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The importance of real estate development has been widely accepted by all countries. Through early warning and avoidance of real estate financial risks, it can effectively promote the healthy and healthy development of the real estate industry, avoiding the impact of accidental factors, such as the COVID-19 pandemic, and promoting the overall economic development. Based on multiple regression analysis and grey prediction methods, this article constructs a real estate financial risk estimation model, and the real estate financial risk is estimated using the relevant data of Liaoning Province from 2001 to 2020. Analyzing the research results of financial risks in Liaoning Province, we can find that the real estate financial risks reached the peak in 2013, and then the real estate financial risks gradually showed a slow decline trend. In general, the financial risks in Liaoning Province are controllable. The study of financial risks in Liaoning Province will help to judge the development of the real estate industry and promote the continuous improvement of the overall economy. The article, through the study of real estate financial risks in Liaoning Province, can promote the development of regional real estate in Liaoning Province and promote the overall economic development of Liaoning Province, which has strong practical significance. The study of real estate financial risks, relevant risk research theories can be enriched, the identification of financial risks can be improved, and the study of real estate financial risks can be strengthened. The article uses a combination of multivariate statistics and grey fuzzy theory to complete the study of real estate financial risks. Therefore, through the exploration of multivariate statistics and grey fuzzy theory, its application value can be elevated.
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COVID-19 , China/epidemiologia , Humanos , COVID-19/epidemiologia , COVID-19/economia , Desenvolvimento Econômico , Análise Fatorial , SARS-CoV-2/isolamento & purificação , Pandemias/economiaRESUMO
This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration.
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Nomogramas , Torção do Cordão Espermático/cirurgia , Testículo/cirurgia , Adolescente , Humanos , Masculino , Orquiectomia , Orquidopexia , Período Pré-Operatório , Reprodutibilidade dos Testes , Estudos Retrospectivos , Torção do Cordão Espermático/diagnóstico por imagem , Torção do Cordão Espermático/patologia , Testículo/diagnóstico por imagem , Testículo/patologia , Ultrassonografia , Adulto JovemRESUMO
The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.
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Nomogramas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangueRESUMO
BACKGROUND: To investigate the functions of the hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells in a rat model of overactive bladder syndrome. METHODS: Rats with OAB were screened using a urodynamic testing device. The whole-cell patch clamp technique was used to investigate changes in excitability and hyperpolarization-activated cation current (Ih) of medium-size cells in the L6 dorsal root ganglia (DRG) of the OAB rats. Intrathecal injection of the specific Ih inhibitor ZD7288 was used to investigate changes of voiding function and Ih of medium-size cells in the L6 DRG. RESULTS: The urinary bladder weight of the OAB rats was significantly increased (p < 0.01); However, 7 days after intrathecally administration of ZD7288 (2 µM), the weight of rat bladder was significantly reduced (p < 0.01). The excitability of the medium-size cells in the L6 DRG of the OAB rats was significantly increased, and the number of action potentials elicited by a 500 pA stimulus was also markedly increased. Furthermore, ZD7288 significantly reduced the excitability of the medium-size DRG cells. The medium-size cells in the DRG of the OAB rats had a significantly increased Ih current density, which was blocked by ZD7288. CONCLUSIONS: The Ih current density significantly increased in medium-size cells of the L6 DRG in the OAB model. A decrease of the Ih current was able to significantly improve the voiding function of the OAB rats, in addition to lowering their urinary bladder weight. Our finding suggested that the observed increase of Ih current in the medium-size DRG neurons might play an important role in the pathological processes of OAB.
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Potenciais de Ação , Gânglios Espinais/citologia , Bexiga Urinária Hiperativa/fisiopatologia , Animais , Cátions , Feminino , Ratos , SíndromeRESUMO
The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus prevalent in east and southeast Asia, the Western Pacific, and northern Australia. Since viruses are obligatory intracellular pathogens, the dynamic processes of viral entry, replication, and assembly are dependent on numerous host-pathogen interactions. Efforts to identify JEV-interacting host factors are ongoing because their identification and characterization remain incomplete. Three enzymatic activities of flavivirus non-structural protein 3 (NS3), including serine protease, RNA helicase, and triphosphatase, play major roles in the flaviviruses lifecycle. To identify cellular factors that interact with NS3, we screened a human brain cDNA library using a yeast two-hybrid assay, and identified eight proteins that putatively interact with NS3: COPS5, FBLN5, PPP2CB, CRBN, DNAJB6, UBE2N, ZNF350, and GPR137B. We demonstrated that the DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6) colocalizes and interacts with NS3, and has a negative regulatory function in JEV replication. We also show that loss of DNAJB6 function results in significantly increased viral replication, but does not affect viral binding or internalization. Moreover, the time-course of DNAJB6 disruption during JEV infection varies in a viral load-dependent manner, suggesting that JEV targets this host chaperone protein for viral benefit. Deciphering the modes of NS3-interacting host proteins functions in virion production will shed light on JEV pathogenic mechanisms and may also reveal new avenues for antiviral therapeutics.
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Vírus da Encefalite Japonesa (Espécie)/fisiologia , Encefalite Japonesa/metabolismo , Encefalite Japonesa/virologia , Proteínas de Choque Térmico HSP40/metabolismo , Interações Hospedeiro-Patógeno , Chaperonas Moleculares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Linhagem Celular , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Interações Hospedeiro-Patógeno/genética , Humanos , Ligação Proteica , Mapeamento de Interação de Proteínas , Transporte Proteico , RNA Helicases/metabolismo , Serina Endopeptidases/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Internalização do VírusRESUMO
BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.
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Antineoplásicos Hormonais/administração & dosagem , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Pamoato de Triptorrelina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Humanos , Injeções Intramusculares , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/diagnósticoRESUMO
PURPOSE: Premature ejaculation (PE) is one of the most common sexual dysfunctions in men. However, there has been little research evaluating alterations in brain structure related to PE. We aimed to investigate the characteristics of nonmedicated PE patients in terms of brain morphometry. MATERIALS AND METHODS: The sample consisted with 32 medication-naïve adult men with clinical diagnosed PE and matched 31 healthy controls. All participants received diagnostic interviews and 3.0 Tesla MRI scans. Automatic segmentation processing of MRI structure images was performed using FreeSurfer software and cerebral cortical thickness between groups was compared. RESULTS: The PE group had thicker cortex in widespread regions, including the frontal, parietal and occipital lobe, and limbic system, compared with the healthy control group (P < 0.05). Moreover, the duration is negatively correlated with the mean cortical thickness of the right medial orbitofrontal cortex, right precentral gyrus and left superior frontal cortex (R2 = 0.29, P < 0.003; R2 = 0.163, P < 0.04; R2 = 0.2, P < 0.02), while the Premature Ejaculation Diagnostic Tool score is negatively correlated with the mean cortical thickness of the left caudal middle frontal cortex (R2 = 0.33, P < 0.005). CONCLUSION: The result highlights the structural features of PE and suggests the relationship with the severity of impairment is related to the severity of anatomic abnormality with the relevant brain region. These results support the value of imaging measures as markers for understanding the physiopathology of PE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:656-662.
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Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Ejaculação Precoce/fisiopatologia , Adulto , Humanos , Masculino , Índice de Gravidade de Doença , Adulto JovemRESUMO
Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1ß. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1-NF-κB pathway.
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BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. METHODS: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells. RESULTS: This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo. CONCLUSION: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.
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Adenocarcinoma/terapia , Antígenos de Superfície , Terapia Genética , Glutamato Carboxipeptidase II , Neoplasias da Próstata/terapia , Adenocarcinoma/patologia , Animais , Antígenos de Superfície/genética , Fusão Gênica Artificial , Caspase 3/genética , Terapia Genética/métodos , Glutamato Carboxipeptidase II/genética , Humanos , Imunotoxinas/genética , Masculino , Camundongos Nus , Neoplasias da Próstata/patologia , Células Tumorais CultivadasRESUMO
BACKGROUND: We analyzed the expression of heme oxygenase-1 (HO-1) in patients undergoing radical nephrectomy for advanced clear cell renal cell carcinoma (CC-RCC) and evaluated the effects of the targeted therapies treated with sorafenib and sunitinib. METHODS: Expression of HO-1 in cancer tissue from 66 patients was measured by immunohis-tochemical staining. The patients received either oral sorafenib (n=40) or oral sunitinib (n=26) within 4 weeks after nephrectomy and were followed up long term to determine the tumor response and prognosis. RESULTS: Our current study revealed a high HO-1 expression level in 57.6% (38/66) of patients and a low HO-1 expression level in 42.4% (28/66) of patients with CC-RCC. The study also revealed that patients with high HO-1 expression did not have a higher objective response rate (2.6% versus 53.6%, P<0.01), clinical benefit rate (47.4% versus 92.9%, P<0.01), longer progression-free survival (4.4 versus 42 months, P=0.022), or overall survival (χ (2)=4.775, P=0.029) than patients with low HO-1 expression. In the low HO-1 level group, a higher tumor response rate and a longer survival time was achieved in patients who received sorafenib or sunitinib. Multivariate analysis showed that HO-1 expression was an independent prognostic factor for tumor response and overall survival. CONCLUSION: High expression of HO-1 was associated with a lower tumor response rate and a shorter overall survival time when compared with low expression of HO-1. Overall, HO-1 expression might be a useful biomarker for predicting the response to sunitinib and sorafenib for patients with metastatic CC-RCC.
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Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .
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Biomarcadores Tumorais/sangue , Carcinoma/sangue , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/sangue , Idoso , Povo Asiático , Biópsia com Agulha de Grande Calibre , Carcinoma/diagnóstico , Carcinoma/patologia , China , Exame Retal Digital , Endossonografia , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To assess the feasibility and safety of robot-assisted laparoscopic radical prostatectomy (RLRP) in the treatment of prostate cancer. METHODS: Using the da Vinci robot surgical system, we performed RLRP for 34 patients with localized prostate cancer and analyzed the intraoperative and follow-up data. RESULTS: The procedures were performed successfully in all the patients, with the mean operation time of 198 min (range 135-340 min), average blood loss of 257 ml (range 50-700 ml), and 1 case of blood transfusion, but no postoperative complications. Three cases had positive surgical margins. Postoperative examination at 4 weeks showed PSA > 0.2 microg/L in 2 cases, suggestive of residual tumor, for which maximal androgen block therapy was administered. The other 32 patients were followed up for 3-10 (mean 7.5) months, during which the average level of serum tPSA remained < 0.2 microg/L. Urinary continence was found in 94% (32/34) and 97% (33/34) of the patients at 3 and 6 months, respectively, of whom 77% (26/34) and 88% (30/34) had no urinary leakage (0 pad per day). CONCLUSION: RLRP, with its advantages of less perioperative blood loss, low rate of positive margin, and good urinary continence, is a safe and effective surgical option for the treatment of prostate cancer.
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Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Although CD44 was overexpressed and considered as a useful prognostic marker in renal cell carcinoma, the prognostic role of CD44s in clear cell renal cell carcinoma (ccRCC) remains controversial. Moreover, the correlation and prognostic significance of CD44s and its downstream signaling target pSTAT3 are unclear in ccRCC. In this study, 75 pairs of carcinoma and paired adjacent non-tumor renal tissue samples were collected from patients with localized ccRCC who underwent a nephrectomy. The expression levels of CD44s and pSTAT3 were analyzed using immunohistochemistry. Correlations between CD44s/pSTAT3 expression and clinical and pathological characteristics were determined using x(2) test, Kaplan-Meier analysis and Cox's proportional hazards model. We found that CD44s is highly expressed in 46.67% of tumor tissues, and its high expression was significantly associated with high tumor grade (P < 0.001), large tumor size (P = 0.009) and advanced T stage (P = 0.004). A strong correlation exists between high expression of CD44s and pSTAT3 (r = 0.4013, P = 0.0004). The joint over expression of CD44s and pSTAT3 was present in 42.66% of tumor specimens and had an additive negative impact on overall survival. Patients with CD44s(high)pSTAT3(high) expression had significantly poor survival as compared to patients with CD44s(low)pSTAT3(low) tumor expression (P = 0.024), though the concurrent overexpression of CD44s and pSTAT3 was not an independent prognostic factor for overall survival. Our data indicate that expression of both CD44s and pSTAT3 in ccRCC is associated with advanced tumor stage and patient survival. The conclusions from this study may improve the prediction of ccRCC prognosis information when CD44s and pSTAT3 expression are evaluated together with classical clinicopathological parameters.
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Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Receptores de Hialuronatos/biossíntese , Neoplasias Renais/patologia , Fator de Transcrição STAT3/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fator de Transcrição STAT3/análise , Análise Serial de TecidosRESUMO
Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a significant challenge in the clinic. Activation of epidermal growth factor receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and crosstalk between these two signaling pathways have been implicated in the development of radiation resistance in PC. This study assessed the effects of targeting both receptors on the regulation of radio-sensitivity in PC cells. Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results showed that co-inhibiting both receptors significantly dampened cellular growth and DNA damage repair, and increased radio-sensitivity in PC cells. These effects were carried out through synergistic inhibition of homologous recombination-directed DNA repair (HRR), but not via inhibition of non-homologous end joining (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors was also confirmed in nude mouse xenograft assay. This is the first study testing co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC and it may provide a promising adjuvant therapeutic approach to improve the outcome of PC patients to radiation treatment.
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Receptores ErbB/antagonistas & inibidores , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Tolerância a Radiação , Receptor IGF Tipo 1/antagonistas & inibidores , Reparo de DNA por Recombinação , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA por Junção de Extremidades , Modelos Animais de Doenças , Receptores ErbB/genética , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Neoplasias da Próstata/radioterapia , Rad51 Recombinase/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/genética , Radiossensibilizantes/farmacologia , Receptor IGF Tipo 1/genética , Reparo de DNA por Recombinação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/farmacologiaRESUMO
Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan-Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.
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Proteínas Adaptadoras de Sinalização CARD/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga TumoralRESUMO
Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/análogos & derivados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Transdução de Sinais/efeitos dos fármacos , Inibidores da Topoisomerase I/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia , Camptotecina/farmacologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Camundongos , Camundongos Nus , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
N-myc downstream regulated gene 2 (NDRG2) is involved in invasion and metastasis of cancer, furthermore it is frequently down-regulated in prostate cancer. Herein we evaluated the effect of NDRG2 overexpression on invasiveness and bone destruction in prostate cancer. The human prostate cancer cell line PC-3 and DU145 were infected with Ad-NDRG2 or Ad-LacZ. Overexpression of NDRG2 not only inhibited the growth of the cells, but also suppressed invasiveness of the cells in an in vitro assay. PC-3 cells infected with Ad-NDRG2 or Ad-LacZ were injected into the tibias of nude mice. Four weeks later, we found the mice injected with PC-3 cells overexpressing NDRG2 had smaller tumors and less bone destruction. These results demonstrate that NDRG2 overexpression can inhibit tumor growth and invasion, furthermore, it can decrease bone destruction caused by prostate cancer bone metastasis.
Assuntos
Neoplasias Ósseas/metabolismo , Proliferação de Células , Neoplasias da Próstata/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transfecção , Transplante Heterólogo , Carga Tumoral/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: To evaluate the safety and efficacy of intraperitoneal anatomical radical nephrectomy (IARN). METHODS: A retrospective analysis was performed for 60 consecutive patients undergoing IARN at our hospital from March 2007 to December 2009. Various clinical parameters were collected and analyzed statistically. RESULTS: Sixty operations were performed successfully. There was neither conversion into open surgery nor blood transfusion. The mean operative time was (106 ± 23) min, mean intraoperative estimated blood loss (112 ± 37) ml, mean time of resuming oral intake (2.1 ± 0.7) d, mean time to ambulation (1.9 ± 1.1) d, mean postoperative analgesics (pethidine) dosage (65 ± 25) mg, average drainage volume 100 (50 - 300) ml, mean time of extracting drainage tube (3.6 ± 1.3) d and mean postoperative hospital stay (9.4 ± 2.1) d. CONCLUSION: IARN offers the advantages of distinct anatomical level, shorter operative time, less hemorrhage, less damage, faster postoperative recovery and a lower rate of complications.
Assuntos
Laparoscopia , Nefrectomia , Perda Sanguínea Cirúrgica , Humanos , Tempo de Internação , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the role played by transforming growth factor beta receptor II (TGFbetaRII) in cryptorchidism-induced spermatocyte apoptosis. METHODS: A unilateral cryptorchidism rat model was surgically established in 20-day-old male SD rats. Testis samples were collected 0, 4, 7, 14, and 21 days after surgery. Histologic changes, apoptosis, TGFbetaRII/smad, and TGFbetaRII/mitogen-activated protein kinase activation were explored by hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and western blot analysis, respectively. TGFbetaRII was knocked down in GC-2 spg cells and the cells were then treated with hyperthermia. Western blot analysis was performed to detect TGFbetaRII, the phosphorylation status of smad2, smad3, and p38 and the cleavage status of caspase-3. RESULTS: Surgically induced cryptorchidism significantly impaired testis growth and spermatogenesis in unilateral undescended testes (UUTs) compared with contralateral descended testes 7, 14, and 21 days after surgery. The mean apoptotic index was significantly higher in UUTs than in contralateral descended testes. Western blot analysis showed that TGFbetaRII and smad2 expression increased. Phosphorylation of smad2, smad3, and p38 and cleavage of caspase-3 increased in UUTs. TGFbetaRII knockdown in GC-2 spg cells reduced hyperthermia-induced apoptosis by inhibiting smad2, smad3, and p38 phosphorylation as well as downstream caspase-3 cleavage. CONCLUSIONS: Cryptorchidism lowered the growth rate of testes by inducing apoptosis, via a mechanism involving the activation of the TGFbetaR/smad and TGFbetaR/mitogen-activated protein kinase pathways.
Assuntos
Apoptose , Criptorquidismo/patologia , Proteínas Serina-Treonina Quinases/fisiologia , Receptores de Fatores de Crescimento Transformadores beta/fisiologia , Espermatócitos/patologia , Animais , Criptorquidismo/metabolismo , Modelos Animais de Doenças , Masculino , Fosforilação , Ratos , Receptor do Fator de Crescimento Transformador beta Tipo II , Proteínas Smad/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: To evaluate the expression of COX10 mRNA in the testes of non-obstructive azoospermia patients and normal men. METHODS: A cDNA microarray containing COX10 and some other genes as RBM and EIF1AY was used to identify the differential gene expression profiles in the normal and azoospermic testes. The cDNA probes were prepared by labeling mRNA from azoospermic and normal testis tissues with Cy5-dUTP and Cy3-dUTP respectively through reverse transcription. The mixed cDNA probes were then hybridized with cDNA microarray. Later the fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were calculated and analyzed. After that an ISH was employed to detect the expression of COX10 mRNA in 10 fertile and 39 non-obstructive azoospermic testes, and the expression levels were compared to evaluate the significance. RESULTS: We obtained 128 differentially expressed genes that might be related with azoospermia, among which 56 were up-regulated and 72 down-regulated, with the expression of COX10 significantly decreased. In situ hybridization confirmed that the mRNA expression of COX10 was stronger in the spermatogenic cells of the normal fertile than the azoospermic testes. CONCLUSION: COX10 may play a certain role in the development and progression of azoospermia. The technique of cDNA microarray can be applied to further studies of screening non-obstructive azoospermia associated genes.