International congress series最新文献_第3页

Differential targeting of tryptophan catabolism in tumors and in tumor-draining lymph nodes by stereoisomers of the IDO inhibitor 1-methyl-tryptophan IDO抑制剂1-甲基色氨酸立体异构体对肿瘤和肿瘤引流淋巴结色氨酸分解代谢的不同靶向作用

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.042

Alexander J. Muller , Richard Metz , George C. Prendergast

{"title":"Differential targeting of tryptophan catabolism in tumors and in tumor-draining lymph nodes by stereoisomers of the IDO inhibitor 1-methyl-tryptophan","authors":"Alexander J. Muller , Richard Metz , George C. Prendergast","doi":"10.1016/j.ics.2007.07.042","DOIUrl":"10.1016/j.ics.2007.07.042","url":null,"abstract":"<div>Increased activity of the tryptophan-catabolizing enzyme indoleamine 2.3-dioxygenase (IDO), encoded by the INDO gene, has been associated with a broad spectrum of cancers and is implicated in the pathophysiological process of tumoral immune escape. Our interest in IDO grew out of the finding that disruption of the Bin1 anti-cancer gene in oncogenically transformed mouse cells can lead to elevated interferon-γ mediated induction of Indo gene expression that is associated with immune escape. Using the prototypical IDO inhibitor 1-methyl-tryptophan (1MT), we demonstrated synergistic cooperativity with cytotoxic chemotherapy in an autochthonous mouse breast cancer model. Of the two stereoisomers of 1MT, the D isomer has been demonstrated to be a substantially less potent inhibitor of the IDO enzyme. However, in tolerogenic, IDO-expressing dendritic cells (DCs), D-1MT is as effective as L-1MT at blocking tryptophan catabolism and is actually superior at abrogating T cell suppression. This is consistent with data obtained in two mouse breast cancer models in which IDO is predominantly expressed in DCs within the tumor-draining lymph nodes. In both of these models D-1MT was more effective than L-1MT as an anti-tumor agent. We have recently discovered that a previously undocumented, IDO-related enzyme, referred to here as IDO2, is preferentially inhibited by D-1MT. The relative importance of targeting IDO versus IDO2 with inhibitory compounds and the possibility of cross-talk between these two enzymes is currently being evaluated.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 250-261"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"102321788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Changes in serum tryptophan during antiviral therapy with recombinant α-interferon in chronic hepatitis C 慢性丙型肝炎重组α-干扰素抗病毒治疗期间血清色氨酸的变化

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.008

A. Bertazzo , S. Comai , L. Cavalletto , L. Chemello , S. Luise , C.V.L. Costa

{"title":"Changes in serum tryptophan during antiviral therapy with recombinant α-interferon in chronic hepatitis C","authors":"A. Bertazzo , S. Comai , L. Cavalletto , L. Chemello , S. Luise , C.V.L. Costa","doi":"10.1016/j.ics.2007.07.008","DOIUrl":"10.1016/j.ics.2007.07.008","url":null,"abstract":"<div>The most effective treatment of chronic hepatitis C (HCV) available to date is represented by interferon-α (IFN-α), alone or in combination with ribavirin. However, the therapy presents adverse effects, including depressive symptoms. As IFN-α can cause an alteration of the tryptophan metabolism and a consequent reduced synthesis of serotonin, we have designed a study aimed to investigate the effect of IFN-α therapy on the serum levels of tryptophan and on the development of depression in patients affected by the hepatitis C virus. Nine patients with HCV were enrolled while treated with IFN-α2a (3 MU thrice/week) plus ribavirin (15 mg/kg/day) for six months. All patients were evaluated by a hepatologist and received two self-administered scales [Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS)]. Blood samples were collected before treatment and at one month and six months of therapy. Tryptophan, 5-hydroxytryptophan and serotonin were analysed by HPLC with a spectrofluorometric detector. In all cases, a significant decrease of serum tryptophan concentrations from baseline (17.60      0.64 mg/ml) with an increase of symptoms of depression was obtained, whereas 5-hydroxytryptophan and serotonin levels did not show any variation during the therapy from baseline values. The preliminary results suggest that IFN-α plays a role in serum tryptophan reduction and the development of depressive symptoms.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 362-366"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"110626706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship between serum kynurenine concentration and exercise performance 血清犬尿氨酸浓度与运动表现的关系

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.044

Yasuhiro Itoh , Reiko Yonekura , Chiharu Kobayashi , Kuniaki Saito , Yoshito Oguri , Kaoru Kawai , Ryoji Teradaira , Yoichi Nagamura

引用次数: 5

Trichloroacetic acid-triggered reaction of kynurenine with nitrite produced by bone marrow-derived myeloid dendritic cells stimulated with CpG CpG刺激骨髓源性骨髓树突状细胞产生的亚硝酸盐与三氯乙酸引发的犬尿氨酸反应

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.027

Toshiaki Hara , Rie Hiramatsu , Hidetoshi Akimoto , Osamu Takikawa , Tsutomu Kawabe , Fumihiko Nagase

引用次数: 0

Interpretation of kynurenine pathway metabolism in osteoporosis 骨质疏松症中犬尿氨酸途径代谢的解释

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.014

L. Gail Darlington , Caroline M. Forrest , Gillian M. Mackay , Lynn Oxford , Nicholas Stoy , Trevor W. Stone

{"title":"Interpretation of kynurenine pathway metabolism in osteoporosis","authors":"L. Gail Darlington , Caroline M. Forrest , Gillian M. Mackay , Lynn Oxford , Nicholas Stoy , Trevor W. Stone","doi":"10.1016/j.ics.2007.07.014","DOIUrl":"10.1016/j.ics.2007.07.014","url":null,"abstract":"<div>Recent evidence that oxidative stress may contribute to the development or progress of osteoporosis may indicate an underlying, or accompanying state of inflammation. In general, inflammatory conditions are associated with the activation of immune-competent cells in which activation of the kynurenine pathway occurs in parallel with the generation and release of cytokines and oxidative stress. We have therefore measured the levels of kynurenine pathway metabolites as well as peroxidation products and inflammatory markers such as neopterin, in patients with osteoporosis before and after two years of drug treatment. At diagnosis, patients showed much higher levels of anthranilic acid than control subjects, but less 3-hydroxy-anthranilic acid. There were also high levels of lipid peroxidation products. All these parameters normalised over two years of treatment, together with a significant improvement in bone density assessed by dual energy X-ray absorptiometry (DEXA) scans. Here, we hypothesise that there may be a causal link between these factors.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 367-371"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"95066668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Organ members (international/local) 机构成员(国际/本地)

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/S0531-5131(07)00471-2

引用次数: 0

Effect of melatonin on serum cholesterol status with formation of alpha-naphthylisothiocyanate-induced liver injury in rats 褪黑素对α -萘基异硫氰酸盐诱导大鼠肝损伤形成过程中血清胆固醇水平的影响

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.001

Yoshiji Ohta , Yoichiro Imai , Akira Kitagawa

引用次数: 0

Characterization of the kynurenine pathway in human oligodendrocytes 人少突胶质细胞犬尿氨酸通路的表征

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.011

Chai K. Lim , George A. Smythe , Roland Stocker , Bruce J. Brew , Gilles J. Guillemin

{"title":"Characterization of the kynurenine pathway in human oligodendrocytes","authors":"Chai K. Lim , George A. Smythe , Roland Stocker , Bruce J. Brew , Gilles J. Guillemin","doi":"10.1016/j.ics.2007.07.011","DOIUrl":"10.1016/j.ics.2007.07.011","url":null,"abstract":"<div>It is important to understand the involvement of oligodendrocytes in the kynurenine pathway (KP) and more particularly, their potential ability to produce neuroprotective metabolites such as kynurenic acid (KYNA) or picolinic acid (PIC), and the possibility of taking up and catabolizing the excitotoxin quinolinic acid (QUIN). These mechanisms may play a crucial role in the pathophysiology of neuroinflammatory diseases, especially multiple sclerosis. We used RT-PCR and HPLC to delineate KP enzyme expression and KP metabolite production. We characterized the KP in oligodendrocytes and showed that they lack IDO expression and are unable to catabolize tryptophan. However, the other enzymes in the pathway are present. These results indicate that human oligodendrocytes are more likely to produce neuroprotective KP metabolites such as KYNA and PIC rather than QUIN. However, because of the lack of IDO they are not able to down-regulate the immune response and as such may be more vulnerable to autoimmune phenomena.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 213-217"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"110472749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan analogues 色氨酸类似物对吲哚胺2,3-双加氧酶(IDO)转录的下调

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.015

Takeaki Okamoto , Shigenobu Toné , Hiroaki Kanouchi , Fumio Ohyama , Yohsuke Minatogawa

{"title":"Down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan analogues","authors":"Takeaki Okamoto , Shigenobu Toné , Hiroaki Kanouchi , Fumio Ohyama , Yohsuke Minatogawa","doi":"10.1016/j.ics.2007.07.015","DOIUrl":"10.1016/j.ics.2007.07.015","url":null,"abstract":"<div>Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumor cells. This enzyme is induced by IFN-γ in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-l-tryptophan (1-MT) and methylthiohydantoin-dl-tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-γ inducible IDO expression of CMT-93. As a result, the IFN-γ inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-γ at the transcriptional level. These results suggest that 1-MT and MTH-trp as inhibitors of IDO enzymatic activity, and Trp suppress IDO induction by IFN-γ at the transcriptional level.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 352-356"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"112897438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Characterization of tryptophan–niacin metabolism in rats fed with an excessive tryptophan diet 色氨酸过量饮食对大鼠色氨酸-烟酸代谢的影响

International congress series Pub Date : 2007-11-01 Epub Date: 2007-11-13 DOI: 10.1016/j.ics.2007.07.019

A. Okuno, T. Fukuwatari, R. Sasaki, K. Shibata

{"title":"Characterization of tryptophan–niacin metabolism in rats fed with an excessive tryptophan diet","authors":"A. Okuno, T. Fukuwatari, R. Sasaki, K. Shibata","doi":"10.1016/j.ics.2007.07.019","DOIUrl":"10.1016/j.ics.2007.07.019","url":null,"abstract":"<div>We investigated tryptophan–niacin metabolism in rats when fed with an excessive tryptophan diet. Male rat of the Wistar strain (3 weeks old) were divided into the four groups of five rats each, and one of the group was fed with a 20% casein diet added with 0, 0.5, 1, 2, and 5% tryptophan for 30 days. The last day urine samples (24-h urine) were collected for analyses for the metabolites of tryptophan such as kynurenic acid (KA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (3-HA), quinolinic acid (QA), nicotinamide (Nam), N1-methylnicotinamide (MNA), N1-methyl-4-pyridone-3-carboxamide(4-Py), and N1-methyl-2-pyridone-5-carboxamide (2-Py). The urinary excretion of KA, XA, and 3-HA were increased according to the intake of tryptophan. However, the excretion of QA was almost the same in the groups between the groups of 2 and 5% tryptophan diets. The sum metabolites of Nam        4-Py)/MNA decreased sharply in the 0.5 and 1% Trp diets. Therefore the adverse effects of dietary Trp were observed from the diet containing 0.5% Trp, which was calculated as 0.45 g/kg of rat body weight.</div>","PeriodicalId":84918,"journal":{"name":"International congress series","volume":"1304 ","pages":"Pages 171-174"},"PeriodicalIF":0.0,"publicationDate":"2007-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ics.2007.07.019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"103086257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0