Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane–dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.
Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas.
Colorectal cancer (CRC) is one of the leading causes of mortality worldwide, with rising cases in individuals under 50 years old, classified as early-onset CRC (EO-CRC). EO-CRC is characterized by having clinical features related to a worse prognosis and outcome. This underscores the critical need for early detection biomarkers. ncRNAs emerge as potential biomarkers for diagnosis, prognosis, and treatment response in other types of cancers. Sequencing data from the NCBI Bioproject PRJNA787417 were analyzed to identify differentially expressed miRNAs in early- and late-onset colorectal cancer (EO-CRC and LO-CRC). Differential expressions were assessed with a log fold change threshold of 1 and an adjusted p-value of 0.05. Predicted mRNA targets were identified via ENCORI and analyzed for pathway enrichment using the SHINYGO algorithm. RNA-seq analysis identified a 25-ncRNA EO-CRC signature, including hsa-miR-195 (downregulated) and hsa-miR-549a (upregulated), with enrichment analyses suggesting associations with MAPK, PI3K, VEGF, and KRAS pathways commonly linked to angiogenesis, migration, and invasion. This preliminary report highlights a 25-gene deregulated signature in EO-CRC, in which hsa-miR-195 and hsa-miR-549a emerge as biomarkers of clinical relevance, regulating key genes involved in angiogenesis, migration, and invasion. Their dysregulation could contribute to the aggressive clinical features and poor outcomes observed in EO-CRC.
Los sarcomas constituyen un grupo heterogéneo y poco frecuente de neoplasias que se originan en tejidos mesenquimales, como hueso, cartílago, músculo y tejido adiposo. Representan menos del 1% de todos los cánceres en adultos; se asocian con tasas elevadas de mortalidad con alto impacto clínico y social. Los enfoques terapéuticos actuales, diseñados de forma general, resultan con frecuencia insuficientes, mostrando eficacia limitada y efectos adversos. En los últimos años, los avances en biología molecular, inmunoterapia y terapias dirigidas han transformado el panorama del tratamiento, generando nuevas oportunidades para el desarrollo de estrategias personalizadas con potencial de mejorar la supervivencia y la calidad de vida de los pacientes. En este artículo se revisan de manera integral aspectos de los sarcomas como origen, clasificación, etiología, epidemiología y tratamientos actuales. También se exploran perspectivas a futuro para la implementación de nuevas estrategias farmacológicas y terapéuticas basadas en la biología específica de cada subtipo.