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)

Normal tissues, primary tumors, and metastases of mammary and salivary glands and oral/laryngeal mucosa have been analyzed with Northern-blots employing 32P-labeled RNA probes for the expression of the neu oncogene. Neu oncogene expression of a mRNA species of 4.6 kilobases was found in all normal salivary (five) and mammary glands (four) as well as in two normal or inflamed samples of tongue mucosa. This expression was regarded as baseline activity of the neu gene for the respective tissues and was used as standard for the evaluation of benign and malignant tumors. None of 14 squamous cell carcinomas of the oral and laryngeal mucosa showed enhanced neu transcription level. Five fibroadenomas, one benign variant of phylloid tumor, one carcinosarcoma, and one of two proliferative fibrocystic diseases of the breast showed lacking or normal baseline expression of the neu oncogene, as did one monomorphous cystadenolymphoma of the parotid gland. In contrast, four parotid pleomorphic adenomas and one salivary gland adenocarcinoma showed enhanced neu expression. For mammary adenocarcinomas, increased neu oncogene expression concerned ten of 34 cases--all being variants of ductal carcinomas--and all metastases analyzed (six) deriving from three primaries. One adenoid cystic carcinoma also showed enhanced neu expression. Neu overexpression may reflect accidents of genomic reconstitutional events occurring regularly within the differentiation pathway of epithelial/myoepithelial cells. This assumption was supported by further immunohistochemical analysis which showed stainings of myoepithelial and myoepithelia-like cell populations in tumors, especially pleomorphic adenomas and adjacent normal-looking tissues.
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PMID:Comparative investigation of c-erbB2/neu expression in head and neck tumors and mammary cancer. 167 62

The incidence and spectrum of spontaneously occurring neoplasms was evaluated in 285 European hamsters (strain Mhh:EPH) ranging in age between 1 and 5 years. The mean lifespan of the 107 male and 135 female hamsters examined amounted to 122 and 135 weeks, respectively. The overall incidence of tumour-bearing animals was 51.2% (males: 57.9%, females: 47.2%). Malignant tumours were more frequent than benign neoplasms and affected more males than females. Neoplasms of the haematopoietic/lymphoreticular system were the most common tumours (males: 16.8%, females: 13.5%). In males, these were followed in a decreasing order of incidence by pheochromocytomas (15.9%), malignant schwannomas (8.4%) and tumours of the prostate (6.5%). In females, pheochromocytomas as well as granulosa cell tumours were the second commonest tumour types (6.2% each), followed by malignant schwannomas (5.1%). Other tumours did not exceed the 5% incidence level. Two unusual rare tumours were a locally invasive cementoblastoma arising in the maxilla and a carcinosarcoma of the skin with components of a squamous cell carcinoma and a neurofibrosarcoma. The results of the study are compared with data on the Syrian and Chinese hamster.
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PMID:Spontaneous tumours of the European hamster (Cricetus cricetus L.). 275

This study investigates the incorporation of three intravenously administered radiolabeled fatty acids, [9,10-3H]palmitate (3H-PAM), [1-14C]arachidonate (14C-ACH) and [1-14C]docosahexaenoate (14C-DHA), into lipids of intracerebrally implanted tumor and contralateral brain cortex in awake rats. A suspension of Walker 256 carcinosarcoma cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of an 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat was infused intravenously for 5 min with 3H-PAM (6.4 mCi/kg), 14C-ACH (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty min after the start of infusion, the rat was killed and intracranial tumor mass and brain cortex were removed for lipids analysis. Each radiolabel was incorporated more into tumor than into brain cortex. Ratios of net incorporation rate coefficients (k*) into tumor as compared with brain were 4.5, 3.4 and 1.7 for 3H-PAM, 14C-ACH and 14C-DHA, respectively. Lipid radioactivity comprised more than 80% of total tumor or brain radioactivity for each probe. Phospholipids contained 58%, 89% and 68% of tumor lipid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for 3H-PAM, 14C-ACH and 14C-DHA, respectively. Incorporation coefficients (k*i) for a phospholipid class (i)--choline phosphoglycerides (PC), inositol monophosphoglycerides (PI), ethanolamine phosphoglycerides (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)--were greater in tumor than in brain for each fatty acid probe, except that values for k*PE and k*PS using 14C-DHA were equivalent. Differences in k*i between tumor and brain were largest for SM and PC and the change in k*PC accounted for 65-90% of the increase in the net phospholipid incorporation rate for each probe. Differences in k*PI, k*PE and k*PS were smaller than those in were smaller than those in k*PC and k*SM, and varied with the probe. Differences in k*i were related to differences in tumor and brain phospholipid composition and metabolism. The results indicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumor in vivo using positron emission tomography.
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PMID:Differences in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids of intracerebrally implanted tumor and brain in awake rats. 819 96

Uterine carcinosarcoma histologically comprises the components of epithelial and mesenchymal malignancies, and is known to be clinically highly aggressive. To reveal the significance of the expression of tyrosine-kinase-receptor-type oncoproteins in this tumor type, the incidence and distribution of the KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins were immunohistochemically examined in 16 surgically resected cases. For 6 cases, the EGFR and HER-2 amplifications were also examined by fluorescence in situ hybridization (FISH). In the epithelial component, overexpressions of KIT, EGFR, and HER-2 were detected in 4 (25%), 5 (31%), and 9 (56%) cases, respectively, whereas these overexpressions in the mesenchymal component were detected in 6 (38%), 8 (50%), and 1 (6%) cases, respectively. KIT and EGFR were co-overexpressed in the mesenchymal component of 4 cases and in the epithelial component of 2 cases. However, HER-2 overexpression was mostly detected in the epithelial component only, and tended to occur independently of KIT and/or EGFR overexpression. By FISH, one of the 4 cases with HER-2 overexpression showed low-level gene amplification. In two cases with EGFR overexpression, the gain of EGFR alleles and/or polyploidization of chromosome 7 had occurred. The expression patterns of KIT, EGFR, and HER-2 differed between the epithelial and mesenchymal components, and the regulation of their expression appeared important in the acquisition of mesenchymal metaplasia in uterine carcinosarcoma. Structural and/or numerical alterations of chromosomes might be in part involved in EGFR and/or HER-2 overexpression in this tumor type.
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PMID:Different expression patterns of KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins between epithelial and mesenchymal components in uterine carcinosarcoma. 1461 76

Inflammatory myofibroblastic tumor (IMT) is an indolent spindle cell proliferation that can histologically resemble various malignant mesenchymal neoplasms; however, it generally behaves as a benign or locally recurrent tumor. Most IMTs involve the lung, mesentery, omentum, or retroperitoneum. We report the clinical and pathologic features of six IMTs of the uterus, one of which was included in a previous report, and emphasize the histologic and immunohistochemical features that distinguish IMTs from uterine spindle cell neoplasms that require aggressive treatment. Recently, translocations of the anaplastic lymphoma kinase (ALK) gene and immunohistochemical expression of ALK have been reported in IMTs of various anatomic sites. We compared ALK expression in uterine IMTs with that in uterine mesenchymal neoplasms with which it may be confused. Patients with IMT were between 6 and 46 years of age. None had a history of abdominal surgery; three were multiparous. The IMTs ranged from 1 to 12 cm in maximum dimension. Three grew as polypoid masses that arose in the lower uterine segment, and two of these prolapsed through the cervical os. The three other tumors grew as bulky myometrial masses with focally irregular borders and infiltrated the endometrium, parametrium, or cervical stroma. There were three main microscopic patterns: a hypocellular pattern, a fascicular pattern, and a hyalinized pattern. A lymphoplasmacytic infiltrate was present in all of the tumors, and most had a myxoid background. Mitotic activity ranged from 0 to 2 mitotic figures per 10 high power fields (HPF) except in one tumor that focally had up to 8 mitotic figures per 10 HPF. No nuclear atypia or necrosis was present. Immunohistochemical expression of ALK was present in a cytoplasmic pattern in all IMTs tested. No ALK expression was identified in uterine leiomyoma (n = 7), leiomyosarcoma (n = 6), carcinosarcoma (n = 4), endometrial stromal sarcoma (n = 4), or normal uterine tissues. Follow-up ranging from 1.5 years to 5 years in 4 patients with uterine IMTs revealed no recurrence or metastasis. IMTs should be differentiated from aggressive uterine mesenchymal tumors because they can be treated conservatively and have a more favorable prognosis. ALK expression appears to be of diagnostic value in conjunction with other immunohistochemical stains.
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PMID:Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. 1616 Apr 78

Overexpression of the erbB-1 (EGFR, epidermal growth factor receptor) and erbB-2 (HER2/neu) proteins contributes to the aggressive behavior of malignant tumors originating from the endometrium. We currently examined whether the trend of these proteins to overexpression is a direct effect of their gene transcriptional activities. Expression of the erbB-1/erbB-2 genes was measured applying the quantitative RT-PCR technique in 25 uterine carcinomas, 12 normal endometria, a carcinosarcoma and a case of botryoid sarcoma of the uterine cervix. We showed that erbB-1 mRNA was overexpressed in 48% (12/25) and erbB-2 mRNA was overexpressed in 8% (2/25) of the analysed tumors. The level of expression appeared to be significantly higher in the malignant tumors as compared to the benign ones for erbB-1 and for erbB-2 (p=0.0001 and p=0.008, respectively). A significant correlation between erbB-1 overexpression and tumor differentiation was found (Spearman rank correlation test, p<0.001). Concomitant erbB-1 and erbB-2 overexpression was detected only in 1 out of 25 (4%) uterine neoplasms. erbB-1 was overexpressed in a sarcoma botryoides of the uterine cervix. Our data suggest that erbB-1/erbB-2 overexpression is a direct effect of higher than normal transcriptional activity of the encoding genes in a subset of human endometrial carcinomas.
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PMID:Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium. 1754 77

Uterine carcinosarcoma (malignant mixed Mullerian tumor) is an uncommon female genital tract neoplasm characterized by an admixture of epithelial and stromal malignant cells. We report a case of 50-year-old peri-menopausal woman diagnosed to have early-stage (IB due to FIGO) uterine carcinosarcoma of the homologous type with superficial (3mm) myo-invasion. The patient showed no clinical symptoms of the disease and had no family history of female genital tract malignancies. Positive immunostaining for steroid receptors (estrogen-alpha and progesterone receptors), cytokeratin, and EGFR was detected only in the carcinomatous area, whereas beta-catenin, BCL-2, COX-2, p16(INK4a), PTEN, RB-1, and vimentin were immunoreactive in both components. Androgen receptor, CD10, desmin, HER-2/neu, and P53 were found to be negative either in the carcinomatous or in the sarcomatous area. Tumor proliferative activity was higher in the carcinomatous (25%) than in the sarcomatous (2%) component. Based on these findings, immunohistochemical evaluation of multiple receptor status in the carcinomatous and sarcomatous areas of carcinosarcoma may provide a clue to the pathogenesis and hormonal receptor status of this uncommon uterine malignancy.
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PMID:Immunohistochemical analysis of carcinomatous and sarcomatous components in the uterine carcinosarcoma: a case report. 1820 53

Carcinosarcoma of the breast, often referred to as metaplastic carcinoma of the breast, is a rare malignancy with two distinct cell lines described as a breast carcinoma of ductal type with a sarcoma-like component. Clinically, carcinosarcoma of the breast is an aggressive breast cancer. The prognosis for carcinosarcoma of the breast is less favorable compared to more common types of breast cancer such as infiltrating ductal or lobular carcinoma. Currently, the evaluation of breast carcinoma includes hormone receptor analysis of the tumor tissue, with those positive for estrogen or progesterone responding better to both hormonal and chemotherapy.Trastuzumab (Herceptin(R)) is available as an adjunct treatment for tumors which over-express the HER2/neu gene. Typically, metaplastic carcinomas of the breast do not express the estrogen or progesterone receptors and do not over-express the HER2/neu oncogene. As a result of this "triple negative" phenotype, such tumors tend to be more aggressive and are unlikely to respond to targeted therapy with Herceptin. The epidermal growth factor receptor HER-1/EGFR protein is expressed in the majority of metaplastic carcinomas and thus may serve as a potential therapeutic target for EGFR inhibitors such as gefitinib and cetuximab. The two cases we describe exemplify the aggressive nature of carcinosarcoma of the breast and support the findings that this tumor type does not express the common receptors found in other breast carcinomas. These case reports also emphasize the need for investigating the role for blockade of the HER-1/EGFR receptor with targeted therapies when found to be over-expressed in the primary tumor.
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PMID:Carcinosarcoma of the breast: two case reports and review of the literature. 1912 25

This report describes 3 cases of a distinctive, hitherto unreported gastric epitheliomesenchymal biphasic tumor that differs from other biphasic tumors of the stomach and elsewhere: carcinosarcoma, biphasic synovial sarcoma, teratoma, and mixed tumor. The tumors occurred in young adults, 2 males and 1 female, of ages 19, 27, and 30 years. Two tumors were located in the greater curvature in the gastric body and one in the antrum. The tumors measured 5, 6, and 15 cm in maximum diameter, and their mitotic rates were 0, 4, and 30 mitoses per 50HPF. There were 2 components: uniform oval or spindled cells in diffuse sheets, and clusters or cords of epithelial cells occasionally forming glandular structures with small lumens. The epithelial elements were positive for keratin cocktail AE1/AE3, keratin 18, and partly for keratin 7, but were negative for keratins 5/6, 20 and epithelial membrane antigen. The spindle cells were positive for vimentin and CD10. All components were negative for CD34, CD99, estrogen receptor, KIT, smooth muscle actin, desmin S100 protein, p63, calretinin, chromogranin, synaptophysin, CDX2, and thyroid transcription factor 1. In situ hybridization for SS18 rearrangement was negative in all cases separating this tumor from synovial sarcoma. All 3 patients were alive after follow-up of 3.5, 5, and 14 years. Because these tumors have some resemblance to blastomas of other organs, we propose the term "gastroblastoma" for this distinctive, at least low-grade malignant epitheliomesenchymal tumor of the stomach.
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PMID:A distinctive novel epitheliomesenchymal biphasic tumor of the stomach in young adults ("gastroblastoma"): a series of 3 cases. 1971 90

Gastroblastoma is a rare gastric epitheliomesenchymal biphasic tumour composed of spindle and epithelial cells, reported by Miettinen et al in a series of three cases in 2009. All those cases arose in stomachs of young adults. Neither the epithelial nor the mesenchymal component displayed sufficient atypia to diagnose a carcinosarcoma or other malignancy. On immunohistochemistry, the epithelial component expressed cytokeratin, and the mesenchymal component was positive for vimentin and CD10. Miettinen et al designated these neoplasms as gastroblastomas based on their similarities with other childhood blastomas such as pleuropulmonary blastoma and nephroblastoma. This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion.
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PMID:Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings. 2020 30


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