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通过半抗原诱导的肿瘤相关自身抗体(iTAA)实现致癌核抗原的原位靶向。

Successful targeting in situ of an oncogenic nuclear antigen by hapten induced tumor associated autoantibodies (iTAA).

机构信息

TaiMei Baofa Cancer Hospital, Dongping, 271500, Shandong Province, China.

Jinan Baofa Cancer Hospital, Jinan, 250000, Shandong Province, China.

出版信息

Sci Rep. 2023 Jun 19;13(1):9902. doi: 10.1038/s41598-023-36757-2.

Abstract

The abscopal is a hypothesis for treating of non-irradiated tumors after localized radiation therapy. It is associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs), with increasing of anti-MAGEA3 and an relationship between the abscopal effect and immune response. The hapten enhanced local chemotherapy (HELC) was studied to kills tumor and release tumor TAAs, then hapten modify the TAAs to neu-TAAs, to produce tumor autologous antibodies, called induced tumor-associated autoantibodies (iTAAs) that is different from natural TAAs. Since the iTAAs and complement (C) are associated with cancer therapy Immunofluorescence (IF) was applied to evaluate the expression of the iTAAs and C3, C5, C9. Traces resulted in a partial staining of the nucleus in C3's perinuclear reaction. The iTTAs of Survivin, C-MYC, and IMP1 increased significantly in the tumor cells' intranuclear regions (P = 0.02, P = 0.00, P < 0.0001). Koc, zeta, RalA, and p53 had a similar trend in the perinuclear regions (P < 0.0001, P = 0.004, P < 0.0001, P = 0.003). Therefore, we can propose that tumor antigens inside the cancer cells' nuclei are targeted by the iTAAs since the iTAAs binding levels are higher after HELC. The iTAA tagging oncogenic nuclear antigens may play a distinctive role in regulating tumor cell growth.

摘要

远隔效应是一种在局部放射治疗后治疗未照射肿瘤的假说。它与肿瘤相关基因的产物(自身抗体,aTAA)有关,这些产物是针对肿瘤相关抗原(TAA)的反应产物,抗 MAGEA3 增加,与远隔效应和免疫反应之间存在关系。半抗原增强局部化疗(HELC)被研究用于杀死肿瘤并释放肿瘤 TAA,然后半抗原修饰 TAA 成为neu-TAAs,从而产生肿瘤自体抗体,称为诱导性肿瘤相关自身抗体(iTAA),与天然 TAA 不同。由于 iTAA 和补体(C)与癌症治疗免疫荧光(IF)有关,因此应用 IF 来评估 iTAA 和 C3、C5、C9 的表达。结果导致 C3 核周反应中核的部分染色。Survivin、C-MYC 和 IMP1 的 iTTAs 在肿瘤细胞核内区域显著增加(P=0.02,P=0.00,P<0.0001)。核周区域 Koc、zeta、RalA 和 p53 也有类似的趋势(P<0.0001,P=0.004,P<0.0001,P=0.003)。因此,我们可以提出,由于 HELC 后 iTAA 的结合水平更高,因此肿瘤细胞核内的肿瘤抗原是 iTAA 的靶点。iTAA 标记致癌核抗原可能在调节肿瘤细胞生长中发挥独特作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a1/10279707/979057ba66b3/41598_2023_36757_Fig1_HTML.jpg

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