Mujeres indígenas, derechos colectivos y violencia de género. Intervenciones en un debate que inicia

En esta oportunidad nos proponemos poner a consideración una serie de debates que tienen lugar respecto a las mujeres indígenas, los derechos colectivos y la violencia de género. Con este objetivo pondremos en articulación escenarios concretos de discusión donde mujeres indígenas, académicas y activistas se encuentran estableciendo posiciones, diálogos y rupturas. En éstos se hace visible una perspectiva sobre las mujeres indígenas que describimos como “idílica o reificada”, en tanto que establece un “deber ser” respecto a “la mujer indígena” que obstruye la visibilidad sobre contextos de violencia y discriminación vividos por las mujeres indígenas en sus comunidades o en espacios de organización social y política. A continuación expondremos dos experiencias de mujeres indígenas organizadas y posicionadas frente a situaciones de violencia de género en las comunidades o espacios de organización social y política indígena. Una de ellas refiere a la experiencia de una activista indígena, Octorina Zamora, cuya voz tomó notoriedad mediática a partir de su discurso crítico frente a determinados posicionamientos mediáticos y académicos en relación al caso conocido como “Lapacho Mocho”. La segunda hace referencia a un espacio colectivo de articulación política que reúne a mujeres indígenas en un taller nacional en los Encuentros Nacionales de Mujeres (ENM), abordando la discusión sobre la legalización/despenalización del aborto.In this article we intend to present a series of debates about indigenous women, collective rights and gender-based violence. With this objective in mind, we will articulate specific scenarios of discussion where indigenous, academic and activist women encounter each other and establish positions, dialogues and ruptures. In those scenarios emerges a perspective on indigenous women that we describe as «idyllic or reified», which establishes a «should be» regarding the «indigenous woman» that obstructs the visibility of the violent contexts indigenous women live in their communities or instances of social and political organization. Then, we will analyze two experiences of organized indigenous women who have taken a position with regard to gender-based violence in the communities or instances of political and social indigenous organization. One of them takes on the experience of an indigenous activist, Octorina Zamora, whose voice gained attention in the media as a result of her critical discourse regarding certain mediatic and academic stances on the case known as «Lapacho Mocho». The second one refers to a collective space of political articulation that gathers indigenous women in a national workshop during the National Women’s Encounters, addressing the discussion on the legalization/decriminalization of abortion.Fil: Gomez, Mariana Daniela. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección de Etnología y Etnografía; ArgentinaFil: Sciortino, María Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; Argentin

TRK fusion positive cancers:From first clinical data of a TRK inhibitor to future directions

Genetic alterations of neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) 1/2/3 genes generate TRK fusion proteins have been reported in a variety of adult and child cancers from diverse cell/tissue lineages. Larotrectinib, a tumour-agnostic TRK inhibitor, has shown remarkable efficacy in a novel "basket" study which has enrolled patients from infants to elderly with different TRK fusion-positive cancers. In this review, we focus on the challenges and expectations on the development of "tumour-agnostic" targeted therapies in rare malignancies.</p

TRK fusion positive cancers:From first clinical data of a TRK inhibitor to future directions

Genetic alterations of neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) 1/2/3 genes generate TRK fusion proteins have been reported in a variety of adult and child cancers from diverse cell/tissue lineages. Larotrectinib, a tumour-agnostic TRK inhibitor, has shown remarkable efficacy in a novel "basket" study which has enrolled patients from infants to elderly with different TRK fusion-positive cancers. In this review, we focus on the challenges and expectations on the development of "tumour-agnostic" targeted therapies in rare malignancies.</p

IGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway.

Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer.In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 upregulation required the activation of the PI3K/AKT pathway while the ERK1/2, the p70/mTOR and the PKC pathways were not involved. Moreover, we observed that DDR1 protein upregulation was induced by translational mechanisms involving miR-199a-5p suppression through PI3K/AKT activation. This effect was confirmed by both IGF-II produced by cancer-associated fibroblasts from human breast cancer and by stable transfection of breast cancer cells with a human IGF-II expression construct. Transfection with a constitutively active form of AKT was sufficient to decrease miR-199a-5p and upregulate DDR1. Accordingly, IGF-I-induced DDR1 upregulation was inhibited by transfection with pre-miR-199a-5p, which also impaired AKT activation and cell migration and proliferation in response to IGF-I.These results demonstrate that, in breast cancer cells, a novel pathway involving AKT/miR-199a-5p/DDR1 plays a role in modulating IGFs biological responses. Therefore, this signaling pathway may represent an important target for breast cancers with over-activation of the IGF-IR axis

Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

ErbB2 overexpression is detected in approximately 20% of breast cancers and is correlated with poor survival. It was previously shown that the adaptor protein p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its overexpression confers invasive properties to ErbB2-positive human mammary epithelial cells. We herein prove, for the first time, that the transcriptional repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness. Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2 cells and correlate with metastatic status in human breast cancer patients. The present study, by using 2D and 3D breast cancer models, shows that the increased Blimp1 expression depends on both MAPK activation and miR-23b downmodulation. Moreover, we demonstrate that Blimp1 triggers cell invasion and metastasis formation via its effects on focal adhesion and survival signaling. These findings unravel the previously unidentified role that transcriptional repressor Blimp1 plays in the control of breast cancer invasiveness

Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

ErbB2 overexpression is detected in approximately 20% of breast cancers and is correlated with poor survival. It was previously shown that the adaptor protein p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its overexpression confers invasive properties to ErbB2-positive human mammary epithelial cells. We herein prove, for the first time, that the transcriptional repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness. Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2 cells and correlate with metastatic status in human breast cancer patients. The present study, by using 2D and 3D breast cancer models, shows that the increased Blimp1 expression depends on both MAPK activation and miR-23b downmodulation. Moreover, we demonstrate that Blimp1 triggers cell invasion and metastasis formation via its effects on focal adhesion and survival signaling. These findings unravel the previously unidentified role that transcriptional repressor Blimp1 plays in the control of breast cancer invasiveness

Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells

Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model

Exploring the effectiveness of the Green Pass Law as Public Health instrument to increase anti-COVID-19 vaccination in a sample of working-age adult population in the Palermo Metropolitan Area.

Counteracting vaccine hesitancy should be considered an absolute priority for Public Health Authorities. A correct health communication represents one of the best ways to increase adhesion to vaccination among hesitant population. In order to increase vaccination coverage rates against COVID-19, the Italian government has issued a legislative decree with a mandatory “Green pass” (GP) to access workplaces for some categories considered at risk. We conducted a cross-sectional study with the aim to highlight the factors associated with the anti-COVID-19 vaccine acceptance and to estimate the influenceof the introduction by law of the Green Pass (GP) on the adhesion to the COVID-19 vaccination campaign in a sample of individual accessing one of the main vaccination centres of the metropolitan area of Palermo, Italy. An anonymous and validated questionnaire was self-administered through the Google Documents® platform, between October 2021 and March 2022. Among the 467 subjects enrolled, 43.3% were influenced on their vaccination choice by the introduction of the GP.&nbsp; The multivariate analysis showed that among the respondents emerged contrasting feelings with a self-reported significantly higher sense of freedom(Adj-OR= 2.45, 95%CIs= 1.51-3.97, p-value: &lt;0.001)but a lower sense of safety (Adj-OR= 0.19, 95%CIs= 0.12-0.29, p-value: &lt;0.001)after vaccine administration. Our findings, in line with the available literature, suggest that the introduction of GP has led to a significant increase in the immunization rate and, together with an appropriate communicative approach, it could represent an effective strategy to counteract vaccine hesitancy