Impact of Mechanical and Architectural Signals in the Tumor Microenvironment on Melanoma.

Compared to sun-exposed melanomas, acral melanomas are genetically diverse and occur in areas with low sun exposure and high mechanical loads. During metastatic growth, melanomas invade from the epidermis to the dermis layers through dense tumor stroma and are exposed to fibrillar collagen architectures and mechanical stresses. However, the role of these signals during acral melanoma pathogenesis is not well understood.

Macrophage-T Cell Physical Interaction Modulates IFN-γ Secretion.

Macrophages and T cells communicate under homeostatic and pathological conditions. Previous studies elucidated biochemical crosstalk between macrophages and T cells. However, recent technological advances in multiplex tissue imaging reveal that these cells are often located proximally.

LZTR1 is a melanoma oncogene that promotes invasion and suppresses apoptosis.

Leucine zipper like transcription regulator 1 (LZTR1) is amplified in acral melanomas, is required for melanocytes and melanoma cell proliferation, and it induces anchorage-independent growth, by yet unknown mechanisms. We therefore performed comprehensive studies to identify its activity in melanomas employing proximity biotinylation and co-immunoprecipitation combined with LC-MS/MS proteomics and molecular characterization. The results show that LZTR1 regulates the ubiquitin proteasome system in melanoma cells and also associates with actin-related proteins and actin cytoskeleton organization.

Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications.

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. Even after surgery and chemoradiotherapy, residual GBM cells can infiltrate the healthy brain parenchyma to form secondary tumors. To mitigate GBM recurrence, we recently developed an injectable hydrogel that can be crosslinked in the resection cavity to attract, collect, and ablate residual GBM cells.

Development of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem-Like Cells with CXCL12-Mediated Chemotaxis.

Glioblastoma (GBM), characterized by high infiltrative capacity, is the most common and deadly type of primary brain tumor in adults. GBM cells, including therapy-resistant glioblastoma stem-like cells (GSCs), invade the healthy brain parenchyma to form secondary tumors even after patients undergo surgical resection and chemoradiotherapy. New techniques are therefore urgently needed to eradicate these residual tumor cells.

Characterization and structure-property relationships of an injectable thiol-Michael addition hydrogel toward compatibility with glioblastoma therapy.

Glioblastoma multiforme (GBM) is an aggressive primary brain cancer and although patients undergo surgery and chemoradiotherapy, residual cancer cells still migrate to healthy brain tissue and lead to tumor relapse after treatment. New therapeutic strategies are therefore urgently needed to better mitigate this tumor recurrence. To address this need, we envision after surgical removal of the tumor, implantable biomaterials in the resection cavity can treat or collect residual GBM cells for their subsequent eradication.

Bubble Cloud Behavior and Ablation Capacity for Histotripsy Generated from Intrinsic or Artificial Cavitation Nuclei.

The study described here examined the effects of cavitation nuclei characteristics on histotripsy. High-speed optical imaging was used to compare bubble cloud behavior and ablation capacity for histotripsy generated from intrinsic and artificial cavitation nuclei (gas-filled microbubbles, fluid-filled nanocones). Results showed a significant decrease in the cavitation threshold for microbubbles and nanocones compared with intrinsic-nuclei controls, with predictable and well-defined bubble clouds generated in all cases.