Final Results of a Phase II Study of Bevacizumab, Cisplatin and Pemetrexed as First-Line Therapy for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

Background: Efficacy and safety data for cisplatin and pemetrexed plus bevacizumabinnon squamousnon non-small cell lung cancer (NSCLC) are still limited. Nevertheless, either bevacizumab plus platinum doublet or pemetrexed plus platinum is approved options for first line therapy. Predictive factors for bevacizumab are needed. KRAS is one of the most common oncogenic drivers in lung cancer. Its prognostic and predictive value in NSCLC is under investigation. Patients and methods: This trial evaluates the addition of bevacizumab 7.5 mg/kg to cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 as first line treatment in stage IV non-squamous NSCLC patients. Maintenance bevacizumab was received as monotherapy until progressive disease, unacceptable toxicityor consent with drawal. The primary objective was progression free survival (PFS). Secondary objectives included overall survival (OS), safety, global objective responses and the determination of KRAS mutation at baseline. Results: From March 2009 to March 2012, 31 patients were enrolled. Mean age was 59.19 (standard deviation (SD) 8.53). From all the patients included in this trial, 67.70% were men. KRAS was wild type in 19 patients (58.06%);in 7 (22.58%) was mutated and was unknown in 6 patients (19.35%). Median PFS for KRAS mutated patients was 4 months, whereas for the KRAS wild type it was 7.9 months (P = 0.0031). Median OS was 4 months for the KRAS population, and 16.1 months for the KRAS wild type (P = 0.0032). Twenty four patients (77.42%) experienced at least a grade 3 - 4 adverse event. The most common grade 3 - 4 toxicity was asthenia. Conclusions: Both PFS and OS were statistically longer for the KRAS wild type patients compared with the KRAS mutated population (P = 0.0031). Median OS was shorter than the reported in previous trials with bevacizumab. Nevertheless, focussing on the OS for KRAS wild type patients, this achieves a result or 16.1 months. Therefore, this would be a consistent data supporting to qualify this parameter as a predictive factor before starting treatment for NSCLC.

Effects of fire history on animal communities:a systematic review

Fire is a natural agent with a paramount role in ecosystem functioning and biodiversity maintenance.Still,it can also act as a negative force against many ecosystems.Despite some knowledge of the interactions of fire and vegetation,there is no clear understanding of how different components of fire regimes(i.e.,severity,history,or frequency)influence known patterns of animal communities.Therefore,we performed a systematic review on the global responses of arthropods,birds,mammals,reptiles,and amphibians to different fire regimes.Specifically,we focused on assessing how fire severity,history,and frequency modulate the effect of fire on the richness and abundance of faunal communities.We conducted a systematic review of 566 papers retrieved from the Scopus database.We also scrutinized all the documents included in the meta‑analysis of Pastro et al.(Pastro et al.Glob Ecol Biogeogr 23:1146–1156,2014).Our selection criteria excluded studies without data on species richness or abundance.We also excluded studies without adequate controls and those without information about the fire regime of the study zone.After careful examination,we used data from 162 studies to perform a quantitative meta‑analysis.From the 162 studies meeting our selection criteria,nearly 60%of the studies are from North America,25%from Australia,11%from Europe,and 4%from the tropics.According to the ecological role of fire,90%of the studies were carried out in fire‑dependent ecosystems(i.e.,conifer forests,natural savannas,pastures).Finally,40%of the studies analyzed birds,22%mammals,and 20%arthropods.The meta‑analysis of the available evidence indicates that fire history is an important modulator of animal richness and abundance.Whether negative or positive,animal responses depended on the time since the last fire event.Considering that short‑term studies may not capture such a long‑term effect on fauna,this translates to more challenges at implementing fire management strategies.Whether or not we can anticipate the impact of the fire will then depend on future efforts to implement long‑term research.

Extensive pollen immigration and no evidence of disrupted mating patterns or reproduction in a highly fragmented holm oak stand

Aims Forest fragmentation and reduced tree population densities can poten-tially have negative impacts on mating patterns,offspring genetic diversity and reproductive performance.the aim of the present study is to test these hypotheses comparing an extremely fragmented,low tree density(~0.02 trees/ha)holm oak(Quercus ilex l.)stand from Central spain with a nearby high tree density stand(~50 trees/ha).Methods We genotyped adult trees and seeds from the low-density stand(436 seeds from 15 families)and the high-density stand(404 seeds from 11 families)using nine microsatellite markers.With these data,we performed paternity analyses,determined pollen flow,mating patterns and pollen pool structure,and estimated progeny genetic diversity in both stands.We also studied seed set and production and performed a pollen supplementation experiment to determine whether reduced tree density has limited foreign pollen availability.Important Findings We have found extensive pollen immigration(>75%)into the low tree density stand and monte Carlo simulations revealed that pollen moves larger distances than expected from null models of random dispersal.mating patterns and differentiation of pollen pools were similar in the high-density stand and the low-density stand but we found higher inter-annual differentiation of pollen pools in the for-mer.Progeny genetic diversity and self-fertilization rates did not dif-fer between the low-density stand and the high-density stand.seed set rates were significantly lower in the low-density stand than in the high-density stand and experimental cross-pollen supplementation evidenced that foreign pollen availability is indeed a limiting factor in the former.However,seed crops did not differ between the low-density stand and the high-density stand,indicating that limitation of foreign pollen is not likely to be of great concern in terms of reduced seed production and potential recruitment.Poor forest regeneration due to other ecological and human factors is probably a more important threat for the persistence of fragmented and low tree density stands than reduced pollen flow and only extremely small and isolated tree populations would be expected to suffer severe loss of genetic diversity in the long term.

p38γand p38δas biomarkers in the interplay of colon cancer and inflammatory bowel diseases

Dear Editor,Colorectal cancer(CRC)is the second leading cause of cancer death according to the World Health Organization.Patients with inflammatory bowel disease(IBD),ulcerative colitis(UC)or Crohn’s disease(CD)are at increased risk of developing colitis-associated CRC(CAC)[1];however,our understanding of the inflammationcancer interplay at the molecular level is still limited.