Joosten J J, Muijen G N, Wobbes T, Ruers T J
Department of Surgery, University Hospital Nijmegen, The Netherlands.
Cryobiology. 2001 Feb;42(1):49-58. doi: 10.1006/cryo.2001.2302.
Cryoablation has been used successfully for the local treatment of several cancers. Besides local destruction, a systemic antitumor response has been postulated after cryoablation of tumor tissue. In this study we evaluate the possible systemic antitumor response induced by cryodestruction of tumor tissue in two mouse tumor models.
Mice received two subcutaneously placed tumor implants (thigh and flank) of the nonimmunogenic mouse colon tumor cell line, colon 26-B. After 7 days, the thigh implant was treated by cryoablation or excision and the effect on secondary tumor growth was determined by volume measurement of the nontreated flank tumor. Cytokine (IL-1alpha and TNF-alpha) levels in plasma were measured after treatment. Similar experiments were performed in nude mice using a human melanoma cell line (MV3). Moreover, in this model the effect of cryoablation on development of spontaneous lung metastases was evaluated.
In the colon 26-B tumor model treatment of primary tumor implants by cryoablation resulted in a significant inhibition of secondary tumor growth compared to animals treated by surgical excision (P < 0.01). Six hours after treatment, plasma levels of IL-1alpha and TNF-alpha were higher after cryoablation than after excision (P < 0.01). Also in the nude mice model cryoablation resulted in inhibition of secondary tumor growth, though not significant. Mice treated by cryoablation showed significantly less lung metastases compared to those treated by excision (P = 0.03).
Cryoablation of tumor tissue can result in inhibition of secondary and metastatic tumor growth. A cytokine response induced by cryoablation of tumor tissue may attribute to this feature.
冷冻消融已成功用于多种癌症的局部治疗。除了局部破坏外,肿瘤组织冷冻消融后还假定存在全身抗肿瘤反应。在本研究中,我们评估了在两种小鼠肿瘤模型中肿瘤组织冷冻破坏诱导的可能的全身抗肿瘤反应。
小鼠皮下植入两个非免疫原性小鼠结肠肿瘤细胞系结肠26 - B的肿瘤移植物(大腿和胁腹)。7天后,对大腿移植物进行冷冻消融或切除治疗,并通过测量未处理的胁腹肿瘤体积来确定对继发性肿瘤生长的影响。治疗后测量血浆中细胞因子(IL - 1α和TNF - α)水平。使用人黑色素瘤细胞系(MV3)在裸鼠中进行了类似实验。此外,在该模型中评估了冷冻消融对自发性肺转移发展的影响。
在结肠26 - B肿瘤模型中,与手术切除治疗的动物相比,冷冻消融原发性肿瘤移植物导致继发性肿瘤生长受到显著抑制(P < 0.01)。治疗后6小时,冷冻消融后血浆中IL - 1α和TNF - α水平高于切除后(P < 0.01)。在裸鼠模型中,冷冻消融也导致继发性肿瘤生长受到抑制,尽管不显著。与切除治疗的小鼠相比,冷冻消融治疗的小鼠肺转移明显较少(P = 0.03)。
肿瘤组织的冷冻消融可导致继发性和转移性肿瘤生长受到抑制。肿瘤组织冷冻消融诱导的细胞因子反应可能归因于此特征。