Desmoplastic small round cell tumor （DSRCT） is a rare, highly aggressive malignancy with distinctive histological features： a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young ...Desmoplastic small round cell tumor （DSRCT） is a rare, highly aggressive malignancy with distinctive histological features： a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.展开更多
Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD）...Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and 展开更多
The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ...The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.展开更多
Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microb...Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacte-riostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insuff iciency, immuno-deficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, f istulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Noninvasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be com-plex, addressing all causes, symptoms and complica-tions, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.展开更多
Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development ...Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development of tumors,cardiovascular diseases,nervous system disorders,nephropathy,and other diseases.The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases.This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of IncRNAs from the role of disease coding to acting as drug candidates,including the current status and progress in preclinical research.Cutting-edge strategies for lncRNA modulation have been summarized,including the sources of LncRNA-related drugs,such as genetic technology and small-molecule compounds,and related delivery methods.The current progress of clinical trials of lncRNA-targeting drugs is also discussed.This information will form a latest updated reference for research and development of lncRNA-based drugs.展开更多
AIM:To study the therapeutic efficacy of a new transnasal ileus tube advanced endoscopically for adhesive small bowel obstruction.METHODS:A total of 186 patients with adhesive small bowel obstruction treated from Sept...AIM:To study the therapeutic efficacy of a new transnasal ileus tube advanced endoscopically for adhesive small bowel obstruction.METHODS:A total of 186 patients with adhesive small bowel obstruction treated from September 2007 to February 2011 were enrolled into this prospective randomized controlled study.The endoscopically advanced new ileus tube was used for gastrointestinal decompression in 96 patients and ordinary nasogastric tube(NGT) was used in 90 patients.The therapeutic efficacy was compared between the two groups.RESULTS:Compared with the NGT group,the ileus tube group experienced significantly shorter time for relief of clinical symptoms and improvement in the findings of abdominal radiograph(4.1 ± 2.3 d vs 8.5 ± 5.0 d) and laboratory tests(P < 0.01).The overall effectiveness rate was up to 89.6% in the ileus tube group and 46.7% in the NGT group(P < 0.01).And 10.4% of the patients in the ileus tube group and 53.3% of the NGT group underwent surgery.For recurrent adhesive bowel obstruction,ileus tube was also significantly more effective than NGT(95.8% vs 31.6%).In the ileus tube group,the drainage output on the first day and the length of hospital stay were significantly different depending on the treatment success or failure(P < 0.05).The abdominal radiographic improvement was correlated with whether or not the patient underwent surgery.CONCLUSION:Ileus tube can be used for adhesive small bowel obstruction.Endoscopic placement of the ileus tube is convenient and worthy to be promoted despite the potential risks.展开更多
Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious eff...Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.展开更多
AIM:To retrospectively analyze the fields of application,diagnostic yields and findings of OMOM capsule endoscopy in Chinese patients.METHODS:A database including 2400 Chinese patients who received OMOM capsule endosc...AIM:To retrospectively analyze the fields of application,diagnostic yields and findings of OMOM capsule endoscopy in Chinese patients.METHODS:A database including 2400 Chinese patients who received OMOM capsule endoscopy in 27 endoscopy centers in China was retrieved from the Jianshan Science and Technology Ltd.OMOM capsule endoscopy database.The patient's age,gender,fields of application,the potentially relevant findings,pyloric transit time(PTT),small bowel transit time(SBTT),and complete small-bowel examination rate(CSER) were recorded and analyzed.RESULTS:Two thousand four hundred patients aged 9-91 years(mean,49 years),of whom 1510 were males(62.9%),underwent 2400 OMOM capsule endoscopy procedures.One thousand two hundred and thirty two(51.3%) were referred with obscure gastrointestinal bleeding(OGIB),642(26.8%) with abdominal pain,and 223(9.3%) with chronic diarrhea.The overall diagnostic yield was 47.7%(1144/2400).The diagnostic yield of OMOM capsule endoscopy in OGIB subgroup was much higher than in the non-OGIB subgroup(62.4% vs 32.1%,P<0.001).The most common findings of the small bowel in Chinese patients with OGIB were arteriovenous malformation(28.1%) and tumors(18.9%).There was no significant difference in the diagnostic yield between the male and female patients with OGIB.However,the diagnostic yield in patients aged more than 60 was higher than in patients aged less than 60(69.8% vs 58.9%,P<0.001).The median PTT was 41 min(range:1-544 min) and the mean SBTT was 247.2 ± 88.9 min.The overall CSER was 86.8%.CONCLUSION:The OMOM capsule endoscopy is a valuable tool for small bowel evaluation with good overall diagnostic yield and CSER.展开更多
Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the firs...Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.展开更多
Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted ...Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.展开更多
Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their ...Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOR） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.展开更多
文摘Desmoplastic small round cell tumor （DSRCT） is a rare, highly aggressive malignancy with distinctive histological features： a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.
文摘Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and
基金Supported by(in part)FARB-ex 60%2012 of the University of Salerno grant to Vajro P
文摘The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.
基金Supported by The Research Project MZO 00179906 from the Ministry of Health, Czech Republicby Research Grant GACR 305/08/0535, Czech Republic
文摘Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacte-riostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insuff iciency, immuno-deficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, f istulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Noninvasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be com-plex, addressing all causes, symptoms and complica-tions, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.
基金supported by the Drug Innovation Major Project of China(Grant No.2018ZX09711001-002-010)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.2016-I2M-3e011,China)Beijing Natural Science Foundation(Grant Nos.7202138 and 7181007,China)
文摘Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development of tumors,cardiovascular diseases,nervous system disorders,nephropathy,and other diseases.The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases.This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of IncRNAs from the role of disease coding to acting as drug candidates,including the current status and progress in preclinical research.Cutting-edge strategies for lncRNA modulation have been summarized,including the sources of LncRNA-related drugs,such as genetic technology and small-molecule compounds,and related delivery methods.The current progress of clinical trials of lncRNA-targeting drugs is also discussed.This information will form a latest updated reference for research and development of lncRNA-based drugs.
文摘AIM:To study the therapeutic efficacy of a new transnasal ileus tube advanced endoscopically for adhesive small bowel obstruction.METHODS:A total of 186 patients with adhesive small bowel obstruction treated from September 2007 to February 2011 were enrolled into this prospective randomized controlled study.The endoscopically advanced new ileus tube was used for gastrointestinal decompression in 96 patients and ordinary nasogastric tube(NGT) was used in 90 patients.The therapeutic efficacy was compared between the two groups.RESULTS:Compared with the NGT group,the ileus tube group experienced significantly shorter time for relief of clinical symptoms and improvement in the findings of abdominal radiograph(4.1 ± 2.3 d vs 8.5 ± 5.0 d) and laboratory tests(P < 0.01).The overall effectiveness rate was up to 89.6% in the ileus tube group and 46.7% in the NGT group(P < 0.01).And 10.4% of the patients in the ileus tube group and 53.3% of the NGT group underwent surgery.For recurrent adhesive bowel obstruction,ileus tube was also significantly more effective than NGT(95.8% vs 31.6%).In the ileus tube group,the drainage output on the first day and the length of hospital stay were significantly different depending on the treatment success or failure(P < 0.05).The abdominal radiographic improvement was correlated with whether or not the patient underwent surgery.CONCLUSION:Ileus tube can be used for adhesive small bowel obstruction.Endoscopic placement of the ileus tube is convenient and worthy to be promoted despite the potential risks.
基金Supported by Grants from the NIH (R21CA111513-01A1, 5 RO1 CA119087, and SPORE Grant 1 P50CA95060)grants from the Arizona Biomedical Research Commission (#0012 & #0803)by Biomedical Diagnostics & Research In., Tucson Arizona, and by a VA Merit Review Grant
文摘Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.
基金Supported by (in part) Shanghai Educational Development Foundation,Shanghai Chenguang Project,No. 2007CG49
文摘AIM:To retrospectively analyze the fields of application,diagnostic yields and findings of OMOM capsule endoscopy in Chinese patients.METHODS:A database including 2400 Chinese patients who received OMOM capsule endoscopy in 27 endoscopy centers in China was retrieved from the Jianshan Science and Technology Ltd.OMOM capsule endoscopy database.The patient's age,gender,fields of application,the potentially relevant findings,pyloric transit time(PTT),small bowel transit time(SBTT),and complete small-bowel examination rate(CSER) were recorded and analyzed.RESULTS:Two thousand four hundred patients aged 9-91 years(mean,49 years),of whom 1510 were males(62.9%),underwent 2400 OMOM capsule endoscopy procedures.One thousand two hundred and thirty two(51.3%) were referred with obscure gastrointestinal bleeding(OGIB),642(26.8%) with abdominal pain,and 223(9.3%) with chronic diarrhea.The overall diagnostic yield was 47.7%(1144/2400).The diagnostic yield of OMOM capsule endoscopy in OGIB subgroup was much higher than in the non-OGIB subgroup(62.4% vs 32.1%,P<0.001).The most common findings of the small bowel in Chinese patients with OGIB were arteriovenous malformation(28.1%) and tumors(18.9%).There was no significant difference in the diagnostic yield between the male and female patients with OGIB.However,the diagnostic yield in patients aged more than 60 was higher than in patients aged less than 60(69.8% vs 58.9%,P<0.001).The median PTT was 41 min(range:1-544 min) and the mean SBTT was 247.2 ± 88.9 min.The overall CSER was 86.8%.CONCLUSION:The OMOM capsule endoscopy is a valuable tool for small bowel evaluation with good overall diagnostic yield and CSER.
文摘Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.
基金Supported by National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiativeNMRC Clinician-Scientist IRG Grant CNIG11nov38(Zhou J)Chng WJ is also supported by NMRC Clinician Scientist Investigator award
文摘Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.
文摘Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOR） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.
