1.Study on the expression of vascular endothelial growth factor and endostatin in the serum of patients with differentiated thyroid cancer at the time of before and after operation and postoperative recurrence
Zhenhu ZHOU ; Ruihong YAN ; Huaiguang XING ; Wei ZHANG
Clinical Medicine of China 2012;28(11):1121-1124
Objective To evaluate the expression of vascular endothelial growth factor (VEGF)and endostatin (ES) in the serum of patients with differentiated thyroid cancer at the time of before and after operation and postoperative recurrence. Methods The serum samples were obtained from 7 patients with postoperative lung metastasis and 21 patients with local recurrence after operation.The serum samples from 30 normal subjects were obtained as control.The levels of serum VEGF and serum endostatin were analyzed by enzyme-linked immunosorbentassay (ELISA).Thelevelsofserumthyroglobulinwereanalyzedby Chemiluminescence method.Statistical analysis was performed with t-test using SPSS 13.0 software.Pearson correlation analysis was performed for the correlation between serum VEGF and serum ES and thyroglobulin.ResultsThe levels of serum VEGF and serum ES in patients with lung metastasis 3 weeks after operation were significantly lower than those before operation and at the time of recurrence [ VEGF:( 210.3 ± 30.4) ng/L vs (412.6 ±57.3) ng/L and(619.5 ± 126.4) ng/L,P <0.05 ;ES:(25.2 ±6.2)ng/L vs (34.3 ±7.6)ng/L and (38.6 ± 8.7) ng/L,P < 0.05 ].And the levels of serum VEGF and serum ES in patients with local regional recurrence 3 weeks after operation were significantly lower than those before operation and at the time of recurrence [ VEGF:(209.3 ±36.7) ng/L vs (399.4 ±56.3) ng/L and (406.5 ±59.2) ng/L,P <0.05;ES:(25.7 ± 4.7 ) ng/L vs ( 35.2 ± 6.8 ) ng/L and ( 31.2 ± 7.6 ) ng/L,P < 0.05 ].The expression of serum VEGF and serum ES in patients with pulmonary metastasis were significantly higher than those in patients with local regional postoperative recurrence ( P < 0.05 ).There was a linear positive correlation between serum VEGF,serum ES and thyroglobulin levels in the patient with recurrent differentiated thyroid cancer( r =0.752,0.349,P <0.01 ).Conclusion The serum VEGF and serum ES level were significantly elevated in patients with differentiated thyroid cancer before operation and recurrence.The serum VEGF and serum ES were importantindicators to reveal the biological behaviors of differentiated thyroid cancer.
2.Clinical significance of perineural invasion among patients with early squamous cell carcinoma of the tongue
Chengzhong LIN ; Chunye ZHANG ; Zhenhu REN ; Tong JI
Chinese Journal of Clinical Oncology 2015;42(16):803-806
Objective:To investigate the effect of perineural invasion (PNI) on patients with early squamous cell carcinoma of the tongue (ESCCT) and the controversial issues related to PNI's effect on loco-regional recurrence, cervical lymph node metastases, and prognosis. Methods:Data of 156 patients with ESCCT were analyzed. Two subgroups comprising 40 patients each were investigated. One was PNI-positive subgroup, and the other subgroup was consisted of patients with PNI-negative carcinomas. These patients had similar histopathological characteristics and were randomly selected from the total number of cases. The relationship among the prevalence of PNI, loco-regional recurrence, cervical lymph node metastases, and prognosis was analyzed. Results:PNI was significantly correlated with high cervical lymph node metastases and poor 5-year survival rates (P=0.045 and P=0.034, respectively) but not with local recurrence (P=0.531). Elective neck dissection was considerably associated with a low risk of regional recurrence among the PNI-positive ESCCT patients (P=0.001). Conclusion:PNI should be considered as a predictor for high cervical lymph node metastases and poor 5-year survival of early tongue squamous cell carcinoma. Elective neck lymph node dissection should be performed among patients with PNI-positive early tongue squamous cell carcinoma.
3.Expression of serum vascular endothelial growth factor in differentiated thyroid cancer
Zhenhu ZHOU ; Wei ZHANG ; Huaiguang XING ; Ruihong YAN
Journal of Endocrine Surgery 2013;7(4):269-271
Objective To evaluate the expression of serum vascular endothelial growth factor(sVEGF) in differentiated thyroid carcinoma(DTC)patients before and after thyroidectomy and when recurrence occured.To analyze the relationship between serum VEGF and serum thyroglobulin(Tg)level.Methods sVEGF levels of 30 cases of DTC (7 patients with pulmonary metastasis,23 patients with locoregional recurrence)were determined by enzyme-linked immunosorbent assay(ELISA) before and after thyroidectomy and when recurrence occured.The levels of serum Tg and thyroglobulin antibodies (TgA) were detected by chemiluminescence method.The results were compared with those of the 30 cases of normal controls.Results sVEGF levels had no significant difference between pulmonary metastasis group and locoregional recurrence group before operation (t =0.373,P > 0.05),but they were significantly higher than those in the normal control group(t =8.597 and 14.14 respectively,all P < 0.05).sVEGF levels in patients with pulmonary metastasis or locoregional recurrence were significantly reduced at the 3rd week after operation and the difference had statistical significance with those before operation(t =5.977,11.50,P < 0.05).The difference of postoperative level of sVEGF in patients with pulmonary metastasis,locoregional recurrence and in patients of normal control group had no statistical significance (t =1.593,1.525,P > 0.05).sVEGF levels in patients with pulmonary metastasis or locoregional recurrence were significantly higher after recurrence than those before recurrence (t =7.387,12.16,P < 0.05).After recurrence sVEGF levels in patients with pulmonary metastasis were significantly higher than those in patients with locoregional recurrence (t =4.167,P < 0.05) It showed a positive linear correlation between serum Tg level and sVEGF level in DTC patients with recurrence(r =0.786,P < 0.01).Conclusion sVEGF is significantly elevated in DTC patients before operation and with postoperative recurrence,making it an important indicator to reveal the biological behaviors of DTC.
4.Relation between the expression of sIL-2R and the relapse in patients with acute lymphoblastic leukemia
Jin LIU ; Dengshu WU ; Shen ZHANG ; Chenhua YAN ; Yu ZHOU ; Yongding ZHANG ; Zhenhu QI
Journal of Peking University(Health Sciences) 2004;0(03):-
Objective: To explore the relation of the serum level of sIL-2R in relapse patients with acute lymphoblastic leukemia(ALL). Methods:With ELISA, we determined the levels of sIL-2R of 48 patients with ALL after their first diagnoses,complete remission 1 and relapse. The levels of sIL-2R of 30 patients from complete remission 1 to relapse were monitored. Results: The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the control. The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the complete remission 1 group. However,the difference between the complete remission 1 and the control had no statistical significance. When we determined the levels of sIL-2R dynamically, we found that after complete remission ,the levels of sIL-2R decreased,however, before one month of hematological relapse, the levels of sIL-2R increased. Conclusion: Monitor of the level of sIL-2R can predict impending relapse of patients with ALL and is helpful to early diagnosis of relapse.
5.Study on the mechanism of CTLA4-Ig in the treatment of mice viral myocarditis
Yi ZHANG ; Bo HAN ; Zhenhu LIU ; Lijian ZHAO ; Junfang XI ; Kang LU ; Xiuzhen HAN
Chinese Journal of Microbiology and Immunology 2009;29(3):239-243
Objective To investigate the effect of CTLA4-Ig chimera protein on mice mortality, histopathological changes, viral fiters, expression of CTLA4 protein on infiltrated T lymphocyte and the balance of Thl/Th2 in mice myocarditis caused by coxsackie virus B3 (CVB3). Methods A total of 106 four to six week-old male BALB/c mice were used in the experiments, which were divided into CTLA4-Ig group (n = 16), CVB3 group (n=40), IgG group (n =40) and normal control group(n = 10) randomly. The mice in CVB3 group, IgG group and CTLA4-Ig group were inoculated intraperitoneally with 0. 15 ml CVB3 and the mice in norreal control group with 0. 15 ml Eagle. The mice in IgG group and CTLA4-1g group were inoculated with IgG (0. I mg/kg) and CTLA4-Ig(0. 1 mg/kg) at 6 h and 72 h post inoculation(p, i. ), respectively, The surplus mice in each group were sacrificed at day 7 p.i. Light microscope was used to quantify the inflammation. The expression of CVB3 mRNA in mycardium were semi-quantified by real-time quantitative polymerase chain reaction (RQ-PCR). The expression of CTLA4 protein were analyzed by immunohistochemistry. The levels of IL-2, IL-4 and 1FN-γ in serum were measured by ELISA. Results The mice mortality, histopathological score and CVB3 mRNA in CTLA4-Ig group were lower than that in CVB3 group ( P < 0.05, P < 0.01, P < 0. 05, respectively). The expression of CTLA4 was significantly increased in CTLA4-Ig therapy group (P < 0.05 ). The serum level of IFN-γ of mice in CVB3 group were significantly higher than that in normal control group( P < 0.01 ). The serum level of IL-4 of mice in CVB3 group were much lower than that in normal control group( P < 0.01 ). The serum level of IL-2 in CVB3 group had no statistical significance with that in normal control group ( P > 0.05 ). The serum level of IFN-γ in mice of CTLA4-Ig group were much lower than that in CVB3 group ( P <0.01 ) and lgG group (P < 0. 01 ). The serum level of IL-4 of mice in CTLA4-Ig group were significantly higher than that in CVB3 group (P<0.01) and IgG group (P<0.01). The serum level of IL-2 in CTLA4-Ig group had no statistical significance with that in CVB 3 control group and lgG group ( P > 0. 0 5 ) . Conclusion CTLA4-Ig may relieve inflammation and reduce mice mortality by blocking the costimulation signals for T lymphocyte activation and reinforcing Th2 response.
6.Stability of FibroTouch in determining liver stiffness measurement and controlled attenuation parameter
Xiaobo ZHAO ; Jing YU ; Zhenhu ZHANG
Journal of Clinical Hepatology 2020;36(1):102-106
ObjectiveTo investigate the stability of FibroTouch (FT) in the determination of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). MethodsA total of 309 patients with chronic hepatitis B virus (HBV) infection, nonalcoholic fatty liver disease (NAFLD), liver function abnormalities, or other diseases who underwent FT in the outpatient service of Department of Hepatology, The Second Affiliated Hospital of Anhui Medical University, were enrolled. FT was performed at three different measurement points for the same subject, and intraclass correlation coefficient (ICC) and the Bland-Altman method were used to evaluate the stability of measured values. The Kendall’s W test and pie charts were used to evaluate the stability of diagnostic results. ResultsLSM and CAP values of the three different measurement points for the same subject had an ICC of >0.75 in different disease groups (all P<0.001), among which the chronic HBV infection group had the highest ICC of LSM of 0.905, the other disease group had the highest ICC of CAP of 0.805, the NAFLD group had the lowest ICC of LSM of 0.785 and the lowest ICC of CAP of 0.780. The Bland-Altman plots were generated for the three measurement points, and the dots within the limits of agreement accounted for about 95%. The diagnostic results of LSM and CAP staging of the three measurement points had a Kendall’s W coefficient of 0.825 and 0.858, respectively (all P<0.001). The proportion of patients with consistency between the diagnostic results for F≥2 stage (LSM>7.3 kPa) and mild (or more severe) fatty liver stage (CAP>240 dB/m) based on mean value of measurement points and all three measurement points was >60%, while the proportion of patients with consistency between the diagnostic results based on mean value of measurement points and only one measurement point was <10%. ConclusionThe values and diagnostic results of FT measurement have good stability; however, in order to improve its stability in diagnosing F ≥2 stage and mild (or more severe) fatty liver, it is suggested to use the mean value of multiple measurement points for diagnosis.
7.Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma
Liu ZHEQI ; Zhang ZHEN ; Zhang YU ; Zhou WENKAI ; Zhang XU ; Peng CANBANG ; Ji TONG ; Zou XIN ; Zhang ZHIYUAN ; Ren ZHENHU
International Journal of Oral Science 2024;16(1):110-121
Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.
8.Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma
Liu ZHEQI ; Zhang ZHEN ; Zhang YU ; Zhou WENKAI ; Zhang XU ; Peng CANBANG ; Ji TONG ; Zou XIN ; Zhang ZHIYUAN ; Ren ZHENHU
International Journal of Oral Science 2024;16(1):110-121
Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.
9.Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma
Liu ZHEQI ; Zhang ZHEN ; Zhang YU ; Zhou WENKAI ; Zhang XU ; Peng CANBANG ; Ji TONG ; Zou XIN ; Zhang ZHIYUAN ; Ren ZHENHU
International Journal of Oral Science 2024;16(1):110-121
Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.
10.Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma
Liu ZHEQI ; Zhang ZHEN ; Zhang YU ; Zhou WENKAI ; Zhang XU ; Peng CANBANG ; Ji TONG ; Zou XIN ; Zhang ZHIYUAN ; Ren ZHENHU
International Journal of Oral Science 2024;16(1):110-121
Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.