<scp>DT</scp><sup>270‐326</sup>, a Truncated Diphtheria Toxin, Increases Blood–Tumor Barrier Permeability by Upregulating the Expression of Caveolin‐1

Lin, Yongcheng; Wang, Ping; Liu, Yunhui; Shang, Xiuli; Chen, Liang‐Yu; Xue, Yixue

doi:10.1111/cns.12519

Cited by 8 publications

(5 citation statements)

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“…Analysis of cell viability was performed as preciously described . Cell survival was evaluated by a nonradioactive cell counting kit (CCK‐8) assay according to the manufacture's instruction, and the fluorescence was measured using a Tecan Infinity M200 plate reader (Tecan Group, Morrisville, NC, USA).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Wang

et al. 2016

CNS Neurosci Ther

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Section: Methodsmentioning

confidence: 99%

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Wang

et al. 2016

CNS Neurosci Ther

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“…Despite extensive resection and a combination of chemo‐ and radiotherapy, the median survival of GBM patients is only 15 months . Caveolae are organelles of the plasma membrane in various types of human cells that play a crucial physiological role in the regulation of various cellular functions, including endocytosis, cell signaling, membrane trafficking, and lipid regulation . Caveolar coat components include two major protein families, cavins and caveolins .…”

Section: Introductionmentioning

confidence: 99%

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

et al. 2018

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Summary Aims Glioblastoma (GBM) is a lethal disease of the central nervous system with high mortality, and novel therapeutic targets and strategies for GBM are urgently needed. Caveolae‐associated protein 1 (CAVIN1) is an essential caveolar component‐encoding gene and has been poorly studied in glioma. To this end, in this study, we evaluated CAVIN1 expression in glioma tissue as well as the correlation between CAVIN1 expression and prognosis in glioma patients using the data collected from clinical samples or from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, and Gene Expression Omnibus (GEO) data sets. Methods Survival analysis was performed with the Kaplan‐Meier curve and log‐rank test. The predictive role of CAVIN1 in progressive malignancy in glioma was evaluated by using a receiver operator characteristic (ROC) curve. Gene ontology (GO), Gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) methods were used to interpret the functions of CAVIN1 in GBM. Results CAVIN1 expression was elevated in GBM compared with that in low‐grade glioma and nontumor brain samples and was correlated with unfavorable outcomes in glioma patients. Additionally, CAVIN1 could serve as an independent predictive factor for progressive malignancy in GBM. Furthermore, CAVIN1 was associated with disrupted angiogenesis and immune response in the tumor microenvironment of GBM. Conclusions We identified CAVIN1 as a prognostic biomarker and potential target for developing novel therapeutic strategies against GBM.

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“…The tumor-cell specificity of DT386F-endoNA2 was based on two mechanisms of recognition: polysialic acid-binding via the non-catalytic endosialidase portion (22) and binding to the surface of cancer cells via the "receptorless" toxin (38). For the latter, the underlying mechanisms are not known but have been suggested to include pH-dependent membrane insertion of the translocation domain that is induced by extracellular acidification near cancer cell surfaces (41), or interaction of the translocation domain with caveolin-1 (42). Most importantly, DT386F-endoNA2 did not show toxicity toward normal polysialic acidnegative cells while the toxin conjugate exhibited a drastic induction of apoptosis in neuroblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

Design of a Cytotoxic Neuroblastoma-Targeting Agent Using an Enzyme Acting on Polysialic Acid Fused to a Toxin

Lehti

Pajunen

Jokilammi

et al. 2021

Molecular Cancer Therapeutics

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Polysialic acid, an abundant cell surface component of the developing nervous system, which declines rapidly postnatally to virtual absence in the majority of adult tissues, is highly expressed in some malignant tumors including neuroblastoma. We found that the binding of a noncatalytic endosialidase to polysialic acid causes internalization of the complex from the surface of neuroblastoma kSK-N-SH cells, a subline of SK-N-SH, and leads to a complete relocalization of polysialic acid to the intracellular compartment. The binding and uptake of the endosialidase is polysialic acid–dependent as it is inhibited by free excess ligand or removal of polysialic acid by active endosialidase, and does not happen if catalytic endosialidase is used in place of inactive endosialidase. A fusion protein composed of the noncatalytic endosialidase and the cytotoxic portion of diphtheria toxin was prepared to investigate whether the cellular uptake observed could be used for the specific elimination of polysialic acid–containing cells. The conjugate toxin was found to be toxic to polysialic acid–positive kSK-N-SH with an IC50 of 1.0 nmol/L. Replacing the noncatalytic endosialidase with active endosialidase decreased the activity to the level of nonconjugated toxin. Normal nonmalignant cells were selectively resistant to the toxin conjugate. The results demonstrate that noncatalytic endosialidase induces a quantitative removal and cellular uptake of polysialic acid from the cell surface which, by conjugation with diphtheria toxin fragment, can be exploited for the selective elimination of polysialic acid–containing tumor cells.

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DT^270‐326, a Truncated Diphtheria Toxin, Increases Blood–Tumor Barrier Permeability by Upregulating the Expression of Caveolin‐1

Abstract: DT(270-326) might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the BTB.

Cited by 8 publications

References 55 publications

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

Design of a Cytotoxic Neuroblastoma-Targeting Agent Using an Enzyme Acting on Polysialic Acid Fused to a Toxin

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DT270‐326, a Truncated Diphtheria Toxin, Increases Blood–Tumor Barrier Permeability by Upregulating the Expression of Caveolin‐1

Abstract: DT(270-326) might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the BTB.

Cited by 8 publications

References 55 publications

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3‐A20 in Ischemic Stroke

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

Design of a Cytotoxic Neuroblastoma-Targeting Agent Using an Enzyme Acting on Polysialic Acid Fused to a Toxin

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DT^270‐326, a Truncated Diphtheria Toxin, Increases Blood–Tumor Barrier Permeability by Upregulating the Expression of Caveolin‐1