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

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7 +/- 17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7 +/- 14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (> or = 44) and AgNOR count (> or = 6) had a significantly poorer prognosis than the remaining 22 (P = 0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.
 ...
PMID:PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis. 764 Apr 65

The prognostic factors for esophageal cancer from the viewpoint of molecular biology are reviewed. Among several oncogenes and suppressor genes erbB, int2/hst1/Cyclin D1 and MDM2 gene amplifications are significant prognostic factors for esophageal cancer. The value of p53 mutation, and expression of matrix metalloproteinase (MMPs) in the prediction of patients' survival are controversial, so further research is needed. High expression of tumor proliferation-related factors (Ki67, PCNA, and AgNOR), abnormalities of adhesion molecule (E-Cadherin, alpha-Catenin), activation of autocrine mechanism of growth factor (EGFR-TGF alpha, EGF), and DNA ploidy pattern, which is thought to be the result of an accumulation of genomic abnormalities are also prognostic factors for esophageal cancer.
 ...
PMID:[Prognostic factors for esophageal cancer--from the viewpoint of molecular biology]. 868 32

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".
 ...
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

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.
 ...
PMID:Clinical significance of dendritic cell infiltration in esophageal squamous cell carcinoma. 968 32

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.
 ...
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

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.
 ...
PMID:[Prognostic factors of esophageal cancer]. 983 1

Changes in cell proliferation and cell death might be key factors in regulating the rate of neoplasm progression and tumor growth. The extent of apoptosis and its possible relationship with cell proliferation at different stages of esophageal carcinogenesis, however, have not been characterized. In this study, 241 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 to analyze the changes of apoptosis and its relationship with cell proliferation as determined by proliferating cell nuclear antigen (PCNA). The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelium. The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm2 of the tissue section) were low in the normal epithelia, and increased significantly as the lesions progressed from basal cell hyperplasia (BCH) to dysplasia (DYS) and to squamous cell carcinoma (SCC). The extent of apoptosis correlated well with the cell proliferation indices. The present findings indicate that apoptosis occurs in the early stage of esophageal carcinogenesis, and as the lesions progress, both the apoptotic index and PCNA labelled index increase, suggesting that hyperproliferative cells might be more susceptible to apoptosis.
 ...
PMID:Apoptosis and cell proliferation in esophageal precancerous and cancerous lesions: study of a high-risk population in northern China. 1022 69

The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis. Alterations in this gene may adversely affect regulation of these processes and increase susceptibility for cancer. We have recently reported a novel polymorphism in the p21(Waf1/Cip1) gene in the Indian population and its association with esophageal cancer. An A-->G transition at codon 149 resulted in amino acid substitution from aspartate to glycine in the proliferating cell nuclear antigen binding COOH-terminal domain of p21(Waf1/Cip1) that may affect PCNA-p21(Waf1/Cip1) interactions, thereby affecting regulation of cellular proliferation, and may increase susceptibility for development of cancer. In a parallel study in our laboratory, we searched for putative p21(Waf1/Cip1) mutations in oral premalignant and malignant lesions. No somatic mutation was detected in exon 2 of p21(Waf1/Cip1). Interestingly, a codon 149 polymorphism variant (A-->G) was identified in 11 of 30 (37%) premalignant lesions (7 of 19 hyperplastic lesions and 4 of 11 dysplastic lesions) and 11 of 30 (37%) squamous cell carcinomas (SCCs). This codon 149 variant was also identified in paired lymphocytes of all of the patients with premalignant lesions and SCCs harboring the variant allele, suggesting the occurrence of a polymorphism. Lymphocyte DNA isolated from 50 unrelated age- and gender-matched healthy subjects was screened for this polymorphism. Seven of 50 (14%) normal controls harbored the A-->G codon 149 variant allele. Immunohistochemical analysis of p21(Waf1/Cip1) protein expression showed immunoreactivity in 19 of these 30 (63%) oral premalignant lesions and 16 of 30 (53%) SCCs. The most intriguing features of the study were: (a) the significant increase in frequency of this polymorphism not only in patients with oral SCCs (P = 0.038), but also in patients with premalignant lesions (P = 0.038), compared with normal controls; and (b) the significantly higher frequency of p21(Waf1/Cip1) variants (codon 149) in oral premalignant lesions (10 of 11 cases) and SCCs (11 of 11 cases) with wild-type p53 (P = 0.045) than in lesions with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play a vital role in oral tumorigenesis. Furthermore, overexpression of p21 protein in oral lesions harboring missense mutations in the p53 gene suggest a p53-independent role for p21 in the pathogenesis of oral cancer.
 ...
PMID:Association between polymorphism in p21(Waf1/Cip1) cyclin-dependent kinase inhibitor gene and human oral cancer. 1087 97

The p16ink4a-cyclin D1/cyclin-dependent kinase 4 (Cdk4)-retinoblastoma (Rb) pathway has emerged as a critical target in oncogenesis. The zinc-deficient (ZD), N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal cancer model provides a tool to study cell proliferation and cell cycle control in cancer initiation. Weanling rats were fed a ZD or zinc-sufficient (ZS) diet for 5 weeks, and then given a dose of NMBA. After 14 weeks, esophageal tumor incidence was 88% in ZD rats with highly proliferative esophagi versus 0% in ZS rats. Expression of p16ink4a, cyclin D1, Cdk4, and Rb in relation to that of proliferating cell nuclear antigen was characterized in esophagi by immunohistochemistry at 0, 24, and 48 h, and 1, 3, 7, 10, and 14 weeks after NMBA treatment. As early as 24 h, proliferating cell nuclear antigen-positive focal hyperplastic lesions were detected in the suprabasal layers of ZD esophagi. At the same time, overexpression of cyclin D1, Cdk4, and Rb was found in the corresponding lesion in adjacent esophageal sections. By contrast, p16ink4a expression was reduced or absent. At all time points, p16ink4a showed reduced nuclear staining in ZD esophagi compared with that in ZS esophagi. In addition, increased expression of the hyperphosphorylated forms of Rb was detected in ZD esophagi by immunoblotting. Importantly, tumors were consistently observed in ZD esophagi at very early time points. These data, obtained using a unique in vivo model for esophageal cancer with rapid tumor induction, provide strong evidence for a link between deregulation of the p16ink4a-cyclin D1/Cdk4-Rb pathway and the initiation of esophageal tumors.
 ...
PMID:Early deregulation of the the p16ink4a-cyclin D1/cyclin-dependent kinase 4-retinoblastoma pathway in cell proliferation-driven esophageal tumorigenesis in zinc-deficient rats. 1096 11

Alpha-difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the first enzyme in polyamine synthesis. Previous work showed simultaneous administration of DFMO and a zinc-deficient (ZD) diet to weanling rats from the beginning inhibited the onset of zinc-deficiency-induced esophageal cell proliferation by activating apoptosis and reduced the incidence of N-nitrosomethylbenzylamine (NMBA)-induced esophageal cancer. Because esophageal cancer initiation by NMBA is very rapid in ZD rats, this study determined whether DFMO is effective in preventing esophageal carcinogenesis when administered after the establishment of a carcinogenic environment. Weanling rats were given a ZD diet for 5 weeks to establish sustained increased esophageal cell proliferation and then an intragastric dose of NMBA. Thereafter, 20 rats were switched to DFMO-containing water while nine control ZD animals remained on deionized water; all of the animals continued on the ZD diet. Esophagi were collected 15 weeks later. The upper portion was processed for immunohistochemical analysis of cell proliferation, apoptosis, and expression of related genes, and the lower was processed for polyamine content. DFMO substantially reduces the levels of esophageal putrescine and spermidine and esophageal tumor incidence from 89 to 10% in ZD rats. Importantly, DFMO-treated ZD esophagi display increased rate of apoptosis accompanied by intense bax expression and greatly reduced cell proliferation by proliferating cell nuclear antigen expression. In addition, the p16(ink4a)/retinoblastoma control at G1 to S, deregulated in ZD esophagi, is restored after DFMO treatment. These results demonstrate that DFMO, a highly effective chemopreventive agent in esophageal carcinogenesis, reverses and counteracts esophageal cell proliferation/cancer initiation in ZD animals by way of stimulating apoptosis.
 ...
PMID:Alpha-difluoromethylornithine induction of apoptosis: a mechanism which reverses pre-established cell proliferation and cancer initiation in esophageal carcinogenesis in zinc-deficient rats. 1130 87


1 2 3 4 Next >>