Inflammatory Changes after Cryosurgery-Induced Necrosis in Human Melanoma Xenografted in Nude Mice

Abstract

There is growing evidence that necrosis, instead of apoptosis, could act as a natural adjuvant, which could activate an immune response. In this work we have investigated if induction of tumor necrosis could trigger the affluence of inflammatory cells at the tumor site, and thus induce an immune response. For this purpose, a liquid N2 spray was applied on human melanoma (IIB-MEL-J cell line) xenografted in nude mice and 24 h later some mice received intratumorally a single 500 U dose of recombinant murine granulocyte macrophage-colony-stimulating factor. 77-100% of the tumor mass underwent necrosis. Congestion, edema, and endothelial cell activation were the first noticeable events. A quick infiltrative response of polymorphonuclear leukocytes around the tumor was detected 24 h after liquid N2 application, peaking at day 3. Massive macrophage recruitment was observed since day 3. An early intratumoral infiltration with inflammatory cells was only detected in the group that received recombinant murine granulocyte macrophage- colony-stimulating factor after necrosis induction by liquid N2. Coexisting DEC 205- and F4/80-positive cells increased in number, and their localization was predominantly peritumoral after necrosis. Antibody response was only detected in the groups with tumor-induced necrosis. Our results suggest that cryosurgery-induced necrosis could be a useful model to analyze the interaction among necrosis, inflammation, and the generation of an immune response.

Antitumor Activity of 3-Ingenyl Angelate

“…The early mitochondrial swelling seen after PEP005 treatment and the necrotic outcome is reminiscent of ischemia reperfusion injury in which plasma membrane disruption (34) and mitochondrial dysfunction and rapid depletion of ATP are central to the induction of cell death (35). Cryotherapy also induces primary necrosis and, like PEP005, is associated with an inflammatory reaction at the treatment site (36). Plasma membrane disruption is likely to cause changes in cytoplasmic ionic concentrations, which can lead to mitochondrial swelling and loss of mitochondrial membrane po- tential (32)(33)(34).…”

Establishment of association of an Mg2+‐dependent endonuclease with the rat liver nuclear matrix in cryonecrosis

“…Freezing tissue in situ induces fast and massive necrosis, 28 and is the basis of cryotherapy of many tissues. [36][37][38][39] Activity gel analysis of the nuclear matrix prepared from the in situ injured liver section showed the increased presence of nuclear matrix-associated p23 ( Figure 1A, lane 8). It should be mentioned that the band that corresponded to p23 was somewhat fainter than in the case of the ex vivo frozen/ thawed whole liver sample (lanes 6 and 7) due to the presence of healthy liver tissue around the necrotic area in the excised sample.…”

Immunologic response induced by synergistic effect of alternating cooling and heating of breast cancer

“…After the alternating treatment, intracellular HSPs greatly increased and tumor cells became necrotic, which favored formation of HSPantigen complex and its release into the surrounding media [15,17,34]. On the other hand, freezing initiated an inflammatory environment, in which many different cytokines were released [16,17].…”

“…On the other hand, cryosurgery caused tumor necrosis could initiate an inflammatory environment. The presence of tumor antigens in such an environment could induce cryoimmunity [12,16,17].…”