Susceptibility Evaluation of EGFR Targeted Small Molecule NXGH/NXGF for Lung Cancer Cell / 现代生物医学进展

Objective:To investigate the sensitivity of novel small molecule tyrosine kinase inhibitors NXGH and NXGF to 4 lung cancer cell lines with different EGFR expression and mutant status.Methods:Novel small molecule tyrosine kinase inhibitors NXGH and NXGF based on NXG structure were designed.Four lung cancer cell lines with different EGFR expression and mutation status:PC9(Exon 19 deletion mutation),H1975(L858R mutation combined T790M mutation),H358(wide EGFR expression) and H520(EGFR negative expression) were chosen.Inhibition ratio of NXGH and NXGF at different concentration (1.25,2.5,5.0,10,20,30,40,60,80 μmoL·L-1)against 4 lung cancer cell lines in 48 h were investigated by MTT method.IC50 and cell viability were calculated,and sensitivity between different cell lines were compared.Results:IC50 of PC9,H358,520 and H1975 cells incubated with NXGH were 0.675 μ moL·L-1,12.097 μmoL·L-1,11.368 μmoL·L-1 and 0.981 μmoL·L-1,respectively.IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25,2.5 and 5 μmoL ·L-1 (P＜0.05).IC50 of PC9,H358,H520 and H1975 cells incubated with NXGF were0.685 μmoL·L-1,4.265 μmoL·L-1,3.097 μmoL·L-1 and 0.331 μmoL·L-1,respectively.IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25 and 5 μmoL·L-1 (P＜0.05).Conclusion:The novel small molecule tyrosine kinase inhibitors NXGH and NXGF,which were designed and constructed in our laboratory successfully,had high affinity for lung cancer cells with different EGFR expression and mutation status.And they were more sensitive to EGFR mutant cell at low concentration as expected.

Minimally invasive and precise treatment of malignant tumor / 中国肿瘤临床

The treatment of malignant tumor is one of the world's worst medical problem and is thus a research hotspot. The occur-rence of tumor development follows the molecule→cell→tissue→organ process. In theory, treatment can be achieved at any stage of tumor-growth by inhibition. Minimally invasive technology for treating tumor embodies the following direction of tumor treat-ment:minimally invasive, precise, and efficient. With endoscopy or imaging as a guide, the purpose of minimally invasive therapy is to have a small wound and to control tumor maximally at the tissue and organ level;thus, this therapy mode is the best and most pre-cise. This kind of technology has a good application prospect, even in the case of distant metastasis, and can be used to relieve the symptoms and improving the quality of survival by treating lesions affecting important organ functions. Minimally invasive therapy is a great challenge following the direction of modern medicine. With the development of medical science and technology, the important role of minimally invasive therapy in future tumor therapy is foreseen.

Molecular imaging and tumor targeted therapy / 中国肿瘤临床

The abnormal expression (level and status) of the key molecular targets of tumors is related to molecular targeted therapy response, effect, and prognosis. Therefore, the expression level and status of key molecular targets of tumors must be accurately evalu-ated, regardless of the status before, during, and after receiving targeted therapy. Molecular imaging is a non-invasive method used for qualitative and quantitative research on key molecular targets of tumor in vivo and in real-time. This technique is also employed to screen treatment beneficiaries, guide therapy, and evaluate prognosis. This paper reviews the application progress of molecular imag-ing using various probes in cancer targeted therapy. The clinical value of molecular imaging in tumor targeted therapy is further ana-lyzed to promote the development of novel targeted therapy for tumors.

In vivo study of the effect of combining endostatin gene therapy with 32P-colloid on hepatocarcinoma and its functioning mechanism.

PURPOSE: To investigate the therapeutic effect of combining 32P colloid radiotherapy with endostatin anti-angiogenesis therapy on hepatocellular carcinoma (HCC) cells. METHODS: HCC mouse models were prepared using H22 cells and randomly divided into four groups. The mice were administered phosphate buffered saline (PBS), (32)Pcolloid, secretory endostatin encoding plasmid and combination of 32P and endostatin, respectively. Seven, 14 and 21 days after treatment the mice were sacrificed. Expression of endostatin was confirmed using western blot. Tumor growth rate, microvessel density (MVD) in the solid tumor and apoptotic index (AI) of tumor cells was analyzed using immunohistochemistry and TUNEL methods. RESULTS: (1): From the western blot results, 1400 bp endostatin specific protein bands were observed in the samples from groups 3 and 4, but not in the other two groups; (2): The tumor growth rate of groups 2, 3 and 4 was significantly decreased compared to group 1 and that of group 4 was significantly lower than group 2 and 3 (3): The MVD of group 1 was greatly higher than in the other groups (4): The AI of group 4 was dramatically higher than in the other groups. CONCLUSIONS: (32)Pcolloid radiotherapy or endostatin anti-angiogenesis therapy were able to inhibit the growth of HCC cells in vivo, while the combination of (32)P and endostatin showed much better therapeutic effect in HCC treatment.

Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma.

OBJECTIVE: The objective of this study was to explore the significance of assessing irreversible airway obstruction (IAO) in asthma patients by high-resolution computed tomography (HRCT), biological markers in induced sputum, and exhaled nitric oxide (FENO). METHODS: The study was conducted in 34 patients with IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did not have airway obstruction (NAO), and 40 healthy subjects serving as controls. These patients received a step therapy for at least 3 months based on the guidelines for the prevention and treatment of asthma. After achieving complete or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in induced sputum were measured. RESULTS: The airway wall area (WA; %) correlated with forced expiratory volume-1 (FEV-1(L); r = -0.67, p < 0.0001), and significant differences in bronchial wall thickening (BWT) of the LEVEL E generation airways were observed between the asthma and control groups (p < 0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p = 0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO were significantly higher than those in the controls (p < 0.05). The level of neutrophilia in the sputum from the IAO group was higher than that from the RAO, NAO and control groups. CONCLUSION: Asthma patients with IAO have an increased BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation of airway remodeling in asthma patients with IAO.

Comparison of dual-source parallel radio frequence transmission liver MRI at 3.0 T with conventional MRI / 中华放射学杂志

Objective To investigate the role of dual-source parallel radio frequence (RF) and single-source excitation in liver imaging at 3.0 T MR.Methods This study was a retrospective analysis.One hundred and seven subjects underwent a 3.0 T TX MR scanning including axial spectrally selective attenuated inversion recovery (SPAIR) T2WI,axial DWI and coronal balanced-fast field echo( Balanced FFE).Each sequence was carried out with both single-source and dual-source RF excitation.Student＇s t test was used to compare the differences between single-source and dual-source RF excitation in the image uniformity,signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).Wilcoxon signed rank test was used to determine whether there was difference between conventional and parallel transmission in the score of image quality.Reader agreement was assessed using the Cohen＇s Kappa test.Results For the image uniformity,there was significant difference between single-source and dual-source excitation (418.40 ± 66.75 for single-source vs.416.26 ± 50.61 for dual-source,t =2.524,P ＜ 0.05 ).There also existed significant difference between single-source and dual-source excitation in SNR and CNR,respectively.The SNR and CNR of parallel transmission (22.03 + 12.16 and 18.33 ± 10.01,respectively) were both higher than those of single transmission (20.36 ± 11.21 and 15.22 ± 8.95,respectively) ( t =- 2.630,P ＜ 0.05 for SNR and t =- 4.238,P ＜ 0.05 for CNR).Image quality comparisons revealed significantly better results with dual-source than single-source RF excitation at SPAIR T2 WI ( 1.40 + 0.42 vs.1.81 ± 0.27 ),DWI ( 1.08 ± 0.40 vs.1.63 ± 0.36 ) and Balanced FFE sequence ( 0.95 ± 0.45 vs.1.65 ± 0.37,Z =- 5.894,- 5.801 and - 6.985,respectively,P ＜ 0.01 ).In the comparison of image quality,the agreement between the two readers was very good ( Kappa ＞ 0.8,P ＜ 0.05 ).Conclusion Dual-source parallel RF excitation MR imaging in liver enables reducing dielectric shading,improving homogeneity of the RF magnetic induction field,and increasing SNR and CNR at 3.0 T.

The relationship between the proliferation of parathyroid cell in rabbit with primary hyperparathyroidism and the bone mineral density / 中华放射学杂志

ObjectiveTo evaluate the relationship between the proliferation of parathyroid cell in rabbit with primary hyperparathyroidism (PHPT) and the bone mineral density (BMD). MethodsEighty adult Chinese rabbits were randomly and equally divided into two groups. The contrast group was fed with normal diet ( Ca ∶ P, 1.0 ∶ 0. 7 ) and the experimental group was fed with high phosphate diet ( Ca ∶ P,1.0∶7.0) to establish the animal model of PHPT. At 3, 4, 5, and 6 months after the diet, bone mineral density of the rabbits was measured by the quantity CT (QCT). Then, the parathyroid and bone of the rabbits were removed for pathological examination. The number of parathyroid cell in PHPT was calculated.Proliferation was determined by immunohistochemistry of proliferation cell nuclear antigen ( PCNA ) and Bcl-2. The t test and Logistic regression was used to analyze the difference of data of two groups. ResultThe number of parathyroid cell in PHPT group was 1.61 times than that in the contrast group[ (673 ± 151 ) HP,(418 ± 25 ) HP,P ＜0. 01]. The rate of PCNA positive-cell was significantly increased in PHPT group than that in contrast group [(50.52 ± 11.62)％o, (26.70 ± 2. 78 )％, P ＜ 0.01], and so was Bcl-2[ (460. 37 ± 190. 05 )‰, (67. 02 ±:4. 38 )％‰,P ＜0. 05]. The value of BMD was significantly decreased in PHPT group than that in contrast group [ ( 152. 5 ± 34. 3 ), ( 188.6 ± 12. 2 ) g/cm3, P ＜ 0. 05]. There was a negative correlation between BMD and PCNA (r ＝ -0. 749, P ＜ 0. 05 ) and between BMD and Bcl-2 (r ＝-0.800, P ＜ 0. 05 ) in PHPT group. ConclusionThe BMD of PHPT is related to the parathyroid cells proliferation which provide a reliable method for early diagnosis of PHPT.

A comparative study of 99Tcm N-mercaptopyridine-N-oxide and 99Tcm-sestamibi myocardial perfusion imaging on acute myocardial infarction canine model / 中华放射学杂志

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.

Clinical application of MR susceptibility weighted imaging in intracranial hemorrhage / 中华放射学杂志

Objective To assess the value of susceptibility weighted imaging(SWI) in the diagnosis of intracranial hemorrhage. Methods Forty patients with intracranial hemorrhage underwent MRI scanning (GE Signa HDe 1.5 T), which included T2WI, T1WI, T2 * WI and SWI. Of them, DWI was conducted in 37 cases and enhanced MRI was conducted in 10 cases additionally. After post processing on the workstation, both magnitude and phase images of SWI were acquired for further analysis. The images of all sequences were scored from 1 to 3, according to their ability of depicting the lesions. Statistical analysis was conducted to compare the scores among these sequences. Results On SWI, the scores in detecting the lesions, their margin and adjacent veins were 2. 8, 2. 8, and 2. 8 respectively. The scores of those were 1.8, 1.7,and 0.0 on T1WI, 2.3, 2.0 and 0.0 on T2WI, 2.0, 2.1 and 0.2 on T2* WI, respectively. There was statistical difference between the scores on SWI and those on T1WI, T2 WI and T2 * WI ( P < 0. 01 ). The numbers of micro hemorrhagic lesions that could be observed on SWI, T1WI, T2WI, DWI and T2 *WI were 402, 55, 61, 84 and 188 respectively. There was statistical difference in showing micro hemorrhagic lesions between SWI and T1WI, T2WI, DWI, T2 * WI (P < 0. 01 ). Conclusion SWI is sensitive to visualize the hemorrhagic region, and has predominant advantage over conventional MR sequences including T2 * WI in detecting intracranial hemorrhage, especially cerebral microbleeding. According to the features of the paramagnetic and diamagnetic lesions, radiologists can differentiate hemorrhage and calcification with phase images.

Molecular imaging of human breast cancer xenografts in nude mice by epidermal growth factor labelled by near infrared fluorescent dye / 中华放射学杂志

can specifically combined with EGFR, which may be applied to noninvasive NIRF imaging of tumors highly expressed EGFR in vivo.

Evaluation of effects of simvastatin on vascular elasticity in fat-fed rabbits by echo-tracking technique / 中华超声影像学杂志

Objective To evaluate the effects of simvastatin on the vascular elasticitv in fat-fed rabbits by echo-tracking(ET)technique.Methods Twenty seven rabbits were divided randomly into 3 groups:normal control group(group A),high fat diet group(group B),simvastatin group(group C:high fat diet for the 1st 4 weeks and high fat diet+simvastatin for the 2nd 4 weeks).β,EP,AC,and PWVβof abdominal aorta (AO) and femoral artery(FA)of rabbits in group A、B、C were measured by ET technique at the end of 4th week and 8th week respectively.The expression of iNOS was measured at the end of 8th week.Results At the end of the 4th week,β,Ep,and PWVβ of FA were significantly inereased and AC was significantly decreased in group B compared to those in group A(P＜0.05).At the end of the 8th week,β,Ep,PWVβof AO were significantly increased and AC was significantly decreased in group B compared to those in group A(P＜0.05);β,Ep,PWVβ of FA were statistically decreased and AC was statistically increased in group C compared to those in group B(P＜0.05),however there was no significant difference of AO between groups B and C.Conclusions Short-term administration of simvastatin can improve the elasticity of some muscular arteries such as FA but not AO.

64-detector Helical CT in Diagnosis of Coronary Heart Disease / 实用放射学杂志

Objective To investigate the accuracy of 64-detector helical CT in assessing stenoses of coronary arteries. Methods 64-detector helical CT angiography was performed in 128 patients with suspected coronary artery disease,and the results were compared with that of invasive coronary angiography. Results Among 128 patients, 1 724 of 1 920 coronary artery segments were assessable (90%). Overall sensitivity for classifying stenoses was 92%, specificity was 94%, positive predictive value was 82%, and negative predictive value was 96%.Conclusion 64-detector helical CT provides a high diagnostic accuracy in assessing coronary artery stenoses.

The comparision of 5-Fu pharmacokinetics on rabbit after left gastric intraarterial infusion and by peripheral intravenous administration / 介入放射学杂志

Objective To compare the pharmacokinetics on rabbit after left gastric regional arterial infusion chemotherapy with peripheral intravenous administration.Methods 18 rabbits were seperated into 6 time groups at random and 5 Fu (50mg/kg) was infused through left gastric artery. Blood of portal vein and peripheral vein were sampled at different times. Finally all rabbits were killed and partial stomach tissues were sampled. Blood and stomach tissue were analysed with high efficacy liquid chromatography after disposed. Control group members were infused 5 Fu (50 mg/kg) by ear marginal vein and then blood and stomach tissue samples taken at different times were analysed with the same method. Results The drug concentration time curve of portal vein and peripheral vein both reached the peak at the fifth minute after drug administration in the two methods, then declined quickly and slowed down after 30 minutes, according with two house models. The drug concentration in portal vein of the experimental group was obviously higher than in the peripheral vein and also higher than in the portal vein of the controll group maintaining for a longer period. Drug concentration in stomach tissue of experimental group was 11 times of that of control group at the fifth minute and was similar after 2 hours in both methods groups.Conclusions Drug concentration in blood of portal vein and stomach tissue can maintain a higher level in a longer period with the same local effect after left gastric arterial infusion chemotheraphy showing high chemotherapeutic efficiency.

The Biological Characteristics in vitro and Anti-Tumor Effect in vivo of Lung Cancer Cells Infected with Recombinant Adenovirus Expressing hTNF-? / 中国肿瘤生物治疗杂志

Objective: To study the biological characteristics of tumor cells infected with recombinant adenovirus expressing hTNF-?, investigate the antitumor effect of recombinant adenovirus. Methods: Human lung adenocarcinoma cell line Anip973 was infected with recombinant adenovirus expressing hTNF-?. Cell growth assay, colone formation test, flowcytometry assay and morphology were used to observe the effects on tumor cells. The hTNF-a gene, which was transduced into cancer cells mediated by recombinant adenovirus, was detected by PCR and agarose gel electrophoresis and its products were detected by ELISA assay. The intratumoral injection of rAd-LacZ and rAd-hTNF-? was carried out to evaluate their antitumor effects. Results: The liter of rAd reached 1010 PFU/ml and more than 90% Anip973 cells could be infected by 30MOI rAd. Except the surface structure and ultrastructure of tumor cells infected with rAd had a light change, cell growth abillity assay, colone formation test, flow cytometry assay showed no significant difference compared with that of the control cells. The TNF-? gene expression at 24 h increased greatly. Antitumor study indicated that on the tumor-bearing mice treated with rAd the tumor grew slowly. Tumor volume was significantly smaller and survive time was prolonged than that of controls. Conclusion: There was no significantly changes occurred on tumoral cells after infected with recombinant adenovirus expressing hTNF-?. The intratumoral injection of rAd-LacZ and rAd-hTNF-? could inhibit the growth of solid tumor.

Analysis of the treatment and prognostic factors of hepatic metastases of colorectal cancer:a report of 52 cases / 中国普通外科杂志

Objective To evaluate the therapeutic effect,prognostic factors and the methods to improve long term survival of liver resection for hepatic metastases of colorectal cancer.Methods 52 patients operated on for hepatic metastases from colorectal cancer were followed up,and the clinical and pathologic data of 11 (cases),who survived more than 5 years,were compared with 41 survivors of less than 5 years after hepatic (resection).Results The 1-,3-and 5-year survival rate was 75.0%,30.8%,and 21.2%,(respectively).The important factors affecting prognosis were pathologic type of the primary cancer,(number) of (hepatic) metastasis,selection of the methods and timing of surgery,and postoperative treatment(P

Interventional Therapy for Ulcerative Colitis / 实用放射学杂志

Objective To introduce a new management for ulcerative colitis. Methods There were eighteen patients underwent inferior mesenteric artery drug infusion who suffered from ulcerative colitis and cannot be cured by internal medicine. We observed the clinical symptoms and laboratory test results at the most resent follow up. Results All the patients’symptoms such as bellyache ,phrexia, abdominal distension were disappeared after interventional therapy. Diarrhea in seventeen patients was stopped. Fifteen patients who had blood stool were be cured. Erythrocyte and leucocyte were no longer be seen with stool laboratory test after drug infusion.Conclusion Inferior mesenteric artery drug infusion is another positively efficacy way for ulcerative colitis.