Hydrogen-Deuterium Exchange Mass Spectrometry Reveals a Novel Binding Region of a Neutralizing Fully Human Monoclonal Antibody to Anthrax Protective Antigen.

Anthrax vaccine adsorbed (AVA) containing protective antigen (PA) is the only FDA-approved anthrax vaccine in the United States. Characterization of the binding of AVA-induced anti-PA human antibodies against the PA antigen after vaccination is crucial to understanding mechanisms of the AVA-elicited humoral immune response. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is often coupled with a short liquid chromatography gradient (e.

Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals.

Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin.

High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma.

Background: HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting.

Results: Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98).

Hypoxia-inducible factor-1alpha polymorphisms and TSC1/2 mutations are complementary in head and neck cancers.

Background: Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF-1alpha) that increases its activity and stability under normoxia have recently been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1alpha. Here, we investigate the novel polymorphisms in exon 12, that approximate the oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28 patients with oral squamous carcinomas.

Endostatin inhibits nitric oxide and diminishes VEGF and collagen XVIII in squamous carcinoma cells.

Low pO(2) values are a common finding among oral squamous cell carcinomas (SCC). Our objective was to determine the role that oxygen tension plays on the direct tumor effect of endostatin (ES). Squamous carcinoma cell lines were grown under normoxic or hypoxic conditions and treated with endostatin (ES), nitric oxide (NO) donors, NO scavengers, NO synthase inhibitors, or transduced with AdenoVec-hEndo or AdenoVec Null vectors.

Inhibition of cysteine proteinases by autolytic digestion is mediated by CBP2/Hsp47.

CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases.

The production of the endostatin precursor collagen XVIII in head and neck carcinomas is modulated by CBP2/Hsp47.

Tumor progression is dependent in large part on angiogenesis and angiogenesis inhibitors have repeatedly been shown to inhibit tumor growth. The present study sought to determine whether the oral squamous carcinoma cells expressed and produced collagen XVIII, a known precursor of endostatin. Four established cell lines of oral squamous cell carcinoma (SCC) were employed for these studies.