-
[show abstract]
[hide abstract]
ABSTRACT: Vascular endothelial growth factor (VEGF) is the important angiogenic factor associated with tumor growth and metastasis in a wide variety of solid tumors. The aim of this study is to investigate the tumor suppressive effect of chitosan/small interfering RNA (siRNA)-VEGF nanoplexes in the rat breast cancer model. Chitosan/siRNA nanoplexes (siVEGF-A, siVEGFR-1, siVEGFR-2) and NRP-1 were prepared in a 15 to1 ratio and injected (intratumorally) into the breast-tumor-bearing Sprague-Dawley rats. Tumor volumes were measured during 21 days. To investigate the effect of chitosan/siRNA nanoplexes on VEGF expression in tumors, VEGF was analyzed with immunohistochemistry and western blotting. The mRNA levels of VEGF in tumor samples were determined with real-time PCR (RT-PCR). After siRNA treatment, a marked reduction in tumor volumes was measured in complex-injected rats (97%). Free siRNA injection showed lower tumor inhibition. Reduction of VEGF protein was also shown with western blotting and immunohistochemistry. Similar results were obtained with RT-PCR also. These results indicate that the chitosan/siRNA targeting to VEGF nanoplexes have a remarkably suppressive effect on VEGF expression and tumor volume in breast cancer model of rats.
Nucleic acid therapeutics. 01/2012; 22(1):40-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Vascular endothelial growth factor (VEGF) plays a critical role in angiogenesis. The aim of this study was to use chitosan/short hairpin VEGF (shVEGF) [short hairpin RNA (shRNA)-expressing pDNA targeting VEGF-A] complexes in the treatment of rat breast cancer model. Therefore, chitosan/shVEGF complexes were prepared in (2/1) ratio and injected to the breast-tumor bearing Sprague-Dawley rats. Intratumoral and intraperitoneal injections were applied and compared. Tumor volumes were measured during the 36 days. To investigate the effect of complexes on the VEGF expression, VEGF were analyzed by immunohistochemistry and western blotting. The mRNA levels of VEGF were determined by real-time polymerase chain reaction. Tumor volume decreased at the end of experiments after shRNA treatment. The highest suppression in the tumor volume was observed after intratumoral complex injection to rats (96%). Compared with intratumoral and intraperitoneal injection, higher tumor inhibition was obtained with intratumoral injection. Free shRNA injection indicated lower tumor suppression. The immunohistochemistry and western blotting results correlated with the real-time polymerase chain reaction and tumor volume measurements. The data suggest that chitosan/shVEGF complexes can be used to inhibit tumor growth in breast carcinoma model of rats.
Oligonucleotides 08/2010; 20(4):183-90. · 2.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this work was to investigate the physical properties of drug-loaded poly(methacrylic acid-g-ethylene glycol) {P(MAA-g-EG)} particles, their biocompatibility with the gastrointestinal tract of rats and also the effects of these particles on the tight junctions of the rat intestinal epithelium. Model drugs such as diltiazem HCl, diclofenac Na, ciprofloxacin HCl and isoniazid were used in this study. P(MAA-g-EG) particles were prepared by free radical solution polymerization of methacrylic acid (MAA) and poly(ethylene glycol) (PEG). The loading efficiency of the model drugs in the particles and in vitro release profiles were investigated in pH 7.4 phosphate buffer and in gradually pH changing buffers (pH 1.2, 5.8, 6.8 and 7.4). The stability of free particles and drug-loaded particles was established by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In conclusion, P(MAA-g-EG) particles controlled the release rate of small molecular weight model drugs according to the pH of the medium. Stability of those particles loaded with drugs did not change in accelerated stability conditions. Histopathological results indicated that loading drugs to the particles prevented cell and tissue damage after 20 h. Free particles showed no change of tight junctions after 2 and 10 h. The results of TEM showed that increasing the amount of P(MAA-g-EG) particles from 100 to 385 mg clearly opened the tight junction, but with serious epithelial cell disruption.
International Journal of Pharmaceutics 04/2006; 311(1-2):130-8. · 3.35 Impact Factor
-
Otolaryngology Head and Neck Surgery 08/2005; 133(1):153-5. · 1.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unrecognized bronchial foreign bodies (Fbs) cause irreversible changes in the airways. However, the exact course of these changes is not well-known. We developed an animal model of bronchial obstruction to radiologically and histopathologically assess the development of postobstructive pulmonary changes. A piece of peanut was placed in the airways of 21 rabbits through a 2.5-mm rigid bronchoscope. Animals were divided into three groups (groups I-III) that were sacrificed on day 3,10, and 30 after Fb placement, respectively. Prior to sacrifice, since there were no differences between the groups prior to Fb placement, computerized tomography (CT) of the lung was taken, and the lungs were harvested for histologic analysis under light microscope. In group I, leukocyte infiltration around the bronchial wall (P = 0.0003) and edema (P = 0.0384) around the alveolar septa were the predominant histological findings. The CT scan was normal. In group II and group III, increased amounts of mononuclear cells and macrophage infiltration around the bronchial wall were observed (P = 0.0008, P = 0.0409, respectively). There were no differences in presence of granuloma formation, emphysema, atelectasis, or thickness of alveolar septa among the three groups. The CT scan of group II showed consolidations plus minimal bronchial dilatation in the involved lung of the rabbits (P not significant). Bronchial cartilage destruction was seen in 4 out of 7 rabbits in group III (P = 0.0071). We conclude that 30-day retention of intrabronchial peanut caused bronchial cartilage destruction and fibrosis that were attributed as bronchiectatic changes in the airways of the lung parenchyma. Therefore, any case with suspected foreign body aspiration should be treated immediately to prevent possible irreversible changes of the lungs.
Pediatric Pulmonology 06/2002; 33(5):362-7. · 2.53 Impact Factor
