Aim To explore the effect of sesquiterpene lactone parthenolide(PL) on primary multiple myeloma(MM) cell and cell lines and its molecular mechanisms.Methods Fresh bone marrow cells from MM patients and MM cell lines KMM-1 and MM1S were used for in vitro culture study.The cell survival rate was examined by Trypan Blue exclusion.The change of nucleolus stained with DAPI was observed under fluorescent microscope.Reactive oxygen species(ROS) levels and mitochondrial membrane potential(MMP) were detected by flow cytometry.Results 2.5 ?mol?L-1 PL induced MM cell apoptosis and MMP was profoundly decreased in KMM-1 and MM1S cells.In contrast,normal lymphocytes cells were unaffected by the same conditions.KMM-1 and MM1S cells showed large increases of ROS levels 10 h after 2.5 ?mol?L-1 PL treatment.The free radical scavenger L-N-acetylcystein(L-NAC) pretreatment completely inhibited ROS generation,cell death and nuclear fragmentation by PL.Diphenylene iodonium chloride(DPI) pretreatment in a dose of 2.5 ?mol?L-1 strongly inhibited PL-mediated ROS generation,nuclear fragmentation in KMM-1 and MM1S cells.Conclusions PL strongly induces apoptosis in MM cell,while normal lymphocytes cells are completely unaffected by the same conditions.Since its proapoptotic activity appears to be mediated through induction of oxidative stress in MM cells,its possible mechanism is that NADPH oxidase activation is involved in PL-mediated ROS generation.

1) A program entitled Doc MMC was broadcast on FM Mie, a local FM radio station.“The Doc MMC Declaration”was performed on this program by residents.
2) The declarations were classified into six groups: “Affection, ”“Contribution to Community Medicine, ”“Knowledge and Skill, ”“Special Training Course Selection or Self-Activation, ”and “Others.”
3) This kind of broadcasting may enhance the motivation of residents and facilitate the understanding of medical issues by the community.

Background:Pancreas ductal adenocarcinoma (PDAC) remains the most malignant digestive disease, but several treatment strategies for PDAC have been developed. Here we describe some current topics regarding the treatment of PDACs in Nagasaki, Japan. 1: Prevention of pancreas fistula (PF) after pancreas resection Adjuvant chemotherapy for PDAC was demonstrated to be useful to prolong patients’ survival after the resection of PDAC. To introduce adjuvant chemotherapy for PDAC quickly, it is important to prevent the development of a PF after pancreas resection. We evaluated the safety and efficacy of early drain removal on postoperative day 1 after distal pancreatectomy (DP; n=71), and we found that early drain removal was safe and effective for preventing grade B/C PFs (0% vs. late removal 16%; p<0.001). 2: Laparoscopic surgery for PDAC Laparoscopic distal pancreatectomy (Lap-DP) for low-grade malignant tumors at the left side of the pancreas has been recognized to be safe and feasible, and a few studies have already obtained similar findings for PDAC compared to open DP. We have been performing the Lap-DP for PDACs without invasion beyond the pancreas, and the modified radical antegrade modular pancreatosplenectomy (mRAMPS) is conducted at our institute. The plexus around the celiac artery or superior mesenteric artery is dissected to a limited extent. Histologically, all of our PDAC patients who underwent a Lap-DP (n=5) achieved an R0 resection. 3: Dendritic cell-based therapeutic vaccination for PDAC The treatment of unresectable or recurrent PDAC is not promising. We started administering a dendritic cell-based therapeutic vaccination in such cases along with the use of the anticancer drugs gemcitabine and/or S-1. A total of eight patients received this therapy, and it seemed that the patients with recurrence after resection and those who had strong delayed-type hypersensitivity around the injected lesion had a favorable prognosis, although the results were obtained with a small number of patients. Conclusions: Our recent treatments for PDAC are feasible and useful. It is important to develop various ways to prolong the survival of PDAC patients.

Background:Pancreas ductal adenocarcinoma (PDAC) remains the mostmalignant digestive disease, but several treatment strategies for PDAC have beendeveloped. Here we describe some current topics regarding the treatment ofPDACs in Nagasaki, Japan.1: Prevention of pancreas fistula (PF) after pancreas resectionAdjuvant chemotherapy for PDAC was demonstrated to be useful to prolongpatients’ survival after the resection of PDAC. To introduce adjuvant chemotherapyfor PDAC quickly, it is important to prevent the development of a PF afterpancreas resection. We evaluated the safety and efficacy of early drain removalon postoperative day 1 after distal pancreatectomy (DP; n=71), and we found thatearly drain removal was safe and effective for preventing grade B/C PFs (0% vs.late removal 16%; p<0.001).2: Laparoscopic surgery for PDACLaparoscopic distal pancreatectomy (Lap-DP) for low-grade malignant tumors atthe left side of the pancreas has been recognized to be safe and feasible, and afew studies have already obtained similar findings for PDAC compared to openDP. We have been performing the Lap-DP for PDACs without invasion beyondthe pancreas, and the modified radical antegrade modular pancreatosplenectomy(mRAMPS) is conducted at our institute. The plexus around the celiac artery orsuperior mesenteric artery is dissected to a limited extent. Histologically, all of ourPDAC patients who underwent a Lap-DP (n=5) achieved an R0 resection.3: Dendritic cell-based therapeutic vaccination for PDACThe treatment of unresectable or recurrent PDAC is not promising. We startedadministering a dendritic cell-based therapeutic vaccination in such cases alongwith the use of the anticancer drugs gemcitabine and/or S-1. A total of eightpatients received this therapy, and it seemed that the patients with recurrenceafter resection and those who had strong delayed-type hypersensitivity aroundthe injected lesion had a favorable prognosis, although the results were obtainedwith a small number of patients.Conclusions:Our recent treatments for PDAC are feasible and useful. It is important to developvarious ways to prolong the survival of PDAC patients.