LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.

Background: G protein-coupled receptor heteromerization is believed to exert dynamic regulatory impact on signal transduction. CXC chemokine receptor 4 (CXCR4) and its ligand CXCL12, both of which are overexpressed in many cancers, play a pivotal role in metastasis. Likewise, lysophosphatidic acid receptor 1 (LPA) is implicated in cancer cell proliferation and migration.

Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies.

Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, and convenient administration to patients. The ability to use computational methods to predict biophysical properties from protein sequence, potentially in combination with high throughput assays, could decrease timelines and increase the success rates for therapeutic developability engineering by eliminating lengthy and expensive cycles of recombinant protein production and testing. To support development of high-quality predictive models for antibody developability, we designed a sequence-diverse panel of 83 effector functionless IgG1 antibodies displaying a range of biophysical properties, produced and formulated each protein under standard platform conditions, and collected a comprehensive package of analytical data, including in vitro assays and in vivo mouse pharmacokinetics.

Safety, Tolerability, and Pharmacokinetics of a Novel Macrocyclic Gadolinium-Based Contrast Agent, HNP-2006, in Healthy Subjects.

Objectives: Gadolinium-based contrast agents (GBCAs) are indispensable in contrast-enhanced magnetic resonance imaging. A higher risk of gadolinium deposition in linear GBCAs required the introduction of macrocyclic GBCAs with a stable molecular structure. We conducted the first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (PKs) of HNP-2006, a novel macrocyclic GBCA, in healthy male subjects.

Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration.

C-X-C chemokine receptor 4 (CXCR4) is widely overexpressed in various types of cancer and is involved in several cancer phenotypes including tumor growth, survival, and metastasis. The roles of histamine and histamine receptor H1 (HRH1) in cancer pathogenesis remain controversial. Here, we show that HRH1 is widely expressed in various cancer cell lines and cancer tissues and that coexpression of CXCR4 and HRH1 is associated with poor prognosis in breast cancer.

Clinical Features and Long-term Prognosis of Crohn's Disease in Korea: Results from the Prospective CONNECT Study.

Background/aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.

Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019).

Patterns and Disparities in Human Papillomavirus (HPV) Vaccine Uptake for Young Female Adolescents among U.S. States: NIS-Teen (2008-2016).

Background: Several studies have reported differential vaccine uptake outcomes that are associated with sociodemographic and socioeconomic characteristics, as well as provider type. However, none has examined a trend over a multiple-year span. In this study, we utilize a longitudinal data-based approach to examine state-level human papillomavirus (HPV) vaccine trends and their influences over time.

Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs.

At present there are no drugs for the treatment of chronic liver fibrosis that have been approved by the Food and Drug administration of the United States. Telmisartan, a small-molecule antihypertensive drug, displays antifibrotic activity, but its clinical use is limited because it causes systemic hypotension. Here, we report the scalable and convergent synthesis of macromolecular telmisartan prodrugs optimized for preferential release in diseased liver tissue.

Predictive factors of submucosal fibrosis before endoscopic submucosal dissection for superficial squamous esophageal neoplasia.

Objectives: Endoscopic submucosal dissection (ESD) is an effective treatment modality for superficial squamous esophageal neoplasia (SSEN). However, submucosal fibrosis is an important obstacle to successful ESD. The aim of this study was to determine the ESD outcome in relationship to the degree of submucosal fibrosis of SSEN and to identify factors for predicting submucosal fibrosis.

High Rates of High-Grade Cervical Dysplasia in High-Risk Young Women With Low-Grade Cervical Cytology.

Objective: The aim of the study was to determine rates of cervical intraepithelial neoplasia (CIN) 2 or greater in high-risk, racially diverse, young women with low-grade cytology.

Materials And Methods: After institutional review board approval, a cross-sectional study of 21- to 24-year-old women with low-grade cytology (atypical squamous cells of undetermined significance, high-risk human papillomavirus+, low-grade squamous intraepithelial lesion, or human papillomavirus+ only) managed with colposcopy at our university-based clinic between May 2011 and April 2013 were identified. Demographics and pathologic data were collected including age, race, parity, smoking status, screening history, and histology.

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.

Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis.

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.

Background: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab.

Methods: We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles.