Toward the Establishment of a Harmonized Physicochemical Profiling Platform for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order Structure Influences Physical Properties.

Oligonucleotides are short nucleic acids that serve as one of the most promising classes of drug modality. However, attempts to establish a physicochemical evaluation platform of oligonucleotides for acquiring a comprehensive view of their properties have been limited. As the chemical stability and the efficacy as well as the solution properties at a high concentration should be related to their higher-order structure and intra-/intermolecular interactions, their detailed understanding enables effective formulation development.

The expression of S100A4 in human pancreatic cancer is associated with invasion.

Objectives: Pancreatic cancer is one of the most lethal malignancies; its poor prognosis is strongly associated with invasion and metastasis. Expression of S100A4 has been reported to correlate with poor prognosis in various cancers. We have investigated the role of S100A4 in pancreatic cancer tumorigenesis and its clinicopathologic significance.

RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells.

S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca(2+)-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis. We observed frequent overexpression of S100A4 in pancreatic cancer cell lines and further analyzed RNAi-mediated knockdown to address the possibility of its use as a therapeutic target for pancreatic cancer. The specific knockdown of S100A4 strongly suppressed cell growth, induced G2 arrest and eventual apoptosis, and decreased cell migration.

Reduced progression to type 2 diabetes from impaired glucose tolerance after a 2-day in-hospital diabetes educational program: the Joetsu Diabetes Prevention Trial.

Objective: We assessed the effects of a 2-day in-hospital diabetes educational program in preventing or delaying progression of impaired glucose tolerance (IGT) to type 2 diabetes, including analysis of changes in serum lipids, body weight, and blood pressure after the program.

Research Design And Methods: A total of 426 subjects (51 +/- 9 years, BMI 24.6 +/- 3.

AL amyloidosis with spontaneous hepatic rupture: successful treatment by transcatheter hepatic artery embolization.

A 42-year-old male patient with primary AL amyloidosis experienced spontaneous hepatic rupture, producing diffuse widespread intrahepatic hemorrhage. Transcatheter hepatic artery embolization saved his life. Hepatic rupture infrequently develops in patients with systemic amyloidosis, but survival after this complication is rare because surgical treatments seldom succeed.

Low molecular weight hyaluronan increases the Uptaking of oxidized LDL into monocytes.

Since accumulation and interaction of immune cells including T cells and monocytes/macrophages are involved in the processes of atherosclerosis, atherosclerosis is currently understood as an inflammatory disorder. Entrapment of extracellular matrices components such as hyaluronan by monocytes and macrophages, as well as uptake of oxidized low-density lipoprotein (ox-LDL) by these cells, plays a central role in foam cell formation and the pathogenesis of atherosclerosis. We investigated the role of CD44, the principal receptor for hyaluronic acid, and ox-LDL in scavenger receptor expression on resting monocytes prepared by counterflow centrifugal elutriation from the endothelium.

Increased esophageal mucosal/submucosal blood flow in patients with gastroesophageal reflux disease: normalization by treatment with a proton pump inhibitor.

Background And Aim: Mucosal injury caused by gastroesophageal reflux may result in changes in esophageal mucosal blood flow. Little is known about esophageal mucosal blood flow in patients with gastroesophageal reflux disease (GERD). Here we examined esophageal mucosal blood flow and the effects of treatment in patients with GERD.

Serum hyaluronan concentration as a marker of angiopathy in patients with diabetes mellitus.

Accumulation of hyaluronan (HA) around smooth muscle cells in lesions of atherosclerosis in diabetic patients suggests that this protein plays an important role in diabetic angiopathy. The aim of this study was to determine the correlation between serum HA concentrations and diabetic angiopathy. Diabetic patients treated with or without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n = 95).

Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus.

Increased monocyte recruitment into subendothelial space in atherosclerotic lesions is one of the hallmarks of diabetic angiopathy. The aim of this study was to determine the state of peripheral blood monocytes in diabetes associated with atherosclerosis. Diabetic patients treated with/without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n=106).

Glycated albumin and cross-linking of CD44 induce scavenger receptor expression and uptake of oxidized LDL in human monocytes.

Functional role of CD44, a principal receptor of hyaluronan, and glycated albumin for differentiation of resting human monocytes isolated by counterflow centrifugal elutriation was investigated. Flow cytometric analysis revealed that amadori-modified glycated albumin induced expression of CD44 as well as macrophage scavenger receptors (MSRs) such as CD36 and CD68 on resting monocytes. Crosslinking of CD44 on monocytes also induced MSR expression.

Management of symptoms in step-down therapy of gastroesophageal reflux disease.

Objective: Majority of studies on gastroesophageal reflux disease (GERD) that include patients with or without erosive disease have documented the efficacy of proton pump inhibitors (PPIs) as well as their superiority to H(2)-receptor antagonist (H(2)-RA). The purpose of this study was to clarify the difference in quality of GERD treatment with PPIs and H(2)-RA in step-down protocol using lansoprazole.

Methods: Forty-three patients with reflux esophagitis were randomly divided into three groups and assessed by severity score; group 1 received 30 mg lansoprazole initially and maintenance therapy with a standard dose H(2)-RA; group 2 received 30 mg of lansoprazole initially and maintenance therapy of 15 mg lansoprazole; and group 3 received 15 mg of lansoprazole once daily for 16 weeks.

Reduced expression of platelet endothelial cell adhesion molecule-1 in bone marrow cells in mice after skeletal unloading.

Unlabelled: One week of tail suspension significantly decreased the expression of PECAM-1 in mouse tibial bone marrow cells but not those of a number of other vascular factors. Anti-PECAM-1 antibody suppressed both ALP+ CFU-f formation and ALP production under co-culture of the osteoblastic cell line and the PECAM-1+ endothelial cell line. This study suggests that the reduced ALP activity after skeletal unloading is related to downregulation of PECAM-1 expression in bone marrow cells in mice.

Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44.

For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers, including breast cancer, do not express integrins.

Monocyte chemoattractant protein-1 induces scavenger receptor expression and monocyte differentiation into foam cells.

Accumulation of monocytes and the entrapment of oxidized-low-density lipoprotein (ox-LDL) in monocytes are important in the differentiation into "foam" macrophages and the pathogenesis of atherosclerosis. We investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the expression of scavenger receptor (SCR) by using resting monocytes prepared by counterflow centrifugal elutriation. Our results showed that: (1) MCP-1 increased the expression of CD36 SCR by flow cytometric analysis.

Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and transendothelial migration of monocytes via the protein kinase C pathway.

Inflammatory and immune responses are highly relevant processes in the pathogenesis of atherosclerosis, as illustrated by the central event of monocyte accumulation in atherosclerotic plaques. Integrin LFA-1-mediated adhesion of circulating monocytes to the endothelium is a prerequisite for recruitment of monocytes to these areas. Integrin-mediated adhesion is tightly regulated and integrins are only functional in response to particular monocyte activation stimuli.