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BACKGROUND: The urinary microbiota of patients with benign prostatic hyperplasia (BPH) has been associated with lower urinary tract symptoms (LUTS), however, little is known about urinary microbiota correlations with clinicopathological parameters associated with BPH. Here, we investigate associations between the urinary microbiota and clinical parameters of patients with BPH undergoing surgery. METHODS: Forty-one patients with BPH undergoing surgery were recruited from two medical centers. Catheterized urine specimens were collected and the microbiota was characterized by 16S rRNA gene sequencing. Patients were segregated into two groups according to each clinical parameter and differences in urinary microbiota diversity and composition were evaluated. RESULTS: Higher prostate weight and prostate-specific antigen (PSA) levels were associated with higher alpha diversity in the urinary microbiota of BPH patients. At the specific microbe level, we found that the greater the prostatic weight, the lower the relative abundance of Streptococcus, while the greater the PSA levels, the higher the abundance of Lactobacillus. Treatment with 5-α-reductase inhibitor was associated with overall urinary microbiota composition, in part due to a higher abundance of Corynebacterium and Anaerococcus in this group. CONCLUSIONS: We demonstrated that the urinary microbiota of BPH patients is associated with clinicopathological features, paving the way for larger studies in which causality between urinary microbiota and BPH can be appropriately explored.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamento farmacológico , Antígeno Prostático Específico/uso terapêutico , RNA Ribossômico 16S/genética , Próstata , Sintomas do Trato Urinário Inferior/etiologiaRESUMO
OBJECTIVE: To compare the outcomes of retrograde flexible ureteroscopy (fURS) with retroperitoneal laparoscopic ureterolithotomy (RLU) for large proximal ureteric stones. PATIENTS AND METHODS: A prospective randomised trial was conducted from January 2018 through December 2022 including patients with impacted proximal ureteric stones of 15-25 mm. Patients underwent fURS or RLU. Primary outcome was the stone-free rate. Demographic data, stone features, and complications rates were also compared between groups. RESULTS: A total of 64 patients were enrolled, 32 in each group. The mean impacted stone time was similar between groups, as well as stone size (17 mm) and stone density (>1000 Hounsfield Units). The ureteric stone-free rates between the two groups (93.7% in fURS vs 96.8% in RLU; odds ratio [OR] 0.72, 95% confidence interval [CI] -1.72 to 3.17; P = 0.554), and overall success rates, which take into account residual fragments in the kidney (84.3% in fURS vs 93.7% in RLU; OR 1.02, 95% CI -0.69 to 2.74; P = 0.23), were similar. Operative time was also not statistically significantly different between groups (median 80 vs 82 min; P = 0.101). There was no difference in hospital length of stay. Retropulsion rate was higher with fURS (65.6% vs 3.1%; p < 0.001). Residual hydronephrosis (34.3% each group) and complication rates did no differ according to treatment. CONCLUSION: Flexible URS and RLU are both highly efficient and present low morbidity for large impacted proximal ureteric stone treatment. RLU is not superior to fURS.
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PURPOSE: Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5). MATERIAL AND METHODS: A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern. RESULTS: A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain. CONCLUSION: In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.
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Hidronefrose , Laparoscopia , Ureter , Obstrução Ureteral , Criança , Adulto , Humanos , Feminino , Adulto Jovem , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/cirurgia , Ureter/cirurgia , Rim , Pelve Renal/cirurgia , Hidronefrose/cirurgia , Laparoscopia/métodos , Dor , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
OBJECTIVE: To evaluate the local tumour progression-free survival (LTPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) of healthy surgical candidates who underwent percutaneous thermoablation (TA) as a first-line therapy for small renal masses (T1a). METHODS: The institutional review board approved this bi-institutional retrospective study of 85 consecutive surgical candidates with 97 biopsy-proven malignant renal masses (T1a) treated with percutaneous TA from 2008 to 2016. The LTPFS, MFS, CSS and OS rates were calculated using the Kaplan-Meier method. Descriptive analysis was also performed. RESULTS: The median tumour size was 2.3 cm (range, 0.7-3.9 cm). The minimal and mean follow-up periods were 24 and 56 months, respectively. Local recurrence was detected in four patients (4.7%) at 8.5, 13.8, 58.0 and 64.0 months of follow-up and retreated successfully with percutaneous TA. No patient developed metastatic renal cell carcinoma, and none died due to renal oncologic complications. One patient died of heart attack. The 5-year LTPFS, OS, MFS and CSS rates were 93.0%, 98.4%, 100% and 100%, respectively. Only two patients (2.3%) had major complications (Clavien-Dindo grade > II), including ureteropelvic junction stenosis and urinary obstruction due to ureteral blood clots. CONCLUSIONS: Our study demonstrates that percutaneous TA is a feasible and effective first-line therapy for healthy surgical candidates with small renal masses (T1a). The 5-year LTPFS, OS, CSS and MFS rates were 93.0%, 98.4%, 100% and 100%, respectively, with a major complication rate of only 2.3%. KEY POINTS: ⢠Image-guided percutaneous thermoablation of small renal malignancies was effective in 95.3% of the healthy surgical candidates. ⢠Major complications were detected in 2.3% of the patients. ⢠The local tumour progression-free survival rate was 97.6% and 93.0% at 3 and 5 years, respectively.
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Carcinoma de Células Renais , Ablação por Cateter , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.
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INTRODUCTION: Robot-assisted radical prostatectomy (RARP) is the most recent surgical technique for localized prostate cancer. The Da Vinci (Intuitive Surgical, Sunnyvale, CA) system was first introduced in Brazil in 2008, with a fast growing number of surgeries performed each year. OBJECTIVE: Our primary endpoint is to analyze possible predictors of functional outcomes, related to patient and tumor features. As secondary endpoint, describe functional outcomes (urinary continence and sexual potency) from RARP performed in the Sírio-Libanês Hospital (SLH), a private institution, in São Paulo, from April 2008 to December 2015. MATERIALS AND METHOD: Data from 104 consecutive patients operated by two surgeons from the SLH (MA and SA) between 2008 and 2015, with a minimum 12 months follow-up, were collected. Patient features (age, body mass index - BMI, PSA, date of surgery and sexual function), tumor features (tumor stage, Gleason and surgical margins) and followup data (time to reach urinary continence and sexual potency) were the variables collected at 1, 3, 6 and 12 month and every 6 months thereafter. Continence was defined as the use of no pad on medical interview and sexual potency defined as the capability for vaginal penetration with or without fosphodiesterase type 5 inhibitors. RESULTS: Mean age was 60 years old and mean BMI was 28.45 kg/m2. BMI >30kg/m2 (p<0.001) and age (p=0.011) were significant predictors for worse sexual potency after surgery. After 1, 3, 6 and 12 months, 20.7%, 45.7%, 60.9% and 71.8% from patients were potent, respectively. The urinary continence was reached in 36.5%, 80.3%, 88.6% and 92.8% after 1, 3, 6 and 12 months, respectively. Until the end of the study, only one patient was incontinent and 20.7% were impotent. CONCLUSION: Age was a predictor of urinary and erectile function recovery in 12 months. BMI was significant factor for potency recovery. We obtained in a private hospital good functional results after 12 months of follow-up.
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Ereção Peniana/fisiologia , Prostatectomia/métodos , Recuperação de Função Fisiológica/fisiologia , Procedimentos Cirúrgicos Robóticos/métodos , Micção/fisiologia , Adenocarcinoma/fisiopatologia , Adenocarcinoma/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Brasil , Disfunção Erétil/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/fisiopatologiaRESUMO
PURPOSE: The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and ß2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty. MATERIAL AND METHODS: We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6 ± 12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation. RESULTS: KIM-1 had an area under the curve of 0.79 (95% CI 0.70-0.89), NGAL 0.71 (95% CI 0.61-0.83), CA19-9 0.70 (95% CI 0.60-0.81), and ß2-microgloblin 0.61 (95% CI 0.50-0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty. CONCLUSIONS: The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.
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Biomarcadores/urina , Obstrução Ureteral/diagnóstico , Adulto , Antígeno CA-19-9/urina , Estudos de Casos e Controles , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Lipocalina-2/urina , Pessoa de Meia-Idade , Nefrotomia , Estudos Prospectivos , Sensibilidade e Especificidade , Obstrução Ureteral/cirurgia , Microglobulina beta-2/urinaRESUMO
PURPOSE: Scientific research originating from Brazil appears to be rising in several medical fields. Research results are often presented at scientific meetings before publication in peer-reviewed journals. We investigated the publication rate of Brazilian studies presented in American Urological Association (AUA) meetings and compared with the rate of publication of Brazilian oncological studies presented at the American Society of Clinical Oncology (ASCO) meetings. MATERIALS AND METHODS: a hand search of 12,454 abstracts presented at aua meetings 2001-2007 was conducted. abstracts for which at least two-thirds of institutions were from brazil were considered as brazilian. final publication was searched in pubmed and lilacs databases. oncological abstracts were also hand searched in the asco meetings proceedings in the same years. RESULTS: There was no significant temporal trend in the proportion of AUA studies originating from Brazil along those 7 years. A total of 195 abstracts (1.57%) were from Brazil. One hundred (51.3%) abstracts were published in full, and the estimated 5-year publication rate was 48.2%. There was a progressive increase in publication rates for studies categorized as video, poster, and podium presentations. Considering abstracts presented in years 2001-2005, urologic publication rate was significantly higher than for abstracts presented at the ASCO meeting. CONCLUSIONS: Our results suggest that the Brazilian contribution to AUA meetings is at a plateau and that the Brazilian literature contribution is greater in urology than in oncology. Efforts must be invested towards raising this plateau and understanding qualitative aspects of the urology scientific output from Brazil.
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Congressos como Assunto/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Editoração/estatística & dados numéricos , Sociedades Médicas/estatística & dados numéricos , Urologia/estatística & dados numéricos , Bibliometria , Pesquisa Biomédica/estatística & dados numéricos , Brasil , Humanos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, nâ¯=â¯32) or benign prostatic hyperplasia (control group, nâ¯=â¯41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Masculino , Bexiga Urinária/patologia , Vacina BCG/uso terapêutico , Disbiose/tratamento farmacológico , RNA Ribossômico 16S/genética , Adjuvantes Imunológicos/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Administração Intravesical , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
Kidney cancer is a common urologic malignancy with either laparoscopic (LPN) or robotic partial nephrectomy as therapeutic options of choice for localized tumors. However, renal resection and suturing are challenging steps of the procedure that can lead to complications such as prolonged warm ischemia, bleeding, and urinary fistulas. LPN with a diode laser is an efficient technique due to its cutting and/or coagulation attributes. Surprisingly, key laser features such as wavelength and power remain undefined. Using a large porcine model, we evaluated the laser range of wavelength and power in a clamp-free LPN and compared it to the established gold-standard LPN technique (i.e., cold-cutting and suturing). By analyzing surgery duration, bleeding, presence of urine leak, tissue damage related to the resected renal fragment and the remaining organ, hemoglobin levels, and renal function, we show that an optimized experimental diode laser clamp-free LPN (wavelength, 980 nm; power, 15 W) had shorter surgery time with less bleeding, and better postoperative renal function recovery when compared to the well-established technique. Together, our data indicate that partial nephrectomy with a diode laser clamp-free LPN technique is an improved alternative to the gold-standard technique. Therefore, translational clinical trials towards human patient applications are readily feasible.
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Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Humanos , Animais , Suínos , Lasers Semicondutores/uso terapêutico , Nefrectomia/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Rim/cirurgia , Rim/patologia , Laparoscopia/métodos , Resultado do TratamentoRESUMO
Background: We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. Methods: The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. Results: We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. Conclusions: We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. Funding: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).
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Neoplasias da Próstata , RNA Longo não Codificante , Humanos , Masculino , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/genética , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , RNA Longo não Codificante/genéticaRESUMO
We have recently identified glucose-regulated protein-78 (GRP78) as a relevant molecular target expressed in metastatic tumors by fingerprinting the circulating repertoire of antibodies from cancer patients. Here we design and evaluate a ligand-receptor system based on the tumor cell membrane expression of GRP78. We show that GRP78 binding peptide motifs target tumor cells specifically in vivo and in human cancer specimens ex vivo. Moreover, synthetic chimeric peptides composed of GRP78 binding motifs fused to a programmed cell death-inducing sequence can suppress tumor growth in xenograft and isogenic mouse models of prostate and breast cancer. Together, these preclinical data validate GRP78 on the tumor cell surface as a functional molecular target that may prove useful for translation into clinical applications.
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Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Animais , Apoptose , Membrana Celular/metabolismo , Chaperona BiP do Retículo Endoplasmático , Humanos , Ligantes , Masculino , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Ligação Proteica , Proteínas Recombinantes de Fusão , Células Tumorais CultivadasRESUMO
We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.
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Células Endoteliais/fisiologia , Glutamil Aminopeptidase/metabolismo , Motivos de Aminoácidos , Animais , Vasos Sanguíneos , Divisão Celular , Hipóxia Celular/fisiologia , Movimento Celular , Embrião de Galinha , Inibidores Enzimáticos , Substâncias de Crescimento/metabolismo , Humanos , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Neoplasias/metabolismo , Neovascularização Patológica , Biblioteca de Peptídeos , Peptídeos/metabolismo , Ligação Proteica , Transplante Heterólogo/patologiaRESUMO
Mammalian cell membranes provide an interface between the intracellular and extracellular compartments. It is currently thought that cytoplasmic signaling adapter proteins play no functional role within the extracellular tumor environment. Here, by selecting combinatorial random peptide libraries in tumor-bearing mice, we uncovered a direct, specific, and functional interaction between CRKL, an adapter protein [with Src homology 2 (SH2)- and SH3-containing domains], and the plexin-semaphorin-integrin domain of beta(1) integrin in the extracellular milieu. Through assays in vitro, in cellulo, and in vivo, we show that this unconventional and as yet unrecognized protein-protein interaction between a regulatory integrin domain (rather than a ligand-binding one) and an intracellular adapter (acting outside of the cells) triggers an alternative integrin-mediated cascade for cell growth and survival. Based on these data, here we propose that a secreted form of the SH3/SH2 adaptor protein CRKL may act as a growth-promoting factor driving tumorigenesis and may lead to the development of cancer therapeutics targeting secreted CRKL.
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Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Citoplasma/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Proteínas Nucleares/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/química , Sequência de Aminoácidos , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Modelos Biológicos , Dados de Sequência Molecular , Transplante de Neoplasias , Proteínas Nucleares/química , Domínios de Homologia de srcRESUMO
Accessibility to next-generation sequencing (NGS) technologies has enabled the profiling of microbial communities living in distinct habitats. 16S ribosomal RNA (rRNA) gene sequencing is widely used for microbiota profiling with NGS technologies. Since most used NGS platforms generate short reads, sequencing the full-length 16S rRNA gene is impractical. Therefore, choosing which 16S rRNA hypervariable region to sequence is critical in microbiota profiling studies. All nine 16S rRNA hypervariable regions are taxonomically informative, but due to variability in profiling performance for specific clades, choosing the ideal 16S rRNA hypervariable region will depend on the bacterial composition of the habitat under study. Recently, NGS allowed the identification of microbes in the urinary tract, and urinary microbiota has become an active research area. However, there is no current study evaluating the performance of different 16S rRNA hypervariable regions for male urinary microbiota profiling. We collected urine samples from male volunteers and profiled their urinary microbiota by sequencing a panel of six amplicons encompassing all nine 16S rRNA hypervariable regions. Systematic comparisons of their performance indicate V1V2 hypervariable regions better assess the taxa commonly present in male urine samples, suggesting V1V2 amplicon sequencing is more suitable for male urinary microbiota profiling. We believe our results will be helpful to guide this crucial methodological choice in future male urinary microbiota studies.
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Microbiota , Bactérias/genética , Primers do DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Microbiota/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodosRESUMO
OBJECTIVES: To systematically summarize the available evidence concerning the impact of pyeloplasty on symptoms and differential renal function (DRF) in adults with unilateral UPJO in poorly functioning kidneys (PFK), and to identify potential predictors of kidney function recovery that could help clinicians select candidates for pyeloplasty. METHODS: A literature search (MEDLINE, Embase, Google Scholar, Scopus, ClinicalTrials.gov, and the WHO Clinical Trials Registry) and systematic review were performed up to September 2020 according to the PRISMA guidelines. PFK were defined as a baseline DRF ≤30% on renal scintigraphy. The primary endpoints were symptom relief and postoperative scintigraphic DRF. Predictors of kidney function recovery were evaluated and compared among studies. RESULTS: Nine studies comprising 731 patients met the inclusion criteria and were included for evidence synthesis. A DRF increase >5% occurred in 13.3%-53.8% of 160 patients with a pre- and postoperative renal scan. Symptoms improved in 73.3%-93.3% of 141 adults after pyeloplasty. Neither patient's age, baseline DFR, comorbidities, degree of hydronephrosis, kidney parenchymal thickness, nor kidney biopsy findings consistently predicted a significant DRF increase among 375 patients undergoing pyeloplasty. CONCLUSION: Based on a low level of evidence, pyeloplasty may relieve symptoms and stabilize kidney function in adults with UPJO in PFK. A significant number of patients showed a DRF increase >5%, yet no consistent predictor of kidney function recovery was identified. Until more evidence becomes available, pyeloplasty could be considered for selected cases after accounting for the risks of a failure requiring a future nephrectomy.
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Pelve Renal/cirurgia , Rim/fisiopatologia , Obstrução Ureteral/fisiopatologia , Obstrução Ureteral/cirurgia , Adulto , HumanosRESUMO
PURPOSE: To evaluate in an experimental model, the mobility of a novel peritoneal dialysis catheter with a metallic tip (Mag-Cath) using an extra-corporeal magnet. MATERIALS AND METHODS: The Mag-Cath was installed in a porcine model under general anesthesia using laparoscopic access. A senior urologist, a urology resident, and a 3rd-year medical student were assigned to complete 2 tasks guided by fluoroscopy: (1) Move the catheter tip from the right flank to the pelvis and (2) move the catheter tip from the pelvis to the left flank. Accomplishment and time to complete the tasks were recorded. Participants were asked independently to grade the difficulty of the tasks using an analog scale from 1 (extremely easy) to 10 (extremely difficult). RESULTS: All participants completed the tasks. The difficulty of the tasks was graded equal to 1 by the senior urologist and urology resident and equal to 3 by the medical student. The time to move the Mag-Cath from the right flank to the target was 14, 10, and 55 s for the senior urologist, urology resident, and medical student, respectively. The time to move the Mag-Cath from the target to the left flank was 17, 18, and 43 s for the senior urologist, urology resident, and medical student, respectively. CONCLUSION: In this preliminary analysis, the use of an extra-corporeal magnet to move the Mag-Cath was feasible, with a low grade of difficulty, and individuals with different levels of expertise could perform it. Further studies in human subjects are needed to evaluate the clinical applicability of the Mag-Cath properly.
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Cateterismo , Imãs , Diálise Peritoneal/instrumentação , Animais , Masculino , Modelos Animais , Diálise Peritoneal/métodos , SuínosRESUMO
OBJECTIVES: To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). METHODS: A retrospective comparative analysis was performed between adult patients who underwent LP due to UPJO with differential renal function (DRF) ≤ 15% and DRF > 15%. LP success rate and complications were assessed. LP success was defined as symptoms improvement and DRF improvement or stabilization. DRF and estimated glomerular filtration rate (eGFR) were analyzed before and 12 months after surgery to evaluate renal function recovery. DRF was estimated using Tc-99 m DMSA renal scintigraphy. RESULTS: Among 121 LP performed in the study period at our institution, 15 and 42 were included in the DRF ≤ 15% and DRF > 15% groups, respectively. At a median follow-up of 17.8 months, all patients with DRF ≤ 15% reported symptoms improvement. LP success rate was 86.7% and 90.5% (p = 0.65) for patients with DRF ≤ 15% and DRF > 15%, respectively. There were no complications in the DRF ≤ 15% group, while there were three complications recorded in the DRF > 15% group (Clavien 2 and 3b). In the DRF ≤ 15% group, mean pre-operative and post-operative DRF was 9.5% ± 3.6 and 10.5% ± 7.8 (p = 0.49), respectively. Median pre-operative and post-operative eGFR was 68.5 ml/min and 79.8 ml/min (p = 0.93), respectively. Two patients had DRF improvement after LP. CONCLUSIONS: LP in adult patients with UPJO and poor function kidneys is an effective and safe procedure. DRF recovery is seen in a minority of the patients; however, LP is an alternative to nephrectomy.
Assuntos
Pelve Renal/cirurgia , Rim/fisiopatologia , Laparoscopia , Nefrectomia/métodos , Obstrução Ureteral/fisiopatologia , Obstrução Ureteral/cirurgia , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To compare symptom resolution and short-term renal function after pyeloplasty or nephrectomy in adults with ureteropelvic junction obstruction (UPJO) in poorly functioning renal units (PFRU). METHODS: Retrospective analysis of adult patients with UPJO and differential renal function (DRF) ≤ 15% who underwent laparoscopic pyeloplasty or nephrectomy. Primary endpoints included symptom resolution and estimated glomerular filtration rate (eGFR) at 12 months. Surgical complications were compared between groups. A secondary analysis was performed comparing baseline and postoperative DRF to evaluate the PFRU recovery potential after pyeloplasty. RESULTS: Sixty-three patients were included; 19 underwent pyeloplasty and 44 underwent nephrectomy. The mean age of the cohort was 39.5 ± 13.8 years. Nephrectomy was associated with significantly higher intra-operative blood loss (p = 0.02). Operative time and length of hospital stay were not significantly different between groups. There were three complications in the nephrectomy group, and none in the pyeloplasty group (p = 0.34). Symptom resolution rates were equivalent between groups (73% vs. 76%; p = 0.78). The eGFR variation was not statistically different after pyeloplasty or nephrectomy (+6.2 vs. +0.1 mL/min/1.73m2, respectively; p = 0.18). Patients undergoing pyeloplasty had no significant change in the mean DRF (baseline 9.5 vs. 10%; p = 0.99). CONCLUSION: Pyeloplasty can be considered for selected patients with UPJO in PFRU as an organ-sparing alternative to nephrectomy. Although there was no significant gain in mean DRF, pyeloplasty prevented further functional loss and relieved symptoms in most cases in the short-term with at least the same complication rates of nephrectomy.