Insights into Spontaneous Solid Electrolyte Interphase Formation at Magnesium Metal Anode Surface from Molecular Dynamics Simulations.

Spontaneous chemical reactivity at multivalent (Mg, Ca, Zn, Al) electrode surfaces is critical to solid electrolyte interphase (SEI) formation, and hence, directly affects the longevity of batteries. Here, we report an investigation of the reactivity of 0.5 M Mg(TFSI) in 1,2-dimethoxyethane (DME) solvent at a Mg(0001) surface using molecular dynamics (AIMD) simulations and detailed Bader charge analysis.

First-principles calculation of the configurational energy density of states for a solid-state ion conductor with a variant of the Wang and Landau algorithm.

In this work, a variant of the Wang and Landau algorithm for calculation of the configurational energy density of states is proposed. The algorithm was developed for the purpose of using first-principles simulations, such as density functional theory, to calculate the partition function of disordered sublattices in crystal materials. The expensive calculations of first-principles methods make a parallel algorithm necessary for a practical computation of the configurational energy density of states within a supercell approximation of a solid-state material.

SMAD4 Loss Is Associated with Cetuximab Resistance and Induction of MAPK/JNK Activation in Head and Neck Cancer Cells.

We previously demonstrated an association between decreased expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC.

A key to the backdoor into the castle: The clinical ramifications of immunoediting driven by antigenic competition.

Over the last decade the field of cancer biology has gained considerable data on genomic heterogeneity. This situation creates challenges and possibly opportunities for cancer treatment. The evolution of the tumor at all stages also requires the growing malignancy to confront and avoid the immune system.

CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.

Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations.

Decreased SMAD4 expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and cetuximab, a monoclonal antibody targeting this receptor, is widely used to treat these patients. In the following investigation, we examined the role of SMAD4 down-regulation in mediating epithelial-to-mesenchymal transition (EMT) and cetuximab resistance in HNSCC. We determined that SMAD4 downregulation was significantly associated with increased cell motility, increased expression of vimentin, and cetuximab resistance in HNSCC cell lines.

Cleaved NOTCH1 Expression Pattern in Head and Neck Squamous Cell Carcinoma Is Associated with NOTCH1 Mutation, HPV Status, and High-Risk Features.

The Notch pathway is frequently altered in head and neck squamous cell carcinomas (HNSCC); however, the clinical significance of NOTCH1 dysregulation is poorly understood. This study was designed to characterize expression of the transcriptionally active NOTCH1 intracellular domain (NICD1) in HNSCCs and evaluate its association with NOTCH1 mutation status and clinical parameters. IHC for NICD1 was performed on 79 previously sequenced archival HNSCCs with known NOTCH1 mutation status.

Notch signaling mediates melanoma-endothelial cell communication and melanoma cell migration.

Stromal and cellular components within the tumor microenvironment significantly influence molecular signals mediating tumor growth and progression. We recently performed a screen to evaluate critical mediators of melanoma-endothelial communication and identified several molecular pathways associated with these cellular networks, including Notch3. Here, we evaluate the nature of melanoma-endothelial communication mediated by Notch3 and its functional significance.

Biology of human papillomavirus-related oropharyngeal cancer.

Recent data show that human papillomavirus-positive oropharyngeal cancer (OPC) has a distinct biological and clinical behavior compared with human papillomavirus-negative OPC. As this subset of head and neck cancer represents an increasing public health concern, a thorough understanding of the causative and mechanistic differences between these diseases and how these distinctions impact clinical treatment is required. In this review, we will summarize recent data in epidemiology, the mechanism of viral carcinogenesis and differences in tumor biology that may provide insights to improve the clinical management of patients with human papillomavirus-positive OPC.

Therapeutic targets in head and neck squamous cell carcinoma: identification, evaluation, and clinical translation.

Head and neck squamous cell carcinoma (HNSCC) encompasses a diverse group of malignancies originating in the oral cavity, oropharynx, larynx and hypopharynx. Although treatment modalities have improved, carefully designed biomarker-driven clinical trials will yield the best opportunities to enhance HNSCC therapy options in the future. Due to the heterogeneous nature of HNSCC, discovering a "silver bullet" for the treatment of HNSCC is unlikely.

Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma.

A mutational analysis of the matrix metalloproteinase (MMP) gene family in human melanoma identified somatic mutations in 23% of melanomas. Five mutations in one of the most commonly mutated genes, MMP8, reduced MMP enzyme activity. Expression of wild-type but not mutant MMP8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression.

Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase II.

Ang II receptor activation increases cytosolic Ca2+ levels to enhance the synthesis and secretion of aldosterone, a recently identified early pathogenic stimulus that adversely influences cardiovascular homeostasis. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a downstream effector of the Ang II-elicited signaling cascade that serves as a key intracellular Ca2+ sensor to feedback-regulate Ca2+ entry through voltage-gated Ca2+ channels. However, the molecular mechanism(s) by which CaMKII regulates these important physiological targets to increase Ca2+ entry remain unresolved.