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1.
J Gene Med ; 22(4): e3155, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31860771

RESUMO

BACKGROUND: Overexpression of sperm-associated antigen 5 (SPAG5) is a marker of poor prognosis in numerous tumors and is recognized as an index of tumor proliferation; however, its expression in liver cancer remains unclear. METHODS: The Oncomine (https://www.oncomine.org) and Timer (https://cistrome.shinyapps.io/timer) databases were used to analyze the expression of SPAG5 in liver hepatocellular carcinoma (HCC) and normal liver tissues. The relationship between the expression of SPAG5 and immune infiltration of HCC was investigated using the Timer and GEPIA (http://gepia.cancer-pku.cn) databases, and the mechanism was analyzed using Gene Set Enrichment Analysis. A Kaplan-Meier Plotter (http://kmplot.com/analysis) was used to evaluate the effect of SPAG5 on the prognosis of patients with HCC. RESULTS: The results revealed that the SPAG5 expression level was positively correlated with the infiltration levels of CD8+ T cells, macrophages, neutrophils, and especially B cells and dendritic cells. In addition, SPAG5 expression was significantly associated with T cell exhaustion. The overall survival time, progression-free survival time, recurrence-free survival time and disease-specific survival time were significantly reduced for HCC patients with high SPAG5 expression (p < 0.01) and high expression of SPAG5 was significantly associated with a poor overall survival time and progression-free survival time of grade and stage II-III HCC (p < 0.05) but not with stage I HCC (p > 0.05). Additionally, the expression of SPAG5 is related to the p53 and cell cycle signal pathways. CONCLUSIONS: In conclusion, SPAG5 is not only a marker of immune infiltration and poor prognosis, but also a potential therapeutic target for liver cancer.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/genética , Expressão Gênica , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Bases de Dados de Ácidos Nucleicos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
2.
J Stroke Cerebrovasc Dis ; 29(8): 104918, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32430237

RESUMO

INTRODUCTION AND OBJECTIVE: At present, there is no hematology marker with high specificity to the diagnosis and differential diagnosis of acute ischemic stroke (AIS). How to use the existing test items to improve the diagnosis efficiency worthy of discussion. D-Dimer (DD) and fibrinogen (FIB) were the common indicators in thrombotic diseases, but D-dimer to fibrinogen ratio (D/F) in AIS has not been used in clinical practice. In this work, we focus on the evaluation of D/F. METHODS: 90 AIS patients were selected as the observation group and 65 other patients without coagulation function disorder as the control group. Meanwhile, a total of 33 patients with other diseases with impaired consciousness in the same period were collected. Based on the AIS patients with or without consciousness disorder divided it into consciousness disorder group and unconsciousness disorder group. Then based on the patients with or without consciousness disorder divided it into other diseases with unconsciousness disorder group and Other diseases with lacunar cerebral infarction (LCI)and disturbance of consciousness group. then compare the differences of plasma DD, FIB and D/F between groups. RESULTS: All plasma DD, FIB and D/F ratio in AIS patients were significantly higher than in other disease group (P = 0.000, P = 0.001, P = 0.000), but DD, D/F in disorders of consciousness group was significantly higher than in unconsciousness disorders group (P = 0.007, P = 0.005). The DD of the AIS with consciousness disorder group were significantly higher than that of the other disease with consciousness disorder group (P = 0.042), and the DD, D/F ratio of Other diseases with lacunar cerebral infarction and disturbance of consciousness group were significantly higher than one(P = 0.000, P = 0.003). All others are undifferentiated. CONCLUSIONS: When DD, D/F ratio is high, other diseases caused by consciousness disorders are likely to be combined with infarcts, which can be used for the diagnosis and differential diagnosis of patients with different types of consciousness disorders, especially hospitalized patients.


Assuntos
Isquemia Encefálica/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/sangue
3.
Cancer Sci ; 109(11): 3416-3427, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30151927

RESUMO

Inhibin B (INHBB), a heterodimer of a common α-subunit and a ßB-subunit, is a glycoprotein belonging to the transforming growth factor-ß (TGF-ß) family. In this study, we observed INHBB expression was reduced in nasopharyngeal carcinoma (NPC) tissues compared to non-tumor nasopharyngeal epithelium tissues, and INHBB was associated with lymph node metastasis, stage of disease, and clinical progress. Positive expression of INHBB in NPC predicted a better prognosis (overall survival, P = 0.038). However, the molecular mechanisms of INHBB have not been addressed in NPC. We induced anoikis-resistant cells in NPC cell lines under anchorage-independent conditions, then found epithelial-mesenchymal transition markers changed, cell apoptosis decreased, cell cycle was modified, and invasion strengthened in anoikis-resistant NPC cells. These anoikis-resistant NPC cells showed decreased expression of INHBB compared with adhesion cells. Furthermore, INHBB was found to influence the above-mentioned changes. In the anoikis-resistant NPC cells with INHBB overexpression, apoptotic cells increased, S phase cells weakened, vimentin, matrix metallopeptidase-9, and vascular endothelial growth factor A expression were downregulated, and E-cadherin expression was upregulated, and vice versa in knockdown of INHBB (INHBB shRNA) anoikis-resistant NPC cells. Diminished INHBB expression could activate the TGF-ß pathway to phosphorylate Smad2/3 and form complexes in the nucleus, which resulted in the above changes. Thus, our results revealed for the first time that INHBB could suppress anoikis resistance and migration of NPC cells by the TGF-ß signaling pathway, decrease p53 overexpression, and could serve as a potential biomarker for NPC metastasis and prognosis as well as a therapeutic application.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Regulação para Baixo , Subunidades beta de Inibinas/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Adulto , Idoso , Anoikis , Carcinoma/genética , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidades beta de Inibinas/genética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Prognóstico , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
5.
Water Environ Res ; 87(1): 61-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25630128

RESUMO

Luria-Bertani broth and acetone were usually used in naphthalene degradation experiments as nutrient and solvent. However, their effect on the degradation was seldom mentioned. In this work, we investigated the effect of LB, naphthalene concentration, and acetone on the degradation of naphthalene by Pseudomonas putida G7, which is useful for the degradation of naphthalene on future field remediation. By adding LB, the naphthalene degradation efficiencies and naphthalene dioxygenase were both decreased by 98%, while the catechol dioxygenase was decreased by 90%. Degradation of naphthalene was also inhibited when naphthalene concentration was 56 ppm and higher, which was accompanied with the accumulation of orange-colored metabolism products. However, acetone can stimulate the degradation of naphthalene, and the stimulation was more obvious when naphthalene concentration was lower than 2000 ppm. By assaying the enzyme activities of naphthalene dioxygenase and catechol dioxygenase, it was thought that the degradation efficiency was depending on the more sensitive enzymes on the complicated conditions.


Assuntos
Acetona/metabolismo , Meios de Cultura/metabolismo , Naftalenos/metabolismo , Pseudomonas putida/metabolismo , Proteínas de Bactérias/metabolismo , Catecol 2,3-Dioxigenase/metabolismo , Dioxigenases/metabolismo , Complexos Multienzimáticos/metabolismo
6.
Clin Biochem ; 116: 52-58, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36965690

RESUMO

BACKGROUND: Quality control (QC) in the laboratory aims to reduce the risk of harm to a patient due to erroneous results, as highlighted by the Clinical Laboratory Standards Institute (CLSI) guidance for Statistical Quality Control (SQC) (C24-Ed4). To effectively reduce patient risk, a convenient spreadsheet tool was developed to assist laboratories in SQC design based on patient risk parameters. METHODS: In accordance with Parvin's patient risk model and the mathematical formula for calculating the expected number of unreliable final patient results [E(Nuf)], the function is edited using Excel software, and the maximum E(Nuf) [MaxE(Nuf)] value and other risk parameters based on the current QC strategy are calculated to assess the risk of the QC strategy. RESULTS: A convenient spreadsheet tool is proposed in this study. After the quality requirements, performance parameters, practical run size, QC rules and the number of QC results of test items are input, the laboratory is enabled to quickly obtain MaxE(Nuf) value, maximum run size and other data based on the strategy. The QC strategy conforming to the risk requirements can be developed by changing the QC rules or the quantity of run size. Moreover, the Power Function Graph of the QC strategy and two risk diagrams are presented simultaneously. CONCLUSIONS: Convenient spreadsheet tools can be adopted by laboratories to assess the risks of QC strategies and design appropriate risk-based SQC strategies to reduce patient risk to acceptable levels.


Assuntos
Serviços de Laboratório Clínico , Laboratórios , Humanos , Controle de Qualidade , Software , Laboratórios Clínicos
7.
Oncol Rep ; 50(3)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37539742

RESUMO

The inhibitory role of curcumin on sperm-associated antigen 5 (SPAG5) and its effects on the cancer­related Wnt classical signaling pathway has been previously demonstrated. Nevertheless, research on the modulatory role of curcumin on the Wnt signaling pathway by acting on SPAG5 has yet to be reported. The activation of the Wnt/ß­catenin pathway is frequently observed in patients suffering from hepatocellular carcinoma (HCC), suggesting that small molecular drugs that target Wnt could present a promising therapeutic strategy. However, these drugs often result in substantial side effects. In the present study, the presence of SPAG5 in the cancer tissues of patients with HCC and cell lines was validated using immunohistochemistry, cellular immunofluorescence, reverse transcription­quantitative polymerase chain reaction, and western blot analyses. Subsequently, the effect of SPAG5 and the regulatory role of curcumin on SPAG5 and the Wnt/ß­catenin pathway were examined using cell function tests, flow cytometry, and western blotting. Techniques of gene knockout and overexpression were employed. The findings revealed a significant overexpression of SPAG5 in the cancer tissues of patients with HCC. Both the mRNA and protein levels of SPAG5 in Huh7 and HCCLM3 cell lines were markedly elevated. Treatment with curcumin led to a decrease in SPAG5 expression, while also inhibiting cell migration and promoting apoptosis. Additionally, suppression of SPAG5 expression resulted in the decreased expression of ß­catenin. Furthermore, curcumin was observed to reduce the expression of cyclin D1 in SPAG5­overexpressing cell lines. However, the degree of inhibition was diminished once SPAG5 expression was silenced. These initial findings indicate that SPAG5 may function as an upstream regulatory protein of the Wnt/ß­catenin pathway, hence offering a potential alternative target for HCC. Moreover, as curcumin has the capacity to inhibit Wnt via suppressing SPAG5, it could potentially serve as a natural drug component for early intervention and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , beta Catenina/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Curcumina/farmacologia , Curcumina/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Via de Sinalização Wnt/genética
8.
Curr Neurovasc Res ; 19(2): 137-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35578847

RESUMO

OBJECTIVE: In this study, we investigated the relationship between serum ischemic modified albumin (IMA) levels and other hematologic features and middle cerebral artery (MCA) severe stenosis/occlusion in acute ischemic stroke (AIS) patients. METHODS: The levels of serum IMA and Albumin (ALB) of 169 AIS patients were measured, and the ratio of IMA to albumin (IMAR) and the albumin-adjusted ischemia-modified albumin index (IMA index) were calculated. Different combinations of other hematologic changes and clinical features of the patients were analyzed. RESULTS: The results indicated that the levels of blood IMA and IMAR were significantly higher in the group with severe intracranial stenosis/occlusion than in the group with non-severe stenosis/ occlusion in AIS patients, while the CHE levels were significantly lower than those in the other groups. In the MCA severe stenosis/occlusion group, the levels of blood IMA and IMAR were significantly higher than that in the other vascular severe stenosis/occlusion groups, while the IMA index, ALB, and CHE were significantly lower than that in the other groups. Multiple linear regression analysis showed a significant negative correlation between IMA and albumin. A combined diagnostic ROC curve analysis showed that among AIS patients, the best combination for determining severe stenosis/occlusion of the great intracranial arteries was the admission NIHSS score + CHE (AUC = 0.783). The best combination for determining severe stenosis or occlusion of the MCA in AIS patients was IMAR combined with the admission NIHSS score and CHE (AUC = 0.827). CONCLUSION: The combined use of IMA, IMAR, and the IMA index has some diagnostic value in AIS caused by severe stenosis or occlusion of the MCA. IMAR, CHE, and the admission NIHSS scores are the best combinations to determine whether an AIS patient has severe stenosis or occlusion of the MCA.


Assuntos
Trombose Intracraniana , AVC Isquêmico , Humanos , Albumina Sérica , Biomarcadores , Constrição Patológica , Curva ROC
9.
J Inflamm Res ; 15: 1117-1131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210815

RESUMO

PURPOSE: To determine the levels of serum HDL-associated apolipoproteins (apoM and apoC) and HDL-binding receptor (scavenger receptor BI, SR-BI) in patients with gram-negative bacteria sepsis (G-sepsis) and to evaluate the value of lipoproteins in the diagnosis, severity and prognosis of G-sepsis. PATIENTS AND METHODS: A total of 128 patients with sepsis, 40 patients with system inflammatory reaction syndrome (SIRS) and 40 healthy subjects were enrolled in the Second People's Hospital of Hunan Province from September 2019 to September 2020. The levels and the correlation of lipoproteins were detected and dynamically monitored by enzyme-linked adsorption method, ROC curve for the diagnostic, severity and prognostic value of lipoproteins in G-sepsis. RESULTS: The levels of serum HDL-associated lipoproteins in patients with G-sepsis were significantly decreased (P < 0.05), and the ROC curve showed that HDL-C, SR-BI, apoM and apoC had cut-off values of 0.915 mmol/L, 122.100 pg/mL, 102.400 ug/mL and 17.55 mg/mL, respectively, for the diagnosis of G-sepsis, with the sensitivity was 85.56%, 97.78%, 93.33% and 73.03%, and the specificity was 95.0%, 82.50%, 61.54% and 82.50%, respectively. There was a correlation between HDL-associated apolipoproteins. Changes in serum HDL-associated lipoproteins were more obvious in shock group than classic inflammation indicators, such as PCT, IL-6 and CRP. They showed a trend change on day 3, with the levels of SR-BI and apoC changing 2-3 times, and the sensitivity of HDL-C, SR-BI, apoM and apoC for the diagnosis of G-septic shock were 32.43%, 72.97%, 65.75%, and 43.24%, and specificity of 94.34%, 81.13%, 83.07%, and 86.79%, respectively. The AUC, sensitivity and specificity of apoM combined with SR-BI were improved. CONCLUSION: HDL-associated lipoproteins were correlated with bacterial-infected types, and serum levels of HDL-associated lipoproteins can be used as potential biomarkers for early diagnosis and progress of G-sepsis. ApoM combined with SR-BI could improve the sensitivity and specificity of prognosis assessment.

10.
Am J Transl Res ; 14(8): 5263-5279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105051

RESUMO

OBJECTIVE: Inhibin B (INHB) is one of the TGF-ß superfamily member, consisting of α (INHA) and ßB (INHBB) subunits. Studies have found that TGF-ß receptor 3 (TGFBR3) binds to a convex α subunit on the surface of INHB, and enhances the binding affinity of activin receptor type-2 (ACVR2A/B) to INHß subunit. This study tried to evaluate the roles of INHB subunits and its receptors (INHA, ACVR2A, ACVR2B, INHBB, TGFBR3) as prognostic biomarkers and therapeutic targets for the effective treatment of lung adenocarcinoma (LUAD). METHODS: We analyzed INHB subunits and its receptors' expression and the influence of LUAD from Oncomine, GEPIA, HCMDB, CancerSEA, TIMER databases and so on. Then, 41 cases of cancer tissue and 41 cases of adjacent epithelium were detected in LUAD patients by immunohistochemistry. RESULTS: INHA, ACVR2A, ACVR2B, INHBB were up-regulated while TGFBR3 was down-regulated in LUAD. INHA, ACVR2A and TGFBR3 were found to be strongly associated with high-grade malignancies and advanced TNM, only TGFBR3 expression was negatively correlated with LUAD metastasis probably mainly through cell adhesion molecules and the PI3K-Akt signaling pathway, univariate and multivariate analysis suggested that overall survival was lower in LUAD cases with low TGFBR3 levels. Further analysis revealed that low TGFBR3 expression was related to reduced infiltration of immune cells into the LUAD, promoting metastasis of LUAD cells. TGFBR3 expression negatively correlates with lymphatic metastasis and clinical stage in patients with LUAD. CONCLUSION: TGFBR3 could be a potential new metastatic biomarker for LUAD, with potential application as a prognostic marker and for immunotherapy of LUAD.

11.
Biomark Med ; 15(9): 637-646, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34039027

RESUMO

Aim: To explore the relationship between the neutrophil-to-lymphocyte ratio (NLR) and renal damage in patients with H-type hypertension. Materials & methods: A total of 618 patients between 2017 and 2019 were analyzed retrospectively. Results: NLR was significantly correlated with renal damage in hypertension patients. Appropriate cut-off value for NLR (2.247) was determined by receiver operating characteristic curve; linear regression analysis showed that NLR and estimated glomerular filtration rate, blood urea nitrogen/creatinine has a significant negative correlation in H-type hypertension group (p < 0.05); logistic regression analysis showed that the risk of renal damage increased by 10% for each 1 umol/l increase of homocysteine, and 51% for each 1.0 increase of NLR in H-type hypertension patients. Conclusion: NLR worth popularizing in prediction of renal damage in patients with H-type hypertension.


Assuntos
Biomarcadores/análise , Hipertensão/complicações , Nefropatias/diagnóstico , Linfócitos/patologia , Neutrófilos/patologia , Idoso , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
12.
Oncol Rep ; 41(4): 2329-2336, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720101

RESUMO

Sperm­associated antigen 9 (SPAG9) is a biomarker and potential therapeutic target for several cancers; however, its involvement in liver cancer progression is not clear. The aim of the present study was to determine whether SPAG9 regulates proliferation of liver cancer. Immunohistochemistry and cell immunofluorescence were used to confirm the expression and the localization of SPAG9 in human liver cancer tissues and the liver cancer­derived HepG2 cells. A small interfering RNA (siRNA) designed to target SPAG9 was transiently transfected into HepG2 cells using Lipofectamine™ 2000, and proliferation, apoptosis and cell cycle progression were analyzed using CCK­8 assay and flow cytometry; western blotting was used to detect the expression of SPAG9, JNK, p38, MKK3 and MKK6, and co­immunoprecipitation was used to assess the interaction between SPAG9 and JNK. SPAG9 was overexpressed in 16 out of 20 (80%) patients with liver cancer. The protein was localized in both the cytoplasm and nucleus of liver cancer cells obtained from patients and in HepG2 cells. Depletion of SPAG9 inhibited the proliferation of HepG2 cells, promoted apoptosis and arrested the cell cycle at the S phase. Moreover, cells deficient in SPAG9 had decreased expression of JNK, p38 and MKK3 compared to HepG2 cells not treated with an siRNA targeting SPAG9. In the present study, SPAG9 was revealed to regulate cell proliferation, apoptosis and cell cycle progression in liver cancer cells through the SPAG9/MKK3/p38 axis. This axis is a novel therapeutic target for liver cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Progressão da Doença , Feminino , Células Hep G2 , Humanos , Fígado/patologia , MAP Quinase Quinase 3/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Oncol Lett ; 15(1): 415-422, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29391885

RESUMO

The incidence and mortality rates of hepatocellular carcinoma (HCC) are higher in China compared with in other countries. Further research is required in order to improve the diagnosis and treatment of HCC. Sperm-associated antigen 9 (SPAG9) protein has been revealed to serve an important function in cancer progression; however, the underlying mechanisms remain to be elucidated. The present study investigated the expression level of SPAG9 in HCC tissues using quantitative-polymerase chain reaction, immunohistochemistry and western blotting, and the results demonstrated that SPAG9 was overexpressed in HCC tissues compared with the adjacent non-cancerous tissues. To explore the potential mechanisms underlying SPAG9 in HCC, the effect of SPAG9 on cell proliferation, cell cycle, migration and invasion capacities were investigated in the QGY HCC cell line by RNA interference. It was revealed that inhibition of SPAG9 mRNA in QGY cells significantly inhibited the expression level of SPAG9 compared with the control. Depletion of SPAG9 expression decreased cell proliferation (P<0.01) and increased the percentage of cells in the G1/G2 cell cycle phase. The percentage of cells in the S phase was decreased, and cell migration and invasion capabilities in vitro were reduced (P<0.01). In summary, the results of the present study suggested that SPAG9 was upregulated in HCC and may serve an important function in cancer cell proliferation, differentiation and invasion. Whether SPAG9 is a potential diagnostic marker and therapeutic target of human HCC requires additional study.

14.
Oncol Rep ; 40(2): 895-901, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901164

RESUMO

Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA S phase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.


Assuntos
Alarminas/antagonistas & inibidores , Curcumina/farmacologia , Proteínas de Choque Térmico HSP72/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Receptor 4 Toll-Like/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica/genética , Fase S/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
15.
Oncol Lett ; 14(6): 7608-7614, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29344208

RESUMO

At present, there is a high incidence of viral hepatitis and high mortality rates due to hepatocellular carcinoma (HCC) in China. In the current study, the quantification of antibodies against the cancer-testis antigen sperm-associated antigen 9 (SPAG9), alone and combined with α-fetoprotein (AFP), were evaluated as biomarkers for the diagnosis of HCC. The levels of anti-SPAG9 antibody and AFP were quantified in serum samples from patients with HCC and hepatitis or cirrhosis, as well as healthy volunteers. The results revealed that the serum levels of anti-SPAG9 immunoglobulin G antibody in patients with HCC were significantly higher compared with those in patients with hepatitis/cirrhosis and healthy controls. Using receiver operator characteristic curves, the area under the curve (AUC, 0.870) of SPAG9 as a diagnostic marker of HCC was significant [P<0.001; 95% confidence interval (CI), 0.793-0.947], whereas the AUC of AFP was 0.832 (P<0.001; 95% CI, 0.736-0.928). Serum anti-SPAG9 antibody levels exhibited significant potential for the differential diagnosis of HCC, with an AUC value of 0.729, (P=0.008; 95% CI, 0.559-0.899). Similarly, serum AFP levels exhibited significant value for the differential diagnosis of HCC, with an AUC value of 0.842 (P<0.001; 95% CI, 0.732-0.953). When combined with quantification of AFP, the diagnostic sensitivity and specificity of anti-SPAG9 levels were increased. In summary, the results suggested that anti-SPAG9 antibody is a potential early diagnostic marker of HCC.

16.
Cell Stress Chaperones ; 22(2): 237-244, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28028759

RESUMO

There are different views of how the immune system participates in the reaction to cancer. Here, we evaluated expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in patients with hepatocellular carcinoma (HCC) and lung cancer to explore tumor immunity. Our analysis showed that levels of HSP70 and SPAG9 antibody were significantly higher in the serum of lung cancer and HCC patients than in the serum of healthy subjects (P < 0.001), but there were no differences in levels of HSP70 antibody in patients and controls. Levels of serum SPAG9 antibody in newly diagnosed lung cancer patients were significantly higher than in treated lung cancer patients (P < 0.05), but there were no differences in levels of HSP70 or HSP70 antibody. Levels of serum HSP70 and SPAG9 antibody, but not HSP70 antibody, were also higher in hepatitis/cirrhosis patients than in healthy subjects (P = 0.005, P < 0.001). Levels of serum SPAG9 antibody were significantly higher in HCC patients than in hepatitis/cirrhosis patients, but there were no differences in HSP70 or HSP70 antibody levels. Finally, levels of serum HSP70 and SPAG9 antibody were significantly higher in HCC patients than in lung cancer patients (P < 0.05, P < 0.001). These results indicate that cancer-testis antigen SPAG9 induces a strong humoral immune response in cancer patients but HSP70 does not. These results show that SPAG9 has potential as a tumor-specific biomarker.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/diagnóstico , Proteínas de Choque Térmico HSP70/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Idoso , Anticorpos/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Proteínas de Choque Térmico HSP70/sangue , Proteínas de Choque Térmico HSP70/imunologia , Humanos , Imunidade Humoral , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
17.
Springerplus ; 5(1): 1044, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27462492

RESUMO

OBJECTIVE: To study changes in blood lipid metabolism in sepsis patients, especially high-density lipoprotein cholesterol (HDL-C) changes in the diagnosis of sepsis and the type of bacteria involved. METHODS: Two-hundred-twenty cases of patients with febrile infections were divided into local infection, systemic inflammatory response syndrome or sepsis (sepsis) group. For controls, 81 cases of patients with a healthy check-up were used. Lipid levels and inflammatory state were supervised, and a comparative analysis of patients admitted to the hospital after 1, 5, 10 days was performed. RESULTS: In patients with sepsis, total cholesterol, HDL-C, and apolipoprotein A 1 (apoA 1) were significantly decreased in this group. Particularly HDL-C was decreased 1 day after admission. Compared with the patients with gram-positive sepsis, HDL-C and apoA1 were significantly reduced in the patients with gram-negative sepsis at admission. The 24-h change ratio of HDL-C was different between the gram-negative and gram-positive sepsis patients with a 70.5 % specificity and 76.5 % sensitivity. The area under the curve was 0.744, and the critical value was -21.1 %. CONCLUSIONS: The sepsis patients had lower HDL-C than the other groups. The 24-h change ratio of HDL-C can be used as a sepsis diagnosis maker and to distinguish between the bacteria involved in sepsis.

18.
Cell Stress Chaperones ; 21(4): 677-86, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27137634

RESUMO

Danger-associated molecular patterns (DAMPs) are activated by endogenous signals that originate from stressed, injured, or necrotic cells, signifying "danger" to the host. In this study, we evaluated the expression of the DAMP heat shock protein 70 (HSP70) in trauma patients with and without secondary infections. Levels of glucose (GLU), procalcitonin (PCT), total cholesterol (T-Chol), and white blood cell (WBC) counts were also evaluated at three time stages after trauma. Our analysis showed that the levels of serum HSP70 in patients with minor, moderate, and severe injuries were significantly higher than in healthy patients at each time point post-injury (P < 0.01), and levels of serum HSP70 in the severe injury group were significantly higher than in the minor injury group at 1-6 h after trauma (P = 0.047). HSP70 was correlated with GLU and was negatively correlated with T-Chol in the period 1-6 h after injury (P = 0.008/0.032). WBC and GLU were elevated after trauma, with mutual positive correlation (P < 0.001). PCT levels increased later than WBC counts and GLU levels; these levels were correlated at the two later time periods, 24-48 h and 60-90 h (P = 0.008/0.041). PCT continued to rise in patients with secondary infection, but PCT dropped at the third time period in patients without secondary infection. In summary, our results suggest that danger and stress theory can be used to predict severity of trauma.


Assuntos
Alarminas/sangue , Proteínas de Choque Térmico HSP70/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Adulto , Análise de Variância , Biomarcadores/sangue , Glicemia/metabolismo , Calcitonina/sangue , Colesterol/sangue , Feminino , Humanos , Contagem de Leucócitos , Masculino , Modelos Biológicos , Fatores de Tempo
19.
Oncol Rep ; 35(5): 2599-605, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26934841

RESUMO

Cancer testis antigen sperm-associated antigen 9 (SPAG9) is highly expressed in many types of cancers. In the present study, to obtain a better understanding of the relevance of SPAG9 in cancer diagnosis and treatment, the expression of SPAG9 mRNA and protein in lung cancer specimens was evaluated by RT-PCR, western blotting and immunohistochemistry. ELISA was used to quantify the SPAG9 autoantibody in the peripheral blood of lung cancer patients. The results showed that the expression of SPAG9 mRNA and protein in the lung cancer tissues was significantly higher than that in the adjacent non-cancerous tissues (P<0.01). The level of the SPAG9 autoantibody in the serum of lung cancer patients was significantly higher than the level in the healthy controls (P<0.001), and the level of the SPAG9 autoantibody in the serum of untreated patients was significantly higher than that in treated patients (P=0.002). SPAG9 IgG antibody levels were significantly lower in treated adenocarcinoma and small cell lung cancer patients than these levels in the untreated patients (P=0.006, P=0.026, respectively), while no statistical difference was found between treated and untreated squamous cell carcinoma patients. Our results suggest that the SPAG9 antibody in serum is a promising marker for the diagnosis of lung cancer, and the level of the humoral immune response to this antigen appears to be related to the type of lung cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunoglobulina G/sangue , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade
20.
Oncotarget ; 7(24): 37121-37131, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27206797

RESUMO

We investigated the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the proliferation and invasion of human cervical cancer cell lines, as well as the molecular pathways underlying these effects. MTT cell proliferation assays revealed a time- and concentration-dependent cytotoxic effect of PA-MSHA on HeLa cells but not H8 cells. Flow cytometry with propidium iodide and annexin-V-fluorescein isothiocyanate labeling (FITC) indicated that various concentrations of PA-MSHA could induce apoptosis and G2-M cell cycle arrest in HeLa cells. PA-MSHA also impaired the migration and invasion abilities of HeLa cells in Wound healing and Transwell invasion assays. Western blot results demonstrated that PA-MSHA reduced the expression of p-AKT, p-GSK3ß, BCL-2, Vimentin and ß-catenin, but increased the levels of PTEN, BAD, BAX and E-cadherin in HeLa cells. Importantly, PTEN siRNA induced the activity of p-AKT, while PA-MSHA partly inhibited this induction, indicating that PA-MSHA may reduce the cell proliferation and invasion potential by activating PTEN and thus inhibiting the AKT pathway in vitro. These data suggest the potential application of PA-MSHA to the treatment of human cervical cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas de Fímbrias/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Antígenos CD , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Movimento Celular/efeitos dos fármacos , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Células HeLa , Humanos , Manose , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/genética , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pseudomonas aeruginosa/química , Interferência de RNA , RNA Interferente Pequeno/genética , Proteínas Recombinantes/farmacologia , Neoplasias do Colo do Útero/patologia , Vimentina/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , beta Catenina/metabolismo
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