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2.
Int. braz. j. urol ; 47(6): 1120-1130, Nov.-Dec. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1340017

RESUMO

ABSTRACT Background: Periodontal disease is reportedly associated with the risk of various systemic diseases, including pancreatic and lung cancers. However, its association with prostate cancer remains inconclusive. Herein, we explored the association of periodontal disease with the risk of prostate cancer through a meta-analysis. Materials and Methods: MEDLINE, Embase, Web of Sciences and Cochrane Library databases were searched for eligible publications up to April 2020. Multivariate adjusted risk estimates with corresponding 95% confidence intervals (CIs) were extracted and calculated using random- or fixed-effect models. Results: Nine cohort studies involving 3.353 prostate cancer cases with 440.911 participants were identified and included in the meta-analysis. We found that periodontal disease significantly increased the risk of prostate cancer by 1.40-fold (hazard ratio [HR]=1.40, 95% CI: 1.16-1.70; P=0.001; I2=76.1%) compared with normal condition. Interestingly, the risk of developing prostate cancer was not significant in patients treated with periodontal therapy (HR=1.22, 95% CI: 0.86-1.73; P=0.272; I2=65.2%). The results of subgroup analyses were also consistent and significant when stratified by study design and follow-up period, whereas conflicting results were observed in periodontal disease ascertainment stratification. These findings were robust as indicated by sensitivity analyses. Conclusions: Periodontal disease was associated with the increased risk of prostate cancer, whereas no significant association was observed in patients treated with periodontal therapy. Hence, the awareness and importance for maintaining oral health should be improved, and the underlying mechanisms linking periodontal disease and prostate cancer should be fully explored in future research.

3.
Front Pharmacol ; 12: 723729, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776951

RESUMO

The Polycomb protein enhancer of zeste homolog 2 (EZH2) has critical roles in prostate cancer (PCa) progression and drug-resistance, which remains an obstacle for PCa treatment. Enzalutamide (ENZ) is a second-generation androgen receptor antagonist employed for treatment of metastatic castration-resistant prostate cancer A considerable proportion of tumors eventually develop resistance during treatment. Thus, agents that can overcome resistance to PCa are needed urgently. Ilicicolin A (Ili-A), an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, shows antiproliferative activity in human PCa cells, but its mechanism of action against Castration-resistant prostate cancer is not known. Herein, RNA-sequencing showed the EZH2 pathway to be involved in PCa proliferation. Ili-A at low doses reduced the protein level of EZH2, leading to transcriptional change. Interestingly, Ili-A suppressed the binding of EZH2 to promoter regions in AR/serine/threonine polo-like kinase-1/aurora kinase A. Moreover, Ili-A could enhance the anticancer activity of enzalutamide in CRPC cancer models. These data suggest that Ili-A could be used in combination with enzalutamide to treat CRPC.

4.
Transl Stroke Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523038

RESUMO

Type 2 diabetes mellitus (T2DM) is a major comorbidity exacerbating ischemic brain injury and impairing post-stroke recovery. Our previous study suggested that recombinant human fibroblast growth factor (rFGF) 21 might be a potent therapeutic targeting multiple aspects of pathophysiology in T2DM stroke. This study aims to evaluate the potential effects of rFGF21 on cerebrovascular remodeling after T2DM stroke. Permanent distal middle cerebral artery occlusion was performed in heterozygous non-diabetic db/ + and homozygous diabetic db/db mice. Daily rFGF21 administration was initiated 1 week after stroke induction and maintained for up to 2 weeks thereafter. Multiple markers associated with post-stroke recovery, including angiogenesis, oligodendrogenesis, white matter integrity, and neurogenesis, were assessed up to 3 weeks after stroke. Our results showed an impairment in post-stroke vascular remodeling under T2DM condition, reflected by the decreased expression of trophic factors in brain microvessels and impairments of angiogenesis. The defected cerebrovascular remodeling was accompanied by the decreased oligodendrogenesis and neurogenesis. However, delayed rFGF21 administration normalized post-stroke hyperglycemia and improved neurological outcomes, which may partially be via the promotion of pro-angiogenic trophic factor expression in brain microvessels and cerebrovascular remodeling. The better cerebrovascular remodeling may also contribute to oligodendrogenesis, white matter integrity, and neurogenesis after T2DM stroke. Therefore, delayed rFGF21 administration may improve neurological outcomes in T2DM stroke mice, at least in part by normalizing the metabolic abnormalities and promoting cerebrovascular remodeling and white matter repair.

5.
Oncogene ; 40(22): 3826-3844, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958720

RESUMO

Gastric cancer (GC) is one of the leading causes of human mortality around the world. We have previously shown that Gαi1 (the inhibitory subunit 1 of the heterotrimeric guanine nucleotide-binding protein) recruitment to ligand-activated receptor tyrosine kinases (RTKs) is essential for signaling. Testing its role in GC cancer-promoting functions, we found that Gαi1 is upregulated in human GC, correlating with poor overall survival. In established and primary human GC cells, Gαi1 shRNA (small hairpin RNA) or knockout produced significant anti-GC cell activity, proliferation and migration was inhibited, and apoptosis was activated. Conversely, ectopic Gαi1 overexpression promoted proliferation and migration of GC cells in vitro. By examining the tumor-suppressive miRNA microRNA-200a (miR-200a), we found that miR-200a directly silenced Gαi1 to induce anti-GC cell activity. The expression of miR-200a was downregulated in human GC, correlating with upregulation of a novel miR-200a-targeting long non-coding RNA (LncRNA), PINK1 (PTEN Induced Kinase 1)-AS. RNA immunoprecipitation, RNA-pull down, and RNA fluorescence in situ hybridization assays confirmed that PINK1-AS directly binds to miR-200a. Silencing PINK1-AS in GC cells led to miR-200a accumulation, Gαi1 downregulation, and inhibition of GC cell progression in vitro, whereas PINK1-AS upregulation produced the converse results. Significantly, anti-GC cell activity induced by PINK1-AS shRNA was ameliorated by the expression of miR-200a antisense or the 3'-UTR (untranslated region)-depleted Gαi1. In vivo, the growth of subcutaneous MGC-803 xenografts in nude mice was inhibited by PINK1-AS shRNA, but accelerated by PINK1-AS overexpression. Patient-derived GC xenograft growth in nude mice was largely inhibited after intratumoral injection of PINK1-AS shRNA lentivirus. In conclusion, PINK1-AS promotes Gαi1-driven GC progression by sponging miR-200a.

6.
Physiol Plant ; 172(2): 1073-1088, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33755204

RESUMO

Drought stress hinders the growth and development of crop plants and ultimately its productivity. It is expected that drought stress will be frequent and intense in the future due to drastic changes in the global climate. It is necessary to make crop plants more resilient to drought stress through various techniques; drought-hardening is one of them. Defining various metabolic strategies used by tobacco plants to confer drought tolerance will be important for maintaining plant physiological functions, but studies addressing this topic are limited. This study was designed to elucidate the drought tolerance and adaptation strategies used by tobacco plants via the application of different circular drought-hardening cycles (control: no drought-hardening, T1: one cycle of drought hardening, T2: two cycles of drought-hardening, and T3: three cycles of drought-hardening) to two tobacco varieties namely Honghuadajinyuan (H) and Yun Yan-100 (Y). The results revealed that drought-hardening decreased the fresh and dry biomass of the tobacco plants. The decrease was more pronounced in the T3 treatment for both H (23 and 29%, respectively) and Y (26 and 31%, respectively) under drought stress. The MDA contents, especially in T1 and T2 in both varieties, were statistically similar compared with control under drought stress. Similarly, higher POD, APX, and GR activities were observed, especially in T3, and elevated amounts of AsA and GSH were also observed among the different circular drought-hardening treatments under drought stress. Thus circular drought-hardening mitigated the oxidative damage by increasing the antioxidant enzyme activities and elevated the content of antioxidant substances, a key metabolic strategy under drought stress. Similarly, another important plant metabolic strategy is the osmotic adjustment. Different circular drought-hardening treatments improved the accumulation of proline and soluble sugars contents which contributed to osmoregulation. Finally, at the molecular level, circular drought-hardening improved the transcript levels of antioxidant enzyme-related genes (CAT, APX1, and GR2), proline and polyamines biosynthesis-related genes (P5CS1 and ADC2), and ABA signaling (SnRK2), and transcription factors (AREB1 and WRKY6) in response to drought stress. As a result, circular drought-hardening (T2 and T3 treatments) promoted tolerance to water stress via affecting the anti-oxidative capacity, osmotic adjustment, and regulation of gene expression in tobacco.


Assuntos
Secas , Tabaco , Antioxidantes , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Osmorregulação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Tabaco/genética , Tabaco/metabolismo
7.
Int Braz J Urol ; 47(6): 1120-1130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33650836

RESUMO

BACKGROUND: Periodontal disease is reportedly associated with the risk of various systemic diseases, including pancreatic and lung cancers. However, its association with prostate cancer remains inconclusive. Herein, we explored the association of periodontal disease with the risk of prostate cancer through a meta-analysis. MATERIALS AND METHODS: MEDLINE, Embase, Web of Sciences and Cochrane Library databases were searched for eligible publications up to April 2020. Multivariate adjusted risk estimates with corresponding 95% confidence intervals (CIs) were extracted and calculated using random- or fixed-effect models. RESULTS: Nine cohort studies involving 3.353 prostate cancer cases with 440.911 participants were identified and included in the meta-analysis. We found that periodontal disease significantly increased the risk of prostate cancer by 1.40-fold (hazard ratio [HR]=1.40, 95% CI: 1.16-1.70; P=0.001; I2=76.1%) compared with normal condition. Interestingly, the risk of developing prostate cancer was not significant in patients treated with periodontal therapy (HR=1.22, 95% CI: 0.86-1.73; P=0.272; I2=65.2%). The results of subgroup analyses were also consistent and significant when stratified by study design and follow-up period, whereas conflicting results were observed in periodontal disease ascertainment stratification. These findings were robust as indicated by sensitivity analyses. CONCLUSIONS: Periodontal disease was associated with the increased risk of prostate cancer, whereas no significant association was observed in patients treated with periodontal therapy. Hence, the awareness and importance for maintaining oral health should be improved, and the underlying mechanisms linking periodontal disease and prostate cancer should be fully explored in future research.


Assuntos
Neoplasias Pulmonares , Doenças Periodontais , Neoplasias da Próstata , Estudos de Coortes , Humanos , Masculino , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia
8.
Oncogene ; 40(15): 2625-2634, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33750894

RESUMO

Castration-resistant prostate cancer (CRPC) almost invariably occurs after androgen-deprivation therapy (ADT) for the advanced metastatic disease. It is generally believed that among multiple mechanisms and signaling pathways, CRPC is significantly driven by the reactivation of androgen receptor (AR) signaling in ADT-treated patients with castrate levels of androgen, partially at least mediated by the androgen biosynthesis within the tumor, also known as intratumoral or intraprostatic androgen biosynthesis. Steroidogenic enzymes, such as CYP11A1, CYP17A1, HSD3B1, AKR1C3 and SRD5A, are essential to catalyze the conversion of the initial substrate cholesterol into potent androgens that confers the CRPC progression. Accumulating evidences indicate that many steroidogenic enzymes are upregulated in the progression setting; however, little is known about the dysregulation of these enzymes in CRPC. Orphan nuclear receptors (ONRs) are members of the nuclear receptor superfamily, of which endogenous physiological ligands are unknown and which are constitutively active independent of any physiological ligands. Studies have validated that besides AR, ONRs could be the potential therapeutic targets for prostate cancer, particularly the lethal CRPC progression. Early studies reveal that ONRs play crucial roles in the transcriptional regulation of steroidogenic enzyme genes. Notably, we and others show that three distinct ONRs, including liver receptor homolog-1 (LRH-1, NR5A2), steroidogenic factor 1 (SF-1, AD4BP, NR5A1) and estrogen-related receptor α (ERRα, NR3B1), can contribute to the CRPC progression by promotion of the intratumoral androgen synthesis via their direct transcriptional regulation on multiple steroidogenic enzymes. This review presents an overview of the current understanding on the intratumoral androgen biosynthesis in CRPC, with a special focus on the emerging roles of ONRs in this process.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Biomarcadores Tumorais/metabolismo , Receptores Nucleares Órfãos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antagonistas de Androgênios/farmacologia , Humanos , Masculino , Receptores Nucleares Órfãos/farmacologia
9.
Transl Neurosci ; 12(1): 32-39, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33552592

RESUMO

Background: Glioblastoma multiforme (GBM) is the leading cause of death among adult brain cancer patients. Glutathione peroxidase 2 (GPX2), as a factor in oxidative stress, plays an important role in carcinogenesis. However, its role in GBM has not been well established. The study aimed to investigate the clinical significance of GPX2 with GBM prognosis. Methods: Data of GBM and healthy individuals were retrospectively collected from oncomine, cancer cell line encyclopedia (CCLE), gene expression profiling interactive analysis (GEPIA), UALCAN, and Human Protein Atlas. GPX2 mRNA expression was first assessed across various cancer types in oncomine and cancer cell lines from CCLE. The mRNA expression of GPX2 was compared between normal and GBM tissues using GEPIA (normal = 207; GBM = 163) and UALCAN (normal = 5; GBM = 156). The GPX2 methylation was analyzed using data from UALCAN (normal = 2; GBM = 140). The prognostic value of GPX2 in GBM was explored in GEPIA and UALCAN using Kaplan-Meier method. STRING database was used to construct protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Statistical significance was set as <0.05. Results: The current study revealed no significant differences in GPX2 expression between normal and GBM from GEPIA data (P > 0.05) and UALCAN (P = 0.257). Patients with higher GPX2 intended to have a poorer prognosis (P = 0.0089). The KEGG pathways found that chemokine-signaling pathway were the more preferred. Conclusions: The findings demonstrated that GPX2 might be a potential diagnosis and prognostic indicator for GBM. Chemokine-signaling pathway may be involved in GPX2 function.

10.
Urol Oncol ; 39(3): 171-179, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33262027

RESUMO

BACKGROUND: Patients with bladder cancer have a high risk of suicide. This study aimed to assess how bladder cancer increases suicide risk and to identify the demographic and clinical factors associated with suicidal death among patients with bladder cancer. METHODS: Literature search of MEDLINE, PsycINFO, Embase, Web of Sciences and Cochrane Library databases was conducted up to April 2020 to identify eligible studies related to the incidence and risk factors of suicide after bladder cancer diagnosis. Summary multivariate-adjusted risk estimates and their associated 95% confidence intervals (CIs) were calculated using inverse variance method with random or fixed-effect modeling. RESULTS: Five retrospective cohorts comprising 563,680 patients with bladder cancer were included. Higher risk of suicide by 1.90-fold was observed among patients with bladder cancer (hazard ratio, HR = 1.90, 95% CI: 1.29-2.81; P = 0.001; I2 = 81.2%), especially in those aged 70 years or older (HR = 1.36, 95% CI: 1.29-1.43; P < 0.001; I2 = 0%), unmarried (HR = 1.72, 95% CI: 1.61-1.83; P < 0.001; I2 = 0%), and those with regional bladder cancer (HR = 1.88, 95% CI: 1.10-3.21; P = 0.021; I2 = 96.3%), compared with those without bladder cancer. Furthermore, gender and race were not associated with increased suicide risk among patients with bladder cancer. CONCLUSIONS: Suicide risk is increased among patients with bladder cancer, particularly those aged 70 years or older, unmarried and those with regional bladder cancer. Hence, early psychological support must be provided during the follow-up period of these special populations with a high suicide risk.


Assuntos
Suicídio/estatística & dados numéricos , Neoplasias da Bexiga Urinária/psicologia , Humanos , Incidência , Fatores de Risco , Neoplasias da Bexiga Urinária/diagnóstico
11.
Oncol Lett ; 21(1): 70, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33365081

RESUMO

Breast cancer is the second most common cause of cancer-associated mortality among women worldwide, and triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Berbamine (BBM) is a traditional Chinese medicine used for the treatment of leukopenia without any obvious side effects. Recent reports found that BBM has anti-cancer effects. The present study aimed to investigate the effects of BBM on TNBC cell lines and the underlying molecular mechanism. MDA-MB-231 cells and MCF-7 cells, two TNBC cell lines, were treated with various concentrations of BBM. A series of bioassays including MTT, colony formation, EdU staining, apoptosis, trypan blue dye, wound healing, transwell, ELISA and western blotting assays were performed. The results showed that BBM significantly inhibited cell proliferation of MDA-MB-231 cells (P<0.05; IC50=22.72 µM) and MCF-7 cells (P<0.05; IC50=20.92 µM). BBM (20 µM) decreased the apoptosis ratio (percentage of absorbance compared with the control group) by 28.4±3.3% (P<0.05) in MDA-MB-231 cells, and 62.4±24.6% (P<0.05) in MCF-7 cells. In addition, BBM inhibited cell migration and invasion of TNBC cells. Furthermore, the expression levels of PI3K, phosphorylated-Akt/Akt, COX-2, LOX, MDM2 and mTOR were downregulated by BBM, and the expression of p53 was upregulated by BBM. These results indicated that BBM may suppress the development of TNBC via regulation of the PI3K/Akt/MDM2/p53 and PI3K/Akt/mTOR signal pathways. Therefore, BBM might be used as a drug candidate for the treatment of TNBC in the future.

12.
Front Cell Dev Biol ; 8: 591067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330470

RESUMO

Age-related macular degeneration (AMD) is a major cause of irreversible blindness among the elderly population. Dysfunction and degeneration of the retinal pigment epithelial (RPE) layer in the retina underscore the pathogenesis of both dry and wet AMD. Advanced age, cigarette smoke and genetic factors have been found to be the prominent risk factors for AMD, which point to an important role for oxidative stress and aging in AMD pathogenesis. However, the mechanisms whereby oxidative stress and aging lead to RPE cell degeneration are still unclear. As cell senescence and cell death are the major outcomes from oxidative stress and aging, here we review the mechanisms of RPE cell senescence and different kinds of cell death, including apoptosis, necroptosis, pyroptosis, ferroptosis, with an aim to clarify how RPE cell degeneration could occur in response to AMD-related stresses, including H2O2, 4-Hydroxynonenal (4-HNE), N-retinylidene-N-retinyl-ethanolamine (A2E), Alu RNA and amyloid ß (Aß). Besides those, sodium iodate (NaIO3) induced RPE cell degeneration is also discussed in this review. Although NaIO3 itself is not related to AMD, this line of study would help understand the mechanism of RPE degeneration.

13.
Urol J ; 18(4): 371-379, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33236334

RESUMO

PURPOSE: The impact of marital status on the prognosis amongst patients diagnosed with prostate cancer remains controversial. Thus, a meta-analysis was performed to determine whether marital status can influence the prognosis in patients with prostate cancer. MATERIALS AND METHODS: Literature search of the MEDLINE, PsycINFO, Embase and Cochrane Library databases was conducted to identify eligible studies published before April 2020. Multivariate adjusted risk estimates and corresponding 95% confidence intervals (CIs) were extracted and calculated using the random effects model. RESULTS: A total of 11 observational studies comprising 1,457,799 patients diagnosed with prostate cancer were identified. Results indicated that unmarried status (separated, divorced, widowed or never married) was associated with an increased risk of all-cause mortality (hazard ratio, HR = 1.39, 95% CI: 1.30-1.50; P < .001; I2 = 92.2%) compared with married status, especially for divorced and never-married patients. Similarly, being unmarried had an elevated risk of cancer-specific mortality (HR = 1.29, 95% CI: 1.17-1.41; P < .001; I2 = 82.5%) in patients with prostate cancer. A significant difference was also observed between unmarried status and shorter overall survival (HR = 1.37, 95% CI: 1.20-1.56; P < .001; I2 = 94.5%). CONCLUSION: Results demonstrated that unmarried status is associated with a worse prognosis regarding mortality and survival in patients diagnosed with prostate cancer, particularly in divorced and never-married patients. Hence, further research should explore the potential mechanisms which can benefit the development of novel, more personalised management methods for unmarried patients with prostate cancer.

14.
BMC Plant Biol ; 20(1): 486, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097005

RESUMO

BACKGROUND: Drought stress is the most harmful one among other abiotic stresses with negative impacts on crop growth and development. Drought-hardening is a feasible and widely used method in tobacco seedlings cultivation. It has gained extensive interests due to its role in improving drought tolerance. This research aimed to investigate the role of drought-hardening and to unravel the multiple mechanisms underlying tobacco drought tolerance and adaptation. RESULTS: This study was designed in which various drought-hardening treatments (CK (no drought-hardening), T1 (drought-hardening for 24 h), T2 (drought-hardening for 48 h), and T3 (drought-hardening for 72 h)) were applied to two tobacco varieties namely HongHuaDaJinYuan (H) and Yun Yan-100 (Y). The findings presented a complete framework of drought-hardening effect at physiological, biochemical, and gene expression levels of the two tobacco varieties under drought stress. The results showed that T2 and T3 significantly reduced the growth of the two varieties under drought stress. Similarly, among the various drought-hardening treatments, T3 improved both the enzymatic (POD, CAT, APX) and non-enzymatic (AsA) defense systems along with the elevated levels of proline and soluble sugar to mitigate the negative effects of oxidative damage and bringing osmoregulation in tobacco plants. Finally, the various drought-hardening treatments (T1, T2, and T3) showed differential regulation of genes expressed in the two varieties, while, particularly T3 drought-hardening treatment-induced drought tolerance via the expression of various stress-responsive genes by triggering the biosynthesis pathways of proline (P5CS1), polyamines (ADC2), ABA-dependent (SnRK2, AREB1), and independent pathways (DREB2B), and antioxidant defense-related genes (CAT, APX1, GR2) in response to drought stress. CONCLUSIONS: Drought-hardening made significant contributions to drought tolerance and adaptation in two tobacco variety seedlings by reducing its growth and, on the other hand, by activating various defense mechanisms at biochemical and molecular levels. The findings of the study pointed out that drought-hardening is a fruitful strategy for conferring drought tolerance and adaptations in tobacco. It will be served as a useful method in the future to understand the drought tolerance and adaptation mechanisms of other plant species. Drought-hardening improved drought tolerance and adaptation of the two tobacco varieties. T1 indicates drought-hardening for 24 h, T2 indicates drought-hardening for 48 h, T3 indicates drought-hardening for 72 h.


Assuntos
Tabaco/fisiologia , Adaptação Fisiológica , Ácido Ascórbico/metabolismo , Clorofila/metabolismo , Produção Agrícola/métodos , Desidratação , Fluorescência , Regulação da Expressão Gênica de Plantas/fisiologia , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Oxirredução , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Prolina/metabolismo , Tabaco/crescimento & desenvolvimento , Tabaco/metabolismo
15.
Am J Transl Res ; 12(9): 5433-5448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042429

RESUMO

Breast cancer is the most common malignant tumor and the leading cause of cancer-related death in women. The ubiquitin-proteasome system regulates the stability of most proteins controlling various biological processes in human cells. PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of breast cancer remain largely unknown. In this study, we assessed the level of PSMD7 in breast cancer tissues and investigated the underlying molecular events by which PSMD7 could play a role in tumor progression. The results showed that the PSMD7 level was significantly upregulated in breast cancer tissues. PSMD7 expression was closely associated with tumor subtype, tumor size, lymph node invasion, and TNM stage. A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in breast cancer patients. Furthermore, univariate Cox regression analysis indicated that lymph node invasion, distant metastasis, and PSMD7 expression were associated with OS and DFS. Multivariate regression analysis indicated that PSMD7 was an independent predictor of OS (HR=1.310, 95% CI=1.038-1.652). Importantly, PSMD7 knockdown induced cell cycle arrest in the G0/G1 phase, leading to cell senescence and apoptosis. PSMD7 knockdown inhibited the expression of key cell cycle-related proteins and promoted the stability of p21 and p27 in breast cancer cells. PSMD7 may be a valuable prognostic indicator and potential therapeutic target for breast cancer.

16.
Int. braz. j. urol ; 46(5): 786-793, Sept.-Oct. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1134218

RESUMO

ABSTRACT Objective: This study aims to design a novel semirigid ureterorenoscope with irrigation and vacuum suction system and a modified ureteral access sheath (UAS) named Sotn ureterorenoscope® (Sotn=ShuoTong Medical Company) to overcome the deficiencies of the current procedure and to improve the efficiency and safety of using Sotn ureterorenoscope® for treatment of upper urinary calculi. Materials and Methods: Fifty-eight patients, comprising 31 males and 27 females, were evaluated. The medical records of 58 patients with upper urinary calculi treated with Sotn ureterorenoscope® from March 2015 to June 2017 were retrospectively reviewed at the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and one month after treatment. The secondary outcome was postoperative complication rate. Results: The mean and SD of operative duration was 48.5 (10.4) min, and the mean and SD of stone size was 15.6 (5.6) mm. The primary overall SFR was 89.7% (52/58) and 100% at 1 month follow-up. Complication, which was Clavien I (minor fever managed by antipyretic therapy), was detected in 1.7% (1/58) of the patients. Conclusions: Sotn ureterorenoscope® is technically feasible, efficacious and safe for treatment of upper urinary calculi because of its advantages of high SFR and low complication rates.


Assuntos
Humanos , Masculino , Neoplasias da Próstata/complicações , Cálculos Ureterais/cirurgia , Cálculos Ureterais/diagnóstico por imagem , Ureteroscopia/métodos , Complicações Pós-Operatórias , Neoplasias da Próstata/patologia , Cálculos Renais , Tomografia Computadorizada por Raios X , China , Estudos Retrospectivos , Resultado do Tratamento , Ureteroscópios
17.
Cell Death Dis ; 11(9): 805, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978368

RESUMO

A1874 is a novel BRD4-degrading proteolysis targeting chimera (PROTAC). In primary colon cancer cells and established HCT116 cells, A1874 potently inhibited cell viability, proliferation, cell cycle progression, as well as cell migration and invasion. The BRD4-degrading PROTAC was able to induce caspase and apoptosis activation in colon cancer cells. Furthermore, A1874-induced degradation of BRD4 protein and downregulated BRD-dependent genes (c-Myc, Bcl-2, and cyclin D1) in colon cancer cells. Significantly, A1874-induced anti-colon cancer cell activity was more potent than the known BRD4 inhibitors (JQ1, CPI203, and I-BET151). In BRD4-knockout colon cancer cells A1874 remained cytotoxic, indicating the existence of BRD4-independent mechanisms. In addition to BRD4 degradation, A1874 cytotoxicity in colon cancer cells was also associated with p53 protein stabilization and reactive oxygen species production. Importantly, the antioxidant N-acetyl-cysteine and the p53 inhibitor pifithrin-α attenuated A1874-induced cell death and apoptosis in colon cancer cells. In vivo, A1874 oral administration potently inhibited colon cancer xenograft growth in severe combined immuno-deficient mice. BRD4 degradation and p53 protein elevation, as well as apoptosis induction and oxidative stress were detected in A1874-treated colon cancer tissues. Together, A1874 inhibits colon cancer cell growth through both BRD4-dependent and -independent mechanisms.


Assuntos
Neoplasias do Colo/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose , Feminino , Humanos , Camundongos , Camundongos SCID , Oncogenes
18.
BMC Urol ; 20(1): 141, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883254

RESUMO

BACKGROUND: Transurethral resection of the prostate (TURP) is the first choice for the treatment of benign prostatic hyperplasia. However, Transurethral split of prostate (TUSP) also seems to have clear clinical efficacy and clinical promotion value. To better clarify the potential and limitations of this treatment of prostate hyperplasia. This study objectively evaluated the clinical efficacy and safety of TUSP. METHODS: The Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), Wanfang (Wanfang data), and SinoMed databases were searched for relevant studies. We then used Revman Manager 5.3 to perform a meta-analysis of all randomized controlled trials that evaluated the efficacy and safety of TUSP versus the classic surgical procedures commonly used in the clinic. RESULTS: A total of 7 studies involving 592 patients were included. The combined data showed that TUSP can shorten the operation time [MD: -33.68; 95% CI: - 38.45 to - 28.91; P < 0.001], reduce intraoperative blood loss [MD: -56.06; 95% CI: - 62.68 to - 49.43; P < 0.001], shorten the time of indwelling catheter [MD: -1.83; 95% CI: - 1.99 to - 1.67; P < 0.001], shorten the postoperative hospital stay length [MD: -1.61; 95% CI: - 1.90 to - 1.32; P < 0.001] and improved postoperative quality of life score (QOL) [MD: 0.16; 95% CI: 0.02 to 0.29; P = 0.02] compared to traditional surgical approaches. There were no statistically significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine volume (RUV), or complications between TUSP and traditional approached. CONCLUSION: TUSP can be an effective alternative for clinical treatment of benign prostatic hyperplasia. Given the limitations of the included studies, more high-quality randomized controlled trials are needed in the future to validate or update the results of this analysis.


Assuntos
Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Dilatação/instrumentação , Desenho de Equipamento , Humanos , Masculino , Prostatectomia/efeitos adversos , Prostatectomia/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Uretra , Cateteres Urinários
19.
Front Microbiol ; 11: 1402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670243

RESUMO

Background: The prevalence of colonization with multidrug-resistant organisms (MDROs) among healthy adults in the community is largely unknown. This study investigated the colonization rate of multidrug-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in the community in Taiwan, and compared the gut microbiota between MDRO carriers and non-carriers. Methods: This prospective cohort study was conducted from March 2017 to February 2018 at the Hsin-Chu and Jin-Shan branches of National Taiwan University Hospital. Nasal swabs and stool samples were obtained from healthy adults attending a health examination to screen for MDROs. Bacteria isolates of MDROs were tested for antibiotic susceptibility and resistant genes. Relevant data were collected using a standardized questionnaire to evaluate the risk factors for MDROs carriage, and 16S rRNA metagenomics sequencing was performed to analyze gut microbiota. Results: Among 187 participants, 4.6% (8/174) carried MRSA and 41.4% (77/186) carried third-generation cephalosporin-resistant (3GC-R) Escherichia coli or Klebsiella pneumoniae. The carriage rate of AmpC beta-lactamases and ESBL-producing strains were 16.1 and 27.4%, respectively. No carbapenem-resistant Enterobacteriaceae (CRE) or VRE were detected. The dominant resistant gene of E. coli isolates was CTX-M-type (73%), while that of K. pneumoniae was AmpC beta-lactamases (80%). In the multivariate analysis, the significant risk factors for carrying 3GC-R E. coli or K. pneumoniae were being an employee of technology company A [adjusted odds ratio (aOR) 4.127; 95% confidence interval (CI) 1.824-9.336; p = 0.001], and traveling to Southeast Asia in the past year (aOR 6.545; 95% CI 1.071-40.001; p = 0.042). The gut microbiota analysis showed that the phylum Proteobacteria and the family Enterobacteriaceae were significantly more abundant in 3GC-R E. coli and K. pneumoniae carriers. Conclusion: A high rate of Taiwanese adults in the community carried 3GC-R Enterobacteriaceae, while no CRE or VRE colonization was noted. Compared with non-carriers, an expansion of Enterobacteriaceae in gut microbiota was found among 3GC-R Enterobacteriaceae carriers.

20.
Int Braz J Urol ; 46(5): 786-793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32539255

RESUMO

OBJECTIVE: This study aims to design a novel semirigid ureterorenoscope with irrigation and vacuum suction system and a modified ureteral access sheath (UAS) named Sotn ureterorenoscope® (Sotn=ShuoTong Medical Company) to overcome the deficiencies of the current procedure and to improve the efficiency and safety of using Sotn ureterorenoscope® for treatment of upper urinary calculi. MATERIALS AND METHODS: Fifty-eight patients, comprising 31 males and 27 females, were evaluated. The medical records of 58 patients with upper urinary calculi treated with Sotn ureterorenoscope® from March 2015 to June 2017 were retrospectively reviewed at the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and one month after treatment. The secondary outcome was postoperative complication rate. RESULTS: The mean and SD of operative duration was 78.5 (30.4) min, and the mean and SD of stone size was 15.6 (5.6) mm. The primary overall SFR was 89.7% (52/58) and 100% at 1 month follow-up. Complication, which was Clavien I (minor fever managed by antipyretic therapy), was detected in 1.7% (1/58) of the patients. CONCLUSIONS: Sotn ureterorenoscope® is technically feasible, efficacious and safe for treatment of upper urinary calculi because of its advantages of high SFR and low complication rates.


Assuntos
Neoplasias da Próstata/complicações , Cálculos Ureterais/diagnóstico por imagem , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , China , Humanos , Cálculos Renais , Masculino , Complicações Pós-Operatórias , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ureteroscópios
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