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

---

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

Some patients who have had prior bladder biopsies or transurethral resections undergo a repeat resection within several months for various reasons. The detection of a few residual tumor cells in bladder specimens with prior biopsy site changes can be challenging based on histology alone. Immunohistochemistry for cytokeratins may be used as an adjunct in this situation. We have noted several cases in which keratin stains were performed and positive cells were noted, raising the issue as to whether the cytokeratin positive cells were residual tumor cells or stromal cells. Immunohistochemistry for a panel of antibodies [AE1/AE3, CAM 5.2, high molecular weight cytokeratin, smooth muscle actin (SMA), desmin, and anaplastic lymphoma kinase (ALK)] was performed on 29 cases of bladder biopsies with prior biopsy site changes. Of 29 patients, 25 had a prior history of bladder tumor: 17 had invasive high-grade urothelial carcinoma (T1, 5 cases; T2, 11 cases; T3,1 case); 7 had noninvasive high-grade papillary urothelial carcinoma; 1 had noninvasive low-grade papillary urothelial carcinoma). One of the patients with noninvasive high-grade papillary urothelial carcinoma and one of the patents with invasive high-grade urothelial carcinoma had associated carcinoma in-situ. Four patients had prior benign bladder diagnoses: cystitis cystica et glandularis; polypoid cystitis; follicular cystitis; and neurogenic bladder with benign prostate hyperplasia. Of the 29 cases, 6 (21%) had cells with staining for at least 2 of the cytokeratin markers. Cytokeratin (CK) AE1/ AE3 was positive for cells in 8/29 cases (28%). In 6 of these cases, cells displayed a spindle cell and 2 cases a more epithelioid morphology. CAM 5.2 was positive in cells in 5/29 cases (17%); 3 of the cases had spindle cell and 2 cases epithelioid morphology. High molecular weight cytokeratin was expressed in cells in 2/29 cases (7%) with 1 case having spindle cell and 1 epithelioid morphology. SMA was positive in cells with a spindle cell morphology and negative in the more epitheloid cytokeratin positive cells. Desmin was positive in 3/6 keratin positive spindle cells and negative in keratin positive epithelioid cells. ALK was negative in all the cases. Three cases with spindle cell morphology and positivity for at least 1 of the keratins and SMA stains were interpreted as aberrant keratin expression in myofibroblastic cells based on the staining and the morphology of the spindle cells. Another 3 cases with concurrent staining for at least 1 of the keratins, SMA and desmin were consistent with smooth muscle cells on the basis of their cellular morphology. Another 2 cases had cells, which expressed at least 2 CK markers but did not express SMA, desmin, or ALK and a more epithelioid morphology. These cells were interpreted as residual tumors cells. When interpreting CK stains for the detection of residual tumor cells, one should pay attention to the nature of the cells and not assume all CK staining cells are residual tumor cells.
...
PMID:Detection of residual tumor cells in bladder biopsy specimens: pitfalls in the interpretation of cytokeratin stains. 1732 80

Embryonic stem (ES) cells are exposed to fluid-mechanical forces, such as cyclic strain and shear stress, during the process of embryonic development but much remains to be elucidated concerning the role of fluid-mechanical forces in ES cell differentiation. Here, we show that cyclic strain induces vascular smooth muscle cell (VSMC) differentiation in murine ES cells. Flk-1-positive (Flk-1+) ES cells seeded on flexible silicone membranes were subjected to controlled levels of cyclic strain and examined for changes in cell proliferation and expression of various cell lineage markers. When exposed to cyclic strain (4-12% strain, 1 Hz, 24 h), the Flk-1+ ES cells significantly increased in cell number and became oriented perpendicular to the direction of strain. There were dose-dependent increases in the VSMC markers smooth muscle alpha-actin and smooth muscle-myosin heavy chain at both the protein and gene expression level in response to cyclic strain, whereas expression of the vascular endothelial cell marker Flk-1 decreased, and there were no changes in the other endothelial cell markers (Flt-1, VE-cadherin, and platelet endothelial cell adhesion molecule 1), the blood cell marker CD3, or the epithelial marker keratin. The PDGF receptor beta (PDGFR beta) kinase inhibitor AG-1296 completely blocked the cyclic strain-induced increase in cell number and VSMC marker expression. Cyclic strain immediately caused phosphorylation of PDGFR beta in a dose-dependent manner, but neutralizing antibody against PDGF-BB did not block the PDGFR beta phosphorylation. These results suggest that cyclic strain activates PDGFR beta in a ligand-independent manner and that the activation plays a critical role in VSMC differentiation from Flk-1+ ES cells.
...
PMID:Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor beta. 1818 12

Only a few synovial sarcomas arising in the gastrointestinal tract have been reported, most of them are from the esophagus. We report clinical, histopathologic, and immunohistochemical features of 10 gastric synovial sarcomas. These tumors occurred in 4 males and 6 females with mean and median age of 52 years (range, 29 to 68 y). None of the patients had evidence of synovial sarcoma elsewhere. The tumor sizes ranged from 0.8 to 15 cm (mean, 3 cm). Two tumors were large transmural masses of 8 and 15 cm, and 8 were 0.8 to 6 cm, ulcerated cuplike or plaquelike or oval lesions predominantly involving the luminal side. Histologically, 9 tumors were monophasic one also having a poorly differentiated round cell component, and one was biphasic. Microscopic calcifications were present in 2 tumors. At least focal keratin (AE1/AE3 cocktail, keratin 7) and/or epithelial membrane antigen-positivity were detected in all tumors, and there was no CD34 or KIT-immunoreactivity. SYT-SSX fusion transcripts were demonstrated in 7 cases studied by a polymerase chain reaction-based fusion transcript assay. Five patients had a partial gastrectomy, and 5 underwent wedge or segmental resections. Two patients had received chemotherapy after surgery, but none had postoperative radiation. Four patients with plaquelike or cuplike tumors < or =3 cm were alive and well 1, 2, 2, and 18.5 years after surgery. Two patients died of tumor 25 and 29 months after surgery. One of them had a large 8-cm tumor, and another had a 2-cm tumor with a poorly differentiated component. Two patients were alive with recurrences 6 and 48 months after diagnosis. Synovial sarcoma rarely occurs as a gastric primary tumor. It has a variable prognosis depending on tumor size and differentiation, and should be considered in the differential diagnosis of KIT-negative gastric spindle cell neoplasms.
...
PMID:Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases. 1822 31

Atopic eczema (AE) is a multifactorial skin disease caused by a variety of factors such as genetic conditions, alterated skin structure, immunologic deviations and environmental factors, among others. There are two main subtypes of AE, i.e. the IgE-associated ("atopic eczema") and the non-IgE-associated type ("nonatopic eczema") with different prognosis concerning the development of respiratory diseases ("atopy march"). Recently, it was demonstrated that Filaggrin (=filament-aggregating protein, FL) is a major gene for atopic eczema. Filaggrin binds to and aggregates the keratin cytoskeleton in the epidermis. Homozygous FLG mutation leads to complete loss of filaggrin expression in skin. Half or more of children with moderate to severe AE carry FLG mutations. Moreover, filaggrin loss-of-function mutations predispose to phenotypes involved in the atopy march. The altered skin structure and a deficiency in antimicrobial peptides favour colonization with Staphylococcus aureus and yeasts (Malassezia sp.). Sensitization to the yeast occurs almost exclusively in AE patients. S. aureus enterotoxins with superantigenic activity stimulate activation of T cells and macrophages. So far, AE skin lesions are orchestrated by the local tissue expression of proinflammatory cytokines and chemokines with activation of T lymphocytes, dendritic cells, macrophages, keratinocytes, mast cells, and eosinophils which lead to the skin inflammatory responses. From the therapeutic point of view, besides emollients and local corticosteroids, topic immunomodulatory drugs (tacrolimus and pimecrolimus) have substantially improved the treatment of AE.
...
PMID:Atopic eczema: genetics or environment? 1824 50

Distant metastases of human breast cancers have been suggested to be more different from each other than from their respective primary tumors, based on expression profiling. The mechanism behind this lack of similarity between individual metastases is not known. We used cDNA microarrays to determine the expression profiles of pulmonary metastases and primary mammary tumors in two distinct transgenic models expressing either the Neu or the Wnt-1 oncogene from the mouse mammary tumor virus long terminal repeat (MMTV LTR). We found that pulmonary metastases are similar to each other and to their primary tumors within the same line. However, metastases arising in one transgenic mouse line are very different from either metastases or primary tumors arising in the other line. In addition, we found that, like their primary tumors, lung metastases in Wnt-1 transgenic mice harbor both epithelial and myoepithelial tumor cells and cells that express the putative progenitor cell marker keratin 6. Our data suggest that both gene expression profiles and cellular heterogeneity are preserved after breast cancer has spread to distant sites, and that metastases are similar to each other when their primary tumors were induced by the same oncogene and from the same subset of mammary cells.
...
PMID:Comparison of expression profiles of metastatic versus primary mammary tumors in MMTV-Wnt-1 and MMTV-Neu transgenic mice. 1828 33

Although mutations in intermediate filament proteins cause many human disorders, the detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. In this study, selected keratin mutations were analysed for their effect on the epidermal stress response. Expression profiles of two keratin-mutant cell lines from epidermolysis bullosa simplex patients (one severe and one mild) were compared to a control keratinocyte line before and after challenge with hypo-osmotic shock, a common physiological stress that transiently distorts cell shape. Fewer changes in gene expression were found in cells with the severely disruptive mutation (55 genes altered) than with the mild mutation (174 genes) or the wild type cells (261 genes) possibly due to stress response pre-activation in these cells. We identified 16 immediate-early genes contributing to a general cell response to hypo-osmotic shock, and 20 genes with an altered expression pattern in the mutant keratin lines only. A number of dual-specificity phosphatases (MKP-1, MKP-2, MKP-3, MKP-5 and hVH3) are differentially regulated in these cells, and their downstream targets p-ERK and p-p38 are significantly up-regulated in the mutant keratin lines. Our findings strengthen the case for the expression of mutant keratin proteins inducing physiological stress, and this intrinsic stress may affect the cell responses to secondary stresses in patients' skin.
...
PMID:Dual-specificity phosphatases in the hypo-osmotic stress response of keratin-defective epithelial cell lines. 1841 Sep 23

Cultured human keratinocytes produce matrix metalloproteinase (MMP)-2 and MMP-9. In this study, using small interfering RNA (siRNA) for MMP-2 or MMP-9, we investigated the functions of these two gelatinases in the regulation of survival by measuring growth, differentiation, apoptosis, and migration of cultured keratinocytes. MMP-2 siRNA treatment significantly decreased keratinocyte growth and migration, and stimulated apoptosis fourfold. In addition, MMP-2 siRNA caused a 70% reduction in keratin-14 (K14) and a fourfold increase in K10. In contrast, MMP-9 siRNA treatment exerted opposite effects on cell growth, apoptosis, and K10 expression. MMP-2 appears to act through the ERK MAP kinase and caspase-3 signaling pathways as evidenced by the 53% reduction in the level of phosphorylated ERK1/2 and threefold increase in phosphorylated p38 and stronger staining for active caspase-3 in response to MMP-2 siRNA. Dual fluorescent staining revealed that almost all cultured cells stained positive for MMP-2, with only a few scattered cells being positive for MMP-9. There were considerably more BrdU-positive cells following MMP-9 siRNA treatment, indicating that MMP-9 inhibited proliferation. In conclusion, MMP-2 stimulates keratinocyte survival whereas MMP-9 promotes terminal differentiation.
...
PMID:Autocrine actions of matrix metalloproteinase (MMP)-2 counter the effects of MMP-9 to promote survival and prevent terminal differentiation of cultured human keratinocytes. 1849 68

Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations are vast. Pseudosarcomatous processes significantly overlap with malignant tumors (sarcomatoid urothelial carcinoma and leiomyosarcoma) in their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth muscle actin (SMA), and desmin]. p63 has been studied rarely and CK 5/6 and CK 34betaE12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial carcinomas, and 13 smooth muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin antibodies (OSCAR or AE1/AE3), as well as antibodies to CK 34betaE12, CK 5/6, p63, SMA, and anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34betaE12 0/10 (0%), CK 5/6 0/9 (0%), p63 0/9 (0%), SMA 10/10 (100%), ALK 2/10 (20%); sarcomatoid urothelial carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%), CK 34betaE12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%), CK 34betaE12 0/12 (0%), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA 11/13 (85%), ALK 0/13 (0%). Positivity for keratin was typically focal to moderate in smooth muscle tumors and more commonly moderate to diffuse in sarcomatoid carcinomas and PMP. Our data indicate that there is significant immunohistochemical overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of broad-spectrum antibodies to cytokeratin as well as antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several cytokeratin and especially CK 34betaE12 and CK 5/6 with p63 favors sarcomatoid carcinoma and SMA positivity with overall absence of other markers favors leiomyosarcoma.
...
PMID:Utility of a comprehensive immunohistochemical panel in the differential diagnosis of spindle cell lesions of the urinary bladder. 1894 4

Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family (HP1Hs alpha, HP1Hs beta and HP1Hs gamma), which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1Hs alpha, HP1Hs beta and HP1Hs gamma was determined by realtime RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow.
...
PMID:Expression of heterochromatin protein 1 in the primary tumor of breast cancer patients in the presence or absence of occult metastatic cells in the bone marrow. 1919 69

Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin and filaggrin, have been identified as the cause of the common skin condition ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations, which are carried by up to 10% of people, also represent a strong genetic predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the major component of the keratohyalin granules within epidermal granular cells. During epidermal terminal differentiation, the approximately 400 kDa profilaggrin polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form monomeric filaggrin (37 kDa), which binds to and condenses the keratin cytoskeleton and thereby contributes to the cell compaction process that is required for squame biogenesis. Within the squames, filaggrin is citrullinated, which promotes its unfolding and further degradation into hygroscopic amino acids, which constitute one element of natural moisturising factor. Loss of profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis), which is also prone to water loss (xerosis). Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens. Filaggrin is therefore in the frontline of defence, and protects the body from the entry of foreign environmental substances that can otherwise trigger aberrant immune responses.
...
PMID:Filaggrin in the frontline: role in skin barrier function and disease. 1938 95


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---