Citations

We previously reported the in vitro selection and characterization of a DNA aptamer capable of stimulating remyelination in a mouse model of multiple sclerosis. This aptamer was selected for its ability to bind to suspensions of crude murine myelin in vitro . Our initial studies in vitro and in vivo involved a 40-nucleotide derivative (LJM-3064) of the original 100-nucleotide aptamer. LJM-3064 retained robust myelin-binding properties. Structural characterization of LJM-3064 revealed that the guanosine-rich 5′ half of the sequence forms different G-quadruplex-type structures that are variably stable in the presence of physiologically relevant ions. We hypothesized that this structured domain is sufficient for myelin binding. In this study, we confirm that a 20-nucleotide DNA, corresponding to the 5′ half of LJM-3064, retains myelin-binding properties. We then optimize this minimal myelin-binding aptamer via systematic evolution of ligands by exponential enrichment after sparse rerandomization. We report a sequence variant (LJM-5708) of the 20-nucleotide myelin-binding aptamer with enhanced myelin-binding properties and the ability to bind cultured human oligodendroglioma cells in vitro , providing the first evidence of cross-species reactivity of this myelin-binding aptamer. As our formulation of DNA aptamers for in vivo remyelination therapy involves conjugation to streptavidin, we verified that the myelin-binding properties of LJM-5708 were retained in conjugates to avidin, streptavidin, and neutravidin. DNA aptamer LJM-5708 is a lead for further preclinical development of remyelinating aptamer technologies.

BACKGROUND Success in skin cancer treatment is determined through outcome measurement. Patients and physicians may prioritize different outcomes of care, and identification of such may enhance patient-centered care. OBJECTIVE To identify gaps between patient and physician attitudes toward skin cancer outcomes. MATERIALS AND METHODS A single-day, 21-patient, modified, in-person Delphi process to solicit and rate the importance of skin cancer–related outcomes was conducted. Twelve masked dermatologic surgeons rated patient-generated outcomes in a 2-round modified Delphi process. Each item was rated on a 1 to 9 scale (1, least important; 9, most important) using the Qualtrics web platform (Qualtrics, Provo, UT). Results of the physician ratings were compared with the patient ratings. RESULTS A list of 53 skin cancer treatment–related themes and outcomes was generated. Eight items were ranked by physicians as “very high” (>80% importance), 5 as “high” (>70% importance), 19 as intermediate, and 21 as low. The physician and patient panels' ratings were concordant for 56% of items, whereas 7 outcome items showed a 2-category discordance. CONCLUSION Physicians and patients were concordant regarding skin cancer treatment on multiple spheres. Areas of discordance include patient fear of unknown future risk, recurrence, or empowering patients to make treatment choices, and may be areas of continued improvement for delivery of patient-centered care.

BACKGROUND Patient-reported outcomes are critical to research directed at maximizing patient benefit. The outcomes patients consider most relevant in the treatment of skin cancer have not been directly investigated. OBJECTIVE To develop a ranked list of outcomes deemed most important by patients with skin cancer through a proctored Delphi process. METHODS Twenty-one patients with a history of skin cancer volunteered to participate in the patient summit. The patient members participated in a guided discussion to generate a long list of potentially relevant outcomes. The list was then condensed and ranked through 2 rounds of a proctored Delphi process. RESULTS Patients were diverse in their skin cancer histories and complexities, ages, and states of residence. Twelve themes were rated as highly important by 70% or more of participants. Most of these themes related to patient education and the collaborative nature of the physician–patient relationship. Fear of recurrence and cosmetic outcome were also highly rated. Limitations include a preponderance of older patients and patients from the midwest and northeast. CONCLUSION Patients with skin cancer overwhelmingly prioritize a shared decision-making process, in which they are actively engaged and value detailed education regarding their disease. This should inform future research directed at skin cancer treatment and current physician–patient interactions.