scholarly journals Implementation of the Chick Chorioallantoic Membrane (CAM) Model in Radiation Biology and Experimental Radiation Oncology Research

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1499 ◽  
Author(s):  
Dünker ◽  
Jendrossek

Radiotherapy (RT) is part of standard cancer treatment. Innovations in treatment planning and increased precision in dose delivery have significantly improved the therapeutic gain of radiotherapy but are reaching their limits due to biologic constraints. Thus, a better understanding of the complex local and systemic responses to RT and of the biological mechanisms causing treatment success or failure is required if we aim to define novel targets for biological therapy optimization. Moreover, optimal treatment schedules and prognostic biomarkers have to be defined for assigning patients to the best treatment option. The complexity of the tumor environment and of the radiation response requires extensive in vivo experiments for the validation of such treatments. So far in vivo investigations have mostly been performed in time- and cost-intensive murine models. Here we propose the implementation of the chick chorioallantoic membrane (CAM) model as a fast, cost-efficient model for semi high-throughput preclinical in vivo screening of the modulation of the radiation effects by molecularly targeted drugs. This review provides a comprehensive overview on the application spectrum, advantages and limitations of the CAM assay and summarizes current knowledge of its applicability for cancer research with special focus on research in radiation biology and experimental radiation oncology.

2021 ◽  
Vol 28 ◽  
Author(s):  
Ana Isabel Fraguas-Sánchez ◽  
Cristina Martín-Sabroso ◽  
Ana Isabel Torres-Suárez

Background: The chick chorioallantoic membrane (CAM) model has attracted a great deal of interest in pharmaceutical and biological research as an alternative or complementary in vivo assay to animal models. Traditionally, CAM assay has been widely used to perform some toxicological studies, specifically to evaluate the skin, ocular and embryo toxicity of new drugs and formulations, and perform angiogenesis studies. Due to the possibility to generate the tumors onto the CAM, this model has also become an excellent strategy to evaluate the metastatic potential of different tumours and test the efficacy of novel anticancer therapies in vivo. Moreover, in the recent years, its use has considerably grown in other research areas, including the evaluation of new anti-infective agents, the development of biodistribution studies and tissue engineering research. Objectives: This manuscript provides a critical overview of the use of CAM model in pharmaceutical and biological research, especially to test the toxicity of new drugs and formulations and the biodistribution and the efficacy of novel anticancer and anti-infective therapies, analyzing its advantages and disadvantages compared to animal models. Conclusion: The chick chorioallantoic membrane model shows great utility in several research areas, such as cancer, toxicology, biodistribution studies and anti-infective therapies. In fact, it has become an intermediate stage between in vitro experiments and animal studies, and, in the case of toxicological studies (skin and ocular toxicity), has even replaced the animal models.


2021 ◽  
pp. 1-16
Author(s):  
Pei-Yu Chu ◽  
Angele Pei-Fern Koh ◽  
Jane Antony ◽  
Ruby Yun-Ju Huang

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.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 66
Author(s):  
Rashmita Pradhan ◽  
Phuong A. Ngo ◽  
Luz d. C. Martínez-Sánchez ◽  
Markus F. Neurath ◽  
Rocío López-Posadas

Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.


1972 ◽  
Vol 20 (6) ◽  
pp. 401-413 ◽  
Author(s):  
JAMES R. COLEMAN ◽  
A. RAYMOND TEREPKA

The chorioallantoic membrane of the developing chick embryo is an epithelium that actively transports calcium. The methodology utilized to prepare this soft tissue for calcium localization with the electron probe x-ray microanalyzer is presented in detail. The preparative procedures are evaluated according to general histochemical principles and in relationship specifically to electron probe investigations. It is shown that the method employed in these studies preserves the normal fine structure of the tissue, prevents selective loss of calcium, permits only minor losses of total calcium and appears to maintain the distribution of calcium that existed in vivo. Examples are presented of artifacts that can be induced during tissue sectioning and mounting procedures. Problems of defining electron probe resolution in biologic specimens are discussed, and the critical importance of evaluating x-ray images in association with simultaneously generated sample current images is emphasized.


1992 ◽  
Vol 119 (2) ◽  
pp. 475-482 ◽  
Author(s):  
M A Moses ◽  
J Sudhalter ◽  
R Langer

An inhibitor of neovascularization from the conditioned media of scapular chondrocytes established and maintained in serum-free culture has been isolated and characterized. To determine whether this chondrocyte-derived inhibitor (ChDI) was capable of inhibiting neovascularization in vivo, this protein was assayed in the chick chorioallantoic membrane assay. ChDI was a potent inhibitor of angiogenesis in vivo (4 micrograms = 87% avascular zones). This inhibitor is also an inhibitor of fibroblast growth factor-stimulated capillary endothelial cell (EC) proliferation and migration, as well as being an inhibitor of mammalian collagenase. ChDI significantly suppressed capillary EC proliferation in a dose-dependent, reversible manner with an IC50 (the inhibitory concentration at which 50% inhibition is achieved) of 2.025 micrograms/ml. Inhibition by ChDI of growth factor-stimulated capillary EC migration was also observed using a modified Boyden chamber assay (IC50 = 255 ng/ml). SDS-PAGE analysis followed by silver staining of ChDI purified to apparent homogeneity revealed a single band having an M(r) of 35,550. Gel elution experiments demonstrated that only protein eluting at this molecular weight was anti-angiogenic. These studies are the first demonstration that chondrocytes in culture can produce a highly enriched, potent inhibitor of neovascularization which also inhibits collagenase.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252233
Author(s):  
Michael I. Dorrell ◽  
Heidi R. Kast-Woelbern ◽  
Ryan T. Botts ◽  
Stephen A. Bravo ◽  
Jacob R. Tremblay ◽  
...  

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.


Author(s):  
Ekta Tomar ◽  
Sonali Wairagade ◽  
Arachana Gharote ◽  
Ranjit S. Ambad ◽  
Dhruba Hari Chandi

Background: Mandur Bhasma is a herbo-mineral compound. It is prepared by Putapaka method. It is described as Raktasanjanan. In the current study, Mandur Bhasma was prepared with a standardized method w.s.r to Rasatarangini and an experimental study was done to observe the Angiogenic property of Mandur Bhasma. The current study will analyze angiogenic potential of Mandur Bhasma using chick CAM model. This research is intended to study the possible role of Mandur Bhasma on angiogenesis and establishing properties of Mandur Bhasma as an angiogenic by newer means. The experimental study inside the egg shell will be carried out on a membrane known as “chorioallantoic membrane”. Objectives: To Prepare Mandur Bhasma Physicochemical and Analytical study of Mandur Bhasma To verify the angiogenic potential of Mandur bhasma using the chicken chorioallantoic membrane (CAM) model. To compare Angeogenic potential of Mandur bhasma with standard drug progesterone Methodology: Relevant classical literature regarding Mandur will be reviewed and the data will be collected. Mandur Shodhan with Gomutra and Mandur Maran with Triphala decoction will be done. Analytical Study like Organoleptic Test for Rasa, Gandha, Varna, Sparsha, Physicochemical Tests and other analytical test like ICP-AES /ICPMS, XRD structure of Bhasma, EDAX-NANO Particle Size will be done. Expected Results: Changes will be observed in objective outcomes. Conclusion: Conclusion will be drawn by suitably analyzing data.


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