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Introduction: Adolescent and young adult cancer survivors, especially racial/ethnic minorities and rural residents are particularly vulnerable to financial toxicity due to limited healthcare access, socioeconomic disparities, and cultural/language barriers. These social determinants of health compound financial hardship and contribute to poor healthcare transitions from pediatric to adult care, leading to worse outcomes and higher mortality rates. Methods: Our cross-sectional survey study examined racial (Black vs White) and geographic (rural vs urban) disparities in financial toxicity and healthcare transition outcomes among 260 adolescent and young adult cancer survivors through the Kentucky Cancer Registry. Survey data were collected on financial toxicity, healthcare transitions, and health-related quality of life. Financial toxicity was measured under three domains: psychological response, material conditions (e.g., loss of income, debt), and coping behaviors. Results: Results revealed moderate levels of financial toxicity and healthcare transition readiness across the sample, with strong associations between financial toxicity and anxiety, depression, and long-term effects of cancer treatment. Black participants showed higher levels of anxiety and coping behaviors compared to Whites, while urban participants experienced lower financial toxicity (as measured by material conditions) than their rural counterparts. Racial disparities were observed in global health and anxiety, even after adjusting for financial toxicity, but the relationship between financial toxicity and healthcare transitions outcomes did not vary by race or geography. Conclusion: This study highlights the importance of developing tailored strategies to mitigate the impact of cancer-related financial toxicity on the health outcomes and quality of life of underserved adolescent and young adult cancer survivors.

We identified a germline TP53 c.758C > T (p.T253I) mutation in the TP53 tumor suppressor gene in a pediatric adrenocortical carcinoma (ACC) patient. Characteristic of pathogenic p53 mutations, we observed upregulation of total p53 protein levels in the patient's ACC and concurrent suppression of the wild-type (WT) TP53 allele. As ACC can be associated with Li-Fraumeni Syndrome (LFS) and the mutation has not yet been linked to LFS, we sought to characterize the functionality of the T253I mutation. We acquired p53-/- HEK293 cells and stably transduced them with GFP-tagged wild type (T253) or T253I p53 as well as two established pathogenic p53 mutants (C176Y and R213X). Compared to p53 WT, levels of T253I p53 increased while MDM2 levels decreased, suggesting a loss of MDM2-mediated regulation of T253I p53. Additionally, T253I showed a reduction in DNA damage responsive events, diminished DNA binding capabilities, and blunted transactivation capacity. These experimental data lead us to conclude that T253I represents a pathologic variant in TP53 that may predispose to LFS-associated tumors.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-020-80467-y .

National lung cancer screening with low dose computed tomography (LDCT) uptake is suboptimal. One factor contributing to slow uptake is lack of awareness. Trained Community Health Workers (CHWs) may be effective in increasing lung cancer screening awareness among disparate populations, however little is known about the processes necessary to scale an intervention for implementation by CHWs in a new area. We examined implementation processes with the RE-AIM framework and pilot tested a CHW-delivered lung cancer education intervention based on the Health Belief Model. We measured pre-post participant knowledge, attitudes and beliefs regarding cancer screening, lung cancer stigma, and intent to obtain LDCT screening. We used community-engaged strategies to collaborate with a local health system, to identify CHWs. CHWs were trained to recruit participants and deliver the one-session lung cancer education intervention. Seven CHWs and eight community sites participated. Participants (n = 77) were female (53%) primarily low income (62.9%); tobacco use was high (36.9%). Post intervention changes in lung cancer screening knowledge (p =  < .0001), attitudes regarding lung cancer screening benefit (p = .034) and lung cancer stigma. (p = .024) We learned important lessons that will be useful in subsequent scaling. Collaborating with a local health system is a promising method to disseminate a lung cancer screening education intervention.

Chronic migraine is a frequent and debilitating condition affecting 14% of the general population. This prospective observational pilot study investigated whether men with chronic migraine have lower than expected total serum testosterone levels. We identified 14 men ages 26-51 at our Institution who fulfilled the ICHD-3b criteria for chronic migraine and obtained serum total testosterone levels. The mean total testosterone level in our 14 patients was 322 ng/dL (range: 120-542 ng/dL) which is in the lower 5% of the reference range for our laboratory (300-1080 ng/dL). Men with chronic migraine had lower total testosterone levels compared to published agematched normative median values by a median difference of 62 ng/dL (P=0.0494). This finding suggests that hypothalamic regulation is altered in patients with chronic migraine. Further studies are warranted to determine whether testosterone supplementation in men with chronic migraine reduces the number of headaches or the associated symptoms of hypogonadism.

Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage. cAMP-enhanced repair of cisplatin-induced DNA damage was dependent on PKA-mediated phosphorylation of ATR on S435 which promoted ATR's interaction with the key NER factor xeroderma pigmentosum A (XPA) and facilitated recruitment of an XPA-ATR-pS435 complex to sites of cisplatin DNA damage. Moreover, we developed an oligonucleotide retrieval immunoprecipitation (ORiP) assay using a novel platinated-DNA substrate to establish kinetics of ATR-pS435 and XPA's associations with cisplatin-damaged DNA. Expression of a non-phosphorylatable ATR-S435A construct or deletion of A kinase-anchoring protein 12 (AKAP12) impeded platinum adduct clearance and prevented cAMP-mediated enhancement of ATR and XPA's associations with cisplatin-damaged DNA, indicating that ATR phosphorylation at S435 is necessary for cAMP-enhanced repair of platinum-induced damage and protection against cisplatin-induced mutagenesis. These data implicate cAMP signaling as a critical regulator of genomic stability against platinum-induced mutagenesis.

Adolescent and young adult survivors of cancer (aged 15-39 years) frequently engage in hazardous alcohol use, which can have multiple mental and physical health effects. The aim of this study was 2-fold, to identify the necessary adaptations to an existing motivational interviewing-based mHealth (mobile health) alcohol reduction intervention, called Tracking and Reducing Alcohol Consumption (TRAC), for posttreatment adolescents and young adults, and to develop a tailored intervention for this vulnerable and underserved population. This was a qualitative study consisting of key informant interviews with posttreatment adolescents and young adults aged 18-39 years, oncology and psych-oncology providers, and community advocates (n=15) to inform the adaptation of TRAC. Thematic qualitative analysis of interview findings was conducted to determine necessary changes to the intervention protocol and content, which would ultimately lead to the development of the new TRAC adolescent and young adult intervention. Key informant interviews revealed a need for the intervention to address cancer-specific alcohol use triggers such as scan-related anxiety, financial toxicity, and reproductive health concerns. They also indicated the need to provide education on the link between alcohol and cancer and to reduce the time burden of the intervention, given the many competing life demands of adolescents and young adults. Significant changes were made to the TRAC intervention to create the TRAC adolescent and young adult. We reduced the number of required sessions from 8 to 4, introduced a session devoted to managing cancer-specific triggers, and provided survivors with more information about alcohol and its relationship to cancer. There is potential to increase alcohol intervention relevance and fit for adolescents and young adults by including tailored content relevant to their life experiences while also maintaining core components of such interventions, such as self-monitoring and goal-setting. Remote, brief interventions are important for ensuring acceptability. The new TRAC adolescent and young adult intervention represents a potentially valuable tool in addressing high rates of hazardous alcohol use among this population and warrants further evaluation in randomized trials.

Background Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. Methods We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m 2 ). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. Results With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS ( p  = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p  = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p  = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p  = 0.003) and PFS (3.6 vs. 8.4 months, p <0.0001). DXM did not reduce OS in patients who received TMZ and BEV concurrently with RT (22.9 vs 22.8 months, p  = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p  = 0.045). Conclusions Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered.

Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. This study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. Participants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. This project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. This trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals' everyday routines. ClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321. DERR1-10.2196/56562.

Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage. cAMP-enhanced repair of cisplatin-induced DNA damage was dependent on PKA-mediated phosphorylation of ATR on S435 which promoted ATR’s interaction with the key NER factor xeroderma pigmentosum A (XPA) and facilitated recruitment of an XPA-ATR-pS435 complex to sites of cisplatin DNA damage. Moreover, we developed an oligonucleotide retrieval immunoprecipitation (ORiP) assay using a novel platinated-DNA substrate to establish kinetics of ATR-pS435 and XPA’s associations with cisplatin-damaged DNA. Expression of a non-phosphorylatable ATR-S435A construct or deletion of A kinase-anchoring protein 12 (AKAP12) impeded platinum adduct clearance and prevented cAMP-mediated enhancement of ATR and XPA’s associations with cisplatin-damaged DNA, indicating that ATR phosphorylation at S435 is necessary for cAMP-enhanced repair of platinum-induced damage and protection against cisplatin-induced mutagenesis. These data implicate cAMP signaling as a critical regulator of genomic stability against platinum-induced mutagenesis.