Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives

A small library of highly functionalized phenylaminopyrazoles, bearing different substituents at position 1, 3 and 4 of the pyrazole ring, was prepared by the one pot condensation of active methylene reagents, phenylisothiocyanate and substituted hydrazine (namely, methyl- and benzyl-hydrazine). The identified reaction conditions proved to be versatile and efficient. Fur-thermore, the evaluation of alternative stepwise protocols affected the chemo- and re-gio-selectivity outcome of the one-pot procedure. The chemical identity of two N-methyl pyrazole isomers, selected as prototypes of the whole series, was unambiguously identified by means of NMR and mass spectrometry studies. Additionally, semiempirical calculations provided a structural rationale for the different chromatographic behaviour of the two isomers. The prepared tetra-substituted phenylaminopyrazoles were tested in cell-based assays on a panel of cancer and normal cell lines. The tested compounds did not show any cytotoxic effect on the selected cell lines, thus supporting their pharmaceutical potentials

CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy

Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αβT lymphocytes. Herein we reviewed biological features, therapeutic potential, and safety of alternative effectors to conventional CAR T cells: γδT, natural killer (NK), NKT, or cytokine-induced killer (CIK) cells. The intrinsic CAR-independent antitumor activities, safety profile, and ex vivo expansibility of these alternative immune effectors may favorably contribute to the clinical development of CAR strategies. The proper biological features of innate immune response effectors may represent an added value in tumor settings with heterogeneous CAR target expression, limiting the risk of tumor clonal escape. All these properties bring out CAR engineering of alternative immune effectors as a promising integrative option to be explored in future clinical studies

Perception of circular economy approach in agricultural cooperatives of Argentina

Circular Economy approach is imposing as a framework for changing the current environmental-socio-economic constrains as well as building a new paradigm where citizens in all their society roles has a key participation on its principles such as to design out waste and pollution, to keep products and material in use and to regenerate natural systems. However, implementation in Argentina is very slow and only applied at some companies’ level, as some agricultural cooperatives, or at urban residues recycling at certain cities. The objective of this paper is to explore the awareness, current state and expectations of the transition towards a circular economy approach within agricultural cooperatives based on opinion and perception/awareness consultation. This paper communicate the results obtained from a wider Project, which analyzed others activity sectors of Argentina. An anonymous questionnaire was designed and implemented in order to obtain the objective, and it was structured into three sections: i) demographic characterization, ii) general awareness about transition towards circular economy (concept, current state, features, advantages, drivers, barriers and governance) and iii) specific issues within the cooperative sector. Results explore the perception/awareness about the transition towards applications, barriers, governance of circular economic mechanisms providing an interpretative framework of current state, expectations and possibilities of action to both researchers and policy makers.EEA OliverosFil: Rotolo, Gloria Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Vassillo, C. University of Naples Federico II. Department of Agriculture; ItaliaFil: Rodriguez Aranza, Ailén. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Magnano, Luciana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Milo Vaccaro, Marcelo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Civit, Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Civit, Bárbara. Universidad Tecnológica Nacional. Sede Mendoza; ArgentinaFil: Arena, Alejandro Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arena, Alejandro Pablo. Universidad Tecnológica Nacional. Sede Mendoza; Argentin

Cytomegalovirus colitis and cow's milk allergy in an immunocompetent infant: Is a causal or casual relationship?

The association between cytomegalovirus (CMV) colitis and cow's milk allergy (CMPA) is rare and still unclear. The authors describe the case of an 8-week old female infant who presented with bloody diarrhea, lack of appetite, weight loss and fever due to CMV colitis. After some months she developed a CMPA. This case report describes the third case of CMV colitis associated with CMPA. This case strongly suggests a causal relationship between the two conditions

Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy

Metastatic bone and soft tissue sarcomas often relapse after chemotherapy (CHT) and molecular targeted therapy (mTT), maintaining a severe prognosis. A subset of sarcoma cancer stem cells (sCSC) is hypothesized to resist conventional drugs and sustain disease relapses. We investigated the immunotherapy activity of cytokine induced killer cells (CIK) against autologous sCSC that survived CHT and mTT. The experimental platform included two aggressive bone and soft tissue sarcoma models: osteosarcoma (OS) and undifferentiated-pleomorphic sarcoma (UPS). To visualize putative sCSC we engineered patient-derived sarcoma cultures (2 OS and 3 UPS) with a lentiviral sCSC-detector wherein the promoter of stem-gene Oct4 controls the expression of eGFP. We visualized a fraction of sCSC (mean 24.2 +/- 5.2%) and confirmed their tumorigenicity in vivo. sCSC resulted relatively resistant to both CHT and mTT in vitro. Therapeutic doses of doxorubicin significantly enriched viable eGFP(+)sCSC in both OS (2.6 fold, n = 16) and UPS (2.3 fold, n = 29) compared to untreated controls. Treatment with sorafenib (for OS) and pazopanib (for UPS) also determined enrichment (1.3 fold) of viable eGFP(+)sCSC, even if less intense than what observed after CHT. Sarcoma cells surviving CHT and mTT were efficiently killed in vitro by autologous CIK even at minimal effector/target ratios (40:1 = 82%, 1:4 = 29%, n = 13). CIK immunotherapy did not spare sCSC that were killed as efficiently as whole sarcoma cell population. The relative chemo-resistance of sCSC and sensitivity to CIK immunotherapy was confirmed in vivo. Our findings support CIK as an innovative, clinically explorable, approach to eradicate chemo-resistant sCSC implicated in tumor relapse