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)

A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +/- 1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.
...
PMID:Intermediate filament expression in normal parotid glands and pleomorphic adenomas. 245 77

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
...
PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

The cross-reactivity of a group of monoclonal antibodies (MABs) generated against human cytokeratins (CKs) was investigated in mouse tissues. Formalin-fixed and paraffin-embedded sections of lung, stomach, small and large intestine, liver, and kidney were immunostained with MABs after epitope retrieval with enzyme digestion. AE1/AE3, a "cocktail" of two MABs that recognizes basic and acidic CKs, 5D3 MAB to low molecular weight CKs (8, 18, and 19), and monospecific MABs to CK 7 and 20 were tested. Additionally, CK 17 and 34betaE12 MABs to high molecular weight CKs were evaluated in the same organs and in sections from skin and preputial glands. We employed the new universal animal system (ARK) as the detection system. The results showed intense reactivity for the first group of antibodies used, with topographic distribution similar to that in human tissues, with the exception of CK 7 in lung parenchyma, which displayed reactivity only in type II pneumocytes, with negativity of adjacent bronchial epithelium. Also of note was the lack of reaction of liver hepatocytes and renal tubular cells to AE1/AE3 and 5D3 MABs. Regarding the second group of antibodies, no reaction was obtained for CK 17 in the tissues tested. On the contrary, 34betaE12 MAB yielded intense reactivity in cells of epidermis and hair follicles. Compared to other detection systems used previously in this animal, ARK produced a well-defined reactivity at the cellular level without any background. We conclude that a useful panel of anti-CK antibodies commonly used in human pathology can be applied successfully to mouse tissues after enzyme digestion, leading to a more accurate definition of cellular populations in this laboratory animal.
...
PMID:Cytokeratin immunoreactivity in mouse tissues: study of different antibodies with a new detection system. 1127 18

A distinctive type of multilayered epithelium (ME) has been described at the neo-squamocolumnar junction and within columnar mucosa in patients with Barrett's esophagus (BE). This epithelium has morphologic and ultrastructural features of both squamous and columnar epithelium. Multilayered epithelium may represent an early or intermediate stage of columnar metaplasia; therefore, we performed this study to determine the morphologic and biologic characteristics of this epithelium and to gain insight into its derivation. Esophageal mucosal biopsies containing ME from 17 patients with BE were evaluated morphologically, stained with a variety of mucin histochemical stains; and also immunostained with antibodies against cytokeratins (CK) 13 (squamous epithelium marker); 14 (basal squamous epithelium marker) 7, 8/18, 19, and 20 (columnar epithelium markers), MIB-1 (proliferation marker); villin (intestinal brush border protein); and TGFalpha, EGFR, pS2, and hSP (enteric proliferation/differentiation regulatory peptides). The results were compared with normal esophageal squamous epithelium, normal gastric cardia epithelium, specialized-type intestinal epithelium (BE), and esophageal mucosal and submucosal gland duct epithelium. Multilayered epithelium expressed a pattern of mucin production (neutral mucin, sialomucin, and sulfomucin in 88%, 100%, and 71% of cases, respectively) and cytokeratin expression (CK 13 and 19 in the basal "squamoid" cells, CK 7, 8/18, 19, and 20 in the superficial "columnar" cells) similar to that of columnar epithelium in BE, and showed a high capacity for cellular proliferation (Ki-67-positive in 88% of cases) and differentiation (TGFalpha, EGFR, pS2 and villin-positive in 100%, 100%, 93%, and 66% of cases, respectively). The mucosal gland duct epithelium showed a similar phenotypic pattern and, in one case, was seen to give rise to ME at the surface of the mucosa. These data provide evidence in support of the hypothesis that ME represents an early or intermediate stage in the development of esophageal columnar metaplasia (BE). The mucosal gland duct epithelium may contain progenitor cells that can give rise to ME.
...
PMID:Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus. 1134 67

Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.
...
PMID:Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma. 1501 Aug 80

Not uncommonly, bile duct adenomas (BDAs) and hamartomas (BDHs) of the liver may be difficult to distinguish from metastatic well-differentiated ductal adenocarcinoma of the pancreas. However, this distinction is critical for proper staging and patient management. The primary purpose of this study was to determine if a panel of immunohistochemical stains can help distinguish BDA or BDH from metastatic pancreatic adenocarcinoma in the liver. Routinely processed tissue sections from 25 BDA, 10 BDH, 25 metastatic pancreatic adenocarcinomas to the liver and 6 cases each of metastatic colorectal, breast, and lung adenocarcinomas were immunohistochemically stained for CK7, CK8/CK18, CK19, CK20, p53, p63, TAG-72, monoclonal CEA (mCEA), polyclonal CEA (pCEA), HER-2/neu, AMACR (alpha-methylacyl-CoA racemase), Dpc4 (Smad4), and mesothelin. The slides were evaluated in a blinded fashion, and the results were compared between the benign and malignant lesions. Significantly more (P < 0.05) metastatic pancreatic adenocarcinomas were positive for CK20 (76%), p53 (60%), TAG-72 (88%), mCEA (92%), HER2/neu (40%), and mesothelin (64%) and showed loss of Dpc4 (44%), in comparison to BDA (CK20, 40%; p53, 0%; TAG-72, 0%; mCEA, 0%; HER2/neu, 12%; mesothelin, 0%; loss of Dpc4, 0%) or BDH (CK20, 10%; p53, 0%; TAG-72, 0%; mCEA, 10%; HER2/neu, 0%; mesothelin, 0%; loss of Dpc4, 0%). Of these antibodies, p53, TAG-72, mCEA, loss of Dpc4, and mesothelin had the highest specificity for pancreatic adenocarcinoma, with mCEA having the highest sensitivity (92%). No significant differences were observed in the degree of CK7, CK8/CK18, CK19, or pCEA expression between the three types of lesions. Although none of the BDA or BDH was positive for either p63 or AMACR, two of the metastatic pancreatic adenocarcinomas (8%) were positive for each of these peptides (P > 0.05). For nonpancreatic adenocarcinomas, mCEA showed a reasonably high sensitivity and 100% specificity in the differential diagnosis versus BDA. Immunohistochemical expression of p53, TAG-72, mCEA, mesothelin, and loss of Dpc4 can help distinguish metastatic pancreatic adenocarcinoma in the liver from BDA or BDH. Although p63 and AMACR are also specific for pancreatic adenocarcinoma, their low sensitivity limits their use in clinical practice.
...
PMID:Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. 1572 8

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1alpha are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin-biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK(+) cells was 236 (range, 20-847) per 5 x 10(4) enriched BM cells. The presence of CK(+) cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK(+) per 5 x 10(4) enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.
...
PMID:Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow. 1613 77

Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case of this rare variant of breast carcinoma was reported in 1996, only 10 cases have been reported in the English-language literature. Reported herein is the first case of primary acinic cell carcinoma of the breast in a Japanese woman. To the naked eye, the tumor appeared well circumscribed and the cut surface was grayish-pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a monotonous proliferation of cells with a finely granular cytoplasm, resembling acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm. In spite of extensive sampling, no common histological patterns of breast carcinoma such as in situ and invasive ductal carcinoma were recognized in the present case, indicating that the present case was pure acinic cell carcinoma. In addition, the immunohistochemical profile of this tumor was identical to that of the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were positive. The patient has been well for 22 months since the wide local excision of the tumor and no signs of salivary neoplasm are evident to date.
...
PMID:Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman. 1719 42

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.
...
PMID:Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications. 1721 55

SS18-SSX fusion genes resulting from a chromosomal translocation t(X;18)(p11.2;q11.2) are a genetic hallmark of synovial sarcoma. Although such cytogenetic or molecular aberrations have mostly been detected by fluorescence in situ hybridization or reverse transcription-polymerase chain reaction, the expression of SS18-SSX has been poorly investigated at a cellular or tissue level. In this study, biotinylated tyramide (BT)-based in situ hybridization (ISH) was performed to detect SS18-SSX transcripts using formalin-fixed, paraffin-embedded tissues from 15 synovial sarcomas. Digoxigenin-labeled cRNA probes flanking the fusion points of SS18-SSX1 and SS18-SSX2 were generated by in vitro transcription, and hybridized signals were detected by a streptavidin-biotin complex method after chemical enhancement with BT. The localizations of signals were compared with the immunohistochemical expressions of epithelial or neuroectodermal markers and those of cell adhesion including cytokeratins (CAM5.2, AE1/AE3, CK7), epithelial membrane antigen, E-cadherin, beta-catenin, c-erbB-2 (HER2/neu), CD56, and claudin-1. The ISH signals of the SS18-SSX transcripts were identified in 13 synovial sarcomas, and their fusion types correlated with those determined by reverse transcription-polymerase chain reaction. In biphasic tumors, the ISH signals tended to localize to epithelial areas, whereas spindle-cell areas or monophasic fibrous tumors showed a less intense or focal expression pattern. Notably, the expression patterns of AE1/AE3, CK7, and c-erbB-2 often colocalized with the ISH signals (7 of 11 cases positive for each marker). Our results suggest that BT-based ISH can be used as a molecular technique for the detection of SS18-SSX using formalin-fixed, paraffin-embedded tissues.
...
PMID:Molecular detection of SS18-SSX fusion gene transcripts by cRNA in situ hybridization in synovial sarcoma using formalin-fixed, paraffin-embedded tumor tissue specimens. 1747 Nov 53


1 2 3 4 5 6 7 8 9 10 Next >>

---