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Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-ß-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-ß-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.
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Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.
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Enfermedades de los Perros , Neoplasias Mamarias Animales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Perros , Femenino , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Enfermedades de los Perros/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transducción de Señal , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacologíaRESUMEN
Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.
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Extractos Vegetales , Sarcopenia , Ulmus , Ulmus/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratones Endogámicos C57BL , Masculino , Animales , Ratones , Sarcopenia/tratamiento farmacológico , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacosRESUMEN
We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer.
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Perfilación de la Expresión Génica/métodos , Separación Inmunomagnética/métodos , Células Neoplásicas Circulantes/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Humanos , Masculino , Técnicas Analíticas Microfluídicas/métodos , Persona de Mediana Edad , TranscriptomaRESUMEN
V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.
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Antígenos B7/metabolismo , Biomarcadores de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
INTRODUCTION: The purpose of this study was to analyze survival outcomes after segmental bile duct resection (BDR) for mid-common bile duct cancer according to the length of the tumor-free BDR margins. METHOD: A total of 133 consecutive patients underwent BDR for mid-bile duct cancers between December 2007 and June 2017. The Cox proportional hazard model was used to verify the cutoff value of the R0 resection margin. The patients were divided into 3 groups according to resection margin status (group 1; R0 resection margin ≥5 mm; group 2, R0 resection margin <5 mm; and group 3, R1 resection margin). RESULTS: The median follow-up period of the study cohort was 24 months. A resection margin of 5 mm in length was verified to be suitable as a reliable cutoff value. The median disease-free and overall survival (OS) periods were 32 and 49 months in group 1, 13 and 20 months in group 2, and 23 and 30 months in group 3, respectively (p = 0.03 and p < 0.001). The length of the tumor-free resection margin (hazard ratio, 2.01; 95% confidence interval, 1.10-3.67; p = 0.022) was independent factor affecting OS. CONCLUSIONS: BDR for mid-bile duct cancer appears to be a feasible surgical option in selected patients with careful preoperative imaging assessment and intraoperative frozen-section diagnosis. Our results suggest achieving a BDR margin ≥5 mm to improve survival outcomes.
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Adenocarcinoma/cirugía , Neoplasias del Conducto Colédoco/cirugía , Márgenes de Escisión , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Femenino , Estudios de Seguimiento , Secciones por Congelación , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Recurrencia Local de Neoplasia , Pronóstico , Puntaje de Propensión , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: Renal artery pseudoaneurysms (RAPs) and arteriovenous fistulas (AVFs) are rare but potentially life-threatening complications after partial nephrectomy (PN). Selective arterial embolization (SAE) is an effective method for controlling RAPs/AVFs. We assessed the clinical factors affecting the occurrence of RAPs/AVFs after PN and the effects of SAE on postsurgical renal function. MATERIALS AND METHODS: Four hundred ninety-three patients who underwent PN were retrospectively reviewed. They were placed in either the SAE or the non-SAE group. The effects of clinical factors, including R.E.N.A.L. scores, on the occurrence of RAPs/AVFs were analyzed. The influence of SAE on the estimated glomerular filtration rate (eGFR) during the first postoperative year was evaluated. RESULTS: Thirty-three (6.7%) patients experienced RAPs/AVFs within 8 days of the median interval between PN and SAE. The SAE group had significantly higher R.E.N.A.L. scores, higher N component scores, and higher L component scores (all, p <0.05). In the multivariate analysis, higher N component scores were associated with the occurrence of RAPs/AVFs (Odds ratio: 1.96, p=0.039). In the SAE group, the mean 3-day postembolization eGFR was significantly lower than the mean 3-day postoperative eGFR (p <0.01). This difference in the eGFRs was still present 1 year later. CONCLUSIONS: Renal tumors located near the renal sinus and collecting system were associated with a higher risk for RAPs/AVFs after PN. Although SAE was an effective method for controlling symptomatic RAPs/AVFs after PN, a procedure-related impairment of renal function after SAE could occur and still be present at the end of the first postoperative year.
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Aneurisma Falso , Fístula Arteriovenosa , Neoplasias Renales , Aneurisma Falso/etiología , Fístula Arteriovenosa/etiología , Tasa de Filtración Glomerular , Humanos , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study is to investigate the cumulative incidence and risk factors of postoperative inguinal hernia (PIH) in patients undergoing radical prostatectomy, i.e., laparoscopic prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RARP). METHODS: This study included 1124 patients who had undergone radical prostatectomy or transurethral resection of bladder tumor from 2011-2016. We compared the cumulative incidence of PIH in the radical prostatectomy groups (460; LRP 341, RARP 119) and the control group (664; transurethral resection of bladder tumor), and we then analyzed the risk factors (age, operative methods, previous abdominal operative history, thickness and width of external oblique muscle and rectus muscle, thickness of abdominal subcutaneous fat layer at Hesselbach's triangle level, body mass index, prostate-specific antigen, operative time, specimen weight, Gleason score, and pathology T-stage) of PIH in the radical prostatectomy groups. RESULTS: The median follow-up period in this study was 39.6 months. In Kaplan-Meier curve analysis, the cumulative incidence of PIH was 5.3, 4.2, and 0.5% for the LRP, RARP, and control groups, respectively (p < 0.001). Multiple logistic regressions showed that thickness of external oblique muscle and width of rectus muscle were significant risk factors (p < 0.001 and p = 0.027). CONCLUSIONS: PIH is considered to be one of the complications of LRP and RARP. Moreover, we suggest that if the thickness of the muscle is <7.3 mm, thoughtful surgical manipulation is needed for radical prostatectomy, and care should be taken to determine whether hernia occurs during follow-up.
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Hernia Inguinal/epidemiología , Hernia Inguinal/etiología , Complicaciones Posoperatorias , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Anciano , Estudios de Casos y Controles , Humanos , Incidencia , Masculino , Clasificación del Tumor , Neoplasias de la Próstata/patología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC. We examined associations between mRNA expression of AR-V7 and clinicopathologic factors. Furthermore, to identify other potential genes involved in the development of CRPC, RNA sequencing was conducted, using paired prostate cancer (PCa) tissues obtained immediately prior to treatment and at the time of therapeutic resistance. RESULTS: A total of 13 HSPC patients and three CRPC patients were enrolled. Neither a high Gleason score (score of 8 and 9) nor a high risk of PCa (a high risk of locally advanced PCa according to NCCN guidelines) was correlated with mRNA expression of AR-V7 in HSPC (P = 0.153 and P = 0.215). The mRNA expression of AR-FL, but not AR-V7, was significantly associated with the mRNA expression of UBE2C level in HSPC (P = 0.007). However, increased expression of AR-V7, not AR-FL, paralleled increased expression of UBE2C in the CRPC specimens (P = 0.03). AR-V7 expression status before ADT was likely related to shorter CRPC development in patients treating ADT. The result of the RNA-sequencing analysis using serial samples from the same patient before and after castration demonstrated an increased level of the PI3K regulatory subunit 1 (P = 0.018). CONCLUSION: Our study revealed the role of UBE2C as a marker of the androgen signaling pathway in PCa. Differential gene expression analysis using serial samples from the same patient before and after castration revealed potential genes and pathways involved in development of CRPC. Further studies are needed to determine whether these genes and pathways are potential therapeutic target for CRPC. Prostate 77:60-71, 2017. © 2016 Wiley Periodicals, Inc.
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Variación Genética/fisiología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/genética , Transcripción Genética/fisiología , Enzimas Ubiquitina-Conjugadoras/genética , Anciano , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Receptores Androgénicos/biosíntesis , Estudios Retrospectivos , Enzimas Ubiquitina-Conjugadoras/biosíntesisRESUMEN
The Manual Function Test (MFT) is a tool to assess upper extremity motor impairment associated with stroke. This study investigated psychometric properties of the Korean version of the MFT and to establish normative data. Eighty-one patients were enrolled to evaluate MFT, Fugl-Meyer Assessment (FMA) and manual muscle test (MMT). MFT was completed by eight raters on two occasions separated by 6 weeks. Absolute and relative reliability and validity were examined. Additionally, MFT was assessed on 75 healthy controls of different ages. Intraclass correlation coefficient (ICC) (2,1) values for total and each dimension of Korean MFT ranged from 0.984 to 0.998 in the affected side of hemiplegic patients, indicating inter-rater reliability. Percentage values of standard error of measurement (SEM) and smallest real difference (SRD) ranged 3.10-10.57% and 8.58-29.29% respectively. Test-retest reliability ICCs for all raters were above 0.98. Effect size (ES) and standardized response mean (SRM) were larger in the acute-subacute group (onset to initial evaluation ≤ 4 months) (ES = 0.12; SRM = 0.41) than those in the chronic group (onset to evaluation > 4 months) (ES = 0.01; SRM = 0.11). MFT score was significantly correlated with FMA score (p < 0.001) and MMT score (p < 0.001). In healthy controls, regression analysis indicated that age significantly predicts manual function scores on both dominant and non-dominant. The Korean MFT showed good reliability and validity. Modest responsiveness was observed in patients evaluated early after stroke onset. The Korean MFT is useful in evaluating upper extremity motor deficits for clinical and research purposes.
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Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. METHODS: The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. RESULTS: A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). CONCLUSIONS: The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney.
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Procesamiento de Imagen Asistido por Computador/métodos , Corteza Renal/diagnóstico por imagen , Neoplasias Renales/cirugía , Radiofármacos/administración & dosificación , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Corteza Renal/anatomía & histología , Corteza Renal/fisiología , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Tamaño de los Órganos , Estudios Retrospectivos , Programas Informáticos , Ácido Dimercaptosuccínico de Tecnecio Tc 99mRESUMEN
BACKGROUND: MicroRNAs are small, gene-regulatory noncoding RNA species present in large amounts in milk, where they seem to be protected against degradative conditions, presumably because of their association with exosomes. OBJECTIVE: We monitored the relative stability of commercial dairy cow milk microRNAs during digestion and examined their associations with extracellular vesicles (EVs). METHODS: We used a computer-controlled, in vitro, gastrointestinal model TNO intestinal model-1 (TIM-1) and analyzed, by quantitative polymerase chain reaction, the concentration of 2 microRNAs within gastrointestinal tract compartments at different points in time. EVs within TIM-1 digested and nondigested samples were studied by immunoblotting, dynamic light scattering, quantitative polymerase chain reaction, and density measurements. RESULTS: A large quantity of dairy milk Bos taurus microRNA-223 (bta-miR-223) and bta-miR-125b (â¼109-1010 copies/300 mL milk) withstood digestion under simulated gastrointestinal tract conditions, with the stomach causing the most important decrease in microRNA amounts. A large quantity of these 2 microRNAs (â¼108-109 copies/300 mL milk) was detected in the upper small intestine compartments, which supports their potential bioaccessibility. A protocol optimized for the enrichment of dairy milk exosomes yielded a 100,000 × g pellet fraction that was positive for the exosomal markers tumor susceptibility gene-101 (TSG101), apoptosis-linked gene 2-interacting protein X (ALIX), and heat shock protein 70 (HSP70) and containing bta-miR-223 and bta-miR-125b. This approach, based on successive ultracentrifugation steps, also revealed the existence of ALIX-, HSP70-/low, and TSG101-/low EVs larger than exosomes and 2-6 times more enriched in bta-miR-223 and bta-miR-125b (P < 0.05). CONCLUSIONS: Our findings indicate that commercial dairy cow milk contains numerous microRNAs that can resist digestion and are associated mostly with ALIX-, HSP70-/low, and TSG101-/low EVs. Our results support the existence of interspecies transfer of microRNAs mediated by milk consumption and challenge our current view of exosomes as the sole carriers of milk-derived microRNAs.
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Bovinos , Digestión , MicroARNs/química , MicroARNs/metabolismo , Leche/química , Animales , Exosomas , Tracto Gastrointestinal , Modelos Biológicos , Factores de TiempoRESUMEN
OBJECTIVES: To evaluate the significance of intravesical prostatic protrusion as a predictor of early urinary continence recovery after laparoscopic radical prostatectomy. METHODS: A total of 242 patients who underwent laparoscopic radical prostatectomy were included in the study. Data on incontinence status and the number of pads required per day for urinary incontinence were collected. Urinary continence was defined as no pad use or occasional security pad use. Intravesical prostatic protrusion was measured by the vertical distance from the tip of the protruding prostate to the base of the urinary bladder in the sagittal plane of preoperative magnetic resonance imaging. Continence at 1, 3, 6 and 12 months postoperatively was assessed by dividing the patients into two groups based on the degree of intravesical prostatic protrusion. The correlation between preoperative factors and urinary continence after laparoscopic radical prostatectomy was examined. RESULTS: The urinary continence rates at postoperative month 1, 3, 6 and 12 were 19%, 50%, 79.8% and 92.1%, respectively. In the multivariate logistic analysis, intravesical prostatic protrusion was a significant independent predictive factor of early urinary continence at 1, 3, 6, 9 and 12 months. Markedly improved urinary continence was observed in the non-significant intravesical prostatic protrusion group (intravesical prostatic protrusion <5 mm) at all periods compared with the significant intravesical prostatic protrusion group (intravesical prostatic protrusion ≥5 mm; P < 0.05). CONCLUSIONS: These findings suggest that the likelihood of postoperative urinary incontinence in patients undergoing laparoscopic radical prostatectomy is markedly higher in those with larger intravesical prostatic protrusion, and that intravesical prostatic protrusion is correlated with the duration of postoperative urinary incontinence.
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Laparoscopía/métodos , Próstata/patología , Prostatectomía/métodos , Hiperplasia Prostática/cirugía , Incontinencia Urinaria/etiología , Anciano , Humanos , Pañales para la Incontinencia , Laparoscopía/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cuidados Posoperatorios , Cuidados Preoperatorios , Prostatectomía/efectos adversos , Recuperación de la Función , Vejiga Urinaria/patologíaRESUMEN
Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.
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Infecciones Bacterianas , Infertilidad , Enfermedades de Transmisión Sexual , Sífilis , Femenino , Humanos , Recién Nacido , Chlamydia trachomatis , Inflamación , República de Corea , Enfermedades de Transmisión Sexual/complicaciones , Enfermedades de Transmisión Sexual/epidemiología , Sífilis/complicacionesRESUMEN
Objective: The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. Methods: This is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either "favorable" or "intermediate" risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. Results: Of the primary patterns of treatment sequences (24 sequences), "sunitinib-pazopanib" and "sunitinib-everolimus-immunotherapy" showed the most beneficial results in both OS and PFS with significantly lower hazards than "sunitinib", which is the most commonly treated agent in Korea. Considering that the "TKI-TKI" structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be "sunitinib-everolimus-immunotherapy". Conclusion: Among several sequential therapy starting with TKIs, "sunitinib-everolimus- immunotherapy" was found to be the best scheme for mRCC patients with "favorable" or "intermediate" risks.
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PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.
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Antígenos de Superficie , Biomarcadores de Tumor , Glutamato Carboxipeptidasa II , Estadificación de Neoplasias , Células Neoplásicas Circulantes , Antígeno Prostático Específico , Humanos , Masculino , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Antígeno Prostático Específico/sangre , Anciano , Glutamato Carboxipeptidasa II/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Persona de Mediana Edad , Pronóstico , ARN Mensajero/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano de 80 o más Años , Estudios Prospectivos , Calicreínas/sangre , Calicreínas/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Estudios Retrospectivos , Clasificación del Tumor , Pronóstico , Organización Mundial de la SaludRESUMEN
Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders.
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Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Proteína HMGB1/metabolismo , Interacciones Huésped-Patógeno/inmunología , Inmunidad/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Animales , Apoptosis/efectos de los fármacos , Ciego/efectos de los fármacos , Ciego/patología , Quimiocinas/metabolismo , Ácido Clorogénico/administración & dosificación , Endotoxemia/complicaciones , Endotoxemia/tratamiento farmacológico , Endotoxemia/microbiología , Endotoxemia/prevención & control , Interacciones Huésped-Patógeno/efectos de los fármacos , Inflamación/complicaciones , Inflamación/metabolismo , Inflamación/patología , Molécula 1 de Adhesión Intercelular/metabolismo , Ligadura , Lipopolisacáridos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Punciones , Sepsis/complicaciones , Sepsis/microbiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Análisis de Supervivencia , Receptor Toll-Like 4/metabolismoRESUMEN
Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.