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)

Image and flow cytometry was used to study the nuclear DNA content (ploidy) during the squamous cell carcinogenesis in the esophagus. The present retrospective study comprised 26 surgical specimens of squamous cell carcinomas (SCC) in patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne, between January 1992 and December 1999. We analyzed 53 healthy tissues, 43 tumors, and six lymph node metastases. Diploid DNA histogram patterns were observed in all non-pathologic tissues analyzed, either distant or proximal to the lesion. Aneuploidy was observed in 30 (70%) of 43 lesions; 20 (62.5%) of 32 early squamous-cell carcinomas; and 10 (91%) of 11 advanced carcinomas. In patients with various tumor stages or with multicentric synchronous or metachronous tumors, DNA content was not different among different tumor stages. Four of six lymph node metastases had the same DNA content as the primary tumor. In four patients, discordance between image and flow cytometry analysis was observed for malignant lesions only. Ploidy status was not statistically associated with the differentiation of the tumor, but it was associated with the stage of tumor (P < 0.001). These findings suggest that early malignant changes in the esophagus are already associated with alteration in DNA content, and aneuploidy tends to correlate with progression to invasive SCC. This cell kinetic information could help clinicians in selecting the optimal treatment for the individual patient.
Dis Esophagus 2001
PMID:Evolution of DNA ploidy during squamous cell carcinogenesis in the esophagus. 1186 16

The level of transforming growth factor beta1 (TGFbeta1) and transforming growth factor betaII receptor (TGFbetaRII) was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, BCH; dysplasia, DYS; carcinoma in situ, CIS; and squamous cell carcinoma, SCC) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linzhou, formerly Linxian, and nearby county Huixian in Henan Province). Peroxidase immunostain (ABC) and conventional hematoxylin and eosin stain were used. The tissue sections were incubated with antibodies of TGFbeta1 and TGFbetaRII overnight. The immunoreactivity was observed in cytoplasm of the esophageal specimen. From normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbeta1 increased significantly (P < 0.05). A linear correlation between the positive immunostaining rates of TGFbeta1 and the different lesions was observed (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbeta1 decreased gradually, but the difference was not significant (P > 0.05). In contrast, with the lesions progressing from normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). There was a linear correlation between the positive rates of TGFbetaRII and different lesions and SCC differentiation (P < 0.05). The present results indicated that the alterations of TGFbeta1 and TGFbetaRII is a frequent event in esophageal multistage carcinogenesis, the absent or lower expression of TGFbetaRII may lead to the loss of cell proliferation control by TGFbeta1 and the overexpression of TGFbeta1 may be a negative feedback response caused by the lower expression of TGFbetaRII protein.
Dis Esophagus 2002
PMID:Changes of TGFbeta1 and TGFbetaRII expression in esophageal precancerous and cancerous lesions: a study of a high-risk population in Henan, northern China. 1206 47

The objective of this study was to characterize the histologic changes from endoscopic screening for early esophageal cancer (EC) on subjects at high-incidence area (HIA) and low-incidence area (LIA) in Henan, China, and to further compare the changes in p53 and proliferating cell nuclear antigen (PCNA) in the multistage of human esophageal carcinogenesis from these two populations. The detection rate of basal cell hyperplasia (BCH) and dysplasia (DYS) was higher in the subjects from HIA than in those from LIA. Out of the 1568 symptom-free subjects examined at HIA, 10 (0.6%) cases with early squamous cell carcinoma (SCC) were identified. Immunoreactivity of p53 and PCNA was observed in cell nuclei of esophageal biopsies and surgically resected esophageal cancer specimens both in HIA and LIA. With the lesions progressed from normal epithelium to BCH to DYS to SCC, the positive-immunostaining cells expanded from basal layer to superficial layer, and the number of positive cells/mm2 for p53 and PCNA increased, and was significantly higher in HIA than in LIA among the similar morphological lesions (P < 0.01). The number of p53 positive cells/mm2 in SCC from HIA was almost fivefold higher than SCC from LIA (P < 0.01). The remarkable difference was also observed between HIA and LIA in DYS and BCH. The present results indicate that p53 protein accumulation is an important early biomarker for identifying high-risk subjects for EC.
Dis Esophagus 2002
PMID:Endoscopic screening and determination of p53 and proliferating cell nuclear antigen in esophageal multistage carcinogenesis: a comparative study between high- and low-risk populations in Henan, northern China. 1206 48

Alterations of cell cycle-regulated genes play an important role in the process of carcinogenesis, and some of them are thought to be prognostic factors in esophageal cancer. The expressions of p53, p16, pRB and Cyclin D1 proteins were evaluated immunohistochemically in 144 patients who underwent curative esophagectomy without any adjuvant therapy before surgery. p53 overexpression was observed in 99 (69%) out of the 144 patients. No significant correlation was noted between p53 and any other gene expression. p16 expression was observed in 12 (8.3%) out of all cases. A negative correlation was recognized between p16 and Cyclin D1 expression (P=0.0004). pRB expression was observed in 130 (90.3%) out of all cases, whereas pRB expression was not observed in 11 out of the 12 patients with p16-positive tumors. A negative correlation was also found between p16 and pRB (P < 0.0001). A positive correlation was noted between pRB and Cyclin D1 expression (P=0.0009). The cumulative survival rate of patients without pRB expression was significantly lower than that of patients with positive expression (P=0.003). In the multivariate survival analysis, pRB expression was an independent prognostic factor. In 98% of all patients with esophageal cancer, impairment of the G1 checkpoint is due to a loss of function by p16, pRB or Cyclin D1, which showed a negative correlation in each factor. In addition, aberrant expression of pRB is useful as a prognostic factor in esophageal cancer.
Dis Esophagus 2002
PMID:Cell cycle-regulated factors in esophageal cancer. 1222 Apr 23

Columnar-lined lower esophagus (CLE) or Barrett's esophagus (BE) is caused by chronic reflux of the gastrointestinal tract and can progress to invasive adenocarcinoma. However, the pathophysiology, cell of origin, and management of this condition is incompletely understood. This review evaluates the role of in vivo models in resolving these debates. A search was performed on the Ovid and Pub Medline for 1964-2001 and Cochrane Collaboration. The keywords used were adenocarcinoma, animal model, Barrett's esophagus, columnar-lined esophagus, esophageal neoplasms, and esophageal carcinogenesis. All relevant papers were scrutinized and an attempt at tabulation was made. In vivo models have been used at several stages of debate on the pathophysiology of BE. They provide conclusive evidence for its acquired nature secondary to duodenogastroesophageal reflux. The cell of origin of experimental BE may arise from adjacent columnar epithelium, basal layer multipotent cells, or esophageal glands. Experimental work on BE is lacking in assessing therapeutic modalities.
Dis Esophagus 2002
PMID:Changing role of in vivo models in columnar-lined lower esophagus. 1247 70

The aim of this research was to determine the occurrence of epidermoid carcinoma of the esophagus induced by diethylnitrosamine (DEN) in Wistar rats. DEN was administered (250-300 g) in drinking water (10 mg/kg body weight) to four groups of rats for 72 h/week, for a duration of 90, 120, 150, or 200 days (groups T90, T120, T150, and T200). Ten animals whose drinking water did not contain DEN constituted the control group. All rats were sacrificed and their esophaguses studied macro- and microscopically. The control group did not exhibit either carcinomas or preneoplasic lesions. The T120 and T200 groups presented, respectively, 47 and 58 in situ carcinomas; 1 and 20 submucosal carcinomas (P < 0.05); 4 and 17 microinvasive carcinomas (P < 0.05); 4 and 11 advanced carcinomas (P < 0.05); and 1 and 1 cases of benign hyperplasia. Pulmonary and liver carcinomas were also found in the T200 group. The majority of advanced macroscopic lesions in the T200 group were polypoid, exophytic, and not microscopically invasive in the esophageal wall. This research confirms the effectiveness of the DEN in bringing about carcinogenesis in the Wistar rat esophagus and also shows that the lesions are dosage dependent.
Dis Esophagus 2002
PMID:Experimental esophageal carcinogenesis: technical standardization and results. 1247 71

We studied the premalignant nature of achalasia using anti-Ki-67 and anti-p53 monoclonal antibodies immunohistochemically. In this study, four patients with esophageal carcinoma and achalasia were investigated. Three tumors were pT4 (UICC pTNM) and one tumor was pT1. The majority of non-malignant esophageal epithelium showed esophagitis and/or dysplasia histologically. Esophageal epithelial cells in the lesions of esophagitis and/or dysplasia had a higher number of Ki-67-positive cells than normal epithelial cells. p53 protein was expressed in two tumors and it was not expressed in non-malignant epithelium. From these results, we found that esophageal epithelium in achalasia lesions is changed to varying degrees of esophagitis and/or dysplasia by stagnation of intake foods, and these abnormal epithelial cells showed a high proliferative state compared with the normal cells without the p53 gene mutation. We suggest that the distinct proliferative status is a cause of carcinogenesis.
Dis Esophagus 2000
PMID:Histopathological analysis of non-malignant and malignant epithelium in achalasia of the esophagus. 1460

To find new genes involved in esophageal squamous cell carcinogenesis, we constructed custom cDNA arrays and used the arrays to compare gene expression profiles of 12 matched normal and malignant esophageal samples including seven superficial cancer tissues. The arrays represented nearly 4000 genes, including 1728 that were specifically selected based on pilot studies to find genes that were differentially expressed in esophageal cancers. Expression values for all genes were normalized for each sample and were compared in normal versus tumor tissues. There was a marked decrease in the levels of the transcriptional elongation factor A gene in all 12 of the squamous cell cancer samples compared to matched normal samples. Because the transcription elongation factor A gene has not been previously reported to be involved in cancer development, our results suggest that further investigation of its role in esophageal carcinogenesis is warranted.
Dis Esophagus 2005
PMID:Differential expression of TCEAL1 in esophageal cancers by custom cDNA microarray analysis. 1577 40

Despite advances in the treatment of esophageal carcinoma, the prognosis for this disease remains poor. Therefore, it is important to obtain a better understanding of the molecular basis of esophageal carcinogenesis. The purpose of this study was to clarify the roles of survivin in esophageal squamous cell carcinoma (ESCC). One hundred 22 ESCC surgical specimens resected from 1989 to 1999 were examined. Survivin expression was assessed by immunohistochemistry. Tumor cells were considered survivin-positive if the immunoreactivity was confined to the nucleus, and a scoring method was applied. Survivin-positive immunostaining was detected in 68 patients (56%). There was a significant association between survivin expression and pN (P = 0.0472). Moreover, the overall survival rate was worse in patients with survivin-positive tumors than in patients with survivin-negative tumors (P = 0.0189). The overexpression of survivin was associated with the overall survival rate and poor prognosis in patients with ESCC. Survivin may be targeted during cancer therapy because of its selective expression in malignant tissue.
Dis Esophagus 2006
PMID:Immunohistochemical analysis of nuclear survivin expression in esophageal squamous cell carcinoma. 1698 32

Esophageal squamous cell carcinoma (SCC) remains the leading cause of cancer related deaths in Linzhou (formerly Linxian), the highest incidence area for esophageal cancer (EC) in Henan, northern China. In China, gastric cardia adenocarcinoma (GCA) shares very similar geographic distribution with SCC, suggesting the possibility of similar risk factors involved in SCC and GCA carcinogenesis in these areas. However, the underlying genetic alterations for esophageal and gastric cardia carcinogenesis, especially for the molecular difference between SCC and GCA, are largely unknown. The present study was thus undertaken to determine the difference in chromosomal aberrations in SCC (n = 37) and GCA (n = 31) using the comparative genomic hybridization method (CGH). All the patients were from Linzhou, Henan, a high-risk geographic region for both SCC and GCA. CGH results showed that chromosomal aberrations with different degrees were identified both in SCC and GCA. In SCC, chromosomal profile of DNA copy number was characterized by most frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%) and 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In GCA, the frequently detected gains were identified at 20q (13/31, 42%), 6q (12/31, 39%) and 8q (11/31, 35%); the DNA copy number losses in GCA occurred frequently at 17p (17/31, 55%), 19p (15/31, 48%) and 1p (14/31, 45%). Statistically, there were evident differences between SCC and GCA in DNA copy number gains at 8q, 3q, 5p and 20q (P < 0.05) and in losses at 3p, 8p, 5q, 17p and 18q (P < 0.05). Gains at 8q were frequently observed in both SCC and GCA. Gains at 3q and 8p were frequently observed in TNM stage III of both SCC and GCA. The present CGH results provide candidate regions that may contain specific related genes involved in SCC and GCA in the Linzhou population. Gains at 8q, 3q and 5p and losses at 3p, 8p and 9q were specifically implicated in SCC; gains at 20q, 6q and 8q and losses at 17p, 19p and 1p were specifically implicated in GCA; gains at 8q were implicated in both SCC and GCA.
Dis Esophagus 2006
PMID:Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China. 1706 89


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