Immunotherapy of carcinomatous pleuritis and peritonitis targeting phosphoglucose isomerase as a vaccine.

肿瘤的进展和转移受细胞外生长因子和细胞因子控制。PGI（EC 5. 3. 1. 9)是一种普遍存在的细胞溶质酶，催化糖酵解的第二步。分子克隆和测序已经确定PGI作为运动因子。即，自分泌运动因子（AMF），也称为神经白细胞介素或成熟因子。AMF/PGI也是一种多功能细胞因子，通过独特的同源78 kDa（gp 78）七跨膜糖蛋白受体（自分泌运动因子受体，AMFR）表现出多功能生长因子样活性。我们已经证明AMF/PGI的过表达与细胞周期蛋白/细胞周期蛋白依赖性激酶活性的上调和p27 β的下调一起增强细胞增殖<Kip1>。AMF/PGI和AMFR的过表达已在广泛的恶性肿瘤中被发现，并且与癌症进展、转移和血管生成相关。 ...更多信息 肿瘤细胞，对正常组织无不良影响。利用化疗和放疗的常规方法受到其毒性和缺乏特异性的限制。近年来，研究人员进行了几项研究，旨在评估人类肿瘤相关抗原是否可以作为免疫治疗的靶点，特别是人类癌症疫苗的开发。临床研究可能难以实施，特别是当无法从相关动物研究中清楚了解免疫策略的潜在疗效、局限性和安全性时。在这项研究中，我们使用小鼠模型评估了PGI在人类癌细胞中的过表达是否会增强肝转移。我们还研究了PGI在人癌细胞系中的细胞内信号转导途径。在体内，植入裸鼠后，对照细胞产生局部相对较小的肿瘤，没有肝转移的证据，而PGI转染的细胞产生大肿瘤和肝转移。本文提交的数据表明，PGI表达显著有助于人类癌症的侵袭性表型。因此，PGI可以作为一个重要的和广泛适用的抗癌免疫策略的目标。少

The progression and metastasis of cancer are controlled by extracellular growth factors and cytokines. PGI (EC 5. 3. 1. 9) is a ubiquitous cytosolic enzyme that catalyzes the second step in glycolysis. Molecular cloning and sequencing have identified PGI as a motility factor. I.e., autocrine motility factor (AMF), also known as and neuroleukin or maturation factors. AMF/PGI is also a multifunctional cytokine that exhibits multifunctional growth factor-like activity via a unique cognate 78 kDa (gp78) seven-transmembrane glycoprotein receptor (autocrine motility factor receptor, AMFR). We have shown that the overexpression of AMF/PGI enhances cell proliferation together with up-regulation of cyclin/cyclin-dependent kinase activities and down-regulation of p27^<Kip1>. Overexpression of AMF/PGI and AMFR has been found in a wide spectrum of malignancies and is associated with cancer progression, metastasis, and angiogenesis.The goal of cancer therapy remains as the long-term eradication of … More tumor cells without adverse effects on normal tissue. Conventional approaches utilizing chemotherapy and radiotherapy are limited by both their toxicity and lack of specificity. In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens can be exploited as targets for immunotherapy, specifically for human cancer vaccine development A major limitation in immunotherapy studies of human cancer is the general lack of appropriate preclinical models. Clinical studies can be difficult to implement, particularly when a clear understanding of the potential efficacy, limitation, and safety of an immunotherapeutic strategy is not available from relevant animal investigations. In this study, we assessed whether overexpression of PGI in human cancer cells enhances the liver metastasis using a mouse model. We also investigated the intracellular signal transduction pathways of PGI in human cancer cell lines. In vivo, after implantation into the nude mice, control cells produced locally relatively small tumors with no evidence of liver metastasis, whereas PGI-transfected cells produced the large tumors and liver metastases. The data submitted here show that PGI expression significantly contributes to the aggressive phenotype of human cancer. Thus, PGI may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Less