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 candidate tumor-suppressor gene hyaluronidase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. The viral envelope (Env) protein alone can transform cultured cells, and we hypothesized that Env could bind and sequester the HYAL2 receptor and thus liberate a potential oncogenic factor bound and negatively controlled by HYAL2. Here we show that the HYAL2 receptor protein is associated with the RON receptor tyrosine kinase (also called MST1R or Stk in the mouse), rendering it functionally silent. In human cells expressing a jaagsiekte sheep retrovirus Env transgene, the Env protein physically associates with HYAL2. RON liberated from the association with HYAL2 becomes functionally active and consequently activates the Akt and mitogen-activated protein kinase pathways leading to oncogenic transformation of immortalized human bronchial epithelial cells. We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer.
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PMID:Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. 1267 86

In this study, we investigated the prognostic value of HER2/neu, p53, and vascular endothelial growth factor in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were immunostained for HER2/neu, p53, and vascular endothelial growth factor. Positivity was scored quantitatively by three observers and correlated with multiple prognostic parameters including survival. In the conventional adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group, p53 showed a significant correlation with recurrence while vascular endothelial growth factor correlated with angiolymphatic invasion (P < 0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, P < 0.05). Patient whose tumors coexpressed both p53 and HER2/neu had the worst outcome. In the bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively which was significantly less than in conventional adenocarcinoma (P < 0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, P < 0.05) in nonmucinous type. In conclusion, vascular endothelial growth factor was associated with angiolymphatic invasion and poor prognosis in conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and HER2/neu expression appeared to be poor prognostic markers, while in bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer prognosis. This immunostaining pattern suggests that conventional adenocarcinoma has different molecular abnormalities than bronchioloalveolar carcinoma.
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PMID:Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor expression in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. 1516 37

Bronchioloalveolar carcinoma (BAC) is an important subtype of pulmonary adenocarcinoma. It has received increasing attention in recent years, due to its increasing incidence and its rate of sensitivity to epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs). This article reviews the epidemiology, risk factors, pathology, clinical presentation, and treatment of this disease. Special focus is paid to the emerging role of oral EGFR-TKIs in Bronchioloalveolar cell carcinoma.
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PMID:Bronchioloalveolar carcinoma: a review of the epidemiology, pathology, and treatment. 1605 36

Cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol; Bristol-Myers Squibb), vinorelbine (Navelbine; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB-IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) in operable NSCLC are planned. One such study includes cisplatin and docetaxel. Effective development of active agents and disease management based on molecular profiling of lung tumors will change tomorrow's standard of care.
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PMID:How today's developments in the treatment of non-small cell lung cancer will change tomorrow's standards of care. 1627 56

Bronchioloalveolar carcinoma is one of the four histological subtypes of adenocarcinoma and its incidence is increasing. It grows in a lepidic fashion along the alveolar septa without invading alveolar walls. The strict histological definition requires complete surgical resection to exclude any evidence of invasion. This definition is thus only applicable in practice to isolated operable pulmonary nodules. For other types high-resolution lung CT-scan is necessary to evaluate pulmonary involvement because of the high frequency of multifocal disease at initial presentation and because of the presence of ground glass opacities, which can be one of the first manifestations of CBA on CT. Therapeutic management does not differ from non-small cell lung cancer. Solitary nodules are treated by surgical resection with a good prognosis whereas multifocal disease is rarely respectable. Diffuse and/or pneumonic forms are treated with systemic chemotherapy with a generally poor prognosis. However, the recent discovery of the particular sensitivity of this form of adenocarcinoma to EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitors offers new possibilities for management.
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PMID:[Bronchioloalveolar carcinoma]. 1634 Aug 39

Synchronous bronchiolo-alveolar cell carcinoma (BAC) in both lungs and squamous cell carcinoma in left lung were found in a 66-year-old male smoker. After two courses of chemotherapy with gemcitabine and carboplatin, the left lung mass had partially resolved, however, the extent of BAC had been increased. When gefitinib was used as a second-line chemotherapy, the consolidation lesions of BAC was improved while the mass of squamous cell carcinoma was aggravated. The analysis of epidermal growth factor receptor-tyrosine kinase (EGFR-TK) mutations showed that BAC had the deletion, delE746-A750 in exon 19, however, squamous cell carcinoma had no mutations. These synchronous tumors with different location, histology, status of EGFR-TK mutations and response to chemotherapy might be caused by different molecular pathogenesis.
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PMID:Synchronous multiple primary lung cancers with different response to gefitinib. 1678 85

In the resected lung, additional small lesions are occasionally found incidentally, and include the full spectrum of preinvasive to invasive lesions under the current putative schema of the sequential development of lung cancer. In this study, we examined EGFR and KRAS gene mutations in 119 synchronous pulmonary lesions, including 40 precursor lesions (atypical adenomatous hyperplasia, AAH), 26 carcinomas in situ (non-mucinous bronchioloalveolar carcinoma, BAC), 14 minimally invasive adenocarcinomas, 34 overt invasive adenocarcinomas, and five of other subtypes of cancer. Although the mutually exclusive nature of KRAS and EGFR gene mutations was maintained even in preinvasive lesions, the incidences of the lesions along the putative progression schema were quite different. The KRAS gene was mutated in 33% of AAH, 12% of carcinomas in situ, 8% of minimally invasive adenocarcinomas and 0% of well-differentiated adenocarcinomas, whereas the frequencies of EGFR mutation did not fluctuate greatly, at 25%, 51%, 36%, 86% and 67%, respectively. These results are consistent with the findings of a published gene-targeted mouse model; the mice expressing oncogenic KRAS developed AAH but not invasive adenocarcinoma, whereas a spectrum of preinvasive to invasive adenocarcinomas was observed in the mice expressing mutant EGFR. Taking these factors together, it is suggested that AAH could develop by either KRAS or EGFR gene mutation, but AAH harbouring a KRAS gene mutation might not progress further to an invasive cancer.
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PMID:Disproportionate representation of KRAS gene mutation in atypical adenomatous hyperplasia, but even distribution of EGFR gene mutation from preinvasive to invasive adenocarcinomas. 1753 46

Non-small cell lung cancer (NSCLC) knows important changes with the development of the use of chemotherapy not only in the advanced forms but also in a perioperative setting. In early stage disease, a wedge resection seems to be sufficient in the tumours with a diameter less than 2 cm and presenting as ground-glass opacity. In all other cases, at least a lobectomy is mandatory with a mediastinal dissection. There have been numerous technical improvements regarding radiation therapy which should lead to improved quality control ... and the need to revisit some concepts among which postoperative radiation therapy. Targeted therapies have been the real novelty in the treatment of non-small cell lung cancer. The inhibitors of EGFR (monoclonal antibodies and tyrosine kinase inhibitors) have been studies with upfront chemotherapy in advanced NSCLC without any benefit. However, they have proved useful in second line setting and in first line setting in diffuse bronchioloalveolar carcinoma. The targeted therapy bevacizumab (Avastin) is now the standard of the treatment of advanced NSCLC in combination with carboplatine and paclitaxel in the United States, whereas its combination with cisplatin and gemcitabine is still under investigation in Europe. Regarding small-cell lung cancer, there has been no real novelty, the standard treatment remains unchanged.
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PMID:[Recent development of the standards of treatment of lung cancer]. 1757 22

Although the 1999 WHO classification, revised in 2004 excludes stage IIIB-IV tumors from the definition of bronchioloalveolar carcinoma (BAC) because they are unresectable, the first international workshop (November 2004, New York) devoted to this tumor emphasized the continuum between the BAC as defined by the WHO and adenocarcinomas with a BAC-like component which presents similar epidemiological, biological, clinical, radiological, prognostic and therapeutic features. These observations led to the suggestion to no include stage IIIB-IV ADC-BAC in studies designed for other non-small-cell lung cancers. The purpose of this review was to analyze the results of prospective studies currently available concerning the treatment of stage IIIB-IV ADC-BAC. No evidence is available with combination regimens using platine. Monotherapy with paclitaxel appears to have efficacy similar to inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib) (TKI-EGFR). The tolerance profile is in favor of using TKI-EGFR. It would appear that tumors responding to paclitaxel and to TKI-EGFR correspond to different diseases. These observations point out the importance of further studies examining the proper strategy and to search for new compounds for the treatment of extensive ADC-BAC.
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PMID:[Therapeutic management of extensive bronchiolo-alveolar adenocarcinoma: chemotherapy or inhibitors of epidermal growth factor receptor tyrosine kinase?]. 1767 38

It has been proposed that stepwise progression occurs from atypical adenomatous hyperplasia (AAH) through bronchioloalveolar carcinoma (BAC) to invasive lung adenocarcinoma. However, the underlying molecular mechanisms have not been identified. We report a patient with a mixed adenocarcinoma of the lung that had different EGFR mutations in the papillary subtype, the acinar subtype, and the surrounding AAH and BAC areas. EGFR mutations may accumulate during tumor progression and lead to heterogeneity of EGFR mutations within the tumor.
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PMID:Heterogeneity of epidermal growth factor receptor mutations within a mixed adenocarcinoma lung nodule. 1788 60


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