AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS...AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.展开更多
BACKGROUND： Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of ...BACKGROUND： Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES： Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings： “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence（NICE） Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS： The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS： Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the 展开更多
There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and ...There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.展开更多
Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, how...Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk 展开更多
China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and ...China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.展开更多
Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologica...Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis- Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.展开更多
In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST tho...In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST （2017 edition） was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.展开更多
AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or d...AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.展开更多
Aim： To study the clinical effects of a disposable circumcision device in treatment of male patients of different ages with either phimosis or excess foreskin. Methods： One thousand two hundred patients between the ...Aim： To study the clinical effects of a disposable circumcision device in treatment of male patients of different ages with either phimosis or excess foreskin. Methods： One thousand two hundred patients between the age of 5 and 95 years underwent circumcision using this procedure in the 2-year period between October 2005 and September 2007. Of these cases, 904 had excess foreskin and 296 were cases of phimosis. Results： In 96.33% of the cases the incision healed, leaving a minimal amount of the inner foreskin with no scarring and producing good cosmetic results. There were no incidents of device dislocation or damage to the frenulum. The average operative time was 2.5 min for excess foreskin, and 3.5 min for phimosis. During the 7 days of wearing the device, mild to moderate edema occurred in 10.08 % of cases with excess foreskin and in 2.58 % of those with phimosis. Edema in the frenulum was seen in 1.67% of patients, and only 0.67% had an infection of the incision. A total of 86.25% of patients reported pain due to penile erection. After removal of the device, 0.58% of the cases had minimal bleeding around the incision, and 2.42% had wound dehiscence. Conclusion： The new device can be applied to an overwhelming majority of patients with phimosis and excess foreskin. This technique is relatively simple to perform, and patients who underwent this surgery had very few complications. Antibiotics were not required and patients reported less pain than those who were circumcised using conventional methods. Circumcision with this device requires minimal tissue manipulation, and is quicker and safer than circumcision using conventional techniques.展开更多
Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IF...Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.展开更多
Background Fluid therapy for severe acute pancreatitis （SAP） should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for...Background Fluid therapy for severe acute pancreatitis （SAP） should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. Methods Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group （Group I, n=36） and a controlled fluid expansion group （Group II n=-40）. Hemodynamic disorders were either quickly （fluid infusion rate was 10-15 ml.kg-1-h-1, Group I） or gradually improved （fluid infusion rate was 5-10 ml-kg1.h-1, Group II） through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome （ACS）, sepsis, and survival rate were obtained. Results The two groups had statistically different （P 〈0.05） time intervals to meet fluid expansion criteria （Group I, 13.5±6.6 hours; Group II, （24.0±5.4） hours）. Blood lactate concentrations were both remarkably lower as compared to the level upon admission （P 〈0.05） and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I （35.6%±6.8%） than in Group II （38.5%±5.4%） （P〈0.01）. Amount of crystalloid and colloid in group I （（4028±1980）ml and （1336±816）ml） on admission day was more than those of group II （（2472±1871）ml and （970±633）ml）. No significant difference was found in the total amount of fluids within four days of admission between the two groups （P〉0.05）. Total amount of fluid sequestration within 4 days was higher in Group I （（5378±2751）ml�展开更多
Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be...Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first.展开更多
Background Respiratory distress syndrome （RDS） is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and th...Background Respiratory distress syndrome （RDS） is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and these characteristics have not been well documented as yet. This study was to investigate the pathogenesis, clinical characteristics and management strategies of RDS in full-term neonates, with the aim of developing a working protocol for improving the outcome in full-term neonates with RDS. Methods A total of 125 full-term infants with RDS were enrolled in this study. Their clinical and laboratory data were collected for analyzing the characteristics of full-term neonatal RDS. Results （1） The 125 cases included 94 male and 31 female infants, vaginal delivery occurred in 80 cases and cesarean section in 45 cases. （2） The onset time of RDS was （3.11±3.59） hours after birth. （3）The possible reasons included severe perinatal infections in 63 patients, elective cesarean section in 34 cases, severe birth asphyxia in 12 patients, meconium aspiration syndrome in 9 patients, pulmonary hemorrhage in 4 patients and maternal diabetes in 3 patients. （4） Complications included multiple organ system failure （MOSF） in 49 patients, persistent pulmonary hypertension of newborn （PPHN） in 25 patients, acute renal failure in 18 patients, severe hyperkalemia in 25 patients, severe metabolic acidosis in 6 cases, severe myocardial injury in 9 cases, pulmonary hemorrhage in 3 cases, disseminated intravascular coagulation in 14 patients and shock in 12 patients.（5） Four patients died, the mortality was therefore 3.2% with the main cause of septicemia complicating of MOSF, but their prognosis was improved while comprehensive treatment measures including early mechanical ventilation and broad spectrum antibiotics were taken into account. Conclusions RDS is not an uncommon disease in full-term infants and is associated with a higher mortality, its clinical characteristics are very different from展开更多
Liver cirrhosis is the final pathological result of various chronic liver diseases,and fibrosis is the precursor of cirrhosis.Many types of cells,cytokines and miRNAs are involved in the initiation and progression of ...Liver cirrhosis is the final pathological result of various chronic liver diseases,and fibrosis is the precursor of cirrhosis.Many types of cells,cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis.Activation of hepatic stellate cells(HSCs)is a pivotal event in fibrosis.Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis.Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs.Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis.At the molecular level,many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis.Recently,miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis.Robust animal models of liver fibrosis and cirrhosis,as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.展开更多
Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated...Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoc- cus multilocularis （E. multi/ocular/s） and Echinococcus granulosus （E. granulosus） infection, respectively. Cys- tic echinococcosis （CE） has a worldwide distribution, while hepatic alveolar echinococcosis （AE） is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the per/cyst; old cysts typically present internal septa- tions and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration （PAIR）] and more effective drugs （such as benzoimidazoles） have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.展开更多
Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polar...Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.展开更多
BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, ...BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.展开更多
文摘AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.
文摘BACKGROUND： Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES： Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings： “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence（NICE） Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS： The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS： Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the
文摘There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.
文摘Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk
文摘China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.
文摘Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis- Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.
文摘In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor （GIST） in China, the members of Chinese Society of Clinical Oncology （CSCO） Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST （2017 edition） was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.
基金Supported by Grants from the Key Project of the Eleventh Five-Year Plan of People's Liberation Army,No.06G041
文摘AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.
基金Acknowledgment The project （The Fundamental Researches of the Reproductive Health） was supported by the National Natural Science Foundation of China （G1999055905, branch topic）.
文摘Aim： To study the clinical effects of a disposable circumcision device in treatment of male patients of different ages with either phimosis or excess foreskin. Methods： One thousand two hundred patients between the age of 5 and 95 years underwent circumcision using this procedure in the 2-year period between October 2005 and September 2007. Of these cases, 904 had excess foreskin and 296 were cases of phimosis. Results： In 96.33% of the cases the incision healed, leaving a minimal amount of the inner foreskin with no scarring and producing good cosmetic results. There were no incidents of device dislocation or damage to the frenulum. The average operative time was 2.5 min for excess foreskin, and 3.5 min for phimosis. During the 7 days of wearing the device, mild to moderate edema occurred in 10.08 % of cases with excess foreskin and in 2.58 % of those with phimosis. Edema in the frenulum was seen in 1.67% of patients, and only 0.67% had an infection of the incision. A total of 86.25% of patients reported pain due to penile erection. After removal of the device, 0.58% of the cases had minimal bleeding around the incision, and 2.42% had wound dehiscence. Conclusion： The new device can be applied to an overwhelming majority of patients with phimosis and excess foreskin. This technique is relatively simple to perform, and patients who underwent this surgery had very few complications. Antibiotics were not required and patients reported less pain than those who were circumcised using conventional methods. Circumcision with this device requires minimal tissue manipulation, and is quicker and safer than circumcision using conventional techniques.
基金The authors would like to thank the patients and their families for their contribution to this studyThis study was supported by the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX10002007001,2017ZX10202203-007,2017ZX10202203-008)+2 种基金the National Natural Science Foundation of China(81171561,30972584)This study was also supported in part by Shanghai Roche Pharmaceuticals LtdWriting assistance was provided by Stefanie Chuah,from Mudskipper Business Ltd,funded by F Hoffmann-La Roche
文摘Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
文摘Background Fluid therapy for severe acute pancreatitis （SAP） should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. Methods Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group （Group I, n=36） and a controlled fluid expansion group （Group II n=-40）. Hemodynamic disorders were either quickly （fluid infusion rate was 10-15 ml.kg-1-h-1, Group I） or gradually improved （fluid infusion rate was 5-10 ml-kg1.h-1, Group II） through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome （ACS）, sepsis, and survival rate were obtained. Results The two groups had statistically different （P 〈0.05） time intervals to meet fluid expansion criteria （Group I, 13.5±6.6 hours; Group II, （24.0±5.4） hours）. Blood lactate concentrations were both remarkably lower as compared to the level upon admission （P 〈0.05） and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I （35.6%±6.8%） than in Group II （38.5%±5.4%） （P〈0.01）. Amount of crystalloid and colloid in group I （（4028±1980）ml and （1336±816）ml） on admission day was more than those of group II （（2472±1871）ml and （970±633）ml）. No significant difference was found in the total amount of fluids within four days of admission between the two groups （P〉0.05）. Total amount of fluid sequestration within 4 days was higher in Group I （（5378±2751）ml�
文摘Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first.
基金This work was supported by the grants from China Postdoctoral Science Foundation （No. 20080431405＆ No. 200801041）.
文摘Background Respiratory distress syndrome （RDS） is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and these characteristics have not been well documented as yet. This study was to investigate the pathogenesis, clinical characteristics and management strategies of RDS in full-term neonates, with the aim of developing a working protocol for improving the outcome in full-term neonates with RDS. Methods A total of 125 full-term infants with RDS were enrolled in this study. Their clinical and laboratory data were collected for analyzing the characteristics of full-term neonatal RDS. Results （1） The 125 cases included 94 male and 31 female infants, vaginal delivery occurred in 80 cases and cesarean section in 45 cases. （2） The onset time of RDS was （3.11±3.59） hours after birth. （3）The possible reasons included severe perinatal infections in 63 patients, elective cesarean section in 34 cases, severe birth asphyxia in 12 patients, meconium aspiration syndrome in 9 patients, pulmonary hemorrhage in 4 patients and maternal diabetes in 3 patients. （4） Complications included multiple organ system failure （MOSF） in 49 patients, persistent pulmonary hypertension of newborn （PPHN） in 25 patients, acute renal failure in 18 patients, severe hyperkalemia in 25 patients, severe metabolic acidosis in 6 cases, severe myocardial injury in 9 cases, pulmonary hemorrhage in 3 cases, disseminated intravascular coagulation in 14 patients and shock in 12 patients.（5） Four patients died, the mortality was therefore 3.2% with the main cause of septicemia complicating of MOSF, but their prognosis was improved while comprehensive treatment measures including early mechanical ventilation and broad spectrum antibiotics were taken into account. Conclusions RDS is not an uncommon disease in full-term infants and is associated with a higher mortality, its clinical characteristics are very different from
文摘Liver cirrhosis is the final pathological result of various chronic liver diseases,and fibrosis is the precursor of cirrhosis.Many types of cells,cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis.Activation of hepatic stellate cells(HSCs)is a pivotal event in fibrosis.Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis.Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs.Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis.At the molecular level,many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis.Recently,miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis.Robust animal models of liver fibrosis and cirrhosis,as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.
文摘Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoc- cus multilocularis （E. multi/ocular/s） and Echinococcus granulosus （E. granulosus） infection, respectively. Cys- tic echinococcosis （CE） has a worldwide distribution, while hepatic alveolar echinococcosis （AE） is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the per/cyst; old cysts typically present internal septa- tions and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration （PAIR）] and more effective drugs （such as benzoimidazoles） have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.
基金The authors’research efforts were supported in part by research grants from the NIH(AT004418 to TCH)the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)+1 种基金the Scoliosis Research Society(to MJL),MKM was a recipient of Howard Hughes Medical Institute Medical Research FellowshipCS was a recipient of the Pritzker Summer Research Fellowship funded through a NIH T-35 training grant(NIDDK).
文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.
文摘BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.
