Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system1. We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 106 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly3. Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.

Objective-To test a 2-year community-and family-based obesity prevention intervention for low-income African-American girls.Design-Randomized controlled trial with follow-up measures scheduled at 6, 12, 18 and 24 months.Setting-Low-income areas of Oakland, CA.Participants-261 8-10 year old African-American girls and their parents/caregivers. Interventions-Families were randomized to two-year, culturally-tailored interventions: (1) after school Hip-Hop, African and Step dance classes and a home/family-based intervention to reduce screen media use or (2) information-based health education. Main Outcome Measure-Body mass index (BMI) change. Results-Changes in BMI did not differ between groups (adjusted mean difference [95% confidence interval] = 0.04 [−.18, .27] kg/m 2 per year). Among secondary outcomes, fasting total cholesterol (−3.49 [−5.28, −1.70] mg/dL per year), LDL-cholesterol (−3.02 [−4.74, −1.31] mg/dL per year), incidence of hyperinsulinemia (Relative Risk 0.35 [0.13, 0.93]), and depressive symptoms (−0.21 [−0.42, −0.001] per year) fell more among girls in the dance and screen time reduction intervention.In exploratory moderator analysis, the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline (P=.02) and/or those whose parents/guardians were unmarried (P<.01).Conclusions-A culturally-tailored after-school dance and screen time reduction intervention for low-income, preadolescent African-American girls did not significantly reduce BMI gain compared to health education, but produced potentially clinically important reductions in lipids,

To evaluate the feasibility, acceptability, and efficacy of an after-school team sports program for reducing weight gain in low-income overweight children.Design: Six-month, 2-arm, parallel-group, pilot randomized controlled trial.

:  There have been few reports of successful long‐term culture of cells established from cutaneous basal cell carcinoma (BCC) tumors. Here, we describe techniques that have enabled us to establish three long‐term cultures of BCC cells isolated from BCC tumors that arose in irradiated Patched 1 (Ptch1)+/− mice. All three cell lines showed cellular morphology similar to that of BCC tumors and could be propagated for at least 20 passages. In addition, similar to BCC tumors, all cell lines had lost the wildtype Ptch1 allele, expressed BCC molecular markers, and responded similarly to cyclopamine, a small molecule inhibitor of Hedgehog signaling. Finally, we describe an efficient electroporation technique for DNA transfection into the BCC cell lines and show that they have activated Hedgehog signaling activity, albeit at a level lower than that of murine BCCs in vivo. These data indicate that the cell lines are bona fide long‐term cultures of BCC cells and that DNA plasmids can be introduced into the BCC cell lines with relatively high transfection efficiency using a modified electroporation technique.

Objective-African-American girls and women are at high risk of obesity and its associated morbidities. Few studies have tested obesity prevention strategies specifically designed for AfricanAmerican girls. This report describes the design and baseline findings of the Stanford GEMS (Girls health Enrichment Multi-site Studies) trial to test the effect of a 2-year community-and family-based intervention to reduce weight gain in low-income, preadolescent African-American girls.Design-Randomized controlled trial with measurements scheduled in girls' homes at baseline, 6, 12, 18 and 24 months post randomization.Setting-Low-income areas of Oakland, CA. Participants-Eight, nine and ten year old African-American girls and their parents/caregivers.Interventions-Girls are randomized to a culturally-tailored after school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education active-placebo comparison intervention. Interventions last for 2-years for each participant.Main Outcome Measure-Change in body mass index over the two-year study.Results-Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample. 261 families were randomized. One girl per family is randomly chosen for the analysis sample. Randomization produced comparable experimental groups with only a few statistically significant differences. The sample had a mean body mass index (BMI) at the 74 th percentile on the 2000 CDC BMI reference, and one-third of the analysis sample had a BMI at the 95 th percentile or above. Average fasting total cholesterol and LDL-cholesterol were above NCEP thresholds for borderline high classifications. Girls averaged low levels of moderate to vigorous physical activity, more than 3 hours per day of screen media use, and diets high in energy from fat. Conclusions-TheStanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen time reduction interventions for obesity prevention in low-income, preadolescent African-American girls.