Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles

Khondee, Supang; Rabinsky, Emily F.; Owens, Scott; Joshi, Bishnu P.; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D.

doi:10.1016/j.jconrel.2014.11.034

Cited by 14 publications

(5 citation statements)

References 33 publications

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“…We also provide evidence that peptide binding does not affect downstream cell signaling. This peptide can potentially be used for therapy by labeling nanocarriers to achieve site-specific drug delivery of high payloads [ 25 ]. These results justify further development of this peptide for clinical imaging in patients at high risk for epithelial-derived cancers in the esophagus and stomach.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia

Zhou

Pang

et al. 2017

Oncotarget

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The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2. We labeled this peptide with a near-infrared fluorophore Cy5.5, and validated the specific binding to FGFR2 overexpressed in cells in vitro. We found high affinity kd = 68 nM and rapid binding k = 0.16 min−1 (6.2 min). In human esophageal specimens, we found significantly greater peptide binding to high-grade dysplasia (HGD) versus either BE or normal squamous epithelium, and good correlation with anti-FGFR2 antibody. We also observed significantly greater peptide binding to excised specimens of esophageal squamous cell carcinoma and gastric cancer compared to normal mucosa. These results demonstrate potential for this FGFR2 peptide to be used as a clinical imaging agent to guide tissue biopsy and improve methods for early detection of EAC and potentially other epithelial-derived cancers.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia

Zhou

Pang

et al. 2017

Oncotarget

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“…injection of EDA (15 mg/kg), EDA (15 mg/kg) plus RAPA (5 mg/kg), NV‐5138 (160 mg/kg), or vehicle on indicated days and were sacrificed on day 10. The doses of EDA, RAPA, or NV‐5138 were determined according to previous studies (Ito et al, 2008; Kato et al, 2019; Khondee et al, 2015). In monoclonal AQP4‐IgG experiments, 2 μl of AQP4‐IgG (5 mg/ml) (or mouse normal IgG) and 1 μl of mouse complement in a total volume of 3 μl were injected intracerebrally.…”

Section: Methodsmentioning

confidence: 99%

Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation

Luo

et al. 2022

Glia

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Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention.

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“…Mice were treated with Rapa/Lps through tail vein injection twice a week, and 5-FU through intraperitoneal injection twice a week. The duration for Rapa/Lps and 5-FU administration was specified by Chen et al 11 and Khondee et al 14 , We monitored the weight twice a week for a month during the experiment.…”

Section: Methodsmentioning

confidence: 99%

Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC (Min/+) Mice and AOM/DSS-Induced Colorectal Cancer Mice

Liu¹,

Zhu²,

Jia³

et al. 2022

IJN

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Background Transgenic C57BL/6-APC (Min/+) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of Rapamycin liposomes (Rapa/Lps) and 5-Fluorouracil (5-FU) has anti-colorectal cancer effects. However, the therapeutic efficacy of Rapa/Lps and 5-FU in other colorectal cancer mice models is yet to be thoroughly explored. The purpose of this study was to investigate the anti-tumor effect of Rapa/Lps combined with 5-FU in vivo and in vitro. Methods In this study, we evaluated the effect of Rapa/Lps and 5-FU on APC (Min/+) mice and AOM/DSS-induced colorectal cancer mice. The small intestine, colorectum, serum, and plasma of mice in each group were collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to intestine tissues. Tube formation assay, Transwell assay, wound healing assay, Western Blot were used to explore the anti-angiogenesis effect of drugs in HUVECs. Results As expected, Rapa/Lps and 5-FU significantly suppressed tumor formation, decreased the number of tumors, and tumor load both in two mouse models, and had no influence on mouse weight. Mechanically, the anti-tumor effect of the drug also was associated in inhibiting angiogenesis and proliferation. Furthermore, we found that Rapa/Lps obviously inhibited HUVECs tube formation and migration. Conclusion Altogether, we revealed the Rapa/Lps synergism with 5-FU decreased colon and small intestinal tumorigenesis in AOM/DSS-treated and APC (Min/+) mice, respectively, and correlated with anti-angiogenesis.

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Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles

Cited by 14 publications

References 33 publications

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia

Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation

Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC (Min/+) Mice and AOM/DSS-Induced Colorectal Cancer Mice

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