Olopatadine Suppresses the Migration of THP-1 Monocytes Induced by S100A12 Protein

Olopatadine hydrochloride (olopatadine) is an antiallergic drug with histamine H(1) receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES)-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H(1) receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H(1) receptor antagonistic activity

Kaonic nuclei excited by the (K−,N)(K^-,N) reaction

We show that kaonic nuclei can be produced by the $(K^-,p)$ and $(K^-,n)$ reactions. The reactions are shown to have cross sections experimentally measurable. The observation of the kaonic nuclei gives a kaon-nucleus potential which answers the question on the existence of kaon condensation in dense nuclear matter especially neutron stars

Status of 48Ca double beta decay search in CANDLES

We study a strategy to reduce veto-time in the search for neutrino-less double-beta decay (0υββ) with CANDLES-III system. We develop a new likelihood analysis and apply it to our new Run010 data. We show that we can increase the un-vetoed live-time by 11.8%. Thanks to this improvements, We expect to increase a limit on the life-time of 0υββ by a factor of three by analyzing both Run009 and Run010 data

Upgrading of shielding for rare decay search in CANDLES

In the CANDLES experiment aiming to search for the very rare neutrino-less double beta decays (0νββ) using 48Ca, we introduced a new shielding system for high energy γ-rays from neutron captures in massive materials near the detector, in addition to the background reduction for 232Th decays in the 0νββ target of CaF2 crystals. The method of background reduction and the performance of newly installed shielding system are described

Kaonic Nuclei Excited by the ͑ ͑ ͑K 2 ,N͒ ͒ ͒ Reaction

We show that kaonic nuclei can be produced by the (K 2 , p) and (K 2 , n) reactions. The reactions are shown to have cross sections experimentally measurable. The observation of kaonic nuclei gives a kaon-nucleus potential which answers the question as to the existence of kaon condensation in dense nuclear matter, especially in neutron stars. PACS numbers: 25.80.Nv, 13.75.Ev, 13.75.Jz, 26.60. + c The kaon-nucleon interaction at low energy region is particularly important nowadays because of the current interest in the dense nuclear matter in neutron stars where the so-called kaon condensed state may be achieved by a strong attractive interaction Recently, effective kaon mass in dense nuclear matter has been derived by the chiral SU(3) effective Lagrangian includingKN, pS, and pL systems Experimental data of K 2 optical potential mostly come from kaonic atoms. The shifts and widths of atomic levels affected by the strong interaction were reproduced by introducing an appropriate optical potential in addition to the Coulomb interaction. Recent extensive analysis of kaonic x-ray data concludes that the potential is strongly attractive TheKN interaction has been derived from kaon scattering experiments. However, the available low-energy data are insufficient for unique multichannel analysis, and the existence of L͑1405͒ makes the extrapolation of the amplitude below the threshold complicated If theK-nuclear potential is as attractive as that derived from the kaonic atom studies suggests Energies and widths of kaonic nuclei are calculated with the potential given by the kaonic atom data. For the analysis of mesonic atoms the Klein-Gordon equation is usually used 0031-9007͞99͞83(23)͞4701(4)$15.0

Statins enhances antitumor effect of oxaliplatin in KRAS-mutated colorectal cancer cells and inhibits oxaliplatin-induced neuropathy

Abstract Background KRAS mutations are fraught with the progression of colorectal cancer and resistance to chemotherapy. There are pathways such as extracellular regulated protein kinase 1/2 (ERK1/2) and Akt downstream and farnesylation and geranylgeranylation upstream that are activated upon mutated KRAS. Previous studies have shown that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are effective to treat KRAS mutated colorectal cancer cells. Increased doses of oxaliplatin (L-OHP), a well-known alkylating chemotherapeutic drug, causes side effects such as peripheral neuropathy due to ERK1/2 activation in spinal cords. Hence, we examined the combinatorial therapeutic efficacy of statins and L-OHP to reduce colorectal cancer cell growth and abrogate neuropathy in mice. Methods Cell survival and confirmed apoptosis was assessed using WST-8 assay and Annexin V detection kit. Detection of phosphorylated and total proteins was analyzed the western blotting. Combined effect of simvastatin and L-OHP was examined the allograft mouse model and L-OHP-induced neuropathy was assessed using cold plate and von Frey filament test. Results In this study, we examined the effect of combining statins with L-OHP on induction of cell death in colorectal cancer cell lines and improvement of L-OHP-induced neuropathy in vivo. We demonstrated that combined administration with statins and L-OHP significantly induced apoptosis and elevated the sensitivity of KRAS-mutated colorectal cancer cells to L-OHP. In addition, simvastatin suppressed KRAS prenylation, thereby enhancing antitumor effect of L-OHP through downregulation of survivin, XIAP, Bcl-xL, and Bcl-2, and upregulation of p53 and PUMA via inhibition of nuclear factor of κB (NF-κB) and Akt activation, and induction of c-Jun N-terminal kinase (JNK) activation in KRAS-mutated colorectal cancer cells. Moreover, simvastatin enhanced the antitumor effects of L-OHP and suppressed L-OHP-induced neuropathy via ERK1/2 activation in vivo. Conclusion Therefore, statins may be therapeutically useful as adjuvants to L-OHP in KRAS-mutated colorectal cancer and may also be useful in the treatment of L-OHP-induced neuropathy