Assessment of breast cancer primary tumor material in a 3D in vivo model

2021 ◽  
pp. 1-10
Author(s):  
Cynthia Kohl ◽  
Thiha Aung ◽  
Silke Haerteis ◽  
Thomas Papathemelis
Keyword(s):  
Breast Cancer ◽  
Treatment Plan ◽  
Tumor Biology ◽  
Chorioallantoic Membrane ◽  
Tumor Model ◽  
In Vivo Model ◽  
Additional Information ◽  
Chick Chorioallantoic Membrane ◽  
The Individual

BACKGROUND: Breast cancer is the most common malignant tumor in women and highly heterogeneous with a variety of different molecular subtypes. The analysis of the individual tumor biology is necessary to develop a specific and individualized treatment plan for every patient. The chick chorioallantoic membrane (CAM) model, a 3D-in-vivo-tumor-model, could potentially provide a methodology that facilitates the gain of additional information regarding the tumor biology as well as the testing of the tumor’s individual sensitivity to different therapies. OBJECTIVE: The objective was to establish the grafting of different breast cancer primaries onto the CAM for tumor profiling and the investigation of different parameters. METHODS: Breast cancer primary tissue of different patients was grafted onto the CAM. Subsequently, 3D volume and perfusion measurements were performed during the engraftment period. Histological analyses of the tumors were carried out after the engraftment period. RESULTS: The grafting of the breast cancer primaries onto the CAM was successful. The tumors remained partially vital and displayed angiogenic development on the CAM. CONCLUSIONS: Breast cancer primary material can be grafted onto the CAM and we observed visible and measurable changes of perfusion over time.

Extended analysis of intratumoral heterogeneity of primary osteosarcoma tissue using 3D-in-vivo-tumor-model

2020 ◽  
Vol 76 (2) ◽  
pp. 133-141
Author(s):  
Anna-Lena Feder ◽  
Eric Pion ◽  
Johannes Troebs ◽  
Ulrich Lenze ◽  
Lukas Prantl ◽  
...  
Keyword(s):  
Chorioallantoic Membrane ◽  
Tumor Model ◽  
Genetic Alterations ◽  
Growth Patterns ◽  
Chick Chorioallantoic Membrane ◽  
Primary Osteosarcoma ◽  
Malignant Group ◽  
High Level ◽  
Tumor Profiling

BACKGROUND: Osteosarcomas are a rare, heterogeneous and malignant group of bone tumors that have a high potential for metastasis and aggressive growth patterns. Treatment of metastasized osteosarcoma is often insufficient and research is compromised by problems encountered when culturing cells or analyzing genetic alterations due to the high level of intratumoral and intertumoral heterogeneity. The chick chorioallantoic membrane (CAM) model, a 3D-in-vivo-tumor-model, could potentially facilitate the investigation of osteosarcoma heterogeneity at an individual and highly specified level. OBJECTIVE: Objective was to establish the grafting and transplantation of different primary osteosarcoma tissue parts onto several consecutive CAMs for tumor profiling and investigation of osteosarcoma heterogeneity. METHODS: Various parts of primary osteosarcoma tissue were grafted onto CAMs and were transplanted onto another CAM for five to seven consecutive times, enabling further experimental analyzes. RESULTS: Primary osteosarcoma tissue parts exhibited satisfactory growth patterns and displayed angiogenic development on the CAM. It was possible to graft and transplant different tumor parts several times while the tissue viability was still high and tumor profiling was performed. CONCLUSIONS: Primary osteosarcoma tissue grew on several different CAMs for an extended time period and neovascularization of serial transplanted tumor parts was observed, improving the versatility of the 3D-in-vivo-tumor-model.

scholarly journals Structure and hemodynamics of vascular networks in the chorioallantoic membrane of the chicken

2016 ◽  
Vol 311 (4) ◽  
pp. H913-H926 ◽  
Author(s):  
Martin Maibier ◽  
Bettina Reglin ◽  
Bianca Nitzsche ◽  
Weiwei Xiang ◽  
Wen Wei Rong ◽  
...  
Keyword(s):  
Shear Stress ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Vascular Networks ◽  
Murray's Law ◽  
Chick Chorioallantoic Membrane ◽  
Murray’S Law ◽  
Flow Pathways ◽  
Hemodynamic Simulations

The chick chorioallantoic membrane (CAM) is extensively used as an in vivo model. Here, structure and hemodynamics of CAM vessel trees were analyzed and compared with predictions of Murray's law. CAM microvascular networks of Hamburger-Hamilton stage 40 chick embryos were scanned by videomicroscopy. Three networks with ∼3,800, 580, and 480 segments were digitally reconstructed, neglecting the capillary mesh. Vessel diameters ( D) and segment lengths were measured, and generation numbers and junctional exponents at bifurcations were derived. In selected vessels, flow velocities ( v) and hematocrit were measured. Hemodynamic simulations, incorporating the branching of capillaries from preterminal vessels, were used to estimate v, volume flow, shear stress (τ), and pressure for all segments of the largest network. For individual arteriovenous flow pathways, terminal arterial and venous generation numbers are negatively correlated, leading to low variability of total topological and morphological pathway lengths. Arteriolar velocity is proportional to diameter ( v∝ D1.03 measured, v∝ D0.93 modeling), giving nearly uniform τ levels (τ∝ D0.05). Venular trees exhibit slightly higher exponents ( v∝ D1.3, τ∝ D0.38). Junctional exponents at divergent and convergent bifurcations were 2.05 ± 1.13 and 1.97 ± 0.95 (mean ± SD) in contrast to the value 3 predicted by Murray's law. In accordance with Murray's law, τ levels are (nearly) maintained in CAM arterial (venular) trees, suggesting vascular adaptation to shear stress. Arterial and venous trees show an interdigitating arrangement providing homogeneous flow pathway properties and have preterminal capillary branches. These properties may facilitate efficient oxygen exchange in the CAM during rapid embryonic growth.

scholarly journals Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miguel Angel Merlos Rodrigo ◽  
Hana Michalkova ◽  
Vladislav Strmiska ◽  
Berta Casar ◽  
Piero Crespo ◽  
...  
Keyword(s):  
Cisplatin Resistance ◽  
Neuroblastoma Cells ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Chick Chorioallantoic Membrane ◽  
High Level ◽  
Cisplatin Chemoresistance ◽  
The Impact ◽  
First Time

AbstractMetallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.

scholarly journals S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2168
Author(s):  
Chien-Chung Huang ◽  
Tzu-Ting Tseng ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Yat-Yin Law ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
In Vivo Model ◽  
Endothelial Progenitor ◽  
Chick Chorioallantoic Membrane ◽  
Cartilage Erosion ◽  
The Impact

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment.

scholarly journals QUANTIFICATION OF ANGIOGENESIS IN THE CHICKEN CHORIOALLANTOIC MEMBRANE (CAM)

2011 ◽  
Vol 23 (3) ◽  
pp. 169 ◽  
Author(s):  
Silvia Blacher ◽  
Laetitia Devy ◽  
Ruslan Hlushchuk ◽  
Etienne Larger ◽  
Noel Lamandé ◽  
...  
Keyword(s):  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
New Developments ◽  
Chick Chorioallantoic Membrane ◽  
Capillary Plexus ◽  
Feeding Vessels ◽  
Two Phases ◽  
Chicken Chorioallantoic Membrane ◽  
Accurate Quantification

The chick chorioallantoic membrane (CAM) provides a suitable in vivo model to study angiogenesis and evaluate several pro- and anti-angiogenic factors and compounds. In the present work, new developments in image analysis are used to quantify CAM angiogenic response from optical microscopic observations, covering all vascular components, from the large supplying and feeding vessels down to the capillary plexus. To validate our methodology angiogenesis is quantified during two phases of CAM development (day 7 and 13) and after treatment with an antiangiogenic modulator of the angiogenesis. Our morphometric analysis emphasizes that an accurate quantification of the CAM vasculature needs to be performed at various scales.

scholarly journals Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jingjing Yang ◽  
Yulu Zhou ◽  
Shuduo Xie ◽  
Ji Wang ◽  
Zhaoqing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Morphological Changes ◽  
Tumor Model ◽  
Independent Manner ◽  
Regulated Cell Death ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Approved Drugs

Abstract Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

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