Identifying mismatch repair deficient colon cancer: near perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series
Objective: Establish a mismatch repair (MMR) status of colorectal cancer is essential to enable the detection of Lynch syndrome that underlie and inform prognosis and therapy. current testing usually involves either PCR-based microsatellite (MSI) testing or MMR protein immunohistochemistry (IHC). We aimed to compare the two approaches, a large population-based cohort of stage 2 and 3 cases of colon cancer in Northern Ireland.
Methods and results: Promega pentaplex Using this test, we determined the status of MSI’s four MMR IHC antibody panel. IHC applied to the tumor tissue microarray tumor samples in triplicate and scored manually. Of the 593 cases with available MSI and MMR IHC results, 136 (22.9%) were MSI-H and 135 (22.8%) displayed abnormal MMR IHC.
Concordance was very high, with 97.1% of MSI-H cases showed normal MMR IHC and 97.8% of cases with normal IHC showed MSI-H status. Under-representation of epithelial tumor cells in a sample of the tumor is very inflamed resulting in misclassification of some cases with microsatellite stable normal MMR IHC. MMR IHC revealed a rare case with unusual patterns of expression of MMR proteins, an unusual combination of loss of secondary clonal expression or loss of expression, is further illustrated by immunostaining repeated in all parts of the network.
Conclusions: PCR MSI and MMR IHC testing can be considered equally adept tests to establish the status of MMR / MSI, while aware of the potential pitfalls either method. Methodology selection may depend on the available services and expertise.
Anti-sclerostin monoclonal antibody romosozumab, treatment for osteoporosis, reduce the risk of vertebral fracture and clinical fracture. laser irradiation triggers a variety of effects, including bio-stimulation, which can induce beneficial effects of therapy and biological response. Initially, we performed in vivo experiments to clarify the mechanism better bone healing in bone laser ablated.
Here, we evaluated a comprehensive gene expression and sequence in the Er: YAG laser ablation, bur-drilled, and bones treated controls, and found the laser irradiation is pressed Sost (protein coding: sclerostin) expression in the bone, possibly through stimulation mechanotransducers. Surprisingly, the effect of laser bio-stimulation suppressed the expression of Sost in primary osteogenic cells.
SPARC is a key mediator of TGF-β-induced metastatic kidney cancer
Aberrant expression of transforming growth factor-β1 (TGF-β1) is associated with renal cell carcinoma (RCC) progression by inducing the cancer metastasis. However, downstream effector (s) in the TGF-β signaling pathway is not fully characterized. In this study, the height of secreted protein acidic and rich in cysteine (SPARC) as regulated TGF-β genes in RCC were identified by applying the analysis of genes expressed differently and microarray analysis, we further confirmed these results in a few RCC cell lines.
Clinically, expression of both genes were positively correlated to the RCC patient specimens. Furthermore, increased expression of SPARC is found in all subtypes of RCC and RCC positively correlated with stage and grade. Instead, SPARC expression is inversely proportional to the overall and disease-free survival of patients with RCC, showing SPARC as a powerful prognostic marker of survival of RCC patients. SPARC knock down significantly inhibit invasion and metastasis of RCC cells both in vitro and in vivo.
Description: CRK, also known as p38, is a protein that in humans is encoded by the CRK gene. This gene is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. It is mapped to 17p13.3. The protein participates in the Reelin signaling cascade downstream of DAB1. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of Crk functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.
Description: This recombinant p38 antibody reacts to human p38 MAPK. It may also react to the rat and mouse protein, as predicted by immunogen homology.
Description: P38 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response.
Description: P38 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response.
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IF, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of T180/Y182
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat. This p38 antibody is for WB, IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human p38 around the non-phosphorylation site of Y323
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Description: A polyclonal antibody for detection of p38 from Human, Mouse, Rat, Chicken. This p38 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the C-terminal region of human p38
Similarly, in vitro cell invasion could be reduced by using a specific monoclonal antibody. Mechanically, SPARC activate protein kinase B (AKT) pathway which leads to an increase in the expression of matrix metalloproteinase-2, which can facilitate the invasion of RCC. Overall, our data support the SPARC is an important role of TGF-β signaling networks that underlie the development of RCC and potential therapeutic targets and prognostic markers.