Antitumor activity of adriamycin-incorporated polymeric micelles of poly(gamma-benzyl L-glutamate)/poly(ethylene oxide)

The multiblock copolymer composed of poly(gamma-benzyl L-glutamate) (PBLG) and poly(ethylene oxide) (PEO) was synthesized to prepare polymeric micelles as an anticancer drug carrier. Adriamycin (ADR) used as an anticancer drug was incorporated into the polymeric micelles prepared by the multiblock copolymer. The higher the drug feeding ratio, the higher the drug loading contents and the lower the drug loading efficiency. The increased drug feeding ratio resulted in increased particle sizes. At all of the formulations, particle sizes were less than 150 nm. The particles were observed as spherical shapes. ADR release from ADR-loaded polymeric micelles in vitro was decreased with an increased drug loading contents. In in vitro antitumor activity test using CT 26 tumor cells, polymeric micelles showed almost similar cytotoxicity when compared to ADR itself while polymeric micelles themselves did not affect cytotoxicity. In in vivo antitumor activity test using mice tumor xenograft model, the polymeric micelles showed improved survivability of mice with minimized weight changes and excellent tumor growth suppression efficacy. Polymeric micelles of the multiblock copolymer suggested to be a good candidate for anticancer drug delivery carrier.     

Urinary Cell-Free DNA IQGAP3/BMP4 Ratio as a Prognostic Marker for Non–Muscle-Invasive Bladder Cancer

BackgroundDisease monitoring in non–muscle-invasive bladder cancer (NMIBC) patients is crucial for early identification of disease recurrence and progression. High IQGAP3/BMP4 and IQGAP3/FAM107A ratios in urinary cell-free DNA (ucfDNA) are a diagnostic biomarker for bladder cancer. We aimed to investigate whether the levels of these biomarkers in ucfDNA can be used to monitor disease recurrence or progression in patients with NMIBC.Patients and MethodsA total of 103 patients with NMIBC (pTa-pT1) were enrolled. The IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were measured by real-time PCR, and the results were compared with clinical outcome by Kaplan-Meier curves and Cox regression analyses.ResultsOverall, 55 patients (53.4%) experienced recurrence and 29 (28.2%) experienced disease progression during a median follow-up of 42.7 months (range, 6.1-172.2 months). Kaplan-Meier analysis revealed that NMIBC patients with a high IQGAP3/BMP4 ratio had worse recurrence-free survival and progression-free survival (PFS) (P = .001 and < .001, respectively), and those with a high IQGAP3/FAM107A ratio had worse PFS (P = .006). Multivariate Cox regression analysis revealed that the IQGAP3/BMP4 ratio was independently associated with recurrence-free survival (hazard ratio, 2.462; P = .003) and PFS (hazard ratio = 3.871; P = .004), whereas the IQGAP3/FAM107A ratio was not an independent factor for PFS (P = .079).ConclusionThe IQGAP3/BMP4 ratio in ucfDNA might be a valuable novel biomarker for predicting disease recurrence and progression in patients with NMIBC.     

Suppression of proliferative cholangitis in a rat model by local delivery of paclitaxel

Background. Proliferative cholangitis (PC) leads to biliary stricture, which is the main cause of hepatolithiasis, recurrent cholangitis, and biliary cirrhosis. The aim of this study was to determine whether local delivery of paclitaxel, which inhibits cell proliferation by overstabilization of microtubules, prevents PC in a rat model.Methods. PC was induced by introducing a fine nylon thread into the bile duct in a rat. Paclitaxel (100µl of 10, 100, and 1000µmol/l) or solvent vehicle was administered into the bile duct for 15min. One week after treatment, histopathologic examination and 5-bromodeoxyuridine (BrdU) labeling of the bile duct were performed.Results. In comparison with the control, the mean thickness of the bile duct was reduced by 29% in the 1000µmol/l paclitaxel-treated group (2.61 ± 0.31µm vs 3.67 ± 0.25µm, P 0.05). The luminal area increased (P 0.0001) and the grade of epithelial–glandular proliferation was decreased (P 0.01) as the dose of paclitaxel increased. Ductal fibrosis and inflammatory cell infiltration were similar in both groups. The BrdU labeling index was significantly lower in the paclitaxel-treated group (P 0.05).Conclusions. Local delivery of paclitaxel suppressed PC in a rat model by the inhibition of epithelial–glandular proliferation and may offer an effective therapeutic option for biliary stricture.     

Ciprofloxacin-encapsulated poly(DL-lactide-co-glycolide) nanoparticles and its antibacterial activity

The aim of this study was to prepare ciprofloxacin HCl (CIP)-encapsulated poly(dl-lactide-co-glycolide) (PLGA) copolymer nanoparticles and its antibacterial potential was evaluated with pathogenic bacteria, Escherichia coli (E. coli), in vitro and in vivo. CIP-encapsulated nanoparticles of PLGA were prepared by multiple emulsion solvent evaporation method. PLGA nanoparticles showed spherical shapes with particle sizes around 100-300 nm. Loading efficiency was lower than 50% (w/w) because of water-solubility properties of CIP. At drug release study, CIP showed initial burst effect for 12 h and then continuously released for 2 weeks. At in vitro antibacterial activity test, CIP-encapsulated nanoparticles showed relatively lower antibacterial activity compared to free CIP due to the sustained release characteristics of nanoparticles. However, CIP-encapsulated PLGA nanoparticles (doses: 25 mg CIP/kg of mice) effectively inhibited the growth of bacteria due to the sustained release characteristics of nanoparticles, while free CIP was less effective on the inhibition of bacterial growth. These results indicated that CIP-encapsulated PLGA nanoparticles have superior effectiveness to inhibit the growth of bacteria in vivo.     

A biodegradable poly(ester amine) based on polycaprolactone and polyethylenimine as a gene carrier

The aim of research was to develop and optimize delivery systems for plasmid DNA (pDNA) based on biodegradable polymers, in particular, poly(ester amine)s (PEAs), suitable for non-viral gene therapy. Poly(ester amine)s were successfully synthesized by Michael addition reaction between polycaprolactone (PCL) diacrylate and low molecular weight polyethylenimine (PEI). PEA/DNA complexes showed effective and stable DNA condensation with the particle sizes below 200nm, implicating its potential for intracellular delivery. PEAs showed controlled degradation and were essentially non-toxic in all three cells (293T: Human kidney carcinoma, HepG2: Human hepatoblastoma and HeLa: Human cervix epithelial carcinoma cell lines) at higher doses in contrast to PEI 25K. PEAs also revealed much higher transfection efficiencies in three cell lines as compared to PEI 25K. The highest reporter gene expression was observed for PCL/PEI-1.2 (MW 1200) complex having transfection efficiency 15-25 folds higher than PEI 25K in vitro. Also PEA/DNA complexes successfully transfected cells in vivo after aerosol administration than PEI 25K. These PEAs can be used as most efficient polymeric vectors which provide a versatile platform for further investigation of structure property relationship along with the controlled degradation, significant low cytotoxicity and high transfection efficiency.     

Ampullary gangliocytic paraganglioma with lymph node metastasis: A case report with literature review

Rationale:Gangliocytic paraganglioma (GP) is a rare tumor that mostly develops in the duodenum and is composed of the following 3 cell types: epithelioid endocrine, spindle-like, and ganglion-like cells. It manifests as symptoms such as abdominal pain, gastrointestinal bleeding, and weight loss; however, occasionally, it is incidentally detected on endoscopic or radiologic examinations. Although GP is usually benign, it can metastasize to the lymph nodes, and distant metastases have been reported in some cases.Patient concerns:A 46-year-old woman presented with anemia on health surveillance examination. She had no other specific symptoms, and her physical examination did not reveal any abnormal finding.Diagnosis:Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed, and the endoscopist obtained samples from the inner side of the ampullary mass. Pathological examination suggested GP or a neuroendocrine tumor.Interventions:Initially, we planned transduodenal ampullectomy with lymph node excision. However, there was severe fibrosis around the duodenum, and an examination of a frozen biopsy sample from the periduodenal lymph node showed atypical cells in the lymph node. Therefore, we performed pylorus-preserving pancreaticoduodenectomy with lymph node dissection.Outcomes:The final pathological diagnosis was GP located in the ampulla of Vater. The GP showed lymphovascular and perineural invasion and invaded the duodenal wall. Furthermore, 4 out of 18 harvested lymph nodes showed metastasis.Lessons:We described a case of GP confined to the ampulla with regional lymph node metastasis and reviewed published literature on ampullary GP with lymph node metastasis.     

Association between iris constitution and apolipoprotein e gene polymorphism in hypertensives

OBJECTIVE: Iridology is a complementary and alternative medicine (CAM) that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong familial aggregation and heredity is implicated. Apolipoprotein E (apoE) gene polymorphism is one of the most well-studied genetic markers for vascular diseases, including hypertension. In this study, we investigated the relationship between iris constitution and apoE polymorphism in hypertensives. DESIGN AND SUBJECTS: We classified 87 hypertensives and 79 controls according to iris constitution and determined the apoE genotype of each individual. RESULTS: A significantly higher percentage of individuals with neurogenic constitutions was found in the hypertensive group when compared with the control group (chi(2) = 40.244, p < 0.001). In addition, a neurogenic constitution increased the relative risk for hypertension for subjects with an apo epsilon2 or an epsilon4 allele (chi(2) = 4.086, p = 0.049, odds ratio = 2.633, confidence interval = 1.004-6.905). CONCLUSIONS: Our results imply that a neurogenic iris constitution enhances the relative risk for hypertension in subjects with the apo epsilon2 or epsilon4 allele. Furthermore, we attempted to evaluate the efficacy of iris constitutional medicine and to find an association with hypertension.     

Clonazepam release from core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) triblock copolymers

The triblock copolymer based on poly(-caprolactone) (PCL) as hydrophobic part and poly(ethylene glycol) (PEG) as hydrophilic one was synthesized and characterized. Core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) (CEC) block copolymer were prepared by a dialysis technique. According to the amphiphilic characters, CEC block copolymer can self-associate at certain concentration and their critical association concentration (CAC) was determined by fluorescence probe technique. CAC value of the CEC-2 block copolymer was evaluated as 0.0030 g/l. CAC values of CEC block copolymer decreased with the increase of PCL chain length, i.e. the shorter the PCL chain length, the higher the CAC values. From the observation of transmission electron microscopy (TEM), the morphologies of CEC-2 core-shell type nanoparticles were spherical shapes. Particle size of CEC-2 nanoparticles was 32.3±17.3 nm as a monomodal and narrow distribution. Particle size, drug loading, and drug release rate of CEC-2 nanoparticles were changed by the initial solvents and the molecular weight of CEC. The degradation behavior of CEC-2 nanoparticles was observed by ¹H NMR spectroscopy. It was suggested that clonazepam (CNZ) release kinetics were dominantly governed by diffusion mechanism.