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)

A series of 51 biopsies derived from the same number of patients with established invasive squamous-cell carcinoma of the esophagus in Linxian, a high-risk area for esophageal cancer in China, were analyzed histologically and by in situ DNA hybridization to demonstrate human papillomavirus (HPV) infection. Epithelial changes suggesting HPV infection within or adjacent to the carcinoma lesions were found in 25 cases (49.0%). Esophageal lesions with HPV morphology showed both flat (25 cases) and inverted condylomas (2 cases) resembling those found in the genital tract. HPV 6, 11, 16 or 18 DNA sequences were detected in 22/51 (43.1%) of the esophageal specimens. HPV DNA was most frequently localized in epithelium adjacent to carcinomas in areas showing either epithelial hyperplasia (36.1%) or dysplasia (22.2%). Of the lesions with morphological HPV changes, 64% (16/22) were shown to contain HPV DNA. In 2 specimens, HPV DNA was found in frankly malignant cells. High-risk types HPV 16 and/or 18 DNA sequences were found in 16 of the 22 HPV DNA-positive cases (72.7%). Our results confirm previously reported HPV involvement in esophageal squamous-cell lesions, and support the hypothesis of HPV as a possible etiological agent in esophageal carcinogenesis.
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PMID:Human papillomavirus (HPV) DNA in esophageal precancer lesions and squamous cell carcinomas from China. 215 38

A review of 195 patients with carcinoma of the esophagus disclosed 41 cases (21.0%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three types according to representative histologic features of glandular and mucus-secreting portions: glandular type (23 cases), cribriform type (11 cases), and mucoepidermoid type (7 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. In all 41 cases, the ordinary element of squamous cell carcinoma, invasive, or noninvasive, was admixed in various proportions with the glandular components, indicating that this type of esophageal tumor had originated not only from the covering squamous epithelium but also from esophageal mucous-gland or ductal epithelium. The findings also support the concept of the field origin of carcinogenesis in esophageal carcinoma.
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PMID:Glandular or mucus-secreting components in squamous cell carcinoma of the esophagus. 298 46

The incidence of human carcinoma of the esophagus is increased in association with environmental nitrosamines and dietary zinc deficiency. For examination of the role of zinc deficiency in esophageal carcinogenesis, methylbenzylnitrosamine [(MBN) CAS: 937-40-6] was used to induce esophageal carcinoma in rats fed either a zinc-deficient or control diet. Histologic examination of the MBN-treated Sprague-Dawley rat esophagi revealed a significantly higher incidence of esophageal carcinoma in the zinc-deficient rats vs. controls (62 vs. 33%). In addition, three distinct cytologic and histologic patterns were observed in the animals with esophageal carcinoma: pattern I--basal cell hyperplasia, atypical basal cells, few dyskeratotic cells; pattern II--basal cell hyperplasia, atypical basal cells, many dyskeratotic cells; and pattern III--many dyskeratotic cells without basal cell hyperplasia. These three patterns did not occur simultaneously in the same esophagi, and zinc deficiency did not alter the appearance of these patterns. A strong correlation between the appearance of moderate or severe dysplasia cytologically and microinvasive carcinoma histologically was demonstrated. In those animals with histologically evident microinvasive carcinoma, there was no cytologic evidence of carcinoma in situ or invasive carcinoma. Cytology of these esophageal carcinomas revealed only moderate or severe dysplasia. To the extent that the rat model represents the evolution of esophageal carcinoma in humans, the results presented here suggest that the cytologic appearance of moderate or severe dysplasia indicates the need for further evaluation of patients at risk for esophageal carcinoma.
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PMID:Histopathology of methylbenzylnitrosamine-induced esophageal carcinoma in the rat: comparison with cytomorphology. 346

The mutation and expression of Rb gene in human esophageal cancer (EC) were investigated by PCR-direct sequencing and Northern blot hybridization. In PCR amplification analysis, in one of 20 (5%) cases of EC was found to have Rb gene deletion in exon 17 and 21; in one of 6 cases of the adjacent non-tumours tissue was found to have deletion in exon 21. Esophageal carcinoma of human fetus induced by NMBzA had Rb gene deletion in exon 17 and 21 too. In PCR-direct sequencing analysis, four of 10 (40%) EC were found to contain Rb gene mutations in exon 17 and 21. In northern blot analysis, seven of 12 (58.3%) EC exhibited abnormal Rb gene expression, including inactivation in 6 abbreviated expression in one. The results suggest that Rb tumor suppressor gene might play an important role in carcinogenesis of EC. The mechanisms of Rb gene mutation, deletion or abnormal expression related to carcinogenic nitrosamine in the environment need further study.
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PMID:[Mutation and expression of Rb gene in human esophageal cancer]. 820 Feb 76

Human papillomavirus (HPV) infection is implicated in squamous cell carcinogenesis. Oesophageal carcinoma has a high incidence in certain geographical regions and, using different methods of detection, HPVs have been found in these tumours. HPV 6 and 11 are frequently detected in laryngeal papillomas, benign lesions which rarely become malignant. HPVs have been detected in squamous carcinoma of the larynx but more frequently, especially HPV 16, in verrucous carcinomas a distinct variant of squamous carcinoma. An increased density of Langerhans cells, important in immunosurveillance in squamous epithelium, has been associated with a more favourable patient prognosis in laryngeal and other carcinomas.
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PMID:Langerhans cells and human papillomaviruses in oesophageal and laryngeal carcinomas. 839 35

Intraepithelial carcinoma contiguous with invasive squamous-cell carcinoma is a conspicuous feature of esophageal cancer. However, whether the mechanism of intraepithelial spreading is due to cell proliferation or field carcinogenesis has yet to be clarified. This study investigated the mechanism of intraepithelial spreading by measuring the cell proliferative activity using argyrophilic nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-positive cell counting. We examined the AgNOR number and PCNA-positive ratio (PCNA ratio) in the center and outer edge of intraepithelial carcinoma and in the center and deep margin of invasive squamous-cell carcinoma of the esophagus in 50 specimens from 18 cases of esophageal squamous-cell carcinoma concomitant with contiguous intraepithelial carcinoma. The proliferative activity was thus found to differ between the normal epithelium and cancerous lesions (p < 0.001), between intraepithelial carcinoma and invasive cancer (p < 0.001) and between deep margin and center areas of invasive cancer (p < 0.005). On the other hand, such activity was observed to be similar in the center and outer edge of the intraepithelial spread. These findings suggest that cell proliferation is the main mechanism of tumor progression at the invasive site of cancer, whereas in intraepithelial carcinomatous areas, "field carcinogenesis" or a paracrine mechanism, and not cell proliferation, is thought to be the cause of intraepithelial spread of esophageal cancer. These results therefore support the concept of field carcinogenesis.
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PMID:Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma. 975 43

beta-Catenin has 2 distinct roles in E-cadherin-mediated cell adhesion and carcinogenesis through APC gene mutation. One occurs at cell-adhesion sites, where cadherins become linked to the actin-based cytoskeleton. The others occur in the cytoplasm and nuclei and are thought to regulate cell transformation. We studied these different beta-catenins and evaluated their significance in carcinogenesis. Fresh surgical specimens were obtained from 22 patients with squamous-cell carcinoma of the esophagus. beta-Catenin in the free soluble fraction and the insoluble fraction was immunoblotted separately. At the same time, its localization was observed by immuno-histochemical techniques. In the normal esophageal epithelium, 91% of beta-catenin was detected in the insoluble fraction and beta-catenin staining occurred at the cell membrane, in co-existence with E-cadherin. In cancerous tissues, the amount of soluble beta-catenin was significantly (about 4-fold) higher than in normal tissues. Also, in cancerous tissues with higher amounts of soluble beta-catenin, immuno-histochemical techniques revealed the presence of beta-catenin in the cytoplasm and nuclei, as well as in the cell membrane. However, in samples with lower amounts of beta-catenin, expression was found only at the cell boundaries. The amount of soluble beta-catenin was not associated with the clinico-pathological grading of the tumors. Our results show that the accumulation of free soluble beta-catenin in the cytoplasm and nuclei frequently occurs during carcinogenesis of the squamous epithelium of the esophagus.
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PMID:Cytoplasmic beta-catenin in esophageal cancers. 1009 51

Ser326Cys polymorphism in the hOGG1 gene, which is involved in the repair of 8-hydroxyguanine in oxidatively damaged DNA, has been identified and the variant genotype appears to be related to susceptibility to certain cancers. We investigated the association between Ser326Cys polymorphism and squamous-cell carcinoma of the esophagus among a Chinese population. hOGG1 gene polymorphism was detected by PCR-based single-strand conformation polymorphism and DNA sequencing among 201 normal controls and 196 patients with esophageal cancer from Linxian, China, a high-risk area for the disease. The association between this genetic polymorphism and risk of the cancer was examined by a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 33.8%; Ser/Cys, 52.8%; and Cys/Cys, 13.4%) was significantly different from that among esophageal cancer cases (39.8%, 38.8% and 21.4%, respectively) (p < 0.05). Homozygosity for the Cys/Cys genotype significantly increased the risk of developing esophageal squamous-cell carcinoma, with the odds ratio (OR) adjusted for age, sex and smoking being 1.9 (95% confidence interval [CI] = 1.3-2.6). Although smoking alone also significantly increased esophageal cancer risk in this case-control study (adjusted OR = 2.6; 95% CI = 1.7-3.9), no significant interaction between smoking and the Cys/Cys genotype was observed in terms of risk. Our results suggest that the hOGG1 326Cys allele might play a role in the carcinogenesis of the esophagus.
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PMID:Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. 1130 45

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.
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PMID:p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients. 1216 11

We previously reported that vascular endothelial growth factor (VEGF) expression correlates with vessel density in human esophageal squamous cell carcinomas. However, tumor angiogenesis is not controlled simply by the presence of VEGF, and is likely regulated by several angiogenic factors produced by tumor and host cells. The goal of the present study was to determine the angiogenic profile of precancerous and cancerous lesions of the esophagus. Expression of mRNAs for VEGF, platelet derived endothelial cell growth factor (PD-ECGF), basic fibroblast growth factor (bFGF), and interleukin (IL)-8 was examined in six esophageal carcinoma cell lines and fresh biopsy specimens from 16 patients with invasive esophageal carcinoma by RT-PCR. Immunohistochemical analyses with antibodies against VEGF, PD-ECGF, bFGF, and IL-8 were performed on archival specimens of 60 normal esophageal mucosa, 11 dysplasias and 49 carcinomas of the esophagus. Microvessels were stained with anti-CD34 antibody and quantified by counting the number of vessels in a x200 field in the most vascularized areas of the tumor. Esophageal carcinoma cell lines and tumor tissues expressed mRNAs for one or more these angiogenic factors at various levels. An initial increase in vessel density and enhanced expression of PD-ECGF and VEGF were observed in dysplastic epithelium. Vessel density was significantly higher in more advanced lesions. bFGF and IL-8 were not expressed in dysplasias and mucosal carcinomas, but expression was increased in late stage squamous cell carcinoma. These findings suggest that the angiogenic switch is a very early event in the development of invasive carcinoma. Several different angiogenic factors produced by tumor cells and host cells may regulate angiogenesis during different steps of esophageal carcinogenesis.
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PMID:Angiogenic switch occurs during the precancerous stage of human esophageal squamous cell carcinoma. 1471 61


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