Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation

Although lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B₄ receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (Kras^G12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a Kras^G12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.Subject terms: Non-small-cell lung cancer, Lipid signalling     

Microstructural investigation of high‐speed melt‐spun nylon 6 fibers produced with variable spinning speeds

The structural details of high‐speed melt‐spun nylon 6 fibers at spinning speeds ranging from 4500 to 6100 m/min were investigated by solid‐state proton nuclear magnetic resonance (¹H NMR) spectroscopy, density and birefringence measurements, differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). The analyses of the proton spin‐lattice relaxation times in the rotating frame and correlation times confirmed the existence of three different phases, the immobile crystalline, intermediate rigid amorphous, and mobile amorphous regions, in the fiber sample. At spinning speeds lower than 5200 m/min, the portion of the crystalline phase increased at the expense of the rigid amorphous region and then reached a plateau afterward, from which the mobile amorphous portion increased. Combined analyses of density and birefringence measurements, DSC, and XRD in conjunction with NMR results indicated that the formation of the γ crystal became predominant compared to that of the α crystal. The orientation factor of the crystalline phase increased slightly with increasing spinning speed, whereas the amorphous orientation factor decreased because of the increase of the purely amorphous region. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1285–1293, 2000     

Regular fourfold coverings with respect to the identity automorphism

The aim of this paper is to count the isomorphism classes of regular fourfold coverings of a graph with respect to the identity automorphism, as M. Hofmeister did for double coverings. © 1993 John Wiley & Sons, Inc.     

Nonorientable triangular embeddings of complete graphs with arbitrarily large looseness

The looseness of a triangular embedding of a complete graph in a closed surface is the minimum integer m such that for every assignment of m colors to the vertices of the embedding (such that all m colors are used) there is a face incident with vertices of three distinct colors. In this paper we show that for every p?3 there is a nonorientable triangular embedding of a complete graph with looseness at least p.     

Detection of single nucleotide insertion of BCR/ABL region in imatinib-resistant human myelogenous leukemia SR-1 cells

Imatinib mesylate is a selective Bcr/Abl kinase inhibitor and an effective anticancer agent for Bcr/Abl-positive chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Mutations within the BCR/ABL kinase domain are the most commonly identified mechanism associated with relapse. To overcome the imatinib resistance in CML, many investigators have tried to clarify molecular mechanism for imatinib resistance in cells of patients who failed to respond to imatinib. Our aim was to invesitigate underlying mechanism for imatinib resistance in SR-1 cells, which were derived from a CML patient in blast crisis. We detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression, which might be possible mechanism for the resistance to imatinib in SR-1 cells.     

Smooth projective varieties with extremal or next to extremal curvilinear secant subspaces

We intend to give a classification of smooth nondegenerate projective varieties admitting extremal or next to extremal curvilinear secant subspaces. Gruson, Lazarsfeld and Peskine classified all projective integral curves with extremal secant lines. On the other hand, if a locally Cohen-Macaulay variety of degree meets with a linear subspace of dimension at finite points, then as a finite scheme. A linear subspace for which the above length attains maximal possible value is called an extremal secant subspace and such for which is called a next to extremal secant subspace.

In this paper, we show that if a smooth variety of degree has extremal or next to extremal curvilinear secant subspaces, then it is either Del Pezzo or a scroll over a curve of genus . This generalizes the results of Gruson, Lazarsfeld and Peskine (1983) for curves and the work of M-A. Bertin (2002) who classified smooth higher dimensional varieties with extremal secant lines. This is also motivated and closely related to establishing an upper bound for the Castelnuovo-Mumford regularity and giving a classification of the varieties on the boundary.

     

Measurements of the mass, total width, and two-photon partial width of the eta(c) meson

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.     

Production and decay of F+(2030) observed in νμ interactions in emulsion

An event representing the production and decay of the charmed F⁺ meson has been identified by means of a 3-constraint fit to decay hypothesis F⁺ → π⁺π⁺π^?π⁰, in which both γ-rays from the π⁰ converted. The event was produced by a charged current ν_μ interaction in an emulsion stack located inside the Fermilab 15-foot bubble chamber. The F⁺ traveled 50 μm, corresponding to a proper time of 1.4 × 10^?13 seconds, before decaying in flight. Its mass was determined to be 2017 ± 25MeV.