Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has become clear that papillary carcinomas of the thyroid often express the receptor for c-Met/hepatocyte growth factor (HGF) receptor, but little is known about the role of the HGF and c-Met system in the pathogenesis of thyroid carcinoma. In this study, the expression of c-Met/HGF receptor was evaluated in thyroid tissue by western blot and immunohistochemistry, and compared with the concentration of HGF. Clinicopathological characteristics were also compared. Fifteen of 20 papillary carcinomas (75%) showed c-Met bands of 145 kDa. No or only a low frequency of c-Met expression was detected in healthy thyroid tissue (0/5), thyroiditis or Basedow's disease (0/2), adenomatous goiters (0/8), follicular adenomas (1/9, 11%) and undifferentiated carcinomas (0/2). These results were confirmed by immunohistochemistry, but a relatively higher frequency of c-Met expression was detected in adenomatous goiters (25%), follicular adenoma (44%) and papillary carcinoma (100%) using formalin-fixed and paraffin-embedded materials. A strong immunoreaction for c-Met was observed in the tumor cytoplasm of papillary carcinomas among the fibrous tissues situated at the periphery of the tumor. The densitometrically measured expression of c-Met had no relation to tumor stage in papillary carcinoma, but did correlate to the concentration of HGF in papillary carcinomas. In conclusion, in thyroid lesions, c-Met was highly expressed specifically in the cytoplasm of papillary carcinomas. c-Met expression was not related to the aggressiveness of the tumor but was related to the concentration of HGF, which was probably derived from the stroma. Also, the c-Met system might play a role in the pathogenesis of papillary carcinoma of the thyroid.
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PMID:c-Met expression of thyroid tissue with special reference to papillary carcinoma. 978 59

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.
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PMID:Study of growth factors and receptors in carcinoma ex pleomorphic adenoma. 2014 60

c-Met plays an important role in colorectal tumorigenesis and disease progression and thus is believed to be an attractive inhibitory target for receptor molecular therapeutic. SU11274 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Our study had investigated the relationship between the high expression of c-Met and colorectal carcinoma and the effect of c-Met inhibitor SU11274 in colorectal carcinoma in vitro and vivo. Immunohistochemistry was used to detect the expression of c-Met in 60 patients with colorectal cancer and 20 patients with benign adenoma and surrounding normal colon tissues. The effect of SU11274 on human colorectal carcinoma LoVo cells was detected by Western blot and MTT. And the influence of SU11274 on cell cycle was determined by flow cytometry. In addition, LoVo cell-transplanted tumor growth and expression of c-Met in nude mice was examined for inhibition of SU11274 in vivo. We found c-Met had high expression and was closely related to lymph node metastasis and TNM stage in colorectal carcinoma tissues. SU11274 significantly suppressed the phosphorylation of c-Met as well as the survival and proliferation of LoVo cell lines. G1-phase arrest was also induced by SU11274. SU11274 apparently restrained the growth of the xenograft tumor in nude mice. Our data suggest developing therapies that specifically inhibit the activation of c-Met may represent a novel therapeutic modality for patients with colorectal carcinoma expressing high levels of c-Met.
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PMID:Study of critical role of c-Met and its inhibitor SU11274 in colorectal carcinoma. 2353

The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was up-regulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma.
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PMID:Mecp2-mediated Epigenetic Silencing of miR-137 Contributes to Colorectal Adenoma-Carcinoma Sequence and Tumor Progression via Relieving the Suppression of c-Met. 2829 Dec 53

Although many modalities can be used to prolong the remission of colorectal cancer (CRC), early diagnosis is essential to improve the therapeutic outcomes. The conventional ways of diagnosing and monitoring the progresses from adenoma to CRC are colonoscopy and fecal occult blood test (FOBT). However, colonoscopy is expensive and invasive; while the FOBT is not sensitive. miRNAs may be a new modality to monitor the transition from adenoma to CRC. We reviewed publications of miRNA profile differences from colorectal normal mucosa (NM) to adenoma, and to CRC and tried to find the roles of miRNA in these transitions. This review also highlighted the possibility of serum miRNAs as markers for monitoring these transitions. The miRNA profiles are different from normal colorectal mucosa to adenoma and to CRC. The miRNAs may have pro- or anti-CRC effects through oncogenes such as c-Met and KRAS. Others may interfere with the immune system. More interestingly, some miRNAs are continuously increased from NM to adenoma and to CRC; others, such as miRNA-30b, are consequently decreased. The literature shows that miRNAs are involved in the whole process of the colorectal carcinogenesis. The miRNAs may be the biomarkers in monitoring the transition from adenoma to CRC.
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PMID:Role of miRNA in transformation from normal tissue to colorectal adenoma and cancer. 3096 98

Exosomes are membrane vesicles which offer potential as blood derived biomarkers for malign tumors in clinical practice. Pancreatic cancer is counted among cancer diseases with the highest mortality. The present work seeks to assess whether pancreatic carcinomas release exosomes which express c-Met (proto-oncogene mesenchymal-epithelial transition factor) and PD-L1 (programmed cell death 1 ligand 1), and whether the detection of such expression in serum has diagnostic or prognostic meaning for the affected patients. Exosome isolation was performed on culture media of one benign pancreatic cell line and ten pancreatic carcinoma cell lines as well as on serum samples from 55 patients with pancreatic ductal adenocarcinoma (PDAC), 26 patients with chronic pancreatitis and 10 patients with benign serous cyst adenoma of the pancreas. Exosomes were bound to latex beads and stained with antibodies against c-Met or PD-L1. Analysis of fluorescence intensity was performed by flow cytometry. In terms of c-Met, the mean fluorescence intensity of PDAC-patients was significantly higher than the fluorescence intensity of the comparative patients with benign disease (p < 0.001). A diagnostic test based on c-Met resulted in a sensitivity of 70%, a specificity of 85% and a diagnostic odds ratio of 13:2. The specificity of the test can be further improved by combining it with the established tumor marker carbohydrate antigen 19-9 (CA 19-9). In addition, c-Met-positive patients showed a significantly shorter postoperative survival time (9.5 vs. 21.7 months, p < 0.001). In terms of PD-L1, no significant difference between fluorescence intensity of PDAC-patients and comparative patients was detectable. However, PD-L1-positive PDAC-patients also showed a significantly shorter postoperative survival time (7.8 vs. 17.2 months, p = 0.043). Thus, both markers can be considered as negative prognostic factors.
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PMID:c-Met and PD-L1 on Circulating Exosomes as Diagnostic and Prognostic Markers for Pancreatic Cancer. 3128 22

Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met-targeted fluorescent peptide, in a population at high risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multidiameter single-fiber reflectance/single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13 mg/kg) at a 1-, 2- or 3-h dose-to-imaging interval (n = 3 patients per cohort). Two cohorts were expanded to 6 patients on the basis of target-to-background ratios. Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly higher fluorescence in the colorectal lesions than in surrounding tissue, with a target-to-background ratio of 1.53, 1.66, and 1.74 for the 1-, 2-, and 3-h cohorts, respectively, and a mean intrinsic fluorescence of 0.035 vs. 0.023 mm-1 (P < 0.0003), 0.034 vs. 0.021 mm-1 (P < 0.0001), and 0.033 vs. 0.019 mm-1 (P < 0.0001), respectively. Fluorescence correlated with histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a 1- to 3-h dose-to-imaging interval. No clinically significant differences were observed among the cohorts, although a 1-h dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies.
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PMID:The Optimal Imaging Window for Dysplastic Colorectal Polyp Detection Using c-Met-Targeted Fluorescence Molecular Endoscopy. 3219 12