RESUMEN
Interactions of N2 at oxide surfaces are important for understanding electrocatalytic nitrogen reduction reaction (NRR) mechanisms. Interactions of N2 at the polycrystalline vanadium oxide/vapor interface were monitored at room temperature and total pressures up to 10-1 Torr using Near-Ambient Pressure X-ray Photoelectron Spectroscopy (NAP-XPS). The oxide film was predominantly V(IV), with V(III) and V(V) components. XPS spectra were acquired in environments of both pure N2 and equal pressures of N2 and H2O vapor. In pure N2, broad, partially resolved N1s features were observed at binding energies of 401.0 and 398.7 eV, with a relative intensity of â¼3:1, respectively. These features remained upon subsequent pumpdown to 10-9 Torr. The observed maximum N surface coverage was â¼1.5 × 1013 cm-2-a fraction of a monolayer. In the presence of equal pressures of H2O, the adsorbed N intensity at 10-1 Torr is â¼25% of that observed in the absence of H2O. The formation of molecularly adsorbed H2O was also observed. Density functional theory-based calculations suggest favorable absorption energies for N2 bonding to both V(IV) and V(III) cation sites but less so for V(V) sites. Hartree-Fock-based cluster calculations for N2-V end-on adsorption show that experimental XPS doublet features are consistent with the calculated shake-up and normal, final ionic configurations for N2 end-on bonding to V(III) sites but not V(IV) sites. The XPS spectra of vanadium oxide transferred in situ between electrochemical and UHV environments indicate that the oxide surfaces studied here are stable upon exposure to the electrolyte under NRR-relevant conditions.
RESUMEN
Metastasis is the leading cause of mortality in patients with solid tumors. In this regard, we previously reported that Pseudopodium-Enriched Atypical Kinase One (PEAK1) is necessary for non-canonical Transforming Growth Factor ß (TGFß) signaling and TGFß/fibronectin-induced metastasis. Here, we demonstrate that inhibition of DHPS-dependent eIF5A1/2 hypusination blocks PEAK1 and E-Cadherin expression, breast cancer cell viability and TGFß/fibronectin-induced PEAK1-dependent breast cancer metastasis. Interestingly, TGFß stimulation of high-grade metastatic breast cancer cells increases and sustains eIF5A1/2 hypusination. We used a suite of bioinformatics platforms to search biochemical/functional interactions and clinical databases for additional control points in eIF5A1/2 and PEAK1-Epithelial to Mesenchymal Transition (EPE) pathways. This effort revealed that interacting EPE genes were enriched for TP53 transcriptional targets and were commonly co-amplified in breast cancer patients harboring inactivating TP53 mutations. Taken together, these results suggest that combinatorial therapies targeting DHPS and protein activities elevated in TP53-mutant breast cancers may reduce systemic tumor burden and improve patient outcomes.
Asunto(s)
Neoplasias de la Mama/metabolismo , Fibronectinas/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Proteínas de Unión al ARN/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Mama/patología , Cadherinas/antagonistas & inhibidores , Cadherinas/genética , Cadherinas/metabolismo , Femenino , Guanina/análogos & derivados , Guanina/farmacología , Humanos , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/antagonistas & inhibidores , Factores de Iniciación de Péptidos/antagonistas & inhibidores , Pronóstico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas de Unión al ARN/antagonistas & inhibidores , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/metabolismo , Factor 5A Eucariótico de Iniciación de TraducciónRESUMEN
Semiconducting boron carbides based on cross-linked carborane (B10C2H12) icosahedra, developed several decades ago, are of significant interest in a variety of emerging areas, including photocatalysis, spintronics, and especially neutron detection. These materials, however, display generally poor charge carrier mobility, high defect levels and other properties that pose significant drawbacks. A class of nanocomposite carborane-based materials has recently been developed, that addresses many of these issues. The films consist of polymerized mixtures of carboranes and aromatic species, including benzene, 1,4-diaminobenzene, pyridine or aniline. In these materials, electronic states corresponding to the aromatic moiety appearing near the top of the valence band, and states associated with the carborane moiety occupy the bottom of the conduction band. Band gap energies are substantially reduced relative to films without aromatic content. Transport measurements also indicate that charge scattering lifetimes are substantially enhanced in aromatic/carborane films compared to corresponding films without aromatic content. This combination of superior electron-hole separation, narrower band gaps, and superior charge scattering lifetimes, yields markedly enhanced charge collection in neutron voltaics studies compared to conventional carborane-derived boron carbides. The implications of these enhanced properties for neutron detection and other applications are discussed.
RESUMEN
The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers.
RESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that affects nearly 50,000 patients each year. The overall 5-year survival rate for this malignancy remains the lowest of any cancer at around 7% due to limited diagnostic methods, disease aggressiveness and a lack of targeted therapeutic interventions. This review highlights the successes achieved over the past several decades as well as the significant cellular and molecular hurdles that remain in combatting this deadly disease at a translational level.
Asunto(s)
Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Animales , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/terapia , Humanos , Mutación , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapiaRESUMEN
Cripto is a developmental oncoprotein that signals via mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and Smad2/3 pathways. However, the molecular basis for Cripto coupling to these pathways during embryogenesis and tumorigenesis is not fully understood. In this regard, we recently demonstrated that Cripto forms a cell surface complex with the HSP70 family member glucose-regulated protein-78 (GRP78). Here, we provide novel functional evidence demonstrating that cell surface GRP78 is a necessary mediator of Cripto signaling in human tumor, mammary epithelial and embryonic stem cells. We show that targeted disruption of the cell surface Cripto/GRP78 complex using shRNAs or GRP78 immunoneutralization precludes Cripto activation of MAPK/PI3K pathways and modulation of activin-A, activin-B, Nodal and transforming growth factor-beta1 signaling. We further demonstrate that blockade of Cripto binding to cell surface GRP78 prevents Cripto from increasing cellular proliferation, downregulating E-Cadherin, decreasing cell adhesion and promoting pro-proliferative responses to activin-A and Nodal. Thus, disrupting the Cripto/GRP78 binding interface blocks oncogenic Cripto signaling and may have important therapeutic value in the treatment of cancer.