ecallantide and Ovarian-Neoplasms

At present, considerable efforts have been made to identify new cancer-specific markers for ovarian cancer (OC) diagnosis and the kallikrein-related peptidases (KLKs) family is one of the most studied candidates. This meta-analysis aims to evaluate the pooled diagnostic value of serum KLK measurement for diagnosing OC.. The Cochrane Library, PubMed, Excerpt Medica Database were searched for all relevant literature. The Quality Assessment for Studies of Diagnostic Accuracy tool was applied to assess the quality of enrolled studies. Statistical analysis was conducted by using Stata 13.0 software and Meta-Disc.. A total of 15 studies from 13 articles were considered eligible for inclusion in the present analysis. The following pooled parameters were calculated by using the bivariate model: sensitivity of 0.582 (95% confidence interval [CI], 0.517-0.644), specificity of 0.909 (95% CI, 0.833-0.952), positive likelihood ratios of 6.367 (95% CI, 3.330-12.172), negative likelihood ratios of 0.460 (95% CI, 0.388-0.546), diagnostic odds ratio of 13.831 (95% CI, 6.460-29.614), respectively.. Kallikrein-related peptidase seems to be a promising candidate biomarker in diagnosing OC, but the associated poor sensitivity of KLK individually may limit its value in clinical application. To resolve this problem, the combination of KLK and other markers may offer improved performance than a single marker.

Topics: Biomarkers, Tumor; Female; Humans; Ovarian Neoplasms; Plasma Kallikrein; Randomized Controlled Trials as Topic

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is an integral membrane protein expressed on epithelial cells and contains two extracellular Kunitz domains (N-terminal KD1 and C-terminal KD2) known to inhibit trypsin-like serine proteases. In tumorigenesis and tissue regeneration, HAI-1 regulates the hepatocyte growth factor (HGF)/c-Met pathway by inhibiting the activity of HGF activator (HGFA) and matriptase, two serine proteases that convert pro-HGF into its biologically active form. By screening a placental cDNA library, we discovered a new splice variant of HAI-1 designated HAI-1B that contains an extra 16 amino acids adjacent to the C terminus of KD1. To investigate possible consequences on Kunitz domain function, a soluble form of HAI-1B (sHAI-1B) comprising the entire extracellular domain was produced. First, we found that sHAI-1B displayed remarkable enzyme specificity by potently inhibiting only HGFA (IC50 = 30.5 nm), matriptase (IC50 = 16.5 nm), and trypsin (IC50 = 2.4 nm) among 16 serine proteases examined, including plasminogen activators (urokinase- and tissue-type plasminogen activators), coagulation enzymes thrombin, factors VIIa, Xa, XIa, and XIIa, and activated protein C. Relatively weak inhibition was found for plasmin (IC50 = 399 nm) and plasma kallikrein (IC50 = 686 nm). Second, the functions of the KD1 and KD2 domains in sHAI-1B were investigated using P1 residue-directed mutagenesis to show that inhibition of HGFA, matriptase, trypsin, and plasmin was due to KD1 and not KD2. Furthermore, analysis by reverse transcription-PCR demonstrated that HAI-1B and HAI-1 were co-expressed in normal tissues and various epithelial-derived cancer cell lines. Both isoforms were up-regulated in eight examined ovarian carcinoma specimens, three of which had higher levels of HAI-1B RNA than of HAI-1 RNA. Therefore, previously demonstrated roles of HAI-1 in various physiological and pathological processes likely involve both HAI-1B and HAI-1.

Topics: Alanine; Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Cell Line; CHO Cells; Cloning, Molecular; Cricetinae; DNA, Complementary; Dose-Response Relationship, Drug; Endopeptidases; Enzyme Inhibitors; Epithelial Cells; Escherichia coli; Exons; Factor VIIa; Factor Xa; Factor XIa; Factor XIIa; Female; Fibrinolysin; Gene Library; Humans; Inhibitory Concentration 50; Introns; Membrane Glycoproteins; Models, Genetic; Molecular Sequence Data; Mutation; Ovarian Neoplasms; Plasma Kallikrein; Plasmids; Plasminogen Activators; Protein C; Protein Isoforms; Protein Structure, Tertiary; Proteinase Inhibitory Proteins, Secretory; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Sequence Homology, Amino Acid; Serine Endopeptidases; Substrate Specificity; Tissue Distribution; Trypsin; Up-Regulation