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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is no scientific study that has investigated the association between human papilloma virus (HPV) and p53 mutation in Hong Kong Chinese patients with esophageal cancers. The aim of this survey is to evaluate in details the prevalence and relationship of HPV and p53 mutation in these patients with esophageal squamous cell carcinomas. Fresh tissues from the resected specimens of 70 Chinese patients (59 men, 11 women) with primary esophageal squamous cell carcinomas (20 well-differentiated, 36 moderately differentiated, and 14 poorly differentiated squamous cell carcinomas) were tested for the presence of HPV and p53 mutation using the polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP) analysis, and DNA sequencing. No HPV type 18 was detected, whereas HPV type 16 was identified in 8.6% (6 of 75) of the cases. p53 mutation was found in 44% (31 of 70) of the tumors. The mean ages of HPV-positive and HPV-negative groups of patients were 55 and 64 years, respectively (P = .046, t-test). There was no correlation between the prevalence of HPV and p53 mutation in these tumors. The presence of HPV and p53 also had no relation to the sex of the patients or to the grade of the carcinomas. It is concluded that the overall low prevalence of HPV in esophageal carcinomas may suggest that the virus may not play an important role in the pathogenesis of these tumors in Hong Kong Chinese patients. Also, p53 mutation and integrated HPV DNA are not mutually exclusive in esophageal cancer.
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PMID:Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong Kong Chinese and its relationship with p53 gene mutation. 919 Sep 99

It has been suggested that the frequency, type, and location of p53 mutations (mutational spectra) can be linked to specific exogenous and endogenous carcinogenic agents and processes. Squamous cell carcinoma of the head and neck (SCCHN) provides an excellent tumor model to evaluate the utility of the p53 mutational spectra, given that it has well-defined and strong risk factors (tobacco and alcohol). The purpose of this analysis was to establish the pattern of p53 mutations in SCCHN and evaluate this mutational spectrum in comparison to the spectra for other cancers with similar and different risk factors, including cancers of the esophagus, lung, and colon. p53 mutational data were obtained from head and neck tumors collected at the University of North Carolina Hospitals and the published literature. A total of 14 of 33 tumors from the University of North Carolina Hospitals (42%) were found to have a p53 mutation. The alterations included three transversions, seven transitions, two deletions, and two suspected codon 47 polymorphisms. In general, SCCHN and esophageal cancer share a similar mutational pattern in contrast to colon cancer. These two aerodigestive tract cancers were statistically different from lung cancer, despite sharing tobacco as a major risk factor. For example, G-->T transversions, a mutation type considered to be characteristic of exogenous DNA-damaging agents including tobacco smoke carcinogens, varied among tobacco-related cancer sites (14% SCCHN, 11% esophageal, and 31% lung) in contrast to colon cancer (6%). The comparison of mutational spectra for SCCHN and other cancers indicates that the effects of both tobacco and alcohol exposure may yield a pattern of p53 mutations that reflects elements of both exogenous and endogenous exposures.
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PMID:p53 mutations in head and neck cancer: new data and evaluation of mutational spectra. 923 36

We describe the result of esophageal cancer treatment in the past era of the Department of Surgery, Chiba University School of Medicine directed by Professor Seo, Nakayama and Sato and the improved results of the treatment at the present time from the view point of diagnosis (early superficial cancer, lymph node metastasis and adjacent organ invasion) and treatment (three-field lymph node dissection, improved result of operative mortality and morbidity, improvement of long-term survival rate). In addition, we prospect the future through the present study such as mutation of P53 gene and malignancy, immunotherapy using cytokine gene transfer, cancer inhibition therapy by induction of cancer suppressor gene, prodrug therapy, heavy particle iron therapy, and clinical application of virtual reality to the surgical field.
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PMID:[Surgical treatment and research of esophageal cancer in the past and the present era in our department--for the view point of the future]. 927 74

To better understand the roles of p53 and cell cycle-regulating protein alterations in human esophageal carcinogenesis, we investigated immunohistochemically the distribution patterns of Waf1p21, pRb, p16 and p53 in 22 cases of surgically resected esophageal cancer as well as in the neighboring non-cancerous squamous epithelia. Waf1p21 protein was detected in 13 of the 20 cases of well-differentiated squamous-cell carcinoma (SCC), where the Waf1p21-positive cells were located mainly in the interior layers of the cancer nests. Conversely, p53-positive cells were found mostly in the peripheral layers. Cells containing both Waf1p21- and p53-positive immunostaining were not observed in a double-immunostaining experiment. p16 was detected in both the nucleus and cytoplasm in 3 of the 22 cases of SCC. All of these p16-positive cancers showed an absence of pRb immunostaining; this result is consistent with the idea that expression of p16 is regulated negatively by pRb. Eleven of the 22 esophageal SCCs (50%) showed extensive pRb immunostaining cells, and the remaining 11 cases displayed a few pRb-positive cells or an absence of pRb immunostaining. In a majority of the morphologically normal squamous-cell epithelia samples, immunostaining of Waf1p21 and pRb was found in most of the cells in the parabasal layers (proliferation compartment), where PCNA-positive cells also resided. In the pre-cancerous lesions, Waf1p21 and pRb were detected in cells surrounding the top of the lesioned region, p16-positive cells were scattered in the basal cell hyperplastic and dysplastic lesions and p53-positive cells existed in 2 distinct patterns: "scattered" and "focal".
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PMID:Immunohistochemical studies on Waf1p21, p16, pRb and p53 in human esophageal carcinomas and neighboring epithelia from a high-risk area in northern China. 931 88

Recently we identified a novel gene, gml, whose expression is regulated in a p53-dependent manner and found that gml expression was correlated with the sensitivity of esophageal cancer cells to anticancer drugs. To further investigate the biological mechanism of gml in determining the chemosensitivity of cancer cells to clinically useful agents, we introduced gml cDNA into TE10, an esophageal cancer cell line that lacks endogenous gml expression. In two resulting stable cell lines which expressed gml cDNA in the absence of wildtype p53, cell death occurred within 6 h after treatment with Taxol. TE10 parent cells or TE10 cells transfected with vector alone displayed relative resistance for 36 h. Induction of gml did not by itself affect viability. Morphological analysis confirmed that the increased chemosensitivity to Taxol conferred by gml was due to apoptosis. These data suggest that reduced expression of gml is likely to be associated with poor response rates to chemotherapy, and that an assay for gml expression might serve a clinical purpose as a predictor of chemotherapeutic sensitivity.
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PMID:GML sensitizes cancer cells to Taxol by induction of apoptosis. 931 6

Esophageal tumors from 29 patients residing in Guangzhou, China were examined for mutations in exons 5-8 of the p53 tumor suppressor gene and for p53 protein accumulation in tumor cell nuclei. Anamnestic data for each patient, which included information on family history of cancer, tobacco smoking, drinking of alcoholic beverages, and dietary habits such as consumption of pickled vegetables, were recorded. Screening of DNA from tumor cells microdissected from biopsies was performed by PCR amplification of p53 gene exons 5-8, denaturing gradient gel electrophoresis analysis, and DNA sequencing. Mutations were identified in 20 of 29 tumors (69%). All tumors harboring a missense mutation in the p53 gene also showed nuclear accumulation of the tumor suppressor protein by immunohistochemistry. The most common p53 mutations in these tumors were guanine to adenine (G-->A) transitions (10 of 20 tumors; 50%). We did not find multiple mutations at codon 176, in contrast to Lung et al. in their recent study of esophageal cancer patients from Guangzhou (M. L. Lung et al., Cancer Epidemiol. Biomark. Prev., 5: 277-284, 1996). The mutation prevalence was high both in smokers (13 mutations in 20 smokers; 65%) and in nonsmokers (7 of 9 tumors with mutations; 78%), an observation that differs from that of studies in European and North American patients, which demonstrate a much higher prevalence of p53 mutations in smokers than in nonsmokers (reviewed in R. Montesano et al., Int. J. Cancer Predict. Oncol., 69: 225-235, 1996.). Our findings in this pilot study of tumor suppressor gene mutations in patients from Guangzhou support a large body of epidemiological observations pointing to dietary mutagenic carcinogens peculiar to populations in China at high risk of esophageal cancer.
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PMID:p53 mutations in esophageal tumors from a high incidence area of China in relation to patient diet and smoking history. 936 71

Expression of the GML gene is regulated in a p53-dependent manner and is correlated with the sensitivity of esophageal cancer cells to anti-cancer drugs. To clarify the effect of GML expression on the sensitivity of cancer cells to ionizing radiation treatment, we established cell lines derived from p53-mutant human osteosarcoma HOS and esophageal carcinoma TE10 lines in which GML expression can be induced using the tetracycline-regulable system. Colony formation assay showed that the growth of cells expressing GML are inhibited in response to ionizing radiation, whereas cells not expressing GML were resistant to irradiation. Further investigation demonstrated that GML expression enhances G2/M arrest and apoptosis induced by gamma-irradiation. These results suggest that GML sensitizes cancer cells to ionizing radiation.
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PMID:Overexpression of GML promotes radiation-induced cell cycle arrest and apoptosis. 942 96

Common and distinct genetic alterations are involved in the multistep mechanism of gastrointestinal carcinogenesis. Inactivation of the p53 and APC genes, activation of teleomerase and anomalous CD44 expression are common events that serve as a genetic marker for differential diagnosis of cancer. Amplification of cyclin D1 gene is preferentially found in esophageal cancer, whereas cyclin E gene amplification is frequently associated with both gastric and colorectal cancers. Multiple genetic alterations differ depending on the two histological types of gastric cancer. These genetic alterations can be applied in the multistep mechanism of the development and progression of gastrointestinal cancers. By application of these observations in clinical practice, we can facilitate and improve the differential diagnosis on cancer, obtain information on the grade of malignancy, determine patient prognosis, and identify patients at high risk for developing multiple cancers.
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PMID:[Molecular diagnosis of gastrointestinal cancers]. 947 27

The p53 gene has been shown to be commonly mutated in various human cancers, and mutant p53 can act as a dominant oncogene. The intact p53 protein is also known to induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and is implicated in cell cycle arrest. We investigated p53 gene alterations in gastric adenocarcinoma and esophageal squamous cell carcinoma to elucidate the association of the nuclear accumulation of the p53 protein and/or p21WAF1/CIP1 protein. Abnormalities of the tumor suppressor gene p53 protein and the expression of p21WAF1/CIP1 protein were analyzed by immunohistochemical techniques in 32 cases of gastric adenocarcinoma and 15 cases of esophageal squamous cell carcinoma. Twenty cases of gastric cancer and five cases of esophageal cancer were also analyzed for p53 gene mutation by polymerase chain reaction and direct nucleotide sequencing. Overexpression of p53 protein was found in 13/32 (41%) of gastric cancers and 5/15 (33%) of esophageal cancers. We found immunodetectable p53 in 10/14 cases with mutations and in none of 11 cases without mutations in gastric and esophageal cancers. Hence, immunohistochemical and genetic analyses gave concordant results in 84% of 25 cases, revealing a good correlation between immunostaining of p53 and missense mutation of the p53 gene. p53 immunostaining was not observed in cases with frameshift or splicing mutation. The expression of p21WAF1/CIP1 protein was found in 9/32 (29%) of gastric cancers and 4/15 (27%) of esophageal cancers and in 2/14 (14%) cases with alteration of the p53 gene and in 5/11 (45%) without. These results suggest that abnormalities of p53 may be closely associated with the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma and that the immunoreactivity of p53 protein is a general indicator of the tumors with altered p53 function. The expression of p21WAF1/CIP1 protein was suppressed in the neoplastic tissues with and without p53 gene alteration.
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PMID:Expression of p53 and p21WAF1/CIP1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene. 951 19

The aim of this study was to investigate the relationship between the expression of p53 protein and radiochemosensitivity in patients with advanced esophageal cancer. We analyzed the expression of p53 protein by an immunohistochemical method in tumors from 28 patients with advanced esophageal cancer who had been treated by absolute noncurative resection. Four patients died from postoperative complications. Fourteen of the remaining 24 patients were treated with postoperative radiochemotherapy. The expression of p53 protein was detected in tumors from 16 of 28 patients (57.1%). The mean survival period was 16.4 months for 14 patients treated with radiochemotherapy, as compared to 6.9 months for 10 patients who were not treated with radiation therapy (P = 0.112). In the case of the 14 patients treated with radiochemotherapy, the mean survival period was 24.7 months for seven patients with p53-negative tumors while it was only 8 months for seven patients with p53-positive tumors. However, difference was not statistically significant (P = 0.149). Postoperative radiochemotherapy prolonged the survival of some patients with noncuratively operated esophageal tumors that were p53-negative. However, the enhanced survival was not statistically significant.
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PMID:Radiochemosensitivity and expression of p53 in patients with esophageal cancer treated by absolute noncurative resection. 956 68


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