Low-dose-melphalan-induced up-regulation of type-1 cytokine expression in the s.c. tumor nodule of MOPC-315 tumor bearers and the role of interferon γ in the therapeutic outcome
Low-dose-melphalan-induced up-regulation of type-1 cytokine expression in the s.c. tumor nodule of MOPC-315 tumor bearers and the role of interferon γ in the therapeutic outcome
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低剂量马法兰诱导 MOPC-315 肿瘤携带者皮下肿瘤结节中 1 型细胞因子表达的上调以及干扰素 γ 在治疗结果中的作用
DOI：
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
M. Mokyr
中科院分区：
文献类型：
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作者：
L. Gorelik;M. Mokyr
我们先前已经证明了内源性肿瘤坏死因子（TNF）的产生对于低剂量美法仑（L-苯丙氨酸氮芥）治疗携带大MOPC-315肿瘤的小鼠的疗效的重要性。在目前的研究中，我们证明了低剂量美法仑实际上与s.c.肿瘤结节此外，干扰素γ（IFNγ）和白细胞介素-12（IL-12; p40）的mRNA表达也在肿瘤部位升高。然而，虽然TNFα和IFNγ的mRNA表达在化疗后24 h内明显升高，但IL-12（p40）的mRNA表达在化疗后72 h首次明显升高。此外，中和性抗IFN γ mAb，如中和性抗TNF mAb但不中和性抗IL-12 mAb，降低了低剂量美法仑对MOPC-315肿瘤携带者的疗效。对IFNγ在低剂量马法兰处理的MOPC-315荷瘤小鼠中介导其抗肿瘤作用的机制的研究表明，对TNF的直接抗肿瘤作用不敏感的MOPC-315肿瘤细胞对高浓度IFNγ的抗增殖活性显示出一定的敏感性。然而，与TNFα不同，IFNγ不能促进抗MOPC-315细胞毒性T淋巴细胞活性的产生，实际上，对CTL产生发挥抑制活性。总之，我们的研究表明，MOPC-315肿瘤携带者的低剂量美法仑治疗与IFNγ和TNF的mRNA表达的快速升高相关，这两种细胞因子对低剂量美法仑的疗效很重要，并且部分通过不同的机制介导其抗肿瘤作用。
We have previously shown the importance of endogenous tumor necrosis factor (TNF) production for the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor. In the current study we demonstrate that low-dose melphalan is actually associated with enhanced expression of mRNA for TNFα in the s.c. tumor nodule. Moreover, the expression of mRNA for interferon γ (IFNγ) and interleukin-12 (IL-12; p40) is also elevated at the tumor site. However, while elevation in the expression of mRNA for TNFα and IFNγ is evident within 24 h after the chemotherapy, elevation in the expression of mRNA for IL-12(p40) is first evident 72 h after the chemotherapy. Moreover, neutralizing anti-IFNγ mAb, like neutralizing anti-TNF mAb but not neutralizing anti-IL-12 mAb, reduced the curative effectiveness of low-dose melphalan for MOPC-315 tumor bearers. Studies into the mechanism through which IFNγ mediates its antitumor effect in low-dose-melphalan-treated MOPC-315 tumor-bearing mice revealed that MOPC-315 tumor cells, which are not sensitive to the direct antitumor effects of TNF, display some sensitivity to the antiproliferative activity of high concentrations of IFNγ. However, unlike TNFα, IFNγ is unable to promote the generation of anti-MOPC-315 cytotoxic T lymphocyte activity and, in fact, exerts an inhibitory activity on CTL generation. Taken together, our studies illustrate that low-dose melphalan therapy of MOPC-315 tumor bearers is associated with the rapid elevation in the expression of mRNA for IFNγ and TNF, two cytokines which are important for the curative effectiveness of low-dose melphalan, and which mediate their antitumor effect, in part, through distinct mechanisms.
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TCR-V beta 8.3 细胞参与低剂量马法兰治疗患有大 MOPC-315 肿瘤的小鼠。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mokyr,MB;Rubin,M;Newell,KA;Prokhorova,A;Bluestone,JA
通讯作者：
Bluestone,JA
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DOI：
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发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gorelik,L;Rubin,M;Prokhorova,A;Mokyr,MB
通讯作者：
Mokyr,MB
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影响因子：
11.2
作者：
Takesue,BY;Pyle,JM;Mokyr,MB
通讯作者：
Mokyr,MB
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影响因子：
11.2
作者：
Mokyr,MB;Barker,E;Weiskirch,LM;Takesue,BY;Pyle,JM
通讯作者：
Pyle,JM
影响因子：
4.4
作者：
J. Pace;S. Russell;B. Torres;H. Johnson;P. Gray
通讯作者：
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