RESUMEN
Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration affecting the inferior olivary nucleus (ION). Its classical description involves a lesion in the Guillain-Mollaret triangle (GMT), characteristic imaging findings, and associated oculopalatal tremor. However, understanding of this disease entity is incomplete, as its overall rarity has limited strong classification. Case reports and small studies indicate that a variety of presentations can occur, including non-existent or non-classical lesions as well as variations in physical symptoms. Here we report the exceedingly rare case of idiopathic, nonlesional, unilateral HOD in a female patient.
RESUMEN
Rapid developments in nucleic acid nanotechnology have enabled the rational design and construction of self-assembling DNA and RNA nanostructures that are highly programmable. We recently developed a replicable single-stranded RNA origami (RNA-OG) technology that allows a long RNA molecule to be programmed to self-assemble into nanostructures of various shapes. Here, we show that such RNA-OG is highly stable in serum/plasma, and we thus exploited its immunostimulatory potential. We demonstrated that the RNA-OG stimulates a potent innate response primarily through a Toll-like receptor 3 (TLR3) pathway. In a murine peritoneal metastatic colon cancer model, intraperitoneally injected RNA-OG induced significant tumor retardation or regression by activating NK- and CD8-dependent antitumor immunity and antagonizing the peritoneal immunosuppressive environment. Unlike polyinosinic/polycytidylic acid (PolyIC), a well-known double-stranded RNA analogue, the RNA-OG treatment did not cause a high level of type-I interferons in the blood nor apparent toxicity upon its systemic administration in the animals. This work establishes the function of RNA-OG as a potent line of TLR3 agonists that are safe and effective for cancer immunotherapy.
