dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4+ and CD8+ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

A Clinical Study of the Warthin's Tumor of the Salivary Gland / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The aim of this study was to define the clinical characteristics and treatment outcome of the salivary Warthin's tumor in order to work out a therapeutic strategy. SUBJECTS AND METHOD: The medical records of 64 patients who underwent surgery and were pathologically diagnosed with Warthin's tumor at our department from January 1997 to December 2009 were reviewed retrospectively. RESULTS: There were 60 (94%) males and 4 (6%) females with an overall male-to-female ratio of 15 : 1. The average age was 59.8+/-9.2 years (range from 35 to 78). All tumors were found in the parotid gland. Of the 66 tumors, 31 (48%) occurred in the right side, 28 (44%) tumors occurred in left side, and 5 (8%) tumors occurred in bilaterally. A superficial parotidectomy was performed in 38 (59%) patients, lumpectomy in 25 (39%) patients and bilateral lumpectomy in one patient. There were 18 (28%) postoperative complications. The most common complication was transient facial palsy that occurred in 11 (17%) patients. Recurrence occurred in 2 (3%) patients, oneipsilaterally and the other contralaterally. All recurrences were found in patients who underwent superficial parotidectomy. CONCLUSION: Warthin's tumor has a very low recurrence rate with a benign nature. The study shows that lumpectomy is an effective surgical treatment for Warthin's tumor with an advantage of reducing facial nerve palsy and recurrence rate.

The Analysis of Induction Chemotherapy Using Docetaxel and Platinum in Treatment of Hypopharyngeal Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the efficacy of induction chemotherapy with docetaxel and platinum in patients with hypopharyngeal carcinoma. SUBJECTS AND METHOD: The medical records of 66 patients who were diagnosed with hypopharyngeal carcinoma at our department from January 1996 to December 2008 were reviewed and retrospectively analyzed. The patients were divided into four groups according to treatment method: Group I was treated with radiation and induction chemotherapy consist of docetaxel and platinum (27); Group II was treated with surgery and induction chemotherapy consist of docetaxel and platinum (28), Group III was treated with radiation and induction chemotherapy consist of 5-FU and platinum (9) and Group IV was treated with surgery and induction chemotherapy consist of 5-FU and platinum (2). A total of 186 chemotherapy cycles were administered to patients and most of the patients received at least 2 cycles. RESULTS: The T-stage distribution at diagnosis was 7.5%, 42.4%, 28.8%, and 21.2% for T1, T2, T3, and T4, respectively. The N-stage distribution at diagnosis was 48.5%, 22.7%, 10.6%, 15.2%, and 9.1% for N0, N1, N2a, N2b, and N2c, respectively. The overall 3-year survival rate was 44.3%. The 3-year survival rate of each group was 42.6% in Group I, 54.8% in Group II, and 11.1% in Group III. There was no significant difference in survival between Groups I and III (p=0.074). There was no difference in sex, age, and N stage for 3-year survival rate. CONCLUSION: Although any valid conclusions could not be drawn because of the small number of patients examined here, induction chemotherapy consisting of docetaxel and platinum may improve the outcome of patients with hypopharyngeal carcinoma.

The Cardiovascular Effects of Thoracic Bolus Epidural Injection of Lidocaine, Morphine and Fentanyl during Sevoflurane General Anesthesia / 대한마취과학회지

BACKGROUND: Sevoflurane is an inhalational anesthetic that produces rapid induction, emergence and little cardiovascular depression. Elevated sympathetic activity during surgery produces undesirable effects on the cardiovascular system, such as hypertension, tachycardia or arrhythmias. So combined general and epidural anesthesia have been used recently for the operation, especially the abdominal surgery. This study was performed to evaluate the cardiovascular effects of thoracic epidural anesthesia during sevoflurane general anesthesia. METHODS: Forty patients of ASA class 1-2 undergoing elective subtotal gastrectomy were divided into 5 groups. Thoracic epidural bolus injection was administered via an epidural catheter during sevoflurane general anesthesia in a double-blind random manner: Group 1; normal saline (N/S) 10 ml (placebo), Group 2; morphine 0.1 mg/kg mixed with N/S in 10 ml, Group 3; fentanyl 1 mcg/kg mixed with N/S in 10 ml, Group 4; 1% lidocaine 10 ml, and Group 5; 1% lidocaine 10 ml mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg. Systolic and diastolic blood pressures, pulse rates, peripheral oxygen saturation levels (SpO2) and end-tidal carbon dioxide partial pressures (ETCO2) were measured every 5 minutes. RESULTS: Systolic and diastolic blood pressures were significantly reduced from 10 minutes after epidural bolus injection in groups 4 and 5, but these decreases in blood pressure were not severe enough to require treatment in either group. Pulse rates were significantly decreased from 10 minutes after injection in groups 3, 4, and 5, but these decreases in pulse rate were not so severe enough to require treatment in 3 groups. SpO2 and ETCO2 were stable, and arrhythmia was not observed. CONCLUSIONS: The thoracic epidural injection of 1% lidocaine mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg can be safely used during sevoflurane anesthesia without severe cardiovascular complications during upper abdominal surgery in ASA 1-2 patients.