Vicente Carre(n)oJavier BartoloméInmaculada CastilloJuan Antonio Quiroga...
2887-2894页
查看更多>>摘要:Occult hepatitis C virus (HCV) infection,defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays,can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology.Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection.Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV.This occult infection has been reported also in healthy populations without evidence of liver disease.Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma.Thus,anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylatedinterferon plus ribavirin.The persistence of very low levels of HCV RNA in serum and in PBMCs,along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C,indicate that occult HCV is a persistent infection that is not spontaneously eradicated.This is an updated report on diagnosis,epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.
查看更多>>摘要:Inflammatory bowel diseases (IBDs) such as Crohn's disease are highly debilitating.There are inconsistencies in response to and side effects in the current conventional medications,failures in adequate drug delivery,and the lack of therapeutics to offer complete remission in the presently available treatments of IBD.This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics.This review examines the arena of the evolving IBD nanomedicine,studied so far in animal andin vitro models,before comprehensive clinical testing in humans.The investigations carried out so far in IBD models have provided substantial evidence of the nanotherapeutic approach as having the potential to overcome some of the current drawbacks to conventional IBD therapy.We analyze the pros and cons of nanotechnology in IBD therapies studied in different models,aimed at different targets and mechanisms of IBD pathogenesis,in an attempt to predict its possible impact in humans.
Marta Herreros-VillanuevaElizabeth HijonaAngel CosmeLuis Bujanda...
2902-2908页
查看更多>>摘要:Spontaneous tumor regression has been subject of numerous studies and speculations for many years.This phenomenon is exceptional,but well reported,in some types of tumors,but not in pancreatic cancer.Pancreatic cancer has the worst five-year survival rate of any cancer.Despite numerous molecular studies and clinical approaches,using several mouse models,this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive.Although pancreatic cancer tumors seldom undergo spontaneous regression,and some authors take that with skepticism,there are some cases reported in the literature.However,the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis.Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential.Diseases such as pancreatic benign tumors,insulinomas,or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer.Here we review different cases reported,their clinical characteristics,and possible mechanisms leading to spontaneous regression of pancreatic cancer.We also discuss the possibilities of misdiagnosis.
查看更多>>摘要:Hepatitis C virus (HCV) hepatitis,initially termed non-A,non-B hepatitis,has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide.With the help of animal models,our understanding of the virus has grown substantially from the time of initial discovery.There is a paucity of available animal models for the study of HCV,mainly because of the selective susceptibility limited to humans and primates.Recent work has focused modification of animals to permit HCV entry,replication and transmission.In this review,we highlight the currently available models for the study of HCV including chimpanzees,tupaia,mouse and rat models.Discussion will include methods of model design as well as the advantages and disadvantages of each model.Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies.Research within animal models is critically important to establish a complete understanding of HCV infection,which will ultimately form the basis for future treatments and prevention of disease.
查看更多>>摘要:AIM:To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis.METHODS:The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) level were determined.A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intracolonic injection of TNBS.RESULTS:TNBS group showed significantly elevated colonic MPO activity and increased TNF-α level.The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively.Altered proteins were found to be involved in a number of biological functions,such as inflammation/immunity,cell signaling,redox regulation,sulfate transport and cellular metabolism.The overexpression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12)and low expression of proteasome subunit α type-1 (psma) were validated by Western blotting analysis.CONCLUSION:TNBS-induced colitis has a profound impact on protein profiling in the nervous system.This result helps understand the neurological pathogenesis of inflammatory bowel disease.
查看更多>>摘要:AIM:To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth.METHODS:The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry,and the results were correlated with clinicopathological parameters,including the mitotic count,proliferative index (Ki-67 immunohistochemical staining),mitotic index (phospho-histone H3 immunohistochemical staining)and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling).Using primary cultured GIST cells,the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting,methyl thiazolyl tetrazolium (MTT),and apoptosis assays.RESULTS:We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples,respectively,and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis,including larger tumor size (P =0.0118),higher mitotic count (P =0.0058),higher proliferative index (P =0.0012),higher mitotic index (P =0.0282),lower apoptosis index (P =0.0484),and increased National Institutes of Health risk level (P =0.0012).We also found that the introduction of exogenous SCF potently increased KIT kinase activity,stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation,while a KIT immunoblocking antibody suppressed proliferation (P =0.01) and promoted apoptosis (P < 0.01)in cultured GIST cells.CONCLUSION:SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth.The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.
查看更多>>摘要:AIM:To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3 (FOXP3) regulatory T cells (Tregs).METHODS:The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients.TLR4 expression was examined in tumor tissues and cell lines.The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues.Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7,the synthesis of cytokines tumor necrosis factor-α,CCL22,and interleukin (IL)-10 by the two cell lines was detected and analyzed.RESULTS:FOXP3+ Tregs were enriched in tumor sites,and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and upregulated TLR4 expression in HCC tissues.Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues.Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS preincubated H22 cells.CONCLUSION:In hepatoma cell lines,TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.
查看更多>>摘要:AIM:To elaborate the clinicopathologic features of colorectal cancer-related pyogenic liver abscess (PLA).METHODS:Reported cases of colorectal cancer-related PLAs were collected from the literature published up to October 2011 and evaluated for their clinicopathologic features.Data of collected cases included demographics,clinical presentation,microbial findings and treatment.Categorical variables were compared byx2 analysis and continuous variables were evaluated using Student's t test.RESULTS:A total 96 cases of colorectal cancer-related PLA were collected from the previous literature.Most patients (60%) were male and 40% cases occurred in the age group of 61-70 years.Apart from some special types of PLA,there were significant differences in the microbiological spectrum between Eastern Asia and non-Eastern Asian countries,which implied different risk factors and courses of the disease.Gram negative bacteria especially Klebsiella pneumoniae (K.pneumoniae) PLA was predominant in Eastern Asia (80.0%)in contrast to non-Eastern Asian countries (P < 0.01).Meanwhile,most of the Eastern Asian patients exhibited smaller size of liver abscess and atypical presentation.Sigmoid colon and rectum (72.73%) were the main sites of tumor in Eastern Asian patients,whereas tumor sites were uneven among most of the nonEaster Asian PLA patients.CONCLUSION:K.pneumoniae PLA was strongly associated with colorectal cancer,especially those occurring in sigmoid colon and rectum,in elderly Eastern Asian male patients.
查看更多>>摘要:AIM:To determine whether lentivirus-mediated shRNA targeting the X-linked inhibitor of apoptosis protein (XIAP) gene could be exploited in the treatment of pancreatic cancer.METHODS:Human pancreatic cancer cells Panc-1,Mia-paca2,Bxpc-3 and SW1990,infected with lentivirus,were analyzed by real-time polymerase chain reaction (PCR).Western blotting was used to examine XIAP protein levels,survivin and p-Akt to confirm the result of real-time PCR and determine the possible mechanism.The 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure IC50 to determine chemosensitivity to the chemotherapeutic drugs 5-fluorouracil (5-FU) and gemcitabine.A colony assay,MTT assay and a tumorigenicity experiment were used to study cell proliferation in vitro and in vivo.Caspase-3/7 activity,4',6-diamidino2-phenylindole-staining and flow cytometric measurements were used to study apoptosis in 5W1990 cells.RESULTS:XIAP proteins were found to be differentially expressed among pancreatic cancer cell lines Panc-1,Mia-paca2,Bxpc-3 and SW1990.Data of realtime PCR and Western blotting showed that XIAP was reduced persistently and markedly by lentivirusmediated shRNA.Downregulation of XIAP by transfection with XIAP shRNA resulted in decreased p-Akt expression.XIAP shRNA also inhibited the growth of pancreatic cancer cells in vitro and in vivo,enhanced drug-induced apoptosis and increased chemosensitivity to 5-FU and gemcitabine.Results also suggest that inhibition of XIAP and subsequent p-Akt depletion may have an anti-tumor effect through attenuating the ability of cancer cells to survive.CONCLUSION:Lentivirus-mediated gene therapy is an attractive strategy in the treatment of pancreatic cancer and justifies the use of lentivirus in pancreatic cancer gene therapy studies.
Christiane SternMichelle Martinot-PeignouxMarie Pierre RipaultNathalie Boyer...
2966-2972页
查看更多>>摘要:AIM:To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients.METHODS:Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV),165(13%) had a relapse.Among these,62 patients were retreated with PEG-IFN-α2a or-α2b and RBV.Clinical,biological,virological and histological data were collected.Initial doses and treatment modifications were recorded.The efficacy of retreatment and predictive factors for SVR were analyzed.RESULTS:An SVR was achieved in 42% of patients.SVR was higher in young (< 50 years) (61%) than old patients (27%) (P =0.007),and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P=0.023).Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%,P =0.04).Also,a better SVR rate was observed with RBV dose/body weight > 15.2mg/kg per day (70% vs 35%,P =0.04).In logistic regression,predictors of a response were age (P =0.018),genotype (P =0.048) and initial RBV dose/body weight (P =0.022).None of the patients without a complete early virological response achieved an SVR (negative predictive value =100%).CONCLUSION:Retreatment with PEG-IFN/RBV is effective in genotype 2 or 3 relapsers,especially in young patients.A high dose of RBV seems to be important for the retreatment response.