PubMed Health⌕ Search

Biomedical subjects

Kazuo Konishi

Publications and source records attributed to Kazuo Konishi.

At least 19 recordsLinked to original sources
PubMed2006

Sivelestat, a specific neutrophil elastase inhibitor, suppresses the growth of gastric carcinoma cells by preventing the release of transforming growth factor-alpha.

Neutrophil elastase is a neutral serine proteinase produced by polymorphonuclear leukocytes and monocytes/macrophages, especially under surgical stress. In the present study, we investigated whether NE promotes cell growth by activation of EGFR to elucidate whether surgical stress induces tumor proliferation and progression. Furthermore, we examined the antitumor effect of a specific NE inhibitor, sivelestat. Cell growth assays were carried out in vitro and in vivo using TMK-1 gastric cancer cells. TMK-1 cell growth was stimulated to 118% of that of the control cells after 48 h stimulation with 1 microg/mL NE according to an MTT assay. Sivelestat inhibited cell growth to 23.4 and 58.0% of control values at concentrations of 100 and 1,000 microg/mL, respectively. NE rapidly phosphorylated EGFR in only 5 min and triggered the ERK1/2-mitogenic signaling pathway in TMK-1. It was further demonstrated that NE-induced EGFR phosphorylation was transactivated through TGF-alpha, using ELISA. NE increased the cleavage of TGF-alpha from the cell surface 30-fold compared with the cells without treatment. Interestingly, sivelestat significantly reduced NE-induced EGFR phosphorylation and ERK1/2 activation and completely blocked the release of TGF-alpha from the TMK-1 cell surface. In a xenograft study, the addition of ventrotomy as a surgical stress promoted tumor growth. Sivelestat significantly suppressed the tumor growth induced by surgical stress. These results indicate that sivelestat suppresses the growth of gastric cancer cells by inhibiting the release of TGF-alpha stimulated by NE, which often occurs after surgical stresses.

Animals↗
PubMed2006

Synergistic effects of docetaxel and S-1 by modulating the expression of metabolic enzymes of 5-fluorouracil in human gastric cancer cell lines.

We have recently demonstrated in a Phase I/II study that combination chemotherapy with docetaxel (TXT) and S-1 is active against metastatic gastric carcinomas. To elucidate the mechanisms underlying the synergistic effects of these drugs, both the growth inhibitory effects and the expression profiles of enzymes involved in fluorouracil (5-FU) metabolism were examined in vitro and in vivo. TXT alone and in combination with 5-FU inhibited the growth of each of the 5 gastric cancer cell lines that we examined (TMK-1, and MKN-1, -28, -45 and -74), in a time- and dose-dependent manner. Moreover, striking synergistic effects were observed in TMK-1 cells in vitro with IC50 values of between 4.73 and 0.61 nM 5-FU. Furthermore, in TMK-1 xenografts, 5-FU/TXT cotreatments exhibited synergistic antitumor effects. The combination of S-1 and TXT, however, exhibited greater growth-inhibitory effects than the 5-FU/TXT cotreatments. The mechanisms underlying these synergistic effects of S-1 and TXT were examined by expression and activity analyses of the 5-FU metabolic enzymes. The expression of thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) were decreased 50 and 73% of control levels, respectively, and that of orotate phosphorybosyl transferase (OPRT) was increased by 3.9-fold at the protein level. These findings suggested that biochemical modulation of the 2 drugs had occurred, which was further confirmed by the results of the activity assays. These data strongly indicate that a combination chemotherapy of TXT and S-1 is effective against gastric carcinomas and is therefore a good candidate as a standard chemotherapeutic strategy in treating these tumors.

Animals↗
PubMed2006

Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: We retrospectively investigated long-term toxicity after concurrent chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC). METHODS: Concurrent chemoradiotherapy was performed in 110 patients with T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil 400 mg/m(2) per 24 h on days 1 to 5 and 8 to 12, combined with 2-h infusion of cisplatin 40 mg/m(2) on days 1 and 8. Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was administered concomitantly with chemotherapy. A course schedule with a 3-week treatment and a 2-week break was applied twice, with a total radiation dose of 60 Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema was adopted. RESULTS: A total of 81 patients were recruited in patients with stage I to IVA. Of 34 patients with complete response, 1 patient died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in 3 patients, 1 patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients; pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and 1 patient, respectively. CONCLUSIONS: Definitive chemoradiotherapy for ESCC is effective with substantial toxicities. Further investigation is warranted to minimize the normal tissue toxicities.

Aged↗
PubMed2006

Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components.

OBJECTIVES: The purpose of this study was to perform histopathologic and immunohistochemical analyses of gastric transcription factor SOX2 and gastric mucin MUC5AC to better understand the stepwise progression of pancreatic carcinoma. METHODS: Twenty-eight representative sections from 14 surgically resected pancreatic carcinomas were assessed microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma (IDC) were determined. The expression of SOX2 and MUC5AC in PanIN and IDC was examined immunohistochemically. RESULTS: One hundred thirty-eight PanINs were identified. In 4 of the 14 cases, gradual transition from PanIN-1A to PanIN-3 was observed in a single duct, suggesting stepwise progression. The expression of MUC5AC increased with the progression of lesions from PanIN-1A to PanIN-3. SOX2 was expressed in only 6 of 107 early PanINs (5.8%). Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis. In addition, SOX2 was frequently and strongly expressed in poorly differentiated (57.1%) and neurally invasive (63.6%) components. CONCLUSIONS: The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.

Aged↗
PubMed2006

Expression of gastric mucin MUC5AC and gastric transcription factor SOX2 in ampulla of vater adenocarcinoma: comparison between expression patterns and histologic subtypes.

The purpose of this study was to examine the expression pattern of MUC5AC and SOX2 in ampulla of vater adenocarcinoma and evaluate the association between expression of these gastric epithelial markers and the histologic phenotype of ampulla of vater carcinoma. Six surgically resected samples of ampulla of vater adenocarcinoma, including four intestinal type carcinomas and two pancreatobiliary type carcinomas, were studied. We performed immunohistochemistry with a monoclonal antibody against MUC5AC and a polyclonal anti-SOX2 antibody. In two of the four intestinal type carcinomas, MUC5AC and SOX2 were focally expressed in the superficial neoplastic mucosa. However, in the centre of the tumour and in other invasive lesions, including vascular invasive lesions and metastatic lymph nodes, neither MUC5AC nor SOX2 was expressed. In contrast, in both pancreatobiliary type carcinomas, expression of MUC5AC and SOX2 was maintained or increased in invasive lesions. Our immunohistochemistry data suggest that MUC5AC and SOX2 are associated with the pancreatobiliary phenotype of ampulla of vater carcinoma and involved in later events in carcinogenesis, such as invasion and metastasis.

Adenocarcinoma↗
PubMed2006

The expression profiles of orotate phosphoribosyltransferase and dihydropyrimidine dehydrogenase in gastric cancer and their clinical significance.

Orotate phosphoribosyltransferase (OPRT) is an enzyme that causes the activation of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is known to catabolize 5-FU, which is widely used in chemotherapeutic treatments for patients with a variety of malignant tumors including gastric and colorectal cancer. The expression and activities of these two enzymes therefore play important roles in the response of cancer patients to chemotherapy. However, little is known about the expression of these enzymes in gastric cancer. In the present study, we further elucidate the expression patterns of ORPT and DPD and their clinicopathological significance by immunohistochemical analysis in 221 and RT-PCR in 36 gastric cancer samples. The expression of OPRT by immunohistochemical analysis was detected in 117 (52.9%) cases, whereas DPD was detected in 66 (29.9%) cases. Moreover, the level of expression of OPRT was found to correlate with the depth of tumor invasion and a poorer prognosis. Although the mRNA and protein expression of OPRT and DPD levels did not correlate, an inverse correlation in the expression of OPRT and DPD was observed by RT-PCR. The survival benefit of post-operative adjuvant chemotherapy could not be confirmed in our present analysis. However, among the patients who had received such treatment with 5-FU or its derivatives, the prognosis in cases with low DPD levels was better than that in cases with high DPD expression by immunohistochemical analysis. These results indicate that the expression of OPRT and DPD are important predictors of both survival and the response to adjuvant chemotherapy in gastric cancer patients.

Adenocarcinoma↗
PubMed2005

Intractable gastrointestinal bleeding from angiodysplasia in a patient of Bernard-Soulier syndrome--report of a case--.

We herein report a case of gastrointestinal bleeding induced by angiodysplasia of the cecum in a case of Bernard-Soulier syndrome with recurrent breast cancer. In spite of endoscopic hemostatic therapy and interventional embolization, she had repeated massive bleeding from the cecal lesion. In addition, she had chronic hepatitis C and progressive liver tumors metastasized from breast cancer, and she finally died of hepatic failure. There are four case reports in the literature describing Bernard-Soulier syndrome with gastrointestinal bleeding angiodysplasia. The reported cases benefited from hormonal, endoscopical hemostasis and surgical therapy. In our case, because of her terminal metastatic breast cancer, only conservative treatments were administered after the third bleed. Both the endoscopic hemostatic method and interventional embolization showed only a temporary effect. Surgical treatment should be considered if the general condition can tolerate a surgical procedure.

Angiodysplasia↗
PubMed2004

Molecular differences between sporadic serrated and conventional colorectal adenomas.

PURPOSE: The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs). EXPERIMENTAL DESIGN: We evaluated the proliferative activity and molecular alterations in 47 SAs (25 pure-type and 22 mixed-type), 71 CADs, and 23 HPs. RESULTS: The proliferative activity of SAs, as evaluated by Ki-67 expression, was intermediate between CADs and HPs. There was no significant difference in the incidence of KRAS or p53 mutations between the three histological groups. In the microsatellite instability (MSI) analysis, 21% of SAs (9 of 43) showed MSI at two or more loci (MSI-H); corresponding values were 5% of CADs (3 of 64) and 8% of HPs (1 of 13; SAs versus CADs, P = 0.0125). MSI-H was more likely to be found in pure-type SAs (36%; 8 of 22) than in mixed-type SAs (5%; 1 of 21; P = 0.0212). Loss of hMLH-1 expression was found in 8 of 9 SAs with MSI-H. The incidence of BRAF or KRAS mutations was 36 and 15% of SAs, respectively; the combined incidence of BRAF and KRAS mutations occurred in 49% of SAs. However, there was no significant difference in the incidence of BRAF or KRAS mutations between SAs with and without MSI-H. CONCLUSIONS: Genetic instability is more frequently implicated in the tumorigenesis of SAs, especially pure-type SAs, than in that of CADs. In contrast, activation of the Ras/Raf/MEK/MAP kinase cascade by BRAF or KRAS mutation, independently of the genetic instability, may be associated with the progression of about half of SAs.

Adaptor Proteins, Signal Transducing↗
PubMed2004

A case of cervical paraganglioma: usefulness of FDG PET imaging and a possibility of rare origination.

Cervical paragangliomas are rare tumors derived from neural crest cells. Anatomic imaging techniques rely upon the characteristic spatial relations and the high vascularity of this tumor. Results of computed tomography (CT), magnetic resonance imaging (MRI), and arteriography initially led us to the preoperative diagnosis of cervical paraganglioma. In our case, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET), a type of functional imaging, was also carried out and demonstrated abnormally increased tracer uptake; this approach was thus successful for visualizing paraganglioma. FDG PET imaging may be useful in the detection of benign paraganglioma. On surgical exploration of the neck, the tumor was found to arise from the vagus nerve, whereas the hypoglossal nerve was encompassed by the tumor in its upper portion. The intraoperative findings suggested the possibility that the tumor had arisen from the hypoglossal nerve.

Adult↗
PubMed2004

Application of modified transmastoid approach methods to congenital atresia of the external ear canal with middle ear infection.

OBJECTIVE: To present our surgical technique for congenital atresia of the external ear canal with middle ear infection. METHODS: A modified transmastoid approach to congenital atresia of the external ear canal with middle ear infection was applied. Our method is to visualize the landmarks of the mastoid cavity such as the antrum, sinodural angle and digastric ridge by the canal-open method to avoid facial nerve injury and then prepare a relatively large external ear canal with reconstruction of the posterior wall of the external ear canal. RESULTS AND CONCLUSION: This method is suitable not only for treating congenital atresia of the external ear canal with middle ear infection, but also for avoiding facial nerve injury and postoperative complications such as re-stenosis of the new ear canal and postoperative middle ear infection.

Adult↗
PubMed2004

Positional and positioning nystagmus in healthy subjects under videonystagmoscopy.

OBJECTIVE: The eye-focused video camera as sensitive to infrared light is very useful for detecting nystagmus with open eyes in the dark. The existence of physiological nystagmus has been reported. We investigated how frequently physiological positional and positioning nystagmus is seen in healthy individuals under infrared video goggles. MATERIALS AND METHODS: Eighty-nine healthy individuals were examined in this study. Positional and positioning nystagmus was examined with infrared video goggles. RESULTS: Positional nystagmus could be detected in 65 of the 89 subjects under infrared video goggles. The majority of nystagmus was horizontal nystagmus, and vertical nystagmus was also seen in four subjects. Nystagmus was most frequently recognized in right or left shoulder down position. Positioning nystagmus was detected in 40 subjects. CONCLUSIONS: Positional and positioning nystagmus frequently exist in healthy subjects. This finding means that the existence of physiological nystagmus must be considered when diagnosing dizzy patients using this equipment.

Adult↗
PubMed2003

Longterm control of advanced and recurrent gastric cancer (ARGC) by S-1.

BACKGROUND: An oral tegafur compound, S-1 (TS-1), was developed to potentiate antitumor activity and to reduce gastrointestinal toxicities for patients with gastric cancer. It has achieved a high response rate against advanced and recurrent gastric cancer (ARGC) in Japan; however, the efficacy and adverse reactions of longterm administration of S-1 remain to be elucidated. METHODS: Sixty-nine patients with ARGC treated with S-1 were studied; 58 patients had measurable lesions, while 11 patients did not. S-1 was orally administered at doses of between 40 and 60 mg/body twice daily for 28 days, followed by 14 days' rest, as one course. RESULTS: The overall response rate was 38% (complete response [CR], 2/58; partial response [PR], 25/58; stable disease [SD], 9/58 progressive disease [PD] 23/58). Response rate by target organ was 40% for the primary lesion, 45% for lymph node metastasis, 38% for peritoneal metastasis, and 25% for liver metastasis. When S-1 was administered as second-line chemotherapy (n = 25), the response rate was 36%. Of the 69 patients, 14 received S-1 for more than a year. The median survival time (MST) after S-1 administration in these 14 patients, including 3 patients with stable disease, was 918 days (range, 536 to 1107 days). There were no grade 3 to 4 toxicities in these 14 patients receiving longterm therapy with S-1. CONCLUSION: S-1 therapy was performed with a high response rate, irrespective of the target organ or the presence of prior chemotherapy. Longterm administration of S-1 may benefit patients with ARGC, providing prolonged disease control with acceptable toxicities.

Adult↗
PubMed2003

Primary small cell carcinoma of the stomach.

We report on an 80-year-old man with primary gastric small cell carcinoma (SmCC). He was admitted to hospital with hematemesis. An upper gastrointestinal examination revealed an irregularly ulcerated tumor, 60 mm in diameter, on the lesser curvature of the stomach body extending to the cardia. An endoscopic biopsy revealed a solid proliferation of intermediate-sized tumor cells with hyperchromatic nuclei and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for neuron-specific enolase and chromogranin A, but negative for carcinoembryonic antigen. No tumor was detected on examination of the chest. Therefore, primary gastric SmCC was diagnosed preoperatively. To date, only 38 cases of primary gastric SmCC, including our case, have been reported. By using endoscopic biopsy, approximately two-thirds of cases have been diagnosed incorrectly. In the reported cases of gastric SmCC, the endoscopic findings frequently indicated a submucosal tumor. Gastric SmCC is clinically aggressive and has an extremely poor prognosis, even when discovered at an early stage. Most patients with gastric SmCC die within 1 year of diagnosis. Although a standard treatment for gastric SmCC has not been established, intensive chemotherapy should be considered to promote long-term survival. We believe that careful examination, including immunohistochemical investigation, is necessary for determining the therapeutic strategy whenever gastric SmCC is suspected during endoscopy.

Aged↗
PubMed2003

A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: A prospective study.

BACKGROUND: Discrimination between neoplastic and non-neoplastic colorectal polyps is essential for determining appropriate treatment. The mucosal crypt pattern of polyps can be observed with a nonmagnifying colonoscope; however, mucosal crypt patterns are better seen by magnifying colonoscopy, which can also be a noninvasive means for predicting histopathology. This study prospectively compared the ability to distinguish between neoplastic and non-neoplastic lesions by magnifying and nonmagnifying colonoscopy. METHODS: Six hundred sixty patients were randomly assigned to undergo magnifying or nonmagnifying colonoscopy (2 groups each of 330 patients). The mucosal crypt pattern of colorectal lesions was classified into types I through V after spraying with 0.2% Indigo carmine dye. The histopathology of all lesions was confirmed by evaluation of endoscopic resection specimens or biopsy specimens. Only lesions 10 mm or less in diameter were included in the study. RESULTS: The accuracy of magnifying colonoscopy in distinguishing neoplastic from non-neoplastic lesions (92%, 372/405) was significantly higher than for nonmagnifying colonoscopy (68%, 278/407). Insertion of magnifying and nonmagnifying colonoscopes to the cecum was successful in, respectively, 321 patients (97%) and 317 patients (96%), with no significant differences in the average time to reach the cecum or average total procedure time. No serious complication was observed during or immediately after the examinations. CONCLUSIONS: Observation of mucosal crypt pattern with magnifying colonoscopy is superior to nonmagnifying colonoscopy for distinguishing between neoplastic and non-neoplastic colorectal lesions.

Colonic Polyps↗
PubMed2002

Evaluation of endoscopic ultrasonography in colorectal villous lesions.

BACKGROUND AND AIMS: The choice of therapeutic procedure for colorectal neoplasias depends largely on the depth of tumor invasion. This study examined the value of endoscopic ultrasonography (EUS) in determining whether local resection is applicable for colorectal villous lesions. MATERIALS AND METHODS: We performed EUS on 125 colorectal neoplasias classified into two categories, villous ( n=35) and nonvillous lesions ( n=90), according to their colonoscopic morphological features. We compared the EUS and clinicopathological findings for each lesion. RESULTS: The overall accuracy of EUS-based evaluation of tumor invasion depth was 60% in villous lesions and 91% in nonvillous lesions. In villous lesions 37% were overstaged and 3% understaged, and in of nonvillous lesions 6% were overstaged and 3% understaged. In differentiating mucosal neoplasias (M)/submucosal cancers with slight invasion (SM-s) from non-M/SM-s, the values in villous and nonvillous lesions were, respectively: sensitivity 60% and 86%, specificity 100% and 99%, and accuracy 66% and 96%. Large (>/=20 mm wide, >/=5 mm high) or rectal villous lesions were more likely than nonvillous lesions to be misjudged with regard to the differentiation between M/SM-s and non-M/SM-s. CONCLUSION: It is difficult to determine the depth of invasion in villous lesions, especially large or rectal lesions, using only EUS. EUS-based evaluation alone cannot determine the appropriate treatment for colorectal villous lesions.

Adenoma, Villous↗
PubMed2002

Unusual survival for more than 2 years with peritoneal metastases of gastric cancer.

We report a patient with peritoneal metastases who was successfully treated with a novel oral fluoropyrimidine anticancer drug, TS-1, as first-line chemotherapy. The patient was a 72-year-old man who had undergone curative resection for type 4 gastric cancer with peritoneal dissemination that was located only at the greater omentum. Final findings were P1, T4, N1, and stage IV. Eighteen months after the gastrectomy, his cancer recurred with peritoneal metastases; these were diagnosed by the presence of multiple stenoses of the colon, an abdominal mass, and elevated levels of the serum tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. He was treated with 100 mg/day of TS-1, given orally, for 28 days, followed by 14 days' rest, as one course. Two courses of the treatment resulted in a marked reduction of the abdominal tumor, without severe toxicity. After 3 courses, barium enema revealed dramatic improvement in the stenoses. Laparoscopy after 11 courses showed neither peritoneal dissemination, nor ascites, and peritoneal lavage cytology was negative. The serum tumor markers were reduced to almost normal levels. Two years after the onset of the peritoneal metastases, the patient is alive without any sign of progressive disease. Our report is the first to demonstrate the advantages of TS-1 as chemotherapy for the treatment of peritoneal metastasis of gastric cancer.

Aged↗
PubMed2002

Solitary metastasis to the left axillary lymph node after curative gastrectomy in gastric cancer.

Regional lymph node metastasis in advanced gastric cancer is common, whereas axillary lymph node metastasis (ALNM) is rare. We experienced a patient with a solitary ALNM in gastric cancer. A 48-year-old woman underwent curative distal gastrectomy for advanced gastric cancer (P0H0T3N3M0CY0, stage IV). Twenty-one months after the surgery, she complained of an asymptomatic left axillary tumor. Mammography and computed tomography (CT) scans showed the presence of tumors in neither breast nor lung. Fine-needle aspiration of the axillary tumor demonstrated poorly differentiated adenocarcinoma cells, which coincided with the cells of the resected gastric carcinoma. We diagnosed ALNM from gastric cancer and operated on the patient with radical left axillary lymph node dissection. One year after the reoperation, she has had no recurrence. We conclude that gastric cancer can metastasize to unusual sites. A re-radical resection is recommended if curative resection is feasible.

Adenocarcinoma↗