UMLS:C0546837 - FACTA Search

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

AIM:To determine the extent of apoptosis and its possible relationship with the changes of p53, Waflp21, bcl-2, and c-myc at different stages of esophageal carcinogenesis.METHODS:Two hundred and forty-one esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China were used in this study.Apoptotic cells and apoptotic bodies were identified by well-established morphological criteria. The extent of apoptosis and its possible relationship with the rate of cell proliferation (PCNA) and changes of p53, Waf1p21, bcl-2,and c-myc were analyzed in samples with esophageal precancerous and cancerous lesions.RESULTS:The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelia as the cells immunostaining-positive for p53, bcl-2, c-myc and PCNA.The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm(2) of the tissue section) were low in the normal epithelia,and increased significantly as the lesions progressed from BCH to DYS and to SCC.The extent of apoptosis correlated well with the cell proliferation indices based on PCNA. The total number of positive cells for p53 stain was much higher than that of apoptotic cells. No difference in apoptotic indices was found between p53-positive and p53-negative samples. Waf1p21-positive cells resided in cell layers were higher in number than p53 and PCNA-positive cells. The number of immunostaining positive cells for Waflp21 increased slightly from normal to BCH,but decreased in DYS and SCC. Positive staining samples for bcl-2 and c-myc increased as the lesions progressed from BCH to DYS and to SCC. No apparent correlation between apoptosis and Waf1p21, bcl-2 or c-myc expression was observed.CONCLUSION:The extent of apoptosis was low in normal esophageal epithelium and increased as the lesions progressed. The apoptotic cells were located in the same hyperproliferative cell compartment as cells immunostaining-positive for p53, bcl-2,c-myc and PCNA,but no apparent correlation between apoptosis and these parameters was observed,possibly due to the complexities of molecular changes in esophageal carcinogenesis.
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PMID:Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China. 1181 1

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.
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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

Excessive alcohol consumption is associated epidemiologically with an elevated risk of esophageal cancer. In this study, we examined the effects of simultaneous administration of ethanol on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Groups 1-3 were treated with NMBA at a dose of 0.5 mg/kg body weight (high dose), and groups 4-6 received a dose of 0.1 mg/kg body weight (low dose), by s.c.-injection, 3 times per week for the first 5 weeks. Groups 1 and 4 were given ethanol free water as controls. Groups 2 and 5 were treated with 10% ethanol in their drinking water only at the time of NMBA treatment, while groups 3 and 6 were administrated the supplement continuously up to the end of the experiment. Macroscopically, with high dose NMBA-initiation, simultaneous 5-week and continuous 24-week ethanol administration demonstrated a tendency to increase the incidence and multiplicity of tumors, and also microscopically the multiplicity of papillary hyperplasias. In low dose groups, the incidence of esophageal papillary hyperplasias was significantly increased by continuous 24-week ethanol administration. Immunohistochemistry, proliferating cell nuclear antigen (PCNA) positive indices tended to be increased in tumors by simultaneous 5-week and continuous 24-week ethanol administration, but cyclin D1 expression was not affected. These data suggest that simultaneous ethanol administration have weak enhancing effects, and also promoting effects in post-initiation phase is present on NMBA-induced rat tumorigenesis.
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PMID:Weak enhancing effects of simultaneous ethanol administration on chemically induced rat esophageal tumorigenesis. 1216 75

Esophageal cancer is still one of the most widespread diseases, and surgery for esophageal carcinoma is very stressful for patients. Even though lymph node metastasis occurs more frequently in cases of early esophageal cancer than it does in cases of gastric cancer, surgeons prefer to avoid lymph node dissection if possible, thereby subjecting patients to less invasion. Thus, the aim of the present study was to examine the possibility of predicting lymph node metastasis on the basis of tumor location, quantification theory II analysis of tumor expression of genetic markers in primary esophageal cancer. Surgical specimens from 63 patients of esophageal cancer with submucosal invasion were examined for the relationship between tumor location and lymph node metastasis. In 19 of these 63 patients, p53, p21(Waf1, and proliferating cell nuclear antigen (PCNA) were examined immunohistologically, and to quantify the risk of lymph node metastasis, computer analysis was performed on the basis of quantification theory II, in which pathological lymph node metastasis (pN) was the objective variable and "high" or "low" expression of each of the three markers was the predictive variable. Tumors located in the lower third of the esophagus had no lymph node metastasis to the upper mediastinal region, and were thus indicated for trans-hiatal esophagectomy. A coefficient greater than 0.91 predicted node negative disease accurately without false-negative results; false-positive results were obtained for 54.5% of patients with a coefficient less than 0.064. Thus, we found that quantification theory II may be useful when considering indications for surgery without lymph node dissection in some cases of T1 esophageal carcinoma.
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PMID:Prediction of lymph node metastasis by p53, p21(Waf1), and PCNA expression in esophageal cancer patients. 1286 74

Overexpression of cyclin D1 and disruption of cell cycle control in G(1) occur frequently in human esophageal cancer. Transgenic (TG) mice with cyclin D1 overexpression targeted to the oral-esophageal tissue by the EBV ED-L2 promoter showed increased severity in esophageal dysplasia without cancer development, after multiple doses of N-nitrosomethylbenzylamine (NMBA). Dietary zinc deficiency (ZD) in mice enhances cellular proliferation in esophagus/forestomach and susceptibility to NMBA-induced carcinogenesis. We investigated whether cyclin D1 overexpression in TG mice, together with ZD, might lead to unchecked cell proliferation and accelerated NMBA-induced tumorigenesis. Five-week-old TG and wild-type (WT) mice were fed a ZD- or -sufficient (ZS) diet, forming four groups: ZD:TG; ZS:TG; ZD:WT; and ZS:WT. After 4 weeks, animals were given a single intragastric NMBA dose and were sacrificed 25 and 77 days later. Without NMBA, cell proliferation was greatest in ZD:TG esophagus/forestomach, followed by ZD:WT, and then ZS:TG>/=ZS:WT. The high rate of cell proliferation was accompanied by overexpression of cell cycle progression and tumorigenesis biomarkers, including proliferating cell nuclear antigen, cyclin D1, cyclin-dependent kinase 4, p53, cytokeratin 14, epidermal growth factor receptor, and by a reduced rate of apoptosis. ZD substantially increased forestomach tumor incidence in TG mice: 85% of ZD:TG versus 14% of ZS:TG mice had forestomach tumors (P < 0.001), with progression to malignancy occurring only in ZD:TG tumors. Additionally, 14% of ZD:TG mice developed esophageal tumors and esophageal intestinal metaplasia at 77 days. Thus, cyclin D1 overexpression, in cooperation with ZD, decontrols cell proliferation, ensuring cell expansion, a prerequisite for cancer development.
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PMID:Combined cyclin D1 overexpression and zinc deficiency disrupts cell cycle and accelerates mouse forestomach carcinogenesis. 1287 33

PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions. PCNA, in contrast, stains the nuclei of cells in the parabasal and basal layers. We examined 201 regions from 47 patients that represented different stages of esophageal neoplasia, comprising 34 areas of normal mucosa, 18 of dysplasia in squamous epithelium (DYS/SC), 39 squamous cell carcinoma (SCCA), 29 areas of Barrett's esophagus, 48 of Barrett's dysplasia (DYS/BAR) and 33 areas of adenocarcinoma (AC). The immunostaining patterns of esophagin and PCNA were evaluated and graded for level of expression. There was loss of esophagin expression in the high- and low-grade dysplasias compared to normal epithelia. In the squamous dysplasias, there was more intense staining (of esophagin) in the atypical nuclei and superficial squamous epithelial cells than in the basal cells. PCNA staining was increased in intensity in the high-grade dysplasias relative to normal basal layer cells. Combined analysis of esophagin and PCNA appears to reveal an inverse relationship between proliferation and differentiation during esophageal neoplastic progression. Moreover, this combined staining approach also offers promise for detecting esophageal cancer in early, precancerous stages.
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PMID:Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression. 1522 70

In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.
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PMID:Localization of heparanase in esophageal cancer cells: respective roles in prognosis and differentiation. 1528 61

Isorhamnetin is one member of flavonoid components which has been used in the treatment of heart disease. Recently the in vitro anti-cancer effect of isorhamnetin on human esophageal squamous carcinoma cell line Eca-109 was investigated in our lab. When Eca-109 cells were in vitro exposed to the graded doses of isorhamnetin (0-80 microg/ml) for 48 h, respectively, isorhamnetin exhibited cytostatic effect on the treated cells, with an IC(50) of 40+/-0.08 microg/ml as estimated by MTT assay. Inhibition on proliferation by isorhamnetin was detected by trypan blue exclusion assay, clone formation test, immunocytochemical assay of PCNA and (3)H-thymidine uptake analysis. Cell cycle distribution was measured by FCM. It was found that the viability of Eca-109 cells was significantly hampered by isorhamnetin. Compared with the negative control group, the treated group which was exposed to isorhamnetin had increased population in G(0)/G(1) phase from 74.6 to 84 while had a significant reduction in G(2)/M phase from 11.9 to 5.8. In addition to its cytostatic effect, isorhamnetin also showed stimulatory effect on apoptosis. Typical apoptotic morphology such as condensation and fragmentation of nuclei and blebbing membrane of the apoptotic cells could be observed through transmission electron microscope. Moreover, the sharp increase in apoptosis rate between the control and treated group were detected by FCM from 6.3 to 16.3. To explore the possible molecular mechanisms that underlie the growth inhibition and apoptosis stimulatory effects of isorhamnetin, the expressions of six proliferation- and death-related genes were detected by FCM. Expressions of bcl-2, c-myc and H-ras were downregulated whereas Bax, c-fos and p53 were upregulated. However, the in vivo experiments were required to further confirm the anti-cancer effects of isorhamnetin. In conclusion, isorhamnetin appears to be a potent drug against esophageal cancer due to its in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.
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PMID:The flavonoid component isorhamnetin in vitro inhibits proliferation and induces apoptosis in Eca-109 cells. 1736 93

ZengShengPing (ZSP), a mixture of six medicinal herbs, has been reported to prevent esophageal squamous cell carcinoma (SCC) in human patients with dysplasia. This study was designed to investigate the chemopreventive effects of ZSP on oral cancer in animal models and human patients. In the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model, ZSP (6g/kgBW/day by gavage for 10 weeks) significantly reduced the number of visible tumor, the tumor volume, and the incidence of SCC (P<0.01). Two biomarkers associated with cell proliferation, silver stained nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-labeling index, were also significantly suppressed by ZSP treatment (P<0.01). In the 4-nitroquinoline 1-oxide (4NQO)-induced oro-esophageal cancer model in mice, ZSP (10% in diet) also significantly reduced the incidence of tongue SCC from 55.2% (16/29) to 22.2% (6/27) (P<0.05), and slightly reduced the incidence of esophageal SCC from 34.5% (10/29) to 22.2% (6/27). Furthermore, in a randomized clinical trial on patients with oral leukoplakia, ZSP (4 tablets, 3 times per day for 8-12months) reduced the size of oral lesion in 67.8% (40/59) patients, whereas the placebo was effective in 17% (9/53) patients (P<0.01). Such an effect was associated with significant decrease of AgNOR and PCNA-labeling index. In summary, our studies have demonstrated the chemopreventive effects of ZSP on two animal models of oral cancer, and human patients with oral leukoplakia.
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PMID:Chemoprevention of oral cancer in animal models, and effect on leukoplakias in human patients with ZengShengPing, a mixture of medicinal herbs. 2002 53

Nowadays, some evidences demonstrate that human mesenchymal stem cells (hMSCs) favor tumor growth; however, others show that hMSCs can suppress tumorigenesis and tumor growth. With the indeterminateness of the effect of hMSCs on tumors, we investigated the effect of hMSCs on lung cancer cell line A549 and esophageal cancer cell line Eca-109 in vitro and in vivo. Our results revealed that hMSCs inhibited the proliferation and invasion of A549 and Eca-109 cells, arrested tumor cells in the G1 phase of the cell cycle and induced the apoptosis of tumor cells in vitro by using a co-culture system and the hMSCs-conditioned medium. However, animal study showed that hMSCs enhanced tumor formation and growth in vivo. Western blotting and immunoprecipitation data showed that the expressions of proliferating cell nuclear antigen (PCNA), Cyclin E, phospho-retinoblastoma protein (pRb), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL, and matrix metalloproteinase 2 (MMP-2) were downregulated and the formation of Cyclin E-cyclin-dependent kinase 2 (CDK2) complexes was inhibited in the tumor cells treated with the hMSCs-conditioned medium. According to the observation of tumor mass and the result of microvessel density (MVD), we found that the promoting role of hMSCs on tumor growth was related with the increase of tumor vessel formation. Our present study suggests that hMSCs have a contradictory effect on tumor cell growth between in vitro and in vivo, and therefore, the exploitation of hMSCs in new therapeutic strategies should be cautious under the malignant conditions.
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PMID:Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. 2144 22

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