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Objective:To observe the distribution of 177Lu-FA-DOTA-PEG-PLGA nanoparticles in vivo, and evaluate the therapeutic effect of nanoparticles intraperitoneal injection on ovarian cancer peritoneal metastases and ascites. Methods:Nanoparticles were prepared and injected into human ovarian cancer xenograft nude mice model by tail vein. Micro-SPECT/CT imaging was performed at different times (4, 24, 72 h and 7 d) after injection to observe the distribution of nanoparticles in vivo. Nude mouse models of intraperitoneal metastases of human ovarian cancer were randomly divided into negative control group (normal saline), chemotherapy group (cisplatin 3 mg/kg, twice a week) and nanoparticle group (18.5 MBq), with 4 mice in each group. After 7 days, intraperitoneal tumor growth was evaluated by in vivo fluorescence imaging. The relative tumor inhibition rate was counted. Tumor cell apoptosis rate was detected by TUNEL method, and the proliferation activity tumor Ki67 was detected by immunohistochemical method. The ascites volume of each group was compared after treatment. Results:Micro-SPECT/CT imaging showed the radioactive uptake of the transplanted tumor, and the 24 h tumor muscle uptake ratio (T/M) was the highest, about 2.81±0.49. Intravital fluorescence imaging showed that, after intraperitoneal administration, the fluorescence intensity of abdominal tumor in particle group, chemotherapy group and control group was (1.45±0.19)×10 10, (2.21±0.36)×10 10 and (2.63±0.79)×10 10( F=6.09, P=0.029), respectively. The relative tumor growth inhibition (TGI) of the particle group and the chemotherapy group were 35.6% and 18.6%, respectively. The tumor cell apoptosis rates in particle group and chemotherapy group were higher than those in control group ( F=9.96, P=0.009). Ki67 indexes in particle group and chemotherapy group were lower than those in control group ( F=9.93, P=0.013). The ascites volume in particle group and chemotherapy group were both smaller than those in control group ( F=13.43, P=0.006). Conclusions:177Lu-FA-DOTA-PEG-PLGA nanoparticles can be used for the targeted imaging of ovarian cancer. After intraperitoneal injection, nanoparticles show local retention, degradation and absorption and thus inhibit the growth of peritoneal metastases and ascites of ovarian cancer, which provides a new idea for the diagnosis and treatment of advanced ovarian cancer with peritoneal metastasis.
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Objective To explore the effects of graphene oxide (GO)-polyethylene glycol (PEG)-folic acid (FA)-pyrenemethylamine hydrochloride (PyNH2)-mediated RNA interference (RNAi) of hypoxia-inducible factor-1α (HIF-1α) on the biological behaviors of human pancreatic cancer Patu8988 cells.Methods GO-PEG-FA-PyNH2 and RNAi targeting HIF-1α gene (GO-PEG-FA-PyNH2-HIF-1α-RNAi)was constructed.The expressions of HIF-1α and glucose transporter 1 (Glut-l) in Patu8988 cells were determined after knockdown of HIF-1α by RNAi.The invasive ability,the proliferation and the cell cycle of Patu8988 cells were investigated.The effect of HIF-1α knockdown on the uptake of 18F-fluorodeoxyglucose (FDG) in Patu8988 cells was also detected.Comparison of data was conducted by one-way analysis of variance and least significant difference t test.Results The GO-PEG-FA-PyNH2 was successfully constructed,and no cytotoxicity was found.Under the hypoxia or normoxia state,the mRNA and protein levels of HIF-1α and mRNA level of Glut-1 in cells transfected with GO-PEG-FA-PyNH2-HIF-1α-RNAi (study group) were lower than those in cells transfected with GO-PEG-FA-PyNH2 (negative group) and cells transfected with Opti-minimal essential medium (Opti-MEM,control group;F=30.25-32.58,t=3.66-5.81,all P＜0.05);the numbers of migrated cells in the study group were much lower than those in the negative group and the control group (F=38.63 and 41.35,t=20.51-35.25,all P＜0.01);the cell proliferation in the study group was significantly lower than that in the negative group and the control group (F=35.19 and 38.11,t =15.11-22.19,all P＜0.05).The proportions of G0/G1 cells in the study group were higher than those in the negative group and the control group (F=34.60 and 34.83,t=11.55-34.56,all P＜0.05);the 18 F-FDG uptake in the study group was lower than that in the negative group and control group (F=29.85 and 31.69,t =3.35-4.35,all P＜0.05).Conclusion GO-PEG-FA-PyNH2-mediated HIF-1α RNAi inhibits the expression of HIF-1α in pancreatic cancer cells,leading to changes in related biological behaviors.
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Objective To predict the tolerance range of set-up errors in clinical practice by predicting the virtual set-up errors of postoperative radiotherapy patients for breast cancer. Methods A retrospective analysis was made of the patients who underwent radiotherapy after breast cancer surgery in recent 3 years. According to different treatment method, 10 cases of breast cancer after modified radical mastectomy and 10 cases after breast conserving radical mastectomy were selected. The target area was delineated, the volume modulated radiation therapy plan was made, the virtual moving error of the center point of the plan was moved, and the maximum moving error was 5 mm by 1 mm step. After recalculating the dose, the corresponding data including the clinical target areas ( CT ) , CTV ( V50 ) , average heart volume, V20 of the affected lung and CTV volume were recorded. SPSS 19. 0 software was used for statistical analysis, and repeated measurement of variance analysis was used to analyze the changes of the actual dose in the target area after moving the center point. Linear regression analysis method was used to analyze the correlation between the CTV volume and the dose change after the CTV moving midline. Results The virtual set-up error had little influence on the axis direction of the approximate mammary tangent direction, while the vertical direction of the approximate mammary tangent direction had greater influence. After moving more than 3 mm on the vertical axis, the CTV ( V50 ) decreased to below 90％, which was lower than the general requirement for the target area of CTV. Statistical analysis of set-up errors in all directions showed that there was significant difference in dosimetric changes ( F=34. 182, 12. 877, 16. 443, 9. 846, 46. 829, 10. 122, 57. 931, P <0. 05) in all directions except the B direction of left breast set-up errors (P>0. 05). Between breast conserving surgery and modified radical mastectomy, there was little effect on target movement. Through correlation analysis, it was found that the volume of CTV in the target area of breast cancer patients was linearly related to the errors caused by the movement of B, C and B directions of left breast and right breast(F=5. 733, 18. 496, 6. 630, P<0. 05). Conclusions In postoperative radiotherapy for breast cancer, the errors perpendicular to the section of breast should be paid special attention to whether left or right breast. When the error of this direction exceeds 3 mm, CTV is obviously less than V50 below 83. 85％. The effect of set-up error on the dose of CTV was not related to the operation mode of breast cancer and there was no obvious correlation with the volume of the target area.
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Objective To investigate the relationship between the biochemical markers of bone turnover and renal osteodystrophy (ROD) in patients with primary nephrotic syndrome (PNS).Methods A total of 30 patients with PNS and 50 healthy subjects (controls) were included in the study.The BMD of lumbar vertebrae and femur was measured by dual-energy X-ray absorptiometry.The levels of total procollagen type Ⅰ amino-terminal propeptide (TP Ⅰ NP),β-isomerized carboxyterminal propeptide (β-CTx),intact PTH (iPTH),serum calcium,serum phosphorus,ALP,25-OH-Vitamin D3 (25-OH-VD3),β2-micro-globulin(β2-MG),and ratio of urinary to creatinine (UA/Cr) were measured and calculated.The risk factors related to ROD in PNS patients were analyzed.Two-sample t test,multiple linear regression and partial correlation analysis were used to analyze data.Results The BMD values of lumbar vertebrae and femur in the PNS group were significantly decreased compared with those in controls (t =6.162,5.583,3.891 (＜40 years),5.923,5.324,3.129 (≥40 years),all P＜0.05) and the serum levels of TPⅠNP,β-CTx,iPTH,ALP,β2-MG and UA/Cr in the PNS group were significantly higher than those in controls (t:2.738-10.129(＜40 years),3.226-12.581 (≥40 years),all P＜0.05),and the levels of serum calcium and 25-OH-VD3 in the PNS group were significantly lower than those in controls (t =3.624,7.223 (＜40 years),2.011,2.564 (≥40 years),all P＜0.05).But there was no significant difference for serum phosphorus between the 2 groups (t=0.811,0.513,both P＞0.05).TP Ⅰ NP was positively correlated with β-CTx,iPTH,ALP,UA/Cr,β2-MG(r:0.512-0.682,all P＜0.01),and TP Ⅰ NP was negatively correlated with serum calcium and 25-OH-VD3(r=-0.314,-0.562,both P＜0.01)in the PNS group.β-CTx was positively correlated with iPTH,ALP,UA./Cr,β2-MG(r:0.459-0.618,all P＜0.01),and negatively correlated with serum calcium and 25-OH-VD3(r=-0.212,-0.589,both P＜0.01).The iPTH was positively correlated with ALP,UA/Cr and β2-MG (r =0.410,0.606,0.508,all P＜0.05),and negatively correlated with serum calcium and 25-OH-VD3(r=-0.315,-0.516,both P＜0.05).Conclusions The BMD in PNS patients is lower than that in healthy subjects.Combined measurement of TP Ⅰ NP,β-CTx and the BMD is helpful for the diagnosis of ROD in PNS patients.
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Objective To optimize the method for radiotherapy target delineation after breast cancer surgery, and to observe its advantage in raising work efficiency. Methods Ten physicians in our department were selected, and 20 patients who received breast?conserving surgery were randomly selected. The 10 physicians delineated the targets for these patients with the method in the control group and the method in the study group, and the time required for each delineation was recorded. The method in the control group was commonly used in daily practice and the method in the study group was optimized. The independent?samples t test was applied to compare the differences between the two groups. Results With the optimized method, the average time of delineation in the study group was less than that in the control group ( 51 min vs. 65 min, P=0. 029) . The time curves for delineation in the control group were relatively flat;the time curves for delineation in the study group were high at first, then decreased gradually, and finally became flat. The time for each physician to finish delineation skillfully was relatively stable, while in the study group, the time started to decrease after delineation for the first few patients, with an apparent learning process. Conclusions The optimized method for target delineation in breast cancer is feasible, reliable, and easy to master, and can increase work efficiency, which is more obvious in physicians with rich experience in delineation.
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Objective To evaluate the significance of tumor markers CEA and CA15-3,and biochemical markers of bone turnover (total procol]agen type Ⅰ amino-terminal propeptide (TP I NP),β-isomerized carboxyterminal propeptide (β-CTx),ALP and PTH) in the diagnosis of bone metastasis from breast cancer.Methods A total of 78 patients (all females) with mean age (56.72 ± 10.76) years,who were diagnosed with breast cancer,were included in this study.The patients were divided into two groups based on radionuclide bone imaging:with bone metastasis (n =32) and without bone metastasis (n =46).The serum concentrations of CEA,CA15-3,TP I NP,[β-CTx,PTH,ALP were measured.Gleason scores were evaluated.The diagnostic value was evaluated by ROC curve.The two groups were compared using two-sample t test.The correlations between bone metastasis and tumor markers,bone metastasis and biochemical markers of bone turnover were analyzed with Pearson correlation and logistic analysis.Results The serum levels of CEA,CA15-3,TPINP,β-CTx,PTH and ALP were significantly higher in the group with bone metastasis than those in the group without bone metastasis (t:4.16-7.56,all P ＜ 0.05).For the diagnosis of bone metastasis from breast cancer,the AUC of CEA,CA15-3,TPINP,[β-CTx,PTH and ALP was 0.815,0.887,0.869,0.852,0.844,0.731,respectively.Using the cut-off values of 4.18 μg/L for CEA,0.04 U/L for CA15-3,49.70 μg/L for TP I NP,0.47 pg/L for β-CTx,54.90 ng/L for PTH and 49.90 U/L for ALP,the sensitivities were 56.3％ (18/32),75.0％ (24/32),78.1％ (25/32),81.3％ (26/32),78.1％ (25/32),68.8％ (22/32) and the specificities were 80.4％ (37/46),84.8％ (39/46),76.1％ (35/46),78.3％ (36/46),69.6％ (32/46),58.7％ (27/46),respectively.CEA,CA15-3,TPINP,β-CTx,PTH,ALP and Gleason score were positively correlated with the presence of bone metastasis (r:0.267-0.636,all P ＜ 0.05).CEA,CA15-3,TP I NP,β-CTx,PTH and Gleason score were independent predictors for bone metastasis of breast cancer (odds ratios:2.45,3.44,1.24,1.54,1.11,2.22,all P ＜0.05).The total coincidence rate of regression model was 81.3％ (26/32) in patients with bone metastasis.Conclusions The diagnostic values of CEA,CA15-3,TP I NP,β-CTx and PTH are comparable.Combined use of these parameters may be helpful for the early diagnosis of bone metastasis from breast cancer.