AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with n...AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.展开更多
AIM:Most cancer cells acquire immortal capability by telornerase activation. The human telornerase reverse transcriptase gene (hTERT) is considered to be the major determinant of the enzymatic activity of human telome...AIM:Most cancer cells acquire immortal capability by telornerase activation. The human telornerase reverse transcriptase gene (hTERT) is considered to be the major determinant of the enzymatic activity of human telomerase,and the hTERTpromoter contains several c-lylyc binding sites that mediate hTERTtranscriptional activation. Few studies have examined the role of hTERTin hepatocarcinogenesis,and the relationship between c-Myc and telomerase in human hepatocellular carcinoma tissue is unknown.METHODS:We measured hTERTmRNA levels and c-Myc oncoprotein expression in 57 patients with hepatocellular carcinoma using in situhybridization and immunohistochemistry,respectively. The transcription regulation of hTERT was evaluated by transient transfection of pGL3-1375 into the human hepatocellular carcinoma cell line J5. To determine the relationship between c-Myc and the hTERTpromoter, a 1375-bp DNA fragment encompassing the promoter was placed upstream of the luciferase reporter gene and transiently transfected into the cell line. Two additional hTERT promoter constructs (-776 and -100 bp region) and an hTERT promoter-LUC construct containing 2 c-Myc mutations (pGL3-181 MycMT) were also used for luciferase assays.RESULTS:In 30 of 57 cases (52%), hTERTmRNA expression was associated with c-Myc protein expression. However,16 of 57 cases (28%) showed strong hTERTmRNA detection without c-Myc protein expression, and 11 cases (19%) showed weak hTERTmRNA expression and strong c-Myc expression.Although luciferase activity was decreased between upstream 1375 bp and 776 bp, there was no significant difference between upstream 776 bp and 100 bp. Finally, there was no significant decrease in activity after transfection of the hTERT promoter-LUC construct.CONCLUSION:The results indicate that c-Myc does not play a major role in gene regulation of the catalytic subunit of telomerase (hTERT) in human hepatocellular carcinoma.Other regulatory elements or epigenetic phenomena should be further investigated to understand hTERTgene regulation in human hepatocellular carcinoma.展开更多
AIM: Malignant gastrointestinal stromal tumors (GISTs)are rare. Tumors larger than 10 cm tend to recur earlier:the larger the volume of the tumor, the worse the prognosis.We hypothesized that treatment with imatinib m...AIM: Malignant gastrointestinal stromal tumors (GISTs)are rare. Tumors larger than 10 cm tend to recur earlier:the larger the volume of the tumor, the worse the prognosis.We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kittyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection.METHODS: We performed a retrospective analysis of the effects of resection on patients with giant GISTs (＞10 cm in diameter) to determine the overall survival and recurrence rates. Twenty-three patients diagnosed with giant GISTs were included from June 1996 to December 2003. STI571 was not available until January 2000. After that time,9 patients received this drug. The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed. We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor.RESULTS: The positive surgical margin group had a significantly higher recurrence rate than the negative margin group (P = 0.012). A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test,P＜0.05). Age, sex and tumor location were not significant prognostic variables. The 5-year survival rate of the surgical margin free patients was 80%and the 2-year survival rate of the surgical margin positive patients was 28%. The 5-year survival rate was 80% for the patients given STI-571 and 30% for the patients not given STI-571. The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection.CONCLUSION: A negative surgical margin and the use of STI-571 after surgical resection were good prognostic indicators. Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors.If STI-571 is used immediately when the surgical margin is positive and the tumor recurs after resection, then the prognosis of patients with giant GISTs can be improved.展开更多
AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study w...AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study was to investigate the Hpylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan.METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA.RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168,74%) strains in the majority of patients. In patients with gastric cancer, the vacA sla and slc subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P= 0.0001 for sla and 13/66 vs93/168, P<0.0001 for slc). In the middle region, the mlT strain in patients with gastric cancer was more than that of non-cancer patients(23/66 vs 33/168, P = 0.02).CONCLUSION: In Taiwan, H pylori with positive vacA sla,cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and slc subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.展开更多
AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to diff...AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility.METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500mL) and fatty meal in 10normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group Ⅱ). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups.RESULTS:In group I, there were significant decreases in gallbladder volumes 5-25 rain after gastric distension,compared to fasting volumes. Compared to normal volunteers and group Ⅱ, group I had significantly decreased gallbladder volumes 10-20min after drinking 500mL of normal saline and 10 to 50min after eating fatty meal.CONCLUSION:Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.展开更多
AIM: Postoperative gastrointestinal-tract motility is normally delayed. Early feeding after colorectal surgery has beenreposed recently, but late feeding is common. Gastrografin not only enhances bowel peristalsis, bu...AIM: Postoperative gastrointestinal-tract motility is normally delayed. Early feeding after colorectal surgery has beenreposed recently, but late feeding is common. Gastrografin not only enhances bowel peristalsis, but also decreases bowel-wall edema. Whether contrast medium allows early oral feeding and reduces the duration of hospitalization requires clarification.METHODS: Fifty patients underwent elective colorectal surgery in a regional medical center. Patients were prospectively randomized into a Gastrografin group or control group (n = 25 each). Patients in the Gastrografin group began their feeding schedule with 100 mL of 5% dextrose water with 100 mL of Gastrografin on postoperative d 3 and were advanced to a full liquid diet when the contrast reached the colon in 4 h. Patients in the control group began their feeding schedule with 200 mL of 5% dextrosewater on postoperative d 3 and were advanced to a full liquid diet after the passage of flatus and stool. Nasogastric tubes were inserted for persistent postoperative vomiting. Fullness, nausea, vomiting, complications, time of anesthesia, time of operation, time of mobilization, time of oral feeding, and duration of hospital stay were recorded and analyzed with Student's t-test.RESULTS: In the Gastrografin group, one patient hadaspiration pneumonia and one patient had anastomotic leakage resulting in sepsis and eventual death. This mortality was excluded from the subsequent statistical analysis. In the control group, two patients had wound infections. There was no significant difference between the two groups at the time of anesthesia, time of operation, or time of mobilization. There were significant differences between the two groups in the time of oral feeding (3.3±0.3 d in the Gastrografin group vs4.8±0.4 d in the control group; P = odds ratio--, 95%CI [-0.5 to +0.7 d]) and in the length of hospital stay (7.6±1.1 d in the Gastrografingroup vs10.2±1.3 d in the control group; P = odds ratio--, 95% CI [-1.2 to +1.4 d]).CONCLUSION: Gastrografin not only allowed early oralfeeding but also reduced the duration of hospitalizationafter elective colorectal surgery.展开更多
文摘AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.
文摘AIM:Most cancer cells acquire immortal capability by telornerase activation. The human telornerase reverse transcriptase gene (hTERT) is considered to be the major determinant of the enzymatic activity of human telomerase,and the hTERTpromoter contains several c-lylyc binding sites that mediate hTERTtranscriptional activation. Few studies have examined the role of hTERTin hepatocarcinogenesis,and the relationship between c-Myc and telomerase in human hepatocellular carcinoma tissue is unknown.METHODS:We measured hTERTmRNA levels and c-Myc oncoprotein expression in 57 patients with hepatocellular carcinoma using in situhybridization and immunohistochemistry,respectively. The transcription regulation of hTERT was evaluated by transient transfection of pGL3-1375 into the human hepatocellular carcinoma cell line J5. To determine the relationship between c-Myc and the hTERTpromoter, a 1375-bp DNA fragment encompassing the promoter was placed upstream of the luciferase reporter gene and transiently transfected into the cell line. Two additional hTERT promoter constructs (-776 and -100 bp region) and an hTERT promoter-LUC construct containing 2 c-Myc mutations (pGL3-181 MycMT) were also used for luciferase assays.RESULTS:In 30 of 57 cases (52%), hTERTmRNA expression was associated with c-Myc protein expression. However,16 of 57 cases (28%) showed strong hTERTmRNA detection without c-Myc protein expression, and 11 cases (19%) showed weak hTERTmRNA expression and strong c-Myc expression.Although luciferase activity was decreased between upstream 1375 bp and 776 bp, there was no significant difference between upstream 776 bp and 100 bp. Finally, there was no significant decrease in activity after transfection of the hTERT promoter-LUC construct.CONCLUSION:The results indicate that c-Myc does not play a major role in gene regulation of the catalytic subunit of telomerase (hTERT) in human hepatocellular carcinoma.Other regulatory elements or epigenetic phenomena should be further investigated to understand hTERTgene regulation in human hepatocellular carcinoma.
文摘AIM: Malignant gastrointestinal stromal tumors (GISTs)are rare. Tumors larger than 10 cm tend to recur earlier:the larger the volume of the tumor, the worse the prognosis.We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kittyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection.METHODS: We performed a retrospective analysis of the effects of resection on patients with giant GISTs (＞10 cm in diameter) to determine the overall survival and recurrence rates. Twenty-three patients diagnosed with giant GISTs were included from June 1996 to December 2003. STI571 was not available until January 2000. After that time,9 patients received this drug. The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed. We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor.RESULTS: The positive surgical margin group had a significantly higher recurrence rate than the negative margin group (P = 0.012). A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test,P＜0.05). Age, sex and tumor location were not significant prognostic variables. The 5-year survival rate of the surgical margin free patients was 80%and the 2-year survival rate of the surgical margin positive patients was 28%. The 5-year survival rate was 80% for the patients given STI-571 and 30% for the patients not given STI-571. The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection.CONCLUSION: A negative surgical margin and the use of STI-571 after surgical resection were good prognostic indicators. Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors.If STI-571 is used immediately when the surgical margin is positive and the tumor recurs after resection, then the prognosis of patients with giant GISTs can be improved.
文摘AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study was to investigate the Hpylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan.METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA.RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168,74%) strains in the majority of patients. In patients with gastric cancer, the vacA sla and slc subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P= 0.0001 for sla and 13/66 vs93/168, P<0.0001 for slc). In the middle region, the mlT strain in patients with gastric cancer was more than that of non-cancer patients(23/66 vs 33/168, P = 0.02).CONCLUSION: In Taiwan, H pylori with positive vacA sla,cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and slc subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.
文摘AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility.METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500mL) and fatty meal in 10normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group Ⅱ). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups.RESULTS:In group I, there were significant decreases in gallbladder volumes 5-25 rain after gastric distension,compared to fasting volumes. Compared to normal volunteers and group Ⅱ, group I had significantly decreased gallbladder volumes 10-20min after drinking 500mL of normal saline and 10 to 50min after eating fatty meal.CONCLUSION:Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.
文摘AIM: Postoperative gastrointestinal-tract motility is normally delayed. Early feeding after colorectal surgery has beenreposed recently, but late feeding is common. Gastrografin not only enhances bowel peristalsis, but also decreases bowel-wall edema. Whether contrast medium allows early oral feeding and reduces the duration of hospitalization requires clarification.METHODS: Fifty patients underwent elective colorectal surgery in a regional medical center. Patients were prospectively randomized into a Gastrografin group or control group (n = 25 each). Patients in the Gastrografin group began their feeding schedule with 100 mL of 5% dextrose water with 100 mL of Gastrografin on postoperative d 3 and were advanced to a full liquid diet when the contrast reached the colon in 4 h. Patients in the control group began their feeding schedule with 200 mL of 5% dextrosewater on postoperative d 3 and were advanced to a full liquid diet after the passage of flatus and stool. Nasogastric tubes were inserted for persistent postoperative vomiting. Fullness, nausea, vomiting, complications, time of anesthesia, time of operation, time of mobilization, time of oral feeding, and duration of hospital stay were recorded and analyzed with Student's t-test.RESULTS: In the Gastrografin group, one patient hadaspiration pneumonia and one patient had anastomotic leakage resulting in sepsis and eventual death. This mortality was excluded from the subsequent statistical analysis. In the control group, two patients had wound infections. There was no significant difference between the two groups at the time of anesthesia, time of operation, or time of mobilization. There were significant differences between the two groups in the time of oral feeding (3.3±0.3 d in the Gastrografin group vs4.8±0.4 d in the control group; P = odds ratio--, 95%CI [-0.5 to +0.7 d]) and in the length of hospital stay (7.6±1.1 d in the Gastrografingroup vs10.2±1.3 d in the control group; P = odds ratio--, 95% CI [-1.2 to +1.4 d]).CONCLUSION: Gastrografin not only allowed early oralfeeding but also reduced the duration of hospitalizationafter elective colorectal surgery.
