决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The role of glypican-3 in hepatocellular carcinoma: Insights into diagnosis and therapeutic potential.
Glypican-3(GPC-3)主要存在于胎盘和胎儿肝脏中,在成人组织中表达有限。
Glypican-3(GPC-3)主要存在于胎盘和胎儿肝脏,在成人组织中的表达有限。其在肝细胞癌(HCC)中重新表达并分泌至血清,凸显了其作为诊断标志物的潜力。GPC-3 通过 Wnt、IGF、YAP 和 Hedgehog 等多种信号通路参与细胞增殖、转移、凋亡和上皮-间质转化等重要过程。本综述旨在总结 GPC-3 的结构、生物合成和翻译后修饰,阐明其信号机制及其作为 HCC 促增殖蛋白的作用,并强调其诊断和治疗潜力。我们开展了全面文献综述,重点关注 GPC-3 在不同肿瘤中的表达,尤其是 HCC。综述综合了实验研究和临床试验结果,分析 GPC-3 在 HCC 中的过表达、其与其他肝病的鉴别价值,以及作为诊断和治疗靶点的潜力。GPC-3 在 HCC 中过表达与侵袭性肿瘤行为和不良预后相关,包括总生存期和无病生存期缩短。此外,GPC-3 已成为有前景的治疗靶点。包括单克隆抗体和 CAR-T 细胞疗法在内的免疫疗法研究显示出抑制肿瘤生长和改善临床结局的潜力。综述详细介绍了 GPC-3 在肿瘤发生中的多重作用,包括其对肿瘤相关巨噬细胞、葡萄糖代谢和上皮-间质转化的影响,这些均会促进 HCC 进展。GPC-3 在 HCC 中重新表达并参与关键致瘤过程,凸显其作为早期诊断生物标志物和治疗干预靶点的价值。仍需进一步研究,以充分发挥 GPC-3 在 HCC 管理中的诊断和治疗潜力。
Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog. To review the structure, biosynthesis, and post-translational modifications of GPC-3, and to elucidate its signaling mechanisms and role as a pro-proliferative protein in HCC, emphasizing its diagnostic and therapeutic potential. A comprehensive literature review was conducted, focusing on the expression of GPC-3 in various tumors, with a special emphasis on HCC. The review synthesized findings from experimental studies and clinical trials, analyzing the overexpression of GPC-3 in HCC, its differentiation from other liver diseases, and its potential as a diagnostic and therapeutic target. GPC-3 overexpression in HCC is linked to aggressive tumor behavior and poor prognosis, including shorter overall and disease-free survival. Additionally, GPC-3 has emerged as a promising therapeutic target. Ongoing investigations, including immunotherapies such as monoclonal antibodies and CAR-T cell therapies, demonstrate potential in inhibiting tumor growth and improving clinical outcomes. The review details the multifaceted roles of GPC-3 in tumorigenesis, including its impact on tumor-associated macrophages, glucose metabolism, and epithelial-mesenchymal transition, all contributing to HCC progression. GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management.
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