Serum immunoglobulin fused interferon-α inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 × : 30 µg/kg and 50 × : 150 µg/kg). A slight anti-tumoral effect was observed in all 10 × groups compared to the control. In the 50 × groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-β. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition

QT Prolongation and Life Threatening Ventricular Tachycardia in a Patient Injected With Intravenous Meperidine (Demerol®)

QT prolongation is a serious adverse drug effect, which is associated with an increased risk of Torsade de pointes and sudden death. Many drugs, including both cardiac and non-cardiac drugs, have been reported to cause prolongation of QT interval. Although meperidine has not been considered proarrhythmic, we present a unique case of a 16-year-old boy without an underlying cardiac disease, who developed polymorphic ventricular tachycardia, ventricular fibrillation and QT prolongation after an intravenous meperidine injection. He had no mutation in long QT syndrome genes (KCNQ1, KCNH2, and SCN5A), but single nucleotide polymorphisms were reported, including H558R in SCNA5A and K897T in KCNH2

Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells

Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism

Comparison of CT and 18F-FDG PET for Detecting Peritoneal Metastasis on the Preoperative Evaluation for Gastric Carcinoma

OBJECTIVE: The aim of our study was to compare the accuracy of CT and (18)FFDG PET for detecting peritoneal metastasis in patients with gastric carcinoma. MATERIALS AND METHODS: One-hundred-twelve patients who underwent a histologic confirmative exam or treatment (laparotomy, n = 107; diagnostic laparoscopy, n = 4; peritoneal washing cytology, n = 1) were retrospectively enrolled. All the patients underwent CT and (18)F-FDG PET scanning for their preoperative evaluation. The sensitivities, specificities and accuracies of CT and (18)FFDG PET imaging for the detection of peritoneal metastasis were calculated and then compared using Fisher's exact probability test (p < 0.05), on the basis of the original preoperative reports. In addition, two board-certified radiologists and two board-certified nuclear medicine physicians independently reviewed the CT and PET scans, respectively. A receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of CT and (18)F-FDG PET imaging for detecting peritoneal metastasis. RESULTS: Based on the original preoperative reports, CT and (18)F-FDG PET showed sensitivities of 76.5% and 35.3% (p = 0.037), specificities of 91.6% and 98.9% (p = 0.035), respectively, and equal accuracies of 89.3% (p = 1.0). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for CT (Az = 0.878) than for PET (Az = 0.686) (p = 0.004). The interobserver agreement for detecting peritoneal metastasis was good (kappa value = 0.684) for CT and moderate (kappa value = 0.460) for PET. CONCLUSION: For the detection of peritoneal metastasis, CT was more sensitive and showed a higher diagnostic performance than PET, although CT had a relatively lower specificity than did PET.ope

Low dietary inorganic phosphate affects the lung growth of developing mice

Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health

Functionalized β-Cyclodextrin Immobilized on Ag-Embedded Silica Nanoparticles as a Drug Carrier

Cyclodextrins (CDs) have beneficial characteristics for drug delivery, including hydrophobic interior surfaces. Nanocarriers with &beta;-CD ligands have been prepared with simple surface modifications as drug delivery vehicles. In this study, we synthesized &beta;-CD derivatives on an Ag-embedded silica nanoparticle (NP) (SiO2@Ag NP) structure to load and release doxorubicin (DOX). Cysteinyl-&beta;-CD and ethylenediamine-&beta;-CD (EDA-&beta;-CD) were immobilized on the surface of SiO2@Ag NPs, as confirmed by transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis) spectrophotometry, and Fourier transform infrared (FTIR) spectroscopy. DOX was introduced into the &beta;-CD on the SiO2@Ag NPs and then successfully released. Neither cysteinyl-&beta;-CD and EDA-&beta;-CD showed cytotoxicity, while DOX-loaded cysteinyl-&beta;-CD and EDA-&beta;-CD showed a significant decrease in cell viability in cancer cells. The SiO2@Ag NPs with &beta;-CD provide a strategy for designing a nanocarrier that can deliver a drug with controlled release from modified chemical types

Alzheimer’s Disease and Different Types of Cancer Likelihood: Unveiling Disparities and Potential Protective Effects in a Korean Cohort Study

The link between Alzheimer’s disease and cancer risk is a concern in public health. However, research has yielded limited and sometimes contrasting results, suggesting the need for more validation. We analyzed a large cohort to examine the long-term association between Alzheimer’s disease (AD) and the risk of developing cancer. In total, 24,664 AD patients and 98,656 control participants were selected from the National Health Insurance Cohort database of Korea, spanning from 2002 to 2019. Propensity score matching and overlap-weighted adjustment techniques were used to balance the standardized differences between the AD and control groups. The Cox proportional hazards model was applied to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for various cancers, considering relevant covariates. Results indicated that patients with AD had a significantly lower likelihood of overall malignancy (HR 0.63; 95% CI, 0.59–0.68) and each of the 10 site-specific cancers compared to the control group. Among these, pancreatic cancer (HR, 0.50) exhibited the strongest inverse association, followed by hepatic (HR, 0.60), gastric (HR, 0.63), kidney (HR, 0.63), lung (HR, 0.64), thyroid (HR, 0.65), colorectal (HR, 0.67), gallbladder and biliary duct (HR, 0.73), hematologic malignancy (HR, 0.73), and bladder cancers (HR, 0.76). This protective effect against certain organ-specific cancers persisted over the 16-year follow-up period, except for in kidney cancer and hematologic malignancies. The protective effect against specific cancer types (gastric, colorectal, lung, hepatic, and pancreatic) was more prominent in individuals aged 60 years and older, regardless of their sex. However, there were some variations in the specific types of cancer observed between males and females. In summary, Korean patients with AD had a lower risk of cancer, especially in individuals 60 years and older, during the 16-year follow-up period