Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD10 is a cell surface endopeptidase that inactivates various potentially growth stimulatory peptides. In lung cancer cell lines this downregulation has been associated with increased proliferation. Downregulation of CD10 in lung cancer tissue is described, suggesting a potential role in carcinogenesis and a possible use of CD10 as a prognostic marker. We aimed to determine the rate of CD10 expression in our non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters and patient survival. 114 NSCLC were analysed immunohistochemically using a monoclonal CD10 antibody (clone NCL-CD10-270) on an NSCLC tissue micro array. The staining was semiquantitatively scored. CD10 expression was observed in 19% of cases, without any significant association with tumour type, -size, -grading, nodal status, clinical stage, and patient survival time. We conclude that a diagnostic use of CD10 immunostaining in NSCLC is unlikely.
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PMID:CD10 expression in non-small cell lung cancer. 1212 82

p107 Links to cyclin A/CDK2 (cyclin-dependent kinase 2) and cyclin E/CDK2 that are important cell cycle regulators. However, p107 expression remains unclear in almost all kinds of human solid tumours. To clarify the expression of p107 in colorectal tumours, 22 normal mucosae, 9 hyperplastic polyps, 60 adenomas, 198 primary carcinomas, 21 lymph-nodal metastases, and 10 hepatic metastases were immunohistochemically stained for p107, cyclin A, cyclin E, CDK2 and Ki67. Results were measured using labelling indices (LIs). p107 LIs surpassed the highest value in normal tissues in six of nine hyperplastic polyps, 54 of 60 adenomas, 144 of 198 primary cancers, 13 of 21 nodal foci and three of 10 hepatic foci. p107 LIs also apparently rose from normal through hyperplasia and adenoma to early carcinoma. However, they declined in liver-metastatic foci, and in primary cancers showing large size, mucinous type, venous invasion, lymphatic invasion, poorly differentiated type, deep invasion, lymph-nodal metastasis, hepatic metastasis or advanced stage. Low p107 LIs were also linked to a poor survival, particularly in stage-III patients. As the p107 LI gradually rose, the CDK2 (in primary cancers only), cyclin A, cyclin E and Ki67 LIs were elevated concurrently-in both adenomas and primary cancers. Thus, in colorectal tumours, p107 expression rises abnormally and gradually during carcinogenesis and then falls during invasion, and thereby probably perturbs the cell-cycle control and promotes carcinogenesis and invasion. Clinically, reduced p107 may indicate a poorer prognosis.
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PMID:p107 Expression in colorectal tumours rises during carcinogenesis and falls during invasion. 1220 65

The aim of this study was to define whether or not the impaired expression of CD44, E-cadherin (E-cad), and beta-catenin (beta-cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety-three primary oral squamous cell carcinomas (OSCCs) with tumour-adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, -v3, -v4, -v5, -v6, -v7, -v9, E-cad, and beta-cat. In non-neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E-cad, and beta-cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E-cad/beta-cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E-cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E-cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased beta-cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody-based tumour therapy.
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PMID:Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression. 1237 67

In head and neck squamous cell carcinomas (HNSCC) the prognostic factors that are routinely considered when deciding therapeutic strategies are still stage and site of the primary tumour, and the presence of nodal or distant metastases. However, it is recognised that these clinical predictors are limited since they do not satisfactorily reflect the biological behaviour of the individual tumour. With the evolving understanding of the genetic and molecular basis of human malignancies, there are an increasing number of factors being claimed to provide prognostic information even in HNSCC. Here we review own and published data on DNA ploidy, karyotyping and molecular cytogenetic changes and its relevance in HNSCC carcinogenesis. The survey suggests that the induction of aneuploidy is a very early event in tumour development being detectable already in non-dysplastic leukoplakia and highly predictive for the subsequent development of a carcinoma. Moreover, specific chromosomal imbalances are associated with different stages of cancer progression and patient's survival, which we have compiled into a progression model of HNSCC.
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PMID:DNA ploidy and chromosomal alterations in head and neck squamous cell carcinoma. 1246 10

Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer.
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PMID:Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma. 1259 61

To identify the genes involved in esophageal carcinogenesis, we compared gene expression profiles in esophageal squamous cell carcinoma (ESCC) and matched normal esophageal epithelial tissues. Differential display analysis revealed significant changes in the expression of 26 genes; 21 genes were upregulated and 5 genes were downregulated. The differentially expressed genes included those associated with cellular metabolism, cell structure, transcription, proliferation, apoptosis, signal transduction, complement pathway, and cell-cell adhesion. The differential expression of these genes was confirmed by reverse Northern blot analysis. Reverse transcription PCR analysis of ESCC and matched normal esophageal tissues provided the first evidence that melanoma metastasis clone D (MEMD), a gene similar to oncostatin M receptor beta, and KIAA0471 gene products are upregulated in ESCCs. Intriguingly, KIAA0471, a novel gene product, is upregulated in esophageal tumors showing nodal invasion. Identification of these differentially expressed genes in esophageal tumors adds to the repertoire of genes associated with esophageal carcinogenesis and they may thus serve as potential novel molecular targets for diagnosis and therapy. Further characterization of known and unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying esophageal tumorigenesis.
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PMID:Transcriptional gene expression profile of human esophageal squamous cell carcinoma. 1270 6

The importance of altered histone acetylation in gastrointestinal carcinogenesis, especially in relation to invasion and metastasis, is described. Histone acetylation and chromatin remodeling linked with CpG island methylation play a major role in epigenetic regulation of gene expression. Acetylation of histones through an imbalance of histone acetyltransferases and deacetylases disrupts nucleosome structure, which leads to DNA relaxation and subsequent increase in accessibility to transcription factors. The expression of acetylated histone H4 is reduced in a majority of gastric and colorectal cancers, indicating the low level of global histone acetylation in tumor cells. Moreover, reduced histone acetylation is significantly associated with depth of tumor invasion and nodal metastasis of gastrointestinal cancers. A histone deacetylase inhibitor, trichostatin A (TSA), induces growth arrest and apoptosis and suppresses invasion of cancer cells. Treatment with TSA, which is followed by increased histone acetylation in the promoters, induces the expression of many genes that are suppressors of invasion and metastasis, including tissue inhibitors of metalloproteinase and nm23H1/H2, in addition to negative cell cycle regulators and apoptosis-related molecules. Our approach, serial analysis of gene expression (SAGE), enabled us to identify a gene that is a novel candidate for a metastasis suppressor, whose expression is induced by histone acetylation. These findings suggest that, by modifying gene expression, histone deacetylation may participate not only in tumorigenesis but also in invasion and metastasis. Therefore, histone acetylation should be a promising target for cancer therapy, especially against invasive and metastatic disease, but also for cancer prevention.
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PMID:Histone acetylation and gastrointestinal carcinogenesis. 1272 27

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.
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PMID:Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma. 1283 18

The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in head and neck squamous cell carcinoma (HNSCC) in relation to vascular endothelial growth factor (VEGF) expression and lymph node metastasis. COX-2 has an important role in the promotion of carcinogenesis, tumor invasiveness and angiogenesis. VEGF is a proangiogenic factor that is up-regulated in various tumors. VEGF has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in HNSCC, we evaluated the immunohistochemical expression pattern of COX-2 and VEGF in relationship with histologic differentiation, clinical stage, and nodal status in 146 HNSCC. The COX-2/VEGF double immunofluorescein staining was evaluated with confocal scanning laser microscope. A positive expression was seen in 96% (140/146: 98 strong positive, 42 weakly positive) for COX-2 and in 98% (143/146: 63 strong positive, 80 weakly positive) for VEGF in HNSCC. A correlation was present in the positive expression of COX-2 with histologic differentiation, clinical stage, and nodal status. VEGF expression was also correlated with nodal status. A significant relation was observed between COX-2 and VEGF expressions. The simultaneous expression of COX-2 and VEGF was statistically significant (p<0.05). These results indicate that elevated COX-2 or VEGF expression is more common in HNSCC with poor prognostic characteristics. The present findings support the efforts to initiate clinical trials on the efficacy of COX-2 inhibitors in adjuvant treatment of HNSCC.
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PMID:Correlation of cyclooxygenase-2 pathway and VEGF expression in head and neck squamous cell carcinoma. 1288 61

Phospholipase D (PLD) has been reported as relevant to some types of human cancer, but its role in human colorectal cancer still remains to be elucidated. Thus, this study was conducted to determine the activity and the expression of PLD2 in human colorectal cancer. A significant elevation of PLD2 activity and higher expression of PLD2 protein were detected in human colorectal cancer in comparison with corresponding normal mucosa. The tendency of higher expression of PLD2 mRNA was also observed. The ratio of PLD2 activity in cancer to that in corresponding normal mucosa was greater in colorectal cancer with nodal involvement and deeper tumor invasion. Our results indicate that PLD2 has a possible implication in carcinogenesis and progression and would be a new therapeutic target and a potential tumor marker for colorectal cancer.
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PMID:Increased activity and expression of phospholipase D2 in human colorectal cancer. 1455 89


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