A novel four-step system for screening angiogenesis inhibitors

Zhou, Qin; Qi, Cuiling; Li, Yan; He, Xiaodong; Li, Jiangchao; Zhang, Qianqian; Tian, Li; Zhang, Ming; Han, Zhe; Wang, Huiping; Yang, Xuesong; Wang, Lijing

doi:10.3892/mmr.2013.1704

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…HMGA1 expression was closely correlated with the clinical stage and histological grade of patients with breast cancer and breast cancer progression in MMTV‐PyMT mice, indicating that the overexpression of HMGA1 can promote breast cancer growth. MMTV‐PyMT mice, a spontaneous breast cancer model, have been shown to exhibit distinctly identifiable stages of breast cancer progression from premalignant to malignant stages (Zhou et al, ). Moreover, MMTV‐PyMT mice are powerful tools for studying processes involved in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

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HMGA1 Overexpression is Associated With the Malignant Status and Progression of Breast Cancer

Cao

et al. 2018

The Anatomical Record

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Breast cancer is the most common malignant tumor among women, and the incidence and mortality of breast cancer has rapidly increased in recent years. Studies have indicated that high mobility group A1 (HMGA1), an important member of the HMGA family, plays a role in the pathogenesis and progression of malignant tumors, including breast cancer. This study aims to evaluate the effect of HMGA1 in breast cancer. Interestingly, we found that HMGA1 expression was significantly higher in breast cancer tissues than in adenoma tissues and closely correlated with the clinical stage and histological grade in breast cancer patients. Further study showed that HMGA1 knockdown inhibited the proliferation and migration of breast cancer cells. Thus, the results demonstrated that HMGA1 could act as an independent prognostic indicator in breast cancer. HMGA1 expression was closely correlated with the clinical stage, histological grade, and tumor size in breast cancer patients and breast cancer progression in transgenic MMTV-PyMT mice. Anat Rec, 301:1061-1067, 2018. © 2018 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

“…In this study, we investigated the expression of HMGA1 in human breast cancer tissues and breast cancer tissues of MMTV‐TyMT mice, a spontaneous breast cancer mouse model, as previously described (Zhou et al, ). The contributions of HMGA1 to breast cancer cell proliferation and migration were also investigated.…”

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confidence: 99%

HMGA1 Overexpression is Associated With the Malignant Status and Progression of Breast Cancer

Cao

et al. 2018

The Anatomical Record

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“…Some of the best studies for screening effective drugs, including drug combinations and angiostatics, come from studies that combine faster screening models such as the CAM with other models of angiogenesis. One such study by Zhou et al describes a four-step system for screening angiogenesis inhibitors [ 78 ]. In this study, 480 compounds were tested for angiostatic activity and 28 were found to inhibit angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis

et al. 2021

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Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.

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“…Allows high throughput screening [Zhou et al, 2013;Dünker and Jendrossek, 2019 Allows multiple tests per individual CAM [Bertossi et al, 1999;Deryugina, 2016] High reproducibility the visualization. As the experiments are always synchronized with the embryonic development of the chick before hatching, the duration to establish the graft only requires 14-18 days which is significantly shorter than what is usually needed for the mouse model.…”

Section: Inexpensivementioning

confidence: 99%

Applications of the Chick Chorioallantoic Membrane as an Alternative Model for Cancer Studies

Chu

Koh

Antony

et al. 2021

Cells Tissues Organs

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A variety of in vivo experimental models have been established for the studies of human cancer using both cancer cell lines and patient-derived xenografts (PDXs). In order to meet the aspiration of precision medicine, the in vivomurine models have been widely adopted. However, common constraints such as high cost, long duration of experiments, and low engraftment efficiency remained to be resolved. The chick embryo chorioallantoic membrane (CAM) is an alternative model to overcome some of these limitations. Here, we provide an overview of the applications of the chick CAM model in the study of oncology. The CAM model has shown significant retention of tumor heterogeneity alongside increased xenograft take rates in several PDX studies. Various imaging techniques and data analysis have been applied to study tumor metastasis, angiogenesis, and therapeutic response to novel agents. Lastly, to practically illustrate the feasibility of utilizing the CAM model, we summarize the general protocol used in a case study utilizing an ovarian cancer PDX.

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A novel four-step system for screening angiogenesis inhibitors

Cited by 10 publications

References 23 publications

HMGA1 Overexpression is Associated With the Malignant Status and Progression of Breast Cancer

HMGA1 Overexpression is Associated With the Malignant Status and Progression of Breast Cancer

A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis

Applications of the Chick Chorioallantoic Membrane as an Alternative Model for Cancer Studies

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