Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.
 ...
PMID:CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. 166 Jan 44

The presence of gene amplification was determined in 66 fresh head-and-neck SCC specimens using a battery of 9 different probes. Amplification of at least one gene was found in 12 samples (18%), of which 7 were amplified at multiple loci (58%). We observed amplifications for EGFR (10% of samples) and c-myc (9%), as well as co-amplification of bcl-1/int-2 (7%). No amplifications were demonstrated for c-Ha-ras-1, TGF alpha, c-mos, c-erbB-2, or c-erbA-2. The incidence of proto-oncogene amplification in head-and-neck SCC patients is comparable to that reported for other solid tumours. There was no statistically significant difference in survival between patients with or without gene amplification. However, the presence of multiple amplifications in several patients with advanced primary tumours suggests that the accumulation of genetic changes may correlate more closely with tumour size than with inherent biologic aggression.
 ...
PMID:Analysis of gene amplification in head-and-neck squamous-cell carcinoma. 204 98

About 80% of neoplasias are epithelial in origin and, as such, understanding the molecular mechanisms involved in the development of epithelial tumours is vital to the diagnosis, prognosis and treatment of the vast majority of human cancers. Obviously this is no easy task but, as outlined above, great efforts are being made to identify important molecules involved in the progression of normal epithelial cells to carcinoma. The development of techniques to identify new oncogenes is of particular importance, and hopefully the cDNA expression cloning system of Stuart Aaronson will be a useful tool in this respect. The potential of some of these molecules to be used as therapeutic targets will require the development of suitable screening procedures, such as that being established by Chris Marshall for the ras-Map kinase pathway in yeast. It is encouraging that the immune response to virally (HPV) induced cancer is being carefully elucidated and the prospects of vaccine development for the treatment of cervical cancer coming nearer since this particular form of SCC is a major cancer globally. Finally it was fitting to end the meeting on an optimistic note with John Mendelsohn's EGFR monoclonal antibody therapy entering clinical trials, and hopefully this will prove efficacious in the treatment of human SSC.
 ...
PMID:1st international Beatson symposium--cellular, molecular and clinical aspects of squamous cell carcinomas. 829 43

Medullary thyroid carcinoma in both sporadic and familial forms is a curable disease if detected early and treated by the proper surgery. The advent of genetic screening for the RET protooncogene portends great promise in the earlier diagnosis and treatment of familial forms of MTC. New chemotherapy protocols have produced some tumor regression in patients with metastatic MTC. Improved use of Adriamycin and hyper-fractionated radiotherapy combined with debulking procedures has prolonged survival in anaplastic thyroid cancer. Thyroid gland lymphoma, if diagnosed early and treated by combined chemoradiotherapy, carries a good prognosis for survival. The best treatment for thyroid sarcomas and SCC of the thyroid is early diagnosis and aggressive surgery combined with radiotherapy.
 ...
PMID:Thyroid cancers. II. Medullary, anaplastic, lymphoma, sarcoma, squamous cell. 884 33

Squamous cell carcinoma of the head and neck is the fourth most common cancer in the United States, and therapy for very advanced cases is relatively ineffective. Paclitaxel has activity against cancers of the breast, lung, prostate, cervix, and ovary. The activity of paclitaxel for squamous cell carcinoma of the head and neck is less certain, and results of its radiosensitization properties have been variable. The radiation responses of two squamous carcinomas, SCC-9 (oropharynx) and HEP-2 (larynx), were examined to determine the radiosensitizing potential of paclitaxel. In vitro exposures for 24 and 48 h with paclitaxel concentrations of 10(-4) to 6 x 10(-2) microg/ml were followed by irradiation of 0.1-10 Gy. Percent survival was calculated by colony count, and the paclitaxel-radiation interaction was quantitated by the median effect principle and the combination index method of Chou and Talalay. The paclitaxel-radiation combination resulted in multiphasic interactions in both 24 and 48 h paclitaxel pretreatment in SCC-9 and HEP-2 cell lines. In general there was slight synergism [combination index (CI) <1] at low dose-low effect levels (e.g., at a paclitaxel concentration of 0.002 microg/ml or lower and radiation of 0.1-0.3 Gy), moderate antagonism (CI >1) at median dose ranges and strong synergism (CI <<1) at high dose ranges (e.g., at a paclitaxel concentration of 0.012-0.06 microg/ml and radiation doses of 3-10 Gy), especially at a surviving fraction of <0.1, which is therapeutically relevant. The median effect principle and combination index method provided a simple way to quantitate the synergism or antagonism of a paclitaxel-radiation interaction under various conditions. This analysis demonstrated that paclitaxel-radiation synergy exists at doses that are readily achievable in the clinical scenario for both agents and that greater synergy occurred at high dose-high effect levels. These results suggest that the combination of both therapies should be explored further in clinical trials assessing the treatment of squamous cell carcinomas of the head and neck.
 ...
PMID:Paclitaxel enhances in vitro radiosensitivity of squamous carcinoma cell lines of the head and neck. 891 57

Hypoxic accumulation of 2-[5,6-3H]fluoro-2-deoxy-D-glucose ([3H]FDG),L-[methyl-3H] methionine ([3H]MET), and L-[1-3H]leucine ([3H]LEU) was evaluated in two cell lines (UT-SCC-5 and UT-SCC-20) obtained from patients with squamous-cell carcinoma of the head and neck. Both cell lines were exposed to decreasing oxygen atmosphere (20%, 1.5%, or 0% O2) for 6 h, after which they were incubated for a further 1 h with tritiated FDG, MET, or LEU. An anoxic atmosphere resulted in a mean increase of [3H]FDG uptake of 120% and 46% over a baseline 20% oxygen atmosphere for UT-SCC-5 and UT-SCC-20A, respectively. Both total and acid-precipitable [3H]MET uptake remained unchanged at 0% versus baseline, whereas acid-precipitable [3H]LEU uptake decreased by 46% for UT-SCC-5 and by 34% for UT-SCC-20A at 0% O2. Our findings demonstrate that [3H]FDG accumulation is increased in hypoxic UT-SCC cell lines probably through activation of the metabolic steps associated with the glycolytic pathway. The decrease in acid-precipitable [3H]LEU uptake in hypoxia may indicate a decline in protein synthesis, whereas the unchanged [3H]MET uptake probably reflects the unaffected amino acid transport and slow incorporation of radiolabeled methyl group of MET in tumor proteins and nucleic acids. FDG and LEU, but probably not MET, warrant additional study as hypoxia-avid or hypoxia-reduced tracers for assessment of treatment effects designed to modify hypoxia.
 ...
PMID:Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. 900 82

EGFR expression in 150 potentially curative resected squamous cell carcinomas of the oesophagus was analyzed immunohistochemically and correlated with survival. Altogether, 124 of 150 (82.7%) tumours expressed different levels of EGFR. The percentage of tumour cells expressing EGFR varied greatly between the different tumours (median: 70%). 62 (50.0%) tumours showed weak and intense staining, respectively. Regarding the staining pattern 19 (15.3%) tumours showed exclusively membraneous immunoreactivity, 27 (21.8%) an exclusively cytoplasmic immunoreactivity and 78 (62.9%) a mixed staining pattern. No significant correlation however could be found between EGFR expression and various clinicopathologic parameters such as pT category, pN category, tumour size, histologic grade and blood vessel invasion. In univariate survival analysis, no correlation between EGFR expression and postoperative survival time was observed. In a forward multivariate Cox regression analysis only the parameters lymphatic-vessel invasion (p = 0.001), pT category (p = 0.0034) and pN category (p = 0.0256), but not the EGFR expression, could be verified as independent prognostic variables. In conclusion, the evaluation of the EGFR expression does not provide prognostic information for patients who underwent potentially curative resection for SCC of the oesophagus.
 ...
PMID:The prognostic significance of epidermal growth factor receptor expression in squamous cell carcinomas of the oesophagus. 942 3

Mitogen-activated protein kinase (MAPK) is a serine-threonine kinase that is activated by various extracellular stimuli. Extracellular signal-regulated kinases (ERK1 and ERK2), an MAPK subfamily, are activated by many oncogenes, such as ras and raf, and they induce cell proliferation. myc is also an oncogene and one of the targets of ERKs. Mutations of ras and overexpression of myc were found in various human cancers, and ERKs were also reported to play a role in carcinogenesis. In this study, we examined 39 biopsy specimens of oral squamous cell carcinoma (OSCC) and 5 of normal gingival mucosa for the expression of ERK protein and the proliferation marker, MIB-1 (Ki-67 antibody). Thirteen OSCC specimens and five normal gingival biopsies were also examined for the expression of ERKs mRNA by in situ hybridization. Double staining for ERKs and MIB-1 was also performed. Histologically, 18 patients (46%) were diagnosed with well-differentiated SCC, 17 (44%) with moderately differentiated SCC, and 4 (10%) with poorly differentiated SCC. The histologic grade correlated with the MIB-1 index. The localization of ERK1 was similar to that of ERK2. Positive signals for ERK proteins were localized in superficial keratinocytes in normal gingival mucosa, whereas these mRNAs were weakly positive in the basal and spinous layer. Basal and suprabasal cells were positive for MIB-1. In well-differentiated and moderately differentiated OSCC, positive signals for ERK mRNA and proteins were found at higher levels than in normal gingival mucosa in keratotic cells around cancer pearls. Some cells showed positive signals for ERKs and MIB-1. Furthermore, most cancer cells in poorly differentiated SCC were positive for both ERK and MIB-1. The histologic grade was statistically related to the percentage of cells positive for both ERK and MIB-1. This suggested that ERKs might be related to proliferation in OSCC.
 ...
PMID:Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma. 975 69

Esophageal SCC is a complex disease involving multiple etiologic factors. A number of preventive approaches could be taken to reduce the occurrence of the disease including changes in lifestyle and improved nutrition, for example, the inclusion of higher quantities of fruits and vegetables in the diet. Unfortunately, these primary prevention approaches are not easily implemented and often fall short in achieving marked reductions in disease occurrence. Chemoprevention offers another approach to reducing the risk of esophageal SCC that is likely to be useful, even though the clinical trials to date have not resulted in the identification of agents that produce marked inhibitory effects on the development of the disease. Given esophageal SCC's complex etiology, it would appear that the most effective chemoprevention strategy would be to employ agents that reduce mutational events associated with exposure to esophageal carcinogens in combination with agents that inhibit the progression of epithelial dysplasia to esophageal SCC. The feasibility of addressing carcinogen-induced mutational events is underscored by the fact that many of the suspected esophageal carcinogens are known, and inhibitors of these carcinogens have been identified in animal model systems. In addition, biomarkers to assess the efficacy of anti-initiation agents, such as levels of phase I and II enzyme activities and of carcinogen: DNA adducts, can be measured. The identification of agents that inhibit the progression of dysplastic lesions to esophageal SCC has proven difficult; however, the results of the trial with ATB and retinamide are encouraging. Clearly, it seems important to identify the active chemopreventives in the antitumor-B herbal mixture. Further studies to identify strong inhibitors of tumor progression in the rat model for esophageal SCC are also needed. Biomarkers of cell proliferation (e.g., PCNA, Ki67), cell differentiation (keratins), apoptosis, gene expression (EGFR, cyclin D1, p53), and nuclear/nucleolar morphometry can be used in studies to assess the efficacy of chemopreventives to either reverse esophageal dysplastic lesions or slow their rate of progression. The development of viable approaches toward the chemoprevention. of esophageal SCC is truly an important goal in view of the poor prognosis of this disease.
 ...
PMID:Clinical models of chemoprevention for the esophagus. 988 21

Interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) promote tumor angiogenesis, growth, and metastasis and are coexpressed by human head and neck squamous cell carcinomas (HNSCCs) and a variety of other cancers. The promoters of the IL-8 and VEGF genes contain different recognition sites for transcription factors nuclear factor (NF)-kappaB and activator protein-1 (AP-1), which we showed previously are coactivated in HNSCCs. NF-kappaB and AP-1 may be modulated by the inhibitor kappaB kinase (IKK) and mitogen-activated protein kinase (MAPK) signal pathways, but the contribution of these pathways to expression of IL-8 and VEGF and as potential targets for antiangiogenesis therapy in HNSCC is not known. In this study, we examined the effects of modulation of the MAPK and IKK pathways on expression of IL-8 and VEGF by UM-SCC-9 and UM-SCC-11B cell lines. Interruption of IKK-mediated activation of NF-kappaB by expression of an inhibitor kappaB alpha mutant (IkappaB alphaM) in UM-SCC-9 cells resulted in partial inhibition of expression of IL-8 but not VEGF. Analysis of possible alternative pathways for induction of these genes revealed activation of the MAPK extracellular signal-regulated kinase (ERK1/2) in cell lines UM-SCC-9 and UM-SCC-11B. Basal and tumor necrosis factor-alpha-inducible phosphorylation of ERK1/2 and secretion of IL-8 and VEGF could be specifically inhibited by a MEK inhibitor, U0126. Expression of IL-8 and VEGF in the cell lines was associated with coactivation of both NF-kappaB and AP-1, and U0126 inhibited both NF-kappaB and AP-1 reporter activity in UM-SCC-9 and UM-SCC-11B cells. The ERK pathway appears to contribute to expression of IL-8 and VEGF and transactivation of NF-kappaB as well as AP-1 in HNSCC. Combined inhibition of both MAPK and IKK pathways may be needed for suppression of the signal transduction mechanism(s) regulating VEGF and IL-8 secretion and angiogenesis by human HNSCC.
 ...
PMID:Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-kappaB signal pathways. 1123 1


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