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1.
BMC Pediatr ; 24(1): 275, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671415

RESUMO

BACKGROUND: To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls. METHODS: In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test. RESULTS: Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index. CONCLUSIONS: Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.


Assuntos
Fibronectinas , Hormônio Foliculoestimulante , Hormônio Luteinizante , Puberdade Precoce , Humanos , Puberdade Precoce/sangue , Puberdade Precoce/diagnóstico , Feminino , Estudos Transversais , Fibronectinas/sangue , Criança , Hormônio Luteinizante/sangue , Hormônio Foliculoestimulante/sangue , Estudos de Casos e Controles , Biomarcadores/sangue , Sensibilidade e Especificidade , Estradiol/sangue , Útero/diagnóstico por imagem
2.
Drug Resist Updat ; 66: 100906, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36565657

RESUMO

It was well known that P-glycoprotein (P-gp/ABCB1) is a master regulator of multidrug resistance (MDR) in cancers. However, the clinical benefit from blocking this pathway remains inconclusive, which motivates a paradigm shift towards alternative strategies for enhancing drug influx. Using a patient-derived organoid (PDO)-based drug screening platform, we report that the combined use of chemotherapy and CCT251545 (CCT) displays robust synergistic effect against PDOs and reduces proliferation of MDR cancer cells in vitro, and results in regression of xenograft tumors, reductions in metastatic dissemination and recurrence rate in vivo. The synergistic activity mediated by CCT can be mainly attributed to the intense uptake of chemotherapeutic agents into the cells, accompanied by alterations in cell phenotypes defined as a mesenchymal epithelial transformation (MET). Mechanistically, analysis of the transcriptome coupled with validation in cellular and animal models demonstrate that the chemosensitizing effect of CCT is profoundly affected by Rac1-dependent macropinocytosis. Furthermore, CCT binds to NAMPT directly, resulting in elevated NAD levels within MDR cancer cells. This effect promotes the assembly of adherents junction (AJ) components with cytoskeleton, which is required for continuous induction of macropinocytosis and consequent drug internalization. Overall, our results illustrate the potential use of CCT as a combination partner for the commonly used chemotherapeutic drugs in the management of MDR cancers.


Assuntos
Antineoplásicos , Neoplasias , Animais , Humanos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Neoplasias/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/farmacologia
3.
Chemistry ; 27(34): 8684-8688, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-33852191

RESUMO

Direct C-H bond transformation has been regarded as one of the most important areas in organic synthesis in both academia and industry. However, the heterogeneous transition-metal-free catalysis of direct C-H bond transformation has remained a contemporary challenge. To tackle this challenge, we designed and constructed a porous phenanthroline-based polymer (namely POP-Phen) via free radical polymerization of vinyl-functionalized phenanthroline monomers. POP-Phen shows excellent catalytic performances in transition-metal-free catalyzed C-H arylation, even better than those of the corresponding homogeneous catalyst, which is mainly attributed to the high density of catalytically active sites in the heterogeneous catalyst. Kinetic isotope experiments and spectral characterizations demonstrate the electron-transfer between the heterogeneous catalyst and the base (t-BuOK), a key step for C-H activation. We believe that this porous organic phenanthroline polymer could open a new door for the design of novel heterogeneous transition-metal-free catalysts for direct C-H activation.

4.
BMC Cancer ; 19(1): 1165, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783819

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs. METHODS: Clinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1. RESULTS: FSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC. CONCLUSIONS: These results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Proteínas de Transporte/metabolismo , Proteína Forkhead Box M1/metabolismo , Proteínas dos Microfilamentos/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/imunologia , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/imunologia , Carcinoma Adrenocortical/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação para Cima , Adulto Jovem
5.
Angew Chem Int Ed Engl ; 58(26): 8670-8675, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-30957347

RESUMO

Herein, we show how the spatial environment in the functional pores of covalent organic frameworks (COFs) can be manipulated in order to exert control in catalysis. The underlying mechanism of this strategy relies on the placement of linear polymers in the pore channels that are anchored with catalytic species, analogous to outer-sphere residue cooperativity within the active sites of enzymes. This approach benefits from the flexibility and enriched concentration of the functional moieties on the linear polymers, enabling the desired reaction environment in close proximity to the active sites, thereby impacting the reaction outcomes. Specifically, in the representative dehydration of fructose to produce 5-hydroxymethylfurfural, dramatic activity and selectivity improvements have been achieved for the active center of sulfonic acid groups in COFs after encapsulation of polymeric solvent analogues 1-methyl-2-pyrrolidinone and ionic liquid.

6.
BMC Urol ; 18(1): 111, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30522461

RESUMO

BACKGROUND: Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer. METHODS: We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed. RESULTS: A total of 329 patients were included. The median duration of follow-up was 54.8 months. Patients with an early post-operative serum albumin level < 32 g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5 months, P = 0.001) and median overall survival (OS; 52.2 versus 57.0 months, P = 0.049) than patients with an early post-operative serum albumin level ≥ 32 g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level < 32 g/L was an independent prognostic factor associated with a decreased RFS (HR = 3.60; 95% CI,1.05-12.42 [months], P = 0.042) and decreased OS (HR = 9.95; 95% CI, 1.81-54.80 [months], P = 0.008). CONCLUSION: An early post-operative serum albumin level < 32 g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Renais/sangue , Neoplasias Renais/cirurgia , Nefrectomia/tendências , Cuidados Pós-Operatórios/tendências , Albumina Sérica Humana/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrectomia/mortalidade , Cuidados Pós-Operatórios/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
7.
Urol Int ; 100(1): 57-65, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29084410

RESUMO

PURPOSE: To assess MRI/Transrectal Ultrasound (TRUS) fusion three-dimensional model-guided targeted biopsy (3D-Tb) versus TRUS-guided systematic biopsy (Sb) in detecting overall and high-Gleason-score (≥7) prostate cancer (PCa). METHODS: Pubmed and Web of science were searched. Studies with men having a suspicious lesion on MRI were included, which were divided into initial biopsy, previous negative biopsy, and mixed groups in meta-analysis. RESULTS: Totally 13 cohorts in 12 studies, with 3,225 men were included. In total population, 3D-Tb and Sb did not differ significantly in the PCa detection rate (43.1 vs. 42.6%, p = 0.36), but after excluding initial biopsy group, the superiority of 3D-Tb became significant (p = 0.01); 3D-Tb had a significantly higher detection rate of high-Gleason-score PCa compared to Sb (30.0 vs. 24.1%, p < 0.05); 3D-Tb plus Sb significantly improved the PCa detection rate based on Sb alone (52.7 vs. 42.6%, p < 0.05). CONCLUSIONS: In men with increased serum PSA and/or abnormal DRE and suspicious lesion on MRI but non-previous evidence of PCa, 3D-Tb plus Sb improves the PCa detection rate based on Sb alone. 3D-Tb alone has better performance in detecting high-Gleason-score PCa, and tends to have a higher PCa detection rate in population with previous negative biopsy compared to Sb.


Assuntos
Imageamento Tridimensional , Imageamento por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Humanos , Biópsia Guiada por Imagem , Masculino , Imagem Multimodal , Reto , Ultrassonografia de Intervenção/métodos
9.
Int Braz J Urol ; 43(5): 805-821, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28379665

RESUMO

AIM: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients. MATERIALS AND METHODS: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1month after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment. RESULTS: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95% confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n=101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n=121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported. CONCLUSION: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and long-term follow-up time studies are needed to confirm our analysis.


Assuntos
Disfunção Erétil/terapia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
Front Oncol ; 12: 970208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158645

RESUMO

Background: The upregulation of amino acid metabolism is an essential form of metabolic reprogramming in cancer. Here, we developed an amino acid metabolism signature to predict prognosis and anti-PD-1 therapy response in clear cell renal cell carcinoma (ccRCC). Methods: According to the amino acid metabolism-associated gene sets contained in the Molecular Signature Database, consensus clustering was performed to divide patients into two clusters. An amino acid metabolism-associated signature was identified and verified. Immune cell infiltrates and their corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correspondence between the signature risk score and the immune therapy response. Results: Two clusters with different amino acid metabolic levels were identified by consensus clustering. The patients in the two clusters differed in overall survival, progression-free survival, amino acid metabolic status, and tumor microenvironment. We identified a signature containing eight amino acid metabolism-associated genes that could accurately predict the prognosis of patients with ccRCC. The signature risk score was positively correlated with infiltration of M1 macrophages, CD8+ T cells, and regulatory T cells, whereas it was negatively correlated with infiltration of neutrophils, NK cells, and CD4+ T cells. Patients with lower risk scores had better overall survival but worse responses to nivolumab. Conclusion: Amino acid metabolic status is closely correlated with tumor microenvironment, response to checkpoint blockade therapy, and prognosis in patients with ccRCC. The established amino acid metabolism-associated gene signature can predict both survival and anti-PD-1 therapy response in patients with ccRCC.

12.
Antioxidants (Basel) ; 11(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35883815

RESUMO

Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and oxidative phosphorylation (OXPHOS), which are critical for cancer survival and progression. However, cancer cells also adapt to such catastrophic oxidative and metabolic stresses by metabolic reprograming, resulting in cancer residuality, progression, and relapse. This adaptation is highly dependent on NADPH and GSH syntheses for ROS scavenging and the upregulation of lipolysis and glutaminolysis, which fuel tricarboxylic acid cycle-coupled OXPHOS and biosynthesis. The underlying mechanism remains poorly understood, thus presenting a promising field with opportunities to manipulate metabolic adaptations for cancer prevention and therapy. In this review, we provide a summary of the mechanisms of metabolic regulation in the adaptation of cancer cells to oxidative stress and the current understanding of its regulatory role in cancer survival and progression.

13.
Front Surg ; 9: 781406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252325

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched, and the hazard ratios were pooled. RESULTS: Patients who underwent resection for recurrence had significantly better OS or OS after recurrence than those who received only nonsurgical treatments (HR 0.34, p < 0.001). Prognostic factors were associated with decreased OS after recurrence, including multiple recurrence (HR 3.23, p = 0.001), shorter disease-free interval (HR 2.94, p < 0.001), stage III-IV of the original tumor (HR 6.17, p = 0.001), sex of male (HR 1.35, p = 0.04), and initial non-R0 resection (HR 2.13, p = 0.001). Prolonged OS after recurrence was observed in those who experienced incomplete resection (HR 0.43, 95% CI 0.31-0.52, I2 = 53%) compared with patients who only received nonsurgical treatments. In the reoperated group, patients who underwent complete resection of recurrence had a prolonged OS after recurrence compared with those who underwent incomplete resection (HR 0.23, p = 0.004). CONCLUSIONS: We confirmed the role of reoperation in the clinical management of recurrent ACC. Select patients might benefit from debulking surgery. The preoperative evaluation of the complete resection of the recurrence is the key means to decide whether patients should undergo surgery. Other prognostic factors associated with prolonged OS include single recurrence site, relatively longer disease-free interval, stage I-II of the original tumor, and female sex.

14.
Front Cell Dev Biol ; 10: 814735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281080

RESUMO

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets. Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA. Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA.

15.
J Inflamm Res ; 15: 6275-6292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386587

RESUMO

Background: Cathepsin Z (CTSZ) is a cathepsin family member that plays a dual role in the adhesion and migration of immune and tumor cells. Methods: The expression pattern of CTSZ in clear cell renal cell carcinoma (ccRCC) was observed by immunohistochemistry and validated by using double-labeling immunofluorescence. Publicly available single-cell sequencing data was used to further define the cell type-specific CTSZ expression in ccRCC. Methylation modification, immune infiltration, and tumor-related signaling enrichment analyses involving CTSZ were performed using multi-omics data. Data from two independent cohorts of anti-programmed death-1 (PD-1) therapeutic clinical trials were used to investigate correlations between CTSZ levels and treatment responses. Results: CTSZ was upregulated in ccRCC tissues compared with adjacent normal tissues at the RNA but not in ccRCC cells. Immunohistochemistry indicated that CTSZ was expressed in tumors infiltrated with lymphocytes. Double immunofluorescence demonstrated that CTSZ was co-expressed with CD68 but not CD8. Single-cell transcriptome data showed macrophage-specific expression of CTSZ in ccRCC. High CTSZ expression was significantly correlated with the enrichment of interferon-γ, epithelial-to-mesenchymal transition, cell cycle, apoptosis pathways, and B cell, macrophage, neutrophil, and dendritic cell infiltrations, as well as the expression of immune checkpoints CTLA4, LAG3, HAVCR2, PDCD1LG2, PDCD1, TIGIT, and SIGLEC15. Hypomethylation modification of cg02744249, cg02744249, and cg22145559 were negatively correlated with CTSZ expression, suggesting an epigenetic mechanism for the regulation of CTSZ expression. Clinically, CTSZ levels were associated with the prognosis of patients with ccRCC (hazard ratio=1.5, P=0.007). Notably, patients with higher CTSZ expression had a worse prognosis with anti-PD-1 monotherapy (hazard ratio=1.51, P=0.039). Conclusion: Macrophage-specific CTSZ was associated with activation of epithelial-to-mesenchymal transition, cell cycle signatures, and a higher infiltration level of B cells, macrophages, neutrophils, and dendritic cells in the tumor microenvironment. High expression of CTSZ could be considered as a prognostic and treatment response biomarker for patients with ccRCC receiving anti-PD-1 immunotherapy.

16.
EMBO Mol Med ; 14(2): e14903, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35023619

RESUMO

Entering a drug-tolerant persister (DTP) state of cancer cells is a transient self-adaptive mechanism by which a residual cell subpopulation accelerates tumor progression. Here, we identified the acquisition of a DTP phenotype in multidrug-resistant (MDR) cancer cells as a tolerance response to routine combination treatment. Characterization of MDR cancer cells with a DTP state by RNA-seq revealed that these cells partially prevented chemotherapy-triggered oxidative stress by promoting NPC1L1-regulated uptake of vitamin E. Treatment with the NPC1L1 inhibitor ezetimibe further enhanced the therapeutic effect of combinatorial therapy by inducing methuosis. Mechanistically, we demonstrated that NRF2 was involved in transcriptional regulation of NPC1L1 by binding to the -205 to -215 bp site on its promoter. Decreased DNA methylation was also related partially to this process. Furthermore, we confirmed that a triple-combination of chemotherapeutic agents, verapamil, and ezetimibe, had a significant anti-tumor effect and prevented tumor recurrence in mice. Together, our study provides a novel insight into the role of DTP state and emphasizes the importance of disrupting redox homeostasis during cancer therapy.


Assuntos
Antineoplásicos , Animais , Antineoplásicos/farmacologia , Homeostase , Proteínas de Membrana Transportadoras , Camundongos
17.
Transl Androl Urol ; 10(2): 879-887, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718089

RESUMO

BACKGROUND: Radical prostatectomy (RP) has heterogeneous effects on survival of patients with metastatic prostate cancer (mPCa). A reliable model to predict risk of cancer-specific mortality (CSM) and the potential benefit derived from RP is needed. METHODS: Patients diagnosed with mPCa were identified using the Surveillance, Epidemiology, and End Results database (2004-2015) and categorized in RP versus nonlocal treatment (NLT). Based on the Fine and Gray competing risks model in 8,463 NLT patients, a nomogram was created to predict CSM in mPCa patients. Decision tree analysis was then utilized for patient stratification. The effect of RP was evaluated among 3 different subgroups. RESULTS: A total of 8,863 patients were identified for analysis. Four hundred (4.5%) patients received RP. The 5-year cumulative incidence of CSM was 52.4% for the entire patients. Based on nomogram scores, patients were sorted into three risk groups using decision tree analysis. In the low- and intermediate-risk group, RP was found to be significantly correlated with a 21.7% risk reduction of 5-year CSM, and 25.0% risk reduction of 5-year CSM, respectively, whereas RP was not associated with CSM in high-risk group (hazard ratio =0.748, 95% confidence interval 0.485-1.150; P=0.190). CONCLUSIONS: We developed a novel nomogram and corresponding patient stratification predicting CSM in mPCa patients. A newly identified patient subgroup with low-, and intermediate-risk of CSM might benefit more from RP. These results should be further validated and improved by ongoing prospective trials.

18.
Chem Asian J ; 16(17): 2469-2474, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34241970

RESUMO

Direct C-H bond activation of heterocycles as a step-economical and environmentally friendly approach to build the heterobiaryls motifs is highly attractive, but it still has a challenge to design and prepare a cheap and regioselective heterogeneous catalyst. To tackle this challenge, we have introduced Ni species into a porous phenanthroline-based organic polymer donated as POP-Phen@Ni. This heterogeneous catalyst shows excellent catalytic performances in regioselective C-H activation of heterocycles, even better than those of the corresponding homogenous catalyst. H/D exchange experiments show that the lithium bis(trimethylsilyl)amide (LiHMDS), a base added in the reaction, play a very important role during the reaction processes. We believe that this heterogeneous catalyst would open a new door for design of heterogeneous catalysts to efficiently catalyze the regioselective C-H activation of heterocycles.

19.
Pharmaceutics ; 13(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34959397

RESUMO

Cancer stem cells (CSCs) are characterized by intrinsic self-renewal and tumorigenic properties, and play important roles in tumor initiation, progression, and resistance to diverse forms of anticancer therapy. Accordingly, targeting signaling pathways that are critical for CSC maintenance and biofunctions, including the Wnt, Notch, Hippo, and Hedgehog signaling cascades, remains a promising therapeutic strategy in multiple cancer types. Furthermore, advances in various cancer omics approaches have largely increased our knowledge of the molecular basis of CSCs, and provided numerous novel targets for anticancer therapy. However, the majority of recently identified targets remain 'undruggable' through small-molecule agents, whereas the implications of exogenous RNA interference (RNAi, including siRNA and miRNA) may make it possible to translate our knowledge into therapeutics in a timely manner. With the recent advances of nanomedicine, in vivo delivery of RNAi using elaborate nanoparticles can potently overcome the intrinsic limitations of RNAi alone, as it is rapidly degraded and has unpredictable off-target side effects. Herein, we present an update on the development of RNAi-delivering nanoplatforms in CSC-targeted anticancer therapy and discuss their potential implications in clinical trials.

20.
Surgery ; 169(5): 1131-1138, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33279225

RESUMO

INTRODUCTION: Adrenocortical carcinoma is a rare endocrine malignancy with a high recurrence rate. The aim of this study was to evaluate the role of surgery for patients with local or distant recurrent adrenocortical carcinoma and to attempt to identify prognostic features related to survival benefit in patients undergoing resection of recurrence. METHODS: The data of 47 patients with recurrent adrenocortical carcinoma in West China Hospital, Sichuan, China, between 2009 and 2019 were retrospectively collected. These patients were divided into 2 groups according to whether resection of recurrence was performed. The correlation between overall survival after recurrence and reoperation was evaluated. Kaplan-Meier and univariate/multivariate Cox regression methods were used to identify any prognostic factors. RESULTS: Included in our study were 21 patients who underwent reoperation and 26 patients who underwent nonoperative treatments were. The operation group had a better median overall survival after recurrence than the nonoperation group (19 months versus 6.5 months; P = .007). In the operated group, disease-free interval >12 months (P = .002), complete resection of recurrent adrenocortical carcinoma (P = .041), and R0 resection of the primary tumor (P = .005) were associated with prolonged survival after recurrence. CONCLUSIONS: Reoperation plays an important role in the management of selected patients with recurrent adrenocortical carcinoma. Disease-free interval, preoperative evaluation for complete resection, and R0 resection of the primary tumor are important prognostic characteristics for the resection of recurrent adrenocortical carcinoma. The overall survival after recurrence was significantly improved for patients who had a disease-free interval >12 months, and initial R0 resection or complete resection of recurrent adrenocortical carcinoma is feasible.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia/estatística & dados numéricos , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem
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