ABSTRACT
Mutualisms play a critical role in ecological communities; however, the importance and prevalence of mutualistic associations can be modified by external stressors. On coral reefs, elevated sediment deposition can be a major stressor reducing the health of corals and reef resilience. Here, we investigated the influence of severe sedimentation on the mutualistic relationship between small damselfishes (Pomacentrus moluccensis and Dascyllus aruanus) and their coral host (Pocillopora damicornis). In an aquarium experiment, corals were exposed to sedimentation rates of approximately 100 mg cm-2 d-1, with and without fishes present, to test whether: (i) fishes influence the accumulation of sediments on coral hosts, and (ii) fishes moderate partial colony mortality and/or coral tissue condition. Colonies with fishes accumulated much less sediment compared with colonies without fishes, and this effect was strongest for colonies with D. aruanus (fivefold less sediment than controls) as opposed to P. moluccensis (twofold less sediment than controls). Colonies with symbiont fishes also had up to 10-fold less sediment-induced partial mortality, as well as higher chlorophyll and protein concentrations. These results demonstrate that fish mutualisms vary in the strength of their benefits, and indicate that some mutualistic or facilitative interactions might become more important for species health and resilience at high-stress levels.
ABSTRACT
PURPOSE: The primary objective of this phase I dose-escalation study was to identify the maximum tolerated dose (MTD) of sunitinib plus pemetrexed in patients with advanced cancer. METHODS: Using a 3 + 3 dose-escalation design, patients received oral sunitinib qd by continuous daily dosing (CDD schedule; 37.5 or 50 mg) or 2 weeks on/1 week off treatment schedule (Schedule 2/1; 50 mg). Pemetrexed (300-500 mg/m(2) IV) was administered q3w. At the proposed recommended phase 2 dose (RP2D), additional patients with non-small cell lung cancer (NSCLC) were enrolled. RESULTS: Thirty-five patients were enrolled on the CDD schedule and seven on Schedule 2/1. MTDs were sunitinib 37.5 mg/day (CDD/RP2D) or 50 mg/day (Schedule 2/1) with pemetrexed 500 mg/m(2). Dose-limiting toxicities included grade (G) 5 cerebral hemorrhage, G3 febrile neutropenia, and G3 anorexia. Common G3/4 drug-related non-hematologic adverse events (AEs) at the CDD MTD included fatigue, anorexia, and hand-foot syndrome. G3/4 hematologic AEs included lymphopenia, neutropenia, and thrombocytopenia. No significant drug-drug interactions were identified. Five (24%) NSCLC patients had partial responses. CONCLUSIONS: In patients with advanced solid malignancies, the MTD of sunitinib plus 500 mg/m(2) pemetrexed was 37.5 mg/day (CDD schedule) or 50 mg/day (Schedule 2/1). The CDD schedule MTD was tolerable and demonstrated promising clinical benefit in NSCLC.
