Cytokines, cellular & molecular therapy最新文献_第5页

Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine. 放射联合干扰素- α肿瘤细胞疫苗对小鼠肾细胞癌肺转移的抑制作用

Cytokines, cellular & molecular therapy Pub Date : 2000-01-01 DOI: 10.1080/MCCM.6.4.199.205

N. Nishisaka, R. Jones, P. Morse, K. Kuratsukuri, R. Romanowski, C. Wang, G. Haas

{"title":"Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine.","authors":"N. Nishisaka, R. Jones, P. Morse, K. Kuratsukuri, R. Romanowski, C. Wang, G. Haas","doi":"10.1080/MCCM.6.4.199.205","DOIUrl":"https://doi.org/10.1080/MCCM.6.4.199.205","url":null,"abstract":"We have previously demonstrated in a murine lung metastasis model that local sublethal radiation of tumors can synergistically enhance their sensitivity to immunotherapy with either systemic high-dose interleukin-2 (IL-2) or vaccination with autologous tumor cells expressing IL-2, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF). Host antitumor activity was mediated in large part by natural killer cells, which can be activated by IFN-alpha. In the present study, we used this lung metastasis model to investigate the efficacy of combined therapy with local tumor radiation and vaccination with IFN-alpha-secreting tumor cells (Renca/IFN-alpha). The in vitro and in vivo growth rates of Renca/IFN-alpha cells were significantly reduced relative to normal controls. Subcutaneous vaccination with Renca/IFN-alpha or selective X-irradiation of the left lung (300 rad) reduced the number of lung tumors by 40% and 27%, respectively. The combination of lung irradiation plus vaccination reduced the number of lung metastases by 60%, and the net tumor volume by 95%. The reductions in tumor volume in both irradiated and non-irradiated lungs were comparable. These results indicate that host antitumor response to subcutaneous vaccination with Renca/IFN-alpha was systemic, and was significantly enhanced by radiation of tumor-bearing lungs. A regimen based on enhancement of IFN-alpha immunotherapy by local tumor radiation may be useful in the treatment of metastatic renal cell carcinoma.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 4 1","pages":"199-206"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/MCCM.6.4.199.205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60766626","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: 7

Phase 1, randomized, double-blind trial of 7-allyl-8-oxoguanosine (loxoribine) in advanced cancer. 7-烯丙基-8-氧鸟苷(洛瑞滨)治疗晚期癌症的1期随机双盲试验。

Cytokines, cellular & molecular therapy Pub Date : 2000-01-01 DOI: 10.1080/MCCM.6.4.171.176

S. Agarwala, J. Kirkwood, J. Bryant

{"title":"Phase 1, randomized, double-blind trial of 7-allyl-8-oxoguanosine (loxoribine) in advanced cancer.","authors":"S. Agarwala, J. Kirkwood, J. Bryant","doi":"10.1080/MCCM.6.4.171.176","DOIUrl":"https://doi.org/10.1080/MCCM.6.4.171.176","url":null,"abstract":"Guanine ribonucleosides substituted at the 8 position of the guanine ring are a unique class of immunomodulators, the lead compound of which is 7-allyl-8-oxoguanosine (loxoribine). We conducted a double-blind randomized phase I study to evaluate the safety, pharmacokinetics, and immunologic effects of single ascending doses of loxoribine in patients with advanced cancer. Twenty-four patients were treated in three dose tiers of 8 patients each, utilizing a unique statistical design, so that within each group, patients were randomized in blocks of 4 to receive loxoribine initially and then placebo 4 weeks later--a sequence that was reversed in the remaining 4 patients. In 23 courses of loxoribine and 20 courses of placebo, toxicity was mild and infrequent at all dose tiers (1 mg/kg, 5 mg/kg and 10 mg/kg. Both antibody-dependent cellular cytotoxicity and lymphokine-activated killer cytotoxicity were transiently depressed following loxoribine administration at all doses. Loxoribine is safe at doses up to 10 mg/kg in patients with advanced cancer, and produces modest immunologic effects. Further testing, particularly in conjunction with other immunologic agents, is warranted.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 4 1","pages":"171-6"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/MCCM.6.4.171.176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60766438","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: 22

Glutathione depletion is associated with augmenting a proinflammatory signal: evidence for an antioxidant/pro-oxidant mechanism regulating cytokines in the alveolar epithelium. 谷胱甘肽耗竭与促炎信号增强有关:证据表明抗氧化/促氧化机制调节肺泡上皮细胞因子。

Cytokines, cellular & molecular therapy Pub Date : 2000-01-01 DOI: 10.1080/MCCM.6.4.177.187

J. Haddad

{"title":"Glutathione depletion is associated with augmenting a proinflammatory signal: evidence for an antioxidant/pro-oxidant mechanism regulating cytokines in the alveolar epithelium.","authors":"J. Haddad","doi":"10.1080/MCCM.6.4.177.187","DOIUrl":"https://doi.org/10.1080/MCCM.6.4.177.187","url":null,"abstract":"Chemioxyexcitation [deltapO2/reactive oxygen species (ROS)] constitutes a potential signaling mechanism for regulating an inflammatory signal associated with oxidative stress. Exposure of fetal alveolar type II epithelial cells to an ascending deltaPO2 regimen with or without the hydroxyl radical (OH) or the superoxide radical anion (O2*-) induces a dose-dependent release of pro-inflammatory cytokines. Similarly, the Escherichia coli-derived lipopolysaccharide (LPS) upregulates cytokine biosynthesis in a dose- and time-dependent manner. Irreversible inhibition by L-buthionine-(S,R)-sulfoximine (BSO) of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), induces intracellular accumulation of ROS and augments chemioxyexcitation and LPS-mediated release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Analysis of the molecular mechanism implicated reveals an inhibitory kappaB (IkappaB-alpha)/nuclear factor kappaB (NF-kappaB)-independent pathway mediating the redox-dependent regulation of inflammatory cytokines. Although BSO stabilizes cytosolic IkappaB-alpha and downregulates its phosphorylation, thereby blockading NF-kappaB activation, it augments cytokine biosynthesis in a dose-dependent manner. These results indicate that glutathione depletion is associated with augmentation of an oxidative stress-mediated pro-inflammatory state in an ROS-dependent mechanism and that the IkappaB-alpha/NF-kappaB pathway is otherwise not necessarily indispensable for redox-mediated regulation of cytokines.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 4 1","pages":"177-87"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/MCCM.6.4.177.187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60766556","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: 72

Enhanced susceptibility to apoptosis in T cells recovering after autologous peripheral blood progenitor cell transplantation: reversal by interleukin-15. 自体外周血祖细胞移植后恢复的T细胞对凋亡的敏感性增强:白细胞介素-15的逆转

Cytokines, cellular & molecular therapy Pub Date : 2000-01-01 DOI: 10.1080/MCCM.6.4.189.198

S. Rutella, G. Bonanno, L. Pierelli, F. Sorà, S. Sica, G. Scambia, G. d'Onofrio, C. Rumi, G. Leone

{"title":"Enhanced susceptibility to apoptosis in T cells recovering after autologous peripheral blood progenitor cell transplantation: reversal by interleukin-15.","authors":"S. Rutella, G. Bonanno, L. Pierelli, F. Sorà, S. Sica, G. Scambia, G. d'Onofrio, C. Rumi, G. Leone","doi":"10.1080/MCCM.6.4.189.198","DOIUrl":"https://doi.org/10.1080/MCCM.6.4.189.198","url":null,"abstract":"T-cell number and competence are profoundly impaired after transplantation of autologous cytokine-mobilized peripheral blood progenitor cells (PBPC). The objective of the present study was to evaluate the occurrence of T-cell spontaneous apoptosis (Aspont) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine interleukin-15 (IL-15) in the peripheral blood of patients transplanted with autologous PBPC for hematological malignancies. An average 45%+/-6% of CD4+ and 55%+/-6% of CD8+ T cells cultured in the absence of exogenous cytokines underwent Aspont; of interest, IL-15 and, to a lesser extent, its structural cousin IL-2 counteracted T-cell Aspont and upregulated Bcl-2 levels. IL-15 did not rescue T cells from Aspont by promoting proliferation, but rather it acted as a genuine survival factor. Furthermore, T-cell preincubation with a gammac-blocking antibody was capable of abrogating both apoptosis inhibition and Bcl-2 induction by IL-15. These in vitro findings suggest that IL-15 might represent a promising immunomodulating agent to improve T-cell function after autologous PBPC transplantation.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 4 1","pages":"189-98"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/MCCM.6.4.189.198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60766601","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: 3

FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats. 细胞因子抑制剂FR167653可减轻大鼠心肌缺血再灌注损伤。

Cytokines, cellular & molecular therapy Pub Date : 2000-01-01 DOI: 10.1080/MCCM.6.4.165.170

S. Hoshida, N. Yamashita, K. Otsu, M. Hori

{"title":"FR167653, a cytokine-suppressive agent, reduces myocardial ischemia-reperfusion injury in rats.","authors":"S. Hoshida, N. Yamashita, K. Otsu, M. Hori","doi":"10.1080/MCCM.6.4.165.170","DOIUrl":"https://doi.org/10.1080/MCCM.6.4.165.170","url":null,"abstract":"FR167653 inhibits the production of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in human monocytes in a dose-dependent manner. We examined the effects of FR167653 on the propagation of myocardial infarction resulting from coronary occlusion-reperfusion and the time course of expression of these cytokines in myocardial tissue in rats. Myocardial infarction was induced by coronary ligation for 20 minutes followed by 2 hours of reperfusion. Although hemodynamic parameters did not differ significantly during coronary occlusion-reperfusion, the size of the infarct was significantly reduced by intravenous administration of FR167653 before occlusion (p < 0.01). mRNA levels of IL-1beta and TNF-alpha assessed by the reverse-transcriptase polymerase chain reaction method were significantly increased during coronary occlusion-reperfusion in the ischemic myocardium. Treatment with FR167653, however, significantly reduced the increased expression of these cytokines. These results indicate that the expression of inflammatory cytokines increases in the ischemic-reperfused myocardium and that the inhibition of the increased expression of cytokines by FR167653 effectively reduces myocardial ischemia-reperfusion injury.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 4 1","pages":"165-70"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/MCCM.6.4.165.170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60766307","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: 8

Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy. 非格昔汀(r-metHuG-CSF)对化疗患者口腔黏膜炎的减轻作用。

Cytokines, cellular & molecular therapy Pub Date : 1999-12-01

J Crawford, D K Tomita, R Mazanet, J Glaspy, H Ozer

{"title":"Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy.","authors":"J Crawford, D K Tomita, R Mazanet, J Glaspy, H Ozer","doi":"","DOIUrl":"","url":null,"abstract":"Mucositis, the inflammation and necrosis of mucosal membranes, is a serious and debilitating consequence of many cancer therapies. We were interested in the potential role of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor, r-metHuG-CSF) in the reduction of mucositis. Patients with newly diagnosed small-cell lung cancer (SCLC) were treated with CAE chemotherapy (cyclophosphamide, doxorubicin, and etoposide) and placebo or filgrastim. If patients had an episode of febrile neutropenia, they received unblinded filgrastim in subsequent CAE cycles. Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral candidiasis. Oral mucositis was analyzed using the unadjusted chi-square test, and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model. During cycle 1, placebo-treated patients had more episodes of mucositis (47%) compared with those patients randomized to filgrastim (28%). Across all cycles of treatment, 70% of placebo-treated patients experienced mucositis, compared with 53% of patients randomized to filgrastim. A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 4","pages":"187-93"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21693919","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

Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects. 注射编码粒细胞-巨噬细胞集落刺激因子的DNA招募树突状细胞进行免疫佐剂作用。

Cytokines, cellular & molecular therapy Pub Date : 1999-12-01

W B Bowne, J D Wolchok, W G Hawkins, R Srinivasan, P Gregor, N E Blachere, Y Moroi, M E Engelhorn, A N Houghton, J J Lewis

{"title":"Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects.","authors":"W B Bowne, J D Wolchok, W G Hawkins, R Srinivasan, P Gregor, N E Blachere, Y Moroi, M E Engelhorn, A N Houghton, J J Lewis","doi":"","DOIUrl":"","url":null,"abstract":"An important issue for effective vaccines is the development of potent adjuvants that can facilitate induction or augmentation of immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for myeloid progenitors of monocytes and dendritic cells (DC), which upon maturation are antigen-presenting cells (APC). The adjuvant effects of inoculation of DNA encoding GM-CSF into skin were studied. Initial experiments examined whether the GM-CSF gene injected into the skin of mice could affect the density of epidermal DC (Langerhans cells). DNA encoding GM-CSF delivered by particle bombardment into skin resulted in a significant increase of epidermal DC at the inoculation site. Kinetic analysis of epidermal recruitment after GM-CSF inoculation showed an increase in DC that peaked at seven days. This increase was accompanied by recruitment of DC into draining lymph nodes. The adjuvant effects of DNA encoding GM-CSF inoculated into skin were measured by the ability to augment antibody and T-cell responses against poorly immunogenic tumor antigens. Peptide immunization at skin sites containing epidermal DC newly recruited by GM-CSF DNA elicited T-cell responses against mutant p53, whereas peptide immunization of control skin sites did not elicit any detectable T-cell responses. Likewise, generation of antibodies following immunization with DNA encoding human gp75TRP1, a tyrosinase family member expressed by melanomas, was accelerated and protection from tumor challenge augmented by GM-CSF DNA.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 4","pages":"217-25"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21693924","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

Major salivary gland involvement in graft-versus-host disease: considerations related to pathogenesis, the role of cytokines and therapy. 移植物抗宿主病中主要唾液腺的参与:与发病机制、细胞因子的作用和治疗相关的考虑。

Cytokines, cellular & molecular therapy Pub Date : 1999-12-01

R M Nagler, A Nagler

引用次数: 0

Differential in vitro maturation of hematopoietic stem cells from wild-type and immunoglobulin transgenic mice. 野生型和免疫球蛋白转基因小鼠造血干细胞体外成熟的差异。

Cytokines, cellular & molecular therapy Pub Date : 1999-12-01

J A Jayne, S Reid, S E Braun, H E Broxmeyer

{"title":"Differential in vitro maturation of hematopoietic stem cells from wild-type and immunoglobulin transgenic mice.","authors":"J A Jayne, S Reid, S E Braun, H E Broxmeyer","doi":"","DOIUrl":"","url":null,"abstract":"During B-cell lymphopoiesis, hematopoietic stem cells commit to the B-cell lineage as monitored by the expression of phenotypic cell surface antigens and the production of immunoglobulin chains. Two cytokines, interleukin-7 (IL-7) and Flt-3 ligand (FL), appear to act in conjunction to drive this development process. Using an in vitro, stroma-free culture system and these cytokines, the commitment of murine Sca+ Lin- bone marrow cells to the B-cell lineage was examined with stem cells from immunoglobulin (Ig) transgenic and wild-type mice. After 12 days of culture in IL-7 and FL, stem cells from wild-type animals had matured to express surface B220, CD19, CD43, BP-1 and heat-stable antigen (HSA). These cells lacked detectable intracellular mu chains while exhibiting partial D-J rearrangement. In contrast, Sca+Lin- cells from Ig transgenic mice that were cultured similarly expressed B220, CD19, IgD, intracellular and surface mu, HSA but not CD43 or BP-1. These results suggest that expression of the Ig transgene during in vitro development overcame a block in B-cell lymphopoiesis and recapitulated in vivo events. Thus, IL-7 and FL treatment allowed uncommitted stem cells to progress to the early pre-B-cell stage while similarly treated Ig transgenic cells progressed completely to the mature B-cell stage.","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"5 4","pages":"195-204"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21693920","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

Prophylactic recombinant epoetin alfa markedly reduces the need for blood transfusion in patients with metastatic melanoma treated with biochemotherapy. 预防性重组促生成素显著降低了接受生物化疗的转移性黑色素瘤患者的输血需求。

Cytokines, cellular & molecular therapy Pub Date : 1999-12-01

J D Wolchok, V M Klimek, L Williams, P B Chapman

引用次数: 0