 years (range, 21-73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25-145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. CONCLUSIONS: SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.


Subject(s)
Lymphedema , Uterine Cervical Neoplasms , Adult , Aged , Female , Follow-Up Studies , Humans , Hysterectomy/methods , Lymph Node Excision/adverse effects , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphedema/pathology , Middle Aged , Neoplasm Staging , Postoperative Complications/pathology , Retrospective Studies , Sentinel Lymph Node Biopsy/adverse effects , Sentinel Lymph Node Biopsy/methods , Uterine Cervical Neoplasms/pathology , Young Adult
19.
Jpn J Clin Oncol ; 52(5): 475-478, 2022 May 05.
Article in English | MEDLINE | ID: mdl-35134177

ABSTRACT

OBJECTIVE: This preliminary study aimed to assess the detection accuracy of sentinel lymph node metastasis in cervical cancer using quantitative reverse transcriptase-polymerase chain reaction. METHODS: We collected cervical cancer tissues and 70 pelvic lymph node samples from patients with cervical cancer. The quantitative reverse transcriptase-polymerase chain reaction assay was performed to investigate the expression of cytokeratin 19 mRNA in cervical cancer tissues and determine the cutoff value of cytokeratin 19 mRNA between the non-metastatic and metastatic lymph nodes. RESULTS: The expression of cytokeratin 19 mRNA in cancer tissues was detected in all (71/71) the tumours, with a median copy number of 7.56 × 105/µl of RNA by quantitative reverse transcriptase-polymerase chain reaction. Sixteen lymph nodes were diagnosed as positive by pathological examination. The median copy numbers of cytokeratin 19 mRNA for positive and negative lymph nodes were 43.3 × 104/µl and 121.1/µl, respectively. The expression of cytokeratin 19 mRNA in pathologically positive lymph nodes was higher than that in the negative lymph nodes (P < 0.0001) by quantitative reverse transcriptase-polymerase chain reaction analysis. Using a receiver operating characteristic plot, the maximum sensitivity (100%) and specificity (94.4%) were obtained when the cutoff value was set at 1169 copies/µl. CONCLUSIONS: After setting the cutoff value at 1169 copies/µl, a quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA showed high accuracy in detecting lymph node metastasis in cervical cancer. We believe that the quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA may be acceptable for lymph node metastasis detection in patients with cervical cancer.


Subject(s)
Keratin-19 , Uterine Cervical Neoplasms , Female , Humans , Keratin-19/genetics , Keratin-19/metabolism , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Directed DNA Polymerase/genetics , RNA-Directed DNA Polymerase/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology
20.
Jpn J Clin Oncol ; 52(1): 24-28, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34718651

ABSTRACT

BACKGROUND: We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer. METHODS: This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery. RESULTS: The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P < 0.0001). There was a significant difference in the mean number of total pelvic sentinel lymph nodes between 99mTc (2.2) and indocyanine green (2.5) (P = 0.028) methods. CONCLUSION: Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.


Subject(s)
Endometrial Neoplasms , Sentinel Lymph Node , Coloring Agents , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/surgery , Female , Humans , Indocyanine Green , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Prospective Studies , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node Biopsy , Technetium
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