Japanese journal of clinical oncology, Jan 12, 2016
Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it rem... more Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it remains unknown whether treatment of early hepatocellular carcinoma can actually result in cure. This study was performed to clarify the cancer risk of the background liver after treating early hepatocellular carcinoma. Early hepatocellular carcinoma is defined as very well-differentiated cancer containing Glisson's triad. The cumulative incidence of classical hepatocellular carcinoma, hypervascular liver cancer detected on imaging studies, after resection of early hepatocellular carcinoma positive for anti-hepatitis C antibody (early hepatocellular carcinoma group, n = 105) was compared with that in patients with chronic liver disease positive for anti-hepatitis C antibody (control group, n = 751) and propensity score-matched patients after resection of classical hepatocellular carcinoma (classical hepatocellular carcinoma group, n = 105). After a median follow-up of 4.8 years (range, ...
Nippon Rinsho Japanese Journal of Clinical Medicine, Mar 1, 1996
Microsatellite polymorphisms are very important tool for linkage analysis. Now we can obtain some... more Microsatellite polymorphisms are very important tool for linkage analysis. Now we can obtain some very fine linkage maps and many highly polymorphic microsatellite markers for linkage analysis. We developed a new efficient system for analysis of microsatellite polymorphism using automated laser fluorescent DNA sequencer. Ordinary PCR method with RI labeled primer has been used for analysis of microsatellite polymorphism, but our system mainly consists of FITC labeled primer and DNA autosequencer. There are some benefits in this system such as short analysis time, easy handling, high safety, and use of computer that enable to automatically detect allele size, save raw data, and connect to linkage analysis program on line.
Hypovascular tumors associated with hepatocellular carcinoma (HCC) can be diagnosed, but it remai... more Hypovascular tumors associated with hepatocellular carcinoma (HCC) can be diagnosed, but it remains unknown whether such lesions should be treated immediately. This study aimed to clarify the clinical significance of treating hypovascular liver nodules. After diagnosis of hypovascular tumors smaller than 3 cm, 104 patients underwent liver resection immediately (Group 1), while 93 patients were placed under observation (Group 2). In Group 1, 98 patients were diagnosed as having HCC (Group 1'), while 80 patients in Group 2 underwent liver resection after vascularization or appearance of other hypervascular HCC (Group 2'), eight patients had been observed, and five patients could not undergo operation due to appearance of other multiple HCCs. To avoid lead time bias for tumor vascularization, survival rates of patients after diagnosis of hypovascular tumors as well as those after operation in the two groups were compared. After a median follow-up of 3.3 years (range 0.6-11.2), ...
Alcoholism Clinical and Experimental Research, 1992
The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 an... more The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.
Journal of Gastroenterology and Hepatology, Apr 1, 1998
Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated us... more Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H2 blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2 cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 +/- 1.3), peaked during the healing stage (15.4 +/- 2.8) and returned to the same level at the scarring stage (10.9 +/- 2.0) as normal controls (10.3 +/- 1.7). However, the index was not elevated in intractable ulcers (10.3 +/- 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.
The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a po... more The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a potent vasoconstrictor peptide, in the pathogenesis of ethanol (EtOH)-induced gastric mucosal injury. Two series of experiments were performed in anesthetized rats. First, we examined the time course of relationships among changes in ET-1 concentrations in gastric mucosal and portal plasma, gastric mucosal hemodynamics, and mucosal damage produced by EtOH. Intragastric EtOH stimulated release of endogenous ET-1 in gastric mucosal tissue. Plasma ET-1 concentrations in the portal vein also increased after intragastric EtOH administration. ET-1 concentrations in gastric mucosal tissue and portal plasma increased significantly before gastric mucosal hemorrhagic damage occurred. Moreover, 30 min after EtOH administration there were significant correlations between gastric mucosal ET-1 concentrations and both area of gastric hemorrhagic damage as well as concentration of EtOH administered intragastrically. After intragastric EtOH administration, increase in gastric mucosal hemoglobin concentration and decrease in gastric mucosal hemoglobin oxygen saturation, estimated using reflectance spectrophotometry, occurred within 2.5 min and continued throughout the experiments. The time course of microcirculatory changes correlated closely with increases in gastric mucosal ET-1 and portal plasma ET-1 concentrations after intragastric EtOH administration. Gastric microcirculatory disturbances induced by EtOH were associated with significant decreases in gastric mucosal ATP content. Second, we examined whether pretreatment with anti-ET-1 antibody protected against EtOH-induced mucosal injury by improving mucosal microcirculation. Pretreatment with anti-ET-1 antibody microscopically and macroscopically reduced gastric mucosal hemorrhagic damage induced by EtOH and significantly reduced EtOH-induced gastric microcirculatory disturbances and decreases in gastric mucosal ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
Nippon rinsho. Japanese journal of clinical medicine
Although many authors reported that proton pump inhibitor showed mucosal protective activity, the... more Although many authors reported that proton pump inhibitor showed mucosal protective activity, the precise mechanism is still unclear. In this study, we investigated the effect of proton pump inhibit on gastric mucosal hemodynamics, using a reflectance spectrophotometry system. The proton pump inhibitors had no effect on the gastric mucosal hemodynamics prior to the state of hemorrhagic shock state. However, during the hemorrhagic shock, proton pump inhibitors significantly inhibited the decrease in tissue oxygenation and significantly reduced ulcer formation. In conclusion, proton pump inhibitors maintained tissue oxygenation resulting in reduction of ulcer formation.
Abstract The influences of intravascular ethanol on gastric mucosal integrity and its relation to... more Abstract The influences of intravascular ethanol on gastric mucosal integrity and its relation to gastric circulation were investigated in rats. Ulcer formation of the gastric mucosa correlated with the blood ethanol concentration in the presence of 150 mM HCl in the rat ...
Nippon rinsho. Japanese journal of clinical medicine
In this review, various aspects of gastrointestinal microcirculation were described. Endothelin-1... more In this review, various aspects of gastrointestinal microcirculation were described. Endothelin-1, vasoconstrictor, is elevated in gastric mucosa, causes gastric ischemia and results in gastric ulceration in human and animals under physical stress. Vasodilators such as NO anticipate the alove actions of endothelin, and thereby protect mucosa from injury. Once ulcer is developed, angiogenesis plays a key role in its healing. Various growth factors, cyclooxygenases-1 and -2, and non-peptide angiogenic factors stimulate this phenomenon and participate in ulcer healing. However, acidic conditions, H. pylori and its product, ammonia, suppress angiogenesis in vitro and in vivo. These evidences may explain why ulcer heals so slowly in gastroduodenal mucosa.
Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colo... more Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (mCRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti-EGFR treatment. Here, We investigated the genome-wide DNA methylation status in metastatic colorectal cancer to identify associations between the methylation status and clinical response to anti-EGFR antibody. We retrospectively reviewed the medical records of 97 patients (45 patients for the 1st cohort and 52 patients for the 2nd cohort) who received anti-EGFR treatment for KRAS wild-type mCRC. Then, we analyzed the associations between the genome-wide DNA methylation status and clinical response to anti-EGFR treatment, and evaluated the predictive power and value of the methylation status statistically. As a result, each cohort was classified into the highly-methylated colorectal cancer (HMCC) and the low-methylated colorectal cancer (LMCC) subgroups by unsupervised clust...
Japanese journal of clinical oncology, Jan 12, 2016
Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it rem... more Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it remains unknown whether treatment of early hepatocellular carcinoma can actually result in cure. This study was performed to clarify the cancer risk of the background liver after treating early hepatocellular carcinoma. Early hepatocellular carcinoma is defined as very well-differentiated cancer containing Glisson's triad. The cumulative incidence of classical hepatocellular carcinoma, hypervascular liver cancer detected on imaging studies, after resection of early hepatocellular carcinoma positive for anti-hepatitis C antibody (early hepatocellular carcinoma group, n = 105) was compared with that in patients with chronic liver disease positive for anti-hepatitis C antibody (control group, n = 751) and propensity score-matched patients after resection of classical hepatocellular carcinoma (classical hepatocellular carcinoma group, n = 105). After a median follow-up of 4.8 years (range, ...
Nippon Rinsho Japanese Journal of Clinical Medicine, Mar 1, 1996
Microsatellite polymorphisms are very important tool for linkage analysis. Now we can obtain some... more Microsatellite polymorphisms are very important tool for linkage analysis. Now we can obtain some very fine linkage maps and many highly polymorphic microsatellite markers for linkage analysis. We developed a new efficient system for analysis of microsatellite polymorphism using automated laser fluorescent DNA sequencer. Ordinary PCR method with RI labeled primer has been used for analysis of microsatellite polymorphism, but our system mainly consists of FITC labeled primer and DNA autosequencer. There are some benefits in this system such as short analysis time, easy handling, high safety, and use of computer that enable to automatically detect allele size, save raw data, and connect to linkage analysis program on line.
Hypovascular tumors associated with hepatocellular carcinoma (HCC) can be diagnosed, but it remai... more Hypovascular tumors associated with hepatocellular carcinoma (HCC) can be diagnosed, but it remains unknown whether such lesions should be treated immediately. This study aimed to clarify the clinical significance of treating hypovascular liver nodules. After diagnosis of hypovascular tumors smaller than 3 cm, 104 patients underwent liver resection immediately (Group 1), while 93 patients were placed under observation (Group 2). In Group 1, 98 patients were diagnosed as having HCC (Group 1'), while 80 patients in Group 2 underwent liver resection after vascularization or appearance of other hypervascular HCC (Group 2'), eight patients had been observed, and five patients could not undergo operation due to appearance of other multiple HCCs. To avoid lead time bias for tumor vascularization, survival rates of patients after diagnosis of hypovascular tumors as well as those after operation in the two groups were compared. After a median follow-up of 3.3 years (range 0.6-11.2), ...
Alcoholism Clinical and Experimental Research, 1992
The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 an... more The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.
Journal of Gastroenterology and Hepatology, Apr 1, 1998
Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated us... more Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H2 blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2 cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 +/- 1.3), peaked during the healing stage (15.4 +/- 2.8) and returned to the same level at the scarring stage (10.9 +/- 2.0) as normal controls (10.3 +/- 1.7). However, the index was not elevated in intractable ulcers (10.3 +/- 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.
The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a po... more The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a potent vasoconstrictor peptide, in the pathogenesis of ethanol (EtOH)-induced gastric mucosal injury. Two series of experiments were performed in anesthetized rats. First, we examined the time course of relationships among changes in ET-1 concentrations in gastric mucosal and portal plasma, gastric mucosal hemodynamics, and mucosal damage produced by EtOH. Intragastric EtOH stimulated release of endogenous ET-1 in gastric mucosal tissue. Plasma ET-1 concentrations in the portal vein also increased after intragastric EtOH administration. ET-1 concentrations in gastric mucosal tissue and portal plasma increased significantly before gastric mucosal hemorrhagic damage occurred. Moreover, 30 min after EtOH administration there were significant correlations between gastric mucosal ET-1 concentrations and both area of gastric hemorrhagic damage as well as concentration of EtOH administered intragastrically. After intragastric EtOH administration, increase in gastric mucosal hemoglobin concentration and decrease in gastric mucosal hemoglobin oxygen saturation, estimated using reflectance spectrophotometry, occurred within 2.5 min and continued throughout the experiments. The time course of microcirculatory changes correlated closely with increases in gastric mucosal ET-1 and portal plasma ET-1 concentrations after intragastric EtOH administration. Gastric microcirculatory disturbances induced by EtOH were associated with significant decreases in gastric mucosal ATP content. Second, we examined whether pretreatment with anti-ET-1 antibody protected against EtOH-induced mucosal injury by improving mucosal microcirculation. Pretreatment with anti-ET-1 antibody microscopically and macroscopically reduced gastric mucosal hemorrhagic damage induced by EtOH and significantly reduced EtOH-induced gastric microcirculatory disturbances and decreases in gastric mucosal ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
Nippon rinsho. Japanese journal of clinical medicine
Although many authors reported that proton pump inhibitor showed mucosal protective activity, the... more Although many authors reported that proton pump inhibitor showed mucosal protective activity, the precise mechanism is still unclear. In this study, we investigated the effect of proton pump inhibit on gastric mucosal hemodynamics, using a reflectance spectrophotometry system. The proton pump inhibitors had no effect on the gastric mucosal hemodynamics prior to the state of hemorrhagic shock state. However, during the hemorrhagic shock, proton pump inhibitors significantly inhibited the decrease in tissue oxygenation and significantly reduced ulcer formation. In conclusion, proton pump inhibitors maintained tissue oxygenation resulting in reduction of ulcer formation.
Abstract The influences of intravascular ethanol on gastric mucosal integrity and its relation to... more Abstract The influences of intravascular ethanol on gastric mucosal integrity and its relation to gastric circulation were investigated in rats. Ulcer formation of the gastric mucosa correlated with the blood ethanol concentration in the presence of 150 mM HCl in the rat ...
Nippon rinsho. Japanese journal of clinical medicine
In this review, various aspects of gastrointestinal microcirculation were described. Endothelin-1... more In this review, various aspects of gastrointestinal microcirculation were described. Endothelin-1, vasoconstrictor, is elevated in gastric mucosa, causes gastric ischemia and results in gastric ulceration in human and animals under physical stress. Vasodilators such as NO anticipate the alove actions of endothelin, and thereby protect mucosa from injury. Once ulcer is developed, angiogenesis plays a key role in its healing. Various growth factors, cyclooxygenases-1 and -2, and non-peptide angiogenic factors stimulate this phenomenon and participate in ulcer healing. However, acidic conditions, H. pylori and its product, ammonia, suppress angiogenesis in vitro and in vivo. These evidences may explain why ulcer heals so slowly in gastroduodenal mucosa.
Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colo... more Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (mCRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti-EGFR treatment. Here, We investigated the genome-wide DNA methylation status in metastatic colorectal cancer to identify associations between the methylation status and clinical response to anti-EGFR antibody. We retrospectively reviewed the medical records of 97 patients (45 patients for the 1st cohort and 52 patients for the 2nd cohort) who received anti-EGFR treatment for KRAS wild-type mCRC. Then, we analyzed the associations between the genome-wide DNA methylation status and clinical response to anti-EGFR treatment, and evaluated the predictive power and value of the methylation status statistically. As a result, each cohort was classified into the highly-methylated colorectal cancer (HMCC) and the low-methylated colorectal cancer (LMCC) subgroups by unsupervised clust...
Uploads
Papers by Shingo Tsuji