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1.
J Clin Ultrasound ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944676

RESUMO

BACKGROUND: Lung ultrasound can evaluate for pneumothorax but the accuracy of diagnosis depends on experience among physicians. This study aimed to investigate the sensitivity and specificity of intelligent lung ultrasound in comparison with chest x-ray, employing chest computed tomography (CT) as the gold standard for diagnosis of pneumothorax in critical ill patients. METHODS: This prospective, observational study included 75 dyspnea patients admitted to the Intensive Care Unit of the Fourth Affiliated Hospital of Soochow University from January 2021 to April 2023. Lung ultrasound images were collected using BLUE-plus protocol and analyzed by artificial intelligence software to identify the pleural line, with CT results serving as the gold standard for diagnosis. Pneumothorax was diagnosed based on either the disappearance of pleural slip sign or identification of lung point. Additionally, chest x-ray images and diagnostic results were also obtained during the same period for comparison. RESULTS: The sensitivity and specificity of intelligent lung ultrasound in diagnosing pneumothorax were 79.4% and 85.4%, respectively. The sensitivity and specificity of x-ray diagnosis were 82.4% and 80.5%. Additionally, the diagnostic time for lung ultrasound was significantly shorter than that for x-ray examination. CONCLUSION: Intelligent lung ultrasound has diagnostic efficiency comparable to that of x-ray examination but offers advantages in terms of speed.

2.
BMC Anesthesiol ; 23(1): 153, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142971

RESUMO

BACKGROUND: This study was conducted to investigate the effects and safety of remimazolam versus propofol on cerebral oxygen saturation and cerebral hemodynamics during the induction of general anesthesia in patients receiving carotid endarterectomy (CEA), so as to provide theoretical basis for better clinical application of remimazolam. METHODS: Forty-three patients (60-75 years old) with carotid artery stenosis (carotid artery stenosis greater than 70%) were randomly divided into the remimazolam group (R group) and the propofol group (P group). Anesthesia was induced with remimazolam (0.3 mg/kg) or propofol (1.5-2 mg/kg) individually. At time of admission (T0), post-anesthesia induction (T1), consciousness disappears (T2), 1 min after loss of consciousness (T3), 2 min after loss of consciousness (T4) and pre-endotracheal intubation (T5), measurement in patients with regional cerebral oxygen saturation (SrO2), average blood flow velocity (Vm), resistance index (RI), mean arterial pressure (MAP), heart rate (HR) and cardiac index (CI) were recorded. RESULTS: SrO2 increased significantly in both groups after induction of anesthesia compared with baseline (P < 0.05) and decreased after loss of consciousness (P < 0.05). There was no difference in the mean value of the relative changes in SrO2 between the groups. Meanwhile, the Vm, RI, HR and CI of each time point between two groups showed no statistically significant difference (P > 0.05) while MAP in group P at T5 was lower than that in group R individually(P < 0.05). In each group, Vm, HR, CI and MAP at T2-T5 were all significantly reduced compared with T1, with statistically differences(P < 0.05). Specifically, there was no difference of RI at each time between or within groups(P > 0.05). CONCLUSIONS: Our study revealed that remimazolam can be administered safely and effectively during the induction of general anesthesia for carotid endarterectomy in elder population and it demonstrated superiority in hemodynamic changes compared with propofol. CLINICAL TRIAL REGISTRATION: This trial was retrospectively registered with the Chinese Clinical Trial Registry. REGISTRATION NUMBER: ChiCTR2300070370. Date of registration: April 11, 2023.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Propofol , Humanos , Idoso , Pessoa de Meia-Idade , Propofol/farmacologia , Estenose das Carótidas/cirurgia , Saturação de Oxigênio , Anestesia Geral , Circulação Cerebrovascular , Inconsciência
3.
Cell Physiol Biochem ; 46(4): 1606-1616, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29694981

RESUMO

BACKGROUND/AIMS: CircRNAs regulate gene expression in different malignancies. However, the role of Cdr1as in the tumourigenesis of bladder cancer and its potential mechanisms remain unknown. METHODS: qRT-PCR was used to detect Cdr1as and target miRNA expression in bladder cancer tissues and cell lines. Biological functional experiments were performed to detect the effects of Cdr1as on the biological behaviour of bladder cancer cells in vivo and in vitro. Bioinformatic analysis was utilised to predict potential miRNA target sites on Cdr1as. Ago2 RNA binding protein immunoprecipitation assay, RNA antisense purification assay, biotin pull down assay and RNA FISH were performed to detect the interaction between Cdr1as and target miRNAs. Western blot was used to determine the expression level of p21 in bladder cancer cells. RESULTS: Cdr1as was significantly down-regulated in bladder cancer tissues compared with adjacent normal tissues. Overexpression of Cdr1as inhibited the proliferation, invasion and migration of bladder cancer cells in vitro and slowed down tumour growth in vivo. Cdr1as sponged multiple miRNAs in bladder cancer. Moreover, Cdr1as directly bound to miR-135a and inhibited its activity in bladder cancer. CONCLUSION: Cdr1as is down-regulated and sponges multiple miRNAs in bladder cancer. It exerts anti-oncogenic functions by sponging microRNA-135a.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/patologia , Animais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Hibridização in Situ Fluorescente , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , RNA Longo não Codificante/genética , Transplante Heterólogo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
4.
Mol Cancer ; 17(1): 19, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29386015

RESUMO

BACKGROUND: Circ-ITCH is a circRNA generated from several exons of itchy E3 ubiquitin protein ligase (ITCH) and tumor suppressor served as a sponge for certain miRNAs targeting their parental transcripts of ITCH. However, the role of circ-ITCH in bladder cancer (BCa) was not reported. In the present study, we investigated the role of circ-ITCH in BCa. METHODS: Quantitative real-time PCR was used to detect the expression of circ-ITCH and survival analysis was adopted to explore the association between circ-ITCH expression and the prognosis of BCa. BCa cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion, cell cycle and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effect of circ-ITCH in BCa. Biotin-coupled probe pull down assay, Biotin-coupled miRNA capture, Fluorescence in situ hybridization and Luciferase reporter assay were conducted to confirm the relationship between the circ-ITCH and the microRNA. RESULTS: In the present study, we found that circ-ITCH, is down-regulated in BCa tissues and cell lines. BCa patients with low circ-ITCH expression had shortened survival. Enforced- expression of circ-ITCH inhibited cells proliferation, migration, invasion and metastasis both in vitro and in vivo. Mechanistically, we demonstrated that circ-ITCH up-regulates the expression of miR-17 and miR-224 target gene p21 and PTEN through 'sponging' miR-17 and miR-224, which suppressed the aggressive biological behaviors of BCa. CONCLUSIONS: circ-ITCH acts as a tumor suppressor by a novel circ-ITCH/miR-17, miR-224/p21, PTEN axis, which may provide a potential biomarker and therapeutic target for the management of BCa.


Assuntos
MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA , Proteínas Repressoras/genética , Ubiquitina-Proteína Ligases/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA/sangue , RNA Circular , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/mortalidade
5.
J Cancer ; 8(17): 3456-3463, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29151929

RESUMO

Circular RNA (circRNA) comprises a class of endogenous species of RNA consisting of a circular loop that is crucial for genetic and epigenetic regulation. The significance of circRNA in bladder cancer (BCa) remains to be investigated. Here we performed genome­wide circRNA analysis of 5 paired tumour and adjacent normal tissue samples from BCa patients via next generation sequencing (NGS) technology. Next we confirmed NGS data in a separate set of 32 paired BCa samples using quantitative real-time reverse transcription polymerase chain reaction. The results showed that circRNA profile presented a total of 88,732 circRNA in BCa samples. Among them, 14 were upregulated and 42 were downregulated with q-values of <0.001 and fold changes of ≥2 or ≤0.5. The expression level changes of hsa_circ_0091017 and hsa_circ_0002024 in the 32 paired samples were in accord with NGS data. In conclusion, we identified a set of circRNAs that are potentially implicated in the tumorigenesis of BCa and could serve as novel diagnostic markers for BCa.

6.
Oncotarget ; 8(47): 82956-82967, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29137315

RESUMO

Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated. Besides, Nrf2, NF-κB, I-kB, HO-1 and NQO-1 expression levels in the testis were measured by immunohistochemical staining or western blot analysis. DBP significantly reduced anogenital distance (AGD) and influenced testes growth in male mice offsprings, while SFN ameliorated these phenotypes. After DBP stimulation, the testicular morphology, testicular cell apoptosis index and the oxidative stress markers exhibited statistical differences compared with Control group, while SFN supplementation showed obvious improvements. In addition, administration of SFN could obviously increase the expression level of Nrf2 and its downstream ARE gene battery, such as HO-1, NQO-1 in the testis. Meanwhile, SFN pretreatment did not confer protection against DBP-induced testicular oxidative stress injury in Nrf2 knockout mice. Therefore, the present findings suggested that SFN could effectively protect against DBP-induced testicular oxidative stress injury through Nrf2/ARE signaling pathways in male mice offsprings.

7.
Oncotarget ; 8(31): 51766-51778, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881685

RESUMO

Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.

8.
Medicine (Baltimore) ; 96(25): e7258, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28640128

RESUMO

BACKGROUND: Previous studies have been conducted to reveal the relationship between androgen receptor CAG polymorphism and risk of prostate cancer, yet the results were elusive and controversial. Thus, this meta-analysis was performed to clarify this association. METHODS: To obtain the relevant available studies, online databases PubMed, Embase, and Web of science were searched until September 1st, 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Subgroup analyses were conducted based on ethnicity and source of controls. Moreover, Begg's funnel plots and Egger's linear regression test were conducted to test the publication bias. RESULTS: Overall, our results enrolled 51 studies indicated that significant increased risk of prostate cancer was associated with androgen receptor CAG polymorphism (OR  =  0.77, 95% CI: 0.67-0.89). In addition, compared with CAG repeat <20, 22, carriers of ≧20, 22 repeats had decreased risk of prostate cancer (cut-off point  =  20: OR  =  0.27, 95% CI: 0.13-0.52; cut-off point  =  22: OR  =  0.82, 95% CI: 0.70-0.97). However, when cut-off point  =  23, no significant result was detected in such association (pooled OR  =  0.88, 95% CI: 0.63-1.24). When cut-off point is 22, the results were positive only in Asian population (OR  =  0.53, 95% CI: 0.32-0.89) in the subgroup analysis by ethnicity. Besides, when the studies were stratified by source of controls, the results were not significant in both the subgroup of population-based controls and hospital-based controls. CONCLUSIONS: This meta-analysis suggested the carriers of short polymorphic CAG repeats might increase susceptibility to prostate cancer, which held potential as a detecting marker of the risk of prostate cancer.


Assuntos
Predisposição Genética para Doença , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Expansão das Repetições de Trinucleotídeos , Humanos , Masculino
9.
Urology ; 107: 126-131, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28606776

RESUMO

OBJECTIVE: To explore the feasibility of extraperitoneal laparoscopic radical nephroureterectomy (EL-RNU) and lymph node dissection in a modified supine position for managing urothelial carcinomas in the renal pelvis or in the upper two-thirds of the ureter. PATIENTS AND METHODS: Consecutively from January 2014 to October 2015, 15 patients with high-risk urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter underwent EL-RNU and extraperitoneal laparoscopic lymph node dissection (EL-LND). Clinical and pathologic data, histologic nodal status, perioperative complications, and recurrence data were collected. RESULTS: All of the 15 patients were treated with EL-RNU and EL-LND in a modified supine position, and none was converted to open surgery. The mean operation time was 178 ± 18 minutes. The mean estimated blood loss was 140 ± 40 mL. The mean postoperative intestinal function recovery time was 2 days. The mean postoperative hospitalization was 7 ± 1 days. Pathologic studies revealed positive lymph nodes in 3 patients (20%). The mean number of harvested lymph nodes was 12 ± 3. No local recurrence and distant metastasis were found after a median follow-up of 14.4 months (7-23 months). CONCLUSION: EL-RNU and EL-LND in the modified supine position are mini-invasive and feasible for patients with urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter. Good exposure and dissection of the abdominal aorta and inferior vena cava and the integrity of the peritoneum are key to the operational success of this approach.


Assuntos
Carcinoma de Células de Transição/cirurgia , Pelve Renal , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Nefroureterectomia/métodos , Ureter/cirurgia , Neoplasias Urológicas/cirurgia , Idoso , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/secundário , Cistoscopia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Peritônio , Estudos Retrospectivos , Decúbito Dorsal , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Urografia , Neoplasias Urológicas/patologia
10.
Oncotarget ; 8(30): 50034-50050, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28489583

RESUMO

The aim of the meta-analysis was to clarify the associations between vascular endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of renal cell carcinoma (RCC). A meta-analysis was performed by searching the databases PubMed, EMBASE and Web of Science for the relevant available studies until August 1st, 2016, and fourteen studies met the inclusion criteria. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of such associations. Besides, the pooled hazard ratios (HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or random-effects models were conducted according to existence of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. Overall, this meta-analysis included a total of 8,275 patients, who had been accrued between November 2002 and September 2015. Meta-analysis indicated that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and -634C/G polymorphisms were found significantly associated with poor OS of RCC. Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C polymorphisms were associated with an elevated susceptibility to RCC, indicating that these three polymorphisms might be risk factors for RCC, especially in Asian populations.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma de Células Renais/patologia , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Renais/patologia , Masculino , Polimorfismo Genético , Prognóstico , Fatores de Risco
11.
Int J Oncol ; 50(5): 1839-1847, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28393205

RESUMO

Annexin A5 has been found to act as an oncogenic protein in a variety of cancers. However, its specific biological role and mechanism in renal cell cancer (RCC) remains unknown. Quantitative Real-time PCR and western blotting were used to evaluate the mRNA and protein expression level of Annexin A5 in human RCC cell lines and tissues. Immunohistochemistry was adopted to measure the Annexin A5 expression in 123 cases of RCC tissues. Survival analysis was performed to explore the association between Annexin A5 expression and the prognosis of RCC. The effect of Annexin A5 on RCC growth and metastasis was studied in vitro and in vivo. Annexin A5 was frequently highly expressed in both human RCC cells and tissues. High Annexin A5 expression was associated with higher clinical stage and histological grade. In addition, Annexin A5 might be used as a predictive factor for the prognosis of RCC. Further research suggested that upregulated Annexin A5 in RCC cells could significantly promote tumor cell proliferation, migration and invasion in vitro. Subcutaneous xenograft tumor model displayed that knockdown of Annexin A5 could impede tumorigenesis in vivo. Moreover, mechanism study exhibited that Annexin A5 could activate PI3K/Akt/mTOR signaling pathway, promote epithelial-mesenchymal transition (EMT) and the expression of MMP2 and MMP9. Annexin A5 may be a potential prognostic biomarker in RCC and promotes proliferation, migration and invasion of RCC cells via activating PI3K/Akt/mTOR signaling pathway and regulating EMT process and MMP expression.


Assuntos
Anexina A5/biossíntese , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Animais , Anexina A5/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Environ Toxicol ; 32(7): 1908-1917, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28295950

RESUMO

di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways.


Assuntos
Dibutilftalato/toxicidade , Poluentes Ambientais/toxicidade , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Reprodução/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Camundongos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Sulfóxidos , Testículo/citologia , Testículo/efeitos dos fármacos , Regulação para Cima
13.
Cell Physiol Biochem ; 41(3): 921-932, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28222430

RESUMO

BACKGROUND/AIMS: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. METHODS: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2', 7'-dichlorodihydro-fluorescein diacetate, respectively. RESULTS: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. CONCLUSIONS: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/genética , MicroRNAs/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Genes Reporter , Glucose/antagonistas & inibidores , Glucose/metabolismo , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/metabolismo , Glutationa/agonistas , Glutationa/metabolismo , Humanos , Concentração Inibidora 50 , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/agonistas , MicroRNAs/metabolismo , Transdução de Sinais , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia
14.
Oxid Med Cell Longev ; 2017: 7612182, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29435098

RESUMO

Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.


Assuntos
Glutationa/biossíntese , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Triterpenos/farmacologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glutationa/genética , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Regulação para Cima
15.
Oncotarget ; 8(2): 3568-3580, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27683040

RESUMO

BACKGROUND: Perioperative treatments have been used to improve prognosis in patients with upper tract urothelial carcinoma (UTUC). However, optimal management remains unestablished. METHODS: We searched the Embase, Web of Science and Cochrane databases for studies published before June 20, 2015. All included studies were categorised into three groups on the basis of the outcome reported (overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS)). Relative hazard ratios (HRs) for death were calculated using random-effects Bayesian network meta-analysis methods. We also ranked the three different treatments in terms of three outcomes. RESULTS: A total of 31 trials with 8100 patients were included. Compared with the control, adjuvant chemotherapy (AC) could improve OS, DSS and RFS by 32% (HR 0.68, 95% CI 0.51-0.89), 29% (HR 0.71, 95% CI 0.54-0.89) and 51% (HR 0.49, 95% CI 0.23-0.85), respectively. We noted a marked prolongation of RFS in both intravesical chemotherapy (HR 0.32, 95% CI 0.09-0.69) as well as concurrent radiotherapy and intravesical chemotherapy (HR 0.32, 95% CI 0.03-0.97) than in the control. Neoadjuvant chemotherapy (NAC) showed a significant improvement in DSS relative to the control (HR 0.25, 95% CI 0.06-0.61) and a distinct advantage over AC (HR 0.36, 95% CI 0.08-0.90) or AR (HR 6.89, 95% CI 1.25-18.66). CONCLUSIONS: Our results showed that AC; intravesical chemotherapy; and concurrent radiotherapy and intravesical chemotherapy could improve the prognosis of UTUC patients. NAC was found to be more favourable for UTUC than AC in terms of DSS.


Assuntos
Assistência Perioperatória , Neoplasias Uretrais/patologia , Neoplasias Uretrais/terapia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , Teorema de Bayes , Terapia Combinada , Gerenciamento Clínico , Humanos , Metanálise em Rede , Assistência Perioperatória/métodos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uretrais/mortalidade , Neoplasias Urológicas/mortalidade
16.
Oncotarget ; 7(52): 87361-87372, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27888634

RESUMO

Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT. Moreover, low CK2α levels suppressed cell growth, and similar results could be reproduced after treatment with CX-4945 with a dose-dependent response. CX-4945 inhibited migration and induced apoptosis. Furthermore, knockdown of CK2α decreased the tumorigenicity of bladder cancer cells in vivo. This study is the first to report that CK2 increases glucose metabolism in human bladder cancer. Blocking CK2 function may provide novel diagnostic and potential therapeutic.


Assuntos
Glucose/metabolismo , Naftiridinas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Animais , Caseína Quinase II/análise , Caseína Quinase II/antagonistas & inibidores , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Imuno-Histoquímica , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fenazinas , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Medicine (Baltimore) ; 95(39): e4801, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27684806

RESUMO

BACKGROUND: Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in order to assess the efficacy and toxicity of combining estramustine with chemotherapy for the treatment of CRPC. METHODS: Relevant randomized clinical trials were systematically searched from the databases Pubmed, Embase, and Web of science up to April 1, 2016. Data were centrally extracted and analyzed from the previous studies by 2 independent reviewers. The primary endpoint was overall survival (OS) with pooled hazard ratios. Secondary endpoints were prostate-specific antigen (PSA) response and grade 3 or 4 toxicity using pooled odds ratios. Stata version 12.0 software was used for statistical analysis. RESULTS: Overall, this meta-analysis identified 9 eligible articles, including a total of 956 patients, who had been accrued between January 1, 1993 and December 1, 2010 and randomly divided into chemotherapy with estramustine and without estramustine. Chemotherapy (with or without estramustine) consisted of docetaxel, paclitaxel, ixabepilone, epirubicin, and vinblastine. Patients who received chemotherapy with estramustine had a better improvement in PSA response rate, comparing those without estramustine (OR = 1.84, 95% CI = 1.20-2.80). However, OS between the 2 groups indicated no significant differences (HR = 0.90, 95% CI = 0.77-1.05). Besides, these results of meta-analysis showed no obvious differences between these 2 groups in grade 3 or 4 adverse effects, including anemia (OR = 0.78, 95% CI = 0.38-1.57), neutropenia (OR = 0.91, 95% CI = 0.59-1.43), thrombocytopenia (OR = 0.68, 95% CI = 0.19-2.42), nausea (OR = 2.34, 95% CI = 0.81-6.72), vomiting (OR = 2.43, 95% CI = 0.69-8.51), diarrhea (OR = 3.45, 95% CI = 0.93-12.76), fatigue (OR = 0.67, 95% CI = 0.32-1.41), neuropathy (OR = 0.54, 95% CI = 0.21-1.44), allergic reaction (OR = 1.60, 95% CI = 0.37-6.84), thromboembolic event (OR = 2.18, 95% CI = 0.86-5.51), and edema (OR = 1.02, 95% CI = 0.18-5.95). CONCLUSIONS: This meta-analysis indicated chemotherapy with additional estramustine increased the PSA response rate. However, OS and grade 3 or 4 toxicity were not improved for these patients with CRPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estramustina/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estramustina/administração & dosagem , Estramustina/efeitos adversos , Humanos , Masculino , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
18.
Onco Targets Ther ; 9: 5091-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27574450

RESUMO

BACKGROUND: Increasing evidence suggests that the dysregulation of certain microRNAs plays an important role in tumorigenesis and metastasis. MiR-200c exhibits a disordered expression in many tumors and presents dual roles in bladder cancer (BC). Therefore, the definite role of miR-200c in BC needs to be investigated further. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction was used to assess miR-200c expression. Cell invasion and migration were evaluated using wound healing and transwell assays. The luciferase reporter assay was used to identify the direct target of miR-200c. The expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK) in BC tissues and adjacent nontumor tissues, as well as in BC cell lines, was detected through quantitative reverse transcription polymerase chain reaction, Western blot assay, and immunohistochemistry. RESULTS: The miR-200c expression was significantly upregulated in the BC tissues compared with the adjacent nontumor tissues. The downregulation of miR-200c significantly inhibited cell migration and invasion in the BC cell lines. The luciferase reporter assay showed that RECK was a direct target of miR-200c. The knockdown of RECK in the BC cell lines treated with anti-miR-200c elevated the previously attenuated cell migration and invasion. CONCLUSION: Our findings indicated that miR-200c functions as oncogenes in BC and may provide a novel therapeutic strategy for the treatment of BC.

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