Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice

Abstract

BackgroundThe aim of this study is to examine the safety and distribution of Ad-EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1), in the mice colon carcinoma model.MethodsAfter bone marrow cells (BMCs) were infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was detected by in situ hybridization and immunohistochemistry. The peripheral hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and platelet (Plt) counts were analyzed.ResultsNeither total adenovirus antibody nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor. No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.ConclusionThe results indicate that IBM-BMT administration of a replication defective adenovirus is a feasible mode of delivery, allowing exogenous transference. The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

Salivary expression of soluble HER2 in breast cancer patients with positive and negative HER2 status

“…Bernardes et al reported that salivary HER2 levels were not elevated in patients with oral squamous cell carcinoma 37. Moreover the clinicopathological data, such as patient age, smoking habit, histological grading, T status, or nodal involvement of the tumor, the difference between patients with positive and negative HER2 overexpression in tumors was not statistically significant 37.…”

P-glycoprotein expression and amyloid accumulation in human aging and Alzheimer's disease: preliminary observations

“…The slides were then placed in a humidity chamber and 400 mL of proteolytic pepsin solution dissolved in 0.1-N HCl was applied to the tissue for a 30 minutes incubation period at 37 C. The solution was tapped off, and the tissue was dehydrated in 70%, 95%, and 100% ethanol for 1 minute each. The slides were allowed to air dry, and 20 mL of digoxigenin-labeled probe solution for P-gp (5 0 TGG TGC TGG GGT GCT GGT TGC TGC TTA CAT TCA 3 0 ) (Integrated DNA Technologies, Coralville, IA, USA) was applied to the tissue (Zhao et al, 2010). Positive and negative control probes were provided in the kit.…”

Efficacy and safety of addition of bevacizumab to FOLFIRI or irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer

“…[28] Rafii et al [29] reported that inhibition of VEGF receptors could inhibit the hematopoietic stem-cell cycling, which will related to the risk of myelosuppression. A previous meta-analysis indicated that the addition of bevacizumab significantly increased the risk of hypertension by 6.2%, [15] whereas no significant differences were found in grade 3–4 proteinuria and bleeding. In our present meta-analysis, the adverse events were graded.…”

“…With respect to the safety and efficacy of bevacizumab on mCRC patients, a recent meta-analysis has been conducted. [15] However, the authors of this study (1) did not explain the efficacy and safety of bevacizumab plus FOLFIRI or IFL on treatment of mCRC, (2) did not report the effect of bevacizumab on complete response rate and treatment discontinued by bevacizumab toxicity; (3) just focused on the first-line treatment. Therefore, we performed this meta-analysis to study the effectiveness of bevacizumab (Be)-containing FOLFIRI and IFL regimens for mCRC patients.…”