Small Methods
·
2023
·Vol. 7
·期 11
·2300681
·
IF 12.4
Dan Ruan,Juan Wang,Tao Ding,Liang Chen,Yawei Du,Yiyin Ruan,Wenguo Cui,Weiwei Feng
Intraperitoneal sporadic tumor is a common and complicated syndrome in cancers, causing a high rate of death, and people find that intraperitoneal chemotherapy (IPC) can treat intraperitoneal sporadic tumors better than intravenous chemotherapy and surgery. However, the effectiveness and side effects of IPC are controversial, and the operation process of IPC is complicated. Herein, the injectable paclitaxel-loaded (PTX-loaded) electrospun short fibers are constructed through a series process of electrospinning, homogenizing, crosslinking, and subsequent polydopamine coating and folate acid (FA) modification. The evenly dispersed short fibers exhibited effective tumor cell killing and good injectable ability, which is convenient to use and greatly improved the complex operation procedure. Mussel-like protein poly-dopamine coating and FA modification endowed short fibers with the ability of targeted adhesion to tumors, and therefore the short fibers further acted as a kind of micro membrane that could release drugs to tumors at close range, maintaining local high drug concentration and prevent paclitaxel killing normal tissues. Thus, the target-adhesive injectable electrospun short fibers are expected to be the potential candidate for cancer treatment, especially the intraperitoneal sporadic tumors, which are hard to treat by surgery or intravenous chemotherapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ONCOGENE
·
2024
·
IF 6.9
Shi Jie,Zhou Rui,Wang Shuo,Liu Yuxin,Tian Baorui,Liu Yanhua,Chen Yanan,Hu Taoyu,Mu Yuhao,Wang Shufan,Shao Xintao,Yan Jie,Qu Pengpeng,Wei Ding,Yang Shuang,Shi Yi,Li Jia,Wang Longlong
Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N 196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveal a functionally important glycosite on EGFR for its abnormal activation in cancer.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-15
·
IF 9.429
Huang Xiuyu,Qiu Miaojuan,Wang Tianqi,Li Binbin,Zhang Shiqiang,Zhang Tianzhi,Liu Peng,Wang Qiang,Qian Zhi Rong,Zhu Chengming,Wu Meiying,Zhao Jing
Background Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect.Methods and resultsIn this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice.Conclusion In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.Graphical Abstract
研究领域:
肿瘤学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS Pathogens
·
2024
·Vol. 20
·期 9
·e1012483
·
IF 5.5
Xi Luo,Litian Zhang,Xiaoyuan Xie,Liyan Yuan,Yanqiang Shi,Yinbo Jiang,Wujian Ke,Bin Yang
Fibronectin (FN) is an essential component of the extracellular matrix (ECM) that protects the integrity of the microvascular endothelial barrier (MEB). However, Treponema pallidum subsp . pallidum ( Tp ) breaches this barrier through elusive mechanisms and rapidly disseminates throughout the host. We aimed to understand the impact of Tp on the surrounding FN matrix of MEB and the underlying mechanisms of this effect. In this study, immunofluorescence assays (IF) were conducted to assess the integrity of the FN matrix surrounding human microvascular endothelial cell-1 (HMEC-1) with/without Tp co-culture, revealing that only live Tp exhibited the capability to mediate FN matrix disaggregation in HMEC-1. Western blotting and IF were employed to determine the protein levels associated with the FN matrix during Tp infection, which showed the unaltered protein levels of total FN and its receptor integrin α5β1, along with reduced insoluble FN and increased soluble FN. Simultaneously, the integrin α5β1-binding protein–intracellular vimentin maintained a stable total protein level while exhibiting an increase in the soluble form, specifically mediated by the phosphorylation of its 39 th residue (pSer39-vimentin). Besides, this process of vimentin phosphorylation, which could be hindered by a serine-to-alanine mutation or inhibition of phosphorylated-AKT1 (pAKT1), promoted intracellular vimentin rearrangement and FN matrix disaggregation. Moreover, within the introduction of additional cellular FN rather than other Tp -adhered ECM protein, in vitro endothelial barrier traversal experiment and in vivo syphilitic infectivity test demonstrated that viable Tp was effectively prevented from penetrating the in vitro MEB or disseminating in Tp -challenged rabbits. This investigation revealed the active pAKT1/pSer39-vimentin signal triggered by live Tp to expedite the disaggregation of the FN matrix and highlighted the importance of FN matrix stability in syphilis, thereby providing a novel perspective on ECM disruption mechanisms that facilitate Tp dissemination across the MEB.
Treponema pallidum subsp . pallidum ( Tp ), dominating the global concerned disease—syphilis, can mediate various pathogenic processes through its dissemination, during which the vascular endothelial barrier plays a vital role in the pathogen-host interaction. Tp alters the characteristics of the barrier components, including vascular endothelial cell and the surrounding extracelluar matrix (ECM), while the initial step of Tp dissemination involves breaching the ECM and moving toward the surface within unknown mechanisms. Here, we demostrated that live Tp triggered the pAKT1/pSer39-vimentin signals in microvascular endothelial cells, which promoted the redistribution of vimentin around the perinucleus. And pSer39-vimentin facilitated the detachment of intergrein α5β1 from fibronectin (FN), which is an essential component of ECM for Tp adhesion. Furthermore, we discovered that pAKT1 inhibition or addition of cellular FN could delay the FN matrix disaggregation, ultimately preventing live Tp from traversing the microvascular endothelial barrier. These results provide insights into ECM disruption employed by Tp and identify potential therapeutic targets against syphilis.
研究领域:
微生物学
·
传染病学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）