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1.
World J Urol ; 42(1): 114, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431764

RESUMO

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.


Assuntos
Cálculos Renais , Litotripsia , Nefrostomia Percutânea , Humanos , Estudos Prospectivos , Nefrostomia Percutânea/métodos , Cálculos Renais/terapia , Fatores de Risco , Resultado do Tratamento
2.
BMC Urol ; 24(1): 29, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310213

RESUMO

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Humanos , Masculino , Neoplasias Renais/patologia , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Recidiva Local de Neoplasia/cirurgia , Nefrectomia/métodos , Carcinoma de Células Renais/patologia , Laparoscopia/métodos , Estudos Retrospectivos
3.
Theranostics ; 14(1): 203-219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164146

RESUMO

Background: Intravesical chemotherapy is highly recommended after transurethral resection of bladder tumor for patients with bladder cancer (BCa). However, this localized adjuvant therapy has drawbacks of causing indiscriminate damage and inability to penetrate bladder mucosal. Methods: Fluorinated polylysine micelles (PLLF) were synthesized by reacting polylysine (PLL) with heptafluorobutyrate anhydride. Anti-apoptotic gene defender against cell death 1 (DAD1) was selected by different gene expression analysis between BCa patients and healthy individuals and identified by several biological function assays. The gene transfection ability of PLLF was verified by multiple in vitro and in vivo assays. The therapeutic efficiency of PLLF nanoparticles (NPs) targeting DAD1 were confirmed by intravesical administration using an orthotopic BCa mouse model. Results: Decorated with fluorinated chains, PLL can self-assemble to form NPs and condense plasmids with excellent gene transfection efficiency in vitro. Loading with the CRISPR-Cas9 system designed to target DAD1 (Cas9-sgDAD1), PLLF/Cas9-sgDAD1 NPs strongly inhibited the expression of DAD1 in BCa cells and induced BCa cell apoptosis through the MAPK signaling pathway. Furthermore, intravesical administration of PLLF/Cas9-sgDAD1 NPs resulted in significant therapeutic outcomes without systemic toxicity in vivo. Conclusion: The synthetized PLLF can transmucosally deliver the CRISPR-Cas9 system into orthotopic BCa tissues to improve intravesical instillation therapy for BCa. This work presents a new strategy for targeting DAD1 gene in the intravesical therapy for BCa with high potential for clinical applications.


Assuntos
Nanopartículas , Neoplasias da Bexiga Urinária , Camundongos , Animais , Humanos , Bexiga Urinária/patologia , Polilisina/metabolismo , Sistemas CRISPR-Cas/genética , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Terapia Genética
4.
BMC Cancer ; 24(1): 127, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267934

RESUMO

PURPOSE: To present the widely unknown perioperative outcomes and continence status of bladder cancer patients following robotic-assisted radical cystectomy (RARC) with Mainz pouch II urinary diversion (UD). MATERIALS AND METHODS: From November 2020 to December 2023, 37 bladder cancer patients who underwent RARC with Mainz pouch II UD were retrospectively assessed (ChiCTR2300070279). The results, which included patient demographics, perioperative data, continence, and complications (early ≤ 30 days and late ≤ 30 days) were reported using the RC-pentafecta criteria. RC-pentafecta criteria included ≥ 16 lymph nodes removed, negative soft tissue surgical margins, absence of major (Grade III-IV) complication at 90 days, absence of clinical recurrence at ≤ 12 months, and absence of long-term UD-related sequelae. A numeric rating scale assessed patient satisfaction with urinary continence 30 days after surgery. The validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire was used to evaluate bowel function. The Kaplan-Meier curve was used to evaluate overall survival (OS). RESULTS: Of the 37 patients evaluated over a median (range) follow-up period of 23.0 (12.0-36.5) months. The median (range) age was 65 (40-81) years. The median (range) time to urinary continence after surgery was 2.3 (1.5-6) months. Of the 37 patients, 31 (83.8%) were continent both during the day and at night, 34 (91.9%) were continent during the day, 32 (86.5%) were continent at night, 35 (94.6%) were satisfied with their urinary continence status, and 21 (56.8%) were very satisfied. The mean (range) voiding frequency was 6 (4-10) during the day and 3 (2-5.5) at night. The mean (range) PAC-SYM total score was 9.50 (4.00-15.00). In 12 (32.4%) of the patients, RC-pentafecta was achieved, and achieving RC-pentafecta was linked to better satisfaction scores (7.3 vs. 5.5, p = 0.034). There was no significant difference between RC-pentafecta and No RC-pentafecta groups in terms of OS (25.6 vs. 21.5 months, p = 0.16). 7 (19.4%) patients experienced late complications. CONCLUSIONS: Mainz pouch II UD following RARC in bladder cancer patients results in a satisfactory continence rate. Achieving RC-pentafecta was correlated with better satisfaction scores. The intracorporeal approach to Mainz pouch II UD is beneficial for female patients due to its reduced invasiveness. TRIAL REGISTRATION: ChiCTR2300070279; Registration: 07/04/2023, Last updated version: 01/06/2023. Retrospectively registered.


Assuntos
Parede Abdominal , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Cistectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Constipação Intestinal , Progressão da Doença
5.
BMC Cancer ; 23(1): 1066, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932689

RESUMO

BACKGROUND: In muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) is critical in reducing disease recurrence, with GC (gemcitabine and cisplatin) being one of the most commonly used NACs. Different GC schedules have been used, but the best neoadjuvant regimen is still unknown. The clinical outcomes of 3 and 4 cycles of neoadjuvant GC are compared in this systematic review and meta-analysis to determine which is best for patients with MIBC. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, WAN FANG DATA, and meeting abstracts to identify relevant studies up to March 2023. Studies that compared 3 and 4 cycles of neoadjuvant GC for MIBC were included. The primary outcomes were pCR, pDS, OS, and CSS. The secondary outcome was recurrence and SAEs. RESULTS: A total of 3 studies, with 1091 patients, were included in the final analysis. Patients that received 4 cycles of GC had a higher pCR (OR = 0.66; 95% CI, 0.50-0.87; p = 0.003) and pDS (OR = 0.63; 95% CI, 0.48-0.84; p = 0.002) than those who received 3 cycles. Regarding recurrence rate (OR = 1.23; 95% CI, 0.91-1.65; p = 0.18), there were no appreciable differences between the 3 and 4 cycles of GC. Survival parameters such as OS (HR, 1.35; 95% CI, 0.86-2.12; p = 0.19) and CSS (HR, 1.06; 95% CI, 0.82-1.38; p = 0.20) were similar. Only one trial reported on the outcomes of SAEs. And there were no statistically significant differences in thrombocytopenia, infection rate, neutropenic fever, anemia, or decreased renal function between patients. The neutropenia of patients was statistically different (OR = 0.72; 95% CI, 0.52-0.99; p = 0.04). CONCLUSION: The 4-cycle GC regimen was superior to the 3-cycle regimen in only the pCR and pDS results. Survival and recurrence rates were similar between the two regimens. In both treatment regimes, the toxicity profile was manageable. However, due to the inherent drawbacks of retrospective research, this should be regarded with caution.


Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/uso terapêutico , Cistectomia , Gencitabina , Músculos , Terapia Neoadjuvante/métodos , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos
7.
Prostate Cancer Prostatic Dis ; 26(3): 483-494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35798855

RESUMO

BACKGROUND: We performed this systematic review and meta-analysis to investigate the efficacy and safety of Li-ESWT combined with or without medications for patients with Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). METHODS: A comprehensive search was conducted of PUBMED, Cochrane Library, and Web of Science databases from inception to February 2022 for randomized controlled trials (RCTs) assessing the efficacy and safety of Li-ESWT with or without the combination of medications compared with the control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Visual Analogue Scale/Score (VAS), International Index of Erectile Function (IIEF), and International prostate symptom score (IPSS) were used to assess the improvements of symptoms in CP/CPPS patients. RESULTS: 651 patients from 12 randomized controlled studies were included in this study. The total NIH-CPSI scores, pain domain scores, and quality of life (QOL) scores were significantly lower in the Li-ESWT group than those in the control group at the termination of treatment, and 1, 4, 12, and 24 weeks after treatment. And these scores were significantly reduced in the Li-ESWT group than in baselines. In the subgroup analysis, reductions of these scores lasted longer and were greater in Li-ESWT combined with medications than in Li-ESWT alone. In the Li-ESWT group, the VAS score; IIEF score; and IPSS score were significant improvements than those in control group at the termination of treatment, and 1, 4, and 12 weeks after treatment; 4, 12, and 24 weeks after treatment; and 1, 4, and 12 weeks after treatment, respectively. CONCLUSIONS: Li-ESWT is a safe, non-invasive, and effective option for patients with CP/CPPS, whether combined with medications or not, should be recommended for widespread use in clinical practice.


Assuntos
Dor Crônica , Neoplasias da Próstata , Prostatite , Masculino , Humanos , Prostatite/tratamento farmacológico , Doença Crônica , Dor Pélvica/terapia , Bases de Dados Factuais , Dor Crônica/terapia
8.
Urol Int ; 107(1): 1-14, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35835038

RESUMO

INTRODUCTION: We conducted a systematic review and meta-analysis to assess the available literature regarding the postoperative effects of anti-reflux anastomosis and direct anastomosis in orthotopic ileal neobladder (ONB). METHODS: We searched PubMed, Embase, and the Cochrane Library in October 2021. We included 11 studies of patients with bladder cancer who underwent radical cystectomy and ONB as urinary diversion. Outcomes evaluated in this review were ureteroenteric anastomotic stricture (UEAS), vesicoureteral reflux, renal function (RFn) impairment, and pyelonephritis. All data were analyzed using Review Manager 5.4.4 and subgroup analyses were applied. RESULTS: A total of 11 studies were eligible for meta-analysis. The synthetic data suggested that anti-reflux anastomosis and direct anastomosis were comparable in terms of RFn impairment (odds ratio (OR) = 1.69; 95% confidence interval (CI): 0.18-15.6; p = 0.65, I2 = 69%) and pyelonephritis (OR = 1.13; 95% CI: 0.65-1.99; p = 0.66, I2 = 1%) without significant difference in each group statistically. The pooled study data showed a significantly higher incidence of UEAS (OR = 2.84; 95% CI: 1.75-4.61, p < 0.0001, I2 = 50%) and a lower incidence of vesicoureteral reflux (OR = 0.24; 95% CI: 0.10-0.59; p = 0.002, I2 = 75%) in anti-reflux anastomosis compared to direct anastomosis. In subgroup analysis, anti-reflux anastomosis was more likely to result in UEAS than direct anastomosis, especially when ureteral stent was removed within 14 days. CONCLUSION: Although meta-analysis showed that overall incidence of vesicoureteral reflux was higher with direct anastomosis than anti-reflux anastomosis, the rate of vesicoureteral reflux was not directly related to impairment of RFn. The anti-reflux mechanism of ONB was positively associated with a higher incidence of significant UEAS compared to the direct approach, which can lead to kidney damage and an increased risk of secondary surgical procedures.


Assuntos
Pielonefrite , Ureter , Neoplasias da Bexiga Urinária , Derivação Urinária , Refluxo Vesicoureteral , Humanos , Derivação Urinária/efeitos adversos , Ureter/cirurgia , Cistectomia/métodos , Anastomose Cirúrgica/efeitos adversos , Refluxo Vesicoureteral/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Íleo/cirurgia , Pielonefrite/complicações
10.
Clin Transl Oncol ; 25(5): 1425-1435, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36512304

RESUMO

BACKGROUND: Gemcitabine (GEM)-based chemotherapy regimens is widely used in bladder cancer (BC) patients. However, GEM resistance may occur and result in treatment failure and disease progression. A disintegrin and metalloprotease 12 (ADAM12) plays a critical role in many cancers. However, the role of ADAM12 in GEM resistance of BC remains unclear. METHODS: We analyzed the relationship between ADAM12 expression and tumor characteristics using the data downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Then, we established GEM resistant BC cell lines and used quantitative real-time PCR, western blot, cell counting kit-8, immunohistochemistry, and xenograft mouse model to investigate the role of ADAM12 in GEM resistance. RESULTS: In general, ADAM12 was found to be upregulated in GEM resistant BC cells. ADAM12 knockdown increased the chemosensitivity of BC cells. We further proved that ADAM12 could promote GEM resistance by activating the epidermal growth factor receptor (EGFR) signaling pathway in BC. Furthermore, the epithelial-mesenchymal transition (EMT) phenotype was observed in GEM resistant BC cells. ADAM12 induced EMT process and promotes tumor progression in BC. CONCLUSION: Our findings suggested that ADAM12 was a key gene for GEM resistance and positively correlated with malignancy of BC. It might serve as a novel and valuable therapeutic target for BC.


Assuntos
Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Gencitabina , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gencitabina/farmacologia , Gencitabina/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
11.
Front Genet ; 13: 1006151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386841

RESUMO

Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated. Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient's disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed. Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy. Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.

12.
Future Oncol ; 18(26): 2933-2942, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35880441

RESUMO

Aim: To investigate the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio and plasma fibrinogen in patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Methods: A total of 371 patients who underwent TURBT were enrolled. The main end points were disease-free survival (DFS) and overall survival (OS). Results: MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative DFS. Age and pathological grade were independent risk factors for postoperative OS. Conclusion: MPVLR is an independent risk factor for DFS in NMIBC patients and could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.


The current study investigated the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio (MPVPCR) and plasma fibrinogen (PF) in peripheral blood of patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Included were 371 patients who underwent TURBT and were followed up. A high level of PF indicated worse survival and age and pathological grade were independent risk factors for postoperative survival. High levels of MPV, MPVLR and MPVPCR were associated with recurrence. MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative recurrence. MPVLR could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.


Assuntos
Neoplasias da Bexiga Urinária , Cistectomia , Fibrinogênio , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias da Bexiga Urinária/patologia
13.
Pharmacol Res ; 182: 106281, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35661711

RESUMO

Homeostasis was initially conceptualized by Bernard and Cannon around a century ago as a steady state of physiological parameters that vary within a certain range, such as blood pH, body temperature, and heart rate [1,2]. The underlying mechanisms that maintain homeostasis are explained by negative feedbacks that are executed by the neuronal, endocrine, and immune systems. At the cellular level, homeostasis, such as that of redox and energy steady state, also exists and is regulated by various cell signaling pathways. The induction of homeostatic mechanism is critical for human to adapt to various disruptive insults (stressors); while on the other hand, adaptation occurs at the expense of other physiological processes and thus runs the risk of collateral damages, particularly under conditions of chronic stress. Conceivably, anti-stress protection can be achieved by stressor-mimicking medicinals that elicit adaptive responses prior to an insult and thereby serve as health risk countermeasures; and in situations where maladaptation may occur, downregulating medicinals could be used to suppress the responses and prevent subsequent pathogenesis. Both strategies are preemptive interventions particularly suited for individuals who carry certain lifestyle, environmental, or genetic risk factors. In this article, we will define and characterize a new modality of prophylactic intervention that forestalls diseases via modulating homeostatic signaling. Moreover, we will provide evidence from the literature that support this concept and distinguish it from other homeostasis-related interventions such as adaptogen, hormesis, and xenohormesis.


Assuntos
Hormese , Transdução de Sinais , Homeostase/fisiologia , Humanos , Oxirredução
14.
Front Genet ; 13: 875128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559013

RESUMO

Objective: This study used homologous recombination (HR) related signatures to develop a clinical prediction model for screening immune checkpoint inhibitors (ICIs) advantaged populations and identify hub genes in advanced metastatic urothelial carcinoma. Methods: The single-sample gene enrichment analysis and weighted gene co-expression network analysis were applied to identify modules associated with immune response and HR in IMvigor210 cohort samples. The principal component analysis was utilized to determine the differences in HR-related module gene signature scores across different tissue subtypes and clinical variables. Risk prediction models and nomograms were developed using differential gene expression analysis associated with HR scores, least absolute shrinkage and selection operator, and multivariate proportional hazards model regression. Additionally, hub genes were identified by analyzing the contribution of HR-related genes to principal components and overall survival analysis. Finally, clinical features from GSE133624, GSE13507, the TCGA, and other data sets were analyzed to validate the relationship between hub genes and tumor growth and mutation. Results: The HR score was significantly higher in the complete/partial response group than in the stable/progressive disease group. The majority of genes associated with HR were discovered to be involved in the cell cycle and others. Genomically unstable, high tumor level, and high immune level samples all exhibited significantly higher HR score than other sample categories, and higher HR scores were related to improved survival following ICIs treatment. The risk scores for AUNIP, SEPT, FAM72D, CAMKV, CXCL9, and FOXN4 were identified, and the training and verification groups had markedly different survival times. The risk score, tumor neoantigen burden, mismatch repair, and cell cycle regulation were discovered to be independent predictors of survival time following immunotherapy. Patients with a high level of expression of hub genes such as EME1, RAD51AP1, and RAD54L had a greater chance of surviving following immunotherapy. These genes are expressed at significantly higher levels in tumors, high-grade cancer, and invasive cancer than other categories, and are associated with TP53 and RB1 mutations. Conclusion: HR-related genes are upregulated in genomically unstable samples, the survival time of mUC patients after treatment with ICIs can be predicted using a normogram model based on HR signature.

15.
Mol Carcinog ; 61(7): 690-701, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35472711

RESUMO

Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) is a highly conserved member of aldehyde dehydrogenase (ALDHs) family. Recent studies reveal that it broadly involved in tumorigenesis and drug metabolism in kinds of cancer. However, the critical role of ALDH6A1 in bladder cancer progression and cisplatin resistance of cancer cells are still poorly understood. In this study, we researched the significant function of ALDH6A1 in bladder cancer. Our results showed that ALDH6A1 exhibited a decreased expression in clinical bladder cancer tissues and bladder cancer cell lines. Stable ALDH6A1 knockdown not only could promote cell growth and colony formation in bladder cancer cells, but also enhance drug resistance to cisplatin treatment. On the contrary, we found the active transcript factor hepatocyte nuclear factor 4α (HNF4α, NR2A1) by alveriene could upregulate ALDH6A1 expression, significantly inhibit the cell growth and colony formation of bladder cancer cells, and improve cisplatin sensitivity of bladder cancer cells. Together, our results show that ALDH6A1 plays as a tumor suppressor in bladder cancer, which regulated by HNF4a. ALDH6A1 could be a promising diagnostic marker and treatment target in bladder cancer.


Assuntos
Aldeído Oxirredutases/metabolismo , Antineoplásicos , Neoplasias da Bexiga Urinária , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Família , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
16.
BMC Urol ; 22(1): 65, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439982

RESUMO

OBJECTIVE: To compare the intraoperative safety profiles of transurethral plasmakinetic resection of the prostate (PK-TURP) with transurethral plasmakinetic endoscopic enucleation of the prostate (PK-EEP) in the treatment of benign prostatic hyperplasia (BPH) based on endoscopic surgical monitoring system (ESMS). METHODS: A total of 128 patients who were diagnosed with BPH were stratified based on prostate volume (PV) and accepted PK-EEP or PK-TURP treatment at 1:1 ratio. The ESMS as a novel method was used to monitor blood loss and fluid absorption during the operation. Clinical parameters such as intraoperative blood loss volume, fluid absorption volume, operation time, tissue weight of resection, preoperative and postoperative red blood cell count (RBC), hemoglobin concentration (HB), hematocrit (HCT), electrolyte, postoperative bladder irrigation time, indwelling catheter time, hospital stay time and other associated complications were documented and compared between two groups. RESULTS: No significant differences in majority of baseline characteristics were observed among patients with different prostate volumes between two surgical methods. For patients with prostate volume < 40 ml, the average operation time of patients who received PK-EEP treatment was much more than those who received PK-TURP (P = 0.003). On the other hand, for patients with prostate volume > 40 ml, the PK-TURP surgery was associated with a significant increase in intraoperative blood loss (P = 0.021, in PV 40-80 ml group; P = 0.014, in PV > 80 ml group), fluid absorption (P = 0.011, in PV 40-80 ml group; P = 0.006, in PV > 80 ml group) and postoperative bladder irrigation time as well as indwelling catheter time but decrease in resected tissue weight compared to the PK-EEP treatment. CONCLUSION: The ESMS plays an important role in comparison of intraoperative safety profiles between PK-TURP and PK-EEP. Our data suggest that PK-TURP treatment is associated with a decreased operation time in patients with prostate volume < 40 ml and the PK-EEP treatment is associated with decreased intraoperative blood loss, fluid absorption and increased tissue resection for patients with prostate volume > 40 ml. Our results indicate that the size of prostate should be considered when choosing the right operation method.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Perda Sanguínea Cirúrgica , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento
18.
Med Oncol ; 39(4): 41, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35092501

RESUMO

The tumor immune microenvironment (TIME) and N6-methyladenosine (m6A) are related to the progression of several types of cancer. Nevertheless, the impact of m6A on the TIME of clear cell renal cell carcinoma (ccRCC) remains unclear. This study used an unsupervised clustering algorithm to divide the samples into distinct subgroups. The single sample gene set enrichment analysis (ssGSEA) algorithm to estimate the TIME. The correlation between m6A regulators and immune cells in different subgroups was calculated using Spearman analysis. At last, the relationship between IGF2BP2 and HMGA2 was validated in several datasets, including TCGA-KIRC, GEO, and HPA datasets. We found that m6A regulators were differently expressed in several clinical groups. Based on the expression of m6A regulators, we divided the samples into three subgroups. Then, the survival analysis for these three subgroups showed that the cluster 2 subgroup had poor overall survival (OS). Further, we found that IGF2BP2 and IGF2BP3 were essential components in the cluster 2 subgroup using the principal component analysis (PCA) algorithm. In addition, the expression of these two genes was significantly correlated with survival time. At last, we found that HMGA2 was significantly correlated with IGF2BP2 in several datasets, which indicated that HMGA2 is an essential role in affecting IGF2BP2 regulating the TIME. There is a close correlation between m6A regulators and TIME. Moreover, IGF2BP2 is related to the progression of ccRCC and plays an essential role in affecting the TIME.


Assuntos
Adenosina/análogos & derivados , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Microambiente Tumoral/genética , Adenosina/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Proteína HMGA2/genética , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Prognóstico , Proteínas de Ligação a RNA/genética , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologia
19.
Int J Gen Med ; 15: 325-342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035230

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a commonly occurring tumor. Through a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, immunotherapy may serve as a potential treatment for cancer patients. This study aimed at identifying the survival-related immune cells and hub genes, which could be potential targets for immunotherapy in ccRCC. METHODS: The gene expression profiles and clinical data of ccRCC patients were extracted from UCSC Xena and Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were utilized to select the survival-related tumor-infiltrating immune cells. Multivariate Cox regression was utilized to develop a signature based on the tumor-infiltrating immune cells (TIICs). Based on the signature, the risk score was calculated, following which the samples were divided into high-risk and low-risk groups. Differentially expressed genes (DEGs) between the two risk groups were identified. Functional enrichment analysis was performed and cytoHubba plug-in of Cytoscape was used to identify the hub genes. Multiple datasets were utilized to validate these hub genes, including the Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and the Human Protein Atlas (HPA), and the GEO datasets. Finally, a correlation analysis was performed to evaluate the relationship between the hub genes and TIICs. RESULTS: Four immune survival-related cells, including T cell CD4 memory-activated, T cell regulatory (Tregs), eosinophils, and mast cell resting were identified. Nine immune-specific hub genes were identified, which included APOE, CASR, CTLA4, CXCL8, EGF, F2, KNG1, MMP9, and IL6. Furthermore, these hub genes were significantly correlated with clinical traits and closely associated with some TIICs. CONCLUSION: A total of four survival-related immune cell types and nine hub genes were found to be closely associated with ccRCC. These findings may have implications for the development of novel potential immunotherapeutic targets for ccRCC.

20.
Chin J Integr Med ; 28(5): 394-402, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33963479

RESUMO

OBJECTIVE: To test the hypothesis that ß -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences". METHODS: A total of 138 participants with PQi deficiency (PQD) were randomized to receive ß -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS). RESULTS: PQi status was not significantly different between the ß -glucan and placebo treatment groups at baseline but improved significantly in the ß -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, ß -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo. CONCLUSIONS: ß -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as ß -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).


Assuntos
beta-Glucanas , Adulto , Método Duplo-Cego , Humanos , Qi , Fatores de Risco , Autorrelato , beta-Glucanas/uso terapêutico
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