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OBJECTIVE@#To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1).@*METHODS@#Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay.@*RESULTS@#The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) μg/ml, which was significantly lower than (0.301±0.04) μg/ml of CA46-C23-KNC cells and (0.338±0.05) μg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle.@*CONCLUSION@#The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.
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Humans , Leukocytes, Mononuclear/metabolism , Apoptosis , Cell Line, Tumor , Lymphoma , Thymidine Kinase/pharmacology , Doxorubicin/pharmacology , Cell Division , RNA, Messenger/geneticsABSTRACT
Objective:To investigate the value of serum thymidine kinase-1 (TK1) and matrix metalloproteinase-9 (MMP-9) level in prognosis evaluation of patients with primary hepatic carcinoma (PHC).Methods:100 PHC patients treated in Panjin Central Hospital from December 2015 to December 2017 were retrospectively selected and divided into survival group ( n=73) and death group ( n=27) according to the prognosis. The clinical characteristics and serum TK1 and MMP-9 levels of the two groups were compared. The relationship between serum TK1 and MMP-9 levels and the clinical characteristics and prognosis of PHC was analyzed. Receiver operating characteristic (ROC) curve was drawn to analyze the value of TK1 and MMP-9 in evaluating the prognosis of PHC. Results:The proportion of multiple lesions, low differentiation, tumor node metastasis (TNM) stage Ⅲ-Ⅳ, extrahepatic metastasis and microvascular invasion in the survival group were lower than those in the death group, and the levels of serum TK1 and MMP-9 were also lower than those in the death group (all P<0.05); The levels of serum TK1 and MMP-9 had no significant correlation with gender, age, tumor length and diameter and child Pugh liver function grade of PHC patients (all P>0.05), but were closely related to the number of lesions, degree of differentiation, TNM stage, extrahepatic metastasis and microvascular invasion (all P<0.05). The areas under the ROC curve of serum TK1 and MMP-9 levels predicting the prognosis of PHC were 0.859 and 0.830. The 3-year survival rate of PHC patients with high level of TK1 and MMP-9 was significantly lower than that of low level patients (all P<0.05). Conclusions:The serum TK1 and MMP-9 levels are correlated with the condition and prognosis of patients with PHC, and can be used as reference indexes for early prognosis evaluation.
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Objective:To investigate the value of combined serum thymidine kinase 1(S-TK1)and thyroglobulin(Tg)detection in the differential diagnosis of benign and malignant thyroid nodules.Methods:S-TK1 and Tg levels were retrospectively detected with an en-hanced chemiluminescence dot blot assay and chemiluminescence immunoassay in 81 cases of malignant thyroid nodules,62 cases of benign thyroid nodules,and 40 cases of normal controls in the Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,between October 2015 and September 2017.To compare the S-TK1 and Tg levels in each group,and to evaluate the clinical value of detecting S-TK1 and Tg,in the differential diagnosis of benign and malignant thyroid nodules,Logistic regression and Receiver Operating Characteristic Curve (ROC) were performed. Results: The S-TK1 and Tg levels in patients with malignant thyroid nodules [(5.33±3.38)pmol/L,(61.86±24.80)ng/mL]were significantly higher than in those with benign nodules[(1.40±0.99)pmol/L,(45.13± 15.80)ng/mL]and in normal controls[(1.35±0.41)pmol/L,(40.88±15.45)ng/mL](P<0.05).The ROC of S-TK1,Tg,and P of the regres-sion equation showed that the S-TK1 and Tg cut-off values were 2.320 pmol/L and 63.40 ng/mL,respectively.The area under the curve (AUC),sensitivity,and total effective rate of S-TK1 were significantly higher than those of Tg(P<0.05).The cut-off value of P was 0.372, and the AUC,sensitivity,and total effective rate were significantly higher than those of S-TK1 and Tg(P<0.05).Conclusions:S-TK1 was indicative than Tg in the differential diagnosis of benign and malignant thyroid nodules.The combined detection of S-TK1 and Tg can significantly improve the sensitivity and total effective rate of diagnosis,and as such,the combined detection of both parameters can assist the differentiation of benign and malignant thyroid nodules.
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Objective To investigate the expression and significance of serum thymidine kinase-1(TK1), soluble intercellular adhesion molecule-1(sICAM-1),miR-210,and carcinoembryonic antigen(CEA)in pa-tients with colorectal cancer.Methods A total of 200 patients with colorectal cancer treated in the hospital from 2015 to 2017 were enrolled as the observation group and 50 healthy subjects were enrolled as the control group.Serum levels of TK1,sICAM-1,miR-210,and CEA were measured before and after treatment,and the trend of each indicator was analyzed.To analyze the relationship between tumor site,degree of tumor differen-tiation,clinical stage,w hether it is the first patient,lymph node metastasis and miR-210 levels in patients with colorectal cancer.Results The concentrations of sICAM-1,CEA,sTK1 and miR-210 in the observation group were significantly higher than those in the control group(P<0.05).The expression of miR-210 was related to the clinical stage and lymph node metastasis(P<0.05).T he sensitivity,specificity,positive predictive value, negative predictive value and accuracy of the combined tests including serum TK 1,sICAM-1,miR-210 and CEA test were higher than those of the single test,and was also higher than the combined tests of TK1,miR-210 and CEA.The sensitivity of the four combined tests was 75.70%,the specificity was 86.00%,the positive predictive value was 82.00%,the negative predictive value was 88.00%,the accuracy was 92.40%.Conclusion The combined detection of serum TK1,sICAM-1,miR-210 and CEA may have some value in the early diag-nosis of colorectal cancer,and can improve the sensitivity and specificity of colorectal cancer diagnosis.
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Objective To investigate the diagnostic value of combined detection of serum alpha fetoprotein (AFP),thymidine kinase 1(TK1)and secreted protein Dickkopf-1(DKK1)in patients with primary liver cancer(PHC).Methods 85 patients with PHC admitted to the hospital from August 2015 to October 2016 were selected as PHC group,and 73 patients with benign liver disease as benign liver disease group,and 80 ca-ses healthy subjects as the control group.The serum levels of AFP,TK1 and DKK1 were detected in three groups,and the differences in each group were compored,and the diagnostic sensitivity,specificity,positive predictive value,negative predictive value and accuracy were calcuated.The diagnostic value of each index was analyzed by logistic regression.Results The serum AFP,TK1 and DKK1 levels in PHC group were signifi-cantly higher than those in benign liver disease group and control group(P<0.05),the serum AFP TK1 and DKK1 levles in benign liver disease group were significantly higher than those in the control group(P<0.05);the sensitivity,accuracy and negative predictive value of AFP + TK1+ DKK1 joint detection were sig-nificantly higher than that in the single index detection(P<0.05);Logistic regression analysis showed that AFP,TK1 and DKK1 were closely correlated with the diagnosis of PHC(P<0.05).Conclusion The com-bined detection of serum AFP,TK1 and DKK1 can significantly improve PHC positive diagnosis rate,which is of great significance for clinical early diagnosis and effective treatment,and is worth popularizing.
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Objective To study the effects of rituximab combined with CHOP chemotherapy on serum Thymidine kinase 1 (TK-1) and vascular endothelial growth factor (VEGF) in patients with non-Hodgkin lymphoma,and to provide guidance for clinical research.Methods A total of 24 patients with non-Hodgkin's lymphoma treated in our hospital from January 2013 to March 2016 were randomly divided into the control group and the observation group,and each with 12 cases.All patients were examined before and after treatment,the control group was only treated with CHOP chemotherapy,and the observation group was treated with rituximab combined with CHOP chemotherapy.The patients were followed up within 1-2 years after treatment.The therapeutic effects of all patients were observed,the TK-1 and VEGF levels were measured and the incidence rate of adverse reactions was recorded.Results The efficiency rates of patients in the observation group and the control group were 66.67％ and 50.00％,respectively after treatment,and the observation group was significantly better than the control group,the difference was statistically significant (P＜0.05);the TK-1 and VEGF levels of the two groups were significantly decreased after treatment (P＜0.05),there was a statistically significant difference.But the two indexes of observation group was significantly lower than the control group,the difference was significant (P＜0.05);the control group showed 1 case of liver dysfunc tion after treatment,4 cases of gastrointestinal dysfunction,1 case of decreased white blood cells,while the observation group were 1,3 and 1 case,respectively.There were no significant differences between two groups (P＞0.05).Conclusion With the treatment of rituximab combined with CHOP chemotherapy,serum TK-1 and VEGF levels of patients with non-Hodgkin lymphoma decreased significantly,the poor prognosis has been significantly improved,and this treatment is worth popularizing in clinical application.
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Objective To investigate the values of serum thymidine kinase 1 (TK1) and soluble NKG2D (natural killer cell group 2D) ligand (soluble major histocompatibility complex class Ⅰ-related chain A,sMICA) in predicting the prognosis of colorectal cancer patients undergoing radical resection.Methods 45 patients and 45 healthy subjects were included.Perioperative serum TK1 and NKG2D ligand levels were measured in 45 patient and 45 healthy controls.Patients were divided into high TK1 group and low TK1 group,and high sMICA group and low sMICA group according to the ROC.Results Perioperative TK1 were (4.42 ± 1.42) and (2.98 ± 0.54) pmol/L,sMICA were (135 ± 79) and (100 ± 81)pg/ml,which were significantly higher than those in healthy controls (P =0.000).The postoperative TKI and sMICA levels decreased significandy (P =0.000 and 0.042).The 3 and 5 years cumulative survival rates in the high TK1 group were 84％ and 34％,compared with that of 90％ and 75％in the low TK1 group (P =0.023).The 3 year and 5 year cumulative survival rates in high sMICA group were 61％ and 31％,compared with 71％ and 52％ in low sMICA group (P =0.148).Conclusion Patients serum thymidine kinase levels were negatively corelated with the prognosis of colorectal cancer after radical resection.
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BACKGROUND: The cell cycle-dependent enzyme thymidine kinase 1 (TK1) is known to increase during cancer cell proliferation and has been reported as a prognostic marker for various hematologic malignancies and solid tumors. This study aimed to determine the reference interval in Korean healthy controls and to evaluate the usefulness of TK1 as a biomarker for aggressive clinical behavior in B-cell lymphoma patients. METHODS: We enrolled 72 previously untreated patients with B-cell lymphoma and 143 healthy controls. Serum TK1 levels were measured by chemiluminescence immunoassay (Liaison(R), DiaSorin, USA). We established the reference intervals in healthy controls. The diagnostic performance of serum TK1 was studied using receiver operating characteristic (ROC) analysis, and the correlation between the cutoff level for serum TK1 and clinical characteristics of B-cell lymphoma was evaluated. RESULTS: The reference range (95th percentile) of serum TK1 in healthy controls was 5.4-21.8 U/L. There was a clear difference in TK1 levels between patients with B-cell lymphoma and healthy controls (40.6+/-68.5 vs. 11.8+/-4.4 U/L, P or =15.2 U/L) correlated with the advanced clinical stage (P<0.001), bone marrow involvement (P=0.013), international prognostic index score (P=0.001), lactate dehydrogenase level (P=0.001), low Hb level (<12 g/dL) (P=0.028), and lymphocyte count (P=0.023). CONCLUSIONS: The serum TK1 level could serve as a useful biomarker for aggressive clinical behavior in B-cell lymphoma patients.
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Humans , B-Lymphocytes , Bone Marrow , Cell Proliferation , Diagnosis , Hematologic Neoplasms , Immunoassay , L-Lactate Dehydrogenase , Luminescence , Lymphocyte Count , Lymphoma, B-Cell , Reference Values , ROC Curve , Sensitivity and Specificity , Thymidine Kinase , ThymidineABSTRACT
Objective To investigate the variation of serum Thymidine Kinase 1(TK1) in patients with non‐small cell lung canc‐er(NSCLC) and its clinical value .Methods Serum TK1 level of 129 patients with NSCLC and 90 healthy volunteers were measured by sensitive chemiluminescence dot‐blot assay .The serum TK1 level variation of 76 patients with NSCLC were compared before and after operation .Results Serum TK1 level of NSCLC patients were significantly higher than the level of healthy control group(PStage Ⅳ >Stage Ⅰ + Ⅱ >Stage Tis ,comparison between each other was of statistical differ‐ence(P<0 .05) .The serum TK1 level of NSCLC patients at 30th day after surgery was remarkably lower than which before surger‐y(P=0 .001 ,P<0 .01) .The serum TKl level was correlated with lymphatic metastasis(P<0 .01) ,but not with other factors such as pathology types ,age ,sex and smoking .The serum TK1 measurement was high sensitivity and specificity to the diagnosis of NSCLC .Conclusion The serum TK1 level detection has important clinical significance in diagnosis and evaluation of NSCLC pa‐tients .
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Objective To investigate the expressions of TK1 (thymidine kinase 1) in PHC (primary hepatic carcinoma). Methods TK1 and AFP in serum of 33 cases of PHC (primary hepatic carcinoma), 38 cases of hepatic cirrhosis,36 cases of hepatitis and 35 cases of healthy people were detected by means of Western blot—enhanced chemiluminecence and electrochemiluminescence. Results The difference of TK1 level in PHC group indicated significance when compared with that in hepatic cirrhosis group , hepatitis group and control group (U value was 436.4, 352.1, 163.6, respectively, all P 0.05). Kaplan-Meier curve analysis revealed that PHC patients with TK1≤ 2.0 pmol/L had a significantly shortened overall survival when compared with those with TK1 > 2.0 pmol/L (χ2 = 3.954,P < 0.05). Multivariable Cox regression analysis indicated that the level of TK1 and TNM stage were the independent risk factors for patients with PHC (all P <0.05). Conclusions The detection of TK1 has a certain clinical value in the diagnosis, monitoring and evaluation of the prognosis of the PHC.
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Objective To investigate the changes and clinical significance of serum thymidine kinase 1(TK1) ,carbohydrate antigen 153 (CA153) and carcinoembryonic antigen(CEA) in the patients with breast cancer .Methods The levels of serum TK1 ,CA153 and CEA were detected in 92 inpatients with breast cancer ,66 patients with benign breast disease and 50 people undergoing the physical examination . The relationship between serum TK1 ,CA153 and CEA with the pathologic parameters in breast cancer was analyzed by the single factor a‐nalysis method .Results Serum TK1 ,CA153 and CEA levels in the breast cancer group were significantly higher than those in the benign breast disease group and control group ,the differences were statistically significant(P<0 .05) .The serum TK1 ,CA153 and CEA levels were related with the degree of pathological stage and lymph node metastasis(P<0 .05) .Conclusion The increase of serum TK1 ,CA153 and CEA levels has an important clinical significance in the diagnosis ,infiltration ,metastasis and severity of breast cancer .
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Objective:This study investigated the positive detection rate of cytoplasm thymidine kinase 1 (TK1) in lung cancer patients and the relationship of TK1 with clinicopathological features and prognosis. Methods:Sensitive chemiluminescence dot-blot assay was used to detect serum TK1 levels in 73 lung cancer patients and 56 normal control subjects. Results:The positive detection rate of TK1 was elevated in the lung cancer patients compared with the controls (P=0.006). The positive detection rate of TK1 was also correlated with distant metastases, but not with other factors, such as smoking, sex, lymph node metastasis, and pathology types. The 2 year survival of the patients with negative TK1 detection was significantly longer than that of the patients positively detected with the marker (P<0.001). Conclusion:Serum TK1, a new tumor marker, has potential applications in the diagnosis and prognosis of lung cancer.
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Objective To investigate the effect of S-1 on serum thymidine kinase-1 ( TK1 ) , vascular endothelial growth factor ( VEGF ) and insulin-like growth factor-1 (IGF-1) and tumor biomarkers, estrgen levels and quality of life in patients with advanced breast cancer.Methods 69 cases with advanced breast cancer from January 2014 to May 2015 in the hospital were selected and randomly divided into two groups.34 cases in control group were treated by conventional therapy, and 34 cases in experimental group were treated with S-1.Serum TK1, VEGF and IGF-1, tumor biomarkers, estrogen level and quality of life score were compared pre-and post-treatment.ResuIts Compared with control group, the levels of VEGF, IGF-1 and TK1 were lower (P<0.05), serum CA125, CEA and CA15-3 concentrations were lower (P<0.05),the LH, E2 and E1 levels were lower (P<0.05) and the survival quality score was higher in experimental group ( P<0.05 ) .ConcIusion S-1 has better clinical curative effect in treatment of patients with advanced breast cancer, and effectively reduce serum TK1, VEGF, IGF-1, tumor biomarker levels, improve the quality of survival, which has important significance.
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Objective To investigate the relations and evaluation value of serum thymidine kinase 1 (sTK1) in the treatment of patients withacute exacerbation of chronic obstructive pulmonarydisease (AECOPD). Methods The retrospective treating studies were performed on 104 patients with AECOPD , sTK1 level was de-tected by chemiluminescence dot-blot assay before and after treatment , and the correlation between the expression of sTK1 and CRP after treatment in the two groups was analyzed. Results The levels of sTK1 and CRP in the ef-fective group significantly lowered after treatment (P < 0.05). The expression of sTK1 in the effective group and in the ineffective group after treatment was significantlycorrelated with CRP (P < 0.05). Conclusion sTK1 can be used as a valuable indicator to evaluate the severity of AECOPD and to estimate the efficacy of AECOPD thera-py.
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Objective To study the clinical application of thymidine kinase 1(TK1) in diagnosis of common malignant tumors . Methods The serum TK1 levels of 444 cancer patients and 161 healthy individual(control group) were tested by western blot-en-hanced chemiluminescence assay .Results Compared with control group ,the levels of TK1 in patients with lung cancer ,gastrointes-tinal cancer or breast cancer were significantly higher(P<0 .05) .The positive rates of TK1 in lung cancer ,esophageal cancer ,colon cancer ,colorectal cancer ,breast cancer ,cervical cancer and ovarian cancer were respectively 52 .0% ,59 .6% ,62 .9% ,60 .0% , 62 .1% ,32 .3% ,21 .4% and 11 .0% .Compared with control group(the positive rate of TK1 was 0 .0% ) ,the positive rate of TK1 in lung cancer ,gastrointestinal cancer or breast cancer were significantly higher(P<0 .01) .Conclusion The test of serum TK1 is a valuable marker in common malignant tumor auxiliary diagnosis .
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Objective: To understand the significance of serum TK1 level change during chemotherapy of patients with non-Hodgkin's lymphoma. Methods: The serum TK1 levels were detected in 37 patients with non-Hodgkin's lymphoma by enhanced chemiluminecence assay before chemotherapy and one day, four weeks after chemotherapy. Results: The changes of serum TK1 levels were significantly different at different stages of treatment (P<0.01). Conclusion: Our findings indicate that serum TK1 change might be of great value in evaluating the treatment outcomes and predicting recurrence of patients with non-Hodgkin's lymphoma.