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1.
Pediatr Surg Int ; 40(1): 239, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167137

RESUMEN

PURPOSE: Biliary atresia (BA) poses a persistent challenge characterized by ongoing liver inflammation and subsequent fibrosis even after the clearance of jaundice (COJ). This study aimed to evaluate the therapeutic potential of eicosapentaenoic acid (EPA) in alleviating liver inflammation and limiting fibrosis during the post-COJ phase of BA. METHODS: Among the BA patients undergoing laparoscopic Kasai portoenterostomy (lapKP) between December 2016 and October 2021, EPA (20-40 mg/kg/day) was administered orally to those whose parents consented. The study included patients from January 2014 to October 2021, classifying them into two groups: EPA-treated (Group E) and untreated (Group N). Their liver fibrosis and clinical course at 1 and 2 years post-lapKP were compared. RESULTS: Group E consisted of 25 patients, while Group N comprised 32 patients. Twenty-one patients in Group E and 25 patients in Group N achieved COJ (p = 0.74). Among jaundice-free patients at 1 and 2 years post-lapKP, Group E exhibited significantly lower M2BPGi levels and platelet counts, and Group E showed a significant reduction in Aminotransferase-to-Platelet Ratio Index (APRI) at 2 years post-lapKP. CONCLUSION: Although EPA administration did not improve COJ, it attenuated the progression of liver fibrosis during the 2 years following lapKP in jaundice-free patients. (200/200Words).


Asunto(s)
Atresia Biliar , Progresión de la Enfermedad , Ácido Eicosapentaenoico , Cirrosis Hepática , Portoenterostomía Hepática , Humanos , Portoenterostomía Hepática/métodos , Ácido Eicosapentaenoico/uso terapéutico , Ácido Eicosapentaenoico/administración & dosificación , Masculino , Femenino , Atresia Biliar/cirugía , Lactante , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento , Preescolar
2.
Asian J Endosc Surg ; 17(4): e13379, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39168481

RESUMEN

The Senhance® robotic system (Senhance [Asensus Surgical Inc., Naderhan, NC, USA]) is a new surgical assistive robot following the da Vinci Surgical System that has been demonstrated to be safe and efficacious. Herein, we report the first case series of pediatric pelvic surgery using Senhance. Two anorectoplasties and one rectal pull-through coloanal anastomosis for rectal stenosis were performed in three children (5-9 months, 7-9 kg) using a 10-mm three-dimensional (3D) 4K camera and 3 and 5 mm forceps operated with Senhance. None of the patients had intraoperative complications or a good postoperative course. Pediatric pelvic surgery with Senhance could be performed precisely and safely with a small body cavity. With its beautiful 3D images, motion of forceps with reduced tremor, and availability of 3-mm forceps, Senhance may be better suited for children compared with other models.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/instrumentación , Lactante , Femenino , Masculino , Recto/cirugía , Anastomosis Quirúrgica/instrumentación , Constricción Patológica/cirugía , Canal Anal/cirugía , Enfermedades del Recto/cirugía
3.
Artículo en Inglés | MEDLINE | ID: mdl-39010283

RESUMEN

The prevalence of obesity is increasing worldwide, resulting in various health issues such as hypertension, dyslipidemia, diabetes mellitus, heart disease, and a lower life expectancy. Importantly, several psychiatric disorders and the use of psychotropic medications have been linked to obesity, and the possible risk factors need further investigation. This study examined the prevalence of obesity and its associated factors using a self-administered questionnaire. Participants were recruited from three outpatient clinics and individuals who met one or more of the ICD-10 F0-F9, G4 diagnoses were included. In total, 1384 participants completed the questionnaire about their lifestyle. Statistical analysis compared the demographic and clinical characteristics of the individuals who were obese (Body Mass Index: BMI ≥25) and those who were non-obese (BMI <25). The results revealed that the factors associated with obesity in psychiatric outpatients were being male, prolonged treatment duration, eating out frequently, and use of both second- and first-generation antipsychotics. The study emphasized the importance of closely monitoring BMI in individuals with multiple obesity-related factors.

4.
CEN Case Rep ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990435

RESUMEN

Patients with chronic kidney disease (CKD) sometimes experience gastrointestinal symptoms, such as nausea and vomiting. In addition, hypertension and CKD are closely linked, and sustained hypertension in children is associated with the progression of CKD, leading to early cardiomyopathy and premature atherosclerosis. These symptoms substantially affect the quality of daily life of CKD patients, and particularly in children with CKD, they may cause growth retardation. Therefore, establishing effective management methods to alleviate these symptoms is very important. Here, we report a case of a male patient who was born at 34 weeks of gestation weighing 1400 g. At birth, abdominal ultrasonography displayed left multicystic dysplastic kidney. From 6 months after birth, he was frequently hospitalized owing to refractory periodic vomiting. At 9 months old, he was diagnosed as having stage 3a CKD, and at 20 months old, he presented with stage 2 high blood pressure. In Japan, the uremic toxin adsorbent AST-120 and angiotensin-converting enzyme inhibitor-I (ACE-I) are not strongly recommended for CKD patients. However, after the patient underwent combination therapy of AST-120 and ACE-I, his frequent hospitalizations for refractory periodic vomiting ceased, and his blood pressure decreased. These results indicate that AST-120 and ACE-I are effective for refractory periodic vomiting and hypertension associated with CKD. The patient's height, weight, and mental development are catching up smoothly. The cause of the patient's refractory periodic vomiting remains unclear. However, his impaired kidney function owing to congenital anomalies of the kidney and urinary tract may have caused the refractory periodic vomiting and dehydration. The production of uremic toxins in CKD patients is thought to lead to the secretion of proinflammatory cytokines into the circulation. However, our patient had low serum levels of proinflammatory cytokines, and his serum levels of the chemokines CX3CL1 and CCL2 decreased with age, together with improvement in his clinical course. Therefore, some specific chemokines might be diagnostic and/or prognostic biomarkers of CKD.

5.
Pediatr Surg Int ; 40(1): 197, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017936

RESUMEN

PURPOSE: The prognostic factors of subsequent liver transplantation (LT) in patients with biliary atresia (BA) who presented with jaundice-free native liver survival were investigated. METHODS: This study retrospectively reviewed patients who underwent portoenterostomy (PE) for BA. Patients with jaundice-free native liver survival at 1 year postoperatively were divided into the autologous liver survivor and liver transplant recipient groups. Peri- and postoperative data were compared between the two groups. RESULTS: Among 97 patients with BA, 29 who received LT within 1 year after PE were excluded from the analysis. Further, 48 patients currently living with native liver and 20 who received LT after 1 year postoperatively were compared. Bile lake (BL) was the strongest risk factor of LT. The risk score was 2.38 ∗ B L s c o r e + 0.00466 ∗ T B A , and the area under the receiver operating characteristic curve was 0.83. Patients with BL and those without significantly differed in terms of the native liver survival rate. Patients with BL who presented with not only cholangitis but also gastrointestinal hemorrhage and hepatopulmonary syndrome received LT. CONCLUSION: BL can cause different pathologies. Moreover, it is an evident risk factor of subsequent LT in patients with BA who are living with native liver at 1 year after PE.


Asunto(s)
Atresia Biliar , Trasplante de Hígado , Portoenterostomía Hepática , Humanos , Atresia Biliar/cirugía , Atresia Biliar/complicaciones , Atresia Biliar/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Lactante , Factores de Riesgo , Portoenterostomía Hepática/métodos , Tasa de Supervivencia/tendencias , Bilis , Pronóstico , Preescolar , Ictericia/etiología , Hígado
6.
Sci Rep ; 14(1): 16264, 2024 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-39009703

RESUMEN

Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience psychological distress associated with daily events that do not meet the threshold for traumatic experiences, referred to as event-related psychological distress (ERPD). Recently, we developed an assessment tool for ERPD, the ERPD-24. This tool considers four factors of ERPD: feelings of revenge, rumination, self-denial, and mental paralysis. We conducted a cross-sectional study between March 2021 and October 2022 to identify the differences and clinical features of ERPD among patients with MDD and BD and healthy subjects who did not experience traumatic events. Specifically, we assessed ERPD using the ERPD-24 and anxiety-related symptoms with the State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, and anxious-depressive attack. Regarding the ERPD-24 scores among the groups, as the data did not rigorously follow the test of normality, the Kruskal-Wallis test was used to compare the differences among the groups, followed by the Dunn-Bonferroni adjusted post-hoc test. Non-remitted MDD patients and BD patients, regardless of remission/non-remission, presented more severe ERPD than healthy subjects. This study also demonstrated the relationships between all anxiety-related symptoms, including social phobia and anxious-depressive attack and ERPD, in both BD and MDD patients and in healthy subjects. In conclusion, patients with non-remitted MDD and with BD regardless of remission/non-remission experience severe ERPD related to anxiety-related symptoms.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Distrés Psicológico , Humanos , Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Transversales , Ansiedad/psicología , Acontecimientos que Cambian la Vida , Estrés Psicológico/psicología
7.
Artículo en Inglés | MEDLINE | ID: mdl-38957048

RESUMEN

Constipation is a prevalent gastrointestinal disorder that affects people globally, decreasing their quality of life and life expectancy. Individuals with schizophrenia often suffer from constipation, which could be a result of the illness itself or the side effects of psychotropic medications. However, little research has been conducted on factors contributing to constipation in individuals with schizophrenia. To address this issue, we conducted a survey using self-administered questionnaires and medical records to identify factors associated with constipation in psychiatric outpatients. This study included 399 patients with schizophrenia, resulting in a high prevalence of constipation (43.4%). The analysis suggested that female gender, the doses of antiparkinsonian medications, and benzodiazepine sleeping pills may be associated with constipation.

8.
Pediatr Surg Int ; 40(1): 149, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829446

RESUMEN

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.


Asunto(s)
Atresia Esofágica , Toracoscopía , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/cirugía , Fístula Traqueoesofágica/complicaciones , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Recién Nacido , Toracoscopía/métodos , Masculino , Femenino , Estudios Retrospectivos , Resultado del Tratamiento , Recién Nacido de Bajo Peso , Fuga Anastomótica/cirugía
9.
Neuropsychiatr Dis Treat ; 20: 697-723, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559773

RESUMEN

Purpose: Sleep plays an essential role in maintaining both physical and mental well-being. Many patients in psychiatric outpatient settings complain of insomnia. However, the causal relationship between insomnia and depressive symptoms in all mental illnesses remains unclear. Moreover, research on insomnia and the continuation of outpatient treatment is lacking. We hypothesize a high correlation between depression and insomnia among patients with diverse mental illnesses. Additionally, we posit that insomnia significantly influences the continuity of outpatient visits. To this end, we evaluated insomnia and depression symptoms in psychiatric patients both at their initial visit and one year later. We also examined factors related to insomnia at the outset and factors associated with the ongoing utilization of outpatient treatment. Patients and Methods: The participants of the study consisted of patients who made their first visit to the outpatient department of psychiatry and neurology at Showa University East Hospital between June 1, 2021, and March 31, 2023, and who continued attending the outpatient clinic for one year. Clinical characteristics were assessed using the Self-rating Depression Scale (SDS) and the Athens Insomnia Scale (AIS). Results: The study's findings were collected from a cohort of 1106 patients and revealed that more than 70% experienced insomnia at the time of their initial visit. In total 137 patients continued to receive outpatient treatment for one year, and their AIS scores improved from 9 points to 5 points. A multivariate analysis revealed that the SDS items of depressed mood and insomnia were confounding factors influencing AIS improvement. Conclusion: Given that 70% of patients complained of insomnia at the time of their first visit and that sleep improved in many of the 12.4% of patients who continued to receive outpatient treatment for at least one year, the results suggest that sleep status is an important determinant of whether a patient continues to attend outpatient clinics.

11.
J Radiol Prot ; 43(4)2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37939385

RESUMEN

The diagnostic reference level (DRL) is an effective tool for optimising protection in medical exposures to patients. However regarding air kerma at the patient entrance reference point (Ka,r), one of the DRL quantities for endoscopic retrograde cholangiopancreatography (ERCP), manufacturers use a variety of the International Electrotechnical Commission and their own specific definitions of the reference point. The research question for this study was whetherKa,ris appropriate as a DRL quantity for ERCP. The purpose of this study was to evaluate the difference betweenKa,rand air kerma incident on the patient's skin surface (Ka,e) at the different height of the patient couch for a C-arm system. Fluoroscopy and radiography were performed using a C-arm system (Ultimax-i, Canon Medical Systems, Japan) and a over-couch tube system (CUREVISTA Open, Fujifilm Healthcare, Japan).Ka,ewas measured by an ion chamber placed on the entrance surface of the phantom. Kerma-area product (PKA) andKa,rwere measured by a built-inPKAmeter and displayed on the fluoroscopy system.Ka,edecreased whileKa,rincreased as the patient couch moved away from the focal spot. The uncertainty of theKa,e/Ka,rratio due to the different height of the patient couch was estimated to be 75%-94%.Ka,rmay not accurately representKa,e.PKAwas a robust DRL quantity that was independent of the patient couch height. We cautioned against optimising patient doses in ERCP with DRLs set in terms ofKa,rwithout considering the patient couch height of the C-arm system. Therefore, we recommend thatKa,ris an inappropriate DRL quantity in ERCP using the C-arm system.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Niveles de Referencia para Diagnóstico , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Dosis de Radiación , Fluoroscopía , Radiografía
12.
Radiol Phys Technol ; 16(2): 299-309, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37046154

RESUMEN

This study aimed to determine the optimal radiographic conditions for detecting lesions on digital chest radiographs using an indirect conversion flat-panel detector with a copper (Cu) filter. First, we calculated the effective detective quantum efficiency (DQE) by considering clinical conditions to evaluate the image quality. We then measured the segmentation accuracy using a U-net convolutional network to verify the effectiveness of the Cu filter. We obtained images of simulated lung tumors using 10-mm acrylic spheres positioned at the right lung apex and left middle lung of an adult chest phantom. The Dice coefficient was calculated as the similarity between the output and learning images to evaluate the accuracy of tumor area segmentation using U-net. Our results showed that effective DQE was higher in the following order up to the spatial frequency of 2 cycles/mm: 120 kV + no Cu, 120 kV + Cu 0.1 mm, and 120 kV + Cu 0.2 mm. The segmented region was similar to the true region for mass-area extraction in the left middle lobe. The lesion segmentation in the upper right lobe with 120 kV + no Cu and 120 kV + Cu 0.1 mm was less successful. However, adding a Cu filter yielded reproducible images with high Dice coefficients, regardless of the tumor location. We confirmed that adding a Cu filter decreases the X-ray absorption efficiency while improving the signal-to-noise ratio (SNR). Furthermore, artificial intelligence accurately segments low-contrast lesions.


Asunto(s)
Aprendizaje Profundo , Neoplasias , Humanos , Cobre , Inteligencia Artificial , Radiografía , Intensificación de Imagen Radiográfica/métodos
13.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36499744

RESUMEN

The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR-122-5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR-122-5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR-122-5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR-122-5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR-122-5p mimic, and the expression level of FOXO3, an anti-fibrotic mRNA, was upregulated by the miR-122-5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR-122-5p inhibitor. These results suggest that miR-122-5p has critical roles in renal fibrosis.


Asunto(s)
Enfermedades Renales , MicroARNs , Obstrucción Ureteral , Ratones , Animales , Fibrosis , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero
14.
Pathogens ; 11(11)2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36365064

RESUMEN

The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue in Japan. Allergen immunotherapy is the only fundamental treatment that modifies the natural course of allergic rhinitis and provides long-term remission that cannot be induced by general drug therapy. Sublingual immunotherapy for Japanese cedar pollinosis has been developed and has been covered by health insurance since 2014 in Japan. The indication for children was expanded in 2018. Clinical trials of sublingual immunotherapy for Japanese cedar pollinosis have demonstrated its long-term efficacy and safety. It is recommended for patients who wish to undergo fundamental treatment regardless of the severity of the practical guidelines for the management of allergic rhinitis in Japan. For sublingual immunotherapy, a long-term treatment period of 3 years or longer is recommended to obtain stable therapeutic effects. In recent years, evidence based on basic research and clinical trials has demonstrated sublingual immunotherapy-induced immunological changes and efficacy in patients; however, biomarkers that objectively predict and judge these therapeutic effects need to be established.

15.
Clin Case Rep ; 10(10): e6444, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36285037

RESUMEN

Hypersensitivity reaction to cisplatin can result in discontinuation of chemoradiotherapy in patients with head and neck squamous cell carcinoma. We describe a patient with nasopharyngeal carcinoma who developed cisplatin hypersensitivity and was successfully treated with cisplatin desensitization. Furthermore, it had little impact on the therapeutic performance of cisplatin-combined chemoradiotherapy.

16.
Medicine (Baltimore) ; 101(37): e30636, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36123836

RESUMEN

RATIONALE: Nodular fasciitis (NF) can be misdiagnosed as a sarcoma because of its rapid growth and pathological features, such as nuclear atypia and mitoses. PATIENT CONCERNS: We present a rare case of a 72-year-old Japanese man who developed NF with suspected postirradiation myxofibrosarcoma (MFS) after segmentectomy for left-sided osteoradionecrosis (ORN) of the mandible. DIAGNOSIS: A mass appeared in the intraoral postoperative wound 1 year after left-sided mandibular segmentectomy and showed rapid growth, reaching a size of 50 mm within 2 months. Incisional biopsy revealed strongly Ki-67-positive spindle-shaped cells with large irregular nuclei and a diagnosis of postirradiation MFS. INTERVENTIONS: The patient was diagnosed with oropharyngeal cancer (T4aN2bM0) and underwent surgical resection of primary oropharyngeal squamous cell carcinoma with selective neck dissection and reconstruction with a rectus abdominis musculocutaneous flap at the age of 57 years, followed by postoperative 66 Gy of radiotherapy combined with cisplatin administration. No recurrent or metastatic lesions of oropharyngeal squamous cell carcinoma have been detected for > 10 years. However, the ORN of the jaw worsened, and the patient underwent sequestrectomy 3 times on the right side of the mandible, followed by a left-sided segmentectomy at the age of 72 years. One year after segmentectomy, a 10-mm mass with soft-to-firm consistency appeared in the buccal mucosa of the wound and grew rapidly. An incisional biopsy revealed MFS. Complete resection under general anesthesia was immediately performed. OUTCOMES: The histopathological diagnosis of the excised specimen was NF without any malignant findings. Two years after surgery, there was no evidence of recurrence or metastasis. LESSONS: NF grows rapidly and has pathological features similar to sarcoma, making differential diagnosis difficult at the time of incisional biopsy. Further studies should be conducted to determine the clinical and pathological features of this tumor.


Asunto(s)
Fascitis , Fibrosarcoma , Neoplasias de Cabeza y Cuello , Histiocitoma Fibroso Maligno , Sarcoma , Adulto , Anciano , Cisplatino , Fibrosarcoma/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Histiocitoma Fibroso Maligno/cirugía , Humanos , Antígeno Ki-67 , Masculino , Persona de Mediana Edad , Neumonectomía , Sarcoma/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello
17.
Clin Case Rep ; 10(7): e6050, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35865779

RESUMEN

Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer with no effective drugs for controlling. This case report has shown genomic and immune microenvironment profiles in metastatic ITTC and emphasized an immunosuppression via a PD-1/PD-L1 pathway, possibly strengthening the rationale for immune checkpoint blockade as a novel treatment.

18.
Mol Cancer Res ; 20(11): 1674-1685, 2022 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-35857355

RESUMEN

The mechanisms of how cancer cells are selected and evolve to establish distant metastatic colonies remain unclear. Tumor heterogeneity and lack of biomarkers are some of the most difficult challenges in cancer biology and treatment. Here using mouse models for triple-negative breast cancer (TNBC) metastasis, we report heterogeneous expression of DNA methyltransferase 3B (DNMT3B) in both mouse and human primary tumors. High levels of DNMT3B were correlated with poor clinical outcomes in multiple human breast cancer datasets. Mechanistically, clonal cells with high DNMT3B (DNMT3BH) showed higher vimentin (VIM) expression and displayed enhanced epithelial-to-mesenchymal transition capacity. Deletion of VIM diminished the metastatic phenotype of DNMT3BH cells. Importantly, in preclinical mouse models in which the primary tumors were surgically removed, perioperative targeting of DNMT3B in combination with chemotherapy markedly suppressed tumor recurrence and metastasis. Our studies identify DNMT3B-mediated transcription regulation as an important mediator of tumor heterogeneity and show that DNMT3B is critical for tumor invasion and metastasis, reinforcing its potential as a target for treating metastatic disease. IMPLICATIONS: Our findings of transcriptome changes mediated by DNMT3B provide new mechanistic insight for intratumor heterogeneity and chemoresistance, and therapeutic targeting of DNMT3B in combination with chemotherapy offer additional treatment options for metastatic disease especially for patients with TNBC.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Recurrencia Local de Neoplasia/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , ADN Metiltransferasa 3B
19.
Front Med (Lausanne) ; 9: 849075, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646947

RESUMEN

Background: Age-dependent renal impairment contributes to renal dysfunction in both the general population and young and middle-aged patients with renal diseases. Pathological changes in age-dependent renal impairment include glomerulosclerosis and tubulointerstitial fibrosis. The molecules involved in age-dependent renal impairment are not fully elucidated. MicroRNA (miRNA) species were reported to modulate various renal diseases, but the miRNA species involved in age-dependent renal impairment are unclear. Here, we investigated miRNAs in age-dependent renal impairment, and we evaluated their potential as biomarkers and therapeutic targets. Methods: We conducted an initial microarray profiling analysis to screen miRNAs whose expression levels changed in kidneys of senescence-accelerated resistant (SAMR1)-10-week-old (wk) mice and SAMR1-50wk mice and senescence-accelerated prone (SAMP1)-10wk mice and SAMP1-50wk mice. We then evaluated the expressions of differentially expressed miRNAs in serum from 13 older patients (>65 years old) with age-dependent renal impairment (estimated glomerular filtration ratio <60 mL/min/1.73 m2) by a quantitative real-time polymerase chain reaction (qRT-PCR) and compared the expressions with those of age-matched subjects with normal renal function. We also administered miRNA mimics or inhibitors (5 nmol) with a non-viral vector (polyethylenimine nanoparticles: PEI-NPs) to SAMP1-20wk mice to investigate the therapeutic effects. Results: The qRT-PCR revealed a specific miRNA (miRNA-503-5p) whose level was significantly changed in SAMP1-50wk mouse kidneys in comparison to the controls. The expression level of miRNA-503-5p was upregulated in the serum of the 13 patients with age-dependent renal impairment compared to the age-matched subjects with normal renal function. The administration of a miRNA-503-5p-inhibitor with PEI-NPs decreased the miRNA-503-5p expression levels, resulting in the inhibition of renal fibrosis in mice via an inhibition of a pro-fibrotic signaling pathway and a suppression of glomerulosclerosis in mice by inhibiting intrinsic signaling pathways. Conclusion: The serum levels of miRNA-503-5p were decreased in patients with age-dependent renal impairment. However, inhibition of miRNA-503-5p had no effect on age-dependent renal impairment, although inhibition of miRNA-503-5p had therapeutic effects on renal fibrosis and glomerulosclerosis in an in vivo animal model. These results indicate that miRNA-503-5p might be related to age-dependent renal impairment.

20.
Artículo en Inglés | MEDLINE | ID: mdl-35595622

RESUMEN

OBJECTIVE: This study aimed to evaluate intercellular bridges in the depth of invasion (DOI) measurement area as prognostic factors in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The mode of invasion was determined based on the Yamamoto-Kohama classification system by observing the hematoxylin-eosin-stained whole-slide images of specimens obtained from 78 patients with OSCC, and the clinicopathologic features were characterized. The presence of intercellular bridges was analyzed in 46 patients with Yamamoto-Kohama classification grade ≥3 whose DOI was measured by dividing the measurement area into 3 parts: the surface, center, and front of the tumor. RESULTS: Univariate analyses identified lymph node metastasis, loss of intercellular bridges in the DOI measurement area, DOI of ≥4500 µm, and pattern of invasion 4C-4D as negative prognostic factors. Multivariate analyses revealed that lymph node metastasis and the loss of intercellular bridges in the entire area were independent factors, with hazard ratios of 9.34 (95% confidence interval, 2.09-42.03; P = .003) and 3.64 (95% confidence interval, 1.10-11.99; P = .045), respectively. CONCLUSIONS: Loss of intercellular bridges in the DOI measurement area is a negative prognostic factor for OSCC and may be useful in selecting treatment.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Metástasis Linfática , Neoplasias de la Boca/patología , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello
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