Bridging the Gap: A Pilot Program to Understand and Meet the Needs of Pediatric Patients and Families as They Transition Off Cancer-Directed Therapy.

Background: With improved curative therapies, over 80% of children and adolescent/young adults diagnosed with cancer are expected to live into adulthood. This population is at risk for increased morbidity and early mortality and requires ongoing health care and surveillance for late effects of treatment. This pilot study assessed the acceptability of a structured medical visit at the completion of cancer-directed therapy as well as patient/family's knowledge of diagnosis and other aspects of care. Method: Patients/families who were 0 to 6 months from completion of cancer-directed therapy attended a one-time transition visit during which they completed a series of questionnaires assessing knowledge about diagnosis, treatment, potential late effects, and duration of ongoing care. They were then given treatment summaries, a plan for follow-up care, information about care after treatment as well as late effects. They completed a questionnaire to assess their satisfaction with this visit. Results: The majority of patients/families knew their diagnosis and treatment modalities. Less knew that their treatment put them at risk for cardiac toxicity or problems with future fertility. A significant number thought follow-up care would continue for only 5 years. Overall participants were satisfied with the visit. Conclusion: The transition period from on to off therapy may be a critical time point to provide patients with cancer and their families with information regarding treatment, follow-up care and testing, and potential late effects. Future studies should assess if this intervention improves compliance with recommended care and surveillance, and improved outcomes.

Monomeric yeast PCNA mutants are defective in interacting with and stimulating the ATPase activity of RFC.

Yeast PCNA is a homo-trimeric, ring-shaped DNA polymerase accessory protein that can encircle duplex DNA. The integrity of this multimeric sliding DNA clamp is maintained through the protein-protein interactions at the interfaces of adjacent subunits. To investigate the importance of trimer stability for PCNA function, we introduced single amino acid substitutions at residues (A112T, S135F) that map to opposite ends of the monomeric protein. Recombinant wild-type and mutant PCNAs were purified from E. coli, and they were tested for their properties in vitro. Unlike the stable wild-type PCNA trimers, the mutant PCNA proteins behaved as monomers when diluted to low nanomolar concentrations. In contrast to what has been reported for a monomeric form of the beta clamp in E. coli, the monomeric PCNAs were compromised in their ability to interact with their associated clamp loader, replication factor C (RFC). Similarly, monomeric PCNAs were not effective in stimulating the ATPase activity of RFC. The mutant PCNAs were able to form mixed trimers with wild-type subunits, although these mixed trimers were unstable when loaded onto DNA. They were able to function as weak DNA polymerase delta processivity factors in vitro, and when the monomeric PCNA-41 (A112T, S135F double mutant) allele was introduced as the sole source of PCNA in vivo, the cells were viable and healthy. These pol30-41 mutants were, however, sensitive to UV irradiation and to the DNA damaging agent methylmethane sulfonate, implying that DNA repair pathways have a distinct requirement for stable DNA clamps.