A biogeographic approach to farming limits in northern Patagonia, Argentina

El sur de la provincia de Mendoza ha sido caracterizado como el límite meridional de la agricultura prehispánica sudamericana específicamente en la vertiente oriental de los Andes. Dicha caracterización ha estado basada en la presencia de plantas domesticadas en los sitios arqueológicos, utilizando una mirada dicotómica entre cazadores-recolectores y agricultores. Los trabajos arqueológicos de las últimas décadas han mostrado una situación compleja y cambiante tanto a nivel espacial como temporal en relación a la dependencia de los grupos humanos sobre este tipo de recursos.A partir de un modelo biogeográfico, se utilizan distintas líneas de análisis del registro arqueológico con el fin de evaluar la incidencia del contexto ambiental en el ingreso de la agricultura a la región. Los resultados obtenidos confirman la escasa importancia de los recursos domesticados entre los grupos humanos de la región y la flexibilidad mostrada por los mismos para enfrentar distintos escenarios ambientales y demográficos.Finalmente, se propone que, en el sur de Mendoza, la estructura ambiental del área biogeográfica de Patagonia habría tenido un rol central en los límites para la dispersión de las plantas domesticadas en esta región de América del Sur.he south of Mendoza province has been characterized as the southern frontier of South American pre-Hispanic agriculture on the eastern slope of the Andes. This characterization has been based on the presence of crops at the archaeological sites and adopting a dichotomic perception of hunter-gatherers and farmers. During the last few decades, the archaeological record has shown a complex and shifting situation both at a spatial and temporal level in relation to the dependence of human groups on this type of resource. Based on a biogeographic model, we evaluated different lines of analysis from the archaeological record to assess the impact of environmental factors on the emergence of agriculture within the region. The results obtained confirm the low importance of agriculture among human groups as well as their flexibility in facing different environmental and demographic scenarios. Finally, we propose that the environmental structure of Patagonia would have played a central role in limiting the spread of domesticated plant use in this region of South America.Fil: Neme, Gustavo Adolfo. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; ArgentinaFil: Gil, Adolfo Fabian. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Salgán, María Laura. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Giardina, Miguel Angel. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; ArgentinaFil: Otaola, Clara. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Pompei, María de la Paz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; ArgentinaFil: Peralta, Eva Ailén. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; ArgentinaFil: Sugrañes, Nuria Andrea. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; ArgentinaFil: Franchetti, Fernando Ricardo. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Abbona, Cinthia Carolina. Universidad Tecnológica Nacional. Facultad Regional San Rafael. Instituto de Evolución, Ecología Histórica y Ambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Evolución, Ecología Histórica y Ambiente; Argentin

Identification, Purification and Characterization of Proteins with Cytotoxic/Antitumor Activity from Chondrosia reniformis

The majority of medicines come from natural resources, and in particular a great number of bioactive molecules (more than 10,000) have been isolated until now from the marine environment, with hundreds of new compounds still being discovered every year [1]. The richest sources of sea natural products are invertebrates with Porifera being the most prolific phylum. Sponge-derived bioactive compounds show the most varied activities: antifungal, anti-HIV, antiviral, antibacterial, but the predominant action is cytotoxic/antitumor with more than 800 compounds so far identified in this category. Sporadic observations on the behavior of the marine sponge Chondrosia reniformis pointed out a possible production of cytotoxic compounds in stress conditions able to kill neighboring organisms. The aim of this work was to purify and possibly characterize the compound causing said activity by means of a step by step purification followed by in vitro cytotoxicity analyses (MTT test) on a series of human tumor cell lines (leukemia, breast cancer, pulmonary carcinoma) as well as on healthy primary cells (fibroblast and blood mononuclear cells). The MTT tests showed a predominant cytotoxicity on tumor cells compared to healthy cells, thus pointing out a possible antitumor activity. Furthermore, preliminary experiments surprisingly showed that most cytotoxic/antitumor activity was confined to the protein fraction of the crude hydrophilic extract. Thus, different methods of protein fractionation were used to isolate the bioactive protein for a final high definition mass spectrometry (HD-MS) characterization. Namely, the purification steps were: a 10 kDa-cut-off dialysis, a 30% ammonium sulphate protein fractionation and a HPLC separation by gel filtration. After the latter step, a particular low-MW HPLC peak retained the antitumor activity, thus this fraction was separated in a 2D gel electrophoresis showing the presence of three protein bands. The bands from the gel were then trypsin-digested and the derived peptides analyzed in HD-MS obtaining the sequence of a series of peptides. Finally, through an in silico analysis comparing the peptide sequences to the C. reniformis transcriptome previously obtained in our lab, we were able to identify three possible protein candidates for the cytotoxic/antitumor activity: a protein with a trefoil factor domain and two unknown proteins showing no homology to known sequences. Actually, homologues of the first protein from higher Metazoa already show in literature an involvement in stress conditions, especially in epithelial injuries. Finally, we plan for the future to obtain the three proteins in recombinant form for further characterization studies. Research supported by EU (FP7 grant agreement n: 266033 SPonge Enzyme End Cell for Innovative AppLication-SPECIAL)

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis

The Role of Cytokinome in the HNSCC Tumor Microenvironment: A Narrative Review and Our Experience

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint inhibitors (ICIs) with or without chemotherapy represent the new first-line option. However, cancer will recur in about two out of five patients with LA HNSCC. If progression occurs within six months from platin-radiotherapy treatment, anti-programmed cell death-1 (PD-1) may be prescribed. Otherwise, immunotherapy with or without chemotherapy might be considered if PD-L1 is expressed. Despite several improvements in the outcome of patients with R/M HNSCC, overall survival (OS) remains dismal, equaling a median of 14 months. In-depth knowledge of the tumor microenvironment (TME) would be required to change the course of this complex disease. In recent years, many predictive and prognostic biomarkers have been studied in the HNSCC TME, but none of them alone can select the best candidates for response to ICIs or targeted therapy (e.g., Cetuximab). The presence of cytokines indicates an immune response that might occur, among other things, after tumor antigen recognition, viral and bacterial infection, and physic damage. An immune response against HNSCC results in the production of some cytokines that induce a pro-inflammatory response and attract cells, such as neutrophils, macrophages, and T cell effectors, to enhance the innate and adaptive anti-tumor response. We revised the role of a group of cytokines as biomarkers for treatment response in HNSCC

How Chemotherapy Affects the Tumor Immune Microenvironment: A Narrative Review

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment. Therefore, the identification of reliable markers for response is an unmet need. Eighteen cytokines, selected based on their prevalent Th1 or Th2 effects, were collected. Peripheral blood samples were gathered at baseline in 25 metastatic colorectal cancer patients treated with regorafenib. Data extracted have been linked to progression-free survival. ROC identified the best cytokines associated with outcome. The relative value of the selected cytokines was determined by PCA. Data analysis identified 8 cytokines (TGF-β, TNF-α, CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21), used to create a signature (TGF-β, TNF-α high; CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21 low) corresponding to patients with a significantly longer progression-free survival. This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient’s outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment. Therefore, the identification of reliable markers for response is an unmet need. Eighteen cytokines, selected based on their prevalent Th1 or Th2 effects, were collected. Peripheral blood samples were gathered at baseline in 25 metastatic colorectal cancer patients treated with regorafenib. Data extracted have been linked to progression-free survival. ROC identified the best cytokines associated with outcome. The relative value of the selected cytokines was determined by PCA. Data analysis identified 8 cytokines (TGF-β, TNF-α, CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21), used to create a signature (TGF-β, TNF-α high; CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21 low) corresponding to patients with a significantly longer progression-free survival. This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient’s outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated