In vitro vessel-forming capacity of endothelial progenitor cells in high glucose conditions

In type 2 diabetes, the impairment of vascular repair processes and angiogenesis are due to endothelial progenitor cell (EPC) dysfunction. In this study, we established a quantitative methodology to assess EPC function by using an in vitro 5-(6)-carboxyfluorescein diacetate succinimidyl ester-labeling vessel formation assay. The EPCs were cultured in three different glucose concentrations (100, 189.5, and 295.5 mg/dl of d-glucose) representing normal control and diabetes with either good or poor glycemic control, respectively. We found that the in vitro vessel-forming capacity was impaired in EPCs cultured in high glucose concentrations compared to normal control (43.4 ± 0.8% and 34.7 ± 0.7% vs. 50.8 ± 2.1%). We further studied expression of various genes involved in vessel formation. There was a lower level of angiopoietin 1 gene expression in EPCs cultured in high glucose concentrations. The addition of recombinant angiopoietin 1 significantly increased the vessel-forming capacity of EPCs cultured in high glucose concentration (35.3 ± 2.0% to 48.8 ± 2.7%), whereas the addition of angiopoietin 2 (a competitive inhibitor of angiopoietin 1) impaired the vessel-forming capacity of EPCs cultured in normal glucose concentration (51.8 ± 1.3% to 41.3 ± 0.6%). We conclude that the in vitro vessel-forming capacity of EPCs cultured in high glucose concentration is impaired due to low levels of angiopoietin 1.     

Comparison of the Nuclear Contour Index (NCI) and T cell Subsets of Erythematous,Plaque and Tumor Lesions in Patients with Mycosis Fungoides (MF)

Using monoclonal T cell antibodies, we compared T cell subsets of skin infiltrates with the nuclear contour index (NCI) of pan T cells of skin infiltrates from erythematous, plaque and tumor lesions in the same patients with mycosis fungoides (MF). In all lesions, the majority of the skin-infiltrate population were T cells; helper T cells were especially dominant in the plaque and tumor lesions. The NCI of the T cells in skin infiltrates increased in parallel with advancing stages of the lesions in the same patient. The NCI data for T cell and T cell subsets in different stages of lesions in the same patient were similar to data from different stages of lesions in different patients. Therefore, even in tumor stage patients, topical treatment should be selected in accordance with the cytological stage of their lesions.     

A regional cooperative clinical study of radiotherapy for cervical cancer in east and south-east Asian countries.

PURPOSE: Radiotherapy differed widely in east and south-east Asia because of technical, cultural, and socio-economic differences. With the purpose of standardizing radiotherapy for cervical cancer in the region, an international clinical study was conducted. MATERIALS AND METHODS: Eleven institutions in eight Asian countries participated in the study. Between 1996 and 1998, 210 patients with stage IIIB cervical cancer were enrolled. Patients were treated with a combination of external beam radiotherapy (total dose, 50Gy) and either high-dose-rate (HDR) or low-dose-rate (LDR) intracavitary brachytherapy (ICBT) according to the institutional practice. The planned point A dose was 20-28Gy/4 fractions for HDR-ICBT and 30-40Gy/1-2 fractions for LDR-ICBT. RESULTS: Hundred patients were treated with HDR-ICBT and 110 were treated with LDR-ICBT. The ICBT doses actually delivered to point A ranged widely: 12-32Gy in the HDR group and 26-52.7Gy in the LDR group. The 5-year follow-up rate among the countries differed greatly, from 29% to 100%. The 5-year major complication rates were 6% in the HDR group and 10% in the LDR group. The 5-year overall survival rates were 51.1% in the HDR group and 57.5% in the LDR group. CONCLUSIONS: Although there were several problems with treatment compliance and patients' follow-up, the study suggests that the protocols provided favorable outcomes with acceptable rates of late complications in the treatment of advanced cervical cancer in east and south-east Asia.     

Concurrent chemoradiotherapy for T3–4 and N0–1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3–4 and N0–1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3–4 N0–1 M0, World Health Organization Type 2–3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m²). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3–4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis–free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.     

Impaired interaction of alpha-haemoglobin-stabilising protein with alpha-globin termination mutant in a yeast two-hybrid system

Alpha-thalassaemia caused by alpha-globin gene termination codon mutations (alphaT-globin) has been explained by their inherent mRNA instability and by oxidative damage arising from the presence of membrane-bound alphaT-globin chains. To better understand the latter phenomenon, a yeast two-hybrid system was used to assay the interaction between alphaT-globin and its molecular chaperone, alpha-haemoglobin-stabilising protein (AHSP) and impaired binding of alphaT-globin with AHSP compared with alpha(wild-type)-globin was observed.     

Chitosan drug binding by ionic interaction.

Three model drugs (insulin, diclofenac sodium, and salicylic acid) with different pI or pKa were used to prepare drug-chitosan micro/nanoparticles by ionic interaction. Physicochemical properties and entrapment efficiencies were determined. The amount of drug entrapped in the formulation influences zeta potential and surface charge of the micro/nanoparticles. A high entrapment efficiency of the micro/nanoparticles could be obtained by careful control of formulation pH. The maximum entrapment efficiency did not occur in the highest ionization range of the model drugs. The high burst release of drugs from chitosan micro/nanoparticles was observed regardless of the pH of dissolution media. It can be concluded that the ionic interaction between drug and chitosan is low and too weak to control the drug release.