[Show abstract][Hide abstract] ABSTRACT: Periplakin (PPL), a member of the plakin family of proteins that localizes to desmosomes and intermediate filaments, is downregulated in human esophageal squamous cell carcinoma (ESCC). Little is known, however, about the molecular mechanism underlying the regulation of PPL expression and the contribution of PPL loss to the malignant property of the cancer is unclear. We demonstrated that PPL mRNA expression was significantly reduced in ESCC tissues compared with that in normal tissues. Therefore, we hypothesized that CpG hypermethylation is the cause of the downregulation of PPL. Bisulfite-pyrosequencing of 17 cases demonstrated that the frequency of PPL methylation was higher in ESCC tissues than in normal tissues. When human ESCC cell lines were treated with 5-aza-2′-deoxycytidine (5-aza-dC), a DNA-methyltransferase inhibitor, PPL transcription was induced. Human KYSE270 ESCC cells do not stratify under ordinary culture conditions and rarely produce desmosomes; however, the forced expression of PPL promoted cell stratification. PPL induction also promoted adhesion to extracellular matrix but delayed cell migration. The abundance of desmosome-like structures was greatly increased in PPL transfectant as determined by transmission electron microscopy. Very low expression of another desmosome protein EVPL in ESCC, even in PPL transfectant, also supported the significant role of PPL in desmosome formation and cell stratification. Our results first indicate that the downregulation of PPL mediated by DNA hypermethylation, which may play an important role in the loss of ESCC stratification and likely in metastatic phenotype.
Cancer Medicine 01/2015; 4(3). DOI:10.1002/cam4.369 · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We review 7 cases of cancer in the reconstructed gastric tube after resection for esophageal cancer in our hospital. From this experience, we report 2 cases which were resected curatively by endoscopic or open surgery. Case 1, a 61-year-old man received a subtotal esophagectomy reconstructed by a gastric tube, retromediastinally. 85 months after operation, cancer in the gastric tube was detected endoscopically, and partial resection was performed. Case 2, a 75-year-old man received subtotal esophagectomy reconstructed by a gastric tube via a retro-mediastinal route. After 104 months, early cancer in the gastric tube was diagnosed and we performed endoscopic mucosal dissection (ESD). Long-term follow-up by regular endoscopy is necessary in patients after esophageal surgery to screen for cancer in the reconstructed gastric tube.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 07/2009; 106(6):793-9.
[Show abstract][Hide abstract] ABSTRACT: The Sd(a) blood group carbohydrate structure is expressed in the normal gastrointestinal mucosa. We reported previously that the expression of Sd(a) carbohydrate structures and beta1,4-N-acetylgalactosaminyltransferase (beta1,4GalNAcT) activity responsible for Sd(a) synthesis were remarkably decreased in cancer lesions of the gastrointestinal tract. In this study, we found that Sd(a) antigen was expressed mainly in chief cells of normal stomach but not in cancer tissue by immunohistologic staining. In separated gastric mucosal cells, the Sd(a) glycolipids and beta1,4GalNAcT activity were concentrated in a fraction that contained chief cells as a major population. We cloned the cDNA encoding the glycosyltransferase that catalyzes the synthesis of Sd(a) (Sd(a)-beta1,4GalNAcT). Introduction of this cloned cDNA into KATO III gastric or HT29 colonic cancer cell lines, which originally expressed the E-selectin ligands, sialyl Lewis(x) and sialyl Lewis(a), resulted in a marked increase in cell-surface expression of Sd(a) along with the concomitant total loss of both sialyl Lewis(x) and sialyl Lewis(a). Both KATO III and HT29 cells transfected with the Sd(a)-beta1,4GalNAcT gene showed significantly decreased adhesion to activated human umbilical vein endothelial cells when compared with mock-transfected cells. Sd(a) determinants showed no direct binding to Siglec-3, -5, -7, and -9. These Sd(a)-beta1,4GalNAcT-transfected cells showed strikingly reduced metastatic potential in vivo when compared with mock-transfected cells. In summary, forced expression of Sd(a) carbohydrate determinant caused remarkable elimination of carbohydrate ligands for selectin and reduced metastasis of human gastrointestinal tract cancer cells.
Cancer Research 08/2005; 65(14):6220-7. DOI:10.1158/0008-5472.CAN-05-0639 · 9.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GISTs) are a specific and rare subset of human gastrointestinal tract tumors. Most GISTs show gain-of-function mutations of KIT, mainly in exon 11, that always maintain the reading frame. We report on data from a 43-year-old Japanese man with recurrent duodenal GIST and a frameshift mutation in KIT exon 13 together with an in-frame deletion in KIT exon 11 detected by genomic DNA sequencing. Deletion of 48 base pairs of KIT exon 11, which preserved the reading frame, was identified in both primary and recurrent tumors, whereas deletion of one nucleotide of codon 642 of KIT exon 13, which changed the reading frame and induced a novel stop codon at amino acid 644, was found only in the recurrent tumor. The predicted protein resulting from the latter would lack part of the kinase domain. To the best of our knowledge, this is the first documentation of a GIST with a frameshift mutation of KIT.
Genes Chromosomes and Cancer 02/2005; 42(2):179-83. DOI:10.1002/gcc.20110 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 58-year-old female was admitted because of hematoemesis and melena. Endoscopic examination was performed down to the 2nd portion of the duodenum but did not disclose obvious bleeding site. The gastrointestinal hemorrhage recurred and the patient became shock. Endoscopic examination eventually revealed duodenal varices at the angle of descending and horizontal portion of the duodenum. We tried to control bleeding with cyanoacrylate injection, but rebled two days later. Endoscopic variceral ligation was performed and it was successful for hemostasis. It seems to be necessary to perform endoscopic examination down to horizontal portion of the duodenum if upper gastroenterological bleeding is suspected and no obvious bleeding site is defined, especially in the case of portal hypertension. For a further therapy, more discussion about choices is needed.