Tomoaki Suga

Implantation-Dependent Expression of Trophinin by Maternal Fallopian Tube Epithelia during Tubal Pregnancies: Possible Role of Human Chorionic Gonadotrophin on Ectopic Pregnancy

Trophinin, tastin, and bystin have been identified as molecules potentially involved in human embryo implantation. Both trophoblasts and endometrial epithelial cells express trophinin, which mediates apical cell adhesion through homophilic trophinin-trophinin binding. We hypothesized that trophinins function in embryo implantation is unique to humans and investigated the expression of trophinin, tastin, and bystin in ectopic pregnancy, a condition unique to humans. In tubal pregnancies, high levels of all three were found in both trophoblasts and fallopian tubal epithelia. Trophinin expression in maternal cells was particularly high in the area adjacent to the trophoblasts, whereas trophinin was barely detectable in intact fallopian tubes from women with in utero pregnancies or without pregnancies. When explants of intact fallopian tube were incubated with the human chorionic gonadotrophin (hCG), trophinin expression was enhanced in epithelial cells. Since the trophectoderm of the human blastocyst secretes hCG before and after implantation, these results suggest that hCG from the human embryo induces trophinin expression by maternal cells. As both beta-subunit of hCG and trophinin genes have diverged in mammals, the present study suggests a unique role of hCG and trophinin in human embryo implantation, including the pathogenesis of ectopic pregnancy.

Functional Correlation of Trophinin Expression with the Malignancy of Testicular Germ Cell Tumor

Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-β were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.

Antimicrobial resistance and characteristics of eradication therapy of Helicobacter pylori in Japan: a multi-generational comparison.

Eradication of Helicobacter pylori (H. pylori) at a younger age is considered to be effective in preventing gastric cancer. This study assessed the characteristics of eradication therapy in young patients.

The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer

Trophinin is a unique adhesion molecule expressed by human trophoblastic cells. Its activity and in vivo expression pattern implicate trophinin in the initial attachment of trophectoderm cells to maternal epithelia. Subsequent to apical adhesion, trophoblasts aggressively invade maternal tissue to form the placenta, a process resembling tumor invasion. Here, we report that trophinin is expressed in tumors from 64% of colon cancer patients (n = 50) and high trophinin expression is closely associated with poor prognosis. To determine the link between trophinin expression and malignancy, colon adenocarcinoma SW480 cells were stably transfected with trophinin. An invasion assay showed that trophinin‐expressing SW480 cells were more invasive than mock‐transfected cells. Microarray analysis comparing SW480 cells transfected with trophinin with mock‐transfected cells identified high‐mobility group box 1 (HMGB1) as the most significantly elevated transcript. Immunohistochemical analysis of tumors from the colorectal cancer patients confirmed positive correlation of HMGB1 protein expression in the nucleus to trophinin expression in tumor. HMGB1 and its ligand RAGE (the receptor for advanced glycation end product) proteins were coexpressed in 65.6% of trophinin‐positive patients (n = 32). These results suggest that trophinin promotes invasion through a mechanism involving HMGB1/RAGE.

Helicobacter pylori-Negative Primary Rectal MALT Lymphoma: Complete Remission after Radiotherapy

Rectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare condition. Although the majority of patients undergo surgical resection, a definitive treatment for rectal MALT lymphoma has not yet been established. In the present study, we report the outcome of radiotherapy in 3 patients with rectal MALT lymphoma. Our cohort ranged from 56 to 65 years of age. The male/female ratio was 1:2, and all patients were in stage I (Lugano classification) of the disease. Endoscopic findings revealed elevated lesions resembling submucosal tumors in 2 patients, and a sessile elevated lesion with a nodular surface in 1 patient. One of the 3 patients underwent magnifying endoscopy with crystal violet staining that demonstrated a type I pit pattern (Kudo’s classification) lesion with a broad intervening area caused by the upthrust of the tumor from the submucosa. All patients tolerated radiotherapy at doses of 30 Gy without major complications and achieved complete remission. Follow-up ranged from 13 to 75 months (mean 51.0 months), revealing no recurrence of MALT lymphoma. As such, we propose radiotherapy to be a safe and effective means for treating rectal MALT lymphoma.

Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma – a possible biomarker to predict the malignant potential of Barrett's oesophagus

Gastric gland mucin contains O‐glycans exhibiting terminal α1,4‐linked N‐acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barretts oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barretts adenocarcinoma (BAC).

Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy

The existence of other primary tumors during the treatment and management of gastric cancer (GC) is an important issue. The present study investigated the prevalence and management of synchronous colorectal neoplasms (CRN) in surgically treated GC patients.

Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.

Screening to Identify and Eradicate Helicobacter pylori Infection in Teenagers in Japan

The purpose of this study was to elucidate the prevalence and effect of Helicobacter pylori infection in Japanese teenagers. The study subjects were students ages 16 to 17 from one high school studied between 2007 and 2013. Students who tested positive on this screening examination underwent esophagogastroduodenoscopy and biopsy samples to determine their H pylori status using culture and histology. Cure of H pylori infections was determined by urea breath test. The low rate of prevalence of H pylori infection in present Japanese teenagers makes it possible and cost effective to perform examinations and carry out treatment of this infection in nationwide health screenings of high school students.

A case of Helicobacter heilmannii-associated primary gastric mucosa-associated lymphoid tissue lymphoma achieving complete remission after eradication

A 46-year-old man underwent gastrointestinal endoscopy while visiting the hospital for a general physical check-up. Coarse mucosa in the antrum with superficial erosions was found by endoscopic gastrointestinal examination, but no atrophic changes were seen in the corpus. Histopathological examination of gastric biopsy specimens revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Although Helicobacter pylori was not detected in our patient, H. heilmannii was identified histologically and by polymerase chain reaction analysis, resulting in the diagnosis of H. heilmannii-associated gastric MALT lymphoma. We successfully eradicated H. heilmannii and achieved complete remission of gastric MALT lymphoma by antibiotic therapy. H. heilmannii usually causes milder gastritis than H. pylori, but it has been more closely associated with MALT lymphoma. As such, when H. pylori infection is excluded in patients with gastric MALT lymphoma, physicians should next consider the possibility of H. heilmannii. Furthermore, our research suggests that eradication therapy is effective for treatment of localized H. heilmannii-associated gastric MALT lymphoma.