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31.
32.
Eric E. Niederkofler David A. Phillips Bryan Krastins Vathany Kulasingam Urban A. Kiernan Kemmons A. Tubbs Scott M. Peterman Amol Prakash Eleftherios P. Diamandis Mary F. Lopez Dobrin Nedelkov 《PloS one》2013,8(11)
Insulin-like growth factor 1 (IGF1) is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM) mode. The resulting quantitative mass spectrometric immunoassay (MSIA) exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories. 相似文献
33.
A homologous family of UDP- N -acetylgalactosamine: polypeptide N -
acetylgalactosaminyltransferases (GalNAc-transferases) initiate O-
glycosylation. These transferases share overall amino acid sequence
similarities of approximately 45-50%, but segments with higher similarities
of approximately 80% are found in the putative catalytic domain. Here we
have characterized the genomic organization of the coding regions of three
GalNAc-transferase genes and determined their chromosomal localization. The
coding regions of GALNT1 , -T2 , and -T3 were found to span 11, 16, and 10
exons, respectively. Several intron/exon boundaries were conserved within
the three genes. One conserved boundary was shared in a homologous C.
elegans GalNAc- transferase gene. Fluorescence in situ hybridization showed
that GALNT1 , -T2 , and -T3 are localized at chromosomes 18q12-q21,
1q41-q42, and 2q24-q31, respectively. These results suggest that the
members of the polypeptide GalNAc-transferase family diverged early in
evolution from a common ancestral gene through gene duplication.
相似文献
34.
Human kallikrein-related peptidase 12 (KLK12) is a new member of the human tissue kallikrein family. Preliminary studies suggest that KLK12 is differentially expressed in breast cancer and may have potential use as a cancer biomarker. It has been predicted that KLK12 is a secreted serine protease. However, the enzymatic properties of this protein have not been reported so far. Here, we report the production of recombinant KLK12 and analyses of its enzymatic characteristics, including zymogen activation, substrate specificity, and regulation of its activity. KLK12 is secreted as an inactive pro-enzyme, which is able to autoactivate to gain enzymatic activity. Through screening of a panel of fluorogenic and chromogenic peptide substrates, we establish that active KLK12 possesses trypsin-like activity, cleaving peptide bonds after both arginine and lysine. Active KLK12 quickly loses its activity due to autodegradation, and its activity can also be rapidly inhibited by zinc ions and by alpha2-antiplasmin through covalent complex formation. Furthermore, we demonstrate that KLK12 is able to activate KLK11 zymogen in vitro. Our results indicate that KLK12 may participate in enzymatic cascades involving other kallikreins. 相似文献
35.
M R Darling L Jackson-Boeters T D Daley E P Diamandis 《The journal of histochemistry and cytochemistry》2006,54(3):337-342
Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied. 相似文献
36.
Darling MR Jackson-Boeters L Daley TD Diamandis EP 《The International journal of biological markers》2006,21(2):106-110
The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors. 相似文献
37.
Renal diseases are prevalent and important. However, despite significant strides in medicine, clinical nephrology still relies
on nonspecific and inadequate markers such as serum creatinine and total urine protein for monitoring and diagnosis of renal
disease. In case of glomerular renal diseases, biopsy is often necessary to establish the diagnosis. With new developments
in proteomics technology, numerous studies have emerged, searching for better markers of kidney disease diagnosis and/or prognosis.
Blood, urine, and renal biopsy tissue have been explored as potential sources of biomarkers. Some interesting individual or
multiparametric biomarkers have been found; however, none have yet been validated or entered clinical practice. This review
focuses on some studies of biomarkers of glomerular renal diseases, as well as addresses the question of which sample type(s)
might be most promising in preliminary discovery phases of candidate proteins. 相似文献
38.
Cancer is a leading cause of death. Early detection is usually associated with better clinical outcomes. Recent advances in genomics and proteomics raised hopes that new biomarkers for diagnosis, prognosis or monitoring therapeutic response will soon be discovered. Proteins secreted by cancer cells, referred also as “the cancer cell secretome”, is a promising source for biomarker discovery. In this review we will summarize recent advances in cancer cell secretome analysis, focusing on the five most fatal cancers (lung, breast, prostate, colorectal, and pancreatic). For each cancer type we will describe the proteomic approaches utilized for the identification of novel biomarkers. Despite progress, identification of markers that are superior to those currently used has proven to be a difficult task and very few, if any, newly discovered biomarker has entered the clinic the last 10 years. 相似文献
39.
Oikonomopoulou K Hansen KK Saifeddine M Vergnolle N Tea I Blaber M Blaber SI Scarisbrick I Diamandis EP Hollenberg MD 《Biological chemistry》2006,387(6):817-824
We tested the hypothesis that human tissue kallikreins (hKs) may regulate signal transduction by cleaving and activating proteinase-activated receptors (PARs). We found that hK5, 6 and 14 cleaved PAR N-terminal peptide sequences representing the cleavage/activation motifs of human PAR1 and PAR2 to yield receptor-activating peptides. hK5, 6 and 14 activated calcium signalling in rat PAR2-expressing (but not background) KNRK cells. Calcium signalling in HEK cells co-expressing human PAR1 and PAR2 was also triggered by hK14 (via PAR1 and PAR2) and hK6 (via PAR2). In isolated rat platelets that do not express PAR1, but signal via PAR4, hK14 also activated PAR-dependent calcium signalling responses and triggered aggregation. The aggregation response elicited by hK14 was in contrast to the lack of aggregation triggered by hK5 and 6. hK14 also caused vasorelaxation in a phenylephrine-preconstricted rat aorta ring assay and triggered oedema in an in vivo model of murine paw inflammation. We propose that, like thrombin and trypsin, the kallikreins must now be considered as important 'hormonal' regulators of tissue function, very likely acting in part via PARs. 相似文献
40.
The tissue kallikrein gene family consists of 15 genes tandemly arranged on human chromosome 19q13.4. Most kallikrein genes are characterized by aberrant expression patterns in various human cancers, a feature that makes them ideal cancer biomarkers. In the present study, we investigated the effect of the epigenetic drug compound 5-aza-2'-deoxycytidine on the expression of downregulated kallikrein genes in prostate, breast, and ovarian cancer cell lines. Reactivation of multiple kallikrein genes was observed, although some of these genes do not contain CpG islands in their genomic sequence. Epigenetic regulation provides a new mechanism for the pharmacological modulation of kallikreins in human cancers with putative therapeutic implications. 相似文献