The FGF1/CPP-C chimera protein protects against intestinal adverse effects of C-ion radiotherapy without exacerbating pancreatic carcinoma

Kawano, Mitsuko; Miura, Taichi; Fujita, Mayumi; Koike, Sachiko; Imadome, Kaori; Ishikawa, Atsuko; Yasuda, Takeshi; Imamura, Toru; Imai, Takashi; Nakayama, Fumiaki

doi:10.1016/j.ctro.2018.10.004

Cited by 5 publications

(2 citation statements)

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“…Interestingly, they have suggested the tumor suppressor role of FGF14 in colorectal cancer [29]. Of note, a recent study reported that FGF12 (the homologue of FGF14 [30]) have a malignancy-inhibitor effect on pancreatic cancer cell lines [31]. Two most recent studies reported that FGF14 overexpression leads to tumor suppressive effects in lung adenocarcinoma and nasopharyngeal carcinoma [32,33].…”

Section: Discussionmentioning

confidence: 99%

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

2021

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Background Fibroblast (FGFs) and insulin (IGF) growth factor pathways are among 10 most recurrently altered genomic pathways in pancreatic ductal adenocarcinoma (PDAC). However, the prognostic and therapeutic relevance of FGF and IGF pathways in PDAC is largely unknown. Methods We investigated the relationship between fibroblast and insulin pathway gene expression and clinicopathological features in three independent transcriptomic cohorts of 532 PDAC patients. Furthermore, we have examined the coexpressed genes specific to the prognostic marker identified from these cohorts. Statistical tests including Fisher-exact\Chi-square, Kaplan–Meier, Pearson Correlation and cox regression analyses were performed. Additionally, pathway analysis of gene-specific co-expressed genes was also performed. Results The dysregulation of six genes including FGF9, FGF14, FGFR1, FGFR4, IGF2BP2 and IGF2BP3 were significantly associated with different clinical characteristics (including grade, stage, recurrence and nodes) in PDAC cohorts. 11 genes (including FGF9, FGF13, FGF14, FGF17, FGFR1, FGFRL1, FGFBP3, IGFBP3, IGF2BP2, IGF2BP3 and IGFBPL1) showed association with overall survival in different PDAC cohorts. Interestingly, overexpression of FGF14 was found associated with better overall survival (OS) in all three cohorts. Of note, multivariate analysis also revealed FGF14 as an independent prognostic marker for better OS in all three cohorts. Furthermore, FMN2 and PGR were among the top genes that correlated with FGF14 in all 3 cohorts. Of note, overexpression of FMN2 and PGR was found significantly associated with good overall survival in PDAC patients, suggesting FMN2 and PGR can also act as potential markers for the prediction of prognosis in PDAC patients. Conclusion FGF14 may define a distinct subset of PDAC patients with better prognosis. Moreover, FGF14-based sub-classification of PDAC suggests that FMN2 and PGR can be employed as good prognostic markers in PDAC and this classification may lead to new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

2021

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“…It has been well-documented that aFGF plays an important role in wound healing (Zheng et al, 2015;Hota et al, 2018;Wang et al, 2018;Kawano et al, 2019). Compared to the lyophilized rh-aFGF currently on the market, the rh-aFGF-loaded carbomer hydrogel has the advantage of increased drug intake and enhanced bioavailability, providing the wound with a "wet healing environment" and avoiding secondary contamination (Hui et al, 2018b).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model

Zhang

Huang

et al. 2020

Front. Pharmacol.

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We developed a highly stable recombinant human acidic fibroblast growth factor (rh-aFGF) carbomer 940 hydrogel for wound healing. This study aimed to reveal toxicity target organs and the toxicity dose-response in the long-term administration of rh-aFGF carbomer 940 hydrogel in a rabbit skin wound model. New Zealand rabbits were topically administrated rh-aFGF carbomer 940 hydrogel at a daily dose of 900 IU/cm 2 , 1,800 IU/cm 2 , and 3,600 IU/cm 2 for 28 days. Lyophilized rh-aFGF agent was used as the positive control group. General behavior, serum chemistry, skin irritation, immunogenicity, immunotoxicity, and histopathology were analyzed at designated time points. Results revealed that food intake, body weight, body temperature, heart rate, and eye examinations were all normal, suggesting no obvious toxicity induced by the rh-aFGF hydrogel. Medium and high dose rh-aFGF hydrogel groups and the positive control group displayed increased cell numbers in the local lymph nodes near the site of administration, likely caused mesenteric lymph node follicular hyperplasia, and this observation was alleviated after 14 days of recovery. Immunogenicity studies demonstrated that the serum antibody titer against rh-aFGF increased with the duration and number of drug applications but were not neutralization antibodies. After administration stopped, antibody titer decreased and disappeared in some mice. In summary, the safe dose for long-term administration of rh-aFGF carbomer 940 hydrogel for persistently damaged skin was 900 IU/cm 2 , which is 10 times that of the proposed clinical dosing.

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Protein Delivery and Mimicry

Langel

2023

CPP, Cell-Penetrating Peptides

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The FGF1/CPP-C chimera protein protects against intestinal adverse effects of C-ion radiotherapy without exacerbating pancreatic carcinoma

Abstract: Graphical abstract

Cited by 5 publications

References 21 publications

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model

Protein Delivery and Mimicry

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