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1.
Int J Urol ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32172529

RESUMO

The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for non-muscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce "The Grading of Recommendations Assessment, Development and Evaluation" system modified to Japanese by the Medical Information Network Distribution Service.

2.
Jpn J Clin Oncol ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32115649

RESUMO

Although surgery with curative intent is critical for management of many localized cancers, multimodal therapy including neoadjuvant and adjuvant therapy has been introduced to increase the effectiveness of local control of surgery and prolong survival. However, strong evidence supporting the utility of such multimodal therapy is limited. The utility of perioperative chemotherapy has been extensively investigated in bladder cancer, and several randomized controlled trials have indicated the benefit of neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Regrettably, perioperative therapy for other urological cancers is controversial; therefore, no definitive conclusions have been drawn. Recently, the number of trials has rapidly increased due to the development of immune checkpoint inhibitors, used alone or in combination with other modalities. In this review, we summarize the current status and supporting evidence for perioperative therapies such as neoadjuvant and adjuvant therapies for urological cancers, including prostate cancer, urothelial cancer and renal cell carcinoma.

3.
Biochem Biophys Res Commun ; 524(2): 477-483, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32008742

RESUMO

Lipin-2 is a phosphatidate phosphatase with key roles in regulating lipid storage and energy homeostasis. LPIN2-genetic deficiency is associated with an autoinflammatory disorder, underscoring its critical role in innate immune signaling; however, the regulatory mechanisms underlying protein stability remain unknown. Here, we demonstrate that Lipin-2 interacts with ß-TRCP, a substrate receptor subunit of the SCFß-TRCP E3 ligase, and undergoes ubiquitination and proteasomal degradation. ß-TRCP-knockout in RAW264.7 macrophages resulted in Lipin-2 accumulation, leading to the suppression of LPS-induced MAPK activation and subsequent proinflammatory gene expression. Consistent with this, treatment with MLN4924, a Cullin-neddylation inhibitor that suppresses SCF E3 activity, increased Lipin-2 protein and concomitantly decreased Il1b expression. These findings suggested that ß-TRCP-mediated Lipin-2 degradation affects macrophage-elicited proinflammatory responses and could lead to new therapeutic approaches to treat inflammatory diseases.

4.
J Vet Med Sci ; 82(1): 14-22, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31776296

RESUMO

Instrument cost is a major problem for the transduction of DNA fragments and proteins into cells. Water-in-oil droplet electroporation (droplet-EP) was recently invented as a low-cost and effective method for the transfection of plasmids into cultured human cells. We here applied droplet-EP to livestock animal cells. Although it is difficult to transfect plasmids into bovine fibroblasts using conventional lipofection methods, droplet-EP enabled us to introduce an enhanced green fluorescent protein (EGFP)-expressing plasmid into bovine earlobe fibroblasts. The optimal transfection condition was 3.0 kV, which allowed 19.1% of the cells to be transfected. For swine earlobe fibroblasts, the maximum transfection efficacy was 14.0% at 4.0 kV. After transfection with droplet-EP, 69.1% of bovine and 76.5% of swine cells were viable. Furthermore, droplet-EP successfully transduced Escherichia coli recombinant EGFP into frozen-thawed bovine sperm at 1.5 kV. Flow cytometry analysis revealed that 71.5% of spermatozoa exhibited green fluorescence after transfection. Overall, droplet-EP is suitable for the transfection of plasmids and proteins into cultured livestock animal cells.

5.
Intern Med ; 59(1): 15-22, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484904

RESUMO

Objective The feasibility of continuous geriatric assessments (GAs) has not been evaluated fully in elderly patients with cancer. We prospectively investigated this issue by administering a recommended-GA set (r-GA) repeatedly to patients undergoing chemotherapy for gastrointestinal cancer on an outpatient basis. Methods We administered the r-GA before chemotherapy and every two months thereafter. Continuous GAs was defined as the completion of at least two assessments, including the pre-treatment evaluation. The r-GA included the Barthel Index [Basic Activities of Daily Living (BADL)], Mini-Mental State Examination-Japanese (MMSE-J), Instrumental Activities of Daily Living (IADL) scale, Vitality Index (VI), and Geriatric Depression Scale-15. We also used the Vulnerable Elders Survey (VES)-13 to screen overall vulnerability. We analyzed the correlations between each baseline GA score and the overall survival (OS) and the association between the OS and changes in each patient's GA scores over time. Patients Patients ≥65 years of age who presented to our department for initial consultation were enrolled and followed between December 2012 and January 2017. Results Twenty-one elderly patients (median age, 76 years old) were enrolled. GAs were completed within 20 minutes. In an age- and performance status (PS)-adjusted Cox proportional hazards analysis, the baseline BADL, MMSE-J, and VI scores correlated significantly with the OS (p=0.012, p=0.032, and p=0.012, respectively). During the clinical course, decreases in the MMSE-J and VES-13 scores were correlated with the OS (p=0.022 and p=0.019, respectively). Conclusion Outpatient GA administration is feasible. Low baseline BADL, MMSE-J, and VI scores and decreased MMSE-J and VES-13 scores over time may prognosticate the OS.

6.
Cancer Sci ; 111(2): 667-678, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31828882

RESUMO

Aberrant activation of NRF2 is as a critical prognostic factor that drives the malignant progression of various cancers. Cancer cells with persistent NRF2 activation heavily rely on NRF2 activity for therapeutic resistance and aggressive tumorigenic capacity. To clarify the metabolic features of NRF2-activated lung cancers, we conducted targeted metabolomic (T-Met) and global metabolomic (G-Met) analyses of non-small-cell lung cancer (NSCLC) cell lines in combination with exome and transcriptome analyses. Exome analysis of 88 cell lines (49 adenocarcinoma, 14 large cell carcinoma, 15 squamous cell carcinoma and 10 others) identified non-synonymous mutations in the KEAP1, NRF2 and CUL3 genes. Judging from the elevated expression of NRF2 target genes, these mutations are expected to result in the constitutive stabilization of NRF2. Out of the 88 cell lines, 52 NSCLC cell lines (29 adenocarcinoma, 10 large cell carcinoma, 9 squamous cell carcinoma and 4 others) were subjected to T-Met analysis. Classification of the 52 cell lines into three groups according to the NRF2 target gene expression enabled us to draw typical metabolomic signatures induced by NRF2 activation. From the 52 cell lines, 18 NSCLC cell lines (14 adenocarcinoma, 2 large cell carcinoma, 1 squamous cell carcinoma and 1 others) were further chosen for G-Met and detailed transcriptome analyses. G-Met analysis of their culture supernatants revealed novel metabolites associated with NRF2 activity, which may be potential diagnostic biomarkers of NRF2 activation. This study also provides useful information for the exploration of new metabolic nodes for selective toxicity towards NRF2-activated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Metabolômica/métodos , Mutação , Fator 2 Relacionado a NF-E2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proteínas Culina/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Pulmonares/genética , Fator 2 Relacionado a NF-E2/genética , Sequenciamento Completo do Exoma
7.
Molecules ; 24(23)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805752

RESUMO

Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.

8.
CEN Case Rep ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834568

RESUMO

Carboplatin is characterized by low nephrotoxicity, including acute tubular necrosis (ATN), compared to a conventional platinum complex due to its low accumulative property in the renal tubules. Therefore, there are extremely few reports of carboplatin-induced kidney injury and only one case has been histologically examined. Herein, we describe the case of a 53-year-old man who presented with acute kidney injury (AKI) that occurred after carboplatin administration and was diagnosed with biopsy-proven acute interstitial nephritis (AIN). To our knowledge, this is the second case report of carboplatin-related AIN. The patient was diagnosed with a pancreatic neuroendocrine tumor, and chemotherapy consisting of cisplatin and irinotecan was initiated. However, 1 week later, he was admitted to our institution with fever, fatigue and an increase in C-reactive protein (CRP) level. The chemotherapy regimen was altered to carboplatin and etoposide, but high fever occurred on the first day, and CRP re-elevation and AKI became apparent 9 days later. Renal biopsy revealed prominent inflammatory cell infiltration into the interstitium, which lead to the pathological diagnosis of AIN. On immunostaining for surface markers, CD3- and CD68-positive cells were found to be predominant, and CD20-positive cells were relatively few. Although the serum creatinine level increased to 6.81 mg/dL, it decreased to 1.43 mg/dL 15 days after steroid therapy. This case demonstrated that carboplatin-related kidney injury includes not only ATN but also AIN. Appropriate pathological diagnosis including renal biopsy and indications for steroid treatment should be carefully considered.

9.
IDCases ; 18: e00640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692509

RESUMO

Nocardia farcinica usually infects the respiratory tract and can sometimes cause central nervous system infections; however, it rarely infects the prostate. Here we report the first case of N. farcinica detected in the purulence specimen drained from a prostate abscess. A 70-year-old Japanese male receiving steroid and cyclosporine treatment came to our department with chief complaint of turbid urine. Computed tomography revealed a low-density lesion in his prostate. Antibiotic administration and prostatic drainage were effective. N. farcinica was detected in the cultures of urine and prostatic drainage purulence specimens. Nocardiosis should be included in the differential diagnosis in immunosuppressive patients with prostate abscess.

10.
Int J Urol ; 26(12): 1121-1127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512280

RESUMO

OBJECTIVES: To investigate the treatment pattern of non-muscle invasive bladder cancer patients among urologists in Japan, Korea and Taiwan, with emphasis on compliance with important treatment guidelines. METHODS: A Web-based questionnaire survey was conceived by representative members of each country's urological oncology society and was open from June 2016 to February 2017 to each society's members. Descriptive statistics and multinomial logistic regression analysis were used. RESULTS: A total of 2334 urologists were invited and 701 responded to the survey with a response rate of 30.0%. Instruments used during transurethral resection of bladder cancer varied significantly between countries and depended on their availability. The re-transurethral resection rate for pT1 or high-grade disease >50% of the time was significantly higher in Japan than in the other two countries, but the collective rate was just 49%. The frequency of intravesical therapy in intermediate- to high-risk disease was generally consistent across countries. However, the choice of agent between chemotherapy and bacillus Calmette-Guérin was significantly different between countries. Maintenance bacillus Calmette-Guérin was used <10% of the time by 45% of respondents, the most important reasons being fear of side-effects, followed by a lack of efficacy and shortage of drug supply. CONCLUSIONS: There are significant differences between Japan, Korea and Taiwan in the management of intermediate- to high-risk non-muscle invasive bladder cancer. The results of this survey can serve as the basis for joint efforts to develop common clinical guidelines.

11.
Clin Med Insights Case Rep ; 12: 1179547619867330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31391783

RESUMO

Epstein-Barr virus (EBV) infection might induce not only posttransplantation lymphoproliferative disorder (PTLD) but also leiomyosarcoma. We report a case of EBV-associated leiomyosarcoma concurrently with PTLD after renal transplantation. The patient was a 30-year-old woman who underwent living donor kidney transplantation at 27 years of age. Preoperative EBV viral capsid antibody immunoglobulin M, immunoglobulin G (IgG), and EBV nuclear antigen IgG were negative. Multiple lung and liver tumors were detected 1.5 years after transplantation. She was diagnosed with PTLD after tumor biopsy. Her EBV DNA was 110 copies/mL detected by real-time polymerase chain reaction when PTLD was diagnosed. She received dose reduction of immunosuppressive therapy and several chemotherapies. Because her hepatic lesion was still progressive while pulmonary lesion was reduced, a liver tumor biopsy was performed, but the biopsy specimens were necrotic. A left lateral segmentectomy was performed as a third biopsy for treatment-resistant hepatic lesion 2.5 years after her first PTLD diagnosis. Pathologically, she was diagnosed with EBV-associated leiomyosarcoma. She was treated with sirolimus, but died 7 months after the operation. This is the first case of the coincidence of leiomyosarcoma associated with EBV and PTLD. This case was exceedingly rare; however, we must consider the coincidence of leiomyosarcoma associated with EBV and PTLD when encountering treatment-resistant PTLD.

13.
Physiol Rep ; 7(14): e14193, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31353872

RESUMO

Ubiquitin-specific protease 2 (USP2) is considered to participate in the differentiation of myoblasts to myotubes, however, its functions in myoblasts under growth conditions remain elusive. In this study, we analyzed the physiological roles of USP2 in myoblasts using Usp2 knockout (KO) C2C12 cells as well as a USP2 specific inhibitor. In addition to the disruption of differentiation, clustered regularly interspaced short palindromic repeats/Cas9-generated Usp2KO cells exhibited inhibition of proliferation compared to parental C2C12 cells. Usp2KO cells reduced the accumulation of intracellular adenosine triphosphate (ATP) content and oxygen consumption. Moreover, Usp2KO cells had fragmented mitochondria, suggesting that mitochondrial respiration was inactive. The deficiency of Usp2 did not affect the enzymatic activities of respiratory chain complexes I, III, IV, and V. However, mitochondrial membrane permeability-evaluated using calcein AM-cobalt staining-was increased in Usp2KO cells. The membrane potential of Usp2KO cells was clearly decreased. Usp2KO cells accumulated reactive oxygen species (ROS) in the mitochondria. The USP2-selective inhibitor ML364 also increased the levels of mitochondrial ROS, and modulated the membrane potential and morphology of the mitochondria. These effects were followed by a decrement in the intracellular content of ATP. Based on these findings, we speculate that USP2 may be involved in maintaining the integrity of the mitochondrial membrane. This process ensures the supply of ATP in myoblasts, presumably leading to proliferation and differentiation.

14.
Int J Urol ; 26(10): 992-998, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342557

RESUMO

OBJECTIVES: To evaluate the effect of pretreatment C-reactive protein/albumin ratio and modified Glasgow prognostic score on the prognosis in patients with metastatic renal cell carcinoma. METHODS: A retrospective study was carried out in 176 patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitors. The effect of adding inflammatory prognostic scores to the International Metastatic Renal Cell Carcinoma Database Consortium model (International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio and International Metastatic Renal Cell Carcinoma Database Consortium-Glasgow prognostic score models) on overall survival was evaluated using receiver operating characteristic curves. The prognostic value of inflammatory prognostic scores (C-reactive protein/albumin ratio-modified Glasgow prognostic score) was tested using the Kaplan-Meier method and Cox proportional regression models. RESULTS: Patients were stratified into two groups using the cut-off value of 0.05: C-reactive protein/albumin ratio-low (<0.05) and C-reactive protein/albumin ratio-high (≥0.05). The area under the curve was significantly higher in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model (0.720) than that of the International Metastatic Renal Cell Carcinoma Database Consortium model (0.689) and the International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score model (0.703). Significant differences were observed in overall survival stratified by the number of risk factors in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio risk model between one or two and three or four factors (P < 0.001), and three or four and five or more factors (P = 0.001). For the patients in the International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk group, overall survival was significantly different between the C-reactive protein/albumin ratio-low and -high groups (P = 0.001), whereas it was not significantly different between the patients with one and two International Metastatic Renal Cell Carcinoma Database Consortium risk factors (P = 0.106). CONCLUSION: The C-reactive protein/albumin ratio is a simple and independent predictor of overall survival in patients with metastatic renal cell carcinoma. The predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model compared with the International Metastatic Renal Cell Carcinoma Database Consortium/International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score models.

15.
Hinyokika Kiyo ; 65(4): 117-121, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31247689

RESUMO

The patient was a 56-year-old female. She was referred to our department for further examination of right hydronephrosis in 2010. Computed tomography (CT) showed right hydronephrosis, and retrograde pyelography (RP) revealed stenosis of the right lower ureter. Urine cytology was negative. Transurethral biopsy of the right ureter was performed using ureteroscopic cup forceps and the histopathlogical diagnosis was ureteral amyloidosis. A whole-body search was performed, including rectal biopsy, but no evidence of amyloidosis was obtained. She was diagnosed with localized amyloidosis of the right ureter. A ureteral stent was indwelled and the patient was given occulusive dressing technique (ODT) therapy using dimethyl sulfoxide (DMSO) for 1 year. After ODT therapy, right hydronephrosis improved. After a 2-year followup, it worsened. ODT therapy was restarted and continued for 2 years. She consulted our department because of fever and right lumbago in April 2017 after a 4-month interruption of ODT therapy. CT revealed progression of the right hydronephrosis. A ureteral stent was indwelled and ODT therapy was restarted. The right hydronephrosis improved after 1 year. ODT therapy using DMSO was effective for localized ureteral amyloidosis, but periodic follow-up was necessary and ODT therapy was also effective when it recurred after the interruption of treatment.


Assuntos
Amiloidose , Dimetil Sulfóxido , Depuradores de Radicais Livres , Ureter , Doenças Ureterais , Amiloidose/tratamento farmacológico , Bandagens , Dimetil Sulfóxido/uso terapêutico , Feminino , Seguimentos , Depuradores de Radicais Livres/uso terapêutico , Humanos , Pessoa de Meia-Idade , Doenças Ureterais/tratamento farmacológico
16.
Jpn J Clin Oncol ; 49(6): 506-514, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30941424

RESUMO

BACKGROUND: Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups. METHODS: Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life. RESULTS: Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%). CONCLUSIONS: At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/mortalidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/etnologia , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade
17.
Nat Commun ; 10(1): 1567, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952864

RESUMO

Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in ß-oxidation following suppression of transactivation by PPARα. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARα to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARα activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARα activation upon fasting by promoting degradation of NCoR1 and thus regulates ß-oxidation and ketone bodies production.


Assuntos
Autofagia , Metabolismo dos Lipídeos , Correpressor 1 de Receptor Nuclear/metabolismo , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/fisiologia , Jejum , Corpos Cetônicos/metabolismo , Fígado/metabolismo , Camundongos , Correpressor 1 de Receptor Nuclear/fisiologia , Oxirredução , PPAR alfa
18.
Diabetes Care ; 42(5): 891-902, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30833372

RESUMO

OBJECTIVE: Clinicopathological characteristics, renal prognosis, and mortality in patients with type 2 diabetes and reduced renal function without overt proteinuria are scarce. RESEARCH DESIGN AND METHODS: We retrospectively assessed 526 patients with type 2 diabetes and reduced renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), who underwent clinical renal biopsy and had follow-up data, from Japan's nationwide multicenter renal biopsy registry. For comparative analyses, we derived one-to-two cohorts of those without proteinuria versus those with proteinuria using propensity score-matching methods addressing the imbalances of age, sex, diabetes duration, and baseline eGFR. The primary end point was progression of chronic kidney disease (CKD) defined as new-onset end-stage renal disease, decrease of eGFR by ≥50%, or doubling of serum creatinine. The secondary end point was all-cause mortality. RESULTS: Eighty-two patients with nonproteinuria (urine albumin-to-creatinine ratio [UACR] <300 mg/g) had lower systolic blood pressure and less severe pathological lesions compared with 164 propensity score-matched patients with proteinuria (UACR ≥300 mg/g). After a median follow-up of 1.9 years (interquartile range 0.9-5.0 years) from the date of renal biopsy, the 5-year CKD progression-free survival was 86.6% (95% CI 72.5-93.8) for the nonproteinuric group and 30.3% (95% CI 22.4-38.6) for the proteinuric group (log-rank test P < 0.001). The lower renal risk was consistent across all subgroup analyses. The all-cause mortality was also lower in the nonproteinuric group (log-rank test P = 0.005). CONCLUSIONS: Patients with nonproteinuric diabetic kidney disease had better-controlled blood pressure and fewer typical morphological changes and were at lower risk of CKD progression and all-cause mortality.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/metabolismo , Rim/patologia , Proteinúria/complicações , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/patologia , Biópsia , Estudos de Coortes , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Japão , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/patologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Urinálise
19.
Clin Genitourin Cancer ; 17(3): e440-e446, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30772204

RESUMO

PURPOSE: To investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis. PATIENTS AND METHODS: We retrospectively evaluated 176 patients with metastatic renal-cell carcinoma who were treated with tyrosine kinase inhibitors as first-line therapy in 5 hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the models was evaluated using the Cohen κ coefficient. Oncologic outcomes were compared between the agreement and disagreement groups. RESULTS: The number of patients with agreement, upgrade, and downgrade was 135 (77%), 39 (22%), and 2 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor risk group was most frequent (n = 34, 19%). The Cohen κ coefficient for agreement was substantial, with κ = 0.613 (P < .001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Neutrophil count, hemoglobin, serum calcium concentration, and C-reactive protein were significantly different between the groups. CONCLUSION: Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with metastatic renal-cell carcinoma. The inclusion of systematic inflammation markers in a risk model may be essential for prognosis prediction.

20.
Am J Hypertens ; 32(5): 486-491, 2019 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-30689693

RESUMO

BACKGROUND: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis. METHODS: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period. RESULTS: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (ß = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years. CONCLUSIONS: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis.

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