Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions <it>in vitro </it>in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays.</p> <p>Methods</p> <p>One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the <it>in vitro </it>screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed <it>in vivo </it>angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line.</p> <p>Results</p> <p>Pentastatin-1 decreased the invasion of vessels into angioreactors <it>in vivo </it>in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density <it>in vivo </it>in a small cell lung cancer xenograft model.</p> <p>Conclusions</p> <p>The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.</p

The Proline/Citrulline Ratio as a Biomarker for OAT Deficiency in Early Infancy

Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood because of the nonspecific character of initial symptoms. Here, we report findings in a neonate who was evaluated because of a positive family history of OAT deficiency. The reversed enzymatic flux in early infancy resulted in borderline low ornithine concentration – evoking urea cycle disturbances – and increased proline. In addition, plasma citrulline was low. Consequently, the proline/citrulline ratio in plasma was increased compared to controls. To find out whether amino acid profiling in neonatal dried blood spots is suitable to detect OAT deficiency, we evaluated the original newborn dried blood spots of two affected patients and compared it with a database of >450,000 newborns tested in Minnesota since 2004. Proline concentrations (777 and 1,381 μmol/L) were above the 99 percentile (776 μmol/L) of the general population, and citrulline concentrations (4.5 and 4.9 μmol/L) only just above the 1 percentile (4.37 μmol/L). The proline/citrulline ratio was 172.9 and 281.8, respectively. This ratio was calculated retrospectively in the normal population, and the 99 percentile was 97.6. Applying this ratio for NBS could lead to early and specific detection of neonatal OAT deficiency, with no additional expense to newborn screening laboratories quantifying amino acids. Given that early diagnosis of OAT disease can lead to earlier treatment and prevent visual impairment, further studies are indicated to evaluate whether newborn screening for OAT deficiency is warranted

Accumulation of 8-hydroxydeoxyguanosine and its relationship with antioxidant parameters in patients with Eales' disease: Implications for antioxidant therapy

10.1076/ceyr.27.2.103.15951Current Eye Research272103-110CEYR