SUMMARY
Histone variants are emerging as key regulatory molecules in cancer. Here we report a novel role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z interacting protein, whose levels are also elevated in melanoma. We further demonstrate that H2A.Z.2 regulated genes are bound by BRD2 and E2F1 in a H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies.
BackgroundTo date, patients with pre-existing autoimmune conditions have been excluded from immunotherapy trials out of concern for severe autoimmune exacerbations.Case PresentationWe describe the first case of a patient with metastatic cKIT mutated acral melanoma, brain metastasis, and pre-existing severe autoimmune bullous pemphigoid (BP) with stable and asymptomatic disease 10 months after treatment with pembrolizumab. The patient experienced severe BP exacerbation after therapy with ipilimumab requiring systemic immune suppression, but nonetheless pembrolizumab was administered on further disease progression.ConclusionsThis case suggests that pembrolizumab may confer more benefit than risk even in patients with known severe autoimmune conditions who require intermittent systemic immunosuppression.
To evaluate the efficacy and safety of photodynamic therapy (PDT) with the novel 10% aminolevulinic acid (ALA) hydrochloride gel (10% ALA gel) and BF-RhodoLED® light (635 nm; 37 J/cm 2 ) in combination with intense pulsed light (IPL) to augment the medical and aesthetic improvement of photodamaged skin of the dećollete. Methods: This was a single-site prospective, randomized, intraindividual split chest pilot study with 20 female subjects with moderate to severe photodamage of the dećollete. Subjects were randomized to ALA-PDT + IPL to one split-side of the chest and ALA-PDT only to the contralateral side. Three blinded raters assessed aesthetic improvement using the global aesthetic improvement scale (GAIS). Results: Eighteen subjects completed the study. Superior GAIS results were achieved on the ALA-PDT + IPL treatment side than on the ALA-PDT only treatment side (p < 0.001) after 24 weeks of follow-up. Conclusions: ALA-PDT using 10% ALA hydrochloride gel and BF-RhodoLED® light had superior rejuvenation effects on the dećolletéwhen combined with IPL compared to ALA-PDT alone.
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