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Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development.

May 1, 2011

Biomarkers

Abstract The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and isomerization. Each PTM results from a specific local physiological or pathobiological process. Identification of […]

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Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy.

May 1, 2011

Diabetes Metab Res Rev

Abstract BACKGROUND Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters […]

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Biochemical markers of ongoing joint damage in rheumatoid arthritis–current and future applications, limitations and opportunities.

April 28, 2011

Arthritis Res Ther

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of preserving function and preventing disability. Joint inflammation is characterized by synovitis, osteitis, and/or peri-articular osteopenia, […]

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Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover.

April 1, 2011

Osteoarthritis Cartilage

Abstract OBJECTIVES Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a traumatic OA model. METHODS Six groups with 10 7-month-old female Sprague […]

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A quantitative assay for lysosomal acidification rates in human osteoclasts.

April 1, 2011

Assay Drug Dev Technol

Abstract The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption lacunae. The electroneutrality of the lacunae is maintained by chloride transport through […]

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Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials.

April 1, 2011

J Clin Pharmacol

Abstract Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings […]

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Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM–increased serum CIIM in subjects with severe radiographic osteoarthritis.

April 1, 2011

Clin Biochem

Abstract OBJECTIVES In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers. METHODS A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against the neoepitope were developed. CIIM was measured in cartilage explants in the presence or absence […]

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Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis.

March 29, 2011

BMC Dermatol

Abstract BACKGROUND The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver fibrosis. The aim was to investigate CO3-610 levels in another well characterised model […]

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Measurement of CO3-610, a potential liver biomarker derived from matrix metalloproteinase-9 degradation of collagen type iii, in a rat model of reversible carbon-tetrachloride-induced fibrosis.

March 24, 2011

Biomark Insights

Abstract BACKGROUND AND AIM The current study utilized a carbon tetrachloride (CCl(4))-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential prognostic role of the biomarker. MATERIALS AND METHODS 72 female Sprague-Dawley rats aged 6 […]

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A microarray analysis of full depth knee cartilage of ovariectomized rats.

March 15, 2011

BMC Res Notes

Abstract BACKGROUND This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA. FINDINGS We investigated, which extracellular matrix (ECM) protein, proteases and different pro-inflammatory factors was up- […]

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