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Esophageal Mucosa (esophageal + mucosa)
Kinds of Esophageal Mucosa Selected AbstractsStructural Features of the NAD-Dependent In Situ Retinoic Acid Supply System in Esophageal MucosaALCOHOLISM, Issue 2010Hirokazu Yokoyama Background:, We previously reported that an NAD-dependent in situ retinoic acid supply system, which comprises some isoforms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and provides retinoic acid from retinol via a 2-step oxidation process, exists in the rat esophagus. Herein, their isoforms responsible for the pathway and its localization in the rat esophagus was examined. Methods:, The expressions of mRNAs of various isoforms of ADH and ALDH were examined in the fraction mainly comprising mucosal layer of the rat esophagus by RT-PCR. Expression levels of Class IV ADH and ALDH 1A1 were compared between the fractions and that mainly comprising muscle layer of the rat esophagus by quantitative PCR. The catalytic activities producing retinoic acid from retinal were compared between the 2 fractions and its optimum pH was also determined. Results:, Classes I, III, and IV ADHs and ALDHs 1A1 and 3A1 were predominant isoforms in the rat esophageal mucosa. The expression levels of mRNA of Class IV ADH and ALDH 3A1 were significantly higher in the mucosal than in the muscle layer. Consistently, the catalytic activities producing retinoic acid from retinal were significantly higher in the former than the latter. The optimum pH of the process was 9.0. Conclusions:, Considering the affinities for retinol and retinal of ADHs and ALDHs expressed in the rat esophagus, the NAD-dependent in situ retinoic acid supply system in the rat esophagus is thought to comprise Class IV ADH and ALDH 1A1. In the rat esophagus, the system exists predominantly in the mucosal layer. [source] Original article: The expression of CFL1 and N-WASP in esophageal squamous cell carcinoma and its correlation with clinicopathological featuresDISEASES OF THE ESOPHAGUS, Issue 6 2010Wei-Sen Wang SUMMARY Cofilin1 (CFL1) is an actin-modulating protein, which belongs to the ADF/Cofilin family. Neural Wiskott,Aldrich syndrome protein (N-WASP) is the key regulator of the actin cytoskeleton, a member of Wiskott-Aldrich syndrome protein family. They have been suggested to be involved in cancer cell invasion and metastasis. In this study, the expression patterns of CFL1 and N-WASP in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and their correlation with clinical characteristics were investigated. Immunohistochemical staining showed that CFL1 was expressed in nuclear and cytoplasm of cancer cells. However, N-WASP was mainly found in the cytoplasm of the cancer cells. There were significant evidences that proved that CFL1 is correlated with clinicopathological factors in ESCC, such as infiltration depth, lymph node metastasis and pathological staging (P < 0.05). It is also proved that N-WASP is related to lymph node metastasis and pathological staging in ESCC (P < 0.05). Kaplan,Meier analysis showed that there was no correlation between CFL1 and N-WASP protein expression and survival (P > 0.05). Moreover, the mRNA expression of CFL1 and N-WASP was detected by quantitative real time PCR in 70 tissue specimens. The results showed that CFL1 mRNA level was over-expressed in ESCC tissue (P < 0.05), while N-WASP mRNA expression level was not different between cancerous tissues and adjacent normal esophageal mucosa (P > 0.05). Also, CFL1 mRNA expression was significantly associated with regional lymph node metastasis and pathological staging (P < 0.05). Kaplan,Meier analysis showed that there was no correlation between CFL1 and N-WASP mRNA expression and survival (P > 0.05). Our findings suggested that CFL1 and N-WASP may play an important role in the tumorigenesis of ESCC, and to be the candidate novel biomarkers for the diagnosis and prognosis of ESCC. These findings may have implications for targeted therapies in patients with ESCC. [source] Gastroduodenal reflux induces group IIa secretory phospholipase A2 expression and activity in murine esophagusDISEASES OF THE ESOPHAGUS, Issue 5 2010David Mauchley SUMMARY Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A2 (sPLA2) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA2 protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA2+/+) mice (n= 28) underwent side-to-side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real-time RT PCR was used to quantitate the influence of GDR on group IIa sPLA2 expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA2 protein. A colorimetric assay was used to quantify total sPLA2 activity after standardization of protein levels. Statistical analysis was conducted using Student's t -test. Group IIa sPLA2 mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time-dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA2 enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA2 as well as sPLA2 activity is induced by GDR. This novel finding indicates that sPLA2 may play a role in the development of the histologic changes produced by GDR in esophageal mucosa. [source] Estrogen and progesterone receptors in esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 4 2008R. Kalayarasan SUMMARY., Information is sparse and contradictory in the literature regarding the role of estrogen receptor (ER) and progesterone receptor (PR) in esophageal carcinoma. This study was conducted over a period of 18 months from September 2004 with the primary aim of determining the PR, ER alpha (ER,) and ER beta (ER,) status of esophageal carcinoma and normal esophageal mucosa (NEM). The receptor status was correlated with tumor type, tumor differentiation and tumor stage. A total of 45 patients with histologically proven squamous cell carcinoma (SCC) (n = 30) and adenocarcinoma (AC) (n = 15) were studied. Receptor status was detected by immunohistochemistry (IHC) and semiquantitative assessment was done by quick score method of endoscopic biopsy specimens. The mean age for SCC and AC were not significantly different. The gender ratio in favor of males was 3 : 2 for SCC and 4 : 1 for AC. None of the specimens from SCC or AC showed positivity for PR both in NEM and tumor tissue. Likewise none of the specimens were positive for ER, by IHC. The mean ER, score for AC was significantly higher than SCC. For SCC it was seen that ER, positivity in tumor cells increases with dedifferentiation and increasing tumor stage. This trend was seen for AC as well. ER, is over-expressed in poorly differentiated SCC and AC compared to NEM. Thus ER, may be a marker for poor biological behavior, that is dedifferentiation or higher stage of disease. In view of these findings we propose a large-scale prospective, longitudinal interventional study using selective estrogen modulators. [source] Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett's esophagus and esophageal adenocarcinomaDISEASES OF THE ESOPHAGUS, Issue 5 2007Yan Li SUMMARY., Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed. [source] Detection of human papillomavirus DNA in squamous cell carcinoma of the esophagus by auto-nested PCRDISEASES OF THE ESOPHAGUS, Issue 2 2006A. P. Souto Damin SUMMARY., The aim of the present study was to investigate the presence of human papillomavirus (HPV) in surgical specimens of esophageal squamous cell carcinoma. One hundred and sixty-five paraffin-embedded specimens of esophageal carcinoma were analyzed through high-sensitivity auto-nested polymerase chain reaction (PCR) using the consensus GP5+/GP6+ primer. Twenty-six specimens of esophageal mucosa without malignant disease were also studied as a control group. Two different specific primer sets targeting the E6 region of the HPVs 16 and 18 were used for typing. Direct DNA sequence analysis was conducted to confirm positive PCR results. HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases, 24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA. Positive PCR results were confirmed by the amplified viral sequences. Our findings suggest that the presence of either HPV-16 or -18 might be related to development of the malignant phenotype in the esophagus. [source] Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Kazue Nakashima Abstract We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers. © 2004 Wiley-Liss, Inc. [source] Structural Features of the NAD-Dependent In Situ Retinoic Acid Supply System in Esophageal MucosaALCOHOLISM, Issue 2010Hirokazu Yokoyama Background:, We previously reported that an NAD-dependent in situ retinoic acid supply system, which comprises some isoforms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and provides retinoic acid from retinol via a 2-step oxidation process, exists in the rat esophagus. Herein, their isoforms responsible for the pathway and its localization in the rat esophagus was examined. Methods:, The expressions of mRNAs of various isoforms of ADH and ALDH were examined in the fraction mainly comprising mucosal layer of the rat esophagus by RT-PCR. Expression levels of Class IV ADH and ALDH 1A1 were compared between the fractions and that mainly comprising muscle layer of the rat esophagus by quantitative PCR. The catalytic activities producing retinoic acid from retinal were compared between the 2 fractions and its optimum pH was also determined. Results:, Classes I, III, and IV ADHs and ALDHs 1A1 and 3A1 were predominant isoforms in the rat esophageal mucosa. The expression levels of mRNA of Class IV ADH and ALDH 3A1 were significantly higher in the mucosal than in the muscle layer. Consistently, the catalytic activities producing retinoic acid from retinal were significantly higher in the former than the latter. The optimum pH of the process was 9.0. Conclusions:, Considering the affinities for retinol and retinal of ADHs and ALDHs expressed in the rat esophagus, the NAD-dependent in situ retinoic acid supply system in the rat esophagus is thought to comprise Class IV ADH and ALDH 1A1. In the rat esophagus, the system exists predominantly in the mucosal layer. [source] Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2005Hideaki Kobayashi MD Abstract Background and Objectives It has been reported that amino acid transport systems play an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. In this study, we investigated whether L-type amino acid transporter 1 (LAT1) is expressed in human non-cancerous esophageal mucosa and esophageal squamous cell carcinoma. We also examined whether LAT1 expression is correlated with histopathological features. Methods From January 1999 to December 2001, sections of formalin-fixed, paraffin-embedded tissue from 11 cases of early esophageal carcinoma (T1) and 19 cases of advanced esophageal carcinoma (T2, T3) were entered in the study. Histopathologically, all 30 cases were squamous cell carcinoma. Immunohistochemical staining was performed using rabbit anti-LAT1 IgG, with the standard avidin-streptavidin immuno-peroxidase method. Measurement was performed by means of computer-assisted image analysis. The ratio of cells with LAT1 expression in esophageal squamous cell carcinoma and non-cancerous esophageal mucosa was used for analysis in this study. Results Non-cancerous esophageal mucosa expressed LAT1 only in the basal layer of the esophageal wall. Esophageal squamous cell carcinoma expressed LAT1 throughout the tumor. LAT1 expression in esophageal squamous cell carcinoma was significantly higher than that in non-cancerous esophageal mucosa. LAT1 expression in esophageal squamous cell carcinoma increased as the depth of invasion progressed (T1,<,T2 (P,=,0.0477), T2,<,T3 (P,=,0.0415), T1,<,T3 (P,=,0.0044)), and as the tumor size increased. Also, high LAT1 expression was significantly associated with well-differentiated carcinoma. Conclusion These results suggest that LAT1 plays a significant role in cell proliferation, differentiation, and invasion in esophageal squamous cell carcinoma. J. Surg. Oncol. 2005;90:233,238. © 2005 Wiley-Liss, Inc. [source] Carcinogenesis in reflux disease,In search for bile-specific effectsMICROSURGERY, Issue 8 2007M.D., Martin Fein Ph.D. Bile reflux may play a key role for esophageal carcinogenesis in reflux disease. In search for bile-specific effects, the animal model of esophageal cancer was applied in a mutagenesis assay. Big Blue® transgenic mice were operated with microsurgical techniques. Seven had total gastrectomy with esophagojejunostomy creating esophageal reflux of bile and five had a sham operation. After 24 weeks, the mutation frequency (MF) was measured through standard Big Blue mutagenesis assay in the esophageal mucosa and the duodenum as control. Esophageal reflux resulted in esophagitis in the distal esophagus. The MF in esophageal mucosa was 1.6 times higher in animals with reflux than in sham-operated animals; it was identical in the duodenum. In conclusion, the mutagenic potential of bile reflux has been confirmed. However, mechanisms of carcinogenesis in the esophageal cancer model other than chronic inflammation could not be identified because of the only moderately increased MF. © 2007 Wiley-Liss, Inc. Microsurgery, 2007. [source] Anatomy of reflux: A growing health problem affecting structures of the head and neckTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2006Michael J. Lipan Abstract Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are sibling diseases that are a modern-day plague. Millions of Americans suffer from their sequelae, ranging from subtle annoyances to life-threatening illnesses such as asthma, sleep apnea, and cancer. Indeed, the recognized prevalence of GERD alone has increased threefold throughout the 1990s. Knowledge of the precise etiologies for GERD and LPR is becoming essential for proper treatment. This review focuses on the anatomical, physiological, neurobiological, and cellular aspects of these diseases. By definition, gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus; when excessive and damaging to the esophageal mucosa, GERD results. Reflux that advances to the laryngopharynx and, subsequently, to other regions of the head and neck such as the larynx, oral cavity, nasopharynx, nasal cavity, paranasal sinuses, and even middle ear results in LPR. While GERD has long been identified as a source of esophageal disease, LPR has only recently been implicated in causing head and neck problems. Recent research has identified four anatomical/physiological "barriers" that serve as guardians to prevent the cranial incursion of reflux: the gastroesophageal junction, esophageal motor function and acid clearance, the upper esophageal sphincter, and pharyngeal and laryngeal mucosal resistance. Sequential failure of all four barriers is necessary to produce LPR. While it has become apparent that GER must precede both GERD and LPR, the head and neck distribution of the latter clearly separates these diseases as distinct entities warranting specialized focus and treatment. Anat Rec (Part B: New Anat) 289B:261,270, 2006. © 2006 Wiley-Liss, Inc. [source] Telomerase activity in small cell esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2001V. Chow Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor. [source] Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Kazue Nakashima Abstract We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers. © 2004 Wiley-Liss, Inc. [source] The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking historyCANCER, Issue 15 2009A target for risk diagnosis, prevention of esophageal cancers Abstract BACKGROUND: Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae. METHODS: Genes that are silenced in human ESCCs were searched for by treating 3 ESCC cell lines with the demethylating agent, 5-aza-2,-deoxycytidine and performing oligonucleotide microarrays. Methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction analysis of 60 ESCCs and their corresponding background mucosae. RESULTS: Forty-seven genes were identified as methylation-silenced in at least 1 of the 3 ESCC cell lines, and 14 of those genes (claudin 6 [CLDN6]; G protein-coupled receptor 158 [GPR158]; homeobox A9 [HOXA9]; metallothionein 1M [MT1M]; neurofilament, heavy polypeptide 200 kDa [NEFH]; plakophilin 1 [PKP1]; protein phosphatase 1, regulatory [inhibitor] subunit 14A [PPP1R14A]; pyrin domain and caspase recruitment domain containing [PYCARD]; R-spondin family, member 4 [RSPO4]; testis-specific protein, Y-encoded,like 5 [TSPYL5]; ubiquitin carboxyl-terminal esterase L1 [UCHL1]; zinc-finger protein 42 homolog [ZFP42]; zinc-finger protein interacting with K protein 1 homolog [ZIK1]; and zinc-finger and SCAN domain containing 18 [ZSCAN18]) were used as markers. In the background mucosae, methylation levels of 5 genes (HOXA9, MT1M, NEFH, RSPO4, and UCHL1) had significant correlations with smoking duration (, = .268; P = .044; , = .405; P = .002; , = .285; P = .032; , = .300; P = .024; and , = .437; P = .001, respectively). In contrast, an inverse correlation between PYCARD methylation levels and alcohol intake was observed (, = ,.334, P = .025) among individuals with the inactive aldehyde dehydrogenase 2 (ALDH2) genotype. CONCLUSIONS: The current results suggested that ESCCs developed from an epigenetic field for cancerization, which was induced by exposure to carcinogenic factors, such as tobacco smoking. The epigenetic field defect will be a novel target for risk diagnosis and prevention of ESCCs. Cancer 2009. © 2009 American Cancer Society. [source] | ||||||||||