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高剂量肿瘤坏死因子α在晚期黑色素瘤区域治疗中的临床经验。

Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma.

作者信息

Lejeune F, Liénard D, Eggermont A, Schraffordt Koops H, Kroon B, Gérain J, Rosenkaimer F, Schmitz P

机构信息

Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland.

出版信息

Circ Shock. 1994 Aug;43(4):191-7.

PMID:7895325
Abstract

Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response compared with 52% after ILP with melphalan alone. Leakage and release of nanograms levels of TNF alpha in the systemic circulation can be abrogated in most patients by low pump flow, continuous leak monitoring, extensive washout, and limb massage. In case of unavoidable leakage, appropriate intensive care results in minimal toxicity. The ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in humans.

摘要

肢体隔离灌注(ILP)能够在副作用可接受的封闭系统中给予高剂量的重组肿瘤坏死因子α(rTNFα)。基于rTNFα与化疗、干扰素-γ以及热疗之间已报道的协同作用,制定了一种三联药物方案。在肢端转移黑色素瘤(IIIA期或AB期)患者中,我们观察到采用该方案的患者完全缓解率达91%,而单独使用美法仑进行ILP治疗的患者完全缓解率仅为52%。通过低泵流量、持续渗漏监测、充分冲洗以及肢体按摩,大多数患者可避免纳克水平的TNFα在体循环中的渗漏和释放。万一发生不可避免的渗漏,适当的重症监护可使毒性降至最低。含rTNFα的ILP似乎是研究人类癌症生物化疗的有用模型。

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Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma.高剂量肿瘤坏死因子α在晚期黑色素瘤区域治疗中的临床经验。
Circ Shock. 1994 Aug;43(4):191-7.
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Rationale for using TNF alpha and chemotherapy in regional therapy of melanoma.在黑色素瘤区域治疗中使用肿瘤坏死因子α和化疗的理论依据。
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Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha.肿瘤坏死因子-α 单独肢体灌注(ILP)后的全身及血流动力学毒性。
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Isolated perfusion of the limb with high-dose tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and melphalan for melanoma stage III. Results of a multi-centre pilot study.
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High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma.高剂量重组肿瘤坏死因子α联合干扰素γ和美法仑用于肢体隔离灌注治疗黑色素瘤和肉瘤
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Isolated limb perfusion with melphalan and tumor necrosis factor alpha for advanced melanoma and soft-tissue sarcoma.使用美法仑和肿瘤坏死因子α进行隔离肢体灌注治疗晚期黑色素瘤和软组织肉瘤。
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Cancer Gene Ther. 2009 Apr;16(4):373-81. doi: 10.1038/cgt.2008.86. Epub 2008 Oct 31.
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The major acute-phase protein, serum amyloid P component, in mice is not involved in endogenous resistance against tumor necrosis factor alpha-induced lethal hepatitis, shock, and skin necrosis.
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High-level constitutive expression of alpha 1-acid glycoprotein and lack of protection against tumor necrosis factor-induced lethal shock in transgenic mice.
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Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience.186例局部晚期肢体软组织肉瘤患者采用肿瘤坏死因子与美法仑进行隔离肢体灌注以挽救肢体。欧洲多中心累积经验。
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