Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is very popular in Hong Kong. The tumor is often prevalent in males and has a modal peak of occurrence in the 7th decade. The pathogenesis of the esophageal neoplasm is still uncertain but likely to be multi-factorial. The commonest histological subtype is squamous cell carcinoma. Besides, mucoepidermoid carcinoma/adenosquamous carcinoma, adenocarcinoma, small cell carcinoma, sarcomatoid carcinoma, adenoid cystic carcinoma, undifferentiated carcinoma, melanoma and gastrointestinal autonomic nerve tumor are also found in a minority of patients. The proportion of various histologic subtypes is different from the Western populations. Concerning the genetic alternation, P53 mutation is common in esophageal squamous cell carcinoma. Esophageal cancer has its unique pattern of P53 mutations in Hong Kong. In addition, intramural metastasis and multiple lesions are characteristic features in esophageal squamous cell carcinoma. Important pathologic factors in determining the prognosis of patients with esophageal cancer includes completeness of surgical resection, stages, tumor dimension as well as MIB-1 scores and the presence of P53 mutations.
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PMID:Pathology of esophageal cancers: local experience and current insights. 959 48

We investigated the clinicopathological significance of dendritic cell infiltration (DCsI) in esophageal squamous cell carcinoma and in regional lymph nodes of 88 patients. The expression of mutated p53 protein and the degree of positive cancer cells of proliferating cell nuclear antigen (PCNA labeling index) in tumors were analyzed as biological markers. These factors were compared with the degree of DCsI in tumors and in lymph nodes. The number of dendritic cells (DCs) were counted and scored as per mm2 in each case. The degree of DCsI of tumors with expression of p53 (19/mm2, n=50) was significantly lower than that of DCsI in 38 tumors without expression of p53 (27/mm2, P=0.0411). However, no significant correlation was detected between the PCNA labeling index and the degree of DCsI in 88 primary tumors (P=0.1273). The degree of DCsI in 53 metastatic lymph nodes (30/mm2) was significantly lower than that of DCsI in 264 cancer-free regional lymph nodes (48/mm2, P=0. 02). Although the degree of DCsI in tumors was not an independent prognostic factor for the 78 surviving patients (P=0.2647), the 3-year survival rate of patients in stage III and IV who underwent curative operation and who had tumors with high DCsI (>9/mm2, n=16, 72%) was significantly higher than that of the 24 patients who had tumors with low DCsI (< or = 9/mm2, 21%, P=0.008). These findings indicate that DCs infiltrated in and around the esophageal cancer may play a defensive role of the hosts against the tumors. This immune defense of the hosts might be an important prognostic factor for patients with advanced esophageal cancer. However, cancer cells which express a mutated p53 protein might regulate the function or activity of DCs.
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PMID:Clinical significance of dendritic cell infiltration in esophageal squamous cell carcinoma. 968 32

Mutations of the tumor suppressor gene TP53 have been detected in tumor tissues of a large variety of human malignancies and contribute to the development, progression and probably the prognosis of the disease. The pattern of somatic mutations in the TP53 gene in human tumors most often consists of a point mutation in one allele accompanied by loss or rearrangement of the second allele. Esophageal cancer is one of the most commonly mutated cancer, p53 mutations having an incidence greater than 80% in squamous cell carcinoma. The profile of distribution of these mutations in the TP53 gene is of interest to establish correlation between the exposure to carcinogens responsible for DNA mutations. The other form of esophageal cancer, Barrett's esophageal is a good model to study the role of TP53 in mammalian tumorigenesis.
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PMID:TP53 and oesophageal cancer. 976 51

Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.
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PMID:Mitoguazone induces apoptosis via a p53-independent mechanism. 977 8

Squamous cell carcinoma of the esophagus has an uneven geographic distribution, with a high incidence in the Transkei region of Eastern Cape Province, South Africa. The precise molecular events associated with tumorigenesis of esophageal cancer in this region have not been characterized. DNA from human esophageal squamous cell carcinomas (n = 76), as well as adjacent tissue samples (n = 9) and blood (n = 50) from the same patients from the Transkei region were screened for somatic mutations. Exons 5-8 of the p53 gene and exons 1-2 of the p16/CDKN2 gene were examined for mutations using PCR-SSCP procedures and DNA sequence analysis. Results show that 17% of the tumors contained small deletions, insertions and point mutations, resulting in frameshifts or amino acid changes in the p53 gene. Among the mutations in the structural p16/CDKN2 gene, 9 were point mutations, 4 were deletions and 3 were insertions. A novel C to T mutation, 25 bp upstream from the ATG start site of p16/CDKN2, which sometimes occurs together with other structural gene variations, was found. The mutations described here are somatic in origin since none of the DNA samples from the adjacent control tissues or blood samples from the same patients had them.
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PMID:p53 and p16/CDKN2 gene mutations in esophageal tumors from a high-incidence area in South Africa. 980 20

A systematic characterization of the cancerization field of esophageal carcinoma based on p53 protein accumulation has not been reported previously. The present report presents such a study based on 50 specimens of esophageal squamous-cell carcinoma from northern China. To gain insight into the etiology of this disease among the 50 subjects, DNA was analyzed for a polymorphism of the aldehyde dehydrogenase-2 (ALDH2) gene, which has been associated with increased risk for esophageal cancer among alcohol-consuming patients in Japan. However, the frequency of this polymorphism among our subjects, 30% (15/50), was within published control frequencies for this allele, suggesting that this allele may not play a role in the etiology of esophageal cancer in this northern Chinese population. Immuno-histochemical staining showed that 66% of the tumors were p53+. Of 420 pieces near or adjacent to p53+ tumors, p53+ cells were present among 64% of basal-cell hyperplasia (BCH), 70% of dysplasia (DYS) and 88% of carcinoma in situ (CIS). Of 216 pieces near or adjacent to p53- tumors, p53+ frequencies were 25% of BCH, 25% of DYS and 0% of CIS. The proportion of BCH cells that were p53+ decreased at increasing distance from the tumor (p = 0.006). The sporadic distribution of p53+ cells and the distribution and frequency of p53+ precursor lesions support the view that accumulation of p53 protein is multifocal and occurs in precursor lesions in early stages of esophageal carcinogenesis.
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PMID:Multifocal accumulation of p53 protein in esophageal carcinoma: evidence for field cancerization. 980 24

Epidemiological studies have demonstrated an association between human esophageal cancer and dietary/nutritional risk factors in developing countries. We examined the expression of p53 protein in 51 cases of esophageal squamous cell carcinomas (ESCCs) and paired normal esophageal tissues by immunohistochemistry. Alterations in the tumor suppressor gene p53 (exons 5-8) were analyzed in 51 cases of ESCC and paired normal tissues by PCR and single-strand conformation polymorphism. p53 protein expression was correlated with major dietary risk factors and common carcinogens identified in India. Immunohistochemical analysis of frozen esophageal tissue sections using anti-p53 monoclonal antibody (D0-1) showed overexpression of the protein in the nuclei of epithelial cells in 39 of 51 (76%) cases. The histopathologically proven normal esophageal tissue sections taken from a distant site from esophageal cancer patients did not show any detectable level of p53 immunoreactivity. The PCR-single-strand conformation polymorphism analysis showed a mobility shift in 37 of 51 (72%) ESCCs. Intake of chilies was positively associated with p53 protein expression (P < 0. 01) in the esophageal cancerous lesions. Our results suggest that p53 alterations are frequent events in esophageal oncogenesis in the Indian population, which has dietary habits that are considerably different from those of the Western population.
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PMID:High prevalence of p53 gene alterations and protein overexpression in human esophageal cancer: correlation with dietary risk factors in India. 981 6

Esophageal adenocarcinoma (SKGT-2, SKGT-4, and SKGT-5) and epidermoid carcinoma (HCE-4) cells containing variable retinoblastoma (Rb), cyclin D1, p16, and p53 expression patterns were exposed to the synthetic flavone, flavopiridol. The IC50 was approximately 100-150 nM for each of these cell lines. Exposure of esophageal carcinoma cells to 300 nM flavopiridol induced cell cycle arrest and apoptosis, resulting in a 90% inhibition of proliferation relative to that of nontreated cells after a 5-day exposure to the drug. Western blot analysis revealed diminution of cyclin D1, Rb, and p107 protein levels after flavopiridol exposure. Whereas cell cycle arrest and overall growth inhibition did not correlate in any obvious manner with the genotype of these cell lines, apoptosis seemed to be more pronounced in SKGT-2 and SKGT-4 cells that lack Rb expression. Pretreatment of esophageal cancer cells with 9-cis-retinoic acid did not substantially potentiate flavopiridol activity in these cell lines. Although the precise mechanism of flavopiridol-mediated cytotoxicity has not been fully defined, this drug is an attractive agent for molecular intervention in esophageal cancers and their precursor lesions; further evaluation of flavopiridol in this clinical context is warranted.
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PMID:Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells. 982 56

A number of molecules involved in the process of invasion and metastasis of cancer cells have been demonstrated as a biological prognostic parameter. In esophageal cancer, overexpression of the oncogenes (c-erbB, int-2/hst-1/cyclin D1, MDM2), altered expression of suppressor genes (p 16, DCC), and abnormal expression of adhesion molecules (E-cadherin, alpha-catenin) has been reported as markers of high malignant potential. Proliferation markers (Ki-67, AgNORs, PCNA) and angiogenetic factors (intratumoral microvessel density, VEGF) are also related to the prognosis of the patients with various cancers including esophageal cancer. Prognostic significance of p53 is still controversial. In addition to the clinicopathological parameters, combination of these biological markers would be important to predict the clinical outcome of the cases and to establish an individualized strategy of the treatment of each case according to the biological behavior of the cancer cells.
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PMID:[Prognostic factors of esophageal cancer]. 983 1

Microsatellite alterations at 3 genetic loci (chromosomes 2p, 3p and 17p) were analyzed in 25 tumors (20 primary tumors and 5 metastatic lymph nodes) from 20 patients after surgical treatment for esophageal cancer. DNA samples from tumors were compared with control DNA from lymphocytes obtained from the peripheral blood of the individual patients. Microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] were detected in 15% of 20 primary tumors with marker D2S123 (chromosome 2p), 55% with marker D3S1067 (chromosome 3p) and 50% with marker TP53 (chromosome 17p). The 3-year disease-free survival rate of the 10 patients who had tumors without alterations or with an alteration at only 1 of 3 microsatellite loci was 75% and it was better than that of the 10 patients who had tumors with alterations at 2 or 3 microsatellite loci (48%, p = 0.049). This finding suggests that esophageal cancer with alterations at multiple microsatellite loci might have strong malignant potential. However, MSI was only detected in one of 20 patients, which suggests that MSI might not play an important role in the development of this cancer. Three of 5 metastatic lymph nodes showed no LOH even though primary tumors of these patients exhibited LOH with 1 or 2 markers, and 1 metastatic lymph node had LOH that was detected with D3S1067 even though the primary tumor of this patient had no LOH with all markers. Thus, clonal heterogeneity might exist in esophageal squamous-cell carcinomas.
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PMID:Detection of loss of heterozygosityat microsatellite loci in esophageal squamous-cell carcinoma. 994 4


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