Reprogramming neuroblastoma by diet-enhanced polyamine depletion.

Neuroblastoma is a highly lethal childhood tumor derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fueled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, with the inhibitor difluoromethylornithine showing clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumor differentiation, and profound survival gains in the TH-MYCN mouse model. Specifically, an arginine/proline-free diet decreases the polyamine precursor ornithine and augments tumor polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at adenosine-ending codons. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by the diet-drug combination, favors a pro-differentiation proteome. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.

Novel technique of detecting inflammatory and osseous changes in the glenohumeral joint associated with patient age and weight using FDG- and NaF-PET imaging.

OBJECTIVE: The glenohumeral (GH) joint is a classic ball-and-socket joint of the shoulder subject to various pathologies including osteoarthritis (OA). Degenerative changes of the OA evident on traditional imaging are proceeded by molecular changes, which if detected early could enhance disease prevention and treatment. In this study, we use 18F-FluoroDeoxyGlucose (FDG) and 18F-sodium-fluoride (NaF)-PET/CT to investigate the effects limb laterality, age, and BMI on the inflammation and bone turnover of the GH shoulder joint. METHODS: FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) were analyzed with a semi-quantitative technique based on predefined region of interest. RESULTS: There was greater FDG uptake in the left side of the GH joint compared to the right in both females (left: 0.79 ± 0.17, right: 0.71 ± 0.2; P < 0.0001) and males (left: 0.76 ± 0.19, right: 0.57 ± 0.18; P < 0.0001). We also observed a strong positive association between BMI and FDG uptakes in females (left: P < 0.0001, r = 0.71, right: P < 0.0001, r = 0.58) and males (left: P < 0.0001, r = 0.56, right: P < 0.0001, r = 0.64). Association between BMI and NaF uptake were found in males as well (left: P = 0.004, r = 0.42, right: P = 0.02, r = 0.35). CONCLUSION: Our study demonstrates the varying effect of limb laterality and BMI on FDG and NaF uptake at the GH joint. Adoption of molecular imaging will require future studies that correlate tracer uptake with relevant medical and illness history as well as degenerative change evident on traditional imaging.

Parkinson's Pals: A Student-Led Program to Facilitate Intergenerational Connections and Promote Psychosocial Well-Being Among Persons with Parkinson's Disease.

Parkinson's disease (PD) causes unique motor and non-motor symptoms. Despite symptomatic treatment with pharmacotherapies, many persons with PD report feelings of loneliness and demoralization as their disease progresses. These symptoms greatly interfere with quality of life, necessitating novel treatment strategies. In this report, we introduce a new student-led program to improve psychosocial well-being among persons with PD by pairing them with college students. Through weekly one-on-one meetings, students gain a deeper understanding of PD, while patients gain a new social outlet and purpose. Based on the program's initial successes, we advocate for the adoption of similar programs at universities worldwide.