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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1026746

ABSTRACT

Objective:To explore the relationship between adipocytokine levels in bone marrow and the onset,progression,and prognosis of myelodysplastic syndromes(MDS).Methods:Retrospective analysis of adipocytokine levels in the bone marrow of 72 patients with MDS and 16 patients with MDS-related secondary acute myeloid leukemia(sAML),including adiponectin(ADP),leptin(LEP),visfatin/nicotinamide phosphoribosyltransferase(NAMPT),adipsin/complement factor D(CFD),and C1q/TNF-related protein 1(CTRP1),detected by enzyme-linked immunosorbent assay(ELISA)at The Affiliated Cancer Hospital of Zhengzhou University from February 2020 to February 2022.High-throughput sequencing was used to detect MDS-related genes in 70 patients and the relationship between adipocytokines and the clinical characteristics,disease subtypes,mutant genes,and prognosis of patients were analyzed.Seventy-eight MDS-related genes were identified.Results:Clinical characteristics showed that ADP(P=0.027)and LEP(P=0.019)levels were significantly lower in men than inwomen;ADP(P=0.020),CFD(P<0.001),and NAMPT(P=0.021)levels were significantly lower in patients aged<65 years than in patients aged≥65,where-as LEP levels were significantly higher(P=0.043).Adiponectin levels were significantly higher in patients with BMI<24 than in patients with BMI≥24(P=0.025),whereas LEP levels were significantly lower(P=0.020);NAMPT levels were significantly higher in the group with in-creased blasts than in the group with no blasts(P=0.037).The CTRP1 levels were significantly higher in the MDS group than in the sAML group(P=0.010).Abnormal gene correlation analysis showed that elevated CTRP1 levels were positively correlated with the occurrence of epigenetically related abnormal genes(P=0.001)and were positively correlated with the occurrence of TET2 and U2AF1(P<0.001 and P=0.036,respectively);ADP and CFD levels were positively correlated with the occurrence of NPM1(P=0.048 and P=0.026,respectively).Multifactorial Cox proportional hazards regression model analysis showed that LEP<0.2 ng/mL was an independent risk factor for progres-sion-free survival(PFS)and overall survival in patients with MDS(P=0.002 and P<0.001,respectively),whereas NAMPT<2.1 ng/mL was a protective factor for PFS in patients with MDS(P=0.043).Conclusions:Adipocytokines in the bone marrow microenvironment are closely as-sociated with the clinical characteristics,gene mutations,and prognosis of patients with MDS,with LEP<0.2 ng/mL being an independent prognostic risk factor and NAMPT<2.1 ng/mL being a prognostic protective factor.

2.
Technol Cancer Res Treat ; 20: 15330338211055953, 2021.
Article in English | MEDLINE | ID: mdl-34855554

ABSTRACT

Introduction: DEAD-box helicase 27 (DDX27) belongs to DEAD-Box nucleic acid helicase family. The function of DDX27 in hepatocellular carcinoma (HCC) remain enigmatic. In light of this, we tried to investigate the regulatory role and underlying mechanism of DDX27 in HCC. Materials and methods: DDX27 expression levels were detected by qRT-PCR, Western blot and immunohistochemistry assays in HCC tissues and cells. Colony formation, CCK-8, growth curve, wound healing and transwell assays were conducted to investigate the effect of DDX27 on the proliferation and metastasis of HCC cells. RNA-sequencing was performed to detect the effect of DDX27 on downstream signaling pathway. The effect of DDX27 on HCC progression was evaluated using in vivo murine xenograft model. Results: we found an increased expression of DDX27 in HCC tissues with comparison to its para-tumor tissues. The high expression levels of DDX27 were associated with poor prognosis in HCC patients. DDX27 upregulation promoted cell metastasis. Mechanistic studies suggested that DDX27 overexpression induces the major vault protein (MVP) expression and enhances the phosphorylation levels of ERK1/2. Inhibition of ERK pathway impaired the cellular metastastic abilities induced by DDX27. The induction of DDX27 in HCC progression was further confirmed from tumors in mouse model. Conclusion: our results disclose a novel mechanism by which DDX27 enhances ERK signaling during HCC progression. DDX27 might be used in targeted therapy for HCC patients.


Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/metabolism , DEAD-box RNA Helicases/genetics , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , MAP Kinase Signaling System , Adult , Aged , Animals , Biomarkers, Tumor , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , DEAD-box RNA Helicases/metabolism , Disease Models, Animal , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Mice , Middle Aged , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Prognosis
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-870129

ABSTRACT

Objective:To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV).Methods:A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients′ general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed.Results:In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF.Conclusions:Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients′ age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.

4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-870180

ABSTRACT

Objective:To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL).Methods:From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated.Results:Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations ( P<0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) ( P<0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ 2=10.330, P=0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ 2=7.974, P=0.047; EFS: χ 2=10.860, P=0.013). Conclusion:Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-798605

ABSTRACT

Objective@#To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV).@*Methods@#A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients′ general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed.@*Results@#In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF.@*Conclusions@#Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients′ age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-456718

ABSTRACT

ObjectiveTo investigate the relationships between traditional Chinese medicine(TCM) syndrome differentiation and serum cystatin C(Cys-C) and homocysteine(Hcy) in patients with chronic heart failure(CHF). Methods 115 cases with CHF admitted into the Department of Cardiology of the First Affiliated Hospital of Zhejiang Chinese Medical University were selected in the CHF group, and 30 cases who had taken health examination in the same period were chosen in the healthy control group. According to the TCM syndrome differentiation, the CHF cases were subdivided into four groups with different types of syndrome: 30 cases of deficiency of both Qi and Yin syndrome, 30 cases of Qi deficiency syndrome and blood stagnation syndrome, 30 cases of heart and kidney Yang deficiency syndrome and 25 casesof flooding due to Yang deficiency syndrome. The serum levels of Cys-C and Hcy in different groups were tested, and the relationships between TCM syndrome differentiation and serum Cys-C and Hcy were analyzed by using Spearman rank correlation analysis.Results The serum levels of Cys-C and Hcy in the patients with CHF were significantly higher than those in the healthy control group〔Cys-C(mg/L):1.24±0.34 vs. 0.77±0.22, Hcy(μmol/L):18.66±4.57 vs. 11.65±3.21,bothP<0.05〕. Compared with the healthy control group, the serum levels of Cys-C and Hcy in the above four groups of different syndromes had a tendency of gradual elevation in the sequence as follows: deficiency of both Qi and Yin, Qi deficiency and blood stagnation, heart and kidney Yang deficiency and flooding due to Yang deficiencygroups〔Cys-C(mg/L):1.02±0.27,1.09±0.31,1.32±0.22, 1.59±0.25; Hcy(μmol/L): 14.94±2.20, 17.66±3.04, 19.79±3.48, 22.96±5.31〕, and the elevation in levels of flooding due to Yang deficiency group was the most prominent compared with that in other groups(P<0.05). The correlation analyses showed that different types of TCM syndrome in patients with CHF were positively correlated with the levels of Cys-C and Hcy(r1=0.73,r2=0.79,bothP<0.05).ConclusionThe changes of serum Cys-C and Hcy levels are consistent with the evolution of regular pattern of TCM syndrome differentiation in patients with CHF, and these two markers can be regarded as the objective indicators of TCM syndrome differentiation of CHF.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-389318

ABSTRACT

Objective To investigate the effect of telmisartan on the expression of APN,hs-CRP,TNF-α and the prognosis of hypertensive patients with unstable angina pectoris. Methods Totally 100 hypertensive patients with unstable angina pectoris were randomly divided into the telmisartan group(n =50) and the losartan group(n =50),each group with oral administration. The blood pressure controlled condition, APN, hs-CRP and TNF-α content changes and the occurrence of cardiovascular accident after treatment were observed in both two groups. Results In both groups, blood pressure returned to normal in 8 weeks,with no significant difference(P > 0.05). After treatment,APN level in the telmisartan group increased faster than that in the losartan group(P <0.05) ,while the hs-CRP,TNF-αdecreased significantly(P < 0.05). After 8 weeks, the occurrence of cardiovascular accident in the telmisartan and losartan groups was 10.0% (5/50) and 24. 5 % (12/49) respectively in the following 4 months (P < 0.05). Conclusion Telmisartan has significant effect in regulating APN, hs-CRP, TNF-α expression in hypertensive patients with unstable angina pectoris, which is able to decrease the short-term occurrence of cardiovascular accident.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-593800

ABSTRACT

LAD(OR=1.209). Conclusion Left atrial diameter was independent risk factor for ischemic stroke in hypertensive patients.

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