Barriers and facilitators to sexual and reproductive health communication between pediatric oncology clinicians and adolescent and young adult patients: The clinician perspective.

BACKGROUND: Sexual and reproductive health (SRH) is identified by adolescent and young adult (AYA) patients with cancer as an important but often neglected aspect of their comprehensive cancer care. The purpose of this study was to investigate the attitudes and perceptions of pediatric oncology clinicians towards discussing SRH with AYAs, and to understand perceived barriers to effective communication in current practice. PROCEDURE: Pediatric oncology clinicians (physicians, certified nurse practitioners, and physician assistants) participated in semi-structured qualitative interviews investigating attitudes about SRH communication with AYAs and barriers to such conversations. Twenty-two clinicians participated from seven institutions in the Northeastern United States. Interviews were audio-recorded, transcribed, and coded using a thematic analysis approach. RESULTS: Interviews with pediatric oncology clinicians revealed the following five primary themes: the role for pediatric oncology clinicians to discuss SRH, the focus of current SRH conversations on fertility, the meaning of "sexual health" as safe sex and contraception only, clinician-reported barriers to SRH conversations, and the need for education and support. Communication barriers included lack of knowledge/experience, lack of resources/referrals, low priority, parents/family, patient discomfort, clinician discomfort, time, and lack of rapport. Clinicians identified resource and support needs, including formal education and SRH education materials for patients and families. CONCLUSIONS: Although the study participants identified a role for pediatric oncology clinicians in SRH care for AYA patients with cancer, multiple barriers interfere with such discussions taking place on a regular basis. Future efforts must focus on resource development and provider education and training in SRH to optimize the care provided to this unique patient population.

Nucleophosmin interacts with and inhibits the catalytic function of eukaryotic initiation factor 2 kinase PKR.

In normal cells the protein kinase PKR effects apoptosis in response to various extra and intracellular cues and can also function to suppress the neoplastic phenotype. Because most neoplastic cells are resistant to certain apoptotic cues, we reasoned that an early molecular event in carcinogenesis or leukemogenesis might be the inactivation of PKR by expression or activation of intracellular PKR inhibitors. Seeking novel PKR-modulating proteins we report here that nucleophosmin (NPM), a protein frequently overexpressed in a variety of human malignancies, binds to PKR, and inhibits its activation. Co-immunoprecipitation and in vitro binding experiments showed that NPM associated with PKR. Kinase assays demonstrated that recombinant NPM inhibited PKR activation in a dose-dependent manner. In addition, purified recombinant NPM was phosphorylated by activated PKR. Most importantly, overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis. Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues, but enforced expression of NPM in these mutant cells reduced aberrant apoptotic responses. Inhibition of PKR by NPM may be one mechanism by which neoplastic clones evolve in sporadic malignancies and in neoplastic cells arising in the context of the cancer predisposition syndrome, Fanconi anemia.