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)

We report the clinical, morphologic, immunophenotypic, and ploidy findings of seven cases of serous borderline tumor of the paratestis. Mean patient age was 56 years (range, 14-77 years), and the clinical presentation was that of a testicular mass. Tumors ranged in size from 1 to 6 cm (mean, 3.5 cm). Six tumors arose from the tunica albuginea, and two of these tumors were intratesticular. One tumor arose from the tunica vaginalis. Serous borderline tumor of the paratestis is histologically identical to its ovarian counterpart. The tumors were cystic with numerous intracystic blunt papillae lined by stratified epithelial cells with minimal to mild cytologic atypia. Psammoma bodies were present in two cases. In all cases, the neoplastic cells stained strongly and diffusely for cytokeratin 7, estrogen receptor, and CD15, and six of seven cases were positive for progesterone receptor and MOC-31. The cells did not stain for cytokeratin 20, carcinoembryonic antigen, calretinin, and HER2/neu. Proliferative activity, as assessed by MIB-1 staining, ranged from 1.3% to 10% (mean, 5.5%). Five of six tumors were diploid, and one was tetraploid. Patients were treated by radical orchiectomy and followed up from 4 months to 18 years (mean, 48 months; median, 8.5 months). No recurrences or metastases occurred. Serous borderline tumor of the paratestis is morphologically and immunophenotypically identical to ovarian serous borderline tumor. To date, no serous borderline tumor of the paratestis reported in the literature or in our series has recurred or metastasized after resection.
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PMID:Serous borderline tumor of the paratestis: a report of seven cases. 1122 8

We have characterized the effects of different short-chain fatty acids (SCFAs) on cell growth and differentiation as well as the phosphorylation state of ERK1 and 2 in the human colon adenocarcinoma cell line HT-29. Of the five SCFAs tested, only butyrate and propionate impaired cellular proliferation. Moreover, butyrate and propionate specifically resulted in a decrease in ERK1 and 2 phosphorylation at 3 and 6 hours post-treatment, suggesting a correlation between the ability of these SCFAs to inhibit cellular proliferation and decrease ERK phosphorylation. Notably, the decrease in ERK phosphorylation was observed prior to the induction of the differentiation markers alkaline phosphatase (AP) and carcinoembryonic antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the case of butyrate- and propionate-induced differentiation, ERK phosphorylation is a marker and may play a role in the proliferation and/or differentiation states of this cell line.
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PMID:Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation. 1153 73

Clinically, it is difficult to differentiate between nipple duct adenomas (NDAs) and Paget's disease of the nipple. These lesions share similar morphological and histological characteristics. Clear cell types present in NDA, epidermal clear cells (ECC) and Toker cells (TC), share immunoreactive similarities to Paget cells which can lead to confusion in classification. The aim of this study was to obtain information on the characteristics and histogenesis of ECC and TC, to distinguish these cells from Paget cells. Ten nipple epidermal with NDA were compared to 25 histologically normal nipples. Samples were analyzed for cytokeratins (CKs) 7, 8 and 18, carcinoembryonic antigen (CEA), c-erbB-2/HER2 expression and human papillomavirus (HPV-) DNA. In 13 out of 25 normal nipples the staining sequence demonstrated that ECC and TC cell types are immunoreactive with CKs 7, 8 and 18 in the basal region of the epidermis. In contrast, aggregated CKs 7, 8 and 18-immunoreactive ECC and TC were identified in the epidermal of 8 of the 10 NDA cases. In 2 cases, TC were continuous with the underlying NDA, suggesting that TC might be of ductal origin and migrate through the galactophorous ostia. In NDAs and 25 histologically normal nipples, ECC and TC were negative for CEA, c-erbB-2/HER2 and HPV-DNA. ECC and TC, normally present in the nipple epidermis, may proliferate and form aggregates in the presence of an underlying NDA. These cells show immunoreactivity for CKs 7, 8 and 18 but are negative for c-erbB-2/HER2, CEA and HPV-DNA and should not lead to the mistaken diagnosis of Paget's disease.
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PMID:Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma. 1255 78

Salivary duct carcinoma is a relatively uncommon aggressive neoplasm, typically found in the parotid glands of older men. The histologic appearance is that of an in situ and invasive high-grade adenocarcinoma, and it closely resembles ductal carcinoma of the breast. Several variants of the latter are very well known, but only papillary, sarcomatoid, and low-grade subtypes have so far been reported in salivary duct carcinoma. This study describes the clinicopathologic and immunohistochemical findings in four examples of an additional previously undescribed variant, rich in mucin. Each tumor showed areas of typical salivary duct carcinoma, but in addition there were lakes of epithelial mucin-containing malignant cells, i.e., mucinous (colloid) carcinoma. All four tumors expressed androgen receptors, cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, and carcinoembryonic antigen, but S-100 protein, other myoepithelial markers, and estrogen and progesterone receptors were negative. The mucin antigen profile showed positivity for MUC2, MUC5B, and MUC6 in all cases but only rare staining with MUC5AC and MUC7. Strong immunohistochemical overexpression of HER2/neu was demonstrated in one tumor, together with amplification by fluorescence in situ hybridization; another case was weakly positive with just one antiserum, but the remaining two tumors were completely negative. Small quantities of mucin have often been described in salivary duct carcinoma but not large extracellular mucinous lakes, which though prominent in the present series, were not as extensive as in mucinous adenocarcinoma. The relatively poor clinical outcome of the patients in our study mirrored that seen in usual-type salivary duct carcinoma and emphasizes the importance of differentiating mucin-rich salivary duct carcinoma from pure mucinous (colloid) adenocarcinoma, a tumor not fully defined, but possibly with a better prognosis.
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PMID:Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases. 1617 3

An engineered antibody fragment (minibody; scFv-C(H)3gamma(1) dimer, M(r) 80 000) specific for carcinoembryonic antigen (CEA) has previously demonstrated excellent tumor targeting coupled with rapid clearance in vivo. In this study, variable (V) genes from the anti- p185(HER-2) 10H8 antibody were similarly assembled and expressed. Four constructs were made: first, the V genes were assembled in both orientations (V(L)-linker-V(H) and V(H)-linker-V(L)) as single chain Fvs (scFvs). Then each scFv was fused to the human IgG1 C(H)3 domain, either by a two amino acid linker (ValGlu) that resulted in a non-covalent, hingeless minibody, or by IgG1 hinge and a GlySer linker peptide to produce a covalent, hinge-minibody. The constructs, expressed in NS0 mouse myeloma cells at levels of 20-60 mg/l, demonstrated binding to the human p185(HER-2) overexpressing breast cancer cell line, MCF7/HER2. Binding affinities (K(D) approximately 2-4 nM) were equivalent to that for the parental 10H8 mAb (K(D) approximately 1.6 nM). Radioiodinated 10H8 hinge-minibody was evaluated in athymic mice, bearing MCF7/HER2 xenografts. Maximum tumor uptake was 5.6 (+/-1.65)% injected dose/g (ID/g) at 12 h, which was lower than that of the anti-CEA minibody, whereas the blood clearance (beta-phase, 5.62 h) was similar. Thus, minibodies with different specificities display similar pharmacokinetics, while tumor uptake may vary depending on the antigen-antibody system.
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PMID:Characterization of engineered anti-p185HER-2 (scFv-CH3)2 antibody fragments (minibodies) for tumor targeting. 1518 22

Germ-line mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma (FMTC). The objective of the present study was the clinical and molecular characterization of the first two Greek Cypriot families diagnosed with MEN2A and FMTC. The clinical diagnosis of the probands was based on clinical presentation and supported with laboratory findings (calcitonin and carcinoembryonic antigen tumor marker levels). We screened the RET gene by direct DNA sequencing of exons 10, 11, and 16 using genomic DNA as templates. After identification of the mutation, we also developed the amplification refractory mutation system (ARMS) as an alternative method to direct sequencing for genetic diagnosis of 22 additional individuals from both families. We identified the germ-line missense mutation T --> C of codon 618 of exon 10 (C618R) in the probands of both families. By using ARMS, two members of the MEN2A family and five members of the FMTC family were also found positive for the C618R mutation. These are the first seemingly unrelated families in Cyprus investigated clinically and molecularly in detail and shown to transmit this common RET proto-oncogene mutation.
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PMID:Description of the first two seemingly unrelated Greek Cypriot families with a common C618R RET proto-oncogene mutation. 1534 14

A cohort of patients with intraductal growth-type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long-term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non-IG-ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non-IG-ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG-ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non-IG-ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non-IG-ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management.
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PMID:Characterization of intrahepatic cholangiocarcinoma of the intraductal growth-type and its precursor lesions. 1611 40

Over the last two decades, various research protocols were applied for scintigraphic imaging, prognosis and treatment of breast cancer, using monoclonal antibodies. Monoclonal antibodies approved by the United States Food and Drug Administration (FDA) include the anti-carcinoembryonic antigen (CEA), and B72.3, prepared against the tumour-associated glycoprotein, TAG-72. The recombinant humanized "cold" anti-HER2 monoclonal antibody (trastuzumab), which targets oncogene receptor HER2 has hitherto been the only monoclonal antibody widely used for the treatment of breast cancer in the USA, with or without chemotherapy. Trastuzumab is constructed against the HER2 oncogene receptor (also known as neu or c-erb-B2), which is overexpressed in 25%-30% of breast cancer cell lines and is associated with poor prognosis. Immuno-lymphoscintigraphy is also applied to guide and monitor the effect of treatment regimes. Radiolabelled, "hot" monoclonal antibodies are currently being applied for the treatment of primary or metastatic breast cancer, in experimental, pre-clinical, or clinical trials, in combination with traditional external beam radiotherapy and/or chemotherapy. Radioimmunotherapy comprises systemically administered monoclonal antibodies, linked to high-energy, beta-emitting radionuclides. Radioactive antibodies, in the form of yttrium-90 (90Y)-BrE-3, 90Y- m170 and 131I- or 90Y- labelled L6 antibody, are applied with adjuvant autologous peripheral blood stem cells transfusion, to prevent myelotoxicity. Partial or rarely complete responses to "hot" antibody treatment, of breast cancer have been reported. Innovative strategies using this combined-modality treatment hold promise for better disease-free and survival rates.
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PMID:Monoclonal antibodies: old and new trends in breast cancer imaging and therapeutic approach. 1614 51

Surgical therapy of incidentally postoperative diagnosed small sporadic medullary thyroid cancer (MTC) is discussed controversially. In principle completion thyroidectomy with neck dissection and regulary tumor follow-up are under discussion. A total of 277 patients with MTC were treated between 1986 and 2004. In 22 cases diagnosis of a small (pT1 or pT2) sporadic MTC was incidental and only postoperatively confirmed. Normally total thyroidectomy with neck dissection is standard surgical therapy of a known MTC. Because of postoperative incidental diagnosis in all 22 cases surgical therapy was less then total thyroidectomy. Mutation analysis of RET Proto-Oncogen and familial history were negative in all cases. All patients were systematically followed-up in defined intervals by calcitonin, pentagastrin stimulation test, carcinoembryonic antigen and ultrasound. Median follow-up is 6.2 years (range: 2-13 years) and although a hemithyroidectomy or less was performed all 22 patients are cured by the MTC. We conclude that completion thyroidectomy and neck dissection are not mandatory in such patients, if the tumor is completely resected and genetic background is excluded. Indispensably a systematic long term follow-up of at least 10 years, better a life-long, is mandatory.
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PMID:[Decision making in postoperative incidentally found small C-cell-carcinoma]. 1622 Apr 40

The characterization of tumor antigens recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. The potential advantages of the vaccines are: (i) the induction of a robust immune response against tumors that are spontaneously weekly immunogenic; (ii) the tumor specificity for some antigens; (iii) the good tolerance and safety profile and (iv) the long-term immune memory, critical to prevent efficiently tumor recurrence. Most trials evaluating breast cancer vaccines have been carried out in patients with extended metastatic breast cancer, characterized by aggressive tumors, resistant to standard cytotoxic treatments, so that clinical efficacy was difficult to achieve. However, some significant immune responses against tumor antigens induced upon vaccinations were recorded. The aim of this review is to analyze the activity of vaccination strategies in current clinical trials. Data of clinical activity have been observed by using vaccines targeting HER2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen and carbohydrate antigen given after stem cell rescue. The review discusses possible future directions for vaccine development and applications in the adjuvant setting.
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PMID:Breast cancer vaccines: a clinical reality or fairy tale? 1629 74


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