RESUMEN
Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.
Asunto(s)
Productos Finales de Glicación Avanzada , Neoplasias Ováricas , Humanos , Femenino , Anciano , Proyectos Piloto , Colágeno , Neoplasias Ováricas/tratamiento farmacológico , Microambiente TumoralRESUMEN
The gut microbiome changes with age and affects regions beyond the gut, including the ovarian cancer tumor microenvironment. In this review summarizing the literature on the gut microbiome in ovarian cancer and in aging, we note trends in the microbiota composition common to both phenomena and trends that are distinctly opposite. Both ovarian cancer and aging are characterized by an increase in proinflammatory bacterial species, particularly those belonging to phylum Proteobacteria and genus Escherichia, and a decrease in short chain fatty acid producers, particularly those in Clostridium cluster XIVa (family Lachnospiraceae) and the Actinobacteria genus Bifidobacterium. However, while beneficial bacteria from family Porphyromonadaceae and genus Akkermansia tend to increase with normal, healthy aging, these bacteria tend to decrease in ovarian cancer, similar to what is observed in obesity or unhealthy aging. We also note a lack in the current literature of research demonstrating causal relationships between the gut microbiome and ovarian cancer outcomes and research on the gut microbiome in ovarian cancer in the context of aging, both of which could lead to improvements to ovarian cancer diagnosis and treatment.
RESUMEN
The Balbiani body (Bb), an organelle comprised of mitochondria, ER, and RNA, is found in the oocytes of most organisms. In Xenopus, the structure is initially positioned immediately adjacent to the nucleus, extends toward the vegetal pole, and eventually disperses, leaving behind a region highly enriched in mitochondria. This area is later transversed by RNP complexes that are being localized to the vegetal cortex. Inhibition of mitochondrial ATP synthesis prevents perinuclear formation of the transport complexes that can be reversed by a nonhydrolyzable ATP analog, indicating the nucleotide is acting as a hydrotrope. The protein composition, sensitivity to hexanediol, and coalescence in the absence of transport provide evidence that the transport RNP complexes are biocondensates. The breakdown of the Bb engenders regions of clustered mitochondria that are used not to meet extraordinary energy demands, but rather to promote a liquid-liquid phase separation.