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A Global Approach to Tumor Immunology

Cellular & Molecular Immunology 2004年第4期1卷 256-265页

作者： EnaWang MonicaCPanelli VladiaMonsurró FrancescoMMarincola immunogenetics Section Department of Transfusion MedicineClinical CenterNational Institutes of HealthBethesdaMaryland20892USA

Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven *** conclusion is derived from our recognition that too many hypotheses or,in other words,no solid single hypothesis exist,based on experimental results,to further drive experimentation in human *** genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven *** believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each ***,immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of *** is reasonable to question what induces inflammation at the tumor *** hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate their microenvironment through cell-to-cell interactions or the secretion of soluble ***,in analogy the observation of immune cells within tumors parallels the presence of paramedics,police and firemen at the scene of an accident,which is reactive to and not causative of the *** this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the *** & Molecular Immunology.2004;1(4):256-265.

关键词： tumor immunology cDNA arrays genetic profiling vaccination melanoma

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Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease

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World Journal of Gastroenterology 2005年第38期11卷 6003-6008页

作者： David G Cox J Bart A Crusius Petra HM Peeters H Bas Bueno-de-Mesquita A Salvador Pe(n|~)a Federico Canzian International Agency for Research on Cancer Laboratory of immunogenetics Julius Center for Health Sciences and Primary Care department of Epidemiology Laboratory of immunogenetics and department of Gastroenterology

AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.

关键词： Inflammatory bowel disease Prostaglandin G/H synthase Cyclooxygenase SNP Haplotype

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Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement

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Cellular & Molecular Immunology 2012年第1期9卷 62-74页

作者： Philippos K Tsourkas Wanli Liu Somkanya C Das Susan K Pierce Subhadip Raychaudhuri department of Biomedical Engineering University of CaliforniaDavisCAUSA Laboratory of immunogenetics National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleMDUSA

B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity,a process known as affinity *** use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial *** find that if B-cell receptors become signaling-capable immediately upon antigen binding,which results in decreasing serial engagement as affinity increases,then increasing affinity can lead to weaker ***,antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable,a process similar to kinetic *** process overcomes the loss in serial engagement due to increasing antigen affinity,and replicates the monotonic increase in B-cell signaling with increasing affinity that has been observed in B-cell activation *** finding matches well with the experimentally observed time(,20 s)required for the B-cell receptor signaling domains to undergo antigen and lipid raft-mediated conformational changes that lead to Src-family kinase *** hypothesize that the physical basis for a threshold time of antigen binding might lie in the formation timescale of B-cell receptor *** time required for dimer formation decreases with increasing antigen affinity,thereby resulting in shorter threshold antigen binding times as affinity *** an affinity-dependent kinetic proofreading requirement results in affinity discrimination very similar to that observed in biological experiments.B-cell affinity discrimination is critical to the process of affinity maturation and the production of high-affinity antibodies,and thus our results have important implications in applications such as vaccine design.

关键词： computational modeling Monte Carlo lymphocyte signaling Lyn Syk

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Multidisciplinary approach to understand the pathogenesis of gastric cancer

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World Journal of Gastroenterology 2005年第27期11卷 4131-4139页

作者： Juan Shang AS Pe(n|~)a Hospital of Guangdong University of Technology Laboratory of immunogenetics and department of Gastroenterology

Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries,gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years,integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors,diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric *** aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.

关键词： Gastric cancer Hpylori , immunogenetics IL-1 Diet Trefoil regulation gp130

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Antidotal effects of curcumin against neurotoxic agents:An updated review

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Asian Pacific Journal of Tropical Medicine 2016年第10期9卷 924-931页

作者： Tahereh Farkhondeh Saeed Samarghandian Fariborz Samini department of immunogenetics BuAli Research InstituteMashhad University of Medical Sciences department of Basic Medical Sciences Neyshabur University of Medical Sciences department of Neurosurgery Faculty of MedicineMashhad University of Medical Sciences

Curcumin(CUR), the main phenolic composition in turmeric, shows preventive effects in various diseases. CUR is commonly found in the Curcuma species and historically applied in herbal medicine. Numerous studies have indicated that CUR possesses protective effects against toxic agents in the various animal tissues including the brain. This study found that CUR may be effective in nervous system problems induced by neurotoxic agents. However, due to the lack of information on human, more investigations are needed to determine the efficacy of CUR as an antidote matter. The current study aimed to critically review the recent literature data from 2014 to 2016 that regarding the therapeutic aspects of CUR versus neurotoxic agents-induced brain damage and its involved mechanisms.

关键词： Curcumin Neurotoxic agents Antioxidant Antidote

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Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

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World Journal of Gastroenterology 2018年第43期24卷 4939-4949页

作者： Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina Matej Roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePrague department of immunogenetics Institute for Clinical and Experimental Medicine department of Clinical and Transplant Pathology Institute for Clinical and Experimental MedicinePrague department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental MedicinePrague

AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical *** Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective *** De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.

关键词： Primary sclerosing cholangitis Inflammatory bowel disease Liver transplantation Acute cellular rejection Autoimmune hepatitis Human leukocyte antigen Immunosuppression

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Inflammatory bowel disease:definition,epidemiology,etiologic aspects,andimmunogenetic studies

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World Journal of Gastroenterology 1998年第5期4卷 83-95页

作者： XIA Bing JBA Crusius SGM Meuwissen AS Pe a department of Gastroenterology The Second Affiliated HospitalHubei Medical UniversityWuhan 430071China Laboratory of Gastrointest in al immunogenetics Medical FacultyFree University Ams terdam1081 BT Ams terdamThe Ne therlands

The etiology of IBD remains unclear. Environmental factors, a genetic predisposition and a disturbed immunological response all contribute to the development of the disease. Even though pathogens have not been identified as a cause of IBD, persistent infections are highly suspected, including Mycobacterium paratuberculosis and measles virus in CD, and an unknown bacterial infection and/ or bacterial products in UC. Smoking has been suggested to be a strong risk factor in CD, and in determining the clinical course of UC and CD. Disturbances of the mucosal immune system and an imbalance of immune regulation presented by cellular and/ or humoral abnormalities as well as functions of pro-inflammatory cytokines and anti-inflammatory cytokines, and other mediators were observed in IBD patients and are considered to be fundamental to the pathogenesis of IBD. Because of the multiplicity and complexity of the interactions of all these elements, it is difficult to distinguish between primary and secondary, and pathogenic and non-pathogenic phenomena[248]. With the development of transgenic and knockout rodent models, it is possible to define the critical immune elements necessary to develop IBD. Recent studies demonstrated that mucosal homeostasis is important and a defective mucosal barrier may allow unrestrained uptake of luminal antigens and pro-inflammatory molecules and thus initiate immune responses. Some evidence for an imbalance of pro-and anti-inflammatory cytokines and of Th1/Th2 lymphocytes have been found in chronic intestinal inflammation. pANCA are present in more than 70% of UC patients, but their role as a subclinical marker of UC needs to be confirmed. As to genetic factors, epidemiological studies have demonstrated the influence of genetic factors on the development of IBD by phenomena such as ethnic variations, familial aggregation, monozygotic twins versus dizygotic twins, and first degree relatives versus spouses. A genetic influence weights mo

关键词： inflammatory bowel disease/epidemiology inflammatory bowel disease/etiology inflammatory bowel disease/genetics inflammatory bowel disease/immunology

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High prevalence of occult hepatitis C infection in predialysis patients

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World Journal of Hepatology 2019年第1期11卷 109-118页

作者： Luís Henrique Bezerra Cavalcanti Sette Edmundo Pessoa de Almeida Lopes Nathália Campello Guedes dos Anjos Lucila Maria Valente Sávio Augusto Vieira de Oliveira Norma Lucena-Silva Nephrology-department of Clinical Medicine Federal University of Pernambuco Gastroenterology-department of Clinical Medicine Federal University of Pernambuco Laboratory of immunogenetics of the Aggeu Magalh?es Institute - Fiocruz Pernambuco

BACKGROUND Occult hepatitis C virus(HCV) infection(OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease(CKD) who are on hemodialysis(HD) present a higher prevalence of this type of infection than the general population, with a worse clinical ***, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy(RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT *** To research the status in predialysis patients when HD patients have high prevalence of *** A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m^2(predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies,and patients showing positivity for serological markers of hepatitis B virus(HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serumnegative, in peripheral blood mononuclear *** Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age(P = 0.002), patients with CKD of mixed etiology(P = 0.019), and patients with markers of previous HBV infection(i.e.,combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody)(P = 0.001).CONCLUSION Among predialysis patients, OCI involved the elderly, patients with CKD of mixed eti

关键词： Occult hepatitis infection Chronic hepatitis C Chronic kidney disease Hemodialysis Hepatitis C virus-RNA Peripheral blood mononuclear cells

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Helicobacter pylori in dental plaque and stomach of patients from Northern Brazil

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World Journal of Gastroenterology 2010年第24期16卷 3033-3039页

作者： Mnica Baraúna Assumpo Luisa Caricio Martins Hivana Patricia Melo Barbosa Katarine Antonia dos Santos Barile Sintia Silva de Almeida Paulo Pimentel Assumpo Tereza Cristina de Oliveira Corvelo Endoscopy department Joo de Barros Barreto University Hospital Immunopathology Laboratory Nucleus of Tropical Medicine Federal University of Pará immunogenetics Laboratory Federal University of Pará Paulo Pimentel Assumpo Surgery Department Joo de Bar-ros Barreto University Hospital

AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA ***: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical ***: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.

关键词： Helicobacter pylori Gastric mucosa Dental plaque cagA vacA

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Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia

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Chinese Medical Journal 1998年第12期000卷 51-54页

作者：倪建华陈国强沈志祥李秀松刘海卫黄燕婷方智雯陈赛娟王振义陈竺 department of immunogenetics Shanghai Institute of Transfusion Shanghai Blood Centre Shanghai 200051 China Shanghai Institute of Hematology Department of Hematology Ruijin Hospital and Renji Hospital Affiliated to Shanghai Second Medical University Shanghai

Objective To study the pharmacokinetics and metabolism of arsenic trioixide (As 2O 3) and its main side effects. Method As 2O 3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas phase chromotography. Results The plasma maximal concentration (Cpmax) was 0.94±0.37 mg/L ( ±s ), time to peak concentration (Tp) was 4 hours, plasma distribution half time (t 1/2α ) and elimination half time (t 1/2β ) were 0.89±0.29 hours and 12.13±3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83±0.45 L, system clearance (CLs) was 1.43±0.17 L/h, and area under curve (AUC) was 7.25±0.97 mg·h/L. The continuous administration of As 2O 3 did not alter its pharmacokinetic behaviors. During As 2O 3 treatment, 24 hour arsenic content in urine accounted for 1% 8% of the dialy dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven fold higher than that of pre treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ impairment was found. Conclusion As 2O 3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.

关键词： intravenous arsenic Pharmacokinetics acute

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