AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-med...AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.展开更多
To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance,Epidemiology and End Results(SEER)database.METHODSSEER database(2010-...To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance,Epidemiology and End Results(SEER)database.METHODSSEER database(2010-2013)has been queried through SEER*Stat program to determine the presentation,treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis.In this study,metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases(liver,lung,bone,brain and distant lymph nodes).We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases.We used Kaplan-Meier analysis and log-rank testing for survival comparisons.We employed Cox proportional model to perform multivariate analyses of the patient population;and accordingly hazard ratios with corresponding 95%CI were generated.Statistical significance was considered if a two-tailed P value<0.05 was achieved.RESULTSA total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis.Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases(for overall survival:lung vs liver metastases:P<0.0001;distant nodal vs liver metastases:P<0.0001)(for pancreatic cancer-specific survival:lung vs liver metastases:P<0.0001;distant nodal vs liver metastases:P<0.0001).Multivariate analysis revealed that age<65 years,white race,being married,female gender;surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival.CONCLUSIONPancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases.Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.展开更多
AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with car...AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.展开更多
BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to...BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low.展开更多
Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm × 18 cm × 16 cm...Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm × 18 cm × 16 cm mass arising from the pancreatic body and tail with a one- day history of abdominal pain. Initial CT scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal bleeding and the patient underwent primary tumor resection including partial gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was confi rmed by histology, immunohistochemistry and FISH analysis. All neoplastic cells were stained positive for MIC2-protein (CD99). Approximately one month after surgery, several liver metastases were observed and the patient underwent chemotherapy according to the Euro- Ewing protocol. Subsequent relaparotomy excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET in the pancreas is an extremely rare entity, it should be considered in the diffential diagnosis of pancreatic masses, especially in young patients. This alarming case particularly illustrates that PNET in the pancreas although in an advanced stage can present with only a short history of mild symptoms.展开更多
AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on...AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on leukocyte kinetics and liver damage. METHODS： Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups （n = 6/group）： controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS： Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids （1.91±0.28 sticker/μm vs 0.5±0.5 sticker/μm in controls, P〈0.05）. The effect enhanced in animals with cirrhosis and IBD （5.4±1.65 sticker/μm）, but reversed after ATIII application （3.97±1.04 sticker/μm, P〈0.05）. Mucosal blood flow showed no differences in cirrhotic animals and controls （5.3±0.31 nL/min vs5.4±0.25 nL/min） and was attenuated in animals wibh cirrhosis and IBD significantly （3.49±0.6 nL/min）. This effect was normalized in the treatment group （5.13±0.4 nL/min, P〈0.05）. Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application （P〈0.05）. CONCLUSION： Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.展开更多
AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present...AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present study was to compare the number and diameter of blood vessels in pancreatic and liver carcinoma with normal tissue.METHODS: Tumor induction of pancreatic (DSL6A) or hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor microvasculature as well as normal pancreatic or liver blood vessels were investigated by intravital microscopy. The number of perfused blood vessels in tumor and healthy tissue was assessed by computer-assisted image analysis.RESULTS: The vessel density in healthy pancreas (565±89n/mm^2) was significantly higher compared to pancreatic cancer (116±36 n/mm^2) (P<0.001). Healthy liver showed also a significantly higher vessel density (689+36 n/ram2) compared to liver carcinoma (286+32 n/mm2) (P<0.01). The comparison of diameter frequency showed a significant increase of vessel diameter in both malignant tumors compared to normal tissue (P<0.05).CONCLUSION: The expansion of endothelial cells during tumor angiogenesis is accompanied to a large extent by an increase of vessel diameter rather than by formation of new blood vessels. This may be a possible adaptive mechanism by which experimental pancreatic and hepatocellular cancers expand their endothelial diffusion surface of endothelium to compensate for inadequate neoangiogenesis.展开更多
The introduction of transjugular intrahepatic portalsystemic stent-shunt （TIPSS） has been a major breakthrough in the treatment of portal hypertension, which has evolved to a large extent, into a routine procedure. ...The introduction of transjugular intrahepatic portalsystemic stent-shunt （TIPSS） has been a major breakthrough in the treatment of portal hypertension, which has evolved to a large extent, into a routine procedure. A 21-year-old male patient with progressive graft fibrosis/cirrhosis requiring TIPSS for variceal hemorrhage in the esophagus due to portal hypertension was unresponsive to conventional measures two years after living related liver transplantation （LDLT）. Subsequently, variceal hemorrhage was controlled, however, liver function decreased dramatically with consecutive multi organ failure. CT scan revealed substantial necrosis in the liver. The patient underwent successful ＂high urgent＂ cadaveric liver transplantation and was discharged on postoperative d 20 in a stable condition.展开更多
AIM: To determine whether IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-α for its synergistic properties.METHODS: Eight pancreatic carcinoma ce...AIM: To determine whether IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-α for its synergistic properties.METHODS: Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these.The role of IFN-α regarding a) direct inhibitory effects; b)radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated.RESULTS: Our results show that IFN-α has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN-α is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN-α but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response.CONCLUSION: In conclusion, IFN-α has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.展开更多
AIM: To evaluate the effects of percutaneous radiation on leukocyte-endothelium interaction (LEI) in experimental hepatocellular carcinoma (HCC). METHODS: Twelve ACI rats underwent HCC-inoculation, six of which on day...AIM: To evaluate the effects of percutaneous radiation on leukocyte-endothelium interaction (LEI) in experimental hepatocellular carcinoma (HCC). METHODS: Twelve ACI rats underwent HCC-inoculation, six of which on day 12 received low-dose external radiation and six did not. After 12 h intravital microscopy was performed. RESULTS: LEI was significantly reduced in tumor tissue. However,irradiation of liver sinusoids and tumor tissue with 6 Gy led to a significant activation of leukocyte adhesion in the tumor with a marked increase of the proinflammatory cytokine TNF-α. CONCLUSION: The findings indicate that the immune-logical tumor-endothelial barrier can be overcome by external irradiation.展开更多
The most important and valuable grass species in Polish grassland swards are known to host symptomless endophytic fungi, from Neotyphodium genera. For agricultural practice, endophyte-plant symbiosis is both positive ...The most important and valuable grass species in Polish grassland swards are known to host symptomless endophytic fungi, from Neotyphodium genera. For agricultural practice, endophyte-plant symbiosis is both positive and negative. Endophyte-infected grasses express range of adaptations to abiotic and biotic stress. However, in certain circumstances endophytes may produce toxic alkaloids that have been linked with animal production and health problems. Intensive research towards identification of endophyte fungi growing symptomless in grasses of semi-natural grasslands was undertaken in Poland. The aims of our studies were to discover endophytes distribution across country with relation to site conditions and few climatic factors. Endophytes were found not to be very frequent, but distributed rather evenly across explored regions. Endophyte fungi were found the most frequently in meadow fescue （Festucapratensis Huds.） plants, which is common fact, as contrary to presence of endophyte hyphae in tufted hairgrass （Deschampsia cespitosa UP.B） and smooth-stalked meadow grass （Poa pratensis L.）. Presence of endophytes in explored regions was related to average longitude of collection site （0.63^＊＊） and number of sunshine hours per year （-0.70^＊＊）. Intensity ofendophyte colonization was related to yearly mean air temperature （-0.69^＊＊） and to the length of winter （0.80^＊＊）. Presence of endophytes was not related to intensity of colonization. The selective pressure of usage intensity towards more frequent endophyte colonization was not confirmed.展开更多
Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (...Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P <0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF,P <0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA,which may profoundly influence the development of AAA.展开更多
文摘AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.
文摘To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance,Epidemiology and End Results(SEER)database.METHODSSEER database(2010-2013)has been queried through SEER*Stat program to determine the presentation,treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis.In this study,metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases(liver,lung,bone,brain and distant lymph nodes).We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases.We used Kaplan-Meier analysis and log-rank testing for survival comparisons.We employed Cox proportional model to perform multivariate analyses of the patient population;and accordingly hazard ratios with corresponding 95%CI were generated.Statistical significance was considered if a two-tailed P value<0.05 was achieved.RESULTSA total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis.Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases(for overall survival:lung vs liver metastases:P<0.0001;distant nodal vs liver metastases:P<0.0001)(for pancreatic cancer-specific survival:lung vs liver metastases:P<0.0001;distant nodal vs liver metastases:P<0.0001).Multivariate analysis revealed that age<65 years,white race,being married,female gender;surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival.CONCLUSIONPancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases.Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.
文摘AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.
基金supported in part by a grant from the Else Kr ner-Fresenius-Stiftung to Christoph Eisenbach(EKFS A72/06)
文摘BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low.
文摘Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm × 18 cm × 16 cm mass arising from the pancreatic body and tail with a one- day history of abdominal pain. Initial CT scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal bleeding and the patient underwent primary tumor resection including partial gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was confi rmed by histology, immunohistochemistry and FISH analysis. All neoplastic cells were stained positive for MIC2-protein (CD99). Approximately one month after surgery, several liver metastases were observed and the patient underwent chemotherapy according to the Euro- Ewing protocol. Subsequent relaparotomy excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET in the pancreas is an extremely rare entity, it should be considered in the diffential diagnosis of pancreatic masses, especially in young patients. This alarming case particularly illustrates that PNET in the pancreas although in an advanced stage can present with only a short history of mild symptoms.
文摘AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on leukocyte kinetics and liver damage. METHODS： Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups （n = 6/group）： controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS： Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids （1.91±0.28 sticker/μm vs 0.5±0.5 sticker/μm in controls, P〈0.05）. The effect enhanced in animals with cirrhosis and IBD （5.4±1.65 sticker/μm）, but reversed after ATIII application （3.97±1.04 sticker/μm, P〈0.05）. Mucosal blood flow showed no differences in cirrhotic animals and controls （5.3±0.31 nL/min vs5.4±0.25 nL/min） and was attenuated in animals wibh cirrhosis and IBD significantly （3.49±0.6 nL/min）. This effect was normalized in the treatment group （5.13±0.4 nL/min, P〈0.05）. Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application （P〈0.05）. CONCLUSION： Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.
文摘AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present study was to compare the number and diameter of blood vessels in pancreatic and liver carcinoma with normal tissue.METHODS: Tumor induction of pancreatic (DSL6A) or hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor microvasculature as well as normal pancreatic or liver blood vessels were investigated by intravital microscopy. The number of perfused blood vessels in tumor and healthy tissue was assessed by computer-assisted image analysis.RESULTS: The vessel density in healthy pancreas (565±89n/mm^2) was significantly higher compared to pancreatic cancer (116±36 n/mm^2) (P<0.001). Healthy liver showed also a significantly higher vessel density (689+36 n/ram2) compared to liver carcinoma (286+32 n/mm2) (P<0.01). The comparison of diameter frequency showed a significant increase of vessel diameter in both malignant tumors compared to normal tissue (P<0.05).CONCLUSION: The expansion of endothelial cells during tumor angiogenesis is accompanied to a large extent by an increase of vessel diameter rather than by formation of new blood vessels. This may be a possible adaptive mechanism by which experimental pancreatic and hepatocellular cancers expand their endothelial diffusion surface of endothelium to compensate for inadequate neoangiogenesis.
文摘The introduction of transjugular intrahepatic portalsystemic stent-shunt （TIPSS） has been a major breakthrough in the treatment of portal hypertension, which has evolved to a large extent, into a routine procedure. A 21-year-old male patient with progressive graft fibrosis/cirrhosis requiring TIPSS for variceal hemorrhage in the esophagus due to portal hypertension was unresponsive to conventional measures two years after living related liver transplantation （LDLT）. Subsequently, variceal hemorrhage was controlled, however, liver function decreased dramatically with consecutive multi organ failure. CT scan revealed substantial necrosis in the liver. The patient underwent successful ＂high urgent＂ cadaveric liver transplantation and was discharged on postoperative d 20 in a stable condition.
基金Supported by a Generous Grant From the Joachim-Siebeneicher-Foundation
文摘AIM: To determine whether IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-α for its synergistic properties.METHODS: Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these.The role of IFN-α regarding a) direct inhibitory effects; b)radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated.RESULTS: Our results show that IFN-α has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN-α is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN-α but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response.CONCLUSION: In conclusion, IFN-α has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.
文摘AIM: To evaluate the effects of percutaneous radiation on leukocyte-endothelium interaction (LEI) in experimental hepatocellular carcinoma (HCC). METHODS: Twelve ACI rats underwent HCC-inoculation, six of which on day 12 received low-dose external radiation and six did not. After 12 h intravital microscopy was performed. RESULTS: LEI was significantly reduced in tumor tissue. However,irradiation of liver sinusoids and tumor tissue with 6 Gy led to a significant activation of leukocyte adhesion in the tumor with a marked increase of the proinflammatory cytokine TNF-α. CONCLUSION: The findings indicate that the immune-logical tumor-endothelial barrier can be overcome by external irradiation.
文摘The most important and valuable grass species in Polish grassland swards are known to host symptomless endophytic fungi, from Neotyphodium genera. For agricultural practice, endophyte-plant symbiosis is both positive and negative. Endophyte-infected grasses express range of adaptations to abiotic and biotic stress. However, in certain circumstances endophytes may produce toxic alkaloids that have been linked with animal production and health problems. Intensive research towards identification of endophyte fungi growing symptomless in grasses of semi-natural grasslands was undertaken in Poland. The aims of our studies were to discover endophytes distribution across country with relation to site conditions and few climatic factors. Endophytes were found not to be very frequent, but distributed rather evenly across explored regions. Endophyte fungi were found the most frequently in meadow fescue （Festucapratensis Huds.） plants, which is common fact, as contrary to presence of endophyte hyphae in tufted hairgrass （Deschampsia cespitosa UP.B） and smooth-stalked meadow grass （Poa pratensis L.）. Presence of endophytes in explored regions was related to average longitude of collection site （0.63^＊＊） and number of sunshine hours per year （-0.70^＊＊）. Intensity ofendophyte colonization was related to yearly mean air temperature （-0.69^＊＊） and to the length of winter （0.80^＊＊）. Presence of endophytes was not related to intensity of colonization. The selective pressure of usage intensity towards more frequent endophyte colonization was not confirmed.
文摘Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P <0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF,P <0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA,which may profoundly influence the development of AAA.
