Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors.

Telomerase reverse transcriptase () mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas.

Biological Validation of RNA Sequencing Data from Formalin-Fixed Paraffin-Embedded Primary Melanomas.

Purpose: Initiatives such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) have generated high-quality, multi-platform molecular data from thousands of frozen tumor samples. While these initiatives have provided invaluable insight into cancer biology, a tremendous potential resource remains largely untapped in formalin-fixed, paraffin-embedded (FFPE) samples that are more readily available, but which can present technical challenges due to crosslinking of fragile molecules such as RNA.

Materials And Methods: We extracted RNA from FFPE primary melanomas and assessed two gene expression platforms -- genome-wide RNA sequencing (RNA-seq) and targeted NanoString -- for their ability to generate coherent biological signals.

Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab.

Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis of heart tissue demonstrated findings consistent with giant cell myocarditis (GCM).

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown.

Tissue resources for clinical use and marker studies in melanoma.

The adequate procurement and preservation of high-quality tissue specimens from patients with melanoma is a critical clinical issue as patients' tumor samples are now used not only for pathological diagnosis but are also necessary to determine the molecular signature of the tumor to stratify patients who may benefit from targeted melanoma therapy. Tissue resources available for physicians and investigators include formalin-fixed paraffin-embedded (FFPE) tissue and frozen tissue, either preserved in optimal cutting temperature (OCT) media or snap frozen. Properly preserved tissue may be used to evaluate melanoma biomarkers by immunohistochemistry (IHC) with tissue microarray (TMA) technology, to perform genetic and genomic analyses, and for other types of translational research in melanoma.

Lysophosphatidic acid induces lymphangiogenesis and IL-8 production in vitro in human lymphatic endothelial cells.

The bioactive phospholipid lysophosphatidic acid (LPA) and its receptors LPA(1-3) are aberrantly expressed in many types of human cancer. LPA has been reported to induce tumor cell proliferation, migration, and cytokine production. However, whether LPA exerts an effect on lymphatic endothelial cells (LECs) or on lymphangiogenesis, a process of new lymphatic vessel formation that is associated with increased metastasis and poor prognosis in cancer patients, has been unknown.

Integrated Molecular and Clinical Analysis of AKT Activation in Metastatic Melanoma.

PURPOSE: Activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway has been implicated in melanoma based primarily on the prevalence of mutations in PTEN and NRAS. To improve our understanding of the regulation and clinical significance of the PI3K-AKT pathway in melanoma, we quantitatively measured the levels of phosphorylated AKT, its substrate GSK3alpha/beta, and its negative regulator PTEN in clinical metastases. Results were compared with mutational status, clinical outcomes, and sites of metastasis.

Transcription of MyoD and myogenin in the non-contractile electrogenic cells of the weakly electric fish, Sternopygus macrurus.

The MyoD family of basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs) are transcriptional activators of skeletal muscle gene expression and are pivotal in inducing the full myogenic program. The expression of these factors after muscle differentiation is complete and the mechanism by which they modulate (or maintain) the muscle phenotype is less well understood. The myogenically derived electric organ (EO) of the electric fish Sternopygus macrurus is an excellent model to address this question.