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.

scholarly journals Sodium Valproate Inhibits Small Cell Lung Cancer Tumor Growth on the Chicken Embryo Chorioallantoic Membrane and Reduces the p53 and EZH2 Expression

Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581877248 ◽  
Author(s):  
Lina Šlekienė ◽  
Donatas Stakišaitis ◽  
Ingrida Balnytė ◽  
Angelija Valančiūtė
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Sodium Valproate ◽  
Cell Lung Cancer ◽  
Chicken Embryo ◽  
Chorioallantoic Membrane ◽  
Small Cell ◽  
Small Cell Lung ◽  
Efficacy Evaluation ◽  
Cancer Tumor

The study aims to test the effect of different sodium valproate (NaVP) doses on small cell lung cancer NCI-H146 cells tumor in chicken embryo chorioallantoic membrane (CAM) model. Xenografts were investigated in the following groups: nontreated control and 5 groups treated with different NaVP doses (2, 3, 4, 6, and 8 mmol/L). Invasion of tumors into CAM in the nontreated group reached 76%. Tumors treated with 8 mmol/L NaVP doses significantly differed in tumor invasion frequency from the control and those treated with 2 mmol/L ( P < .01). The calculated probability of 50% tumor noninvasion into CAM was when tumors were treated with 4 mmol/L of NaVP. Number of p53-positive cells in tumors was significantly reduced when treated with NaVP doses from 3 to 8 mmol/L as compared with control; number of EZH2-positive cells in control significantly differed from all NaVP-treated groups. No differences in p53- and EZH2-positive cell numbers were found among 4, 6, and 8 mmol/L NaVP-treated groups. Invaded tumors had an increased N-cadherin and reduced E-cadherin expression. The results indicate the increasing NaVP dose to be able to inhibit tumors progression. Expression of p53 and EZH2 may be promising target markers of therapeutic efficacy evaluation.

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 Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development.

1994 ◽  
Vol 180 (1) ◽  
pp. 53-66 ◽  
Author(s):  
A Bartolazzi ◽  
R Peach ◽  
A Aruffo ◽  
I Stamenkovic
Keyword(s):  
Tumor Growth ◽  
Cell Attachment ◽  
Tumor Development ◽  
Tumor Formation ◽  
Wild Type ◽  
Cd44 Isoforms ◽  
Secondary Tumor ◽  
Mediate Cell ◽  
Melanoma Growth

CD44 is implicated in the regulation of tumor growth and metastasis but the mechanism by which expression of different CD44 isoforms determines the rate of primary and secondary tumor growth remains unclear. In the present study we use a human melanoma transfected with wild-type and mutant forms of CD44 to determine which functional property of the CD44 molecule is critical in influencing tumor behavior. We show that expression of a wild-type CD44 isoform that binds hyaluronic acid augments the rapidity of tumor formation by melanoma cells in vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment to hyaluronate, fails to do so. The importance of CD44-hyaluronate interaction in tumor development is underscored by the differential inhibitory effect of soluble wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44-Ig is shown to block tumor development. Taken together, these observations suggest that the tumor growth promoting property of CD44 is largely dependent on its ability to mediate cell attachment to hyaluronate.

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 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 Monitoring of Tumor Growth and Vascularization with Repetitive Ultrasonography in the Chicken Chorioallantoic-Membrane-Assay.

2020 ◽  
Author(s):  
Jonas Eckrich ◽  
Philipp Kugler ◽  
Christoph Raphael Buhr ◽  
Benjamin Philipp Ernst ◽  
Simone Mendler ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Imaging Techniques ◽  
Tumor Development ◽  
Three Dimensional ◽  
Chorioallantoic Membrane ◽  
Shielding Effect ◽  
Cam Assay ◽  
In Ovo ◽  
Cost Efficient

Abstract Background: The chorioallantoic-membrane (CAM)-assay is used for versatile experimentation and eligible for the analysis of tumor angiogenesis, development and metastasis. In contrast to rodent xenograft models, the CAM-assay does not require breeding of immunodeficient strains for tumor experimentation due to native immunodeficiency. This allows xenografts to grow on the non-innervated CAM without pain or impairment for the embyo.Taking into account the variability of multidirectional tumor growth, limited size monitoring capability is a major disadvantage of the CAM-assay as the enclosure of the tumor in ovo by the eggshell only allows for two-dimensional monitoring from above. The small size and the eggshell’s shielding effect further challenge established imaging techniques. We report the eligibility of ultrasonographic imaging for repetitive monitoring of tumor growth and vascularisation in the CAM-assay.Methods: Chicken eggs were placed in an incubator and cut open laterally on day three. On day seven a three-dimensional tumor was placed onto the CAM. Ultrasonographic imaging was then repetitively performed starting from day twelve. On day 14 the tumor was excised, fixed and histologically analyzed using light microscopy.Results: Tumor volume and vascularization were repetitively visualized using a commercial ultrasonographic scanner, allowing a longitudinal monitoring of tumor growth and tumor angiogenesis. Findings in ultrasonographic imaging significantly correlated with results obtained in histological analysis. Conclusion: Ultrasonography is cost efficient and widely available. It allows repetitive in ovo imaging and thereby enables visualization of tumor development. This increases the applicability of the CAM-assay as an alternative to xenograft rodent models in tumor research.

scholarly journals Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

2017 ◽  
Vol 26 (2) ◽  
pp. 144
Author(s):  
Lina Šlekienė ◽  
Raminta Mozūraitė ◽  
Ruta Vosyliūtė ◽  
Ingrida Balnytė ◽  
Angelija Valančiūtė
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Sodium Valproate ◽  
Cell Lung Cancer ◽  
Chicken Embryo ◽  
Chorioallantoic Membrane ◽  
Treated Group ◽  
Small Cell ◽  
Small Cell Lung

Small cell lung cancer (SCLC) is an aggressive form of cancer with 5-year survival rate and poor prognosis. Since patients' initial response to therapy is rapidly followed by a relapse with the drug-resistant disease, new therapies are required. The aim was to evaluate whether H146 cell line tumor was able to maintain the morphological pattern when grafted on the chicken embryo chorioallantoic membrane (CAM). Also, to evaluate the morphological changes in the CAM after grafting the tumor without or with treatment with sodium valproate (NaVP). The cell culture of the commercial NCIH146 cell line was used for the formation of the tumor. The tumor of 1x106 cells and I type rat tail collagen was dropped onto the absordable sponge and instantly grafted on CAM. After 5 days of incubation chicken embryos were sacrificed and CAMs were cut out. Standard H&E staining and immunohistochemistry (CD56) were performed. The histomorphometrical analysis of non-treated (n=5), 4 mM NaVP-treated (n=5) and 8 mM (n=5) of NaVP-treated groups was performed. The thickness of the CAM was measured in all the investigated groups in the areas under the onplant and in the neighbouring sites. H146 cells are able to maintain morphological appearance on the CAM and retained the expression of specific profile for CD56. H146 cell tumor increased the thickness of the CAM under the tumor in the non-treated group (509.2±184μm). After treatment with 4 mM and 8 mM of NaVP CAM thickness decreased (362±232.6 μm and 147.8±98.4 μm respectively; p<0.0001). The effect of NaVP on CAM increased with increasing solution concentrations of 4 mM and 8 mM. CAM thickness in the non-treated group neighbouring to the tumor site was 139.1±138.4 μm, in 4 mM NaVP-treated group – 104.9±81 μm and in 8 mM NaVP-treated group CAM thickness reached only 70.8±51.5 μm. CAM thickness in the non-treated group significantly differs compared to 4 mM and 8 mM of NaVP – the treated groups (p<0.05, p<0.0001). Difference between both NaVP-treated groups is also significant (p<0.05). CAM is a suitable model for in vivo analysis of human H146 cell line formed tumor. Cells grafted on the CAM preserved their morphology and expressed characteristic immunohistochemical markers. CAM mesenchyme proliferation was suppressed under the influence of NaVP in concentration–dependent manner.

scholarly journals Investigating New Therapeutic Strategies Targeting Hyperinsulinemia's Mitogenic Effects in a Female Mouse Breast Cancer Model

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1701-1710 ◽  
Author(s):  
Ran Rostoker ◽  
Keren Bitton-Worms ◽  
Avishay Caspi ◽  
Zila Shen-Orr ◽  
Derek LeRoith
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Breast Tumor ◽  
Experimental Studies ◽  
Tumor Development ◽  
Treated Group ◽  
Tumor Growth Rate ◽  
Breast Cancer Patients ◽  
Mitogenic Effect

Abstract Epidemiological and experimental studies have identified hyperinsulinemia as an important risk factor for breast cancer induction and for the poor prognosis in breast cancer patients with obesity and type 2 diabetes. Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. Although IGF-IR has been intensively investigated, and anti-IGF-IR therapies are now in advanced clinical trials, the role of the IR in mediating hyperinsulinemia's mitogenic effect remains to be clarified. Here we aimed to explore the potential of IR inhibition compared to dual IR/IGF-IR blockade on breast tumor growth. To initiate breast tumors, we inoculated the mammary carcinoma Mvt-1 cell line into the inguinal mammary fat pad of the hyperinsulinemic MKR female mice, and to study the role of IR, we treated the mice bearing tumors with the recently reported high-affinity IR antagonist-S961, in addition to the well-documented IGF-IR inhibitor picropodophyllin (PPP). Although reducing IR activation, with resultant severe hyperglycemia and hyperinsulinemia, S961-treated mice had significantly larger tumors compared to the vehicle-treated group. This effect maybe secondary to the severe hyperinsulinemia mediated via the IGF-1 receptor. In contrast, PPP by partially inhibiting both IR and IGF-IR activity reduced tumor growth rate with only mild metabolic consequences. We conclude that targeting (even partially) both IR and IGF-IRs impairs hyperinsulinemia's effects in breast tumor development while simultaneously sparing the metabolic abnormalities observed when targeting IR alone with virtual complete inhibition.

scholarly journals Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5826-5834 ◽  
Author(s):  
Shoshana Yakar ◽  
Nomeli P. Nunez ◽  
Patricia Pennisi ◽  
Pnina Brodt ◽  
Hui Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tumor Growth ◽  
Glucose Intolerance ◽  
Tumor Development ◽  
Tumor Growth Rate ◽  
Obese Mice ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Obese Female

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors

2017 ◽  
Vol 18 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Andres Morales La Madrid ◽  
Mark W. Kieran
Keyword(s):  
Nervous System ◽  
Brain Tumors ◽  
Children And Adolescents ◽  
Tumor Biology ◽  
Tumor Development ◽  
Integrated Approach ◽  
Cell Types ◽  
Pediatric Brain Tumors ◽  
Tumor Formation ◽  
Molecular Profile

Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages –not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the “classic boxes” heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we reviewed the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.

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