Enzyme Inhibitory and Anti-cancer Properties of Moringa peregrina / Propiedades inhibidoras Enzimáticas y Anticancerígenas de la Moringa peregrina

Background: Moringa peregrina is widely used in the traditional medicine of the Arabian Peninsula to treat various ailments, because it has many pharmacologically active components with several therapeutic effects. Objective: This study aimed to investigate the inhibitory effect of Moringaperegrina seed ethanolic extract (MPSE) against key enzymes involved in human pathologies, such as angiogenesis (thymidine phosphorylase), diabetes (α-glucosidase), and idiopathic intracranial hypertension (carbonic anhydrase). In addition, the anticancer properties were tested against the SH-SY5Y (human neuroblastoma). Results: MPSE extract significantly inhibited α-glucosidase, thymidine phosphorylase, and carbonic anhydrase with half-maximal inhibitory concentrations (IC50) values of 303.1 ± 1.3, 471.30 ± 0.3, and 271.30 ± 5.1 µg/mL, respectively. Furthermore, the antiproliferative effect of the MPSE was observed on the SH-SY5Y cancer cell line with IC50 values of 55.1 µg/mL. Conclusions: MPSE has interesting inhibitory capacities against key enzymes and human neuroblastoma cancer cell line.

Antecedentes: La Moringa peregrina se utiliza ampliamente en la medicina tradicional de la Península Arábiga para tratar diversas dolencias, ya que posee numerosos componentes farmacológicamente activos con varios efectos terapéuticos. Objetivo: Este estudio tenía como objetivo investigar el efecto inhibidor del extracto etanólico de semillas de Moringaperegrina (MPSE) frente a enzimas clave implicadas en patologías humanas, como la angiogénesis (timidina fosforilasa), la diabetes (α-glucosidasa) y la hipertensión intracraneal idiopática (anhidrasa carbónica). Además, se comprobaron las propiedades anticancerígenas frente al SH-SY5Y (neuroblastoma humano). Resultados: El extracto de MPSE inhibió significativamente la α-glucosidasa, la timidina fosforilasa y la anhidrasa carbónica con concentraciones inhibitorias semimáximas (IC50) de 303,1 ± 1,3, 471,30 ± 0,3 y 271,30 ± 5,1 µg/mL, respectivamente. Además, se observó el efecto antiproliferativo del MPSE en la línea celular del cáncer SH-SY5Y con valores de IC50 de 55,1 µg/mL. Conclusiones: MPSE posee interesantes capacidades inhibitorias frente a enzimas clave y línea celular de neuroblastoma canceroso humano.

Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1 / 中国实验血液学杂志

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.

The value of serum TK1 and MMP-9 level in prognosis evaluation of primary hepatic carcinoma / 中国医师杂志

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.

Application of thymidine kinase 1 and circulating tumor cell in malignant solid tumor / 中国医师杂志

Thymidine kinase 1 (TK1) is associated with the occurrence of early malignant tumor,tumor metastasis,recurrence,and the changes of TK1 in the treatment can also reflect the sensitivity of tumor to treatment.Circulating tumor cells (CTC) are removed from the primary tumor or metastatic tumor to blood.The appearance of CTC in malignant tumors is usually related to the poor prognosis,such as metastasis and recurrence,short survival time and so on.The combination of TK1 and CTC can also be used as an independent predictor of survival.Now we analyse and summarize the role of TK1 and CTC in tumorigenesis and development.

Application of thymidine kinase 1 and circulating tumor cell in malignant solid tumor / 中国医师杂志

Thymidine kinase 1 (TK1) is associated with the occurrence of early malignant tumor, tumor metastasis, recurrence, and the changes of TK1 in the treatment can also reflect the sensitivity of tumor to treatment. Circulating tumor cells (CTC) are removed from the primary tumor or metastatic tumor to blood. The appearance of CTC in malignant tumors is usually related to the poor prognosis, such as metastasis and recurrence, short survival time and so on. The combination of TK1 and CTC can also be used as an independent predictor of survival. Now we analyse and summarize the role of TK1 and CTC in tumorigenesis and development .

Preparation and identification of folate-targeting liver cancer phase-transition nanoparticles carrying suicide gene / 肿瘤

Objective: To develop the folic acid (FA)-targeting poly (lactic-co-glycolic acid) (PLGA) phase-transition nanoparticles loaded with herpes simplex virus type(HSV1)-thymidine kinase (TK) suicide gene and perfluoropentane (PFP) (named as FA-PLGA/PFP-TK), as well as to identify the targeting performance, enhancement effect of ultrasound imaging and inhibitory effect on the proliferation of hepatocellular carcinoma cells. Methods: The FA-PLGA/PFP-TK nanoparticles were prepared by double emulsion method and carbodiimide method. The size distribution and Zeta potential of these nanoparticles were measured using a Malvern measuring instrument, and the morphological characteristic was observed by electron microscopy. The human liver cancer SMMC-7721 cells were used to verify the targeting performance of FA-PLGA/PFP-TK nanoparticles. Low intensity focused ultrasound (LIFU) was used to detect the results of ultrasound enhanced imaging and TK gene transfecting into SMMC-7721 cells. The expression of TK protein was detected by Western blotting, and the viability of SMMC-7721 cells was evaluated by CCK-8 assay. Results: The size of nanoparticles was (207.00 ± 46.06) nm with the shape of regular sphere. The entrapment efficiency of TK gene was (34.95 ± 3.14)%. In vitro targeting experiments showed the targeting nanoparticles were gathered around SMMC-7721 cells. After LIFU irradiation, the nanoparticles could enhance the ultrasound imaging, the expression level of TK protein was increased, and the viability of SMMC-7721 cells was decreased in the FA targeting group (all P < 0.01). Conclusion: FA-PLGA/PFP-TK targeting nanoparticles are prepared successfully, which is expected to be used in ultrasound imaging-guided gene targeted therapy.

Generation and evaluation of a recombinant myxomavirus expressing the VP60 protein of rabbit haemorrhagic disease virus / 生物工程学报

Rabbit haemorrhagic disease virus (RHDV) and myxoma virus (MYXV), are two pathogens that have harmful effect on rabbit breeding and population decline of European rabbits in their native range, causing rabbit haemorrhagic disease (rabbit fever) and myxomatosis, respectively. The capsid protein VP60 of the RHDV represents the major antigenic protein. To develop a recombinant bivalent vaccine candidate that can simultaneously prevent these two diseases, we used the nonessential gene TK (thymidine kinase) of MYXV as the insertion site to construct a recombinant shuttle vector p7.5-VP60-GFP expressing the RHDV major capsid protein (VP60) and the selectable marker GFP. Then the shuttle vector p7.5-VP60-GFP was transfected into rabbit kidney cell line RK13 which was previously infected with MYXV. After homologous recombination, the recombinant virus expressing GFP was screened under a fluorescence microscope and named as rMV-VP60-GFP. Finally, the specific gene-knock in and expression verification of the vp60 and gfp genes of the recombinant virus was confirmed by PCR and Western blotting. The results showed that these two genes were readily knocked into the MYXV genome and also successfully expressed, indicating that the recombinant MYXV expressing the vp60 of RHDV was generated. Protection against MYXV challenge showed that the recombinant virus induced detectable antibodies against MYXV which would shed light on development of the effective vaccine.

Choice of Capecitabine or S1 in Combination with Oxaliplatin based on Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase Expression Status in Patients with Advanced Gastric Cancer

PURPOSE: To study the efficacy of capecitabine or S-1 plus oxaliplatin (CAPOX or SOX) for treating thymidine phosphorylase (TP)- or dihydropyrimidine dehydrogenase (DPD)-positive advanced gastric cancer.MATERIALS AND METHODS: Eighty-six patients with stage IIIC to IV gastric cancer were assessed for TP and DPD expression by immunohistochemistry. The association between CAPOX or SOX efficacy and TP/DPD expression was retrospectively analyzed.RESULTS: There were no significant differences in the objective remission rate (ORR, 52.27% vs. 47.62%; P>0.05), disease control rate (72.73% vs. 73.81%, P>0.05), progression-free survival (hazard ratio [HR], 1.119; 95% confidence interval [CI], 0.739–1.741; P=0.586), and overall survival (OS; HR, 0.855; 95% CI, 0.481–1.511; P=0.588) between CAPOX and SOX. A higher number of stage IV patients showed TP positivity, while DPD-positive patients predominantly showed intestinal type of gastric cancer. In TP-positive patients, the ORRs associated with CAPOX and SOX treatments were 57.14% and 38.10%, respectively; OS was better with CAPOX than with SOX (HR, 0.447; 95% CI, 0.179–0.978; P=0.046). Among DPD-positive patients, the SOX treatment-associated ORR (60.87%) was significantly higher than the CAPOX treatment-associated ORR (43.48%). Furthermore, SOX treatment resulted in better OS than did CAPOX treatment (HR, 2.020; 95% CI, 1.019–4.837; P=0.049).CONCLUSIONS: No significant difference in clinical efficacy was found between CAPOX and SOX. TP-positive patients might respond better to CAPOX while DPD-positive patients may respond better to SOX. Our findings might serve as a guide for personalized chemotherapy for gastric cancer.

Serum thymidine kinase 1 and soluble NKG2D ligand predict prognosis of colorectal cancer patients after operation / 中华普通外科杂志

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.

Detection and analysis of serum TK1,sICAM-1,miR-210 and CEA in patients with colorectal cancer / 国际检验医学杂志

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.

Diagnostic value of combined serum AFP,TK1 and DKK1 levels in primary liver cancer / 国际检验医学杂志

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.

Effects of rituximab combined with CHOP chemotherapy on serum TK-1 and VEGF levels in patients with non-Hodgkin's lymphoma / 国际检验医学杂志

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.

Influence of thymidine phosphorylase polymorphisms on the efficacy of capecitabine-based adjuvant chemotherapy in colorectal cancer patients / 中国肿瘤临床

Objective: To inrestigate the association between thymidine phosphorylase (TYMP) polymorphisms and efficacy of postop-erative capecitabine-based adjuvant chemotherapy in colorectal cancer (CRC) patients. Methods: Two hundred and thirty-five patients with colorectal cancer who received surgical treatment and adjuvant chemotherapy between January 2010 and December 2016 from People's Hospital of Zhengzhou, were included in this study. Peripheral blood and postoperative tissue specimens of the CRC patients were collected for genotyping polymorphisms and measuring TYMP mRNA expression, respectively. The correlation between the poly-morphisms and efficacy of postoperative chemotherapy in CRC patients was analyzed. Results: The prevalence of 5633C>T in TYMP gene among the CRC patients was as follows: CC genotype, 149 cases (63.40%); CT genotype, 73 cases (31.06%); and TT genotype, 13 cases (5.54%); the minor allele frequency of 5633C>T was 0.21. Survival analysis of the patients revealed that the median overall sur-vival (OS) of patients with the CT/TT genotype and those with the CC genotype was 5.9 and 4.5 years, respectively; the result was sta-tistically significant (P=0.009). Following adjustment in multivariate Cox regression analysis, the CT/TT genotype was found to be an in-dependent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, results show that the levels of TYMP mRNA in cancer tissues of patients with the CT/TT genotype were significantly higher than those with the CC genotype (P=0.019). Conclusions: TYMP mRNA expression may be influenced by the 5633C>T polymorphism, making CRC patients benefit from capecitabine treatment.

Value of combined thymidine kinase 1 and thyroglobulin detection in differential diag-nosis of benign and malignant thyroid nodules / 中国肿瘤临床

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.

The expression and significance of serum microRNA-183 and TK1 in patients with colorectal cancer / 天津医药

Objective To detect the expression and significance of serum miRNA-183 and TK1 in patients with colorectal cancer, and the mechanism thereof. Methods Fifty-two serum samples of colorectal cancer patients and paired health serum samples were collected. The expression of miRNA-183 was detected by real-time quantitative PCR, and TK1 was detected by Western blot enhanced chemiluminescence assay. The correlation between miRNA-183 and TK1 and their relations with the clinicpathologic characteristics were analyzed. Results The serum miRNA-183 expression was significantly higher in colorectal cancer group than that in normal control group (P<0.01). The expression of serum miRNA-183 was significantly higher in stage Ⅲ-Ⅳ group than that in stage Ⅰ-Ⅱ group (P < 0.01). There was more significant increase in serum miRNA-183 in lymphatic metastasis group than that without lymphatic metastasis group (P < 0.01). Receiver operating characteristic (ROC) curve showed that of there was a diagnostic value for serum miRNA-183 in colorectal cancer, with an optimal value of 1.15. The diagnostic sensitivity and specificity were 78.8%and 67.3%, and the positive predictive value and negative predictive value were 78.9%and 70.2%. The serum TK1 expression was also higher in colorectal cancer group compared with that of normal control group (P<0.01). And the TK1 expression was also higher in stageⅢ-Ⅳgroup than that in stageⅠ-Ⅱgroup (P<0.01). Furthermore, miRNA-183 expression was positively correlated with TK1 expression (rs=0.692, P<0.01). Conclusion The serum expression levels of miR-183 and TK1 may act as tumor markers for early colorectal cancer diagnosis, and also can be used to predict the malignant degree and prognosis of colorectal cancer.

Comparison on the diagnostic values of 18F-FDG and 18F-FLT PET/CT in patients with suspicious recurrence of glioma after multimodal treatment / 中华核医学与分子影像杂志

Objective To compare the diagnostic values of 18F-FDG and 18F-FLT PET/CT in patients with suspicious recurrence of glioma after multimodal treatment.Methods A total of 20 patients (13 males,7 females;age range:12-73 years) with glioma who underwent 18F-FDG and 18F-FLT PET/CT due to abnormal enhancement on MRI from January 2012 to June 2015 were enrolled in this retrospective study.According to the pathological or follow-up results,patients were divided into therapy-related benign changes (TRBC) group and recurrent glioma group,the later was subdivided into initial low-grade glioma (LGG) group and initial high-grade glioma(HGG) group.T/NT ratios of 18F-FDG and 18F-FLT between HGG (LGG) group and TRBC group were compared using one-way analysis of variance and the least significant difference t test.ROC curve analysis was conducted to calculate the differential diagnostic efficiency of 18F-FDG and 18F-FLT between TRBC and recurrent glioma.Results A total of 14 patients were proved as recurrent glioma and 6 patients as TRBC.The mean 18F-FDG T/NT ratios of HGG group,LGG group and TRBC group were 2.31±0.86,1.32±0.86 and 1.32±0.64,respectively.The 18F-FDG T/NT ratio of the HGG group was significantly higher than that of the TRBC group(F=3.671,t=-2.471,P＜0.05).The mean 18F-FLT T/NT ratios of HGG group,LGG group and TRBC group were 8.94±3.14,7.18±3.29 and 1.92±1.20,respectively (F=13.301,t values:-5.150 and-2.360,both P＜0.05).The optimal T/NT cutoff values for 18 F-FDG and 18F-FLT PET/CT were 1.62 and 4.58,respectively.The sensitivity,specificity and accuracy of detecting recurrent glioma with optimal T/NT cutoff value were 11/14,5/6 and 16/20 for 18F-FDG PET/CT,and those for 18F-FLT PET/CT were 13/14,6/6 and 19/20,respectively.No significant difference was observed between the diagnostic efficiencies of the two imaging modalities (x2 values:1.167,1.091 and 2.057;all P＞0.05).Conclusion There were no statistical significances between 18F-FDG and 18F-FLT PET/CT on the differential diagnosis of glioma recurrence.

Expressions and clinical significances of TK1 and Ki-67 in triple negative breast cancer / 国际肿瘤学杂志

Objective To analyze the expressions of thymidine kinase 1 (TK1) and nuclear-associated antigen Ki-67 in triple negative breast cancer (TNBC) and their clinical significances.Methods One hundred and twenty tumor tissue sections of patients with breast cancer who were performed breast conservation treatment or modified mastectomy in the Second Affiliated Hospital of Qingdao University Medical College from June 2009 to December 2010 were collected,and there were 60 cases with TNBC and 60 cases with non-TNBC.The expressions of TK1 and Ki-67 in different breast tissues were detected by immunohistochemistry.The relationships between the expression status and clinicopathologic features were analyzed.Results The positive expression rates of TK1 in TNBC and non-TNBC were 83.33％ and 51.67％ respectively,with a significant difference (x2 =13.713,P =0.000).The positive expression rates of Ki-67 expression in TNBC and nonTNBC were 68.33％ and 31.67％ respectively,with a significant difference (x2=16.133,P =0.000).In TNBC,the expression of TK1 was related to histological staging (x2 =6.125,P =0.013),but it was not related to onset age (x2 =0.809,P =0.369),menopausal stutas (x2 =1.615,P =0.204),tumor size (x2 =0.054,P =0.816) and lymphatic metastasis (x2 =0.672,P =0.412).In TNBC,the expression of Ki-67 was related to histological staging (x2 =13.145,P =0.000) and lymphatic metastasis (x2 =6.182,P =0.013),but it was not related to menopausal stutas (x2 =1.018,P =0.313),onset age (x2 =2.377,P =0.123) and tumor size (x2 =2.401,P =0.121).The expression of TK1 was positively correlated with that of Ki-67 (r =0.369,P =0.023).The results of survival analysis showed that the disease-free survival rates of 5-year were 28.20％ and 66.70％ in the TK1 positive group and TK1 negative group,and the disease-free survival rates of 5-year were 24.30％ and 64.30％ in the Ki-67 positive group and Ki-67 negative group,with significant differences (x2 =4.194,P=0.041;x2 =4.540,P =0.033).Conclusion TK1 and Ki-67 are highly expressed in TNBC,and their expressions are correlated with histological staging and survival,which are expected to become prognostic indicators.

Expression of thymidine kinase 1 in primary hepatic carcinoma and its value in prognostic prediction / 实用医学杂志

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.

Application of serum TK1 levels in diagnosis of non small cell lung cancer / 国际检验医学杂志

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 .

Changes and clinical significance of serum TK1,CA153,CEA in breast cancer patients / 国际检验医学杂志

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 .