scholarly journals Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1578
Author(s):  
Anna Guller ◽  
Inga Kuschnerus ◽  
Vlada Rozova ◽  
Annemarie Nadort ◽  
Yin Yao ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Chick Embryo ◽  
Drug Development ◽  
Cancer Biology ◽  
Mesoporous Silica Nanoparticles ◽  
In Vivo Model ◽  
Primary Tumors ◽  
Angiogenic Switch ◽  
Experimental Platform ◽  
Organ Specific

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

scholarly journals Chick Embryo Experimental Platform for 3D Tissue Engineering Modelling of Cancer Micrometastases for Tumor Biology, Drug Development and Nanomaterials Testing

2021 ◽  
Author(s):  
Anna Guller ◽  
Inga Kuschnerus ◽  
Vlada Rozova ◽  
Annemarie Nadort ◽  
Yin Yao ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Chick Embryo ◽  
Drug Development ◽  
Cancer Biology ◽  
Mesoporous Silica Nanoparticles ◽  
Tumor Biology ◽  
In Vivo Model ◽  
Primary Tumors ◽  
Experimental Platform ◽  
Organ Specific

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

scholarly journals MALATE DEHYDROGENASE ISOZYMES OF THE CHICK EMBRYO

1965 ◽  
Vol 13 (6) ◽  
pp. 510-514 ◽  
Author(s):  
JAMES L. CONKLIN ◽  
EDWARD J. NEBEL
Keyword(s):  
Lactate Dehydrogenase ◽  
Chick Embryo ◽  
Malate Dehydrogenase ◽  
Molecular Basis ◽  
Specific Pattern ◽  
Starch Gel Electrophoresis ◽  
Organ Specific ◽  
Malate Dehydrogenase Isozymes ◽  
Starch Gel ◽  
Mitochondrial Malate Dehydrogenase

Malate dehydrogenase fractions of the chick embryo were demonstrated after starch gel electrophoresis of homogenates of liver, brain and spleen. A total of seven malate dehydrogenase fractions were observed to occur in the chick embryo in an organ specific pattern. Treatment of the homogenates with urea, sodium chloride-sodium phosphate, and p-chloromercuribenzoate prior to electrophoresis revealed that only three distinct malate dehydrogenase-active proteins were presence. Two of these proteins exhibited properties similar to those previously reported for the supernatant malate dehydrogenase and mitochondrial malate dehydrogenase of other species. Becuase of the differing properties of chick malate and lactate dehydrogenase it is concluded that the molecular basis for malate dehydrogenase isozymes is different from that reported for lactate dehydrogenase isozymes.

scholarly journals Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jongmin Lee ◽  
Hye Kyung Hong ◽  
Sheng-Bin Peng ◽  
Tae Won Kim ◽  
Woo Yong Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Mirna Target ◽  
Target Genes ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Primary Tumors ◽  
Significant Difference

Abstract Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

scholarly journals Clinical, Pathological, and Ethical Considerations for the Conduct of Clinical Trials in Dogs with Naturally Occurring Cancer: A Comparative Approach to Accelerate Translational Drug Development

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Daniel Regan ◽  
Kelly Garcia ◽  
Douglas Thamm
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Translational Research ◽  
Cancer Biology ◽  
Comparative Approach ◽  
Cancer Drug ◽  
Comparative Oncology ◽  
Pet Dogs ◽  
Naturally Occurring

Abstract The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’ large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.

Rapid/warm autopsy to reveal APOBEC-mutagenesis as driver of heterogeneity of metastatic thoracic tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9023-9023
Author(s):  
Nitin Roper ◽  
Tapan K Maity ◽  
Shaojian Gao ◽  
Abhilash Karavattu Venugopalan ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Thymic Carcinoma ◽  
Driver Mutations ◽  
Patient Specific ◽  
Primary Tumors ◽  
Metastatic Lung ◽  
Organ Specific ◽  
Proteomic Analyses ◽  
Copy Number Changes

9023 Background: Intratumor heterogeneity has been characterized among multiple cancer types. In lung adenocarcinoma, APOBEC-mutagenesis has been shown to be a source of heterogeneity. However, these data are largely limited to early stage primary tumors. There is limited information about the role of APOBEC-mutagenesis and somatic variants, copy number changes, transcript and protein expression in influencing tumor heterogeneity in metastatic lung adenocarcinoma and other thoracic tumors. Methods: We applied whole exome sequencing, RNA-seq, OncoScan CNV and mass spectrometry-based proteomic analyses on 46 tumor regions from metastatic sites including lung, liver and kidney, obtained by rapid/warm autopsy from 4 patients (pts) with stage IV lung adenocarcinoma, 1 pt each with pleural mesothelioma and thymic carcinoma. The autopsy procedure was initiated between 2-4 hours of death. Results: All tumors displayed organ-specific, branched evolution that was consistent across exome, transcriptome and proteomic analyses. The degree of heterogeneity at the genomic and proteomic level was patient-specific. There was extensive heterogeneity within the tumors of one of four patients with lung adenocarcinoma and in the thymic carcinoma patient (both non-smokers) with multiple driver mutations and copy number changes occurring in only some of the tumors suggesting ongoing late tumor evolution. Further examination of the heterogenous thymic and lung adenocarcinoma tumors showed strong enrichment with the APOBEC-mutagenesis pattern and high associated levels of APOBEC3B mRNA. Conclusions: Metastatic lung adenocarcinoma, thymic carcinoma and mesothelioma evolve through a branched, organ-specific process with marked differences in the acquisition of significant driver mutations and copy number changes. APOBEC3B is a potential driver of heterogeneity in pts with advanced, heterogeneous metastatic lung adenocarcinoma and thymic carcinoma and needs to be evaluated further.

Engineering Tumors: A Tissue Engineering Perspective in Cancer Biology

2010 ◽  
Vol 16 (3) ◽  
pp. 351-359 ◽  
Author(s):  
Emily Burdett ◽  
F. Kurtis Kasper ◽  
Antonios G. Mikos ◽  
Joseph A. Ludwig
Keyword(s):  
Tissue Engineering ◽  
Cancer Biology

scholarly journals Tissue engineering toward organ-specific regeneration and disease modeling

2017 ◽  
Vol 7 (3) ◽  
pp. 332-347 ◽  
Author(s):  
Christian Mandrycky ◽  
Kiet Phong ◽  
Ying Zheng
Keyword(s):  
Tissue Engineering ◽  
Disease Modeling ◽  
Organ Specific ◽  
Image Position

Abstract

Acellular Scaffold Implantation – No Alternative to Tissue Engineering

2003 ◽  
Vol 26 (3) ◽  
pp. 225-234 ◽  
Author(s):  
T. Walles ◽  
C. Puschmann ◽  
A. Haverich ◽  
H. Mertsching
Keyword(s):  
Tissue Engineering ◽  
Carotid Artery ◽  
Inflammatory Reaction ◽  
Inflammatory Cell ◽  
Dna Isolation ◽  
In Vivo Model ◽  
Degradation Mechanisms ◽  
Immunohistochemical Methods ◽  
Acellular Scaffold

Objective Degradation mechanisms of cardiovascular bioprostheses may play an important role in bioartificial implants. The fate of acellular implanted and cellular cardiovascular scaffolds was examined in an in vivo model. Methods Decellularized or native ovine carotid artery (CA, n=42) and aorta (AO, n=42) were implanted subcutaneously into rats for 2, 4 and 8 weeks. Immunohistochemical methods were used to monitor repopulation. Desmin-vimentin, CD31-, CD4- and CD18-antibodies for myocytes, endothelium, and inflammatory cell-infiltration, respectively. Calcification was detected by von-Kossa staining. Cell density was quantified by DNA-isolation. Results Acellular AO and CA matrices showed progressive calcification. Cellular AO and CA matrices trigger a strong inflammatory reaction which subsides after two weeks. CA scaffolds are revascularized progressively, whereas AO biocomposites degenerate. Calcification is less pronounced in cellular AO scaffolds and lacking in CA. Conclusions Acellular bioartificial implants demonstrate degradation mechanisms similar to currently applied cardiovascular bioprostheses. Cellularized viable implants are promising clinical alternatives.

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