Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography.

OBJECTIVE: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. METHODS: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. RESULTS: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). CONCLUSIONS: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer.

BACKGROUND: The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. METHODS: We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. RESULTS: There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors. CONCLUSION: Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

[A retrospective analysis: comparison of the clinical characteristics and prognosis in elderly and young patients with locally advanced or metastatic non-small cell lung cancer.].

OBJECTIVE: To investigate whether the clinical characteristics, treatment modalities and prognosis of elderly (>/= 70 years) patients with advanced non-small cell lung cancer (NSCLC) differed from those of young (

[The detection by denaturing high performance liquid chromatography of epidermal growth factor receptor mutation in tissue and peripheral blood from patients with advanced non-small cell lung cancer].

OBJECTIVE: To study the application of denaturing high performance liquid chromatography (DHPLC) as a screening tool in detecting plasma and matched tissue epidermal growth factor receptor (EGFR) mutations for advanced non-small-cell lung cancer (NSCLC). METHODS: Plasma DNA samples and matched tumors from 230 cases of NSCLC were analyzed for EGFR mutations in exons 19 and 21 using DHPLC. The mutations in the plasma samples and the matched tumors were compared, and the association between EGFR mutations and the clinicopathological features were evaluated. RESULTS: Mutation of EGFR was found by DHPLC to be 33.5% (77/230) in tissues and 34.3% (79/230) in matched peripheral blood samples. Consistency of EGFR mutation status between tissues and matched plasma DNA was confirmed (kappa is 0.74, P < 0.01). The sensitivity and specificity of DHPLC for detecting EGFR mutation were 96.9% and 91.9%, respectively (kappa is 0.88). EGFR mutations in both tissue and blood was correlated with histology type (OR = 3.38, 95% CI 1.81 - 6.36, P < 0.05) and smoking status (OR = 1.61, 95% CI 1.13 - 2.28, P < 0.05), but no association with age, sex and stage was found (P > 0.05). CONCLUSION: The detection of EGFR mutation is highly consistent in tissues and in plasma DNA samples. DHPLC may serve as a preliminary screening tool for detecting EGFR mutations.

[Distinguishing second primary tumors from lung metastasis in patients with postoperative non-small cell lung cancer by microsatellite analysis].

OBJECTIVE: In patients with resected early stage non-small cell lung cancer (NSCLC), intrapulmonary solitary tumor represents either second primary tumor (SPT) or a metastasis. This study is to discern SPT from lung metastasis in patients with postoperative NSCLC followed a solitary intrapulmonary tumor by microsatellite analysis. METHODS: Twenty-one patients with stage I - III(A) NSCLC resected by surgery during 1994.1 - 2002.8 were studied. Paired tumors from 21 patients with NSCLC and a solitary lung nodule were analyzed for their loss of heterozygosity (LOH) on chromosomal arms 3p, 9p and 17p. DNA from microdissected tumors and non-malignant lung tissues was subjected to polymerase chain reaction-based microsatellite analysis using 8 microsatellite markers. An effort was also made to distinguish SPT from lung metastasis on the basis of clinical and histopathologic features. RESULTS: The paired tumors from 7 patients had concordant patterns of LOH at all microsatellite loci suggesting the same clonal origin, and supporting metastatic spread, where 4 paired tumors had discordant patterns of at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. Additional 6 paired tumors had concordant allelic loss on 3p and discordant loss on the other, clinical characteristics supporting metastatic disease. In contrast, 2 paired tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p, clinical data supporting SPT. CONCLUSIONS: The paired tumors from 7 patients had concordant patterns of LOH at all microsatellite loci suggesting the same clonal origin, and supporting metastatic spread, where 4 paired tumors had discordant patterns of at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. Additional 6 paired tumors had concordant allelic loss on 3p and discordant loss on the other, clinical characteristics supporting metastatic disease. In contrast, 2 paired tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p, clinical data supporting SPT.