Browsing by Author "Araya, Mariela"

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    Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model
    (2024) Araya, Mariela; Sepúlveda, Francisca; Villegas, Jaime; Alarcón, Luis; Burzio, Luis; Burzio, Verónica; Borgna, Vincenzo
    Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.
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    Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors.
    (Ivyspring International Publisher, 2020) Borgna, Vincenzo; Lobos-González, Lorena; Guevara, Francisca; Landerer, Eduardo; Bendek, Maximiliano; Ávila, Rodolfo; Silva, Verónica; Villota, Claudio; Araya, Mariela; Rivas, Alexis; López, Constanza; Socías, Teresa; Castillo, Jorge; Alarcón, Luis; Burzio, Luis; Burzio, Verónica; Villegas, Jaime
    Knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, supporting a selective therapy against different types of cancer. In this work, we evaluated the effects of knockdown of ASncmtRNAs on bladder cancer (BCa). We transfected the BCa cell lines UMUC-3, RT4 and T24 with the specific antisense oligonucleotide Andes-1537S, targeted to the human ASncmtRNAs. Knockdown induced a strong inhibition of cell proliferation and increase in cell death in all three cell lines. As observed in UMUC-3 cells, the treatment triggered apoptosis, evidenced by loss of mitochondrial membrane potential and Annexin V staining, along with activation of procaspase-3 and downregulation of the anti-apoptotic factors survivin and Bcl-xL. Treatment also inhibited cell invasion and spheroid formation together with inhibition of N-cadherin and MMP 11. In vivo treatment of subcutaneous xenograft UMUC-3 tumors in NOD/SCID mice with Andes-1537S induced inhibition of tumor growth as compared to saline control. Similarly, treatment of a high-grade bladder cancer PDX with Andes-1537S resulted in a strong inhibition of tumor growth. Our results suggest that ASncmtRNAs could be potent targets for bladder cancer as adjuvant therapy.
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    Vivencia del núcleo familiar frente al padecimiento de esquizofrenia en uno de sus miembros durante el transcurso de la enfermedad
    (Universidad del Desarrollo. Facultad de Medicina. Escuela de Enfermería, 2017) Araya, Mariela; Jiménez, Josefa; Moreno, Camila; Ramírez, Macarena; Ramos, Constanza; Araya, Mariela; Jiménez, Josefa; Moreno, Camila; Ramírez, Macarena; Ramos, Constanza; Fuentes, Daniela; Fuentes, Daniela
    el objetivo de la presente investigación es explorar la vivencia del núcleo familiar frente al padecimiento de esquizofrenia en uno de sus miembros desde el diagnóstico hasta la actualidad.

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