scholarly journals The CAM Model for CIC-DUX4 Sarcoma and Its Potential Use for Precision Medicine

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2613
Author(s):  
Aoi Komatsu ◽  
Kotaro Matsumoto ◽  
Yuki Yoshimatsu ◽  
Yooksil Sin ◽  
Arisa Kubota ◽  
...  
Keyword(s):  
Second Generation ◽  
Fusion Gene ◽  
Chorioallantoic Membrane ◽  
Tumor Formation ◽  
Cancer Type ◽  
Membrane Expression ◽  
Chicken Chorioallantoic Membrane ◽  
Cam Model ◽  
Chorioallantoic Membrane Assay ◽  
Potential Use

(1) Background: CIC-DUX4 sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there is a need to develop a model that mimics the features of each of these cancers. We evaluated the idea that the chicken chorioallantoic membrane assay (CAM), a convenient and versatile animal model, can be established for the CIC-DUX4 sarcoma. (2) Methods: Patient-derived cell lines of CIC-DUX4 were applied. These cells were transplanted onto the CAM membrane and tumor formation was examined by H&E staining, immunohistochemistry and Western blotting. The CAM tumor was transferred onto a fresh CAM and was also used to form organoids. Retention of the fusion gene was examined. (3) Results: H&E staining as well as molecular characterization demonstrated the formation of the CIC-DUX4 tumor on the CAM membrane. Expression of cyclin D2 and ETV4 was identified. The CAM tumor was transferred to a fresh CAM to form the second-generation CAM tumor. In addition, we were successful in forming tumor organoids using the CAM tumor. Retention of the fusion gene CIC-DUX4 in the CAM, second-generation CAM, and in the CAM-derived organoids was confirmed by RT-PCR. (4) Conclusions: The CAM assay provides a promising model for CIC-DUX4 sarcoma.

scholarly journals Patient Derived Chicken Egg Tumor Model (PDcE Model): Current Status and Critical Issues

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 440 ◽  
Author(s):  
Aoi Komatsu ◽  
Kotaro Matsumoto ◽  
Tomoki Saito ◽  
Manabu Muto ◽  
Fuyuhiko Tamanoi
Keyword(s):  
Cancer Patients ◽  
Chorioallantoic Membrane ◽  
Tumor Model ◽  
Tumor Formation ◽  
Current Status ◽  
Cam Assay ◽  
Chicken Egg ◽  
Critical Issues ◽  
Chicken Eggs ◽  
Chorioallantoic Membrane Assay

Chorioallantoic membrane assay (CAM assay) using fertilized chicken eggs has been used for the study of tumor formation, angiogenesis and metastasis. Recently, there is growing realization that this system provides a valuable assay for a patient-derived tumor model. Several reports establish that tumor samples from cancer patients can be used to reproduce tumor in the chicken egg. High transplantation efficiency has been achieved. In this review, we discuss examples of transplanting patient tumors. We then discuss critical issues that need to be addressed to pursue this line of experiments. The patient-derived chicken egg model (PDcE model) has an advantage over other models in its rapid tumor formation. This raises the possibility that the PDcE model is valuable for identifying optimum drug for each individual patient.

scholarly journals STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

2020 ◽  
Vol 21 (3) ◽  
pp. 1106 ◽  
Author(s):  
Sruthi V. Hindupur ◽  
Sebastian C. Schmid ◽  
Jana Annika Koch ◽  
Ahmed Youssef ◽  
Eva-Maria Baur ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Cycle Progression ◽  
Chorioallantoic Membrane ◽  
Oncolytic Adenovirus ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Division Cell ◽  
Chicken Chorioallantoic Membrane ◽  
Cam Model ◽  
Phosphorylated Stat3

The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.

scholarly journals Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay

2005 ◽  
Vol 93 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Serafim Kiriakidis ◽  
Oliver Högemeier ◽  
Susanne Starcke ◽  
Frank Dombrowski ◽  
Jens Claus Hahne ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Chorioallantoic Membrane ◽  
Endothelial Cell Proliferation ◽  
Inhibition Of Angiogenesis ◽  
Chicken Chorioallantoic Membrane ◽  
Chorioallantoic Membrane Assay

Anti-angiogenic strategies are emerging as an important tool for the treatment of cancer and inflammatory diseases. In the present investigation we isolated several isoflavones from a tempeh (fermented soyabean) extract. The isolated isoflavones were identified as 5,7,4′-trihydroxyisoflavone (genistein), 7,4′-dihydroxyisoflavone (daidzein), 6,7,4′-trihydroxyisoflavone (factor 2), 7,8,4′-trihydroxyisoflavone (7,8,4′-TriOH) and 5,7,3′,4′-tetrahydroxyisoflavone (orobol). The effects on angiogenesis of these isoflavones were evaluated in the chicken chorioallantoic membrane assay; their capacity to inhibit vascular endothelial growth factor-induced endothelial cell proliferation and expression of the Ets 1 transcription factor, known to be implicated in the regulation of new blood vessel formation, were also investigated. We found that all isoflavones inhibited angiogenesis, albeit with different potencies. Compared with negative controls, which slightly inhibited in vivo angiogenesis by 6·30 %, genistein reduced angiogensis by 75·09 %, followed by orobol (67·96 %), factor 2 (56·77 %), daidzein (48·98 %) and 7,8,4′-TriOH (24·42 %). These compounds also inhibited endothelial cell proliferation, with orobol causing the greatest inhibition at lower concentrations. The isoflavones also inhibited Ets 1 expression, providing some insight into the molecular mechanisms of their action. Furthermore, the chemical structure of the different isoflavones suggests a structure–activity relationship. Our present findings suggest that the new isoflavones might be added to the list of low molecular mass therapeutic agents for the inhibition of angiogenesis.

scholarly journals Establishment of xenografts of urological cancers on chicken chorioallantoic membrane (CAM) to study metastasis

2019 ◽  
Vol 2 (3) ◽  
pp. 140-151 ◽  
Author(s):  
Junhui Hu ◽  
Moe Ishihara ◽  
Arnold I Chin ◽  
Lily Wu
Keyword(s):  
Prostate Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Cancer Biology ◽  
Prostate Gland ◽  
Tumor Biology ◽  
Chorioallantoic Membrane ◽  
Testing Stage ◽  
Chicken Chorioallantoic Membrane ◽  
Cam Model

Abstract Cancer of the urological system commonly occurs in the kidney, bladder, and prostate gland. The clear cell subtype of renal cell carcinoma (ccRCC) constitutes the great majority of kidney cancer. Metastatic ccRCC portends a very poor outcome with no effective treatment available. Prostate cancer is the most common cancer in males in the US. Despite recent advances in selective kinase inhibitors and immunotherapies, the rate of developing new treatment from bench to bedside is slow. A time-consuming step is at the animal drug testing stage, in which the mouse model is the gold standard. In the pursuit to streamline the in vivo cancer biology research and drug development, we explored the feasibility of the chicken chorioallantoic membrane (CAM) model to establish xenografts. The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice. We generated CAM xenografts from ccRCC, bladder and prostate cancer, with established cancer cell lines and freshly isolated patient-derived tissues, either as primary tumor cells or small pieces of tumors. The successful CAM engraftment rate from the different tumor sources is 70% or above. Using our previously established metastatic ccRCC mouse model, we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice. Taken together, CAM can serve as a valuable platform to establish new patient-derived xenografts (PDXs) to study tumor biology, thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.

scholarly journals The Effectiveness of Dichloroacetate on Human Glioblastoma Xenograft Growth Depends on Na+ and Mg2+ Cations

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582199016
Author(s):  
Donatas Stakišaitis ◽  
Eligija Damanskienė ◽  
Rūta Curkūnavičiūtė ◽  
Milda Juknevičienė ◽  
Marta Maria Alonso ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Cell Biology ◽  
Tumor Response ◽  
Chorioallantoic Membrane ◽  
Study Groups ◽  
Salt Treatment ◽  
Ezh2 Expression ◽  
Chicken Chorioallantoic Membrane ◽  
Proliferating Cell ◽  
Cam Model

The study’s aim was to investigate the effectiveness of sodium dichloroacetate (NaDCA) or magnesium dichloroacetate (MgDCA) on adult U87 MG and pediatric PBT24 cell lines glioblastoma (GB) xenografts in a chicken chorioallantoic membrane (CAM) model. The study groups were: treated with 10 mM, 5 mM of NaDCA, and 5 mM, 2.5 mM of MgDCA, and controls. The U87 MG and PBT24 xenografts growth, frequency of tumor invasion into CAM, CAM thickening, and the number of blood vessels in CAM differed depending on the dichloroacetate salt treatment. NaDCA impact on U87 MG and PBT24 tumor on proliferating cell nunclear antigen (PCNA) and enhancer of zeste homolog 2 (EZH2) expression in the tumor was different, depending on the NaDCA dose. The 5 mM MgDCA impact was more potent and had similar effects on U87 MG and PBT24 tumors, and its impact was also reflected in changes in PCNA and EZH2 expression in tumor cells. The U87 MG and PBT24 tumor response variations to treatment with different NaDCA concentration on tumor growth or a contrast between NaDCA and MgDCA effectiveness may reflect some differences in U87 MG and PBT24 cell biology.

scholarly journals The Aqueous Soluble Polyphenolic Fraction ofPsidium guajavaLeaves Exhibits Potent Anti-Angiogenesis and Anti-Migration Actions on DU145 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Chiung-Chi Peng ◽  
Chiung-Huei Peng ◽  
Kuan-Chou Chen ◽  
Chiu-Lan Hsieh ◽  
Robert Y. Peng
Keyword(s):  
Chorioallantoic Membrane ◽  
Psidium Guajava ◽  
Elisa Assay ◽  
Scratch Assay ◽  
Anti Cancer ◽  
Assay Methods ◽  
Du145 Cells ◽  
Chicken Chorioallantoic Membrane ◽  
Chorioallantoic Membrane Assay ◽  
Wound Scratch Assay

The aqueous extract ofPsidium guajavabudding leaves (PE) bears an extremely high content of polyphenolic and isoflavonoids. Whether it could be used as an anti-tumor chemopreventive in view of anti-angiogenesis and anti-migration, we performed the assay methods including the MTT assay to examine the cell viability; the ELISA assay to test the expressions of VEGF, IL-6 and IL-8; the western blot analysis to detect TIMP-2; the gelatinolytic zymography to follow the expression of MMPs; the wound scratch assay to examine the migration capability; and the chicken chorioallantoic membrane assay to detect the suppressive angiogenesis. Results indicated that the IC50 of PE for DU145 cells was ∼0.57 mg ml−1. In addition, PE effectively inhibited the expressions of VEGF, IL-6 and IL-8 cytokines, and MMP-2 and MMP-9, and simultaneously activated TIMP-2 and suppressed the cell migration and the angiogenesis. Conclusively, PE potentially possesses a strong anti-DU145 effect. Thus, clinically it owns the potential to be used as an effective adjuvant anti-cancer chemopreventive.

scholarly journals CE-CAM model for evaluating CD133lo Cancer Stem Cells in Retinoblastoma

2020 ◽  
Author(s):  
Rohini M Nair ◽  
Narayana VL Revu ◽  
Sucharita Gali ◽  
Prathap Reddy Kallamadi ◽  
Varsha Prabhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Chorioallantoic Membrane ◽  
Metastatic Potential ◽  
Preliminary Evidence ◽  
Tumor Formation ◽  
Feasible Alternative ◽  
Y79 Cells ◽  
Cam Model

Abstract BackgroundCancer Stem Cells (CSCs) reported in various tumors, play a crucial role in tumorigenesis and metastasis. Following the efforts to reduce, replace and refine the use of mammalian models, we aimed to establish a short-term xenograft for Retinoblastoma (Rb) to evaluate the tumorigenic and metastatic potential of CD133lo CSCs in Rb Y79 cells, using the well-established chick embryo (CE) model. MethodsTotal and CD133 sorted Rb Y79 cells, labelled with eGFP/CM-Dil tracking dye, were transplanted onto the chorioallantoic membrane (CAM) of day-7 chick embryos and incubated for 7 days. The tumor formation on CAM and metastasis to the embryos were evaluated by confocal microscopy, in-vivo imaging, and histopathology. ResultsY79 cells formed pink-white raised perivascular nodules on the CAM with CD133lo CSCs exhibiting larger nodules when compared to CD133hi cells and total Y79 (p<0.05). In-vivo imaging revealed that the labeled cells metastasized to the embryos with the fluorescent signals visible in the abdominal area, cephalus and the limbs. Histopathologic studies confirmed the presence of tumor cells on the CAM, organs of embryos transplanted with Y79 cells, more so with CD133lo CSCs. ConclusionsThis study highlights that the CE-CAM is a feasible alternative non-mammalian model for evaluating tumorigenicity and metastatic potential of Rb CSCs. The study also provides preliminary evidence that Rb Y79 CD133lo CSCs show higher propensity to form tumor nodules on the CAM and are more invasive than non CSCs, thus, supporting our earlier evidence that they are endowed with CSC properties.

scholarly journals Optimization of the chicken chorioallantoic membrane assay as reliable in vivo model for the analysis of osteosarcoma

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215312 ◽  
Author(s):  
Pierre Kunz ◽  
Astrid Schenker ◽  
Heiner Sähr ◽  
Burkhard Lehner ◽  
Jörg Fellenberg
Keyword(s):  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Chicken Chorioallantoic Membrane ◽  
Chorioallantoic Membrane Assay

scholarly journals The Effect of Sodium Valproate on the Glioblastoma U87 Cell Line Tumor Development on the Chicken Embryo Chorioallantoic Membrane and on EZH2 and p53 Expression

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Dovilė Kavaliauskaitė ◽  
Donatas Stakišaitis ◽  
Justė Martinkutė ◽  
Lina Šlekienė ◽  
Arūnas Kazlauskas ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Sodium Valproate ◽  
Chicken Embryo ◽  
Tumor Development ◽  
Chorioallantoic Membrane ◽  
Tumor Formation ◽  
P53 Expression ◽  
Human Gbm ◽  
Patients Experience ◽  
Cam Model

Literature data support evidences that glioblastoma (GBM) patients experience prolonged survival due to sodium valproate (NaVP) treatment. The study assessed the human GBM cell U87 xenograft studied in the chicken embryo chorioallantoic membrane (CAM) model evaluating NaVP effect on tumor. Three groups of tumors (eachn= 10) were studied: nontreated, treated with 4 mM, and treated with 8 mM of NaVP. The majority of tumors without NaVP treatment during tumor growth destroyed the chorionic epithelium, invaded the mesenchyme, and induced angiogenesis. Incidence of tumor formation on CAM without invasion into the mesenchyme was higher when U87 cells were treated with NaVP; the effect significantly increased with NaVP concentration. Treatment with 8 mM of NaVP did not show clear dynamics of tumor growth during 5 days; at the same time, the angiogenesis failed. With a strong staining of EZH2, p53 in tumors without NaVP treatment was found, and NaVP significantly decreased the expression of EZH2- and p53-positive cells; the effect was significantly higher at its 8 mM concentration. NaVP has a function in blocking the growth, invasion, and angiogenesis of tumor in the CAM model; tumor growth interferes with EZH2 and p53 molecular pathways, supporting the NaVP potential in GBM therapy.

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