Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT+ CD11c+ cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-gamma, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-alpha) and immunosuppressive cytokine (TGF-beta) secretion, IFN-gamma production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

The Effects of Neuromuscular Electrical Stimulation on Cardiopulmonary Function in Healthy Adults

OBJECTIVE: To evaluate the effect of neuromuscular electrical stimulation (NMES) on cardiopulmonary function in healthy adults. METHOD: Thirty-six healthy adults without a cardiac problem were enrolled. All patients were randomly assigned to either a control (17 subjects, mean age 29.41) or an electrical stimulation group (19 subjects, mean age 29.26). The electrical stimulation group received NMES on both sides of quadriceps muscle using a Walking Man II(R) in a sitting position for 30 minutes over 2 weeks. Maximum oxygen consumption (VO2max), metabolic equivalent (MET), resting, maximal heart rate (RHR, MHR), resting, maximal blood pressure (RBP, MBP), and maximal rate pressure product (MRPP), exercise tolerance test (ETT) duration were determined using an exercise tolerance test and a 6 minute walk test (6MWT) before and after treatment. RESULTS: The electrical stimulation group showed a significant increase in VO2max (p=0.03), 6MWT (p<0.01), MHR (p<0.04), MsBP (p<0.03), ETT duration (p<0.01) and a significant decrease in RsBP (p<0.02) as compared with the control group after two weeks. NMES induced changes improved only in RsBP (p<0.049) and ETT duration (p<0.01). The effects of NMES training were stronger in females. CONCLUSION: We suggest that NMES is an additional therapeutic option for cardiopulmonary exercise in disabled patients with severe refractory heart failure or acute AMI.

Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34+ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-beta secretion were higher in SDC but CCR7 expression, IFN-gamma and IL-10 secretion were higher in MoDC. The proportion of CD11c+CD8a+ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-gamma secreting CD8+ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

Immunocell Therapy for Lung Cancer: Dendritic Cell Based Adjuvant Therapy in Mouse Lung Cancer Model

BACKGROUND: The anti-tumor therapeutic effect of autologous tumor cell lysate pulsed-dendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. METHODS: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-r secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. RESULTS: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. CONCLUSION: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

Main Pulmonary Artery Stenosis Caused by Fibrocalcified Mass in a Young Infant

We present a rare case of main pulmonary artery stenosis secondary to protruding fibrous material in the main pulmonary artery associated with patent ductus arteriosus. A 1-month-old baby boy manifested cardiac murmur. Echocardiogram showed circumferential high echogenic mass inside the main pulmonary artery with pressure gradient of 49 mmHg and patent ductus arteriosus. The mass did not regress during 3 months' follow-up period. Angiographic images showed that the circular filling defect was located at the main pulmonary artery distal to pulmonary valve, and pulmonary valve and both pulmonary arteries were normal. After surgical removal of the circumferential material and ductus ligation, the pressure gradient became negligible. The material was consisted of scarcely cellular fibrous tissue, abundant coagulum of fibrinous material and dense calcification.

Use of Quantitative CT to Predict Postoperative Lung Function (Comparison of Quantitative CT and Perfusion Lung Scan) / 대한흉부외과학회지

BACKGROUND: the prediction on changes in the lung function after lung surgery would be an important indicator in terms of the operability and postoperative complications. In order to predict the postoperative FEV1 - the commonly used method for measuring changes in lung function- a comparison between the quantitative CT and the perfusion lung scan was made and proved its usefulness. MATERIAL AND METHOD: The subjects included 22 patients who received perfusion lung scan and quantitative CT preoperatively and with whom the follow-up of PFT were possibles out of the pool of patients who underwent right lobectomy or right pneumonectomy between June of 1997 and December of 1999. The FEV1 and FVC were calibrated by performing the PFT on each patient and then the predicted FEV1 and FVC were calculated after performing perfusion lung scan and quantitative CT postoperatively. The FEV1 and FVC were calibrated by performing the PFT after 1 week and after 3 momths following the surgery. RESULTS: There was a significant mutual scan and the actual postoperative FEV1 and FVC at 1 week and 3 months. The predicted FEV1 and FVC(pneumonectomy group : r=0.962 and r=0.938 lobectomy group ; r=0.921 and r=913) using quantitative CT at 1 week postoperatively showed a higher mutual relationship than that predicted by perfusion lung scan(pneumonectomy group : r=0.927 and r=0.890 lobectomy group : r=0.910 and r=0.905) The result was likewise at 3 months postoperatively(CT -pneumonectomy group : r=0.799 and r=0.882 lobectomy group : r=0.934 and r=0.932) CONCLUSION: In comparison to perfusion lung scan quantitative CT is more accurate in predicting lung function postoperatively and is cost-effective as well. Therefore it can be concluded that the quantitative CT is an effective method of replacing the perfusion lung scan in predicting lung function post-operatively. However it is noted that further comparative analysis using more data and follow-up studies of the patients is required.

Unusual association of pulmonary artery sling with right aortic arch and aberrant left subclavian artery

We present an unusual case of vascular sling, tracheal stenosis by complete cartilaginous ring, and aberrant left subclavian artery with right aortic arch that underwent successful surgical repair for the sling. These abnormalities were suspected from unusual multiple indentations found on esophagogram. Complete preoperative diagnosis was established with chest computerized tomogram combined with angiography.

Tracheobronchial Rupture during Double-lumen Endobronchial Tube Insertion for One-lung Ventilation: 2 cases / 대한마취과학회지

A number of complications during the use of double-lumen endobronchial tubes are reported, specifically tracheobronchial rupture, a rare but serious complication. Risk factors associated with tracheobronchial rupture include inexperienced endoscopists, intubating stylets, multiple vigorous attempts at intubation, overdistension of the tracheal or bronchial cuff with high pressure, position change with an inflated cuff, and anatomical abnormality. We report 2 cases of tracheobronchial rupture which occurred during the use of double-lumen endobronchial tubes.

Brainstem Auditory Evoked Potential and Visual Evoked Potential of High Risk Infants

OBJECTIVE: Maturation of the acoustic and visual pathways in brainstem can be reflected by the brainstem auditory evoked potential(BAEP) and visual evoked potential(VEP) response studies. The purpose of this study was to evaluate the high-risk infants by the BAEP and VEP studies as a screening test for Their brainstem maturities. METHOD: The BAEP and VEP studies were used as a screening test in 142 high-risk infants with 31 to 42 weeks of conceptional age. Further follow-up data were obtained within 1 year in the same infants who showed the abnormal findings in BAEP and VEP at an initial screening test. RESULTS: On an initial BAEP and VEP study, the proportion of the abnormal findings was significantly higher among infants with below 36weeks(53.8%, 28.2%) of conceptional age than above 36 weeks(27.2%, 3.9%). At the follow-up study, 3 of 21 infants with no responses in BAEP and 1 of 6 infants with no responses in VEP on an initial test showed the persistent abnormal findings. However, normal configurations of BAEP and VEP were observed in infants with prolonged latencies or with distorted waveforms of BAEP and VEP at the first examination. CONCLUSIONS: These results suggest that the BAEP and VEP studies on the useful screening tests in infants above 36weeks of conceptional age. Because of the risk of persistent abnormal results, infants with no responses on an initial screening test need a follow-up study.

Comparison between the Electric and Magnetic Stimulations for a Repetitive Nerve Stimulation Test

The low rate repetitive nerve stimulation test(RST) using the electric stimulation has been known the best procedure among the electroliagnostic evaluations for the neuromuscular transmission. However, the electric stimulation often causes a considerable discomfort and pain during the procedure. On the contrary, the magnetic stimulation is much easier and less painful in activating to activate the deep seated nerves. The purpose of this study was to compare the effect of repetitive magnetic and electric stimulation for the induction of compound muscle action potentials(CMAP) of abductor digiti quinti and deltoid muscles in 25 healthy subjects. The results were showed there were no significant differences in the amplitudes of CMAP of axillary and ulnar nerves between the magnetic and electric stimulations. And there were no significant differences in the decremental ratio of CMAP between the magnetic and electric stimulations. The magnetic stimulations were less painful for the subjects than electric stimulations in both proximal and distal muscles. In conclusion, the magnetic stimulation proved to be a useful method for repetitive nerve stimulations in the diagnosis of neuromuscular disease.

Effect of Nitric Oxide on the Viability of Bone Marrow - Derived Cultured Mast Cells / 대한면역학회지

It is well established that mast cell proliferation and maturation are regulated by two principle cytokines, IL-3 and the c-kit ligand stem cell factor (SCF). Previous reports have demonstrated that bone marrow-derived IL-3-dependent mast cells exhibit the characteristic apoptosis on removal of IL-3. To know how the number of mast cells is controlled, we observed the effects of nitric oxide (NO) on the murine bone marrow-derived cultured mast cells (BMCMC). Apoptosis was measured by the analysis of flow cytometric data and electrophoretic evidence of DNA fragmentation. Our data showed that sodiurn nitroprusside (SNP)-a NO releasing substance- induced apoptosis in BMCMC. Cell cycle analysis showed that the number of the G,/G, and S phase decreased markedly, while the percentage of cell in G,/M phase was increased. Also, SNP alone induced cell death, whereas SNP in combination with SCF markedly decreased cell death of BMCMC. SNP-induced apoptosis was partially inhibited by the treatment of BMCMC with SCF. Our results suggest that NO might have sorne role in the regulation of the number of mast cells.

Surgical analysis of mediastinal tumors / 대한흉부외과학회지

No abstract available.

Modified fontan procedure with extracardiac edicardial lateral tunnel: New surgical technique / 대한흉부외과학회지

No abstract available.