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Bioactive gibberellin (GA) regulates the growth and development of a wide array of plant species. GA exerts its effects via members of the DELLA protein family of putative transcriptional regulators. The GAI gene encodes GAI, a DELLA protein from Arabidopsis thaliana (L.) Heyhn. A mutant allele, gai, encodes a mutant protein (gai) that has altered properties, and confers a dominant, reduced GA-response, dwarf phenotype. Here we describe experiments to investigate the effects of transgenic expression of GAI and gai in tobacco. Constructs permitting the expression of the GAI and gai open reading frames (ORFs) at higher (driven by the cauliflower mosaic virus 35S promoter) and lower (driven by the original Arabidopsis GAI promoter) levels in tobacco were made. We show that low-level expression of GAI has no detectable effect on tobacco GA-responses. In contrast, high-level expression of GAI clearly affects the growth of adult tobacco plants and the GA-responsiveness of tobacco hypocotyls. Both low- and high-level expression of gai have effects on tobacco GA responses. Thus, tobacco GA-responses are affected by transgenic expression of GAI/gai, and the degree to which these responses are affected is related to the level of transgene expression. [ABSTRACT FROM AUTHOR]

Purpose: PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m(2) or paclitaxel 200 mg/m(2) combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS)., Results: Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug-related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev., Conclusion: OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.