ObjectiveTo study the biologic distribution of 131I-Herceptin in BALB/c-neu nude mice bearing HER-2 positive SK-BR-3 human breast cancer xenografts and the radioimmunoimaging characteristics of nude mouse bearing human SK-BR-3 breast cancer xenografts. MethodSK-BR-3 breast cancer cells were implanted subcutaneously to athymic mice to establish animal model.Tumor bearing mice were continuously imaged with SPECT. The radiocounting per minute (cpm) of different organ on a γ-arithmometer was measured at 4,12,24,48 h postinjection of 131I-Herceptin or 131I-mlgG,and the T/NT ratios and the uptake percentages per gram of the injection dose (％ ID/g) was gained. ResultsModel was established in 96％ nude mouse.Compared with the control group,there was a significantly stronger contrast enhancement of tumor imaging,bigger T/NT and ％ ID/g in experimental group ( P ＜ 0.0l ).Conclusions 131I-Herceptin concentrates obviously in implanting tumor tissues of nude mouse,hence it is a good radiopharmaceutical agent targeting SK-BR-3 xenografts.

Objective:To label monoclonal anti-GPⅢa antibody (SZ21) with 99 Tcm and evaluate the value of 99 Tcm-SZ-21 for detecting thrombi in vivo.Methods:SZ-21 was modified with 2-iminotholane and labeled with 99 Tcm-GH and radiochemical purity was determined by ITLC-SG.99Tcm-SZ-21 was injected via ear edge vein in 5 rabbits in which thrombi were induced in the right femoral arteries.As control,99 Tcm-GH was administered in 1 rabbit.Static images were acquired and irregularly shaped ROIs were drawn on the images to calculate the ratios of T/M and T/B.Vein blood was drawn at 2 min,5 min,10 min,30 min and 1 h-3 h after injection in 2 rabbits so as to observe the blood clearance of 99 Tcm-SZ-21.Rabbits were sacrificed after 3 h of imaging.The vessels including clots were harvested and imaged.Cardiac muscle,liver,spleen,lung,kidney,etc.were excised and weighed.Radioactivity counts were measured to calculate % ID/g.Results:The radiochemical purity of 99 Tcm-SZ21 was beyond 90% and stable in vitro.Thrombi could be visualized at 30 min after injection,and at 2 h image of thrombi was clearly visualized,T/M (2.55?0.72) and T/B (1.94?0.51) ratios were high.In vitro imaging showed that T/B was 4.43?1.5.Conclusion:99Tcm-SZ-21 could be a potential agent for imaging diagnosis of thrombotic disease.

23 cases of the patients with supraorbital neuralgia were treated by puncturing Yangbai (GB 14) toward Yuyao (Extra), Zanzhu (BL 2), Taiyang (Extra), Touwei (ST 8),Zhongzhu (TE 3) and Neiting (ST 44) on the sick side, plus laser radiation on a site about 1 cm apart from the midpoint of the eyebrow of the sick side. After 10 treatments, the results showed cure in 19 cases and remarkable effect in 4 cases.

Objective To explore the clinical value of dual-phase 99Tcm-MIBI scintigraphy in the localization and diagnosis of secondary hyperparathyroidism (SHPT).Methods A total of 20 patients (8 males,12 females; average age 49.6 years) with uremic SHPT who underwent parathyroidectomy from 2010 to 2013 were retrospectively analyzed.All patients underwent 99Tcm-MIBI SPECT/CT and 19 underwent color Doppler ultrasonography (CDUS).Post-excisional histopathology was considered as the gold standard.The diagnostic efficacies of 99Tcm-MIBI and CDUS for SHPT were calculated.The correlation between T/NT ratio in delayed imaging and the volume of excised parathyroid and the intact PTH (iPTH) were analyzed.x2 test,Pearson or Spearson correlation analysis were used to analyze the data.Results The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 99Tcm-MIBI SPECT/CT and CDUS in the diagnosis of SHPT were 66.67％ (44/66),100％(14/14),100％ (44/44),38.89％(14/ 36),72.50％ (58/80) and 78.19％(43/55),52.38％(11/21),81.13％(43/53),47.83(11/23),71.05％ (54/76),respectively.There were significant differences in specificity and positive predictive value (x2 =9.33,9.26,both P＜0.05),but no significant differences in the sensitivity,negative predictive value and accuracy (x2 =1.97,0.04,0.46,all P＞0.05).T/NT ratio correlated with serum iPTH and parathyroid volume (r=0.638,rs =0.571,both P＜0.05).Conclusions The specificity of 99Tcm-MIBI SPECT/CT is superior to CDUS in the diagnosis of SHPT.Dual-phase 99Tcm-MIBI SPECT/CT could locate the hyperfunctional parathyroid gland and provide the basis for surgical treatment.

Objective To study the serum levels of progastrin-releasing peptide (pro-GRP) and neuron-specific enolase (NSE) for the clinical diagnosis,therapy monitoring and survival time analysis of small cell lung cancer (SCLC).Methods All 41 SCLC samples (30 males,11 females,age range from 46 to 78 years),95 NSCLC samples (55 males,40 females,age range from 42 to 88 years),and 127 normal individuals samples (80 males,47 females,age range from 35 to 78 years) which were diagnosed by People's Hospital of Zhengzhou from May 1,2008 to April 30,2011 were collected.Serum levels of pro-GRP,NSE and their changes in SCLC patients before and after therapy were evaluated.ANOVA analysis,randomized block design analysis of variance and the log-rank test were collected SPSS 16.0 to evaluate the survival time.Results The serum levels of pro-GRP (median 357.8 ng/L) and NSE (median 89.5 μg/L) in SCLC group were significantly higher than those in the NSCLC group (pro-GRP:39.9 ng/L;NSE:11.43 μg/L) and normal individuals group (pro-GRP:12.7 ng/L;NSE:10.03 μg/L) (P=0.000).The sensitivity of pro-GRP and NSE for the diagnosis of SCLC were 80.4％ and 78.0％,while the specificity were 92％ and 87％,respectively.There is a poor correlation between pro-GRP and NSE serum levels,but when combined the sensitivity can be 95％ and specificity can be 85％.Significantly statistical difference of pro-GRP levels was observed in the different stages of treatment (before and after therapy) in SCLC-LD patients (F =3.53,P =0.038),and significant statistical difference of NSE levels was also observed in SCLC-ED patients in different stages (F =16.049,P =0.000).In partied response SCLC patients,the group with NSE level lower than cut-off value had longer survival time than the other group with NSE level higher than cut-off value (P =0.001).Conclusions The sensitivity of the combined analysis of pro-GRP and NSE is better than single marker for the diagnosis of SCLC.The serum level of pro-GRP has better correlation with therapeutic effect of SCLC-LD patient than NSE.The serum level of NSE are well correlated with therapeutic effect in SCLC-ED patients.There are some certain value of NSE level for evaluation the survival time of SCLC patients who were in partial response.

Purpose: Most lung adenocarcinoma (LUAD) patients are diagnosed at the advanced stage and have poor prognosis. DNA methylation plays an important role in the prognosis prediction of cancers. The objective of this study was to identify new DNA methylation sites as biomarkers for LUAD prognosis. Materials and Methods: We downloaded DNA methylation data from The Cancer Genome Atlas data portal. Cox proportional hazard regression model and random survival forest algorithm were applied to identify the DNA-methylation sites. Methylation of sites were validated in the Gene Expression Omnibus cohorts. Function annotation were done to explore the biological function of DNA methylated sites signature. Results: Six DNA methylation sites were identified as prognosis signature. The signature yielded acceptable discrimination between the high-risk group and low-risk group. The discrimination effect of this DNA methylation signature for the OS was obvious, with a median OS of 21.89 months vs. 17.74 months for high-risk vs. low-risk groups. This prognostic prediction model was validated by the test group and GEO dataset. The predictive survival value was higher for the prognostic prediction model than that for the tumor node metastasis stage. Adjuvant hemotherapy could not affect the prediction of the signature. Functional analysis indicated that these signature genes were involved in protein binding and cytoplasm. Conclusion We identified the prognostic signature for LUAD by combining six DNA methylation sites. This could service as potential robust and specificity signature in the prognosis prediction of LUAD.

OBJECTIVETo evaluate the toxic effects of mixture of volatile organic compounds (VOCs) on Mice Testis related enzymes and hormones.

METHODSAfter determining the median lethal dose (LD₅₀) of VOCs using the acute toxicity test, 40 male clean inbred Kunming mice were assigned to 1/8 LD₅₀ VOCs exposure group, 1/4 LD₅₀ VOCs exposure group, and 1/2 LD₅₀ VOCs exposure group, as well as positive control group with cyclophosphamide (60 mg/kg) and negative control group with tea oil, with 8 mice in each group. The mice were intraperitoneally injected with respective agents for 5 days. The levels of testis testosterone, estradiol, follicle stimulating hormone, and luteinizing hormone were determined by ELISA. Meanwhile, the activity of testicular marked enzymes such as lactate dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase, and glucose-6-phosphate dehydrogenase were examined.

RESULTSCompared with the negative control group, the 1/8 LD₅₀ exposure group had a significantly increased testis coefficient (P<0.05). Both the activity of testicular marked enzymes and the levels of testicular sex hormones in all exposure groups showed significant downward trends with increasing VOC doses compared with those in the negative control group (P<0.05).

CONCLUSIONVOCs have obvious toxicity to mouse testis by changing the levels of testicular sex hormones and the activity of testicular marked enzymes.

Animals ; Estradiol ; chemistry ; Follicle Stimulating Hormone ; chemistry ; Gonadal Steroid Hormones ; chemistry ; Luteinizing Hormone ; chemistry ; Male ; Mice ; Testis ; chemistry ; drug effects ; Testosterone ; chemistry ; Volatile Organic Compounds ; toxicity

BACKGROUNDMonoclonal antibodies (mAbs) such as DD3, raised against progastrin-releasing peptide(31-98) (ProGRP (31-98)) antigen, have been used to target small cell lung cancer (SCLC). However, as an intact mAb, DD3 is cleared slowly from the body, with an optimal radioimmunoimaging time of 72 hours. More recently, a single-chain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research. Thereby, it potentially increases the radioimmunoimaging efficacy. However, there have been few studies with this antibody fragment. The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of (131)I-anti-ProGRP(31-98) scFv in nude mice bearing SCLC xenografts.

METHODSAnti-ProGRP(31-98) scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry. (131)I-anti-ProGRP(31-98) scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram (%ID/g) in various organs was calculated. Similarly, the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated. After injection of (131)I-anti-ProGRP(31-98) scFv, treated mice were imaged at 1, 24, and 30 hours. Then the tumor/base ratios were calculated.

RESULTSProGRP was highly expressed in NCI-H446 cells and xenograft tissue. The metabolism of (131)I-anti-ProGRP(31-98) scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes, respectively. The %ID/g of (131)I-anti-ProGRP(31-98) scFv in xenografts was much higher than in healthy tissues at 12 hours after injection, reaching a maximum of (5.38±0.92) %ID/g at 24 hours. Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours, with 24 hours proving optimal.

CONCLUSION(131)I-anti-ProGRP(31-98) scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance, indicating that it could be a promising agent for SCLC radioimmunoimaging.

Animals ; Female ; Flow Cytometry ; Humans ; Immunoglobulin Fragments ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peptide Fragments ; immunology ; Radioimmunodetection ; methods ; Recombinant Proteins ; immunology ; Small Cell Lung Carcinoma ; diagnostic imaging ; metabolism ; Xenograft Model Antitumor Assays