RESUMEN
OBJECTIVES: This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. METHODS: This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. RESULTS: In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). CONCLUSIONS: IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.
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Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Radioterapia de Intensidad Modulada/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/radioterapiaRESUMEN
OBJECTIVES: To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. METHODS: Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. RESULTS: Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. CONCLUSIONS: The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.
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Trasplante de Riñón , Donadores Vivos , Creatinina , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Urinary tract infection (UTI) is one of the most common infectious complications in kidney transplant recipients. The aims of our study were to identify possible predictive factors for UTI and advocate for the management of UTI after kidney transplantation (KT). METHODS: Between January 2013 and December 2018, 182 adult patients with end-stage kidney disease who underwent KT were retrospectively analyzed. Patients who had urinary symptoms and positive urine culture were diagnosed with UTI. The types of urinary bacteria causing UTIs were also examined. RESULTS: UTIs occurred in forty-one patients (25.1%), and the median time to UTI onset (UTI-free survival) after KT was 189 days. The Cox hazard regression analysis showed that the predictive factors for UTI onset were as follows: posttransplant urinary catheterization, including indwelling urinary catheterization and clean intermittent catheterization; a maximum bladder capacity before KT of less than 150 ml; and a low serum albumin level at 1 month after KT. The most common causative agent was Escherichia coli (56.6%), followed by Enterococcus spp. (15.6%) and Klebsiella spp. CONCLUSIONS: Kidney transplant recipients with prolonged postoperative malnutrition, posttransplant voiding dysfunction and/or urinary storage disorder had an increased risk of UTI. Bladder function tests, such as uroflowmetry, postvoid residual urine tests, and urodynamic tests, were needed to predict UTI. For patients with malnutrition, care should be taken to ensure sufficient calorie intake. Kidney transplant recipients who develop UTI should be treated as complicated UTI patients.
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Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/etiología , Infecciones Urinarias/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Albúmina Sérica/análisis , Infecciones Urinarias/terapiaRESUMEN
We retrospectively compared the post-transplantation graft survival and the donor's estimated glomerular filtration rates (eGFRs) following living donor kidney transplantations (LDKTs) involving medically complex living donors (MCLDs) (the elderly and patients with obesity, hypertension, diabetes mellitus, or reduced renal function) and standard living donors (SLDs). The clinical data on patients who underwent LDKTs at our institution from 2006-2019, including 192 SLDs and 99 MCLDs, were evaluated. Regarding recipients, the log-rank test and multivariable Cox proportional hazards analyses showed a higher incidence of overall and death-censored graft loss in the recipients who received kidneys from MCLDs (Hazard ratio = 2.16 and 3.25, P = 0.015 and 0.004, respectively), after adjusting for recipient-related variables including age, sex, duration of dialysis, ABO compatibility, and donor-specific antibody positivity. Regarding donors, a linear mixed model showed significantly lower postdonation eGFRs (-2.25 ml/min/1.73 m2 , P = 0.048) at baseline in MCLDs than SLDs, but comparable change (difference = 0.01 ml/min/1.73 m2 /year, P = 0.97). In conclusion, although kidneys from MCLDs are associated with impaired graft survival, the donation did not adversely affect the MCLDs' renal health in at least the short-term. LDKTs involving carefully selected MCLDs would be an acceptable alternative for recipients with no SLDs.
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Trasplante de Riñón , Donadores Vivos , Anciano , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Sistema de Registros , Estudios RetrospectivosRESUMEN
BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease and is associated with increased mortality; however, limited data are available on whether kidney transplantation can improve muscle wasting. Therefore, the present study aimed to assess changes in body composition before and after kidney transplantation. METHODS: Between April 2015 and January 2018, 80 de novo consecutive adult patients with end-stage kidney disease who underwent kidney transplantation were prospectively enrolled. Muscle and fat masses were measured via bioelectrical impedance analysis using InBody 770 at - 2 and 7 days and 3, 6, and 12 months after transplantation. Presarcopenia is characterized by low muscle mass according to the skeletal muscle mass index. Changes in body composition and prevalence of presarcopenia were compared before and after transplantation. Risk factors for presarcopenia were identified using logistic regression analysis. RESULTS: Muscle mass significantly decreased at 3 months after transplantation. Consequently, the prevalence of presarcopenia was significantly higher after transplantation (3 months: 47.5%, 6 months: 42.5%, and 12 months: 38.8%) than that before transplantation (25.0%). Similarly, the body fat percentage was significantly higher at 3 months after transplantation than that before transplantation. Presarcopenia before transplantation was an independent risk factor for presarcopenia at 12 months after transplantation (odds ratio: 51.8, 95% CI 5.77-464, p < 0.001). CONCLUSIONS: Muscle wasting deteriorated and body fat percentage increased from 3 months after kidney transplantation. Presarcopenia before transplantation led to presarcopenia after transplantation, which may deteriorate with an increase in body fat percentage.
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Composición Corporal , Trasplante de Riñón , Complicaciones Posoperatorias/epidemiología , Sarcopenia/epidemiología , Adulto , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios ProspectivosRESUMEN
Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of transplantation. There is no clear consensus on the treatment of PTLD. In most cases, the pathogenetic mechanism of PTLD involves the Epstein-Barr virus (EBV). We report the case of an elderly kidney transplant recipient who developed EBV-positive monomorphic T-cell PTLD 14 years after transplantation. Conversion from conventional immunosuppressants to everolimus induced complete remission of PTLD accompanied by a decrease in blood EBV-DNA level without chemotherapy.
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Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/virología , Inducción de Remisión , Anciano , Herpesvirus Humano 4 , Humanos , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Receptores de TrasplantesRESUMEN
BACKGROUND: Hepatitis E virus (HEV) infection can lead to chronic hepatitis in solid organ transplant recipients. To investigate whether HEV infection influences outcomes following kidney transplantation, we examined the prevalence of HEV infection and clinical characteristics of kidney transplant recipients in our hospital. METHODS: Our cross-sectional study included 184 kidney transplant recipients. Blood samples were obtained from all patients to detect anti-HEV immunoglobulin (Ig)A, IgM, and IgG by enzyme-linked immunosorbent assay and HEV RNA by reverse transcription polymerase chain reaction. Clinical data were collected from medical charts for all patients. RESULTS: The prevalence of anti-HEV IgG was 8/184 (4.3%). Anti-HEV IgA, anti-HEV IgM, and HEV RNA were not detected in any patients. Compared to their anti-HEV IgG-negative counterparts, anti-HEV IgG-positive patients were significantly older at the time of transplantation, and they were more likely to receive kidneys from deceased donors. No significant differences in other characteristics such as the prevalence of primary cause of end-stage renal disease, blood transfusion, and immunosuppressive therapy use; liver and renal function; and the frequencies of hepatitis B and hepatitis C virus infection were observed according to the patients' anti-HEV IgG status. CONCLUSION: HEV infection had no significant influence on the outcomes of kidney transplantation at our institution. However, HEV infection should be recognized in kidney transplant recipients similarly as hepatitis B and hepatitis C virus infection in cases of liver dysfunction.
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Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis E/inmunología , Hepatitis E/epidemiología , Trasplante de Riñón/efectos adversos , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Hepatitis E/inmunología , Virus de la Hepatitis E/genética , Humanos , Huésped Inmunocomprometido , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral/análisis , Estudios Seroepidemiológicos , Receptores de Trasplantes , Adulto JovenRESUMEN
Diacylglycerol lipase alpha (DAGLA), which catalyzes the hydrolysis of diacylglycerol to 2-arachidonoylglycerol and free fatty acid, is required for axonal growth during the brain development and for retrograde synaptic signaling at mature synapses. So far, no information was found regarding the possible role of DAGLA in human tumorigenesis. Thus, the current study sought to clarify the contribution of DAGLA in oral squamous cell carcinomas (OSCCs) and assess the clinical possibilities for OSCC treatment. Using real-time quantitative reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry, we found a significant up-regulation of DAGLA in OSCCs compared with normal cells and tissues both at mRNA and protein expression levels. Knockdown models in OSCC-derived cell lines for DAGLA (siDAGLA) and treatment with a lipase inhibitor (orlistat) showed several depressed cellular functions, including cellular proliferation and migratory activities through cell-cycle arrest at G1 phase. Furthermore, we found that DAGLA-positive OSCC samples were correlated highly with the primary tumoral size. We concluded that DAGLA may be a key determinant in tumoral progression and might be a therapeutic target for OSCCs.
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Carcinogénesis/genética , Carcinoma de Células Escamosas/patología , Ciclo Celular/efectos de los fármacos , Lipoproteína Lipasa/metabolismo , Neoplasias de la Boca/patología , Animales , Carcinoma de Células Escamosas/enzimología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Lipoproteína Lipasa/antagonistas & inhibidores , Lipoproteína Lipasa/genética , Ratones , Ratones Desnudos , Neoplasias de la Boca/enzimología , Orlistat/farmacología , Cultivo Primario de Células , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Hypercalcemia and bone mineral density (BMD) loss are serious problems associated with post-transplant chronic kidney disease-mineral and bone disorder. The present study aimed to clarify the effects of denosumab on hypercalcemia complicated with BMD loss in kidney transplant recipients. MATERIALS AND METHODS: Among 100 consecutive adult kidney transplant recipients, 16 patients with serum corrected Ca (cCa) levels ≥ 11.0 mg/dL were included in a severe hypercalcemia group. In 14 patients (excluding 2 patients who underwent parathyroidectomy) with severe hypercalcemia and low BMD at the lumbar spine (T-score < -1.0), 60 mg of denosumab were administered by subcutaneous injection at 6-month intervals. Serum cCa and alkaline phosphatase (ALP) levels were analyzed before and after denosumab administration. Lumbar spinal BMD was compared between, before, and 12 months after denosumab administration. RESULTS: Both serum cCa (11.7 mg/dL) and ALP (525 U/L) levels declined promptly after denosumab administration, with only the cCa level showing rebound. Additionally, serum cCa and ALP levels were significantly lower after denosumab administration (all time points) than before denosumab administration. Lumbar spinal BMD increased significantly 12 months after denosumab administration when compared with the value before denosumab administration in both anterior-posterior (increase rate: 5.0%) and lateral (increase rate: 5.4%) projections. CONCLUSION: Denosumab could improve hypercalcemia and BMD loss in kidney transplant recipients. Therapeutic intervention involving denosumab should be considered for hypercalcemia and BMD loss associated with post-transplant chronic kidney disease-mineral and bone disorder.
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Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Denosumab/farmacología , Hipercalcemia/sangre , Hipercalcemia/tratamiento farmacológico , Trasplante de Riñón , Adulto , Fosfatasa Alcalina/sangre , Calcio/sangre , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Hypercalcemia (HC) after kidney transplantation (KTx) can deteriorate both graft and patient survival. However, HC as a clinical condition and its clinical significance after KTx remain unknown. We evaluated the prevalence and risk factors of early HC after KTx. METHODS: We performed a nested case-control study using a cohort of 100 KTx patients. KTx patients were divided into the HC and normocalcemia (NC) groups based on the baseline serum-corrected calcium (cCa) levels (≥ 10.5 and < 10.5 mg/dL) within 1 year after KTx. RESULTS: Overall, the median value of maximum serum cCa level within 1 year after KTx was 10.1 (9.1-13.8) mg/dL. Of the 100 KTx patients within the cohort, 31 patients (31.0%) were classified as the HC group. The maximum serum cCa level was reached significantly earlier in the HC group compared with the NC group (2 vs. 4 months, p = 0.024). In univariate analysis, the risk factors of early HC after KTx were dialysis duration ≥ 10 years, serum cCa level the day before KTx, and cinacalcet administration before KTx. Among these risk factors, serum cCa level the day before KTx and cinacalcet administration before KTx were identified as significant independent risk factors of early HC after KTx in multivariate analysis. CONCLUSIONS: One-third of the KTx patients presented early HC within 1 year after KTx. Early HC after KTx resulted from persistent hyperparathyroidism. Therapeutic strategies to manage HC after KTx must be established.
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Calcio/sangre , Hipercalcemia/epidemiología , Trasplante de Riñón/efectos adversos , Adulto , Biomarcadores/sangre , Femenino , Humanos , Hipercalcemia/sangre , Hipercalcemia/diagnóstico , Hiperparatiroidismo/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.
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Antioxidantes/metabolismo , Glucuronidasa/metabolismo , Riñón/enzimología , Estrés Oxidativo , Anciano , Animales , Femenino , Regulación Enzimológica de la Expresión Génica , Glucuronidasa/deficiencia , Glucuronidasa/genética , Humanos , Proteínas Klotho , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
BACKGROUND: Renal prognosis in living kidney donors with diabetes is currently not known. In this study, we sought to investigate renal prognosis in living kidney donors with diabetes. METHODS: We retrospectively investigated 241 living kidney donors who underwent nephrectomy at Jichi Medical University Hospital between January 2000 and December 2015. Donors with a follow-up period of less than 1 year were excluded. The remaining donors were divided into a diabetic group and a non-diabetic group. Their clinical parameters before donation and renal prognosis after donation were compared. RESULTS: Of the 241 donors, 16 were excluded due to their follow-up period being less than 1 year. Of the remaining 225 donors, 14 were diabetic and 211 were non-diabetic. There were no significant differences in variables at pre-donation. The median follow-up period was 4.3 (1.5-10.7) and 4.6 (1.0-13.0) years in kidney donors with and without diabetes, respectively. At the end of follow-up, the estimated glomerular filtration rate was 51.7 ± 7.1 ml/min/1.73 m2 in the diabetic group and 52.1 ± 12.2 ml/min/1.73 m2 (p = 0.906) in the non-diabetic group; urine albumin excretion was 9.5 (2-251) mg/day (or mg/g creatinine) in the diabetic group and 6 (0-626) mg/day (or mg/g creatinine) in the non-diabetic group (p = 0.130); and urine protein excretion was 0.079 (0-0.41) g/day in the diabetic group and 0.051 (0-3.7) g/day in the non-diabetic group (p = 0.455). CONCLUSIONS: There were no significant differences in short-term renal prognosis between kidney donors with and without diabetes.
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Diabetes Mellitus/orina , Donadores Vivos/estadística & datos numéricos , Nefrectomía , Anciano , Diabetes Mellitus/patología , Femenino , Humanos , Riñón/patología , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
TEA domain transcription factor 4 (TEAD4), which has critical functions in the process of embryonic development, is expressed in various cancers. However, the important role of TEAD4 in human oral squamous cell carcinomas (OSCCs) remain unclear. Here we investigated the TEAD4 expression level and the functional mechanism in OSCC using quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. Furthermore, TEAD4 knockdown model was used to evaluate cellular proliferation, cell-cycle analysis, and the interaction between TEAD4 and Yes-associated protein (YAP) which was reported to be a transcription coactivator of cellular proliferation. In the current study, we found that TEAD4 expression increased significantly in vitro and in vivo and correlated with tumoral size in OSCC patients. TEAD4 knockdown OSCC cells showed decreased cellular proliferation resulting from cell-cycle arrest in the G1 phase by down-regulation of cyclins, cyclin-dependent kinases (CDKs), and up-regulation of CDK inhibitors. We also found that the TEAD4-YAP complex in the nuclei may be related closely to transcriptions of G1 arrest-related genes. Taken together, we concluded that TEAD4 might play an important role in tumoral growth and have potential to be a therapeutic target in OSCCs.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma de Células Escamosas/genética , Proteínas de Unión al ADN/genética , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/genética , Proteínas Musculares/genética , Fosfoproteínas/genética , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Línea Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proliferación Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclina E/genética , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/genética , Quinasa 6 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Proteínas Musculares/antagonistas & inhibidores , Proteínas Musculares/metabolismo , Fosfoproteínas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Factores de Transcripción de Dominio TEA , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Transcripción Genética , Proteínas Señalizadoras YAPRESUMEN
Zrt-Irt-like protein 4 (ZIP4) is critical molecule for proper mammalian development and releasing zinc from vesicular compartments. Recent studies suggested that ZIP4 plays an important role of tumor progression in pancreatic, prostate, and hepatocellular cancers, however, little is known about the detail mechanism of ZIP4 in their cancers. In the present study, we examined the possibility of ZIP4 as a new molecular target for oral squamous cell carcinoma (OSCC). We evaluated ZIP4 expression in OSCC-derived cell lines and primary OSCC samples by quantitative RT-PCR, immunoblotting, and immunohistochemistry (IHC). We also analyzed the clinical correlation between ZIP4 status and clinical behaviors in patients with OSCC. In addition, ZIP4 knockdown cells (shZIP4 cells) and ZnCl2 treatment were used for functional experiments, including cellular proliferation assay, zinc uptake assay, and cell-cycle analysis. ZIP4 mRNA and protein were up-regulated significantly in OSCCs compared with normal counterparts in vitro and in vivo. IHC showed that ZIP4 expression in the primary OSCC was positively correlated with primary tumoral size. The shZIP4 cells showed decrease accumulation of intercellular zinc and decreased cellular growth by cell-cycle arrest at the G1 phase, resulting from up-regulation of cyclin-dependent kinase inhibitors and down-regulation of cyclins and cyclin-dependent kinases. Since cellular growth of OSCC cells after treatment with zinc was significantly greater than control cells, we speculated that intercellular ZnCl2 accumulation is an important factor for cellular growth. Consistent with our hypothesis, not only decreased zinc uptake by ZIP4 knockdown but also chelating agent, N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), showed inhibitory effects of cellular proliferation. Therefore, our data provide evidence for an essential role of ZIP4 and intracellular zinc for tumoral growth in OSCC, suggesting that zinc uptake might be a potential therapeutic targeting event for OSCCs.
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Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte de Catión/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/metabolismo , Zinc/química , Carcinogénesis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Quelantes/química , Cloruros/química , Suplementos Dietéticos , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Etilenodiaminas/química , Humanos , Inmunohistoquímica , ARN Interferente Pequeño/metabolismo , Compuestos de Zinc/químicaRESUMEN
We recently identified a novel family of neutrophil-activating peptides including mitocryptide-1 and mitocryptide-2 (MCT-2) that are endogenously produced from various mitochondrial proteins. Among them, MCT-2 is an N-formylated pentadecapeptide derived from mitochondrial cytochrome b and is found to promote neutrophilic migration and phagocytosis efficiently. Signaling mechanisms of neutrophil activation by MCT-2 have been investigated at the cellular level, and MCT-2 has been demonstrated to be an endogenous specific ligand for formyl peptide receptor-2 (also referred to as formyl peptide receptor-like 1). It was also found that MCT-2 promoted neutrophilic functions via the activation of Gi2 proteins and phosphorylation of ERK1/2 consecutively. However, the physiological production, distribution, and functions of MCT-2 are not yet elucidated. Here, to investigate the roles of MCT-2 in vivo, we generated monoclonal antibodies (mAbs) against human MCT-2 (hMCT-2) that have two different characteristics. One mAb, NhM2A1, not only bound to the region of positions 10-15 of hMCT-2 but also recognized its C-terminal cleavage site that is presumably produced upon enzymatic hydrolysis of cytochrome b, indicating that NhM2A1 specifically interacts with hMCT-2 but not its parent protein. Moreover, we succeeded in acquiring a specific neutralizing mAb, NhM2A5, which blocks the bioactivities of hMCT-2. Specifically, NhM2A5 inhibited hMCT-2-induced ß-hexosaminidase release in neutrophilic/granulocytic differentiated HL-60 cells by binding to the region of positions 5-12 of hMCT-2. Functional analysis using obtained mAbs that specifically recognize hMCT-2 but not its parent protein, cytochrome b, and that neutralize bioactivities of hMCT-2 is expected to reveal the physiological roles of MCT-2, which are presently very difficult to investigate. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
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Anticuerpos Monoclonales/inmunología , Proteínas Mitocondriales/inmunología , Animales , Citocromos b/metabolismo , Ensayo de Inmunoadsorción Enzimática , Células HL-60 , Humanos , Ratones , Proteínas Mitocondriales/metabolismo , Péptidos/inmunología , Péptidos/metabolismo , PorcinosRESUMEN
The effects of stone composition on transurethral lithotripsy (TUL) have not been sufficiently elucidated. The purpose of this study was to identify how calcium phosphate stone composition impacts TUL. Two hundred eighty-nine cases of semi-rigid and/or flexible TUL for upper urinary tract calculi were reviewed retrospectively. Inclusion criteria were a preoperative assessment by noncontrast computed tomography (NCCT) and a stone composition analysis. Small stones and those without calcium composition were excluded. Stone core radiodensity (SCR) was measured by taking the average of the upper 3 of 5 points in the proximity of the center of the stone on NCCT. Fifty-three patients with calcium phosphate composition (CaP) and 118 patients with calcium oxalate and without phosphate composition were eligible for analysis. SCR was significantly higher in the CaP group (pï¼0.01). The CaP patient group needed a significantly longer operation time (pï¼0.014) and more laser energy (pï¼0.085), and tended to have a lower rate of complete lithotripsy (pï¼0.096) and higher incidence of postoperative pyelonephritis (pï¼0.181). Stones containing calcium phosphate are harder, demand more laser energy, and require a longer operating time. NCCT evaluation can estimate stone composition preoperatively, and may be a useful tool for predicting operative outcomes.
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Fosfatos de Calcio/química , Litotripsia por Láser , Cálculos Urinarios/química , Cálculos Urinarios/terapia , Oxalato de Calcio/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Cálculos Urinarios/diagnóstico por imagenRESUMEN
Upper urinary tract calculi are common; however, there is no recommended treatment selection for elderly patients. Ureteroscopic holmium laser lithotripsy (URS lithotripsy) is minimally invasive, and it provides a high stone-free rate (SFR) treatment for upper urinary tract calculi. Here, we retrospectively evaluated the surgical outcomes of URS lithotripsy after dividing the 189 cases into 3 groups by patient age: the 'ï¼65 group' (ï¼65 years old, nï¼108), the '65-74 group' (65-74 years old, nï¼42), and the ' 75 group' ( 75 years old, nï¼39). The patients' characteristics, stone status, and perioperative outcomes were assessed. The 65-74 group and the 75 group had a significantly higher prevalence of hypertension compared to theï¼65 group. Compared to theï¼65 group, the 65-74 group had a significantly higher prevalence of hyperlipidemia, and the 75 group had significantly higher the American Society of Anesthesiologists (ASA) scores. Despite these preoperative risk factors, SFR and postoperative pyelonephritis in the 65-74 group and the 75 group were similar to those of theï¼65 group. In conclusion, URS lithotripsy is the preferred treatment for upper urinary tract calculi, even for elderly patients who have multiple preoperative risk factors.
Asunto(s)
Litotripsia por Láser/instrumentación , Litotripsia por Láser/métodos , Ureteroscopía/instrumentación , Cálculos Urinarios/cirugía , Anciano , Femenino , Holmio , Humanos , Complicaciones Intraoperatorias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Ureteroscopía/métodosRESUMEN
Introduction: Histological outcome of the targeted focal therapy is in principle confirmed by targeted needle biopsy from the treated area in clinical trial. Herein, we report a rare case in which the MFT was followed by RARP. Case presentation: A 68-year-old man with PSA 9.6 ng/mL and PI-RADS 4 lesion in the right transition zone on multi-parametric MRI underwent MR/ultrasound fusion-guided targeted biopsy, which revealed grade-group 1 cancer. Targeted focal therapy with microwave ablation was performed, resulting in disappearance of the PI-RADS 4 lesion at post-operative 4 months. However, PSA rose to 11.5 ng/mL, and a new PI-RADS 4 lesion, was identified in the left peripheral zone. RARP was performed to reveal new grade-group 3 cancer, and no viable cells in the previously treated area with MFT. Conclusion: RARP was safely performed even after MFT and proved the pathological complete response of microwave ablation.
RESUMEN
Since 2002, the Japan Young Psychiatrists Organization (JYPO) has conducted an annual face-to-face Course for Academic Development of Psychiatrists (CADP). Since 2021, we held two international online meetings and studied whether it was possible to acquire professional and leadership skills. We found that participants were able to acquire knowledge and become acquainted with professional and leadership skills in online meetings. However, they didn't enough enable participants to get to know each other, develop friendships, or acquire professional and leadership skills. The advantages of online meetings included lower cost, avoiding infection during the pandemic, and the easy use of course materials.
Asunto(s)
Liderazgo , Psiquiatría , Humanos , Japón , PandemiasRESUMEN
Lower limbs' arterial calcification is significantly associated with the clinical severity of lower extremity artery disease (LEAD) in patients undergoing hemodialysis (HD). However, the association between arterial calcification of the lower limbs and long-term clinical outcomes in patients on HD has not been elucidated. Calcification scores of the superficial femoral artery (SFACS) and below-knee arteries (BKACS) were quantitatively evaluated in 97 HD patients who were followed for 10 years. Clinical outcomes, including all-cause and cardiovascular mortality, cardiovascular events, and limb amputation were evaluated. Risk factors for clinical outcomes were evaluated using univariate and multivariate Cox proportional hazard analyses. Furthermore, SFACS and BKACS were divided into three groups (low, middle, and high), and their associations with clinical outcomes were evaluated using Kaplan-Meier analysis. SFACS, BKACS, C-reactive protein, serum albumin, age, diabetes, presence of ischemic heart disease, and critical limb-threatening ischemia were significantly associated with 3-year and 10-year clinical outcomes in the univariate analysis. Multivariate analysis showed that SFACS was an independent factor associated with 10-year cardiovascular events and limb amputations. Kaplan-Meier life table analysis showed that higher SFACS and BKACS levels were significantly associated with cardiovascular events and mortality. In conclusion, long-term clinical outcomes and the risk factors in patients undergoing HD were evaluated. Arterial calcification of the lower limbs was strongly associated with 10-year cardiovascular events and mortality in patients undergoing HD.