A mouse model of lung cancer induced via intranasal injection for anticancer drug screening and evaluation of pathology

Tanaka, Ryo; Yoshinouchi, Shosei; Karouji, Kento; Tanaka, Yuki; Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Itoh, Yoshifumi; Miyaura, Chisato; Inada, Masaki

doi:10.1002/2211-5463.13486

Cited by 3 publications

(3 citation statements)

References 32 publications

(45 reference statements)

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“…Additionally, there were clear neoplastic lesions such adenomas, adenocarcinomas, and adenosquamous carcinomas. These findings are consistent with a prior study that found that Ure initiates stage-2 carcinogenesis, and BHT then stimulates the development of started cells (Tanaka et al, 2023).…”

Section: Discussionsupporting

confidence: 93%

Antitumor efficacy of atorvastatin in lung cancer mice model

El-Said,

Attia,

Salim

2024

Biological and Biomedical Journal

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One of the most prevalent cancers in the world is lung cancer. Various factors, multiple inherited, and acquired mechanisms contribute to lung carcinogenesis. The cholesterol-lowering medication atorvastatin (ATOR) has been demonstrated to have additional intriguing biological uses, such as anticancer effects. This study aimed to evaluate the effects of ATOR treatment against lung cancer in mice model. Forty-five male CD-1 mice were divided into 3 groups (n = 15) as the follows: Group 1 (G1) was used as a normal control. Gps 2 and 3 were administered with urethane (Ure) (1mg/g) and butylated hydroxytoluene (BHT) (200 mg/kg) for lung cancer initiation and promotion, respectively. G2 was left as a cancer-bearing group. G3 was post-treated with 10 mg/kg ATOR. The results showed that the treatment of Ure/BHT-administered mice with ATOR led to a significant decreased in the tumour incidences, multiplicities, and sizes as compared with each treatment alone. Further, the treatment with ATOR has significantly induced apoptosis in lung tumour cells without adverse side effects.

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Section: Discussionsupporting

confidence: 93%

Antitumor efficacy of atorvastatin in lung cancer mice model

El-Said,

Attia,

Salim

2024

Biological and Biomedical Journal

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“…Studies of the miRNA content of circulating tumor EVs, specifically those purified from the circulation or those from other biofluids, have identified unique profiles, which can be associated with their tumor cells of origin [84] . Therefore, it is well perceived that the isolation of tumor EVs from biofluids, followed by the analysis of their miRNA cargos, has the potential to enable the development of non-invasive tumor detection assays for diagnostic and prognostic applications [85][86][87][88][89][90][91] .…”

Section: Introductionmentioning

confidence: 99%

“…In this proof-of-principle study, we sought to explore the potential of utilizing exhaled miRNAs for non-invasive detection of secondary lung cancer in orthotopic animal models. For these analyses, we chose to inoculate a highly metastatic breast cancer cell line that has been well documented to rapidly establish significant pathological lung tumor burden in athymic nude mice, which provided an adequate model to test the collection and analysis of exhaled breath condensates [ 92 – 95 ] .…”

Section: Introductionmentioning

confidence: 99%

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles

Mitchell,

Ben-Dov,

Liu

et al. 2024

Extracell Vesicles Circ Nucleic Acids

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Aim: The lung is the second most frequent site of metastatic dissemination. Early detection is key to improving survival. Given that the lung interfaces with the external environment, the collection of exhaled breath condensate (EBC) provides the opportunity to obtain biological material including exhaled miRNAs that originate from the lung. Methods: In this proof-of-principal study, we used the highly metastatic MDA-MB-231 subline 3475 breast cancer cell line (LM-3475) to establish an orthotopic lung tumor-bearing mouse model and investigate non-invasive detection of lung tumors by analysis of exhaled miRNAs. We initially conducted miRNA NGS and qPCR validation analyses on condensates collected from unrestrained animals and identified significant miRNA expression differences between the condensates of lung tumor-bearing and control mice. To focus our purification of EBC and evaluate the origin of these differentially expressed miRNAs, we developed a system to collect EBC directly from the nose and mouth of our mice. Results: Using nanoparticle distribution analyses, TEM, and ONi super-resolution nanoimaging, we determined that human tumor EVs could be increasingly detected in mouse EBC during the progression of secondary lung tumors. Using our customizable EV-CATCHER assay, we purified human tumor EVs from mouse EBC and demonstrated that the bulk of differentially expressed exhaled miRNAs originate from lung tumors, which could be detected by qPCR within 1 to 2 weeks after tail vein injection of the metastatic cells. Conclusion: This study is the first of its kind and demonstrates that lung tumor EVs are exhaled in mice and provide non-invasive biomarkers for detection of lung tumors.

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Comparative analysis of two arecoline‐induced oral submucous fibrosis models

Tang,

Jiang,

Zhou

et al. 2023

Oral Diseases

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ObjectiveThe limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline‐induced water drinking and injection mouse models.Materials and MethodsThe mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4‐week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively.ResultsDuring arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water‐drinking model also demonstrated multi‐organ fibrosis involving the tongue, lungs, and small intestine.ConclusionBoth the water drinking and injection mouse models effectively induced OSF, but the water‐drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF.

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A mouse model of lung cancer induced via intranasal injection for anticancer drug screening and evaluation of pathology

Cited by 3 publications

References 32 publications

Antitumor efficacy of atorvastatin in lung cancer mice model

Antitumor efficacy of atorvastatin in lung cancer mice model

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles

Comparative analysis of two arecoline‐induced oral submucous fibrosis models

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