ABSTRACT
Background@#and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. @*Conclusion@#This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).
ABSTRACT
OBJECTIVE: Multidrug resistance to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The aim of this study is to establish secondary anticancer drug resistant cell line from original SNU-8/WT resistant to cisplatin and characterize it. METHODS: After establishing secondary drug resistant cell line (SNU-8/Fac), drug sensitivity was measured by MTT assay. Multidrug resistance (MDR) was analyzed by RT-PCR and western blotting analysis. RESULTS: MTT assay data demonstrated that MDR was expressed in SNU-8/Fac. In addition, mRNA expression of MDR1, ATP7B in SNU-8/Fac was increased. However, overexpression of MRP1, BCRP, TS and MT mRNA was not observed. At the protein level, protein P-gp, ATP7B were overexpressed in SNU-8/Fac. CONCLUSION: We established a new anticancer drug resistant cell line from original SNU-8/WT. Overexpression of P-gp and ATP7B was observed in SNU-8/Fac.
Subject(s)
Humans , Blotting, Western , Cell Line , Cisplatin , Drug Resistance, Multiple , Drug Therapy , Ovarian Neoplasms , ATP Binding Cassette Transporter, Subfamily B, Member 1 , RNA, MessengerABSTRACT
OBJECTIVE: Resistant, recurrent ovarian cancer patients who had first chemotherapy with Cisplatin have showed low reactivity and high recurrence in the secondary chemotherapy. Therefore, multi-drug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian cancer patients. The aim of our study is to analyze the sensitivity of some chemotherapy drugs when we co-use Cyclosporine A (CsA), which suppresses MDR, in the secondary drug resistant cell line. METHODS: After establishing the secondary drug resistant cell line, drug sensitivity was measured by MTT assay. MDR gene and protein were analyzed by RT-PCR and western blotting assay. RESULTS: MDR gene (MDR1) and protein (P-gp) were overexpressed in the secondary drug resistant cell line. When we measured the sensitivity of some chemotherapy drug after using the amounts of CsA that can suppress MDR1/P-gp, the sensitivity of Paclitaxel was highest. CONCLUSION: CsA has a role that makes the sensitivity of chemotherapy drug higher in the secondary drug resistant cell line by suppression of multi-drug resistance. Therefore, we could expect that the proper use of MDR suppresser like CsA with secondary chemotherapy drug would help to cure resistant, recurrent ovarian cancer patients.