Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy

Almeida, Cátia Rebelo de; Mendes, R. Vilela; Pezzarossa, Anna; Gago, Joaquim; Carvalho, Carlos; Alves, António; Nunes, Vítor; Brito, María José; Cardoso, Maria João; Ribeiro, Joana; Cardoso, Fátima; Ferreira, Miguel Godinho; Fior, Rita

doi:10.1038/s42003-020-1015-0

Cited by 47 publications

(48 citation statements)

References 50 publications

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“…In zPDX CRC cell lines and cell suspension derived from the patient, biopsies were microinjected, without in vitro passaging, into multiple zebrafish larvae, and the therapy response was evaluated in just 4 days (Fig. 2 ) [ 136 – 138 ]. Increasing shreds of evidences demonstrated that the zPDX were able to recapitulate several cancer features such as proliferation, metastatic potential and angiogenesis and to predict tumor responses to radiotherapy [ 136 ] and standard chemotherapy, such as FOLFOX (5-FU + oxaliplatin + folinic acid) and FOLFIRI (5-FU + irinotecan + folinic acid) [ 137 ].…”

Section: Patient-derived Modelsmentioning

confidence: 99%

Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

Rizzo

Bertotti

Leto

et al. 2021

J Exp Clin Cancer Res

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Colorectal cancer (CRC), despite the advances in screening and surveillance, remains the second most common cause of cancer death worldwide. The biological inadequacy of pre-clinical models to fully recapitulate the multifactorial etiology and the complexity of tumor microenvironment and human CRC’s genetic heterogeneity has limited cancer treatment development. This has led to the development of Patient-derived models able to phenocopy as much as possible the original inter- and intra-tumor heterogeneity of CRC, reflecting the tumor microenvironment’s cellular interactions. Implantation of patient tissue into immunodeficient mice hosts and the culture of tumor organoids have allowed advances in cancer biology and metastasis. This review highlights the advantages and limits of Patient-derived models as innovative and valuable pre-clinical tools to study progression and metastasis of CRC, develop novel therapeutic strategies by creating a drug screening platform, and predict the efficacy of clinical response to therapy.

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Section: Patient-derived Modelsmentioning

confidence: 99%

Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

Rizzo

Bertotti

Leto

et al. 2021

J Exp Clin Cancer Res

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“…With numerous xenografts, many different treatments can be tested w results produced within days. Patient biopsies were transplanted into zebrafish and te for responsiveness to the anti-angiogenic drug bevacizumab in a proof-of-concept st for zebrafish avatars [73]. Tumor responsiveness, the impact on angiogenesis, and num of micrometastases in zebrafish, were measured before administering drugs to the Patient-derived xenografts (PDX) provide a more authentic view to investigate cancer.…”

Section: Zebrafish Xenografts For Cancer Drug Screeningmentioning

confidence: 99%

The Zebrafish Xenograft Models for Investigating Cancer and Cancer Therapeutics

Gamble

Elson

Greenwood

et al. 2021

Biology

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In order to develop new cancer therapeutics, rapid, reliable, and relevant biological models are required to screen and validate drug candidates for both efficacy and safety. In recent years, the zebrafish (Danio rerio) has emerged as an excellent model organism suited for these goals. Larval fish or immunocompromised adult fish are used to engraft human cancer cells and serve as a platform for screening potential drug candidates. With zebrafish sharing ~80% of disease-related orthologous genes with humans, they provide a low cost, high-throughput alternative to mouse xenografts that is relevant to human biology. In this review, we provide background on the methods and utility of zebrafish xenograft models in cancer research.

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“…pylori virulence factor cagA (cagA) with wild-type (WT) or tp53 mutated zebrafish [25][26][27][28]. The zebrafish xenograft model also provides an excellent platform for studying CRC tumor metastasis and drug screening [29][30][31]. Previous research has shown zebrafish patient-derived xenografts (zPDX) derived from surgically resected human CRC samples and treated with the same treatment administered to the donor patient.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharides Enhance Epithelial Hyperplasia and Tubular Adenoma in Intestine-Specific Expression of krasV12 in Transgenic Zebrafish

Sun

Fong

et al. 2021

Biomedicines

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Intestinal carcinogenesis is a multistep process that begins with epithelial hyperplasia, followed by a transition to an adenoma and then to a carcinoma. Many etiological factors, including KRAS mutations and inflammation, have been implicated in oncogenesis. However, the potential synergistic effects between KRAS mutations and inflammation as well as the potential mechanisms by which they promote intestinal carcinogenesis remain unclear. Thus, the objective of this study was to investigate the synergistic effects of krasV12, lipopolysaccharides (LPS), and/or dextran sulfate sodium (DSS) on inflammation, tumor progression, and intestinal disorders using transgenic adults and larvae of zebrafish. Histopathology and pathological staining were used to examine the intestines of krasV12 transgenic zebrafish treated with LPS and/or DSS. LPS and/or DSS treatment enhanced intestinal inflammation in krasV12 transgenic larvae with concomitant increases in the number of neutrophils and macrophages in the intestines. The expression of krasV12, combined with LPS treatment, also enhanced epithelial hyperplasia and tubular adenoma, demonstrated by histopathological examinations and by increases in cell apoptosis, cell proliferation, and downstream signaling of phosphorylated AKT serine/threonine kinase 1 (AKT), extracellular-signal-regulated kinase (ERK), and histone. We also found that krasV12 expression, combined with LPS treatment, significantly enhanced changes in intestinal morphology, specifically (1) decreases in goblet cell number, goblet cell size, villi height, and intervilli space, as well as (2) increases in villi width and smooth muscle thickness. Moreover, krasV12 transgenic larvae cotreated with DSS and LPS exhibited exacerbated intestinal inflammation. Cotreatment with DSS and LPS in krasV12-expressing transgenic adult zebrafish also enhanced epithelial hyperplasia and tubular adenoma, compared with wild-type fish that received the same cotreatment. In conclusion, our data suggest that krasV12 expression, combined with LPS and/or DSS treatment, can enhance intestinal tumor progression by activating the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway and may provide a valuable in vivo platform to investigate tumor initiation and antitumor drugs for gastrointestinal cancers.

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Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy

Cited by 47 publications

References 50 publications

Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer

The Zebrafish Xenograft Models for Investigating Cancer and Cancer Therapeutics

Lipopolysaccharides Enhance Epithelial Hyperplasia and Tubular Adenoma in Intestine-Specific Expression of krasV12 in Transgenic Zebrafish

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