Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The assessment of HER2/neu status is performed to predict monoclonal antibody therapeutic (trastuzumab) responsiveness of invasive breast cancer. The determination is usually performed by immunohistochemistry (IHC), using commercial kits approved by the Food and Drugs Administration (FDA) or by in-house protocols. The authors evaluated HER2 expression using different IHC protocols, to obtain the most concordant results with the FDA-approved system. A tissue microarray paraffin block with 110 samples of several types of histologic specimens was built. On the basis of commercially available kit HercepTest, several protocol steps modifications were made and further compared with HercepTest results. HER2 protein expression was evaluated both semiquantitatively (0, 1+, 2+, 3+ scoring) and qualitatively (specificity and nonspecific background). The most reliable results (98.2% concordance; 0.9% of background) were obtained using a 1:800 primary antibody dilution (Dako-A0485), Tris/EDTA as antigen retrieval solution (Dako-S2367) and a polymer as detection system (EnVision). Tissue microarray controls provided an important contribution, ensuring a rapid and low cost way to standardize and optimize IHC, using in-house protocol, for HER2 expression detection. This in-house protocol for HER2 expression evaluation can be an efficient, specific, and accurate alternative to the FDA-approved kit in a more cost effective manner.
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PMID:HER2/neu detection by immunohistochemistry: optimization of in-house protocols. 1897 84

Most Her2 testing guidelines recommend that all cases scoring Her2 2+ by immunohistochemistry should be analyzed by fluorescent in situ hybridization (FISH) to determine HER2 status to confirm eligibility for Trastuzumab therapy in breast cancer. The aim of our study was to determine HER2 gene and chromosome 17 (CEN17) status in a series of 108 Her2 2+ consecutive cases and study the correlation between pathological characteristics of the tumors and HER2 amplification. Invasive breast cancers were tested by FISH using the Dako HER2 FISH pharmDx kit. The Her2 immunohistochemistry protocol was performed using the polyclonal AO485 antibody (Dako) diluted to 1:1500. HER2 and CEN17 status were correlated to tumor SBR grade, mitotic count, estrogen receptor, progesterone receptor status and percentage of Her2 immunohistochemistry-positive cells. Following Food and Drug Administration guidelines, ie, HER2/CEN17 ratio >or=2 and an HER2 copy number >4, amplified cases were observed in 36 (33%) and 49 (45%) cases, respectively, and following American Society of Clinical Oncology/College of American Pathologists guidelines, ie, HER2/CEN17 ratio >2.2 and an HER2 copy number >6, amplified cases represented 30 and 24% of the study population, respectively. Chromosome 17 polysomy (CEN17 >2.25) was observed in 39 (36%) tumors. Significant positive correlations were found between FISH HER2 amplified cases and Her2 immunostaining >60% (P=1.1.10(-5)), SBR grade 3 (P=0.0001), nuclear atypia (P=0.03) and mitotic count (P=0.008). By multivariate analysis, Her2 immunostaining >60% (P<10(-3)) and SBR grade 3 (P<10(-3)) were independent factors predicting HER2 amplification status irrespective to cutoff guidelines. All SBR grade 3 cases with more than 60% Her2+ cells had an HER2/CEN17 ratio >or=2, only one had a ratio <or=2.2. In our series of consecutive Her2 2+ cases, one-third demonstrated HER2 amplification, and one-third had chromosome 17 polysomy. Pathological factors, in particular SBR grade 3 and more than 60% Her2+ cells, were significantly correlated with HER2 amplification.
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PMID:Prediction of HER2 gene status in Her2 2+ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations. 1906 Aug 46

The multiplex ligation-dependent probe amplification (MLPA) method was used to analyze 118 DNA samples from 90 alpha-thalassemia (alpha-thal) patients and 28 normal persons from Southern China, where the main causes of alpha-thal are three large deletions (-alpha3.7, -alpha4.2, and --SEA) and two point mutations in the alpha-globin gene cluster on chromosome 16. The results, detected by the P140B HBA kit, were in complete concordance with the results detected by multiplex polmymerase chain reaction (m-PCR) and real-time PCR. The advantages and limitations of the techniques are discussed. We concluded that MLPA was a rapid and reliable method to determine the cause of both deletional and nondeletional alpha-thal in China.
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PMID:Detection of alpha-thalassemia in China by using multiplex ligation-dependent probe amplification. 1906 34

C-kit gene gain of function mutations are important in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase inhibitor of KIT and achieves a partial response or stable disease in most patients with metastatic GIST, but there is increasing evidence of acquired resistance. We report a case of GIST with acquired resistance to imatinib during therapy and secondary c-kit mutation besides the primary mutation.
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PMID:Secondary C-kit mutation is a cause of acquired resistance to imatinib in gastrointestinal stromal tumor. 1909 80

The overexpression of HER-2/neu is an independent prognostic factor of clinical outcome of breast cancer, therefore determination of HER-2/neu status is now an integral part of the clinicopathologic workup. The ways of measuring the copy number of the HER-2/neu gene in tumor cells comprise in situ hybridization techniques and real-time polymerase chain reaction (PCR). Quantitative real-time PCR is a relatively new technique for assessing HER-2/neu gene amplification with high sensitivity. However, the HER-2/neu Quantification Kit developed by Roche designed for a LightCycler 1.5 platform had been withdrawn from the commercial market; therefore, we were encouraged to design an alternative LightCycler-based method that offers the desired level of reliability. One hundred breast cancer cases with known HER-2/neu status have been examined with the original Roche developed HER-2/neu Quantification kit and the custom real-time PCR assay. The newly developed, custom PCR showed sensitivity of 91.43%, specificity of 90.63%, and accuracy of 90.91% taking fluorescence in situ hybridization results as the end point. We have described a novel real-time PCR technique for the relative quantification of the HER2/neu gene on a LightCycler 1.5 platform. We have determined that our method is eligible and ideal for the supplement of regular fluorescence in situ hybridization reactions, concerning its high sensitivity and reliability.
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PMID:An alternative and reliable real-time quantitative PCR method to determine HER2/neu amplification in breast cancer. 1909 80

HER2 detection is important for breast cancer (BC) treatment and prognosis, but the detection methods currently used have some disadvantages. Quantum dots (QDs)-based probes provide a potentially important new method for HER2 detection in clinical practice. This potential is examined in this paper. A QDs HER2 probe kit and QDs image acquisition and analysis software were developed and applied to 94 clinical samples of BC. Compared to conventional immunohistochemistry techniques, this method provided a superior accurate and sensitive method for the detection of HER2 in clinical breast cancer diagnosis.
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PMID:Quantum dots-based immunofluorescence technology for the quantitative determination of HER2 expression in breast cancer. 1925 16

Chemotaxis has recently been implicated in tumor metastasis. Protein Kinase C(PKC)zeta is often over-activated and is a key signal transducer shared by both EGFR- and CXCR4-mediated chemotactic signaling in human breast and lung cancers, as well as CSF-1-induced macrophage migration. In order to develop potential inhibitors targeting PKCzeta for effective blockage of cancer cell chemotaxis and tumor metastasis, the Z'-lyte kinase assay -SER/THR 7 peptide kit was used and a compound called PKCzI257.3 was identified with IC50 of 28 microM. As a result of treatment, chemotactic migration potency of the human breast cancer cell MDA-MB-231 were impaired, while no significant effect was observed on cell proliferation. Furthermore, EGF-induced cofilin phosphorylation, a critical step of cofilin recycle and actin polymerization, was also dampened, which was relevant to the decreased cell migration. Our results suggest that PKCzI257.3 is a PKCzeta-specific compound inhibitor which blocked cancer cell migration and may serve as a potential therapeutic drug for cancer treatment.
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PMID:Screening of a PKC zeta-specific kinase inhibitor PKCzI257.3 which inhibits EGF-induced breast cancer cell chemotaxis. 1932 49

The determination of estrogen (ER) and progesterone (PR) receptor status has become standard practice in the evaluation of patients with invasive breast cancer, having important prognostic and therapeutic implications. HER2 assessment is important to evaluate the response to Herceptin (Trastuzumab) therapy for primary and metastatic breast cancer. This study is undertaken to compare rabbit monoclonal antibodies (RabMAb) for ER, PR, and HER2 against FDA-approved monoclonal and polyclonal antibodies (FDAMpab). Cell blocks from primary and metastatic/recurrent breast carcinomas of 52 breast cancer patients were used. Immunohistochemistry was performed, following optimized epitope retrieval, with a polymer based detection system using RabMAb: ER (SP1), PR (SP2), and HER2 (SP3). FDA approved Mpab (Dako) used were: ER (1D5); PR (PgR636); and HercepTest kit according to manufacturer's instructions. HER2 immunostain is correlated with FISH results. Overall, positive, and negative agreement is as follows: 88.5, 88.9, and 88.2% for ER; 84.6, 70.5, and 91.4% for PR; 58.3, 100, and 50% for HER2. There is substantial to moderate agreement between RabMAb and FDAMpab for ER (kappa = 0.75) and PR (kappa = 0.64), respectively. There is poor agreement (kappa = 0.25) between RabMAb (SP3) and FDApab (HercepTest). SP3 shows better concordance (93.8%) than HercepTest (46.9%) with FISH results. RabMAb SP clones are almost comparable with FDA-approved ER and PR, with fair to moderate agreement. Both are as sensitive as their FDA-approved clones. SP3, on the other hand, is superior to HercepTest for detecting HER2 overexpression, with an excellent concordance with FISH.
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PMID:Estimation of hormone receptor status and HER2 in cytologic cell blocks from breast cancer using the novel rabbit monoclonal antibodies (SP1, SP2, and SP3). 1953 Jan 1

Masitinib is the first veterinary drug recently approved in Europe to treat mast cell tumours in dogs (Hahn et al. JVIM, Masivet). This inhibitor is selective and highly efficient in blocking c-Kit, PDGFR, and Lyn tyrosine kinase activities. It showed good efficacy and acceptable toxicity in several animal studies such as mice, rats, rabbits and dogs (Dubreuil P, et al. submitted, and Hahn et al. (J Vet Intern Med 22(6):8, 2008)). C-kit is a tyrosine kinase receptor that plays a critical role in the biology of mast cells including differentiation, survival, migration and cytokine/mediator release. Mast cells are involved in a number of allergy-and immune-related diseases in cats such as asthma (Reinero Carol et al. Vet Immunol Immunopathol 121(3-4):9, 2008), inflammatory bowel disease, (Janeczko et al. Vet Mic 128(1-2):15, 2008), and feline mast cell tumours (Rassnick et al. J Am Vet Med Assoc 232(8):1200-1205, 2008). Therefore, there might be a strong rationale to use masitinib in these indications. Here, we report the results of a preliminary pharmacokinetic study of masitinib in cats which showed a good bioavailability of ~60% in both sexes. We propose that an oral dose of 10-15 mg/kg masitinib is appropriate to achieve adequate plasma concentrations.
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PMID:Pharmacokinetics of masitinib in cats. 1953 3

Considerable progress was realized these last years in the understanding of the molecular mechanisms and the treatment of the GIST. Their diagnosis remains based on the morphology and immunohistochemistry. The evaluation of GIST prognosis was till know difficult to establish but a new histopronostic classification currently used allows a better therapeutic approach. The search for KIT and PDGFRA mutations is recommended to adapt a targeted therapy by KIT inhibitors. The pathologist plays a crucial role in the management of the GIST because it is on him that is based the diagnosis, the evaluation of the prognosis and the treatment (surgery and kit inhibitors).
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PMID:[The role of the pathologist in the management of gastrointestinal stromal tumors (GIST)]. 1969 60


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