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Background Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. Subjects, materials, and methods An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. Results Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend .018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10-10.33) and median OS was 7.31 months (3.70-14.03). The treatment was associated with mild toxicity. Conclusion Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. Implications for practice A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who are frequently elderly or frail. The assessment of geriatric parameters in the decision-making process can contribute to direct toward the most appropriate therapeutic plan and preserve the quality of life of patients. Eribulin does not seem to affect quality of life or worsen the overall geriatric status; therefore, it can be considered a suitable option for elderly patients with metastatic breast cancer.

Arundo donax L. is an invasive grass species with high tolerance to a wide range of environmental stresses. The response of potted A. donax plants to soil stress characterized by prolonged exposure (43 days) to salinity (+Na), to high concentration of phosphorus (+P), and to the combination of high Na and P (+NaP) followed by 14 days of recovery under optimal nutrient solution, was investigated along the entire time-course of the experiment. After an exposure of 43 days, salinity induced a progressive decline in stomatal conductance that hampered A. donax growth through diffusional limitations to photosynthesis and, when combined with high P, reduced the electron transport rate. Isoprene emission from A. donax leaves was stimulated as Na+ concentration raised in leaves. Prolonged growth in P-enriched substrate did not significantly affect A. donax performance, but decreased isoprene emission from leaves. Prolonged exposure of A. donax to + NaP increased the leaf level of H2O2, stimulated the production of carbohydrates, phenylpropanoids, zeaxanthin and increased the de-epoxidation state of the xanthophylls. This might have resulted in a higher stress tolerance that allowed a fast and full recovery following stress relief. Moreover, the high amount of ABA-glucose ester accumulated in leaves of A. donax exposed to + NaP might have favored stomata re-opening further sustaining the observed prompt recovery of photosynthesis. Therefore, prolonged exposure to high P exacerbated the negative effects of salt stress in A. donax plants photosynthetic performances, but enhanced activation of physiological mechanisms that allowed a prompt and full recovery after stress.

Drought compromises plant's ability to replace transpired water vapor with water absorbed from the soil, leading to extensive xylem dysfunction and causing plant desiccation and death. Short-term plant responses to drought rely on stomatal closure, and on the plant's ability to recover hydraulic functioning after drought relief. We hypothesize a key role for abscisic acid (ABA) not only in the control of stomatal aperture, but also in hydraulic recovery. Young plants of Populus nigra L. were used to investigate possible relationships among ABA, non-structural carbohydrates (NSC) and xylem hydraulic function under drought and after re-watering. In Populus nigra L. plants subjected to drought, water transport efficiency and hydraulic recovery after re-watering were monitored by measuring the percentage loss of hydraulic conductivity (PLC) and stem specific hydraulic conductivity (Kstem). In the same plants ABA and NSC were quantified in wood and bark. Drought severely reduced stomatal conductance (gL) and markedly increased the PLC. Leaf and stem water potential, and stem hydraulic efficiency fully recovered within 24 h after re-watering, but gL values remained low. After re-watering, we found significant correlations between changes in ABA content and hexoses concentration both in wood and bark. Our findings suggest a role for ABA in the regulation of stem carbohydrate metabolism and starch mobilization upon drought relief, possibly promoting the restoration of xylem transport capacity.

The potential of Arundo donax to grow in degraded soils, characterized by excess of salinity (Na+), and phosphorus deficiency (-P) or excess (+P) also coupled with salinity (+NaP), was investigated by combining in vivo plant phenotyping, quantification of metabolites and ultrastructural imaging of leaves with a transcriptome-wide screening. Photosynthesis and growth were impaired by + Na, -P and + NaP. While + Na caused stomatal closure, enhanced biosynthesis of carotenoids, sucrose and isoprene and impaired anatomy of cell walls, +P negatively affected starch production and isoprene emission, and damaged chloroplasts. Finally, +NaP largely inhibited photosynthesis due to stomatal limitations, increased sugar content, induced/repressed a number of genes 10 time higher with respect to + P and + Na, and caused appearance of numerous and large plastoglobules and starch granules in chloroplasts. Our results show that A. donax is sensitive to unbalances of soil ion content, despite activation of defensive mechanisms that enhance plant resilience, growth and biomass production of A. donax under these conditions.

This is the accepted manuscript of the paper "Dynamic changes in ABA content in water-stressed Populus nigra: effects on carbon fixation and soluble carbohydrates", published as final paper in "Annals of Botany Volume 124, Issue 4, 13 September 2019, Pages 627–643 https://doi.org/10.1093/aob/mcz005”. Background and Aims Hydraulic and chemical signals operate in tandem to regulate systemic plant responses to drought. Transport of abscisic acid (ABA) through the xylem and phloem from the root to shoot has been suggested to serve as the main signal of water deficit. There is evidence that ABA and its ABA-glycosyl-ester (ABA-GE) are also formed in leaves and stems through the chloroplastic 2-C-methylerythritol-5-phosphate (MEP) pathway. This study aimed to evaluate how hormonal and hydraulic signals contribute to optimize stomatal (gs), mesophyll (gm) and leaf hydraulic (Kleaf) conductance under well-watered and water-stressed conditions inPopulus nigra(black poplar) plants. In addition, we assessed possible relationships between ABA and soluble carbohydrates within the leaf and stem. Methods Plants were subjected to three water treatments: well-watered (WW), moderate stress (WS1) and severe stress (WS2). This experimental set-up enabled a time-course analysis of the response to water deficit at the physiological [leaf gas exchange, plant water relations, (Kleaf)], biochemical (ABA and its metabolite/catabolite quantification in xylem sap, leaves, wood, bark and roots) and molecular (gene expression of ABA biosynthesis) levels. Key Results Our results showed strong coordination betweengs,gmandKleafunder water stress, which reduced transpiration and increased intrinsic water use efficiency (WUEint). Analysis of gene expression of 9-cis-epoxycarotenoid dioxygenase (NCED) and ABA content in different tissues showed a general up-regulation of the biosynthesis of this hormone and its finely-tuned catabolism in response to water stress. Significant linear relationships were found between soluble carbohydrates and ABA contents in both leaves and stems, suggesting a putative function for this hormone in carbohydrate mobilization under severe water stress. Conclusions This study demonstrates the tight regulation of the photosynthetic machinery by levels of ABA in different plants organs on a daily basis in both well-watered and water stress conditions to optimize WUEintand coordinate whole plant acclimation responses to drought.

Over the past decades, introduction of many fast-growing hygrophilic, and economically valuable plants into xeric environments has occurred. However, production and even survival of these species may be threatened by harsh climatic conditions unless an effective physiological and metabolic plasticity is available. Moringa oleifera Lam., a multipurpose tree originating from humid sub-tropical regions of India, is widely cultivated in many arid countries because of its multiple uses. We tested whether M. oleifera can adjust primary and secondary metabolism to efficiently cope with increasing water stress. It is shown that M. oleifera possesses an effective isohydric behavior. Water stress induced a quick and strong stomatal closure, driven by abscisic acid (ABA) accumulation, and leading to photosynthesis inhibition with consequent negative effects on biomass production. However, photochemistry was not impaired and maximal fluorescence and saturating photosynthesis remained unaffected in stressed leaves. We report for the first time that M. oleifera produces isoprene, and show that isoprene emission increased three-fold during stress progression. It is proposed that higher isoprene biosynthesis helps leaves cope with water stress through its antioxidant or membrane stabilizing action, and also indicates a general MEP (methylerythritol 4-phosphate) pathway activation that further helps protect photosynthesis under water stress. Increased concentrations of antioxidant flavonoids were also observed in water stressed leaves, and probably cooperate in limiting irreversible effects of the stress in M. oleifera leaves. The observed metabolic and phenotypic plasticity may facilitate the establishment of M. oleifera in xeric environments, sustaining the economic and environmental value of this plant.

The effect of different light qualities on growth, photosynthesis, leaf anatomy and isoprenoid emission was studied in two different fast-growing plant systems: a herbaceous crop, tomato (Solanum lycopersicum L.), and a tree, oriental plane (Platanus orientalis L.). Both plant species were subjected to three different light quality regimes: RGB (Red 33%, Green 33%, Blue 33%) and RB (Red 66%, Blue 33%), provided by light emitting diodes (LED); and white light (WL), considered as a control and provided by white fluorescent lamps. Compared to WL, RGB and RB reduced plant height, plant biomass and leaf area. The CO2 assimilation rate (A) was lower in tomato grown under WL than RGB and RB, while A was similar in oriental plane leaves exposed to the three light regimes. In tomato, stomatal (g(s)) and mesophyll (g(m)) conductance were higher under RGB and RB compared to WL. In plane, gs was also higher under RGB and RB, while gm was not significantly influenced by different light qualities. In both species, leaf lamina thickness (LT) and stomata size were the anatomical traits most affected by the different light regimes. In tomato, leaf lamina thickness was significantly reduced in RGB and RB leaves, whereas in oriental plane leaf lamina thickness was significantly higher in RGB and RB than in WL leaves. In both species, RB leaves showed bigger stomata size than WL and RGB leaves. Light quality also affected photosynthesis dependent volatile isoprenoids. In tomato, beta-phellandrene was lower under RB and RGB compared to WL. However, RGB and RB stimulated alpha-pinene, carene and alpha-terpinene emissions. Oriental plane released about 14 nmol m(-2) s(-1) isoprene when growing at WL, while the emission was reduced under RGB and even more under RB. In summary, photosynthetic performance, leaf anatomy, biomass production, and volatile isoprenoids are affected by light quality differently in tomato and plane plants. Light quality control may have important applications to modulate plant productivity and increase biosynthesis of useful biochemical compounds. (C) 2016 Elsevier B.V. All rights reserved.

A number of second line treatments have been proposed in patients with advanced pretreated non-small cell lung cancer (NSCLC). However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over monotherapy. We have treated 42 patients (30 males) affected by advanced/metastatic NSCLC progressing during front line cisplatin-based chemotherapy with a combination of topotecan (1.2 mg/m2) plus ifosfamide (1200 mg/m2) for 3 consecutive days every 3 weeks. The median age was 63 years (range 43-76); cell types were: squamous carcinoma (n=17), adenocarcinoma (n=16), large cell carcinoma (n=3), broncho-alveolar carcinoma (n=2) and undifferentiated carcinoma (n=4). All patients were treated with a platinum containing chemotherapy: 39 patients with cisplatin, 2 patients with carboplatin and 1 patient with oxaliplatin, respectively. The ECOG PS was 0 in 8 patients (19%), 1 in 11 patients (26%), and 2 in 23 patients (55%). The median number of courses administered was 3 (range 1-8). Grade 3-4 neutropenia was the dose limiting toxicity, observed in 36% of patients. Moreover, grade 3-4 anemia and thrombocytopenia were observed in 17% and in 12% of patients, respectively. One PS 2 patient died of grade 4 hematological toxicity after the first cycle. No complete response was observed. Six (14.2%) subjects obtained a partial response (PR). In addition, 1 (2.4%) minimal response (MR) plus 14 (34%) stable diseases (SD) and 21 (51%) progressive diseases (PD) were observed. Median time to disease progression and median survival were 9 weeks (range 1-13) and 26 weeks (range 1-91+), respectively. The 1-year survival rate was 14%. Combination of topotecan and ifosfamide demonstrated antitumor activity in patients with relapsing or refractory NCSLC with a modest side effect profile and an overall disease control (PR + MR + SD) of 50.7%. Nevertheless, the still low response rate and the shortness of median survival indicates the need for more effective second line treatments in this disease.