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Dwarf shrubs and herbaceous steppes are the dominant physiognomic types in Pampa Vaca (Central District), southeastern Chubut, while shrubs and herbaceous steppes dominate in Pampa Salamanca (San Jorge Gulf District), but the latter with variable proportions of dwarf shrubs, shrubs and grasses. The aims of this study were 1) to describe the life forms spectra in both "pampas" and 2) to report the seasonal fluctuations in green, dry and dead biomass sorted into life forms. Chi squared test (X2) was used to compare the spectra obtained with the Normal Biologic Spectrum of Raunkiaer. Finally the spectra obtained were related to the climate of the area. A total of 28 species, belonging to 10 families, were recorded in Pampa Vaca; most of the species were Poaceae and Asteraceae. The dominant life forms were Chamaephytes (dwarf shrubs) and Hemicryptophytes (graminoids). Significant differences (a< 0,05) were obtained when the observed and theoretical biologic spectra were compared. The seasonal fluctuation showed that the Chamaephytes green biomass was related to wet years. In Pampa Salamanca a total of 80 species, distributed in 25 families, was found and similarly to Pampa Vaca, the Poaceae and Asteraceae were the richest families. The dominant life form was the Nanophanerophytes (shrubs), followed by the Chamaephytes and Hemicryptophytes. Highly significant differences were observed for Nanophanerophytes and Chamaephytes when the observed and theoretical biologic spectra were compared. According to the seasonal fluctuation observed in the biomass data, it is assumed that the Hemicryptophytes green biomass had a better response to the rain. [ABSTRACT FROM AUTHOR]

Getting to know the forage available in arid ecosystems is one of the basic problems at the moment of make an assessment of Patagonian grasslands. The aim of this work was the adjustment to the forage production estimation model through pastoral value in two ecosystems in the southeast of Department Escalante (Chubut province). The analyzed ecosystems belong to different ecologic areas, one of them corresponds to herbaceous steppes of Festuca pallescens, Festuca argentina, Poa ligularis with Adesmia volkmanii, Senecio filaginoides and Verbena sp shrubs to Golfo San Jorge Distric, meanwhile, the other one is located in Central District, Chubutense Subdistrict (Soriano, 1956) is a dwarfs shrubs steppe of Nassauvia glomerulosa y N. ulicina with Poa dusenii grasses. The samples have been made in exclousures to ovine grassing in Pampa de Salamanca (Golfo San Jorge District) and in Pampa Vaca (Central District). The forage biomass was determined from seasonal crops clipping aboveground material with 0,2 m² frames. The forage PPNA was estimated following the methodology of Singh et al (1975), for the period 1990-1994. On the other hand, line transects have been made from which ones the pastoral values were obtained, for the period 1998-2001. Besides the time difference, the periods can be compared because their rain means are alike. A regression model was obtained for each ecosystem from which one is feasible estimate the forage PPNA from the VP. These models let assess different productive situations taking into account the structural and functional features of the ecosystem, as well as determine the stock capacity, with the corresponding use factor. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but deficiency of environmental signals and insufficient tumor recognition may limit their activity. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to a spliced isoform of the extracellular matrix (ECM) glycoprotein tenascin-C would potentiate NK-cell-mediated antibody-dependent cellular cytotoxicity against leukemic blasts. In this novel-novel combination, dose-escalation, phase 1 trial, we enrolled patients with posttransplant acute myeloid leukemia (AML) relapse to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of the antibody-cytokine fusion F16IL2 (10 × 106 to 20 × 106 IU IV; days 1, 8, 15, and 22 of each 28-day cycle) in combination with the anti-CD33 antibody BI 836858 (10-40 mg IV, 2 days after each F16IL2 infusion). Among the 15 patients (median [range] age, 50 [20-68] years) treated across 4 dose levels (DLs), 6 (40%) had received 2 or 3 prior transplantations. The most frequent adverse events were pyrexia, chills, and infusion-related reactions, which were manageable, transient and of grade ≤2. One dose-limiting toxicity occurred at each of DLs 3 (pulmonary edema) and 4 (graft-versus-host disease). Three objective responses were observed among 7 patients treated at the 2 higher DLs, whereas no responses occurred at the 2 starting DLs. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the FcγRIIIA/CD16 receptor. ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT as 2015-004763-37., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy. Volasertib (BI 6727) is a cell-cycle regulator targeting polo-like kinase which has been evaluated in clinical trials in AML. We evaluated effects of volasertib in primary patient samples and NK cells. At equivalent doses, volasertib is cytotoxic to AML blasts but largely spares healthy NK cells. We then evaluated the effect of volasertib treatment in combination with BI 836858 on primary AML blast samples using antibody-dependent cellular cytotoxicity (ADCC) assays. Volasertib treatment of NK cells did not impair NK function as evidenced by comparable levels of BI 836858 mediated ADCC in both volasertib-treated and control-treated NK cells. In summary, volasertib is cytotoxic to AML blasts while sparing NK cell viability and function. Higher BI 836858 mediated ADCC was observed in patient samples pretreated with volasertib. These findings provide a strong rationale to test combination of BI 836858 and volasertib in AML., Competing Interests: CONFLICTS OF INTEREST B.R., I.W. and K.H.H. are employees of Boehringer Ingelheim.

Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML. Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets. BI 836858-opsonized AML cells significantly induced both autologous and allogeneic natural killer (NK)-cell degranulation and NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating agents that show efficacy in older patients, did not compromise BI 836858-induced NK-cell-mediated ADCC. Evaluation of BI 836858-mediated ADCC in serial marrow AML aspirates in patients who received a 10-day course of DAC (pre-DAC, days 4, 11, and 28 post-DAC) revealed significantly higher ADCC in samples at day 28 post-DAC when compared with pre-DAC treatment. Analysis of ligands to activating receptors (NKG2D) showed significantly increased NKG2D ligand [NKG2DL] expression in day 28 post-DAC samples compared with pre-DAC samples; when NKG2DL receptor was blocked using antibodies, BI 836858-mediated ADCC was significantly decreased, suggesting that DAC enhances AML blast susceptibility to BI 836858 by upregulating NKG2DL. These data provide a rationale for combination therapy of Fc-engineered antibodies such as BI 836858 with azanucleosides in elderly patients with AML., (© 2016 by The American Society of Hematology.)