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1.
Chemosphere ; 249: 126212, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32088459

RESUMO

The ecological risk of heavy metals (HM) resulting from the use of sewage sludge compost (SSC) as an amendment to flower garden soil (FGS) and to abandoned phosphate mine soil (APMS) influenced by acid rain were simulated in lysimeter trials and the potential ecological risk index (PERI) was evaluated with minor modifications. The use of SSC indeed increased the mobility and release of HMs in FGS and APMS under conditions of acid rain. The leaching dynamics of HMs was found to be influenced by Fe/Al oxides and organic matter (OM) in the soil. The application of SSC as a fertilizer to barren APMS dramatically decreased the mobility of Cr, Cu and Pb by 51-56% due to their retention by particulate organic matter, while the leaching of As, Cd and Ni was increased as the result of competition with OM for available Fe/Al oxides (As) and proton-metal exchange reactions that occurred in HM-OM complexes (Cd and Ni). The ecological risk of FGS and APMS resulting from HM migration was actually low (PERI = 0.07-0.12), but the increased potential ecological risk resulting from the use of SSC were estimated to be moderate (a 16.0-33.5% increase in PERI for SSC-amended FGS) or high (a 140% increase in PERI for SSC-amended APMS). Ni, Cd and Cu were identified as the three main HMs responsible for increasing the ecological risk in soil which was mainly composed of fine-grained particles, whereas Cd and As were key ecological risks HMs in soil that was mainly composed of coarse-grained particles.

2.
Appl Immunohistochem Mol Morphol ; 28(2): 103-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32044878

RESUMO

Gallbladder cancer (GBC) is a rare disease with high mortality. However, no biomarkers for the carcinogenesis, progression, prognosis, and early diagnosis are clinically available. This study investigated the expressions of cystathionine-ß-synthase (CBS) and C-C chemokine receptor 7 (CCR7) protein and their clinical and pathologic significances in gallbladder squamous cell/adenosquamous carcinomas (SC/ASC) and adenocarcinomas (AC). CBS and chemokine ligand 21 (CCL21) expression was measured using immunohistochemistry in 69 SC/ASCs and 146 ACs. A significantly high percentage of patients with an age above 45 years, lymph node metastasis, and invasion was observed in the SCs/ASCs compared with ACs (P<0.05). Both AC and SC/ASC patients with positive CBS and CCL21 expression exhibited a high tumor-lymph node-metastasis stage, lymph node metastasis, and invasion compared with patients with negative CBS and CCL21 expression (P<0.05 or P<0.01). SC/ASC patients with positive CBS expression was prone to have a larger tumor size than those with negative expression (P<0.05). Positive CBS and CCL21 expression correlated with poor differentiation and larger tumor size in AC patients. Positive CBS and CCL21 are closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.01) and were independent factors for a poor-prognosis. Both CBS and CCL21 showed a good overall diagnostic performance for SC/ASC (AUC=0.742 and AUC=0.764, respectively) and AC (AUC=0.734 and AUC=0.718, respectively). In conclusion, positive CBS and CCL21 expression are closely associated with the clinical severity and poor prognosis in GBC, and can be a marker for the diagnosis of AC and SC/ASC type of GBC.

3.
World J Surg ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773219

RESUMO

BACKGROUND: Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. METHODS: This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. RESULTS: A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. CONCLUSION: For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

4.
Biomed Pharmacother ; 119: 109397, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31514071

RESUMO

Micro-RNAs regulate multiple biological behaviors of cancers, making them potential targets of new cancer therapies. MiR-1181 has been demonstrated to perform oncogenic or tumor-suppressing function in a tissue-dependent way, but its role in hepatocellular carcinoma (HCC) was unclear. Here, we showed that miR-1181 was significantly overexpressed in HCC tissues when compared with tumor-adjacent normal ones or normal liver tissues from donated organ, and that inhibition of miR-1181 could repress the growth of HCC cells. Through bioinformatics analysis and luciferase reporter assays, we found that axis inhibition protein 1 (AXIN1) was a direct target of miR-1181, and the expression of AXIN1 showed a negative correlation with that of miR-1181 in HCC. Therefore, these data indicated an oncogenic function of miRNA-1181 in the development of HCC and a potential target for the clinical treatment of HCC.

5.
Surg Oncol ; 29: 41-47, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196492

RESUMO

AIMS: Extrahepatic cholangiocarcinoma is a malignant tumor and poor prognosis with intrinsic resistance to cytotoxic agents. The molecular mechanism associated with high malignancy and resistance to chemotherapy and radiotherapy has not been fully elucidated. This study aims to investigate the clinicopathological significances of HMGA2 and Thy1 expression in extrahepatic cholangiocarcinoma. METHODS: The expressions of HMGA2 and Thy1 in 100 extrahepatic cholangiocarcinoma, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues were assayed using EnVision immunohistochemistry. RESULTS: The HMGA2 and Thy1 proteins were overexpression in extrahepatic cholangiocarcinoma compared to peritumoral tissues, adenoma, and normal biliary tract tissues (P < 0.05 or P < 0.01). Adenoma and pericancerous tissues with positive HMGA2 or/and Thy1 protein expression exhibited atypical hyperplasia. The positive correlation was found between the expression of HMGA2 and Thy1 in extrahepatic cholangiocarcinoma (P < 0.01). The positive rates of HMGA2 and Thy1 expression were significantly higher in cases with poor differentiation, lymph node metastasis, invasion, and TNM stage III or IV and no resection (biopsy only) (P < 0.05 or P < 0.01). Kaplan-Meier survival analysis showed that the survival of extrahepatic cholangiocarcinoma patients with positive HMGA2 and/or Thy1 expression is significantly shorter than patients with negative HMGA2 and/or Thy1 expression (P = 0.000). Cox multivariate analysis revealed that positive HMGA2 and/or Thy1 expressions were independently poor prognosis factors in extrahepatic cholangiocarcinoma patients. We calculated the AUC for HMGA2 (AUC = 0.610, 95%CI: 0.519-0.702), or Thy1 (AUC = 0.675, 95%CI: 0.588-0.762), respectively. CONCLUSIONS: The present study indicated that positive HMGA2 and Thy1 expression are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in patients with extrahepatic cholangiocarcinoma.


Assuntos
Adenocarcinoma/secundário , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/patologia , Proteína HMGA2/metabolismo , Recidiva Local de Neoplasia/patologia , Antígenos Thy-1/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Nucl Med Commun ; 40(7): 711-719, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31095043

RESUMO

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing sharply, the current statement about whether PTMC patients should undergo radioactive iodine (RAI) remnant ablation is still controversial, mainly because it is uncertain whether RAI treatment can reduce the recurrence rate. OBJECTIVE: To evaluate the effectiveness of RAI remnant ablation for thyroid cancer-related outcomes of PTMC patients. METHODS: We comprehensively searched PubMed, Cochrane Library, Scopus and Science Direct for studies that compared the effectiveness after total-thyroidectomy or near total-thyroidectomy, with or without RAI remnant ablation treatment. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. RESULTS: Twenty-two studies, which included 8724 patients, met our search criteria and were assessed. For PTMC patients treated by total thyroidectomy or near-total thyroidectomy, the locoregional recurrence rates were 1.92 and 7.36% [risk ratio (RR)=0.45; 95% confidence interval (CI)=0.18-1.11; P=0.08] for patients with or without RAI treatment respectively, the distant metastasis rates were 1.39 and 2.46% (RR=0.64; 95% CI=0.28-1.48; P=0.30), and the thyroid cancer-related mortality rates were 0.98 and 1.76% (RR=0.68; 95% CI=0.22-2.09; P=0.50). CONCLUSION: For PTMC patients who have already treated by total thyroidectomy or near-total thyroidectomy, incremental RAI remnant ablation may significantly improve thyroid cancer-related outcomes.


Assuntos
Técnicas de Ablação/métodos , Carcinoma Papilar/terapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Carcinoma Papilar/patologia , Humanos , Metástase Linfática , Neoplasias da Glândula Tireoide/patologia
7.
Onco Targets Ther ; 12: 2955-2965, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114239

RESUMO

Aims: Extrahepatic cholangiocarcinoma (EHCC) is a highly malignant tumor with poor prognosis and intrinsic resistance to cytotoxic agents. The molecular mechanisms associated with high malignancy and resistance to chemotherapy and radiotherapy have not been fully elucidated. This study investigated the clinicopathological significances of FOXP1 and FOXO3a expression in EHCC. Methods: We assayed FOXP1 and FOXO3a expressions in 100 EHCC, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues using EnVision immunohistochemistry. Results: The positive rates of FOXP1 and FOXO3a proteins were significantly lower in EHCC tumors than in peritumoral tissues, adenoma, and normal bile tract tissues (P<0.05 or P<0.01). Adenoma and pericancerous tissues with negative FOXP1 and/or FOXO3a protein expressions exhibited atypical hyperplasia. The positive correlation was established between the expression of FOXP1 and FOXO3a in EHCC (P<0.01). The positive rates of FOXP1 and FOXO3a expression were significantly higher in cases with well differentiation, no metastasis in lymph node, no invasion to surrounding tissues and organs, TNM I + II stage and radical resection (p<0.05 or p<0.01). Kaplan-Meier survival analysis showed that EHCC patients with positive FOXP1 and FOXO3a expression survived significantly higher than patients with negative FOXP1 and FOXO3a expression, respectively (P<0.001). Cox multivariate analysis revealed that negative FOXP1 or FOXO3a expressions were independent poor prognostic factors in EHCC patients. The AUCs for FOXP1 and FOXO3a were 0.676 (95% CI: 0.589-0.763, P<0.001) and 0.652 (95% CI: 0.563-741, P=0.002), respectively. Conclusion: The present study indicates that negative FOXP1 and FOXO3a expressions are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in EHCC.

8.
Clin Lab ; 65(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30775881

RESUMO

BACKGROUND: Renal involvement is rare in B lymphoblastic lymphoma (B-LBL). The authors describe a rare case of renal involvement in a 21-year-old male patient with B lymphoblastic lymphoma leukemia, presenting with severe lactic acidosis. METHODS: Hematologic investigation, bone marrow aspirate and biopsy, cytogenetic analysis and renal biopsy were performed. RESULTS: The patient achieved complete hematological remission (CHR) after induction therapy with the regimen of VDCP and received consolidation chemotherapy regularly. He remained CHR until now. CONCLUSIONS: Renal biopsy, bone marrow aspirate, and biopsy are important to confirm a correct diagnosis. Renal involvement in B-LBL as a prognostic factor needs further studies.


Assuntos
Rim/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Acidose Láctica/classificação , Acidose Láctica/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Rim/efeitos dos fármacos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Indução de Remissão , Adulto Jovem
9.
Appl Immunohistochem Mol Morphol ; 27(1): 40-47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531392

RESUMO

BACKGROUND: Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers for the diagnosis, prediction of prognosis, and target therapy have not yet been identified. OBJECTIVE: To investigate the expression of aquaporin-1 (AQP1) and AQP3 protein and their clinicopathological significances in PDACs. MATERIALS AND METHOD: AQP1 and AQP3 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues was measured by immunohistochemistry. RESULTS: Western blot showed that AQP1 and AQP3 protein expression was significantly higher in PDAC tissues than that in benign pancreatic tissues (P<0.01). Immunohistochemistry showed that the percentages of positive AQP1 and AQP3 expressions were significantly higher in PDAC tumors than that in peritumoral tissues, benign, and normal pancreatic tissues (P<0.01). Benign pancreatic lesions with positive AQP1 and AQP3 expression exhibited a dysplasia or intraepithelial neoplasia. The percentage of cases with positive AQP1 and AQP3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion, and having low Tumor, Node and Metastasis (TNM) stage disease than in patients with lymph node metastasis, invasion, and high TNM stage disease (P<0.05 or <0.01). Kaplan-Meier survival analysis showed that positive AQP1 and AQP3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive AQP1 and AQP3 expression was independent poor prognosis factors in PDAC patients. The area under the curve of receiver operating characteristic curve was 0.669 for AQP1 and 0.707 for AQP3, respectively. CONCLUSIONS: Positive AQP1 and AQP3 expressions are associated with the tumorigenesis and progression of PDAC. Both AQP1 and AQP3 are a diagnostic marker of PDAC and a predictive marker of poor prognosis in PDAC patients.

10.
J Cell Physiol ; 234(7): 11440-11450, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30548582

RESUMO

microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia-reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia-reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-ß (TGF-ß1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-ß1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-ß1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-ß1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-ß1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.

11.
Pathol Oncol Res ; 25(1): 157-167, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29043607

RESUMO

This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2 was significantly higher in SC/ASC patients with large tumor sizes than patients with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1 expressions was significantly higher in AC patients with high TNM stages that didn't receive resection surgery compared to patients with low TNM stages that did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1 was significantly higher in AC patients with lymph node metastasis and invasion than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and IFITM1 expression was closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC.


Assuntos
Adenocarcinoma/secundário , Antígenos de Diferenciação/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/secundário , Carcinoma de Células Escamosas/secundário , Receptor com Domínio Discoidina 2/metabolismo , Neoplasias da Vesícula Biliar/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/cirurgia , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Taxa de Sobrevida
12.
Cell Commun Signal ; 16(1): 92, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30497491

RESUMO

BACKGROUND: Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. METHODS: We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. RESULTS: We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. CONCLUSIONS: Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.


Assuntos
Proteínas de Transporte/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citocinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Retroalimentação Fisiológica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos
13.
World J Surg Oncol ; 16(1): 11, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29347944

RESUMO

BACKGROUND: This study investigated UGP2 (uridine diphosphate-glucose pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal tissue (NT) and their clinicopathological significance. METHODS: Surgical specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35 cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional paraffin-embedded sections. EnVision immunohistochemical was used to stain for UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the correlation of expression pattern with survival. RESULTS: We found that positive UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL, and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe atypical hyperplasia or intraepithelial neoplasia of grades II-III was observed in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high differentiation, no lymph node metastasis, no surrounding invasion, and TNM (tumor-node-metastasis) staging I or/and II were significantly lower than those in cases with poor differentiation, lymph node metastasis, surrounding invasion, and TNM stage III and/or IV. Positive UGP2 expression in male patients was significantly lower than that in female patients. UGP2 and CFL1 expression in PDC were positively correlated. Kaplan-Meier survival analysis showed the degree of differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and surrounding invasion, and UGP2 and CFL1 expression were closely related to the average survival time of patients with PDC. The survival time of patients with positive UGP2 and CFL1 expression was significantly shorter than that of patients with negative expression. Cox multivariate analysis showed that poor differentiation, tumor maximal diameter ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was negatively correlated with the postoperative survival rate and positively correlated with the mortality of patients with PDC. CONCLUSION: Positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/secundário , Cofilina 1/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , UTP-Glucose-1-Fosfato Uridililtransferase/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pâncreas/metabolismo , Pâncreas/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Prognóstico , Taxa de Sobrevida
14.
Clin Cancer Res ; 24(2): 445-459, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29084921

RESUMO

Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress-related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified.Experimental Design: The expression of REDD1 in BUC was detected by Western blot analysis and immunohistochemistry (IHC). The correlation between REDD1 expression and clinical features in patients with BUC were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo Then the targeted-regulating mechanism of REDD1 by miRNAs was explored.Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is first reported as an independent prognostic factor in patients with BUC. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. In addition, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1-EEF2K-autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Finally, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant carcinoma model in vivoConclusions: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel. Clin Cancer Res; 24(2); 445-59. ©2017 AACR.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Paclitaxel/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Pathol Oncol Res ; 24(4): 899-906, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28921449

RESUMO

Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers have not yet been identified. This study was to investigate the clinical significance of FZD1 and CAIX in PDACs. FZD1 and CAIX protein expression was measured using EnVision immunohistochemistry. Positive FZD1 or CAIX expression was significantly higher in PDAC than that in precursor lesions (p < 0.01). Positive FZD1 or CAIX expression was significantly lower in cases with well-differentiated adenocarcinoma, no-metastasis of the lymph node, no-invasion of regional tissues, and TNM I/II stage disease than in cases with poorly-differentiated adenocarcinoma, metastasis and invasion, and TNM stage III+ IV stage disease (p < 0.05 or p < 0.01). The expression of FZD1 positively correlated with CAIX in PDAC (P = 0.000). Univariate Kaplan-Meier analysis showed that FZD1 and/or CAIX expression (p < 0.001) was significantly associated with shorter overall survival (p < 0.05). Cox multivariate analysis showed that differentiation, tumor mass, lymph node metastasis, invasion, TNM stage, FZD1 and CAIX levels negatively correlated with overall survival. Positive FZD1 and CAIX expressions are poor prognostic factors in PDAC patients. FZD1 and CAIX might be important biological markers for the carcinogenesis, metastasis, invasion, and prognosis of PDAC.


Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/análise , Anidrase Carbônica IX/biossíntese , Carcinoma Ductal Pancreático/patologia , Receptores Frizzled/biossíntese , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Antígenos de Neoplasias/análise , Anidrase Carbônica IX/análise , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Progressão da Doença , Feminino , Receptores Frizzled/análise , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico
16.
Planta ; 247(1): 113-125, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28879514

RESUMO

MAIN CONCLUSION: We found a new in vivo route to produce maternal doubled haploid of Brassica napus . The pollen donor, an allooctaploid rapeseed, acts as a DH inducer. Inbred line has a powerful advantage in cultivar breeding and genetic analysis. Compared to the traditional breeding methods, doubled haploid production can save years off the breeding process. Though genotype-dependent tissue culture methods are widely used in the Brassica crops, seed-based in vivo doubled haploid developing systems are rare in nature and in the laboratory. As interspecific cross and interploid hybridization play an important role in genome evolution and plant speciation, we created a new Brassica artificial hybrid, a Brassica allooctaploid (AAAACCCC, 2n = 8× = 76), by interspecific crossing and genome doubling. A homozygous line was observed at the third self-generation of a synthesized Brassica allohexaploid (AAAACC, 2n = 6× = 58). Crosses between B. napus as female and Brassica allooctaploid as pollen donor were conducted, which yielded maternal doubled haploid B. napus that were identified based on phenotype, ploidy, and molecular analysis. The Brassica octaploid acted as a maternal doubled haploid inducer and had a relatively high induction rate. Our research provides a new insight for generation of homozygous lines in vivo using a single-step approach, as well as promotes the understanding in breeding programs and genetic studies involving the Brassicas.


Assuntos
Brassica napus/genética , Brassica/genética , Hibridização Genética , Brassica rapa/genética , Cruzamento , Genótipo , Haploidia , Fenótipo , Pólen/genética , Poliploidia , Sementes/genética
17.
Protein J ; 36(5): 407-416, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28856545

RESUMO

Protein disulfide isomerase is a type of enzyme that catalyses the oxidation, isomerization and reduction of disulfide bonds. Conotoxins that containing disulfide bonds are likely substrates of protein disulfide isomerise. Here, we cloned 12 protein disulfide isomerise genes from 12 different cone snail species that inhabited the sea near Sanya in China. The full-length amino acid sequences of these protein disulfide isomerase genes share a high degree of homology, including the same -CGHC- active site sequence and -RDEL- endoplasmic reticulum retention signal. To obtain enough conus protein disulfide isomerase for functional studies, we constructed the expression vector pET28a-sPDI. Conus protein disulfide isomerase was successfully expressed using Escherichia coli expression system and purified using chromatography method of affinity chromatography. The recombinant conus protein disulfide isomerase showed the ability to catalyse disulfide bond formation and rearrangement in the lysozyme enzyme activity assay. The role of conus protein disulfide isomerase in the in vitro oxidative folding of conotoxins was investigated using synthetic linear conotoxin lt14a, a peptide composed of 13 amino acids. It was confirmed by high performance liquid chromatography and mass spectrometry analysis that conus protein disulfide isomerase can catalyse the disulfide bond formation of linear lt14a. Then, conus protein disulfide isomerase was acted as a fusion partner during the production of engineered peptidyl-prolyl cis-trans isomerase and lt14a derived from cone snails. It was shown that peptidyl-prolyl cis-trans isomerase and conotoxin lt14a are successfully expressed in a highly soluble form by fusion with conus protein disulfide isomerase. Thus, conus protein disulfide isomerase functions not only as an enzyme that catalyses oxidative process but also a fusion partner in recombinant conotoxin expression.


Assuntos
Conotoxinas/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Conotoxinas/química , Caramujo Conus , Estabilidade Enzimática , Escherichia coli , Isomerases de Dissulfetos de Proteínas/química , Isomerases de Dissulfetos de Proteínas/genética , Dobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(6): 767-773, 2017 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-28669950

RESUMO

OBJECTIVE: To screen the genes related with leukocyte responses in mice early after burn injury by bioinformatic analysis of the gene expression profiling data. METHODS: The gene expression profiles were obtained from GEO (GSE7404, Mouse musculus, 25% TBSA, full-thickness) database. T test, fold changes and GO functional enrichment analysis were used to identify the differentially expressed genes (DEGs) related to leukocyte responses to burns; the interacting genes were transferred to STRING to construct the protein-protein interaction (PPI) network. Biological annotation of the sub-networks was executed using the software Cytoscape. Real-time PCR and Western blotting were used to verify the DEGs in mice. RESULTS: In mice at 1 day post-burn, a total of 658 genes were up-regulated and 1167 were down-regulated. PPI network and module analysis suggested that some of the genes (Stat1, Cdk1, Cd19, Lck and Jun) may play critical roles in the PPI network post-burn. Real-time PCR and Western blotting results in mice were consistent with those of bioinformatic analysis of Stat1, Cdk1 and Jun. CONCLUSION: Stat1, Cdk1 and Jun might be critical players in the development of leukocyte response in mice early after burn injury. Our finding provides new insights into the pathogenesis of leukocyte response to burn injury and identifies several biomarkers as potential targets for burn treatment.


Assuntos
Queimaduras/metabolismo , Perfilação da Expressão Gênica , Leucócitos/citologia , Animais , Biomarcadores/metabolismo , Biologia Computacional , Redes Reguladoras de Genes , Camundongos , Mapas de Interação de Proteínas
19.
World J Gastroenterol ; 23(14): 2601-2612, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28465645

RESUMO

AIM: To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS: EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS: Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION: SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Carcinoma Adenoescamoso/química , Neoplasias da Vesícula Biliar/química , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/análise , Proteína Wnt-5a/análise , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Diferenciação Celular , Distribuição de Qui-Quadrado , China , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
20.
Tumour Biol ; 39(5): 1010428317699129, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28466777

RESUMO

Pancreatic ductal adenocarcinoma is a highly malignant tumor with poor prognosis, and the biomarkers for the early diagnosis, targeting therapy, and prognosis are still not clinically available. This study investigated the expression of forkhead box P1 and forkhead box O3a proteins in human pancreatic ductal adenocarcinoma tumor tissues and pancreatic tissues with and without benign lesions using immunohistochemical staining. Results showed that the positive rates of forkhead box P1 and forkhead box O3a protein expression were significantly lower in pancreatic ductal adenocarcinoma tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (p < 0.01). Pancreatic tissues with negative forkhead box P1 and forkhead box O3a protein expression exhibited dysplasia or intraepithelial neoplasia. The positive rates of forkhead box P1 and forkhead box O3a expression were significantly lower in cases with tumor mass >5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and tumor-node-metastasis III + IV stage disease compared to cases with tumor mass ⩽5 cm (p < 0.05), no lymph node metastasis (p < 0.001 and p = 0.001, respectively), no invasion (p = 0.003 and p = 0.004, respectively), and tumor-node-metastasis I or II stage disease (p < 0.05). Kaplan-Meier survival analysis showed that pancreatic ductal adenocarcinoma patients with negative forkhead box P1 and forkhead box O3a expression survived significantly shorter than patients with positive forkhead box P1 and forkhead box O3a expression (p = 0.000). Cox multivariate analysis revealed that negative forkhead box P1 and forkhead box O3a expression was an independent poor prognosis factor in pancreatic ductal adenocarcinoma patients. The area under the curve of a receiver operating characteristic curve was 0.642 for forkhead box P1 (95% confidence interval: 0.553-0.730) and 0.655 for forkhead box O3a (95% confidence interval: 0.6568-0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Proteína Forkhead Box O3/genética , Fatores de Transcrição Forkhead/genética , Proteínas Repressoras/genética , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
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