Cytokines, GM-CSF and IFNgamma administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin.
Cytokines, GM-CSF and IFNgamma administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin.
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细胞因子，GM-CSF和IFNGAMMA通过复发性卵巢癌患者的启动和化学疗法循环施用。
DOI：
10.1186/1479-5876-4-16
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发表时间：
2006-04-07
影响因子：
7.4
通讯作者：
Freedman, RS
中科院分区：
文献类型：
--
作者：
Apte, SM;Vadhan-Raj, S;Cohen, L;Bassett, RL;Gordon, IO;Levenback, CF;Ramirez, PT;Gallardo, ST;Patenia, RS;Garcia, ME;Iyer, RB;Freedman, RS
单核细胞/巨噬细胞（MO/MA），先天免疫细胞的多态性群体，具有介导抗肿瘤作用的潜力，也可能有助于促肿瘤作用。已经开发了骨髓细胞动员和免疫刺激生长因子、粒细胞单核细胞刺激因子（GM-CSF，Leukine®）和MO/MA活化细胞因子重组干扰素γ 1b（rIFN-γ1b，Actimmune®）的预激和化疗后方案。化疗前和化疗后的设计是基于这些分子的已知体内动力学和免疫调节作用。卡铂（Paraplatin®）被选为治疗上皮性卵巢癌（EOC）的基石。我们研究了卡铂治疗前后GM-CSF和rIFN-γ1b对复发性EOC患者造血和免疫功能的影响。具有复发性可测量肿瘤的潜在化疗敏感患者接受皮下GM-CSF（起始剂量为400 μg/天）7天，并在静脉内卡铂之前和之后的第5天和第7天皮下注射rIFN-γ1b（100 μg）（曲线下面积为5）。我们进行了标准血液学评估，并监测了单核细胞（MO）、树突状细胞、主要细胞亚群计数和针对Her 2neu+肿瘤细胞系的抗体依赖性细胞介导的细胞毒性（ADCC），以及选定的血浆炎性细胞因子、趋化因子和生长因子水平。我们的分析仅包括最初25名患者的前3个月治疗。相对于治疗前基线值，白色血细胞、中性粒细胞、MO和嗜酸性粒细胞计数增加（每个P ≤ 0.001）;第二次给药后9天血小板比例增加（P ≤ .002）和第三次卡铂治疗组（P ≤ .04）;活化MO亚群CD 14 +HLA-DR+、CD 14 + CD 64+和CD 14 + CXCR 3+中的细胞数量增加（各P ≤ .04）;促血管生成白细胞介素1α、6和8的血浆水平较低（P ≤ 0.03）; M-CSF（活化MO/MA的产物）在第9天增加（P = 0.007）; GM-CSF给药后血浆中GM-CSF增加（P ≤ 0.04）。GM-CSF/IFN-γ1b周期内生活质量测量值降低，而仅FACT-G评分在化疗前基线时恢复。25例接受卡铂治疗的EOC患者接受了一种新的GM-CSF + IFN-γ1b治疗方案，在最初3个月内增加了髓系细胞、血小板和总活化MO数量;然而，在此期间ADCC应答并未持续增强。
Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine®) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-γ1b, Actimmune®) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin®) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC). We studied hematopoietic and immunologic effects of GM-CSF and rIFN-γ1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 μg/day) for 7 days plus subcutaneous rIFN-γ1b (100 μg) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu+ tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels. Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased (P ≤ .001 for each); the proportion of platelets increased 9 days after the second (P ≤ .002) and third (P ≤ .04) carboplatin treatments; and the number of cells in the activated MO subsets CD14+HLA-DR+, CD14+CD64+, and CD14+CXCR3+ increased (P ≤ .04 for each); plasma levels of the proangiogenic interleukins 1α, 6, and 8 were lower (P ≤ .03 for each); M-CSF, a product of activated MO/MA, was increased on day 9 (P = .007); and GM-CSF was increased in plasma after GM-CSF administration (P ≤ .04). Quality of life measurements were reduced during the GM-CSF/IFN-γ1b cycle while recovering at pre-chemotherapy baseline for FACT-G scores only. A novel regimen of GM-CSF plus IFN-γ1b administered to 25 EOC patients receiving carboplatin increased myeloid cells, platelets and total activated MO populations during the initial 3 months; however, ADCC responses were not consistently enhanced during this period.
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与 CXCR3 结合的趋化因子： 新型多功能治疗靶标
DOI：
10.2174/1568008053174723
发表时间：
2005-03-05
期刊：
Current Drug Targets - Immune Endocrine and Metabolic Disorders
影响因子：
--
作者：
Lazzeri, E.;Romagnani, P.
通讯作者：
Romagnani, P.
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K
影响因子：
11.5
作者：
Gordon, IO;Freedman, RS
通讯作者：
Freedman, RS
影响因子：
56.9
作者：
GRABSTEIN, KH;URDAL, DL;CONLON, PJ
通讯作者：
CONLON, PJ
DOI：
10.1128/cdli.8.6.1248-1257.2001
发表时间：
2001-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Kouwenhoven, M;Özenci, V;Link, H
通讯作者：
Link, H