Bcl-2 is a central regulator of cell survival that is overexpressed in the majority of small cell lung cancers (SCLC) and contributes to both malignant transformation and therapeutic resistance. We compared primary SCLC xenografts prepared from de novo human tumors with standard cell line-based xenografts in the evaluation of a novel and highly potent small molecule inhibitor of Bcl-2, ABT-737. ABT-737 induced dramatic regressions in tumors derived from some SCLC cell lines. In contrast, only one of three primary xenograft SCLC tumors showed significant growth inhibition with ABT-737. Explanations for this apparent dichotomy may include relatively low expression of Bcl-2 in the primary xenografts or inherent differences in the model systems. The addition of etoposide to ABT-737 in the primary xenografts resulted in significant decreases in tumor growth, underscoring the clinical potential of ABT-737 in combination therapy. To identify factors that may contribute to resistance to ABT-737 and related inhibitors, we isolated resistant derivatives of an initially sensitive cell line-based xenograft. Acquired resistance in this model was associated with decreases in the expression of the primary target Bcl-2, of proapoptotic partners of Bcl-2 (Bax and Bim), and of Bcl-2:Bim heterodimers. Expression profiling reveals 85 candidate genes demonstrating consistent changes in gene expression with acquired resistance. Taken together, these data have specific implications for the clinical development of Bcl-2 inhibitors for SCLC and broader implications for the testing of novel anticancer strategies in relevant preclinical models. [Cancer Res 2008;68(7):2321-8]

This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

No abstract

No abstract

On the basis of tri-section stepped-impedance resonator (SIR), a novel triple-band bandpass filter (BPF) is presented, which has a triple-band feature of three passbands at desired frequencies and high out-of-band suppression. The new coupling scheme at the input and output can improve the performance of the BPF, and the hairpin structure helps to reduce the size. A microstrip filter was designed and simulated, proving the concept in an excellent way. The prototype of the BPF achieved insertion loss of 2.2, 1.8 and 1.7 dB at 1.0, 2.4, 3.6 GHz, respectively.Index Terms--Triple-band filter, stepped-impedance resonator (SIR), bandpass filter (BPF), microstrip, hairpin.

No abstract

No abstract

No abstract