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1.
Dis Markers ; 2019: 2724948, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565097

RESUMO

Background: Colony-stimulating factor-1 (CSF-1) is a homodimeric glycoprotein. The main role of CSF-1 is as a hematopoietic growth factor that modulates proliferation, differentiation, and survival of macrophages. Moreover, CSF-1 has also been reported to be aberrantly expressed in several human cancers. However, the precise role of CSF-1 in upper tract urothelial carcinomas (UTUC) has not been studied. In this research, we examined the clinical significance of CSF-1 expression in UTUC. Materials and Methods: One hundred twelve cancer tissue samples of UTUC from patients were included in this study, and the other cohort of 35 UTUC were paired cancer-adjacent normal samples. CSF-1 expression was evaluated by immunohistochemistry, and the association of CSF-1 expression with different clinicopathological variables was analyzed. Results: CSF-1 expression was higher in UTUC than in the normal urothelium (P = 0.005). The CSF-1 expression was primarily localized in the nucleus and was significantly correlated with tumor size (P = 0.04) and patients who had a high stage (P < 0.001), distant metastasis (P = 0.006), recurrence (P = 0.003), and cancer death (P = 0.005). High CSF-1 expression was correlated with poor disease-free survival (P = 0.008) and cancer-specific survival (P = 0.001). Our results also used univariate and multivariable analyses, which found that high CSF-1 expression was an independent predictor of poor disease-free survival (hazard ratio = 2.56; P = 0.007) and cancer-specific survival (hazard ratio = 5.14; P = 0.022). Conclusions: Our findings indicate that the expression of CSF-1 is a potential prognostic marker for predicting patient survival and recurrence in UTUC.

2.
Kaohsiung J Med Sci ; 35(9): 559-565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339657

RESUMO

CSN6 is a subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN). CSN is involved in cellular and developmental processes such as signal transduction, transcriptional activation, cell cycle control, and tumorigenesis. CSN6 is highly expressed in several human cancers, including colorectal cancer, and breast cancer. However, no previous research has elaborated on the relationship between CSN6 expression and survival in patients with upper tract urothelial carcinoma (UTUC). Therefore, the purpose of this study is to evaluate the clinical significance of CSN6 in UTUC. CSN6 expression in 89 patients with UTUC enrolled in this study was examined using immunohistochemistry. The associations between CSN6 expression and clinicopathological variables were analyzed. CSN6 expression was significantly correlated with patients with high pathological stage (P = .006), male gender (P = .025), and high serum creatinine levels (P = .014). In univariate and multivariable analysis, high CSN6 expression was associated with a higher bladder recurrence (P = .005) and poor cancer-specific survival (P = .001) for UTUC. In conclusion, CSN6 expression is a potential biomarker for predicting cancer recurrence and clinical survival in UTUC. Further research is necessary to investigate its role in the progression of UTUC.

3.
BMC Neurosci ; 19(1): 72, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413143

RESUMO

BACKGROUND: Glycine receptors (GlyRs) are involved in the development of spinal pain sensitization. The GlyRα3 subunit has recently emerged as a key factor in inflammatory pain pathways in the spinal cord dorsal horn (DH). Our study is to identify the extent of location and cell types expressing different GlyR subunits in spinal cord and dorsal root ganglion (DRGs). To tease out the possible actions of GlyRs on pain transmission, we investigate the effects produced by GlyRs on acute inflammatory pain by behavioral testing using prostaglandin E2 (PGE2) intrathecal injection models. Furthermore, we investigate the changes of GlyR expression in DRGs and spinal cord in rats after the induction of acute inflammatory pain. RESULTS: Compared to the vehicle administration, the PGE2 intrathecal injection model produced significantly higher hyperalgesia, which started 3 h after PGE2 injection and lasted more than 5 h. PGE2 intrathecal injection significantly decreased GlyRα1 and GlyRα3 protein expressions in the L5 DH at 1 h and lasted to 5 h, and similar results were observed in the L5 DRG at 5 h. Confocal microscopic images showed the co-existence of punctate gephyrin and GlyRα3 immunoreactivity (IR) throughout the gray matter of the spinal cord, mainly in DH laminae I-III neurons and in ventral horn neurons. It also showed the co-existence of punctate gephyrin and GlyRα3 IR in DRG neurons. CONCLUSIONS: In this study, PGE2 intrathecal injection significantly decreased protein expression of gephyrin, GlyRα1 and GlyRα3 in spinal cord DH and DRG. The gephyrin and GlyRα3 were localized on neuron cells both in the DH and DRG.

4.
Adv Exp Med Biol ; 1099: 65-76, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306515

RESUMO

Peripheral nerve blockade (PNB) is advantageous for patients undergoing surgery to decrease the perioperative opioid consumptions and enhance recovery after surgery.Inadvertent local anesthetic (LA) administration into nerve fiber intrafascicularly easily results in unrecognized nerve injury. Using nerve block guidance either by ultrasound, electrical nerve stimulator, or using pressure devices does not prevent nerve damage, even though most of the nerve injury is transiently. The incidence of neurologic symptoms or neuropathy is in the range of 0.02-2.2%, and no significant difference of postoperative neurologic symptoms is found as compared with using ultrasound or guided nerve stimulator technique. However, intrafascicular lidocaine brought about macrophage migration into the damaged fascicle, Schwann cell proliferation, increased intensity of myelin basic protein, and shorten withdrawal time to mechanical stimuli. In dorsal root ganglion (DRG), intrafascicular LA injection increased the activated transcriptional factor 3 (ATF-3) and downregulated Nav1.8 (Nav1.8). In spinal dorsal horn (SDH), the microglia and astrocytes located in SDH were activated and proliferated after intrafascicular LA injection and returned to baseline gradually at the end of the month. This is a kind of neuropathic pain, so low injection pressure should be maintained, the correct needle bevel used, nerve stimulator or ultrasound guidance applied, and careful and deliberately slow injection employed as important parts of the injection technique to prevent intrafascicular LA administration-induced neuropathic pain.

5.
Sci Rep ; 8(1): 3821, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29491476

RESUMO

Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E2 (PGE2) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry. In a trans-well co-culture system, significantly upregulated DC-derived IL-23 expression was found when DCs were co-cultured with Hp-infected GSCs (Hp-GSCs). Further, PGE2 from Hp-GSCs was discovered to possess the priming effect, which could be inhibited by anti-COLEC12 (Collectin subfamily member 12) Abs, COLEC12 knockdown or when alpha3-fucosyltransferase-null (futB; HP0651) strain of Hp was used. Also, the expression of COLEC12 was co-localized with CD90+ stromal cells in cancerous tissues. Hp-GSCs-conditioned DCs were able to induce the expression of IL-17 from CD4+ T cells, which could be inhibited by IL-23-neutralizing Abs. These results suggested the importance of COLEC12 as a receptor involved in Hp-stromal cell interaction and its subsequent conditioning effect on DCs.

6.
Int J Med Sci ; 14(13): 1360-1367, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200949

RESUMO

Background: Signal transducer and activator of transcription proteins (STATs) play important roles in gene regulation, cell proliferation, and cell differentiation. We aimed to establish the relationship between phosphorylated STAT3 (p-Ser-STAT3) expression and the prognosis of upper tract urothelial carcinoma (UTUC). Methods: This study retrospectively reviewed 100 patients with pathologically confirmed UTUC at Kaohsiung Medical University Hospital. We quantified the expression of p-Ser-STAT3 in cancer cells by immunohistochemistry, and determined the clinicopathological significance of p-Ser-STAT3 expression and prognostic outcomes in patients with UTUC. Results: High p-Ser-STAT3 expression was detected in 52% of UTUC patients. High p-Ser-STAT3 expression was associated with poor recurrence-free survival (p = 0.018) and overall survival (p = 0.026). In advanced cancer samples (stage T3/T4), p-Ser-STAT3 expression is the only independent prognostic factor for recurrence-free survival (hazard ratio = 5.91, p = 0.01) and cancer-specific survival (hazard ratio = 8.83, p = 0.039). Conclusions: The expression of p-Ser-STAT3 can be a potential prognostic marker for cancer recurrence and survival in UTUC, especially in advanced stage cases.


Assuntos
Carcinoma de Células de Transição/genética , Recidiva Local de Neoplasia/genética , Fator de Transcrição STAT3/genética , Neoplasias Urológicas/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Ureter/patologia , Neoplasias Urológicas/patologia , Urotélio/patologia
7.
Int J Med Sci ; 14(6): 578-584, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638274

RESUMO

BACKGROUND: Hypoxia has been shown to facilitate tumor progression. Hypoxia-regulated microRNA-210 (miR-210) may play an important role in carcinogenesis and tumor progression. In this study, we evaluated the clinical significance of miR-210 expression in upper tract urothelial carcinoma (UTUC). METHODS: Eighty-three UTUC patients participated in this study. All of them provided cancer tissue samples and 50 of them provided non-cancerous urothelium samples. Clinicopathologic data were collected by reviewing medical records. The expression of miR-210 and hypoxia-inducible factor-1α (HIF-1α) was determined by quantitative real-time polymerase chain reaction. The relationship between clinicopathologic variables and the expression of miR-210 and HIF-1α was analyzed statistically. RESULTS: MiR-210 is overexpressed in UTUC compared to non-cancerous urothelium (p < 0.001); it is also upregulated in high-stage and high-grade tumors (p = 0.020 and 0.049, respectively). HIF-1α is overexpressed in UTUC and correlates positively with miR-210 expression (r = 0.442, p = 0.001). CONCLUSION: Both miR-210 and HIF-1α are involved in promoting UTUC carcinogenesis. MiR-210 is also correlated with tumor progression. Further studies are needed to clarify the underlying mechanism.


Assuntos
Carcinoma de Células de Transição/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Adulto , Idoso , Carcinogênese/genética , Carcinoma de Células de Transição/patologia , Hipóxia Celular/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Urotélio/patologia
8.
Clin Genitourin Cancer ; 15(4): e653-e659, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28188048

RESUMO

OBJECTIVES: Leptin and its receptor (LEPR) are key players in the regulation of energy balance and body weight control and act as a growth factor for specific organs in both normal and disease states. However, LEPR accumulation may be involved in carcinogenesis, progression, and metastasis in many cancers. This study evaluated the clinical significance of LEPR expression in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: LEPR expression was examined in 110 tissue samples from patients with UTUC, using immunohistochemistry, and an analysis was performed to identify evidence of association between LEPR expression and different clinicopathologic variables. RESULTS: LEPR expression was significantly correlated with patients with increased body mass index (P < .001) and high serum creatinine levels (P = .005). We found, using the log-rank test, that high LEPR expression was associated with poor recurrence-free (P = .009) and cancer-specific survival (P = .001). This finding was supported by our results using Cox regression analysis, which showed that LEPR expression was an independent predictor of poor recurrence-free survival (hazard ratio = 2.55; P = .011) and cancer-specific survival (hazard ratio = 2.26; P = .006). CONCLUSIONS: Our findings indicate that LEPR expression is a potential biomarker for predicting patient survival in UTUC. Further study is necessary to investigate the role of LEPR in carcinogenesis of UTUC.


Assuntos
Carcinoma de Células de Transição/metabolismo , Receptores para Leptina/metabolismo , Regulação para Cima , Neoplasias Urológicas/metabolismo , Índice de Massa Corporal , Carcinoma de Células de Transição/sangue , Creatinina/sangue , Feminino , Humanos , Masculino , Prognóstico , Análise de Regressão , Análise de Sobrevida , Taiwan , Neoplasias Urológicas/sangue
9.
J Mol Neurosci ; 61(2): 169-177, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28012097

RESUMO

The role of microRNAs (miRNAs) in the regulation of nerve injury-induced neuropathic pain is unclear. The aims of this study were to assess and compare miRNA expression profiles in dorsal root ganglia (DRG) following three different kinds of peripheral nerve injury, including spinal nerve ligation (SNL), dorsal root transection (DRT), and ventral root transection (VRT), in Sprague-Dawley rats. Responses to thermal and mechanical stimuli were measured preoperatively and on postoperative days (PODs) 1, 4, and 7. A miRNA microarray analysis was used to detect the miRNA expression profiles in injured L5 DRG from SNL, DRT, and VRT on POD 7. Validation of miRNA expression was performed by qPCR and in situ hybridization. Rats receiving SNL displayed significantly higher mechanical hypersensitivity, but those receiving DRT developed higher thermal hypersensitivity. The number of miRNAs that were significantly upregulated in L5 DRG was 49 (7.2%), 25 (3.7%), and 146 (21.5%) following SNL, DRT, and VRT, respectively. On the other hand, 35 (5.1%) miRNAs were significantly downregulated in the SNL group, 21 (3.1%) miRNAs in the DRT group, and 41 (6.0%) miRNAs in the VRT group. Of the four miRNAs that were mutually aberrant in all three models, two were significantly upregulated (twofold), miR-21 and miR-31, and two were significantly downregulated, miR-668 and miR-672. Using in situ hybridization, miRNA-21, miRNA-31, miRNA-668, and miRNA-672 were found to localize to neurons in the DRG. Collectively, the mutual abnormal miRNA expression of miR-21, miR-31, miR-668, and miR-677 implied that these miRNAs may be therapeutic targets for alleviating multiple forms of neuropathic pain.


Assuntos
Gânglios Espinais/metabolismo , MicroRNAs/genética , Traumatismos dos Nervos Periféricos/genética , Animais , Masculino , MicroRNAs/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Microb Drug Resist ; 23(1): 98-106, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27148814

RESUMO

We analyzed the replicon types, sizes, and restriction fragment length polymorphism (RFLP) typing of plasmids carrying extended-spectrum ß-lactamase (ESBL) genes in Klebsiella pneumoniae isolates from Taiwan. Fifty-one Escherichia coli transconjugant strains with plasmids from ESBL-producing K. pneumoniae from the Taiwan Surveillance of Antimicrobial Resistance III Program in 2002 were included. All the 51 plasmids carried a blaCTX-M gene, the majority of which were blaCTX-M-3 (28/51 [54.9%]). Plasmids ranged in size from 126 to 241 kb by S1 nuclease digestion and subsequent pulsed-field gel electrophoresis, and the most common plasmid size (37.3%) was 161-170 kb. The most common replicon type of plasmids was incompatibility group (Inc)A/C (60.8%). The IncA/C plasmids all carried blaCTX-M (blaCTX-M-3, -14, -15), and some also carried blaSHV (blaSHV-5, -12) genes. All 51 plasmids could be typed with PstI, and 27 (52.9%) belonged to 10 clusters. Thirty-eight of the 51 plasmids were typable with BamHI, and 21 plasmids (55.3%) fell into 7 clusters. Plasmids in the same cluster belonged to the same incompatibility group, with the exception of cluster C6. In conclusion, IncA/C plasmids are the main plasmid type responsible for the dissemination of ESBL genes of K. pneumoniae from Taiwan. RFLP with PstI possessed better discriminatory power than that with BamHI and PCR-based replicon typing for ESBL-carrying plasmids in K. pneumoniae in this study. Greater than 50% of plasmids fell into clusters, and >60% of cluster-classified plasmids were present in clonally unrelated isolates, indicating that horizontal transfer of plasmids plays an important role in the spread of ESBL genes.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Regulação Bacteriana da Expressão Gênica , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Plasmídeos/metabolismo , beta-Lactamases/genética , Antibacterianos/farmacologia , Células Clonais , Conjugação Genética , Eletroforese em Gel de Campo Pulsado , Transferência Genética Horizontal , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/química , Plasmídeos/classificação , Polimorfismo de Fragmento de Restrição , Vigilância em Saúde Pública , Replicon , Taiwan/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia , beta-Lactamases/metabolismo , beta-Lactamas/farmacologia
11.
Oncotarget ; 7(47): 77777-77792, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27780919

RESUMO

Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC.


Assuntos
Carcinoma de Células de Transição/genética , Perfilação da Expressão Gênica/métodos , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Proteínas de Manutenção de Minicromossomo/genética , Regulação para Cima , Neoplasias Urológicas/genética , Carcinoma de Células de Transição/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas de Manutenção de Minicromossomo/metabolismo , Projetos Piloto , Prognóstico , Neoplasias Urológicas/metabolismo
12.
Medicine (Baltimore) ; 95(21): e3458, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27227911

RESUMO

Because Helicobacter pylori (H pylori) would cause carcinogenesis of the stomach, we need sufficient information for deciding on an appropriate strategy of eradication. Many factors affect the efficacy of eradication including antimicrobial resistance (especially clarithromycin resistance) and CYP2C19 polymorphism. This study was to survey the efficiency of gastric juice for detecting H pylori infection, clarithromycin resistance, and CYP2C19 polymorphism.The specimens of gastric juice were collected from all patients while receiving gastroscopy. DNA was extracted from gastric juice and then urease A and cag A were amplified by polymerase chain reaction (PCR) for detecting the existence of H pylori. By PCR-restriction fragment length polymorphism (PCR-RFLP), the 23S rRNA of H pylori and CYP2C19 genotypes of host were examined respectively. During endoscopy examination, biopsy-based specimens were also collected for rapid urease test, culture, and histology. The blood samples were also collected for analysis of CYP2C19 genotypes. We compared the results of gastric juice tests with the results of traditional clinical tests.When compared with the results from traditional clinical tests, our results from gastric juice showed that the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy to detect H pylori infection were 92.1% (105/114), 92.9% (143/154), 90.5% (105/116), 94.1% (143/152), and 92.5% (248/268), respectively. The SEN, SPE, PPV, and NPV to detect clarithromycin resistance were 97.3% (36/37), 91.5% (43/47), 90.0% (36/40), and 97.7% (43/44), respectively. By using PCR-RFLP, the consistency of human CYP2C19 gene polymorphism from blood samples and gastric juice was as high as 94.9% (149/157).The manipulated gastric juice is actually an effective diagnostic sample for evaluation of H pylori existence, clarithromycin resistance, and host CYP2C19 polymorphism.


Assuntos
Claritromicina/farmacologia , Citocromo P-450 CYP2C19/genética , Suco Gástrico , Gastroscopia/métodos , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Citocromo P-450 CYP2C19/análise , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Sensibilidade e Especificidade , Urease/genética
13.
World Neurosurg ; 91: 532-541.e1, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26947729

RESUMO

BACKGROUND: Matrix metalloproteinase (MMPs) and endothelin-1 may prove to be important in the generation of pain induced by inflammation and nerve lesion. This study aimed to investigate the relationship between endothelin receptors and MMPs. METHODS: Male Sprague-Dawley rats (250-300 g) were divided into 5 groups: a normal (control) group; an L5 spinal nerve ligation (SNL) group; a CGS-26303 IT + L5 SNL group; a BQ-123 IT + L5 SNL group; and a BQ-788 IT + L5 SNL group. The expression of glial fibrillary acidic protein, endothelin-A receptor (ETAR), endothelin-B receptor, MMP-2, and MMP-9 in the ipsilateral L5 dorsal root ganglion (DRG) and the activation of microglia and astrocytes in the L5 spinal dorsal horn (SDH) were quantified by immunofluorescence and Western blotting. RESULTS: Intrathecal pretreatment with CGS-26303 significantly attenuated the hyperalgesic and mechanical responses induced by SNL for 4 days, whereas BQ-123 administration alleviated the hyperalgesia only for 3 hours and mechanical allodynia for only 1 hour. Pretreatment with CGS-26303 significantly down-regulated the glial fibrillary acidic protein, ET-A, MMP-2, and MMP-9 expressions in DRG and their effect lasted for 6 hours, 1 day, 7 days, and 1 day, respectively. By immunofluorescence and Western blotting, there was colocalization of ETAR and MMP-9 in the DRG neurons, whereas MMP-2 was expressed in DRG satellite cells. Furthermore, CGS-26303 treatment also reduced SNL-induced microglia and astrocyte activation on the SDH for 7 days. CONCLUSIONS: In this study, CGS-26303 can attenuate SNL-induced neuropathic pain by down-regulating MMP-9, MMP-2, and ETAR expressions in the DRG and by glia cell activation in the SDH.


Assuntos
Analgésicos/administração & dosagem , Neuralgia/prevenção & controle , Organofosfonatos/administração & dosagem , Tetrazóis/administração & dosagem , Analgésicos/farmacologia , Animais , Regulação para Baixo , Injeções Espinhais , Ligadura/efeitos adversos , Masculino , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Organofosfonatos/farmacologia , Ratos Sprague-Dawley , Nervos Espinhais , Tetrazóis/farmacologia
14.
J Surg Oncol ; 113(6): 700-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26861489

RESUMO

BACKGROUND AND OBJECTIVES: Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs. METHODS: We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease-specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses. RESULTS: High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026). CONCLUSIONS: MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707. © 2016 Wiley Periodicals, Inc.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/diagnóstico , Metaloproteinase 11 da Matriz/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Regulação para Cima , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
15.
Ann Surg Oncol ; 23(1): 343-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26242371

RESUMO

BACKGROUND: Inflammation-related parameters based on blood cells, including white blood cell (WBC) count, neutrophil-lymphocyte ratio, platelet count, and red cell distribution width (RDW), have been shown to be associated with prognosis in many cancers. However, no previous study evaluated these inflammation-associated markers simultaneously in upper tract urothelial carcinoma (UTUC). METHODS: A total of 195 patients with UTUC who received radical nephroureterectomy between 2005 and 2010 were included retrospectively as the derivation cohort to investigate the impact of inflammation markers on overall survival (OS) and cancer-specific survival (CSS). In turn, another independent set of 225 patients were used for validation. Finally, we performed survival analysis in the combined cohort consisting of 420 UTUC patients. RESULTS: The predictive value of RDW and WBC count on outcome was replicable in different cohorts. Multivariate analysis showed high RDW was independently associated with poor OS (P < 0.001), and WBC count was a significant prognosticator for both OS and CSS (both P < 0.001). In subgroup analysis, we found the prognostic significance of RDW for OS was limited in organ-confined disease (≤pT2 without pN+). More importantly, a clear survival difference can be demonstrated by combining RDW and WBC count with other known prognostic factors in the risk stratification model. CONCLUSIONS: RDW and WBC count have the advantage of their common accessibility and are useful markers to predict outcome of UTUC in the preoperative setting. RDW and WBC count could provide additional prognostic value and help physicians identify patients at high risk for mortality and formulate individualized treatment strategy.


Assuntos
Biomarcadores/sangue , Células Sanguíneas/patologia , Inflamação/patologia , Nefrectomia , Neoplasias Urológicas/patologia , Idoso , Células Sanguíneas/metabolismo , Feminino , Seguimentos , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Metástase Linfática , Masculino , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Urológicas/sangue , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/cirurgia
16.
World J Urol ; 34(6): 835-46, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26433386

RESUMO

PURPOSE: Bladder cancer (BC) is the most common malignancy in urinary system. The prognosis of metastatic BC is poor, but there remains no reliable marker to early detect metastasis. Dysregulated prenylated protein tyrosine phosphatases (PTPs) are commonly associated with cancer metastasis. From a published BC transcriptome, we identified that PTP IVA3 (PTP4A3) was the most significantly upregulated gene implicated in tumor progression among genes related to prenylated PTPs. We therefore analyzed PTP4A3 expression in our well-characterized cohort of BC. METHODS: By immunohistochemistry, PTP4A3 expression was determined using H-score. PTP4A3 expression of 295 BCs was compared with clinicopathological parameters, and the effect of PTP4A3 on cancer-specific survival (CSS) and metastasis-free survival (MFS) was also examined. Two independent sets of BCs were used to assess PTP4A3 protein and transcript expression in normal urothelium and different stage tumors. RESULTS: PTP4A3 overexpression was significantly associated with higher pT stage (P < 0.001), nodal metastasis (P < 0.001), vascular invasion (P < 0.001), and perineural invasion (P = 0.021). In multivariate analysis, PTP4A3 overexpression was an independent predictor for CSS (P < 0.001) and MFS (P = 0.007). Notably, the difference in CSS and MFS between high and low PTP4A3-expressing tumors was also significant in muscle-invasive BCs. PTP4A3 protein expression showed significant and stepwise increments from normal urothelium to noninvasive BC, invasive BC, and metastatic foci (P < 0.001). PTP4A3 transcript was also obviously upregulated in high-stage BC (P < 0.001). CONCLUSIONS: PTP4A3 may play a role in BC oncogenesis and is a predictive marker of metastasis. PTP4A3 overexpression represents an independent prognosticator for BC, suggesting its potential theranostic value.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Proteínas Tirosina Fosfatases/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/biossíntese , Prognóstico , Proteínas Tirosina Fosfatases/biossíntese , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
17.
Clin J Pain ; 32(6): 513-21, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26340654

RESUMO

OBJECTIVE: Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. METHODS: A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. RESULTS: Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. DISCUSSION: Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.


Assuntos
Anestésicos Locais/toxicidade , Antibacterianos/uso terapêutico , Lidocaína/toxicidade , Minociclina/uso terapêutico , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Fator 3 Ativador da Transcrição/metabolismo , Análise de Variância , Animais , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Proteína Básica da Mielina/metabolismo , Neuroglia/metabolismo , Medição da Dor , Ratos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Canais de Sódio/metabolismo
18.
Emerg Infect Dis ; 21(12): 2217-20, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26583537

RESUMO

In Taiwan, Q fever cases in humans began increasing in 2004 and peaked in 2007 but dramatically declined in 2008 and 2011. Cases were significantly correlated with the number of goats. The decline might be associated with the collateral effects of measures to control goat pox in 2008 and 2010.


Assuntos
Criação de Animais Domésticos , Coxiella burnetii/patogenicidade , Febre Q/epidemiologia , Animais , Surtos de Doenças/veterinária , Cabras/sangue , Cabras/microbiologia , Humanos , Taiwan/epidemiologia , Zoonoses/epidemiologia
19.
Am J Cancer Res ; 5(8): 2447-54, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26396920

RESUMO

Visfatin, a newly discovered adipocytokine, is a pro-inflammatory cytokine. This study aimed to evaluate the predictive value of visfatin on prognosis of patients with upper tract urothelial carcinoma. One-hundred and five patients (median age=64, range=24-84 years) were included in this study. Visfatin expression in upper tract urothelial carcinoma tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables using the χ(2) test. The prognostic value of visfatin for recurrence-free and cancer-specific survival was evaluated by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Cox regression model was also used to evaluate the hazard ratios of visfatin on survival. High visfatin expression in upper tract urothelial carcinoma tissues was significantly correlated with tumor stage (P=0.001), grade (P=0.007) and p53 expression (P=0.07). High visfatin expression was associated with poor recurrence-free and cancer-specific survival. Cox regression analysis also revealed that visfatin is an independent predictor of recurrence-free (HR=3.22, P=0.009) and cancer-specific survival (HR=5.74, P=0.023). Our findings indicated that higher visfatin expression is a potential biomarker to predict patient survival. Further study is necessary to investigate the role of visfatin in the carcinogenesis of upper tract urothelial carcinoma.

20.
Diagn Microbiol Infect Dis ; 83(2): 187-92, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26234479

RESUMO

Fluoroquinolone-nonsusceptible Streptococcus pyogenes has rapidly emerged in several countries. The aim of this study was to survey the epidemiology and molecular characteristics of fluoroquinolone-nonsusceptible S. pyogenes in Taiwan. A total of 350 consecutive S. pyogenes isolates were collected between January 2005 and December 2012, including 152 (43.4%) invasive and 198 (56.6%) noninvasive isolates. Thirty-nine isolates (11.1%) of S. pyogenes were nonsusceptible to fluoroquinolones, including one emm1/ST28, 4 emm4/ST39, 33 emm12/ST36, and 1 emm87/ST62. Of all the isolates, emm12 (50%) demonstrated the highest prevalence of fluoroquinolone nonsusceptibility. Alterations of Ser79Phe and Ala12Val in ParC were the most frequently mutations in fluoroquinolone-nonsusceptible S. pyogenes isolates. There were no amino acid substitutions in GyrB, and 1 emm87 isolate exhibited 3 nonsynonymous mutations in ParE. Our study reveals the emergence of fluoroquinolone-nonsusceptible S. pyogenes emm12/ST36 in Taiwan. Regular surveillance of fluoroquinolone susceptibility in S. pyogenes is suggested.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/isolamento & purificação , Adulto , DNA Girase/genética , DNA Topoisomerase IV/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Humanos , Tipagem Molecular , Mutação de Sentido Incorreto , Prevalência , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Taiwan/epidemiologia
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