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Biomedical subjects

Yuichi Shimizu

Publications and source records attributed to Yuichi Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation.

Activation of the tumor suppressor protein p53 is a critical cellular response to various stress stimuli and to inappropriate activity of growth-promoting proteins, such as Myc, Ras, E2F, and beta-catenin. Protein stability and transcriptional activity of p53 are modulated by protein-protein interactions and post-translational modifications, including acetylation. Here, we show that inappropriate activity of prothymosin alpha (PTMA), an oncoprotein overexpressed in human cancers, triggers a p53 response. Overexpression of PTMA enhanced p53 transcriptional activity in reporter gene assays for p53 target gene promoters hdm2, p21, and cyclin G. Overexpressed PTMA resulted in increased mRNA and protein levels for endogenous p53 target genes, hdm2 and p21, and in growth suppression. In contrast, reduction of endogenous PTMA through RNA interference decreased p53 transcriptional activity. Histone acetyltransferases (HATs) act as p53 coactivators and acetylate p53. PTMA, known to interact with HATs, led to increased levels of acetylated p53. PTMA did not increase the transcriptional activity of an acetylation-deficient p53 mutant, suggesting that p53 acetylation is an indispensable part of the p53 response to PTMA. Chromatin immunoprecipitation assays showed that excess PTMA associates with the p21 promoter and results in increased levels of acetylated p53 at the p21 promoter. Our findings indicate that overexpressed PTMA elicits a p53 response that involves p53 acetylation.

Acetylation↗
PubMed2006

Histologic results of EMR for esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by endoscopic biopsy.

BACKGROUND: Biopsy specimens obtained from esophageal lesions detected in endoscopic screening with iodine staining have often been diagnosed as high-grade intraepithelial squamous neoplasia (WHO 2000). However, a management strategy for such lesions has not been established. The purpose of this study was to perform EMR for such lesions and to determine the actual tumor stage in patients with complete resection and the outcomes after EMR. PATIENTS: During the study period, 51 patients were found to have esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by using endoscopic iodine staining in biopsy specimens. All of the patients underwent EMR, and resected specimens were reviewed microscopically. RESULTS: Histologic examination of totally resected specimens revealed that 12 (23.5%) of the 51 patients had tumor invasion of the lamina propria mucosae and that 4 (7.8%) had tumor invasion of the muscularis mucosae. The remaining 35 patients (68.6%) were confirmed to have high-grade intraepithelial squamous neoplasia. The invasive focus in all of the 16 lesions of invasive squamous-cell carcinoma was surrounded by high-grade intraepithelial squamous neoplasia. After a median of 23 months of follow-up, there were two recurrences, and those patients required second EMR. CONCLUSIONS: Histologic results suggested that high-grade intraepithelial squamous neoplasia of the esophagus has characteristics of carcinoma in the preinvasive stage. EMR should be performed for esophageal lesions diagnosed by endoscopic biopsy as high-grade intraepithelial squamous neoplasia, not only because of its probable malignant potential but also because more than 30% of such lesions are actually invasive carcinoma.

Aged↗
PubMed2006

Endoscopic submucosal dissection for treatment of early stage hypopharyngeal carcinoma.

BACKGROUND: Early detection of hypopharyngeal carcinoma is increasingly possible and patients with such early lesions can be treated with endoscopic resection. OBJECTIVE: To identify the optimal relationship between the mucosal defect of the hypopharynx and malfunction of the hypopharynx after endoscopic resection of early hypopharyngeal carcinoma. DESIGN: Case series. SETTING: Referral center in Japan. PATIENTS: Four patients with early-stage squamous cell carcinoma of the hypopharynx underwent endoscopic submucosal dissection (ESD). By using ESD, an accurate incision line close to the tumor margin could be confirmed while performing treatment. ESD was performed with a small-caliber-tip transparent hood (ST-hood) to open the incision line for better visualization of the submucosa. MAIN OUTCOME MEASUREMENTS: Feasibility of en bloc resection, complications, and recurrence after ESD. RESULTS: No early or late complications due to treatment occurred in the patients. Histological examination of resected specimens revealed that 2 patients had carcinoma in situ and 2 patients had tumor invasion of the subepithelium. There was no local recurrence or distant metastasis in any of the patients during the follow-up period (3-14 months). CONCLUSIONS: We consider that ESD is the optimal method for endoscopic resection not only because it enables an en bloc resected specimen to be obtained but also because it can prevent removal of excess mucosa of the hypopharynx, which is a very narrow and important organ related to swallowing and speech.

Aged↗
PubMed2004

EMR combined with chemoradiotherapy: a novel treatment for superficial esophageal squamous-cell carcinoma.

BACKGROUND: Esophagectomy or chemoradiotherapy (CRT) are the procedures of choice for patients with superficial esophageal squamous-cell carcinoma. However, esophagectomy is highly invasive, and CRT is associated with the risk of local failure. A study was conducted of a novel treatment, EMR combined with CRT, for patients with superficial esophageal carcinoma. EMR was performed for the purpose of complete local tumor control and chemoradiotherapy was performed for regional and distant control. METHODS: EMR combined with CRT was performed for patients with esophageal carcinoma invading the muscularis mucosae or upper submucosa who refused esophagectomy. The planned treatment after EMR was 40 to 46 Gy of external beam radiation to the mediastinum, including the supraclavicular fossa or cardia. Chemotherapy was given during weeks 1 and 5 (5-fluorouracil, 700 mg/m(2) per 24 hours in a 120-hour infusion, and cisplatin 15 mg/m(2) per day intravenously on days 1 to 5). RESULTS: During the study period, 16 patients underwent EMR combined with CRT (EMR plus CRT group) and 39 patients with similar stage cancer underwent esophagectomy (surgical resection group). None of the patients in the EMR plus CRT group have had local recurrence or metastasis. Overall survival rates at 5 years in the EMR plus CRT and surgical resection groups were estimated to be, respectively, 100% and 87.5%. CONCLUSIONS: Although this study was not randomized, the results suggest that EMR combined with CRT is a safe and effective method for treating patients with superficial esophageal carcinoma. The results were equivalent or, in view of the lower degree of invasiveness, superior to surgical resection.

Aged↗
PubMed2004

Endoscopic clip application for closure of esophageal perforations caused by EMR.

BACKGROUND: With increasing use of EMR for early stage esophageal carcinoma, the number of cases of iatrogenic esophageal perforation is likely to increase. This study evaluated the results of endoscopic clip application for treatment of perforations caused by EMR in patients with esophageal carcinoma. METHODS: Among 185 patients who underwent EMR for esophageal carcinoma, esophageal perforation occurred in 3 patients (1.6%). Metallic clips were immediately applied endoscopically to close the perforations. OBSERVATIONS: All 3 patients were observed closely and were managed conservatively (intravenous hyperalimentation, antibiotics) after closure of the perforation. They were discharged without any further serious complication. CONCLUSIONS: When esophageal perforation caused by EMR is immediately recognized, endoscopic application of metallic clips is appropriate therapy. However, patients must be carefully monitored for the development of generalized mediastinitis.

Aged↗
PubMed2004

[Immunological rapid urease test].

Immunological rapid urease test for detection of Helicobacter pylori infection, composed of a solid-phase tip coated with monoclonal antibody against H. pylori's urease and ion-sensitive field transistor (ISFT)-based pH sensor system, was developed. The monoclonal antibody against H. pylori's urease was useful to avoid the contamination of urease activity in other bacteria. Because ISFTT had high ability to detect pH change, the sensitivity and specificity of immunological rapid urease test was significantly improved comparing with that of conventional rapid urease test. The utility of immunological rapid urease test was evaluated in some clinical studies.

Antibodies, Monoclonal↗
PubMed2003

Relationship between histopathologic gastritis and mucosal microvascularity: observations with magnifying endoscopy.

BACKGROUND: The purpose of this study was to determine the usefulness of magnifying endoscopy for the diagnosis of Helicobacter pylori-induced histopathologic gastritis. METHODS: A total of 92 patients scheduled to undergo routine endoscopic examination were enrolled. After routine endoscopic examination, 3 sites in the stomach were studied by magnified observation. Visualized collecting venulae were classified into the following 3 patterns: regular, irregular, and obscured. The sites observed by magnifying endoscopy were assessed histopathologically with an Updated Sydney System; 4 morphologic parameters (activity, inflammation, atrophy, metaplasia) were assessed and graded from 0 to 3. RESULTS: The regular pattern cases were negative for H pylori infection at all sites observed by magnifying endoscopy (antrum greater curve, 0/11; body greater curve, 0/24; body lesser curve, 0/23). The scores for all 4 morphologic parameters were significantly lower in the regular pattern group than the irregular and obscured groups (p < 0.01). The value of the atrophy parameter in the irregular group was significantly higher than that in the obscured group (p < 0.05 for a single test of hypothesis; correction for multiple testing of data removed significance). CONCLUSION: Visibility of collecting venulae in the gastric mucosa is influenced by H pylori-induced histopathologic gastritis. Magnifying endoscopy is useful for the diagnosis of histopathologic gastritis.

Cohort Studies↗
PubMed2003

[Rapid urease test].

Rapid urease test(RUT) is one of the invasive methods for detection of H. pylori infection. H. pylori in the biopsy specimen splits the urea to ammonia in the test container. Elevation of pH by ammonium hydroxide are detected as color change of pH indicator. The advantage of RUT are low-priced, easy-to-use, and rapid time to diagnosis. The disadvantage of RUT are necessity of endoscopy performance and occurrence of false negative. RUT is useful for diagnosis of H. pylori infection before and after eradication treatment. However, the sensitivity of RUT is comparatively low within 6 months after completion of eradication.

Biopsy↗
PubMed2002

Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper.

BACKGROUND: Endoscopic mucosal resection is recommended for squamous cell carcinoma of the esophagus confined to the lamina propria. However, endoscopic mucosal resection is often performed in patients with tumors that invade the muscularis mucosa or upper submucosa to minimize surgical invasiveness, despite the increased risk of lymph node metastasis. This study prospectively evaluated long-term outcome in such patients. METHODS: Twenty-six consecutive patients with squamous cell esophageal carcinoma invading the muscularis mucosa or submucosa who underwent endoscopic mucosal resection from June 1992 through March 2000 (extended endoscopic mucosal resection group) were studied. As control group, 44 consecutive patients with esophageal carcinoma invading the muscularis mucosae or upper third of the submucosa and no preoperative evidence of lymph node metastasis who underwent esophagectomy during the same period (surgical resection group) were studied. RESULTS: Overall survival rates at 5 years in the extended endoscopic mucosal resection group and surgical resection group were, respectively, 77.4% and 84.5%. There was no significant difference between survival distributions. Cause-specific survival rates at 5 years in extended endoscopic mucosal resection and surgical resection groups were, respectively, 95.0% and 93.5%. Survival curves for the groups were similar. CONCLUSION: Although patients were not randomized to extended endoscopic mucosal resection or surgical resection in this study, the results suggest that endoscopic mucosal resection may be safe and effective for management of squamous cell esophageal carcinoma invading the muscularis mucosae or upper submucosa.

Adult↗
PubMed2002

Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer.

BACKGROUND: The optimum management of esophageal cancers with synchronous second primary cancer (SPC) has not been determined. The aim of this study was to evaluate the efficacy of intense screening and treatment for esophageal cancers with synchronous SPC. METHODS: Between 1981 and 1997, 1479 patients with esophageal cancers were screened for synchronous SPC during the process of initial staging. Radical treatment was recommended for esophageal cancer and synchronous SPC in cases for whom both cancers were curable. Treatment results for esophageal cancer patients with or without synchronous SPC were compared. RESULTS: Among 1479 patients, 155 (10.5%) were found to have 166 synchronous SPC. Primary sites included the stomach in 65, the head and neck in 44, the colon/rectum in 27, the lung in 14 and other sites in 16 patients. Clinical stages of synchronous SPC were stage I in 41%, stage II in 20%, stage III in 25% and stage IV in 14%. The 5-year overall survival rates by clinical stages of esophageal cancers (stage 0, I, II, III, IV) in patients with synchronous SPC were 51% (95% CI, 23-78%), 43% (95% CI, 18-68%), 11% (95% CI, 0-22%), 14% (95% CI, 0-28%) and 12% (95% CI, 1-22%), respectively. The 5-year overall survival rate for patients with or without synchronous SPC were 20% (95% CI, 13-28%) and 32% (95% CI, 29-35%), respectively. No significant difference was observed between both groups (p = 0.2562). CONCLUSIONS: Intense screening and treatment may be justifiable in the light of the high detection rate of curable SPC and the reasonable survival of patients with synchronous SPC. However, a prospective study including cost-benefit analysis is needed to provide the evidence to justify the intense screening and treatment.

Adult↗