Abstract. Lung cancer is still the leading cause of cancerrelated deaths worldwide. Identifying new oncogenic drivers and developing efficient inhibitors through molecular targeting approaches are crucial for improving therapies. The aim of this study was to investigate whether targeting fibroblast growth factor receptor 1 (FGFR1) with ponatinib inhibits the cell growth in both established and primary lung cancer cells overexpressing FGFR1. Eighty-eight non-small cell lung cancer (NSCLC) and paired normal tissue specimens were analyzed by real-time RT-PCR for FGFR1 gene expression. We identified four cell lines and two newly established primary lung cancer cultures that showed high FGFR1 expression levels, and evaluated the effect of the novel FGFR1 inhibitor ponatinib on cell growth. Approximately 50% (30 out of 59) NSCLC specimens expressed FGFR1 >2-fold compared with their adjacent normal counterparts using quantitative RT-PCR. Ponatinib treatment of established NSCLC cell lines expressing higher levels of FGFR1 resulted in marked cell growth inhibition and suppression of clonogenicity. This growth inhibition was associated with inactivation of FGFR1 and its downstream targets. FGFR1 knockdown by shRNA achieved similar results when compared to treatment with ponatinib. Furthermore, ponatinib was able to significantly inhibit the growth of primary lung cancer cultures in vitro. Our data indicate that pharmacological inhibition of FGFR1 kinase activity with ponatinib may be effective for the treatment of lung cancer patients whose tumors overexpress FGFR1.
The wild species, Thinopyrum intermedium. (Genome StStJSJSJJ), serves as a valuable germplasm resource providing novel genes for wheat improvement. In the current study, non-denaturing fluorescence in situ hybridization (ND-FISH) with multiple probes and comparative molecular markers were applied to characterize two wheat-Th. intermedium chromosome additions. Sequential ND-FISH with new labeled Th. intermedium specific oligo-probes were used to precisely determine the chromosomal constitution of Th. intermedium, wheat—Th. intermedium partial amphiploids and addition lines Hy36 and Hy37. The ND-FISH results showed that the added JS-St translocated chromosomes in Hy36 had minor Oligo-5S ribosomal DNA (rDNA) signals at the short arm, while a pair of J-St chromosomes in Hy37 had major Oligo-pTa71 and minor Oligo-5S rDNA signals. The 90K SNP array and PCR-based molecular markers that mapped on wheat linkage group 5 and 3 facilitated the identification of Thinopyrum chromosome introgressions in the addition lines, and confirmed that added chromosomes in Hy36 and Hy37 were 5JSS.3StS and 5JS.3StS, respectively. Complete coding sequences at the paralogous puroindoline-a (Pina) loci from Th. intermedium were cloned and localized on the short arm of chromosome 5JS of Hy36. Line Hy36 showed a reduction in the hardness index, which suggested that Th. intermedium-specific Pina gene sequences may be associated with the softness trait in wheat background. The molecular cytogenetic identification of novel wheat—Th. intermedium derivatives indicated that the frequent chromosome rearrangement occurred in the progenies of wheat-Thinopyrum hybridization. The new wheat-Thinopyrum derived lines may increase the genetic diversity for wheat breeding.
Quasi-periodic planar metamaterials substrate, Appl Phys Lett 86 (2005), 121108 -121111. 25. D.R. Smith, D.C. Vier, T. Koschny, and C.M. Soukoulis, Electromagnetic parameter retrieval from inhomogeneous metamaterials, Phys Rev E Stat Nonlin Soft Matter Phys 71 (2005), 036617-0366118). 26. H. Chen, B.I. Wu, L. Ran, T.M. Grzegorczyk, and J.A. Kong, Robust method to retrieve the constitutive effective parameters of metamaterials, Phys Rev E Stat Nonlin Soft Matter Phys 70 (2004), 016608 -0166015. ABSTRACT: Effective microwave hyperthermia of cancer is proposed by using slightly lossy flat left-handed material lenses. High-resolution focusing of microwave without any auxiliary foci can be achieved in tissue by jointly adjusting the sources behind the flat lenses. Two-dimensional numerical simulations demonstrate that, for tumor of diameter of 0.6 cm immersed in lossy breast tissue, microwave power can be effectively localized in tumor volume and temperature in tumor may be raised to ϳ43.5°C, while keeps below 42°C in the surrounding normal tissue as required in hyperthermia treatment. The proposed ⌫-shaped two-lens system is proved to an efficient scheme for microwave hyperthermia. Figure 1 Potential schemes for microwave hyperthermia by using flat LHM lenses: (a) two-lens system; (b) four-lens system ABSTRACT: A novel dual-mode filter using circular high-order mode cavities based on substrate integrated waveguide technology is presented. Its dual-mode character and transmission responses are carefully investigated. Filters in both Ka-and Q-band using two congruent cavities in folded configuration are designed, fabricated with standard PCB process, and measured. Small insertion loss, flat group delay, and good tolerance are observed, which is consistent with the simulation.
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