번호 | 연구제목 | 연구자 | 연구기간 | 발표실적 |
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내용 | ||||
15 | Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons | 이지환, 강주안, 양은희, 김우진, 진영호 | 2020-09-30 ~ | 학회지 |
Oxaliplatin is a third-generation platinum-based chemotherapeutic drug widely used in colorectal cancer treatment. Although potent against this tumor, it can induce cold and mechanical allodynia even after a single injection. The currently used drugs to attenuate this allodynia can also cause unwanted eects, which limit their use. Bee venom acupuncture (BVA) is widely used in Korean medicine to treat pain. Although the eect of BVA on oxaliplatin-induced neuropathic pain has been addressed in many studies, its action on dorsal root ganglia (DRG) neurons has never been investigated. A single oxaliplatin injection (6 mg/kg, intraperitoneally) induced cold and mechanical allodynia, and BVA (0.1 and 1 mg/kg, subcutaneous, ST36) dose-dependently decreased allodynia in rats. On acutely dissociated lumbar 4?6 DRG neurons, 10 min application of oxaliplatin (100 M) shifted the voltage-dependence of sodium conductance toward negative membrane potentials in A- but not C-fibers. The resting membrane potential remained unchanged, but the action potential threshold decreased significantly compared to that of the control (p < 0.05). However, 0.1 g/mL of BVA administration increased the lowered action potential threshold. In conclusion, these results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber DRG neurons. |
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14 | Evaluation of the Efficacy and Safety of the Herbal Formula PM014 in a Cisplatin- and Paclitaxel-Treated Tumor-Bearing Mouse Model | 이찬주, 정현주, 이광현, 박세현, 강미정, 배수경, 배현수 | 2020-06-26 ~ | 학회지 |
PM014 (HL301) is a standardized herbal mixture derived from a traditional Korean medicine, Chung-Sang-Bo-Ha-Tang. Previously, we reported that PM014 treatment significantly suppressed pulmonary fibrosis, one of the frequent adverse effects of anticancer therapy in lung cancer. Before the clinical application of PM014 in anticancer therapy, the safety and efficacy of PM014 in combination with conventional anticancer drugs should be addressed to determine whether PM014 can be used in lung cancer. Lewis lung cancer?bearing mice were injected with 10 mg/kg of cisplatin or paclitaxel on day 5. Starting on day 7, the mice were administered 200 mg/kg PM014 every 2 days. On day 15, all mice were assessed by biochemical and histological analyses. PM014 did not block the antitumor activity of cisplatin and paclitaxel. Coadministration of PM014 and antitumor agents did not elevate the aspartate transaminase/alanine transaminase ratio or the blood urea nitrogen/creatinine ratio. Histopathological analysis also showed that PM014 did not induce hepatic or renal injury. Moreover, PM014 had no apparent inhibitory effects on drug metabolizing enzymes, indicating that PM014 did not alter the pharmacokinetics of chemotherapeutic drugs. Overall, these data show the safety and compatibility of combination therapy of PM014 and chemotherapies for the treatment of lung cancer. | ||||
13 | Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide | 이찬주, 정현주, 배용현, 신경문, 강신우, 김익경, 오재영,배현수 | 2019-06-07 ~ | 학술대회 |
Background: Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating immune cells. Macrophages are broadly categorized as M1 or M2 types, and TAMs have been shown to express an M2-like phenotype. TAMs promote tumor progression and contribute to resistance to chemotherapies. Therefore, M2-like TAMs are potential targets for the cancer immunotherapy. In this study, we targeted M2-like TAMs using a hybrid peptide, MEL-dKLA, composed of melittin (MEL), which binds preferentially to M2-like TAMs, and the pro-apoptotic peptide d (KLAKLAK)2 (dKLA), which induces mitochondrial death after cell membrane penetration. Methods: The M1 or M2-differentiated RAW264.7 cells were used for mitochondrial colocalization and apoptosis test in vitro. For in vivo study, the murine Lewis lung carcinoma cells were inoculated subcutaneously in the right flank of mouse. The dKLA, MEL and MEL-dKLA peptides were intraperitoneally injected at 175 nmol/kg every 3 days. Flow cytometry analysis of tumor-associated macrophages and immunofluorescence staining were performed to investigate the immunotherapeutic effects of MEL-dKLA. Results: We showed that MEL-dKLA induced selective cell death of M2 macrophages in vitro, whereas MEL did not disrupt the mitochondrial membrane. We also showed that MEL-dKLA selectively targeted M2-like TAMs without affecting other leukocytes, such as T cells and dendritic cells, in vivo. These features resulted in lower tumor growth rates, tumor weights, and angiogenesis in vivo. Importantly, although both MEL and MEL-dKLA reduced numbers of CD206 M2-like TAMs in tumors, only MEL-dKLA induced apoptosis in CD206 M2-like TAMs, and MEL did not induce cell death. Conclusion: Taken together, our study demonstrated that MEL-dKLA could be used to target M2-like TAMs as a promising cancer therapeutic agent. |
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12 | Intratracheal Ovalbumin Administration Induces Colitis Through the IFN-γ Pathway in Mice | 정경화, 신다솜, 김세준, 민다은, 김우경, 김진주, 이기현, 배현수 | 2019-03-21 ~ | 학술대회 |
Recent studies have reported an increased incidence of inflammatory bowel disease (IBD) in patients with pulmonary diseases. Despite clinical and epidemiological studies of the interplay between colitis and asthma, the diseases’ related underlying mechanisms remain unclear. In this study, we evaluated the development of colitis in a model of allergic airway inflammation. We revealed that intratracheal chronic ovalbumin (OVA) exposure induces colitis and allergic airway inflammation. Interestingly, induction of colitis was largely regulated by Th1, rather than Th2 responses, whereas allergic airway inflammation was primarily mediated by Th2 responses. Experiments in Tbx21 (T-bet) and Ifng (IFN-g) deficient mice have confirmed that IFN-g is a major mediator involved in OVA-induced colitis. These findings broaden current understanding of allergen induced colitis pathology and could play a role in the development of novel clinical treatment strategies for asthmatic patients who are at risk of developing colitis. |