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1.
Int J Mol Sci ; 25(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474084

RESUMO

Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for its treatment. Despite these advances, the molecular mechanisms underlying the progression to CRPC remain unclear, and currently, no effective treatments for CRPC are available. Here, we characterized the key genes involved in CRPC progression to gain insight into potential therapeutic targets. Bicalutamide-resistant prostate cancer cells derived from LNCaP were generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified. The Cytohubba plug-in in Cytoscape was used to identify seven hub genes (ASNS, AGT, ATF3, ATF4, DDIT3, EFNA5, and VEGFA) associated with CRPC progression. Among these hub genes, ASNS and DDIT3 were markedly upregulated in CRPC cell lines and CRPC patient samples. The patients with high expression of ASNS and DDIT3 showed worse disease-free survival in patients with The Cancer Genome Atlas (TCGA)-prostate adenocarcinoma (PRAD) datasets. Our study revealed a potential association between ASNS and DDIT3 and the progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying CRPC progression, aiming to improve clinical efficacy in CRPC treatment.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Linhagem Celular Tumoral , Biologia Computacional , Neoplasias de Próstata Resistentes à Castração/patologia , Fator de Transcrição CHOP , Resultado do Tratamento
2.
BMC Cancer ; 23(1): 304, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013485

RESUMO

BACKGROUND: Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. METHODS: This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. DISCUSSION: This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. TRIAL REGISTRATION: NCT05046756. Registered on 11 May 2021.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Humanos , Resultado do Tratamento , Estudos Prospectivos , Medicina de Precisão , Neoplasias Colorretais/cirurgia
3.
BMC Urol ; 22(1): 192, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434618

RESUMO

OBJECTIVES: To evaluate the incidence of positive cystic fluid cytology and its risk factors in cystic renal cell carcinoma (RCC) addressing its implication on the current surgical practice. METHODS: All clinically diagnosed Bosniak III, IV cystic renal masses from March 2019 to August 2022 were studied prospectively. Database of patients' demographics and cystic tumor characteristics were recorded. Partial or radical nephrectomies were performed by either laparoscopic or robotic approach. Cystic fluid was collected right after specimen retrieval in the surgical field and examined by pathologist. Cytology results were compared to the demographic, perioperative variables using univariate and multivariate analysis. RESULTS: A total of 70 patients of histologically confirmed cystic RCC were included. Sixty seven patients underwent radical nephrectomy with laparoscopic or robotic approaches, while 3 patients underwent radical nephrectomy. There was no intraoperative cystic rupture or fluid spillage. Positive cystic fluid cytology findings were identified in 34 (48.6%) patients, while negative cystic fluid cytology were identified in 36 (51.4%) cases. Definite malignant cells were observed in 28 patients while the other six patients showed highly suspicious atypical cells. Histologically, 24 (70.8%) patients were proven clear cell RCC and 25 (73%) showed Fuhrman grade 1 or 2 in final histologic review in positive group. Univariate and multivariate regression analysis between positive and negative cytology groups showed that the presence of the malignant cells in cystic fluid was significantly associated with patients' age (> 55 years) and Bosniak grade of cystic tumor (p < 0.05). CONCLUSIONS: Definite malignant cells in cystic fluid cytology were observed through our study. Additionally, patients' age (> 55 years) and Bosniak grade were the significant risk factors of positive cytology in cystic RCC. Therefore, necessity of meticulous manipulation of cystic renal tumors, despite their clinical features, should not be underemphasized to avoid the least possible tumor cell seeding in case of cystic rupture when operating such high risk of positive cytology.


Assuntos
Carcinoma de Células Renais , Doenças Renais Císticas , Neoplasias Renais , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Doenças Renais Císticas/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Rim/patologia
4.
Int J Urol ; 29(9): 939-946, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35137466

RESUMO

OBJECTIVES: To evaluate postoperative complications following robot-assisted radical cystectomy in patients diagnosed with bladder cancer and reveal if there are predictors for postoperative complications. METHODS: Prospectively collected medical records of 730 robot-assisted radical cystectomy patients between 2007/04 and 2019/05 in 13 tertiary referral centers were reviewed. Perioperative outcomes were compared between two groups by postoperative complications (complication vs non-complication). We assessed recurrence-free survival, cancer-specific survival, and overall survival between groups. Regression analyses were implemented to identify factors associated with postoperative complications. RESULTS: Any total and high-grade complication (Clavien-Dindo grade ≥3) rates were 57.8% and 21.1%, respectively. Patients in complication group had significantly higher proportion of diabetes mellitus (P = 0.048), chronic kidney disease (P = 0.011), dyslipidemia (P < 0.001), longer operation time (P = 0.001), more estimated blood loss (P = 0.001), and larger intraoperative fluid volume (P < 0.001). There was a significant difference in cancer-specific survival (log-rank P = 0.038, median cancer-specific survival: both groups not reached). Dyslipidemia (odds ratio 2.59, P = 0.002) and intraoperative fluid volume (odds ratio 1.0002, P = 0.040) were significantly associated with high-grade postoperative complications. Diabetes mellitus (odds ratio 1.97, P = 0.028), chronic kidney disease (odds ratio 1.89, P = 0.046), dyslipidemia (odds ratio 5.94, P = 0.007), and intraoperative fluid volume (odds ratio 1.0002, P = 0.009) were significantly associated with any postoperative complications. CONCLUSIONS: Patients with diabetes mellitus, chronic kidney disease, dyslipidemia, or a relatively large intraoperatively infused fluid volume are more likely to develop postoperative complications. Patients with postoperative complications might have a possibility of lower cancer-specific survival rate.


Assuntos
Insuficiência Renal Crônica , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Cistectomia/efeitos adversos , Análise Fatorial , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
5.
N Engl J Med ; 378(15): 1408-1418, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29420164

RESUMO

BACKGROUND: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODS: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTS: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONS: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Tioidantoínas/uso terapêutico , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Método Duplo-Cego , Exantema/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/prevenção & controle , Modelos de Riscos Proporcionais , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Tioidantoínas/efeitos adversos
6.
BJU Int ; 127(2): 182-189, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32682331

RESUMO

OBJECTIVES: To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS: Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS: Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS: Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.


Assuntos
Cistectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Duração da Cirurgia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade
7.
BMC Surg ; 21(1): 397, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772374

RESUMO

BACKGROUND: Primary plantar hyperhidrosis (PPH) is an idiopathic disease, characterized by excessive sweating of the feet. It leads to significant disturbance in private and professional daily lifestyle, due to excessive sweating. The aim of this study is to present the safety, efficacy and procedures of retroperitoneoscopic lumbar sympathectomy (RLS) for treatment of PPH. METHODS: RLS was performed 60 times in 30 patients (18 men, 12 women) with PPH in our institution from May 2019 to October 2020. All procedures were carried out by laparoscopy with retroperitoneal approach. Clinical data including patient demographics and perioperative, postoperative outcomes were evaluated. Recurrence of symptoms, and any adverse effects of surgery were evaluated after 7 to 30 days in outpatient clinic, and thereafter every 6 months. RESULTS: Mean age of patients was 33.6 (± standard deviation 10.8) years. Fourteen and fifteen patients were previously treated with medical therapy or endoscopic thoracic sympathectomy (ETS) respectively. Mean preoperative quality of life (QoL) score of patients was 91.8 (VERY BAD), but postoperative 12 months (QoL) score decreased to 29.1 (MUCH BETTER). There was no serious postoperative complication. During the mean 22 months of follow-up period, no compensatory sweating was observed. CONCLUSIONS: RLS can be a safe and effective surgical treatment for severe PPH, especially for the patients with persistent plantar sweating even after conservative management and ETS. RLS also could be offered to surgeons who are familiar with retroperitoneal space anatomy as feasible surgical treatment for PPH.


Assuntos
Hiperidrose , Laparoscopia , Criança , Feminino , Humanos , Hiperidrose/cirurgia , Masculino , Satisfação do Paciente , Qualidade de Vida , Sudorese , Simpatectomia , Resultado do Tratamento
8.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575959

RESUMO

Renal cell carcinoma (RCC) is a malignancy of the kidney originating from the tubular epithelium. Inactivation of the von Hippel-Lindau tumor-suppressor gene (VHL) is found in most clear cell renal cell carcinomas (ccRCCs). The VHL-HIF-VEGF/VEGFR pathway, which involves the von Hippel-Lindau tumor suppressor protein (VHL), hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), and its receptor (VEGFR), is a well-studied therapeutic target for metastatic ccRCC. Therefore, over the past decade, anti-angiogenic agents targeting VEGFR have served as the standard treatment for metastatic RCC. Recently, based on the immunomodulatory effect of anti-VEGFR therapy, anti-angiogenic agents and immune checkpoint inhibitor combination strategies have also emerged as therapeutic strategies. These advances were made possible by the improved understanding of the VHL-HIF pathway. In this review, we summarize the historical evolution of ccRCC treatments, with a focus on the involvement of the VHL-HIF pathway.


Assuntos
Carcinoma de Células Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Transdução de Sinais
9.
BMC Cancer ; 20(1): 1203, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287735

RESUMO

BACKGROUND: While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer. METHODS: Bladder cancer tissue was collected by transurethral resection of the bladder and preserved by snap-freezing. Circulating tumor cells were Isolated from the blood obtained before treatment. We performed whole exome sequencing of 20 matched pairs of primary bladder cancers and circulating tumor cells to identify and compare somatic mutations of these two different genomic resources. RESULTS: We observed that mutation abundances of primary bladder cancers and circulating tumor cells were highly variable. The mutation abundance was not significantly correlated between matched pairs. Of note, the mutation concordance between two resources was only 3-24% across 20 pairs examined, suggesting that the circulating tumor cell genomes of bladder cancer patients might be genetically distinct from primary bladder cancers. A relative enrichment of mutations belonging to APOBEC-related signature and a depletion of C-to-G transversions were observed for primary- and circulating tumor cells specific mutations, respectively, suggesting that distinct mutation forces might have been operative in respective lesions during carcinogenesis. CONCLUSIONS: The observed discrepancy of mutation abundance and low concordance level of mutations between genomes of primary bladder cancers and circulating tumor cells should be taken into account when evaluating clinical utility of circulating tumor cells for treatments and follow-up of bladder cancers. TRIAL REGISTRATION: Patients were selected and registered retrospectively, and medical records were evaluated.


Assuntos
Biomarcadores Tumorais/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias da Bexiga Urinária/genética , Feminino , Seguimentos , Humanos , Masculino , Mutação
10.
Aging Male ; 23(4): 287-296, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30269620

RESUMO

Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH).Materials and methods: Thirty 18-month-old male Sprague-Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined.Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue.Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.


Assuntos
Hipogonadismo/tratamento farmacológico , Lycium , Extratos Vegetais/farmacologia , Testosterona/sangue , Envelhecimento , Animais , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos
11.
BMC Urol ; 20(1): 41, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303205

RESUMO

BACKGROUND: DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. The aims of this study were to investigate the effects of DA-8010 on OAB in a rat model. METHODS: Study animals were divided into the following five groups of seven animals each: a sham-operated control group, a control group with partial bladder outlet obstruction (BOO) (OAB group), and three DA-8010 (doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day, respectively) with partial BOO groups. Oral administration of the drugs was continued for 14 days after 2 weeks of partial BOO. After 4 weeks of partial BOO, cystometrography was performed in all groups. Additionally, pro-inflammatory cytokines, Rho-kinases, and histology of the bladder were analyzed. RESULTS: There was a significant increase in the contraction interval and a decrease in contraction pressure in the 3 mg/kg/day DA-8010 group versus those in the OAB group. Rho kinase was also significantly decreased in the DA-8010 3 mg/kg/day dosage treatment group. The increased ratio of collagen to smooth muscle after partial BOO was significantly attenuated in the DA-8010 3 mg/kg/day dosage group. CONCLUSIONS: Oral administration of DA-8010 at 3 mg/kg/day improved findings in an OAB rat model induced by partial BOO. Our results suggest that the novel muscarinic receptor antagonist DA-8010 may be a promising drug for treating patients with OAB.


Assuntos
Antagonistas Muscarínicos/administração & dosagem , Fenilcarbamatos/administração & dosagem , Pirrolidinas/administração & dosagem , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Administração Oral , Animais , Masculino , Ratos , Ratos Sprague-Dawley
12.
Altern Ther Health Med ; 26(3): 24-31, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31221940

RESUMO

CONTEXT: Not all men presenting varicocele-associated infertility exhibit improved sperm quality or achieve pregnancy following varicocelectomy. Some combinations of specific natural herbs have been shown empirically to reduce oxidative stress and improve sperm quality. OBJECTIVE: We conducted a study to determine the effects of an herbal combination on sperm quality in varicocele-induced rats following varicocelectomy, hoping to find a new treatment approach to restore sperm quality following varicocelectomy. DESIGN: The research team designed an animal study. SETTING: The study took place in the Department of Urology at Seoul St. Mary's Hospital (Seoul, Republic of Korea). ANIMALS: Fifty white, male, Sprague-Dawley rats weighing 250 to 300 g each were used in the study. INTERVENTION: The rats were randomly assigned to 5 groups: (1) a control group (n = 10), (2) varicocele group (n = 10), (3) rats with varicocele and receiving varicocelectomy only (varicocelectomy group, n = 10), (4) rats with varicocele received varicocelectomy and oral administration with 200 mg/kg of an herbal combination for 4 wk (varicocelectomy + 200 mg/kg group, n = 10), and (5) rats with varicocele received varicocelectomy and oral administration with 400 mg/kg of an herbal com for 4 wk (varicocelectomy + 400 mg/kg group, n = 10). OUTCOME MEASURES: The study measured (1) sperm concentration and motility, (2) levels of reactive oxygen species (ROS), (3) concentrations of interleukin 6, interleukin 1ß, and tumor necrosis factor alpha (TNF-α), (4) apoptotic change, and (5) levels of heat shock protein (HSP). RESULTS: The sperm concentrations and motilities recovered after treatment in the varicocelectomy, varicocelectomy + 200 mg/kg, and varicocelectomy + 400 mg/kg groups. Significantly increased SOD and decreased ROS and cytokine levels were also observed. The apoptosis in the testes also was significantly decreased compared with the varicocele group. HSP70 in groups received varicocelectomy and administered with herbal combination was significantly decreased compared with the varicocelectomy group. CONCLUSIONS: The herbal combination was found to improve the sperm qualities, oxidative stress, and inflammation after varicocelectomy. Therefore, the herbal combination may provide a new and additional treatment for varicocele-associated infertility. For clinical application, further studies are needed to identify active ingredients in each herb and the mechanism by which each ingredient works, to standardize the herbal combination.


Assuntos
Medicina Herbária , Infertilidade Masculina/cirurgia , Espermatozoides/fisiologia , Varicocele/cirurgia , Animais , Feminino , Humanos , Infertilidade Masculina/etiologia , Masculino , Estresse Oxidativo , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Resultado do Tratamento
13.
Prostate ; 79(13): 1498-1504, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376214

RESUMO

BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 ß-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Tratamento por Ondas de Choque Extracorpóreas , NF-kappa B/metabolismo , Prostatite/terapia , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Doença Crônica , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , NF-kappa B/antagonistas & inibidores , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Dor Pélvica/terapia , Prostatite/metabolismo , Prostatite/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/biossíntese
15.
J Natl Compr Canc Netw ; 17(5): 441-449, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085754

RESUMO

BACKGROUND: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. MATERIALS AND METHODS: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. RESULTS: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. CONCLUSIONS: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Tomada de Decisão Clínica , Gerenciamento Clínico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prognóstico , Modelos de Riscos Proporcionais , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
16.
Support Care Cancer ; 27(5): 1747-1754, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30145738

RESUMO

PURPOSE: Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. METHODS: Three hundred fifty-six participants were assigned to two groups: "Smart After-Care" (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire-Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. RESULTS: At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received "Smart After-Care" have a 64% higher chance of increasing physical activity. CONCLUSION: Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. "Smart After-Care" was more effective than education only in increasing physical activity.


Assuntos
Neoplasias da Mama Masculina/fisiopatologia , Neoplasias da Mama Masculina/reabilitação , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/reabilitação , Terapia por Exercício/métodos , Actigrafia , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/terapia , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Qualidade de Vida , Smartphone
17.
BMC Health Serv Res ; 19(1): 408, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234845

RESUMO

BACKGROUND: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. METHODS: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. RESULTS: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. CONCLUSIONS: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.


Assuntos
Gastos em Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias da Próstata/economia , Neoplasias da Próstata/terapia , Idoso , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , República da Coreia , Estudos Retrospectivos
18.
Telemed J E Health ; 25(12): 1231-1236, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30758247

RESUMO

Background: Recently, the application of smartphone in medical field has received great attention.Introduction: The objective of this study was to compare the effectiveness of smartphone-based and conventional pedometer-based exercise monitoring systems in promoting home exercise among prostate cancer patients.Methods: Prostate cancer patients who have undergone surgery or androgen deprivation therapy were recruited. All participants were provided with physical activity goals based on their activities and were advised to achieve these goals during their home exercise period. The intervention group was instructed to use smartphone application to record their activities; they also received weekly remote consultations based on the activity record from the application, without visiting a clinic. The control group was instructed to keep a written record of their daily activities based on pedometer readings; these records were checked by clinicians during follow-up visits. The uptake, adherence, and completion rates of two groups were compared by intention-to-treat analysis. Changes in physical function during the exercise period were analyzed.Results: In total, 100 patients were recruited (smartphone: 5 and pedometer: 50). No significant differences were detected between groups in rates of uptake (80.0% vs. 88.0%, p = 0.28), adherence (92.5% vs. 79.5%, p = 0.12), or completion (76.0% vs. 86.0%, p = 0.20). Physical functions were significantly improved in both groups.Conclusions: The smartphone-based exercise monitoring system and the pedometer yielded comparable results in promoting physical activity, as assessed by rates of uptake, adherence, and completion. Exercise monitoring was effective in improving physical functions, in both methods.


Assuntos
Exercício Físico , Promoção da Saúde/métodos , Neoplasias da Próstata/reabilitação , Smartphone , Dispositivos Eletrônicos Vestíveis , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , República da Coreia
19.
World J Urol ; 36(4): 585-593, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29396785

RESUMO

PURPOSE: To compare the clinical outcomes of laparoendoscopic single-site plus one-port donor nephrectomy (LESSOP-DN) and mini laparoscopic donor nephrectomy (MLDN). METHODS: A prospective randomized controlled trial was conducted from December 2014 to February 2016 in donors scheduled for left donor nephrectomy. Donor and recipient demographics and clinical outcomes including pain scores and questionnaires (BIQ: body image questionnaire, SF-36, patient-reported overall convalescence) were also compared. RESULTS: A total of 121 eligible donors were recruited, of which 99 donors who were scheduled to undergo an operation on their left side were randomized into LESSOP-DN (n = 50) and MLDN (n = 49) groups. There were no significant demographic differences between the two groups. The renal extraction time in the LESS-DN group was shorter than that in the MLDN group (75.89 ± 13.01 vs. 87.31 ± 11.38 min, p < 0.001). Other perioperative parameters and complication rates were comparable between the two groups. The LESSOP-DN group had a smaller incision length than the MLDN group (4.89 ± 0.68 vs. 6.21 ± 1.11 cm, p < 0.001), but cosmetic scores and body image scores were similar in the two groups (p = 0.905, 0.217). Donor quality of life (SF-36) and recovery and satisfaction data were comparable between the two groups. Delayed graft function (DGF) occurred in one recipient undergoing MLDN procedure (2.1%) and progressed to graft failure. CONCLUSIONS: There were no differences in cosmetic satisfaction between groups despite the smaller incision size of LESSOP-DN. Safety parameters and subjective measures of postoperative morbidity were similar between the two groups.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Laparoscopia , Procedimentos Cirúrgicos Minimamente Invasivos , Nefrectomia , Dor Pós-Operatória , Qualidade de Vida , Adulto , Feminino , Humanos , Transplante de Rim/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/psicologia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Duração da Cirurgia , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Coleta de Tecidos e Órgãos/métodos
20.
Int J Mol Sci ; 19(12)2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30477146

RESUMO

Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague⁻Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.


Assuntos
Quimiocina CXCL12/genética , Disfunção Erétil/genética , Expressão Gênica , Engenharia Genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Animais , Glicemia , Peso Corporal , Movimento Celular/genética , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Disfunção Erétil/terapia , Masculino , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais
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