Cytokines, cellular & molecular therapy最新文献

{"title":"Antisense IL-10 abrogates the inhibitory effects of IL-10 production by transfected tumor cells.","authors":"G Parker,&nbsp;H Fernandes,&nbsp;S Y Chong,&nbsp;J Czarneski,&nbsp;H Ra,&nbsp;Y C Lin,&nbsp;E Raveche","doi":"10.1080/mccm.6.3.113.119","DOIUrl":"https://doi.org/10.1080/mccm.6.3.113.119","url":null,"abstract":"<p><p>Interleukin-10 (IL-10) is a pleiotropic cytokine that has a variety of downregulatory effects on immunologic and inflammatory processes. Ectopic tumor expression of IL-10 inhibited tumor growth, and local administration of antisense IL-10 significantly reversed the effects of IL-10 transfection in P815 mastocytoma. Tissue inhibitors of metalloproteinase (TIMPs) have been associated with decreased tumorigenesis and reduced metastasis, and TIMPs were increased in the region surrounding P815/IL-10 tumors and reduced in antisense IL-10-treated mice. In addition, the antisense IL-10 group had the largest tumor volume and poorest survival when compared with the P815/IL-10 control or sense groups. In summary, our data suggest that, in a mouse model, antisense IL-10 has substantive effects in reducing IL-10 translation and inhibiting IL-10-mediated TIMP upregulation, and, by doing so, allows IL-10-transfected mastocytoma to grow unchecked. Thus, ectopic tumor expression of IL-10 inhibits tumor growth, and antisense IL-10 administration in vivo reverses this protective effect.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"113-9"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.113.119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21961806","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}

{"title":"Effect of endogenous interleukin-6 on Fas (APO-1/CD95) receptor expression in advanced melanoma patients.","authors":"R Mouawad,&nbsp;E C Antoine,&nbsp;D Khayat,&nbsp;C Soubrane","doi":"10.1080/mccm.6.3.135.140","DOIUrl":"https://doi.org/10.1080/mccm.6.3.135.140","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) has been shown to support either autocrine or paracrine growth in melanoma, and may prevent programmed cell death in different cell types. We have previously demonstrated that the endogenous IL-6 level is significantly correlated with tumor burden and nonresponse to biochemotherapy in metastatic malignant melanoma patients. In the present study, we investigated the relationship between endogenous IL-6 and apoptosis signal through Fas (APO-1/CD95) receptor expression in 9 responder and 15 refractory patients with metastatic disease treated by biochemotherapy. Before any treatment, double immunostaining demonstrated that 61.5% of the tumor cells were HMB45+CD95+. At day 49 in refractory patients, a significant decrease (p = 0.04) of total Fas expression was observed. Furthermore, a significant reduction (p = 0.032) in the percentage of HMB45+CD95* cells occurred. An 11-fold increase in serum IL-6 level was detected (p < 0.002). This increase was negatively correlated (r = -0.2, p = 0.008) with the decrease in total Fas expression. However, in responding patients, no detectable decrease in Fas expression was observed, while a very low increase in serum IL-6 (2-fold) was detected. These results suggest that the increased endogenous IL-6 level in refractory patients may inhibit apoptosis via modulation of Fas expression. These preliminary results must be interpreted with caution, and further study with a greater number of patients is needed to understand the mechanism by which IL-6 inhibits apoptosis in melanoma.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"135-40"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.135.140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21961809","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}

{"title":"Effects of interferon-alpha on peripheral neutrophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients.","authors":"A Fukuda,&nbsp;H Kobayashi,&nbsp;K Teramura,&nbsp;S Yoshimoto,&nbsp;N Ohsawa","doi":"10.1080/mccm.6.3.149.154","DOIUrl":"https://doi.org/10.1080/mccm.6.3.149.154","url":null,"abstract":"<p><p>Granulocytopenia is commonly observed in interferon-alpha (IFN-alpha) therapy. Granulocyte colony-stimulating factor (G-CSF) has been identified as a primary cytokine that regulates neutrophil production, but the kinetics of G-CSF in IFN-alpha-induced granulocytopenia remains unclear. We investigated the effects of IFN-alpha on serum G-CSF levels and peripheral neutrophil counts (NC) in 15 chronic hepatitis C patients treated with standard-dose (10 MU) recombinant IFN-alpha for 24 weeks by using a chemiluminescent enzyme immunoassay for G-CSF. The time course of change after a single IFN-alpha injection showed that mean serum G-CSF levels and NC increased significantly compared with pretreatment values (p < 0.05), and were statistically correlated (r = 0.914, p = 0.0015). On repeating IFN-alpha administration, this change gradually became unclear, and granulocytopenia occurred, accompanied by a significant increase in serum G-CSF (p < 0.01). Both values reached a plateau within 2 weeks after starting treatment, and recovered rapidly after the cessation of therapy. Although continuous administration of IFN-alpha caused a time-dependent granulocytopenia, our results suggest that a single injection of IFN-alpha would be a potent inducer of G-CSF and NC in vivo as a short-term effect and that there would be negative-feedback regulation between them during long-term IFN-alpha therapy.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"149-54"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.149.154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21962329","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}

{"title":"Shrinkage of desmoid tumor with interferon alfa treatment: a case report.","authors":"L Hardell,&nbsp;M Breivald,&nbsp;S Hennerdal,&nbsp;J O Fernberg,&nbsp;H Strander","doi":"10.1080/mccm.6.3.155.156","DOIUrl":"https://doi.org/10.1080/mccm.6.3.155.156","url":null,"abstract":"<p><p>We report on a case with desmoid tumor sucessfully treated with low-dose interferon alfa. A desmoid tumor was diagnosed in August 1998 in the right shoulder area of a 23-year-old woman. Surgery would probably have permanently impaired muscle function in her shoulder and arm. Therefore, interferon alfa treatment (0.9 million units twice daily subcutaneously) was started in November 1998 (time = 0). The tumor volume based on magnetic resonance imaging (MRI) was initially 16 cm3. The size of the tumor decreased gradually during 12 months of treatment, and in November 1999 (time = 12 months) MRI showed no clear tumor demarcation. This treatment modality may be considered as an alternative to mutilating surgery in patients with desmoid tumor.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"155-6"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.155.156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21962330","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}

{"title":"Correlation between enhancement of graft-versus-leukemia effects following allogeneic bone marrow transplantation by rIL-2 and increased frequency of cytotoxic T-lymphocyte precursors in murine myeloid leukemia.","authors":"B Leshem,&nbsp;U Vourka-Karussis,&nbsp;S Slavin","doi":"10.1080/mccm.6.3.141.147","DOIUrl":"https://doi.org/10.1080/mccm.6.3.141.147","url":null,"abstract":"<p><p>A model of mouse acute myeloid leukemia (mAML) was used to study the effector mechanism mediating the graft-versus-leukemia (GVL) effects in recipients of allogeneic bone marrow cells (BMC). mAML-bearing SJL/J (H-2s) mice were lethally irradiated and then transplanted with a mixture of BMC and spleen cells (SC) derived from normal syngeneic or allogeneic mice. To augment the GVL effect, recipients were injected intraperitoneally with recombinant human interleukin-2 (rIL-2) (1.2 x 10(5) IU) for 3 consecutive days, starting one day post BMC + SC transplantation. Spleen cells from treated recipients were adoptively transferred to untreated secondary SJL/J mice to test for the existence of residual tumor cells. All the secondary recipients of SC from mAML-bearing SJL/J mice rescued with syngeneic (SJL/J) or allogeneic (B10.S) BMC+SC (H-2s) differing at minor antigens of the histocompatibility complex (MiHC) developed leukemia and died. In sharp contrast, none of the secondary recipients of SC obtained from identical mAML-bearing mice rescued with B10.S BMC + SC but activated in vivo with IL-2 developed leukemia. Adoptive recipients of SC obtained from mAML-bearing recipients of major histocompatibility complex (MHC)-disparate (C57BL/6, H-2b) cells remained free of leukemia regardless of the use of rIL-2. In parallel with the in vivo findings, a 4-day in vitro exposure of splenocytes to 6 x 10(3) IU/ml rIL-2 resulted in a 5- to 20-fold increase in the frequency of alloreactive cytotoxic T-lymphocyte (CTL) precursors (CTLp) across MiHC and MHC barriers and a 2- to 6-fold increase in their cytotoxic activity. Our data suggest that augmentation of GVL effects by rIL-2 may be due to CTL activation by rIL-2, not excluding the potential beneficial role of rIL-2-activated allogeneic natural killer cells and MHC non-restricted killer cells. Cumulatively, our results suggest potentially beneficial effects of rIL-2, when used jointly with bone marrow transplantation or allogeneic cell therapy, on eradication of leukemia.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"141-7"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.141.147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21962328","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}

{"title":"Gene transfer to primary acute myeloid leukaemia blasts and myeloid leukaemia cell lines.","authors":"P H Roddie,&nbsp;T Paterson,&nbsp;M L Turner","doi":"10.1080/mccm.6.3.127.134","DOIUrl":"https://doi.org/10.1080/mccm.6.3.127.134","url":null,"abstract":"<p><p>The transfer of genes encoding co-stimulatory molecules and/or cytokines to leukaemia cells in order to create autologous tumour vaccines represents a potential immunotherapeutic strategy for treating acute myeloid leukaemia (AML). One of the essential requirements for this strategy if it is to be applicable in a clinical setting is a high efficiency of gene transfer to primary human AML blasts. Using green fluorescent protein (GFP) as a reporter gene, we have systematically evaluated a variety of physical, chemical and viral vector-based gene transfection systems in order to determine which gave the highest gene transfer efficiency to myeloid leukaemia cell lines and primary AML blasts. Transfection efficiency was low for all the physical and chemical transfection methods tested. Retroviral vector-based infection gave a high efficiency of gene transduction in two of the four leukaemia cell lines (KG1a and U937), but was low in primary AML blasts. An adenoviral vector gave a high transduction efficiency in all of the leukaemia cell lines with the exception of the HL60. In primary AML blasts, derived from 19 patients, gene transduction efficiency was variable, ranging from 1.1% to 67.1% (mean 12.1%). Following culture in cytokines GM-CSF/IL-4/CD40L, which induced differentiation of AML blasts to dendritic-like cells, transduction efficiency was increased between two- and eightfold in 6 out of the 15 cases that underwent differentiation.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"127-34"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.127.134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21961808","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}

{"title":"Inhibition of in vivo neutrophil transmigration by a novel humanized anti-CD11/CD18 monoclonal antibody.","authors":"W C Liles,&nbsp;D C Dale,&nbsp;T H Price,&nbsp;J M Gaviria,&nbsp;T Turner,&nbsp;J Saoud,&nbsp;L R Frumkin","doi":"10.1080/mccm.6.3.121.126","DOIUrl":"https://doi.org/10.1080/mccm.6.3.121.126","url":null,"abstract":"<p><p>Leukocyte adhesion receptors, including the beta-integrin (CD11/CD18) family, play an important role in inflammation via their regulatory effects on leukocyte adhesion, transmigration, and function. A randomized, placebo-controlled, double-blind study was conducted in healthy volunteers to evaluate the in vivo effects of a humanized anti-CD11/CD18 monoclonal antibody, Hu23F2G, on leukocyte activation and transmigration. Neutrophil migration to a site of cutaneous inflammation in vivo, as measured by the skin chamber technique, was significantly reduced in subjects 24 hours after Hu23F2G administration. At 96 hours, neutrophil migration was not significantly different in subjects who received Hu23F2G or placebo. In contrast, delayed-type hypersensitivity (DTH) testing, which involves activation and migration of T lymphocytes and macrophages, was unaffected by the Hu23F2G treatment. These responses to Hu23F2G in vivo are similar to the clinical phenotype of leukocyte adhesion deficiency (LAD) type 1, a congenital disorder of CD18 deficiency. The in vivo properties of Hu23F2G suggest therapeutic potential for use in the treatment of acute non-infectious inflammatory disorders mediated predominantly by neutrophils.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 3","pages":"121-6"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/mccm.6.3.121.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21961807","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}

{"title":"Use of G-CSF for granulocyte transfusion therapy.","authors":"K Hübel,&nbsp;D C Dale,&nbsp;A Engert,&nbsp;W C Liles","doi":"10.1080/13684730050515813","DOIUrl":"https://doi.org/10.1080/13684730050515813","url":null,"abstract":"<p><p>Patients with neutropenia, especially neutropenia following aggressive myeloablative therapy, are at high risk for developing infectious complications caused by bacteria and opportunistic fungi. Infections remain one of the leading causes of treatment failure in patients with cancer. Thus, new and innovative therapeutic strategies are needed for management of neutropenic patients with infection. Because neutrophils represent the first line of host defense, granulocyte transfusion therapy should be a logical therapeutic approach. Although such therapy has been employed sporadically for several decades, clinical benefit has been compromised by technical problems and low granulocyte yields resulting from inadequate donor stimulation. The discovery of granulocyte colony-stimulating factor (G-CSF) as a means to elevate blood neutrophil counts when administered to normal donors has rekindled interest in granulocyte transfusion therapy. Extensive experience has been gained worldwide with G-CSF in clinical practice, and adverse events have been minimal when G-CSF has been administered to patients or healthy persons in human trials. This review focuses on the use of G-CSF in granulocyte transfusion therapy, including technical considerations of granulocyte leukapheresis and storage, donor selection and stimulation, as well as treatment results and associated risks.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 2","pages":"89-95"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730050515813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21931978","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}

{"title":"Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis.","authors":"S Kaneko,&nbsp;T Satoh,&nbsp;J Chiba,&nbsp;C Ju,&nbsp;K Inoue,&nbsp;J Kagawa","doi":"10.1080/13684730050515796","DOIUrl":"https://doi.org/10.1080/13684730050515796","url":null,"abstract":"<p><p>Concentrations of interleukin (IL)-6 and IL-8 in serum and synovial fluid obtained from patients with osteoarthritis (OA) of the knee were determined by the chemiluminescence-ELISA (CL-ELISA) method, the sensitivity of which is 100-1,000 times greater than that of the conventional ELISA method. The results were compared with those obtained from patients with rheumatoid arthritis (RA) and from healthy subjects. The mean IL-6 and IL-8 levels in synovial fluid indicated higher concentrations in RA than in OA. The IL-6 and IL-8 levels in serum were significantly higher in RA and OA relative to controls. Among OA patients in whom remarkable improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the initial examination were relatively higher, and were markedly decreased after treatment with sodium hyaluronate (NaHA). Among those in whom no improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the time of initial examination were relatively lower, and hydrarthrosis was not significantly improved even after treatment with NaHA. In addition, there was a tendency for the synovial fluid IL-6 and IL-8 levels to decrease as HA levels increased. Evaluation of X-ray findings revealed that the IL-6 levels in synovial fluid at the initial examination in low-grade cases tended to be significantly higher than in high-grade cases. In low-grade cases, as determined by X-ray findings, there was a significant decrease in IL-6 levels in synovial fluid after treatment with NaHA.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 2","pages":"71-9"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730050515796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21931976","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}

{"title":"Ex vivo expansion of human hematopoietic progenitors and cells to support high-dose chemoradiation therapy: five years of clinical experience.","authors":"C Chabannon,&nbsp;S Olivero,&nbsp;D Blaise,&nbsp;D Maraninchi,&nbsp;P Viens","doi":"10.1080/13684730050515822","DOIUrl":"https://doi.org/10.1080/13684730050515822","url":null,"abstract":"<p><p>The identification of cytokines-soluble or membrane-bound regulators of hematopoietic stem and progenitor cell survival, proliferation, and differentiation - and the definition of culture conditions that enable cell and progenitor expansion, has lead to the first clinical trials using cultured cells in addition to or in place of unmanipulated cells. The use of ex vivo expanded cells can improve several aspects of autologous and allogeneic hematopoietic cell and progenitor transplantation, such as reducing or abolishing the nadir that follows high-dose chemoradiation therapy regimens, or reducing the clinical risks associated with the use of small numbers of progenitors as in cord blood transplantation and in autologous transplantation for poor mobilizers. In addition, biological questions raised by ex vivo expansion are shared by scientists and clinicians interested in gene transfer into hematopoietic stem cells. We here review the biological problems associated with ex vivo expansion: defining efficient culture conditions, considering not only scientific and biological issues but also regulatory and commercial issues, defining appropriate surrogate endpoints that predict engraftment and superior clinical efficacy to that obtained with the use of unmanipulated grafts. We also review the results of the first clinical trials that have demonstrated the feasibilty of this approach, and have shown some of its limitations; demonstration of clinical efficacy will require more preclinical and clinical work.</p>","PeriodicalId":79485,"journal":{"name":"Cytokines, cellular & molecular therapy","volume":"6 2","pages":"97-108"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13684730050515822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21931979","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}