胰腺癌的肿瘤微环境研究进展

肿瘤微环境在肿瘤发生发展与转移中扮演着重要角色。胰腺癌作为临床常见的消化系统肿瘤,其肿瘤微环境具有特殊性。对胰腺癌肿瘤微环境的研究有助于我们进一步认识胰腺癌发生发展的机制,并为临床诊断、治疗胰腺癌提供依据。此文综述了近年来胰腺癌肿瘤微环境方面的研究进展。     

肿瘤酸性微环境与抗肿瘤耐药对策研究进展

与正常细胞相比,肿瘤细胞具有细胞外低pH值,细胞质内高pH值的特点。酸性产物生成和膜内外转运的增多加上清除障碍,导致了肿瘤细胞外酸性微环境的产生。另外,肿瘤的酸化还存在于细胞内多种囊泡状细胞器中。这种特殊的pH梯度不但造成化学治疗药物被隔离在酸性区室内,还能上调p-糖蛋白表达和活性,结果使化学治疗药物无法到达细胞内靶点发挥作用,导致肿瘤对化学治疗药物耐药。新近研究表明,应用质子泵抑制剂(PPI)及碱性药物碱化肿瘤,特异性抑制肿瘤多种pH调节因子而抑制膜内外H+转运交换等,可提高化学治疗敏感性及降低耐药。     

肿瘤微环境在食管癌中的研究进展

食管癌(esophageal cancer, EC)是常见的消化系统恶性肿瘤,起病隐匿、侵袭性强,多数患者治疗效果欠佳。肿瘤微环境(tumor microenvironment, TME)是肿瘤细胞生存的局部环境,参与肿瘤细胞增殖、转移和免疫逃逸等重要生物学过程。TME可通过与肿瘤细胞及其细胞因子等协同作用,调控EC的发生发展及治疗。本文就EC微环境的组成,以及靶向TME治疗EC的最新进展进行综述,以期为EC预防和诊疗提供新思路和理论依据。     

胆管癌肿瘤微环境与免疫治疗

肿瘤微环境在胆管癌细胞增殖、促进肿瘤侵袭和转移过程中扮演重要角色,其复杂的作用机制,决定了胆管癌的异质性与恶性潜能,针对微环境中某些因子作为靶点进行抑制,重塑肿瘤微环境中免疫环境,增强自然抗肿瘤免疫反应,经过改善的免疫环境和免疫功能在预测免疫治疗的反应性和确定新的治疗策略方面具有巨大的临床潜力,为胆管癌的定向治疗提供了潜在的研究方向。     

环状RNA在肿瘤微环境中的研究进展

肿瘤的发生、发展是极其复杂的过程,受神经支配,通过血管、淋巴结或经体腔播散转移,涉及整个机体。肿瘤微环境(TME)构成了肿瘤发展过程中的周围环境,并且已经有研究证明其通过与肿瘤细胞的相互作用在癌症疾病中发挥作用。环状RNA(circRNA)是一类具有独特环状结构的小分子非编码RNA,具有重要的基因调控功能。circRN...     

炎症和肿瘤微环境与食管癌防治研究进展

炎症可通过多种分子机制促进恶性肿瘤发生发展,现已被认为是肿瘤治疗的靶点。本文旨在总结炎症促进肿瘤发生和转移的分子机制,分析炎症对抗肿瘤免疫反应的抑制作用,总结炎症与食管癌领域的研究现状及未来主要发展方向,以期为食管癌治疗提供科学依据和有效治疗措施。     

食管癌肿瘤微环境中癌相关细胞研究进展

长期以来,食管癌领域的研究主要集中在肿瘤细胞本身的癌变机制,但近年来研究发现,在肿瘤发生、发展及浸润转移过程中肿瘤微环境中的免疫细胞以及其他各种间质细胞同样扮演着重要的角色,发挥各自重要的作用。要更加全面地了解食管癌,在关注肿瘤细胞的同时,肿瘤微环境的作用同样不可忽视。肿瘤微环境中含有不同种类的细胞群体及其分泌的各类细胞因子,微环境中癌相关细胞与肿瘤细胞之间相互作用,影响肿瘤的发生发展。本文对食管癌微环境中癌相关细胞及其与食管癌细胞之间的相互作用进行综述。     

肿瘤微环境与耐药的发生在恶性血液病中研究进展

肿瘤微环境与肿瘤细胞相互作用可以导致肿瘤细胞发生耐药,称为肿瘤微环境介导的细胞耐药(EM-DR)。EM-DR主要包括细胞黏附介导的耐药(CAM-DR)、可溶性因子介导的耐药(SM-DR)和其它途径诱导的耐药。SM-DR涉及大量的因子,这些因子主要通过促进恶性血细胞存活与增殖,抑制恶性血细胞凋亡导致细胞对药物不敏感。CAM-DR的研究主要通过肿瘤耐药细胞模型完成的,常见模型包括:球形模型、FN模型、间质模型。通过对模型研究发现肿瘤微环境可通过不同信号通路向细胞提供存活信号,从而导致耐药发生。另外肿瘤微环境还可调节耐药基因表达或局部的pH值诱导恶性血细胞发生耐药。本文就肿瘤微环境介导的恶性血液病细胞耐药的研究进展做一综述。     

肺癌微环境中免疫细胞与肿瘤免疫逃逸相关研究进展

肺癌肿瘤局部浸润的免疫细胞、间质细胞及所分泌的活性介质等与肺癌细胞共同构成的局部内环境又被称之为肺癌微环境。肺癌微环境中浸润的免疫细胞参与了肺癌的疾病进展和免疫逃逸。本文对这一群细胞的浸润特征、功能和相互关系进行阐述,探讨其在肺癌发生发展过程中的作用。     

肺癌转移的炎症微环境机制研究进展

近年来,炎症微环境在肿瘤进展过程中的作用日益受到重视,多项研究表明肺癌的炎症微环境在肺癌的转移中起着重要作用.炎症微环境可以通过直接或间接促进肿瘤血管生成、细胞增殖和抑制细胞凋亡进程,从而促进肺癌的转移,而这一过程主要是借助炎症因子、炎症信号通路等途径而实现的.本文就近年来肺癌转移的炎症微环境机制相关的研究进展作一综述.     

The influence of the microenvironment on liver-specific tumor cell colonization in a murine tumor model

Summary Malignant tumors often show an organ-specific metastatic spread. Some cells of the primary apparently bear an affinity for growing in the microenvironment of certain organs. After i.v. injection of myofibrosarcoma cells from the primary ER 15-P into the tail vein of male C57/BI₆J mice, metastases developed in various organs. A tumor cell line (ER 15-Me₃) isolated from liver metastases of the primary was found to colonize preferentially to the liver. To find out whether the liver specificity of the tumor cell line ER 15-Me₃ depended on the hepatic microenvironment, tumor cells from this line were transplanted i.m. into the thighs of mice once (ER 15-Me₃ i.m.₁) or 5 times (ER 15-Me₃ i.m.₅), and then injected into the tail vein of mice. A part of the 5-times passaged tumor cell line was also injected into the mesenteric vein (ER 15-Me₃ i.m.₅-Me₁) prior to reinjection into the tail vein. Results: After i.v. administration of tumor cells from the first i.m. passage of the tumor cell line (ER 15-Me₃ i.m.₁) into the tail vein, the liver-specific metastatic behavior of tumor cells remained stable. Following the i.v. injection of tumor cells from the 5th i.m. transplant generation of the tumor cell line (ER 15-Me₃ i.m.₅) into the tail vein, organ distribution was similar to that of the primary. After only 1 mesenteric vein passage of the 5-times i.m. transplanted line ER 15-Me₃ i.m.₅-Me₁ followed by i.v. injection into the tail vein, did tumor cells regain their liver-specific colonizing potential. Thus, the liver-specific tumor cell line seems to contain a small number of other tumor cell populations from the unselected primary. In the muscle, these tumor cells have a growth advantage over the liver-specific cells, while the latter will grow better in the liver. This indicates that the microenvironment may be one important factor influencing the organ-specific metastatic pattern of tumor cells.     

Hedgehog signaling in the murine melanoma microenvironment

The Hedgehog intercellular signaling pathway regulates cell proliferation and differentiation. This pathway has been implicated to play a role in the pathogenesis of cancer and in embryonic blood vessel development. In the current study, Hedgehog signaling in tumor related vasculature and microenvironment was examined using human umbilical vein endothelial cells and B16F0 (murine melanoma) tumors models. Use of exogenous Sonic hedgehog (Shh) peptide significantly increased BrdU incorporation in endothelial cells in vitro by a factor of 2 (P < 0.001). The Hedgehog pathway antagonist cyclopamine effectively reduced Shh-induced proliferation to control levels. To study Hedgehog signaling in vivo a hind limb tumor model with the B16F0 cell line was used. Treatment with 25 mg/kg cyclopamine significantly attenuated BrdU incorporation in tumor cells threefold (P < 0.001), in tumor related endothelial cells threefold (P = 0.004), and delayed tumor growth by 4 days. Immunohistochemistry revealed that the Hedgehog receptor Patched was localized to the tumor stroma and that B16F0 cells expressed Shh peptide. Furthermore, mouse embryonic fibroblasts required the presence of B16F0 cells to express Patched in a co-culture assay system. These studies indicate that Shh peptide produced by melanoma cells induces Patched expression in fibroblasts. To study tumor related angiogenesis a vascular window model was used to monitor tumor vascularity. Treatment with cyclopamine significantly attenuated vascular formation by a factor of 2.5 (P < 0.001) and altered vascular morphology. Furthermore, cyclopamine reduced tumor blood vessel permeability to FITC labeled dextran while having no effect on normal blood vessels. These studies suggest that Hedgehog signaling regulates melanoma related vascular formation and function. L. Geng and K.C. Cuneo contributed equally to this work.     

Inflammatory microenvironment contributes to epithelial-mesenchymal transition in gastric cancer

Gastric cancer (GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori (H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition (EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT.     

精准医学时代下肝内胆管癌的发病机制与临床转化

肝内胆管癌(ICC)是仅次于肝细胞癌的第二大肝脏恶性肿瘤,占所有原发性肝癌的15%~20%。近年来,全球ICC的发病率呈上升趋势。但因其起病隐匿,恶性程度高,侵袭能力强,多数患者就诊时就已处于终末期,失去了手术的最佳时机。随着二代测序技术的不断发展,使得ICC治疗不断向个体化、精准化方向发展。介绍了ICC在发病机制、分子分型、早期诊断方面等基础研究的进展,并回顾了近几年ICC的临床转化研究。希望通过其进展,为ICC的治疗和临床研究提供新思路。     

毒蕈碱胆碱受体与肿瘤关系的研究进展

非神经元性胆碱能信号通路与肿瘤关系密切,许多肿瘤细胞表达胆碱能自分泌环。肿瘤细胞自分泌及旁分泌乙酰胆碱,作用于自身或邻近细胞的烟碱胆碱受体及毒蕈碱胆碱受体,调节肿瘤细胞的增殖、血管发生及凋亡。毒蕈碱胆碱受体是 G 蛋白耦联受体,主要有 M1R-M5R 共5个亚型。研究发现毒蕈碱胆碱受体在肺癌、结肠癌、黑色素瘤、乳腺癌、卵巢癌、前列腺癌、胃癌和脑星形细胞瘤等多种恶性肿瘤中均有表达,与肿瘤细胞的增殖、迁移、血管发生、凋亡有密切关系,其中尤以毒蕈碱胆碱受体3最为重要,这为肿瘤的治疗提供了一个新的研究方向。     

蛋白质组学在胰腺癌中的研究进展

胰腺癌是一种常见的恶性肿瘤,迫切需要早期诊断及治疗。快速发展的蛋白质组学技术为探讨胰腺癌发生的分子机制、发现新的肿瘤标记物及治疗靶点提供了新的手段,在胰腺癌研究中显示出巨大的前景。