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1.
J Cell Biochem ; 121(3): 2197-2208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31724223

RESUMO

Acetylated Kruppel-like factor 5 (KLF5) is essential for transforming growth factor-ß (TGF-ß) to properly regulate gene transcription in the inhibition of cell proliferation and tumor growth. Ras oncogenic signaling can convert TGF-ß from a tumor suppressor to a tumor promoter; however, its ability to utilize the KLF5 transcription factor to modulate TGF-ß functions is still unknown. Therefore, in this study, we sought to determine whether Ras signaling altered TGF-ß-induced KLF5 acetylation and the assembly of the p300-KLF5-SMADs transcriptional complex in gene regulation. Not only did we determine that Ras signaling inhibited TGF-ß-induced KLF5 acetylation and interfered with TGF-ß function in p15 induction and Myc repression, but also TGF-ß-induced SMAD3 C-terminal region phosphorylation was necessary for TGF-ß to induce KLF5 acetylation. Moreover, Ras activation further interrupted the interactions amongst p300, KLF5, and SMAD4, as well as the binding of p300-KLF5-SMADs complex onto the TGF-ß-responsive promoter elements for both p15 and Myc. These findings suggested that KLF5 mediated the crosstalk between TGF-ß and Ras signaling, and that suppression of TGF-ß-induced KLF5 acetylation by Ras activation; this altered TGF-ß-induced assembly of p300-KLF5-SMADs complex onto gene promoters to convert the function of TGF-ß in gene regulation.

2.
J Virol Methods ; 275: 113757, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669331

RESUMO

The outbreak of an infectious disease characterized by severe symptom of gout has set great threat to several major goose-producing regions in China since December 2016. The causative agent for the novel infection has been identified was a novel goose-origin astrovirus (GoAstV). Lack of effective detection methods indeed hinders further research, as well as prevention and control of GoAstV. Keep this in mind, a TaqMan-based one-step real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay for rapid detection of GoAstV was developed. Primers and probe were targeting the capsid protein gene sequence (ORF2). The method is capable of detecting quite low number of targeting nucleic acid as low as 10 copies/µL. What's more, it is also of great specificity and repeatability for GoAstV detection. No cross-activity was found with other goose-origin viruses. The assay had excellent intra-assay and inter-assay repeatability with the coefficient of variation (CV) value from 0.48% to 0.99%. A total of 340 GoAstV specimens from different regions of China were used in this study to verify the feasibility and effectiveness of this method in clinical diagnosis. The results indicated that qRT-PCR is a highly sensitive, specific and repeatable method for quantitative detection of GoAstV, which can be used to detect this virus, thereby facilitating epidemiological investigations of gout in goslings.

3.
Urol Oncol ; 38(1): 2.e11-2.e17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672485

RESUMO

OBJECTIVE: Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. We have previously shown that time to nadir (TTN) of prostate-specific antigen (PSA) is an important prognostic factor in patients from a single center in Northwestern China. In this study, we performed a multicenter validation of the prognostic role of TTN in additional Chinese patients with mCRPC receiving docetaxel treatment. MATERIALS AND METHODS: The data were gathered from 170 eligible Chinese patients who received docetaxel chemotherapy from January 2007 to October 2018 in 11 Chinese Prostate Cancer Consortium member hospitals in China. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS). RESULTS: Patients with a TTN ≥ 15 weeks had a longer OS and PFS compared to those with a TTN < 15 weeks (43 vs. 15 months, P < 0.001; 24 vs. 6 months, P < 0.001, respectively). In addition, Patients with a TTN ≥ 15 weeks and PSA nadir <4.55ng/ml were associated with longer OS than others (HR 0.093, 95% CI 0.044-0.188, P < 0.001; HR 4.002, 95% CI 1.890-8.856, P = 0.001, respectively) and TTN, PSA nadir, PSA baseline (optimal threshold 56.07 ng/ml), and PSA reduction (optimal threshold 50%) were associated with PFS (HR 0.238, 95% CI 0.149-0.382, P < 0.001; HR 1.676, 95% CI 1.033-2.722, P = 0.037; HR 1.770, 95% CI 1.134-2.763, P = 0.012; HR 0.573, 95% CI 0.428-0.756, P < 0.001; respectively). Furthermore, patients with a PSA nadir <4.55 ng/ml had longer OS and PFS compared to other patients when TTN was ≥15 weeks. CONCLUSION: In this multicenter validation study, TTN and PSA nadir remain important prognostic markers in predicting therapeutic outcomes in Chinese men who receive chemotherapy for mCRPC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31832810

RESUMO

PURPOSE: 6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. METHODS: The effects of 6-gingerol on proliferation, colony formation, and cell cycle in RCC cells were detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and propidium iodide (PI) staining, respectively. Western blotting, an immunofluorescence assay, and immunohistochemical staining were performed to assess the expression of relevant proteins. A subcutaneous tumor model was set up to investigate the 6-gingerol effects on tumor growth in vivo, and the pharmacokinetics of 6-gingerol in mice were detected by LC/MS assays. RESULTS: 6-Gingerol treatment exerted time- and dose-dependent inhibition of the growth and colony formation of ACHN, 786-O, and 769-P cells, leading to a concomitant induction of cell-cycle G1-phase arrest and decrease in Ki-67 expression in the cell nucleus. Western-blotting results showed that 6-gingerol reduces phosphorylation of protein kinase B (AKT) Ser 473, cyclin-dependent kinases (CDK4), and cyclin D1 and, meanwhile, increases glycogen synthase kinase (GSK 3ß) protein amount. Furthermore, the efficacy of 6-gingerol was demonstrated in an in vivo murine model of 786-O. CONCLUSION: The above results indicate that 6-gingerol can induce cell-cycle arrest and cell-growth inhibition through the AKT-GSK 3ß-cyclin D1 signaling pathway in vitro and in vivo, suggesting that 6-gingerol should be useful for renal-cell carcinoma treatment.

6.
Medicine (Baltimore) ; 98(48): e18000, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770212

RESUMO

RATIONALE: Bladder cancer (BC) is commonly diagnosed in the urinary system and the most common subtype is transitional urothelial carcinoma (TCC). Even with the best treatment, tumor recurrence and metastases always occur. While clinicians commonly observe the metastases to pelvic lymph nodes, liver, lung, and bone, it may infrequently spread to some uncommon locations. PATIENT CONCERNS: The patient was a 67-year-old man with a diagnosis of high-grade TCC with squamous differentiation in the bladder and prostate. Subsequently, radical cystoprostatectomy, adjuvant radiotherapy, and chemotherapy were performed. However, he felt intermittent right scrotal pain about 1 year later. DIAGNOSIS: Ultrasound strongly suggested a testicular neoplasm of right testis, but the left was normal. INTERVENTIONS: The patient underwent a right radical orchiectomy and histopathology confirmed testicular metastatic neoplasm from bladder. Moreover, further examination with positron emission tomography revealed no visible distant spread of the urothelial carcinoma. OUTCOMES: No signs of tumor recurrence or distant metastasis were visible under follow-up 1 year after radical orchiectomy. LESSONS: Testicular mass may be metastatic tumor during follow-up for patients who were diagnosed as BC, especially for TCC with variant histology. The reason of this could be explained of residual micrometastases after surgery and need more examination to discover local micrometastases to apply more aggressive treatment.


Assuntos
Carcinoma de Células de Transição/secundário , Cistectomia/efeitos adversos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Neoplasias Testiculares/secundário , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Humanos , Masculino , Período Pós-Operatório , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/patologia
7.
Theranostics ; 9(19): 5464-5477, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534497

RESUMO

KLF5 is frequently deleted or downregulated in prostate cancer. However, it is not known whether downregulation of KLF5 is associated with the response of prostate cancer cells to chemotherapy and/or prognosis of patients. Methods: We monitored cell growth by MTT and colony formation assays, and cell autophagy through tandem fluorescence microscopy and transmission electron microscopy. Gene expression was analyzed by RT-qPCR and Western blotting. We determined the binding of KLF5 together with HDAC3 on the beclin-1 (BECN1) promoter by the ChIP assay, oligonucleotides pulldown, and co-immunoprecipitation. The effect of docetaxel on cell growth in vivo was examined in a CWR22RV1 xenograft tumor mouse model. Results: In the present study, we found that KLF5 down-regulation was associated with progression of prostate cancer and poor prognosis of patients. KLF5 knockdown reduced the sensitivity of prostate cancer cells to docetaxel in vitro and in vivo, and docetaxel treatment decreased the expression of KLF5. Moreover, we confirmed that docetaxel treatment inhibited cell death by inducing autophagy in prostate cancer cells. Thus, we hypothesized that KLF5 could be a regulator of cell autophagy. Interestingly, KLF5 could inhibit prostate cancer cell autophagy by suppressing the transcription of BECN1 cooperatively with HDAC3. Another significant finding was that docetaxel treatment repressed KLF5 expression through AMPK/mTOR/p70S6K signaling pathway resulting in increased BECN1, induction of cell autophagy, and promotion of cell survival in castration-resistant prostate cancer cells. Conclusions: Our results indicated that downregulation of KLF5 promoted cell autophagy in prostate cancer. Furthermore, reduced KLF5 also facilitated cell autophagy induced by docetaxel resulting in desensitization to the drug and cell survival. Decreased levels of KLF5 led to increased BECN1 via AMPK/mTOR/p70S6K signaling. Thus, repression of BECN1 and cell autophagy was critical for KLF5 to increase the sensitivity of prostate cancer cells to docetaxel.

8.
Oncol Rep ; 42(4): 1307-1318, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364741

RESUMO

Hypoxia is a tumorigenesis­related microenvironment change which usually occurs in the earliest stage of prostate cancer (PCa) development. Accumulating evidence has demonstrated that hypoxia/hypoxia­inducing factor (HIF) is involved in the induction of epithelial­mesenchymal transition (EMT) and increased metastatic potential in PCa. However, the mechanism by which hypoxia/HIF regulates EMT remains unclear. In the present study, we demonstrated the molecular mechanisms of hypoxia­induced EMT in PCa, focusing on HIF­1α/Forkhead box M1 (FoxM1) signaling pathway. PCa PC3 and DU145 cell lines were used as the model system in vitro. Our data revealed that hypoxia induced EMT in PCa cells. Bioinformatics analysis identified the possible association between HIF­1α and FoxM1. Additionally, FoxM1 was significantly associated with PCa development and Gleason scores of PCa. Exposure to hypoxia resulted in the increased expression of HIF­1α and FoxM1. Genetic knockdown FoxM1 abolished hypoxia­induced EMT in PCa, while exogenous overexpression of FoxM1 facilitated hypoxia­induced EMT. Furthermore, the increase of FoxM1 during hypoxia was due to the transcriptional regulation on the FoxM1 promoter by HIF­1α. We also confirmed the binding site of HIF­1α on the FoxM1 promoter by different lengths promoter sequences. These findings provide new insights into how EMT is regulated in PCa under hypoxic stress. It is worthwhile to investigate in future that inhibition of FoxM1 as a potential target may be an effective therapeutic strategy against PCa.


Assuntos
Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Sequência de Bases , Sítios de Ligação , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Masculino , Células PC-3 , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Transcrição Genética , Regulação para Cima
9.
Cell Death Dis ; 10(6): 437, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164632

RESUMO

The prognosis of bladder cancer (BCa) depends on several key factors including anatomical site, tumor grade, and stage. In general, muscle-invasive bladder cancer (MIBC) is associated with higher incidence of distant metastasis compared with Non-muscle-invasive bladder cancer (NMIBC). Treatment outcome of the patients with metastatic BCa has been very poor with ~15% of overall survival rate. Thus, it is apparently important to understand the underlying biology for metastatic progression of BCa. Although epithelial-mesenchymal transition (EMT) has long been implicated in BCa metastasis and treatment resistance, the underlying mechanism is not fully understood. In this study, we have identified that the expression of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is positively correlated with pathological characteristics, and predicts a poor prognosis of BCa patients. Since the function of IFIT5 in BCa has not yet been characterized, we demonstrate that IFIT5 can induce EMT, promote cell migration and invasion, and increase the expression of ICAM1 in BCa via down-regulation of mature miR-99a. Moreover, ICAM1 is shown as a direct target of miR-99a. Overall, we conclude that IFIT5 is a new oncogene in BCa.

10.
Cancer Med ; 8(10): 4792-4805, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250978

RESUMO

AIM: JQ1, a BET bromodomain inhibitor, is a promising therapeutic approach for bladder cancer (BC). Our study aimed to determine whether autophagy is induced by JQ1 and its potential role toward proliferation in BC. METHODS: Cell proliferation was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, cell counting assay, and colony formation assay. Autophagosomes and autolysosomes were observed by transmission electron microscopy and mRFP-EGFP-LC3 fluorescence assay. 3-MA, BAFA1, NH4 Cl, and siATG5 were used to inhibit autophagy. AMPK siRNA was used to knock down AMPK. T24 xenograft model in mice was chosen to perform in vivo studies. Autophagy markers LC-3B and p62, p-AMPKα, p-ACC, p-ULK1, p-mTOR and p-LKB1 were determined by western blot in vitro studies and by immunohistochemistry (IHC) in vivo specimens. RESULTS: We found that BC cell proliferation was suppressed by JQ1; moreover, JQ1 induced the accumulation of autophagosomes and autolysosomes, and autophagy flux, and the growth suppression capacity of JQ1 was attenuated by autophagy inhibitors. Furthermore, we found that JQ1 induced the phosphorylation of AMPKα, and AMPKα knockdown attenuated autophagy induction and anti-proliferation effect induced by JQ1 in BC cells, indicating that autophagy induced by JQ1 is dependent on AMPKα. Through endogenous immunoprecipitation analysis, we found that JQ1 dramatically increased the interaction between LKB1 and AMPKα, which may lead to more AMPK activation. Proliferation inhibition, autophagy induction, and LKB1/AMPK activation capacities of JQ1 were further confirmed in vivo. CONCLUSIONS: Taken together, our results demonstrate that autophagy is induced by JQ1 through activation of LKB1/AMPK pathway, and the autophagy induced by JQ1 positively contributes to the inhibition of BC cell proliferation. These findings provide a novel point of view to understand the mechanism of how targeting BET bromodomain suppress cancer cell growth and suggest that targeting BET bromodomain might be a potential approach to treat BC in the future.

11.
Prostate ; 79(11): 1226-1237, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31212363

RESUMO

BACKGROUND: We previously reported the presence of prostate-specific antigen (PSA) in the stromal compartment of benign prostatic hyperplasia (BPH). Since PSA is expressed exclusively by prostatic luminal epithelial cells, PSA in the BPH stroma suggests increased tissue permeability and the compromise of epithelial barrier integrity. E-cadherin, an important adherens junction component and tight junction regulator, is known to exhibit downregulation in BPH. These observations suggest that the prostate epithelial barrier is disrupted in BPH and E-cadherin downregulation may increase epithelial barrier permeability. METHODS: The ultra-structure of cellular junctions in BPH specimens was observed using transmission electron microscopy (TEM) and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate (FITC)-dextran in transwell assays. RESULTS: The number of kiss points in tight junctions was reduced in BPH epithelial cells as compared with the normal adjacent prostate. Immunostaining confirmed E-cadherin downregulation and revealed a discontinuous E-cadherin staining pattern in BPH specimens. E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation without affecting cell density. CONCLUSIONS: Our results indicate that tight junctions are compromised in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting targeting E-cadherin loss could be a potential approach to prevent or treat BPH.


Assuntos
Caderinas/metabolismo , Regulação para Baixo , Células Epiteliais/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Junções Íntimas/metabolismo , Caderinas/genética , Humanos , Masculino , Permeabilidade
12.
Photobiomodul Photomed Laser Surg ; 37(1): 25-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31050941

RESUMO

Objective: Our study aimed to detect whether 450 nm blue laser can be applied effectively and safely in endosocopic submucosal dissection (ESD) system for surgery in colonic tissue. Background data: Semiconductor blue laser has been applied in surgery due to its excellent cutting property, however, whether blue laser can be applied in colonic surgery has not been reported. Materials and methods: Porcine colon tissues were vaporized by 450 nm blue semiconductor laser at 10-25 W and at working distances from 0.5 to 3 mm, with a three-dimensional scanning system. Moreover, we designed an ESD model and applied blue laser at 10 W on porcine colonic tissues with this system. Dimensions of the vaporized tissues and coagulation zones were assessed under microscopy. Results: Since the thickness of colonic wall is no more than 1 mm, first we determined the cutting property and safety of blue laser on porcine colon tissue and found that blue laser at 10 W made lesions shallower than 1 mm and the depth of vaporization can be controlled effectively within muscularis mucosa and submucosa. Moreover, a large scale of porcine colonic tissue was vaporized precisely by blue laser at power of 10 W with the ESD system ex vivo. Conclusions: Our results indicate that 450 nm blue laser at 10 W can be well controlled for laser-tissue interaction with excellent cutting efficiency and less thermal damage in adjacent tissues especially side of the submucosa. Therefore, 450 nm semiconductor blue laser could be a safe alternative approach for colonic surgery.

13.
Clin Cancer Res ; 25(14): 4542-4551, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31000589

RESUMO

PURPOSE: Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment. EXPERIMENTAL DESIGN: Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA. In vivo ubiquitination assay was used to test PARP-1 degradation. Furthermore, in vivo mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR. RESULTS: We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model. CONCLUSIONS: In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.

14.
Cancer Lett ; 453: 193-205, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30928381

RESUMO

The prostate-specific G protein-coupled receptor (PSGR) is a class A G protein-coupled receptor (GPCR) that is specifically expressed in prostate epithelial cells, and its expression has been linked to prostate cancer (PCa) progression. Here, we show that activation of PSGR with its ligand ß-ionone, an end-ring analog of ß-carotenoid, can suppress PCa cell growth both in vitro and in vivo model. Dissection of the mechanism underlying this relationship reveals that activation of PSGR by ß-ionone suppresses AR nuclear translocation via phosphorylation of AR at residue Ser650 by p38 and JNK, which leads to the suppression of AR transactivation, further suppressing PCa cell growth. Overall, we link a cancer cell-specific GPCR with the nuclear AR and show that targeting PSGR can provide us a new target to combat PCa better.

15.
J Cell Physiol ; 234(11): 20002-20012, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30945310

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a common urinary neoplasm, looking for useful candidates to establish scientific foundation for the therapy of ccRCC is urgent. We downloaded genomic profiles of GSE781, GSE6244, GSE53757, and GSE66271 from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze the derivative genes, while hub genes were screened by protein-protein interactions and cytoscape. Further, overall survival, gene methylation, gene mutation, and gene expression were all analyzed using bioinformatics tools. Colony formation and cell-cycle assay were used to detect the biological function of GNG7 in vitro. We found that GNG7 was downregulated in ccRCC tissues and negatively associated with overall survival in ccRCC patients. We also found that promoter methylation and frequent gene mutation were responsible for GNG7 gene suppression. GNG7 low expression was related to upregulation of enhancer of zeste homolog 2 and downregulation of disabled homolog 2-interacting protein. Further, Gene Set Enrichment Analysis results showed that mTOR1, E2F, G2M, and MYC pathways were all significantly altered in response to GNG7 low expression. In vitro, A498 and 786-O cells in which GNG7 expression was silenced, exhibited a lower G1 phase when compared to the negative control cells. Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment.

16.
Vet Microbiol ; 231: 218-225, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955813

RESUMO

Infection with duck Tembusu virus (DTMUV) can cause large economic losses to the duck-rearing industry in China. In this study, we isolated a virulent strain of DTMUV (SDS) from sparrows near a duck farm and attenuated it via serially passaging (alternately for 100 passages) in specific pathogen-free chicken and duck embryos. We attenuated the virus after the 60th passage (SDS-60), based on the production of embryos that were free of visible lesions and still alive. The 70th adapted strain (SDS-70), obtained with a virus titer of 10-2.46 EID50 was chosen to be the live attenuated vaccine. After immunizing ducklings with the SDS-70 strain, they obtained 100% protection against infection by the SDS-10 virulent strain. Our data demonstrate that the vaccine can protect ducks from becoming infected with TMUV. Our study also shows that this newly developed attenuated vaccine candidate provides excellent immunogenicity, is safe, and has the potential to control DTMUV infections in ducks.


Assuntos
Infecções por Flavivirus/veterinária , Flavivirus , Doenças das Aves Domésticas/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Patos/virologia , Infecções por Flavivirus/prevenção & controle , Imunização , Imunogenicidade da Vacina , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Baço/patologia , Baço/virologia , Vacinas Atenuadas/imunologia , Proteínas do Envelope Viral/imunologia , Carga Viral
17.
Asia Pac J Clin Oncol ; 15(3): 144-150, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30873737

RESUMO

AIM: To investigate the use of docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-world clinical practice in China. METHODS: This single-arm, prospective, observational study was conducted at 32 study centers in China and included male patients aged ≥18 years with histologically confirmed prostate cancer who received ≥1 dose of docetaxel following failure of hormonal therapy (disease progression with serum testosterone <50 ng/dL). The primary aim was to investigate patterns of docetaxel treatment. RESULTS: Overall 403 patients were included between August 2011 and June 2016; patients initiated docetaxel after failure of first- (42.2% [170]), second- (31.0% [125]) and ≥third-line (12.7% [51]) hormonal therapy, estramustine (11.4% [46]) or other (2.7% [11]). The planned cycles of docetaxel therapy were completed by 30.8% of patients, and the mean (SD) number of cycles received was 4.4 (2.86). Median overall survival (mOS) was 22.4 (95% CI, 20.4-25.8) months and the prostate-specific antigen (PSA) response rate in patients with available data was 70.9% (168/237), with no differences in mOS and PSA response rates between treatment settings. Subgroup analysis revealed higher mOS in patients without visceral metastasis versus those with such metastases (22.9 vs. 17.4 months; P = 0.022). No new safety signals were observed and the most common adverse events associated with docetaxel were granulocytopenia (5%) and leukopenia (4.5%). CONCLUSION: Data from this study showed that around three-quarters of Chinese patients with mCRPC treated with docetaxel initiated treatment following first- or second-line hormonal therapy and no new safety signals were observed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue
18.
World J Urol ; 37(12): 2671-2675, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30843089

RESUMO

PURPOSE: To describe a green-laser marking technique to assist partial cystectomy, which allows accurate identification of tumour margins, and provide our initial experience with ten patients. METHODS: Between January 2014 and February 2018, ten patients suspected with muscle-invasive bladder cancer and request of bladder-preserving treatment were selected. In each case, bilateral pelvic lymphadenectomy was performed before green-laser assisted laparoscopic partial cystectomy. Under the direct view of cystoscope, the front-firing green-laser incision was performed 0.5-1 cm away from the exterior margin of lesion with adequate depth into the fat tissue. Tumours were then en bloc removed via laparoscope under the tracing of laser beam. RESULTS: The location of 12 tumours in 10 patients was superior wall in 7 cases, lateral wall in 3 cases, anterior wall in 1 case, and posterior wall in 1 case. All procedures were completed without serious complications. The median operating time was 270 (210-360) min with a median haemoglobin decrease of 11 (3-38) g/L. Nine patients were high-grade transitional cell carcinoma and one patient was urachal carcinoma, and the clinical stage was pT1 in 1 case, pT2 in 4 cases, and pT3 in 5 cases. The pathological evaluation of tumour margins was negative in 10 patients. During the follow-up, no recurrence or metastasis were detected in 8 patients, but 2 patients presented regional recurrence. CONCLUSION: The use of green-laser marking technique during laparoscopic partial cystectomy is a feasible manoeuvre in assisting the accurate incision and minimizing injury to the remaining bladder.

19.
World J Urol ; 37(12): 2677-2682, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30830276

RESUMO

PURPOSE: The T1 substage, according to the relationship between muscularis mucosae (MM) and tumors, is a promising prognostic factor for T1 bladder cancer. However, the identification rate of MM is low in specimens, and it is, therefore, not widely used in clinical practice. In this study, we investigated whether en bloc resection of non-muscle invasive bladder cancer (NMIBC) could improve the identification of muscularis mucosae (MM), which may further accurate identification of the T1 substage. PATIENTS AND METHODS: Specimens from 158 patients with primary NMIBC were retrospectively reviewed by two independent pathologists to assess the presence of MM and stratify the T1 substage. Of 158 specimens, 70 specimens were obtained via TURBt with a plasma kinetic loop and 88 were obtained via front-firing potassium-titanyl-phosphate (KTP) green-light laser en bloc resection. Univariable and multivariable logistic regression models were used to analyze the relationship between the clinical characteristics and the presence of MM. RESULTS: The mean age was 58.22 years (range 18-85 years). Multivariable logistic regression analysis showed that the KTP laser resection method was associated with the presence of MM in specimens (P = 0.008). In addition, tumors with smaller sizes, which could also be en bloc resected with TURBt (e.g., ≤1 cm), had a higher presence of MM (P = 0.047). CONCLUSIONS: En bloc resection improves the identification rate of MM, which may enhance the accurate identification of the T1 substage.

20.
Medicine (Baltimore) ; 98(5): e14237, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702581

RESUMO

Recent studies have confirmed the efficacy of sorafenib for patients with advanced renal cell carcinoma; however, its efficacy and safety as an adjuvant therapy in patients with non-metastatic and loco-regional renal cell carcinoma after surgery remains controversial. Thus, the aim of the present retrospective study was to evaluate the efficacy of adjuvant sorafenib therapy in such patients from 8 centers in northwestern China that were treated from August 2009 to December 2016.After surgery, the patients (n = 48) received oral sorafenib for 3 months. The control group (n = 48) comprised patients that underwent the same surgery from December 2009 to June 2016 but without adjuvant therapy who were matched 1:1 with the sorafenib group with respect to sex, age, pathological findings, disease stage and grade, operation time, and surgical procedure. The primary outcome compared between the groups was disease-free survival. Adverse events were also recorded to evaluate the safety of sorafenib. The influence of patients' characteristics and laboratory tests on recurrence was analyzed using unconditional logistic regression.Overall, the demographic characteristics of the 2 groups were similar. There was no significant difference in the rate of recurrence (8.3% for sorafenib patients and 6.2% for the matched patients, P = .66) or median disease-free survival between the 2 groups (hazard ratio = 1.561, 95% confidence interval = 0.349-6.987, P = .56). In multiple logistic regression analysis, increased blood urea nitrogen (BUN) emerged as an independent predictor of recurrence risk (P = .02).These results indicate that postoperative sorafenib adjuvant therapy did not achieve the expected beneficial effect, pointing to the need for further studies to evaluate its utility in such cases.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nefrectomia/métodos , Sorafenibe/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos
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