Enhancing the Anticancer Activity of Attenuated by Cell Wall Functionalization with "Clickable" Doxorubicin.

Among bacteria used as anticancer vaccines, attenuated (Lm) stands out, because it spreads from one infected cancer cell to the next, induces a strong adaptive immune response, and is suitable for repeated injection cycles. Here, we use click chemistry to functionalize the Lm cell wall and turn the bacterium into an "intelligent carrier" of the chemotherapeutic drug doxorubicin. Doxorubicin-loaded Lm retains most of its biological properties and, compared to the control fluorophore-functionalized bacteria, shows enhanced cytotoxicity against melanoma cells both in vitro and in a xenograft model in zebrafish.

A cyanine-based NIR fluorescent Vemurafenib analog to probe BRAF in cancer cells.

BRAF represents one of the most frequently mutated protein kinase genes and BRAF mutation may be found in many types of cancer, including hairy cell leukemia (HCL), anaplastic thyroid cancer (ATC), colorectal cancer and melanoma. Herein, a fluorescent probe, based on the structure of the highly specific BRAF inhibitor Vemurafenib (Vem, 1) and featuring the NIR fluorophore cyanine-5 (Cy5), was straightforwardly synthesized and characterized (Vem-L-Cy5, 3), showing promising spectroscopic properties. Biological validation in BRAF-mutated cancer cells evidenced the ability of 3 to penetrate inside the cells, specifically binding to its elective target BRAF with high affinity, and inhibiting MEK phosphorylation and cell growth with a potency comparable to that of native Vem 1.

PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation.

In human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3'UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3'UTR in melanoma cells.

A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy.

Background: The ability to increase their degree of pigmentation is an adaptive response that confers pigmentable melanoma cells higher resistance to BRAF inhibitors (BRAFi) compared to non-pigmentable melanoma cells.

Methods: Here, we compared the miRNome and the transcriptome profile of pigmentable 501Mel and SK-Mel-5 melanoma cells vs. non-pigmentable A375 melanoma cells, following treatment with the BRAFi vemurafenib (vem).