Objective To study the different induced expressions of FOXP3 by transforming growth factor-β1 (TGF-β1) between CD4+ and CD8+ T lymphocytes.Methods After the cultures of CD4+ cells and or CD8 + cells under an anti-TCR stimulation condition with an addition of TGF [β1 or not for 4 days respectively,the induced FOXP3 expressions were detected through the flow cytometric intracellular staining.Meanwhile we also examined the proliferative activity of TGF β1 induced FOXP3 expressing lymphocytes through a CFSE labeling experiment and the effect of TGF-β1 on cell apoptosis by annexin V staining.Results TGF-β1 selectively induced the CD4+ T lymphocytes to express FOXP3 (PBMC:29.66±3.624 vs 7.430±0.643; NIL:31.74±2.612 vs 8.637±1.146); The induced cells also had a proliferative activity (94.39 ± 1.179) and could secrete IFN-γ efficiently after activation (39.58±1.611); TGF-β1 could reduce the apoptosis rate of CD8+T lymphocytes(25.39±2.158 vs 9.320±0.3219).Conclusions Consistent with the discovery that ＞95％ of the FOXP3+lymphocytes in TIL (tumor infiltrating lymphocytes) of HCC (human hepatocelluar carcinoma) patients were concentrated in CD4+ T lymphocytes (97.15±0.3807,n=10),TGF-β1 induced the CD4 +T lymphocytes to express FOXP3 in preference to CD8+T lymphocytes; But with different to natural Tregs,the induced cells still could proliferate and secrete IFN-γactively after an effective stimulation;CD8+ T lymphocytes were more easily suffering cell apoptosis after activation than CD4+ T lymphocytes,and TGF-β1 could rescue the more cell apoptosis.

As an important in vivo noninvasive molecular imaging modality, PET imaging can quantify and visualize the serial trafficking, tumor targeting, cell number maintenance, cell expansion, activation and immunological function of adoptive immune cells in cancer cell therapy. Thereby it may play a significant role in the treatment options and efficacy evaluation for cellular immunotherapy in cancer. This review focuses on PET reporter gene imaging which has been studied intensively and applied widely in the research on imaging monitoring of cellular immunotherapy for cancer, with the purpose to provide innovative clues for the preclinical study and clinical translation research.

Epidermal growth factor receptor (EGFR) inhibitors are currently widely used for targeted lung cancer therapy. Target-ed therapy evaluation principally relies on genetic testing or rough clinical estimation. PET receptor imaging is highly sensitive and spe-cific. According to domestic and foreign literature, PET imaging using radiolabeled EGFR-targeting agents can be used to predict and monitor therapy response. This paper presents new evaluating methods for targeted lung cancer therapy.

Objective To evaluate if 18F-FLT PET imaging could be used as a new clinical method to predict tumor radiosensitivity.Methods MDA-MB-231 and LN229 cells were irradiated with doses of 0,8 and 16 Gy of 6 MV photon energy,then soft agar assay and cellular uptake of 18F-FLT were performed on the 2 cell lines.The t test and one-way analysis of variance were used for the two groups and data before and after irradiation.The MDA-MB-231 and LN229 tumor xenografts were prepared by injecting the tumor cells into the right limbs of female BALB/c nu/nu mice.Once tumors reached a diameter of 10 mm,the two types of mice were divided randomly into 3 groups (20 mice per group) according to the irradiation doses (0,8 and 16 Gy).After irradiation,18F-FLT PET imaging and immunohistochemical staining were conducted.Then correlations between 18F-FLT SUVtumor/SUVmuscle ratio (T/M ratio) and TK1 labeling index percentages (LITK1) were tested using linear correlation analysis.Results The survival fraction of MDA-MB-231 and LN229 cells after irradiated with 8 Gy were (59.73 ± 4.3) ％ and (93.41 ± 3.75) ％,respectively (t =-13.20,P ＜ 0.001).When the dose increased to 16 Gy,the survival fraction decreased to (43.57 ±4.06) ％ and (81.77 ± 4.42) ％,respectively(t =-14.24,P ＜ 0.001).In MDA-MB-231 cells,the cellular uptake of 18F-FLT after irradiation with 8 Gy declined rapidly to (18.32 ± 1.38) kBq/105 cells ((128.22 ± 8.24) kBq/105 cells with the dose of 0 Gy,F =266.41,P ＜ 0.01),and maintained this low level till 72 h.For the LN229 cells,the cellular uptake decreased to (9.87 ± 1.30) kBq/105 cells after 8 Gy irradiation ((134.88 ± 6.59) kBq/105 cells with the dose of 0 Gy,F =346.06,P ＜ 0.01),then increased gradually to (127.17 ± 9.08) kBq/105 cells at 72 h (F =346.06,P ＞ 0.05).The dynamic changes of 18F-FLT cellular uptake in the two cells had the same pattern after being treated with 16 Gy irradiation.In the 18F-FLT PET image of MDA-MB-231 tumor mice after 8 Gy radiotherapy,the T/M ratio decreased to 0.78 ± 0.39 at the first day,but it was 2.84 ± 0.29 before radiotherapy (F =39.78,P ＜0.01).Then the ratio increased slowly,and it was still lower than the baseline at 7 d after radiation (F =39.78,P ＜0.01).The same pattern could be seen in the group of 16 Gy irradiation.In LN229 tumor mice treatment with 8 Gy irradiation,the T/M ratio increased to 2.41 ±0.47 at the first day,and it was 1.58 ±0.29 before radiotherapy (F =34.01,P ＜ 0.05).The ratio decreased steadily to 0.66 ± 0.32 (F =34.01,P＜0.05) at 7 d after radiotherapy.However,in the treatment group with 16 Gy,the T/M ratio decreased gradually and reached 0.44 ± 0.22 at 7 d (F =41.85,P ＜ 0.01).A correlation was found between 18F-FLT T/M ratio and LITK1 (8 Gy:r=0.67,0.73; 16 Gy:r=0.73,0.69; all P＜0.01) in both tumor models.Conclusion 18F-FLT PET imaging may be used as a new assay to predict tumor radiosensitivity,but further investigation is needed before clinical application.

Objective To investigate the inhibitory effects and mechanisms of a nature product derivate oridonin on in?vasion of human lung cancer. Methods Human lung cancer A549 and PC-9 cell lines were treated with oridonin. MTS as?say was used to determine cell proliferation. Transwell assay was used to determine the cell invasion, and adhesion assay to determine the cell adhesion. Flow cytometry was used to determine cell cycle. Western blotting and realtime-PCR were used to detect expression levels of CDK1, mTOR, p53, p21, E-cadherin, CD44,β-catenin, uPA, MMP-2/9, p-AKT and p-Src. The luciferase reporter assay was used to detect the NF-κB promoter activity. Results In vitro proliferation, invasion and adhesion of A549 and PC-9 cells were significantly inhibited by oridonin. The cell cycle was halted by G2/M phase, and ex?pressions of E-cadherin, p53 and p21 were promoted, while expressions of CDK1, mTOR, CD44,β-catenin, uPA, MMP-2/9, p-AKT and p-Src and promoter activity of NF-κB were down-regulated. Conclusion Oridonin is able to inhibit the in vitro invasion of human lung cancer A549 and PC-9 cell lines, which might be correlated with its abilities to regulate the ty?rosine kinase activity.

Objective To explore the value of 18 F-fluorodeoxyglucose (i8 F-FDG) PET/CT examination in the differential diagnosis of the gastric cancer and primary gastric lymphoma (PGL).Methods The clinical data of 80 patients with gastric cancer (60 with non-mucinous adenocarcinoma and 20 with mucinous adenocarcinoma) and 47 patients with PGL [22 with mucosa-associated lymphoid tissue (MALT) and 25 with diffuse large B-cell lymphoma (DLBCL)] who were admitted to the Tianjin Medical University Cancer Institute and Hospital from June 2006 to May 2014 were retrospectively analyzed.Spiral CT scan was first done and then followed by PET.The CT value of the lesions,maximum standardized uptake value (SUVmax) of patients and maximal gastrointestinal wall thickness (THKmax) were analyzed by the ANOVA test.The SUVmax comparison between groups was evaluated with the Student-Newman-Keuls.The lesions type was analyzed by the chi-square test.The THKmax and SUVmax among groups were analyzed by the Pearson correlation analysis.Results 18 F-FDG PET/CT imaging of patients with gastric cancer and PGL showed different types of gastric wall thickening,segmental and limited thickening of gastric wall were the main features of gastric cancer and diffuse and segmental thickening of gastric wall were the main features of PGL.The type Ⅰ,Ⅱ and Ⅲ of lesions were detected in 12,21 and 27 of 60 patients with nonmucinous adenocarcinoma,in 2,7 and 11 of 20 patients with mucinous adenocarcinoma,in 8,8 and 6 of 22 patients with MALT and in 13,7 and 5 of 25 patients with DLBCL respectively.There were significant differences in the 4 pathological types of lesions among all the patients (x2 =14.849,P ＜ 0.05).The lymph nodes beneath the renal hilum and at the retroperitoneum were involved in 16 patients with gastric cancer and in 10 patients with PGL,and 7 patients with gastric cancer and 12 patients with PGL were complicated with splenomegalia,respectively,showing a significant difference in the splenomegalia between patients with PGL and gastric cancer (x2=7.506,P ＜0.05).There was no significant difference in the metastasis of lymph nodes beneath the renal hilum and at the retroperitoneum between patients with PGL and gastric cancer (x2=0.178,P ＞0.05).Among 80 patients with gastric cancer,positive 18F-FDG was detected in 79 patients and negative 18F-FDG in 1 patient with T3 stage of mucinous adenocarcinoma.Among 47 patients with PGL,positive 18 F-FDG was detected in 46 patients and negative 18F-FDG in 1 patient with stage Ⅰ of MALT.The CT value of the lesion,SUVmax and THKmax in patients with non-mucinous adenocarcinoma,mucinous adenocarcinoma,MALT and DLBCL were (40 ± 8)HU,(39±11)HU,(41±11)HU,(38±9)HU and 9.9 ±6.6,5.6±1.9,4.6 ±2.9,18.3±7.6 and (2.1 ± 1.2) cm,(1.9 ± 0.9) cm,(1.3 ± 1.1) cm and (2.6 ± 1.5) cm,respectively,showing significant differences in the SUVmax among all the groups (F =26.920,P ＜ 0.05).In the pairwise comparisons,there were no significant difference between the MALT group and mucinous adenocarcinoma group (P ＞ 0.05),and significant differences among the other groups (P ＜ 0.05).The CT value of the lesions and THKmax among all the patients were compared,with no significant differences (F =0.578,4.510,P ＞ 0.05).There were no significant differences in the SUVmax and THKmax among all the patients (r =0.055,0.346,0.226,0.133,P ＞ 0.05).Conclusions There is an important diagnosis value of PET/CT examination in patients with gastric cancer and PGL.The pathological types of the lesions in patients with gastric cancer and PGL are different.The occurrence of splenomegalia in patients with PGL is easier than that with gastric cancer.SUVmax of patients with DLBCL is higher than those with gastric cancer and MALT.FDG uptake in patients with mucinous adenocarcinoma and MALT are not enough,and these may lead to false negative result of PET/CT examination.

Objective To explore the value of urinary N-terminal telopeptide of type Ⅰ collagen (uNTX) combined with bone scintigraphy (BS) for the diagnosis of bone metastases.Methods A total of 227 patients suspected of bone metastases by BS were selected from Jan to May of 2012.UNTX was tested for each subject.The threshold of uNTX was chosen as 65 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr) for the diagnosis of bone metastasis.Patients with uNTX greater than 65 nmol BCE/mmol Cr would be diagnosed as having bone metastasis.Other examinations (CT,MRI,PET/CT or bone biopsy) were also performed to confirm the diagnosis.The uNTX values of benign and malignant bone lesions were compared using two-sample t test.The diagnostic efficacy of uNTX combined with BS was evaluated.A ROC curve was analyzed to evaluate the cut-off value of uNTX for the diagnosis of bone metastasis.Results The mean value of uNTX of all 227 patients was (84.30± 13.29) nmol BCE/mmol Cr,which was significantly higher than the upper limit of normal range (t =21.875,P＜0.01).Using 65 nmol BCE/mmol Cr as the threshold,197 cases were diagnosed as with and 30 without bone metastases,in which 188 and 27 were respectively confirmed by other examinations.The mean uNTX was (88.73 ± 8.37) and (60.76± 9.14) nmol BCE/mmol Cr in patients with and without bone metastases,respectively (t =-18.134,P＜0.01).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index of uNTX combined with BS were 98.4％ (188/191),75.0％ (27/36),95.4％ (188/197),90.0％ (27/30),94.7％ (215/227) and 73.4％ respectively.The cut-off value by ROC curve analysis was 78.88 nmol BCE/mmol Cr and the area under the curve was 0.982.Using 78.88 nmol BCE/mmol Cr as threshold,the corresponding sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index were 97.4％(186/191),94.4％(34/36),98.9％(186/188),87.2％(34/39),96.9％(22/227) and 91.8％ respectively.Conclusions Using the cut-off value of 78.88 nmol BCE/mmol Cr,uNTX may have clinical value in helping the differential diagnosis of bone scintigraphy for patients suspected of metastatic bone disease.

Objective:To explore the effects of body mass index (BMI) and gender on primary lung cancer 18F-FDG uptake param-eters, standardized uptake value (SUV), and standard uptake value of lean body mass (SUL). Methods:Data of 50 patients with prima-ry lung cancer confirmed by 18F-FDG positron emission tomography (PET)/computed tomography (CT) were retrospectively analyzed. AW4.6 workstation was employed to measure the SUVmean and SUVmax. Meanwhile, PETVCAR (PET Volume Computed Assisted Reading, GE Healthcare) software was used to automatically measure the SULmean, SULmax, and SULpeak. The SUVmean, SUV-max, SULmean, and SULmax of the liver (central region of the right lobe) were also measured automatically by PETVCAR. Afterward, T/N ratios (lesion SUVmax/liver SUVmean, lesion SULmax/liver SULmean, and lesion SULpeak/liver SULmean) of the lung cancer lesions were calculated. Correlations of the 18F-FDG metabolic parameters with BMI and gender of the patients were analyzed. Results:Liver SUVmean and SUVmax demonstrated significant positive correlations with BMI in all the patients (γ=0.38 and 0.36, P<0.05), and the SUVmean and SUVmax were positively correlated with BMI in male and female groups (γ=0.47 and 0.44, P<0.05), respective-ly. By contrast, no correlation existed between the liver SULmean and SULmax and BMI (P>0.05). No significant correlation was not-ed between the SUVmean, SUVmax, SULmean, SULmax, and SULpeak of the lung cancer lesions and BMI (P>0.05). The correlation trend is the same as that in different gender groups. Only the SUVmax T/N ratio of the lung cancer lesions showed a significant nega-tive correlation with BMI (γ=?0.29, P<0.05). The T/N ratios did not correlate with BMI in the different gender groups (P>0.05). Con-clusion:Patient BMI and gender mainly affect SUV values, particularly SUVmax, by contrast, patient BMI and gender did not signifi-cantly influence SUL and T/N ratio (SUL). Hence, SUL can be more suitable to quantitatively analyze and assess treatment response ob-jectively. This result will be helpful to the clinical application and promotion of PERCIST, which evaluates treatment response mainly by SUL.

Objective To compare the recent adverse reactions caused by 131I-Metuximab (licartin) treatment via two different routes and to assess the safety and advantages of peripheral intravenous bolus of licartin for the treatment of advanced HCC.Methods Clinical data of 54 patients (45 males,9 females,age 33-80 years) with advanced HCC treated with Licartin in Tianjin Medical University Cancer Institute and Hospital from October 2010 to March 2013 were collected and analyzed.The patients were divided into vein group (n=33) with Licartin injected through peripheral vein and artery group (n =21) with Licartin injected through hepatic artery.The results of blood routine examination,liver and kidney function and thyroid function between the two groups (1 week before treatment,4 and 12 weeks after treatment) were compared.The adverse reaction rate (ARR) and adverse reaction progression rate (ARPR) were also compared between the 2 groups.Ten days after Licartin treatment,all patients underwent gamma imaging to access the drug distribution in vivo.x2 test and two-sample t test were used to analyze data.Results There were no significant differences on age,gender and TNM staging between the vein group and the artery group (t =0.721,x2=0.561 and 4.769,all P＞0.05).The vein group showed temporary drug-related leucopenia (x2=7.041,P＜0.05) and increased level of serum total bilirubin (STB;x2 =10.297,P＜0.05) 4 weeks post-treatment.Twelve weeks later,the above parameters returned to baseline.In artery group,no influence on liver and kidney functions was observed,but the numbers of WBC and PLT decreased significantly (x2 =8.949 and 8.778,both P＜0.05) and returned to baseline 12 weeks post-treatment.The ARR in patients who had normal ALT levels before treatment between the two groups was significantly different(3.33％(1/30) vs 5/19,x2=5.718,P＜0.05).No significant difference was observed on ARR in patients with normal level of other parameters,and on ARPR in patients with abnormal preoperative parameters between the two groups (x2 =0.000-2.500,all P＞0.05).The drug's in vivo biodistribution and the thyroid function between the 2 groups showed no significant difference.Conclusion The peripheral intravenous bolus administration of Licartin is safe to treat patients with advanced HCC.

Objective: To evaluate and compare the safety and efficiency of the combined therapy of 89Sr plus zoledronic acid and those of 89Sr-chloride alone, in patients with painful bone metastases. Methods: A total of 87 patients with osseous metastasis were ran-domly divided into treatment groups of 89Sr-chloride alone (group A, 53 patients) and 89Sr plus zoledronic acid (group B, 34 patients). A total of 17 patients in group B received zoledronic acid 2-14 days after 89Sr therapy, and 13 other patients in the group received 89Sr 4-7 days after zoledronic-acid therapy. Pain response and KPS score were evaluated after the different treatments. Results: No obvious bone marrow suppression and liver damage were found in all cases. All patients who received both 89Sr-chloride and 89Sr plus zoledronic acid showed reduced bone pain and total discomfort, as well as improved KPS score, but the response was more pronounced in group B (P=0.047; P=0.036). No statistical differences in pain score and KPS scores were observed between the groups treated with zoledronic acid first and 89Sr therapy first (P=1.000; P=0.667). Comparison of bone pain relief and changes in the KPS score of different primary tumors after treatment with 89Sr-chloride or 89Sr plus zoledronic acid showed no statistical significance. Conclusion: Compared with 89Sr-chloride, treatment with 89Sr plus zoledronic acid was more effective in patients with painful bone metastases. The safety of these two treatments are similar.