Cytokines, cellular & molecular therapy最新文献_第8页

Biological and clinical implications of interleukin-7 and lymphopoiesis. 白细胞介素-7和淋巴生成的生物学和临床意义。

Cytokines, cellular & molecular therapy Pub Date : 1999-03-01

P M Appasamy

{"title":"Biological and clinical implications of interleukin-7 and lymphopoiesis.","authors":"P M Appasamy","doi":"","DOIUrl":"","url":null,"abstract":"Interleukin 7 (IL-7) is a stromal cell-derived cytokine that stands out as being the only cytokine identified to date on which development of B and T lymphocytes is absolutely dependent. IL-7 functions primarily as a growth and antiapoptosis factor for B- and T-cell (alphabeta and gammadelta TCR+ cells) precursors, and is essential for differentiation of gammadelta TCR+ cells. IL-7 can function as a cofactor during myelopoiesis, and is capable of activating monocytes/macrophages and natural killer (NK) cells. Its receptor (IL-7R) is a heterodimer of an alpha chain that specifically binds IL-7 and the common gamma chain gammac that is also a component of the receptors for IL-2, IL-4, IL-9 and IL-15. The functions of IL-7 in normal lymphocyte development and activation have led to the demonstration of the ability of IL-7 to stimulate lymphopoiesis in lymphopenic mice, suggesting a possible clinical application of IL-7 in accelerating lymphoid reconstitution in lymphopenic patients. There have also been a number of preclinical studies pointing to the possible utility of IL-7 in antitumor clinical applications, and clinical trials involving IL-7 gene therapy of metastatic disease are underway. IL-7 has also been shown to promote engraftment of stem cells in mice receiving bone marrow transplants, pointing to a possible use of IL-7 in patients receiving bone marrow or peripheral blood stem cell transplants. Areas of IL-7 biology that are essentially unexplored include the mechanisms of regulation of the expression of IL-7 and IL-7Ralpha, as well as the mechanisms by which IL-7 is a growth and differentiation factor for gammadelta T cells but a growth factor only for alphabeta T cells.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 1","pages":"25-39"},"PeriodicalIF":0.0,"publicationDate":"1999-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21256775","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

Interferons in the management of viral hepatitis. 干扰素在病毒性肝炎治疗中的应用。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

N N Zein

{"title":"Interferons in the management of viral hepatitis.","authors":"N N Zein","doi":"","DOIUrl":"","url":null,"abstract":"Since their discovery in 1957, interferons (IFNs) have been noted to have protective effects against human viral infections. The use and safety of IFNs in patients with acute or chronic hepatitis B or C infections have evolved over the last 20 years. The most studied IFN for the management of viral hepatitis is IFN-alpha, but others have recently been evaluated through controlled clinical trials. IFN treatment is not currently indicated for patients with acute hepatitis B, but has proven beneficial in chronic hepatitis B. The success of treatment in this group of patients has been measured by the normalization of liver enzymes, loss of hepatitis B e antigen and loss of detectable serum DNA of hepatitis B. It has been estimated in several clinical trials that as many as 40% of treated patients will respond to therapy, as defined above. Although only a few and limited studies have evaluated the use of IFNs in acute hepatitis C, treatment appears to decrease the likelihood of chronicity, and should be considered. In chronic hepatitis C, treatment has been effective in achieving sustained viral eradication in up to 20% of patients taking the FDA-approved dosage of three million units, three times weekly for 6-12 months. However, higher doses, longer duration of treatment or combining IFN with other antiviral agents may improve the rate of response. It has become clear during the last two decades that IFNs have beneficial effects for patients with viral hepatitis B or C. Much more effort is needed to establish the optimal dose and duration of therapy. Studies addressing the pharmacokinetics of IFNs in patients with viral hepatitis are needed, and methods to improve the bioavailability of these products to affected tissues such as the liver may improve efficacy and minimize side-effects.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 4","pages":"229-41"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20941303","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

Signalling by cytokines interacting with the interleukin-2 receptor gamma chain. 细胞因子与白细胞介素-2受体γ链相互作用的信号传导。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

J B Demoulin, J C Renauld

{"title":"Signalling by cytokines interacting with the interleukin-2 receptor gamma chain.","authors":"J B Demoulin, J C Renauld","doi":"","DOIUrl":"","url":null,"abstract":"The interleukin-2 (IL-2) receptor gamma chain (gammac) is shared by receptor complexes used by IL-2, IL-4, IL-7, IL-9 and IL-15, all of which are cytokines involved in lymphocyte development and/or activation. Gammac is physically and functionally associated with the JAK3 tyrosine kinase. This molecular pair may be considered as the trigger of the signalling cascades, inducing the activation of JAK1 upon heterodimerization with a cytokine-specific receptor component. JAK1, JAK3 and other tyrosine kinases, the nature of which varies between cytokines, phosphorylate the receptor, thereby creating docking sites for signalling molecules. Among them, PI 3-kinase and downstream effectors play a central role in the signalling processes involved in proliferation and inhibition of apoptosis for every gammac-interacting cytokine, although the mechanism of activation may vary between cytokines. Other important mediators--STAT transcription factors--regulate the expression of specific genes. IL-2, IL-7, IL-9 and IL-15 activate STAT3 and STAT5, in contrast to IL-4, which activates STAT6. These cytokines also trigger specific pathways, such as the MAP kinase cascade for IL-2 and IL-15, and the cascade responsible for immunoglobulin gene V-D-J rearrangement in response to IL-7.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 4","pages":"243-56"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20941304","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

Human dendritic cells: natural adjuvants in antitumor immunotherapy. 人树突状细胞:抗肿瘤免疫治疗中的天然佐剂。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

M Di Nicola, A Anichini, R Mortarini, M Bregni, G Parmiani, A M Gianni

{"title":"Human dendritic cells: natural adjuvants in antitumor immunotherapy.","authors":"M Di Nicola, A Anichini, R Mortarini, M Bregni, G Parmiani, A M Gianni","doi":"","DOIUrl":"","url":null,"abstract":"Although T-cell-defined tumor antigens have recently been identified in several tumors, human neoplastic cells are considered to be poorly immunogenic. The development of clinical approaches to the immunotherapy of human tumors thus requires the identification of effective adjuvants. Dendritic cells (DC) are a specialized system of antigen-presenting cells (APC) that could be utilized as natural adjuvants to elicit antitumor immune responses. In an attempt to overcome the problem of the low frequency of mature DC in peripheral blood, several methods have been applied for the ex vivo generation of human DC by culturing mobilized CD34+ cells or monocytes with combinations of cytokines. As shown in murine models as well as in the human system, after loading with peptides or tumor lysates or infection with recombinant viral vectors, DC expressing tumor antigens are able to elicit specific antitumor T cells and to mediate tumor regression. These initial results suggest that this new approach may lead to effective antitumor responses even in heavily pretreated patients bearing advanced cancers, but further clinical trials are required to validate the efficacy of vaccination with tumor-antigen-loaded DC.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 4","pages":"265-73"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20941306","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

Mechanisms of cell signaling in immune-mediated inflammation. 免疫介导炎症中的细胞信号传导机制。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

Y Bayón, A Alonso, M Hernández, M L Nieto, M Sánchez Crespo

引用次数: 0

Clinical applications of ex vivo cultured CD34+ cells and myeloid progenitors. 体外培养CD34+细胞与髓系祖细胞的临床应用。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

T M Zimmerman, S F Williams

引用次数: 0

Increased sensitivity of IL-6-deficient mice to carbon tetrachloride hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera. IL-6缺失小鼠对四氯化碳肝毒性的敏感性增加及IL-6受体-IL-6嵌合体的保护作用

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

A Katz, J Chebath, J Friedman, M Revel

引用次数: 0

Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery. 综述白细胞介素-7作为胸腺生成和免疫恢复的促进剂的潜在用途。

Cytokines, cellular & molecular therapy Pub Date : 1998-12-01

R Or, A Abdul-Hai, A Ben-Yehuda

{"title":"Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery.","authors":"R Or, A Abdul-Hai, A Ben-Yehuda","doi":"","DOIUrl":"","url":null,"abstract":"The identification of interleukin-7 (IL-7) as a critical cytokine in early B- and T-cell development, combined with the discovery that it acts on mature T cells, opens new avenues for investigating the thymopoietic machinery and manipulation of the immune system. Initially, IL-7 was thought to be a growth factor in the context of the B-cell lineage in that it stimulates proliferation of early B-cell progenitors. However, it appears that this cytokine has a much broader field of activity within the network of signal transduction. Indeed, evidence exists to support the pivotal involvement of IL-7 in the gene rearrangement of the T-cell receptor repertoire that ultimately leads to thymocyte commitment. The finding that IL-7 is an inducer of both cytotoxic T-cell- and lymphocyte-activated killer cells is one of the significant recent developments in the field of tumor immunology. Lately, it has been demonstrated that administration of IL-7 to mice after myeloablative treatment accelerates immune recovery via a unique pathway. This review of the literature dealing with IL-7 in the realm of immune function shows, inter alia, the value of the cytokine in immunosuppressed animals. The collection of findings noted in this paper may be considered the forerunner for clinical application of IL-7 in a variety of conditions of hematolymphopoietic failure.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 4","pages":"287-94"},"PeriodicalIF":0.0,"publicationDate":"1998-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20941859","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

IL-4, IL-10 and IL-13 in acute myelogenous leukemia. IL-4、IL-10和IL-13在急性髓性白血病中的作用。

Cytokines, cellular & molecular therapy Pub Date : 1998-09-01

O Bruserud

{"title":"IL-4, IL-10 and IL-13 in acute myelogenous leukemia.","authors":"O Bruserud","doi":"","DOIUrl":"","url":null,"abstract":"Cytokines are important regulators of acute myelogenous leukemia (AML) blast proliferation. For a subset of patients the AML blasts show constitutive cytokine secretion and can undergo autonomous proliferation in vitro, whereas for other patients the blasts are dependent on exogenous cytokines for proliferation. The capability of autocrine proliferation is an adverse prognostic factor in AML. The three cytokines interleukin (IL)-4, IL-10 and IL-13 modulate in vitro blast proliferation, but the final effect of each cytokine (enhancement/inhibition/no effect) depends on differences between individual patients as well as the presence of other exogenous cytokines. In contrast to these divergent effects on blast proliferation, all three cytokines inhibit constitutive in vitro cytokine secretion by AML blasts. Because of the divergent effects on blast proliferation, it seems less likely that clinical therapy with these cytokines can be used to directly modulate AML blast proliferation. However, their effects on normal immunocompetent cells (and possibly the antigen-presenting capacity of AML blasts) are easier to predict. Thus direct (therapy with exogenous IL-4, IL-10 or IL-13) or indirect (enhancement of endogenous release of IL-4, IL-10 or IL-13) modulation of these cytokine effects on immunocompetent cells may become a useful clinical approach for enhancement of antileukemic immune effects. Such a modulation of immune reactivity can be used either as in vivo patient therapy or as manipulation of stem cell grafts prior to transplantation.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"187-98"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20736697","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

p53: prospects for cancer gene therapy. P53:癌症基因治疗的前景。

Cytokines, cellular & molecular therapy Pub Date : 1998-09-01

S Soddu, A Sacchi

{"title":"p53: prospects for cancer gene therapy.","authors":"S Soddu, A Sacchi","doi":"","DOIUrl":"","url":null,"abstract":"Initially described as an oncogene, at the end of the 1980s, the wild-type p53 gene (TP53) was later shown to be capable of suppressing the proliferation of transformed cells. In the following years, an increasing number of studies demonstrated that intact p53 function is essential for the maintenance of the non-tumorigenic phenotype of cells. Indeed, functional inactivation of the p53 protein is one of the most common alterations observed in human cancers. More recently, it has been shown that inactivation of the TP53 tumor suppressor gene may lead to radioresistant and chemoresistant tumors, possibly by the induction of apoptosis-resistant phenotypes. Finally, a large number of in vitro and in vivo transduction experiments have demonstrated that exogenous TP53 overexpression can suppress the transformed phenotype of many cell types by inducing growth arrest, apoptosis or cell differentiation. All of these findings have rendered p53 a potentially helpful target for the therapy of many types of human cancers. In this review we shall discuss the different approaches to p53-related cancer therapy that have been proposed on the basis of this large number of experimental studies, and we shall try to dissect the biological questions that are still open and need to be clarified to improve p53-based therapy.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"4 3","pages":"177-85"},"PeriodicalIF":0.0,"publicationDate":"1998-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20736696","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