Pancreatic cancer is one of the most lethal types of cancer with a mortality rate of almost 95%. Treatment with current chemotherapeutic drugs has limited success due to poor responses. Therefore, the development of novel drugs or effective combination therapies is urgently required. Piperlongumine (PL) is a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular reactive oxygen species (ROS) levels. In the present study, we demonstrated that PL induced cancer cell death through, at least in part, the induction of ferroptosis, as the cancer cell-killing activity was inhibited by the antioxidant, N‑acetylcysteine, ferroptosis inhibitors (ferrostatin‑1 and liproxstatin‑1) and the iron chelator, deferoxamine (DFO), but not by the apoptosis inhibitor, Z-VAD-FMK, or the necrosis inhibitor, necrostatin‑1. Cotylenin A (CN‑A; a plant growth regulator) exhibits potent antitumor activities in several cancer cell lines, including pancreatic cancer cell lines. We found that CN‑A and PL synergistically induced the death of pancreatic cancer MIAPaCa‑2 and PANC‑1 cells for 16 h. CN‑A enhanced the induction of ROS by PL for 4 h. The synergistic induction of cell death was also abrogated by the ferroptosis inhibitors and DFO. The present results revealed that clinically approved sulfasalazine (SSZ), a ferroptosis inducer, enhanced the death of pancreatic cancer cells induced by PL and the combined effects were abrogated by the ferroptosis inhibitors and DFO. SSZ further enhanced the cancer cell-killing activities induced by combined treatment with PL plus CN‑A. On the other hand, the synergistic induction of cell death by PL and CN‑A was not observed in mouse embryonic fibroblasts (MEFs), and SSZ did not enhance the death of MEFs induced by PL plus CN‑A. These results suggest that the triple combined treatment with PL, CN‑A and SSZ is highly effective against pancreatic cancer.

ObjectiveTo better define the clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome (AAHS) in adults.MethodsAdults with AAHS (defined as pathologic evidence of hemophagocytosis without any obvious cause other than an autoimmune disease) were identified through a review of the literature.ResultsAmong 116 patients identified, underlying diseases included systemic lupus erythematosus (SLE) in 52.3%, adult-onset Still's disease (AOSD) in 26.7%, and dermatomyositis in 6.9%. Fever, lymphadenopathy, hepatomegaly, and splenomegaly were found in 86.8%, 41.0%, 41.8%, and 45.5% of patients, respectively. Cytopenia, liver dysfunction, and hyperferritinemia developed frequently, and coagulopathy was seen in 50.6% of patients. Normal or low C-reactive protein levels were characteristic of patients with underlying SLE. The most commonly used therapy was corticosteroids, which were initially administered in 95.7% of patients, with 57.7% responding. Patients with corticosteroid-refractory disease were usually treated with cyclosporine, intravenous cyclophosphamide (IV CYC), or intravenous immunoglobulin (IVIG), with IV CYC being highly effective. Treatment with biologic agents resulted in favorable effects in the majority of patients. The mortality rate was 12.9%. Male sex (odds ratio [OR] 6.47, 95% confidence interval [95% CI] 2.06–30.39, P < 0.01), dermatomyositis (OR 5.57, 95% CI 1.08–28.65, P < 0.05), and anemia (hemoglobin <8 gm/dl; OR 3.74, 95% CI 1.02–13.8, P < 0.05) were identified as factors associated with mortality.ConclusionAAHS is potentially fatal. Corticosteroids are a mainstay of initial treatment. For corticosteroid-refractory disease, IV CYC may be beneficial as compared with cyclosporine or IVIG. Treatment that proceeds directly from corticosteroids to biologic agents is promising.

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SUMMARYA seroprevalence survey on measles, mumps, rubella and varicella was conducted on healthcare workers (HCWs) at Shimane University Hospital, Japan utilizing an enzyme immunoassay. Of 1811 HCWs tested, 91·8% were seropositive to measles, 92·1% to mumps, 89·5% to rubella and 96·3% to varicella. Sex-related differences in seroprevalence were found in rubella (males vs. females: 84·7 vs. 92·2%, P < 0·001). Moreover, males aged 30–39 years were most susceptible to rubella (22·4%), which may be attributed to the design of childhood immunization programmes in Japan. Individuals aged ⩽29 years were more susceptible to measles (14·3%) and mumps (10·9%), compared to other age groups. There were no significant sex- and age-related differences in varicella seroprevalence. The physician occupational group was more susceptible to rubella, but no significant occupational-related difference was observed in the other diseases. Susceptible subjects, with negative or equivocal serological results were given a vaccine which induced seroconversion in most vaccinees. Seroconversion occurred more frequently in the equivocal group than in the negative group. These findings provide a new insight for the seroprevalence survey of vaccine-preventable diseases in Japanese HCWs with special reference to vaccine efficacy.