TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.Instituto de Salud Carlos III European Commission PI15/00336 PI19/01533 CP14/00197 CP19/00029 PIE16/00045Ministry of Science and Innovation, Spain (MICINN)Instituto de Salud Carlos IIISpanish Government RTI2018.101309B-C22Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS963European Regional Development Fund (European Union)Ministerio de Universidades FPU19/04450Junta de Andalucia RH-0139-2020Sistema Nacional de Garantia Juvenil (Fondo Social Europeo) 8064Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades DOC_01686Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC) PRDJA19001BLA

¿Qué queda de mí?

Este libro es una reclamación a quienes hemos sido, somos o seremos docentes. A quienes no hemos respetado a las personas que se han puesto junto a nosotros y nosotras, confiando su bien más preciado: la libertad. Estas páginas denuncian cada vez que convertimos una visión en la visión, una emoción en la emoción, un saber en el saber, un comportamiento en el comportamiento. Es un grito contra la imposición, la normalización, la neutralización y la universalización de una perspectiva particular. Una pugna contra cada proceso que no se ha conectado con las vidas de los aprendices. Un texto colaborativo realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga y coordinado por Ignacio Calderón Almendros

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on "redoxidomics" or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.This work and S.G.-P. are funded by Instituto de Salud Carlos III (CP19/00029, CP14/00197, PI19/01533, PI15/00336) and PIE16-00045 (J.A.M.), Ministerio de Ciencia, Innovación y niversi dades (RTI2018-101309-B-C22) (J.A.M.), and European Regional Development Fund (FEDER Funds,European Union) (S.G.-P., J.A.M.). C.G.-L. is funded by Junta de Andalucía, Consejería de Salud y Familias (RH-0139-2020), J.L.B.-C. is supported by Fundación Científica Asociación Española Contra el Cáncer, Junta Provincial de Jaén (AECC) (PRDJA19001BLAY), and A.L.-T. is funded by Ministerio de Ciencia, Innovación y Universidades (FPU19/04450).Ye

Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer

S.G.-P. was supported by Instituto de Salud Carlos III (CP14/00197, CP19/00029) and the European Regional Development Fund (European Union). This work was funded by Instituto de Salud Carlos III (PI15/00336, PI19/01533), Ministerio de Ciencia e Innovacion (PID2020-115087GB-100, RTI2018.101309B-C22) and Junta de Andalucia (B-CTS-410-UGR-20). A.N.-O. was supported by Sistema Nacional de Garantia Juvenil (Fondo Social Europeo). J.L.B.-C. was supported by Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC) (PRDJA19001BLAY), and A.L.T. was funded by Ministerio de Ciencia, Innovacion y Universidades (FPU19/04450). C.G.-L. was funded by Junta de Andalucia, Consejeria de Salud y Familias (RH-0139-2020), J.C. was funded by Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (DOC_01686).Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various mechanisms of cancer immune escape that produce tumor variants that are resistant to treatment. Thus, a further understanding of the molecular events underlying immune evasion in breast cancer may guarantee a significant improvement in the clinical success of immunotherapy. Furthermore, nanomedicine provides a promising opportunity to enhance the efficacy of cancer immunotherapy by improving the delivery, retention and release of immunostimulatory agents in targeted cells and tumor tissues. Hence, it can be used to overcome tumor immune escape and increase tumor rejection in numerous malignancies, including breast cancer. In this review, we summarize the current status and emerging trends in nanomedicine-based strategies targeting cancer immune evasion and modulating the immunosuppressive tumor microenvironment, including the inhibition of immunosuppressive cells in the tumor area, the activation of dendritic cells and the stimulation of the specific antitumor T-cell response.Instituto de Salud Carlos III European Commission CP14/00197 CP19/00029 PI15/00336 PI19/01533European Regional Development Fund (European Union) Instituto de Salud Carlos IIISpanish GovernmentEuropean Commission PID2020-115087GB-100 RTI2018.101309B-C22Junta de Andalucia B-CTS-410-UGR-20Sistema Nacional de Garantia Juvenil (Fondo Social Europeo)Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC) PRDJA19001BLAY Spanish Government FPU19/04450Junta de Andalucia RH-0139-2020Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades DOC_0168