Preclinical therapeutics ex ovo quail eggs as a biomimetic automation-ready xenograft platform.
Ontology highlight
ABSTRACT:
SUBMITTER: Rasmussen SV
PROVIDER: S-EPMC8639741 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The present study investigated the influence of exposing quail eggs to low-dose gamma radiation (GR) and in ovo feeding with 2 sources of a mixture of trace elements (Zn, Fe, and Cu), including sulfate (TES) and loaded with montmorillonite (TEM), on embryonic development activities and prehatch quality. A total of 960 eggs on the seventh day of incubation were randomly divided into 6 groups (160 eggs/group) with 4 replicate of 40 eggs in each. A 3 × 2 factorial arrangement experiment was performed and included 3 sources in ovo feeding with a mixture of trace elements (Zn, Fe, and Cu), including 0 mg/egg, 50 mg TES/egg, and 50 mg TEM/egg with egg irradiation using 0 and 0.2 Gy from GR. Eggs injected with 50 mg TEM/egg and exposed to 0.2 Gy from GR (TEM/GR) was significantly (P ≤ 0.05 and 0.01) higher in hatchability, hatch body weight, and relative organ weight (liver, gizzard, proventriculus, heart, and intestine). The obtained results indicated significant (P ≤ 0.05) decreased in the serum concentration of malondialdehyde (MDA) in TEM/GR group. There was significant (P ≤ 0.05) increased of catalase (CAT) activity and the concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in TEM/GR group; however; total antioxidant capacity (T-AOC) was significant (P ≤ 0.05) increased in CT/GR group. Serum concentrations of immunoglobulin M (IgM) (P ≤ 0.05) and tumor necrosis factor-alpha (TNF-α) were increased in the TEM/CR group; the concentration of transforming growth factor beta (TGF-β) significant (P ≤ 0.05) increased in the TEM/GR group; and interleukins (IL6 and IL10) showed no significant differences among the groups. Our results showed increase in thyroxine and myostatin concentrations with TES/CR and CT/GR of our study groups, respectively. The relative mRNA expression levels of the GH, IGF-1, and Fas cell surface death receptor (FAS) genes were significantly (P ≤ 0.05 and 0.01) upregulated in the liver tissue of the TEM/GR group compared with the other groups. In conclusion, TEM/GR was the best treatment for improving prehatch quality, increasing serum antioxidant enzyme activities, and promoting the expression of growth and immune genes in fertilized quail eggs.
| S-EPMC10825557 | biostudies-literature
Project description:Purpose: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease.Experimental Design: Clinically annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures. Models were characterized by IHC and by molecular analyses. Each PDX was luciferized to allow for reproducible in vivo assessment of intraperitoneal tumor burden by bioluminescence imaging (BLI). Plasma assays for CA125 and human LINE-1 were developed as secondary tests of in vivo disease burden.Results: Fourteen clinically annotated and molecularly characterized luciferized ovarian PDX models were generated. Luciferized PDX models retain fidelity to both the nonluciferized PDX and the original patient tumor, as demonstrated by IHC, array CGH, and targeted and whole-exome sequencing analyses. Models demonstrated diversity in specific genetic alterations and activation of PI3K signaling pathway members. Response of luciferized PDX models to standard-of-care therapy could be reproducibly monitored by BLI or plasma markers.Conclusions: We describe the establishment of a collection of 14 clinically annotated and molecularly characterized luciferized ovarian PDX models in which orthotopic tumor burden in the intraperitoneal space can be followed by standard and reproducible methods. This collection is well suited as a platform for proof-of-concept efficacy and biomarker studies and for validation of novel therapeutic strategies in ovarian cancer. Clin Cancer Res; 23(5); 1263-73. ©2016 AACR.
| S-EPMC5332350 | biostudies-literature
Project description:Preclinical evaluation of novel cancer agents requires models that accurately reflect the biology and molecular characteristics of human tumors. Molecular profiles of eight pancreatic ductal adenocarcinoma patient tumors were compared to corresponding passages of xenografts obtained by grafting tumor fragments into immunocompromised mice. Molecular characterization was performed by copy number analysis, gene expression and microRNA microarrays, mutation analysis, short tandem repeat (STR) profiling, and immunohistochemistry. Xenografts were found to be highly representative of their respective tumors, with a high degree of genetic stability observed by STR profiling and mutation analysis. Copy number variation (CNV) profiles of early and late xenograft passages were similar, with recurrent losses on chromosomes 1p, 3p, 4q, 6, 8p, 9, 10, 11q, 12p, 15q, 17, 18, 20p, and 21 and gains on 1q, 5p, 8q, 11q, 12q, 13q, 19q, and 20q. Pearson correlations of gene expression profiles of tumors and xenograft passages were above 0.88 for all models. Gene expression patterns between early and late passage xenografts were highly stable for each individual model. Changes observed in xenograft passages largely corresponded to human stromal compartment genes and inflammatory processes. While some differences exist between the primary tumors and corresponding xenografts, the molecular profiles remain stable after extensive passaging. Evidence for stability in molecular characteristics after several rounds of passaging lends confidence to clinical relevance and allows for expansion of models to generate the requisite number of animals required for cohorts used in drug screening and development studies.
| S-EPMC3819630 | biostudies-literature
Project description:Natural products include a diverse set of compounds of drug discovery that are currently being actively used to target tumor angiogenesis. In the present study, we evaluated the anti-angiogenic activities of secondary metabolite usnic acid isolated from Usena antarctica. We investigated the in vitro effects on proliferation, migration, and tube formation of VEGF- and bFGF-stimulated HUVECs. Ex ovo anti-angiogenic activity was evaluated using the CAM assay. Our findings demonstrated that usnic acid in the concentration of 33.57 µM inhibited VEGF (25 ng/mL) and bFGF (30 ng/mL)-induced HUVECs proliferation, migration, and tube formation. The ex ovo CAM model was used to confirm the results obtained from in vitro studies. VEGF- and bFGF-induced vessel formation was inhibited by usnic acid after 72 h in over 2-fold higher concentrations compared to in vitro. Subsequently, histological sections of affected chorioallantoic membranes were stained with hematoxylin-eosin and alcian blue to determine the number and diameter of vessels as well as the thickness of the individual CAM layers (ectoderm, mesoderm, endoderm). Usnic acid was able to suppress the formation of VEGF- and bFGF-induced vessels with a diameter of less than 100 μm, which was demonstrated by the reduction of mesoderm thickness as well.
| S-EPMC9503005 | biostudies-literature
Project description:IntroductionOlder adults with preclinical Alzheimer's disease (AD) show changes in on-road driving performance. The impact of preclinical AD on using automated vehicle (AV) technology is unknown. The aim was to evaluate safety and cognitive workload while operating AV technology in drivers with preclinical AD.IntroductionThis cross-sectional study included 40 participants: 19 older adults (age 74.16 ± 4.78; MOCA scores 26.42 ± 2.52) with preclinical AD, evidenced by elevated cortical beta-amyloid; and 21 controls (age 73.81 ± 5.62; MOCA scores 28.24 ± 1.67). All participants completed two scenarios in a driving simulator. Scenario 1 included conditional automation with an emergency event that required a manual take-over maneuver. Scenario 2 was identical but with a cognitive distractor task. Emergency response time was the main safety outcome measure. Cognitive workload was calculated using moment-to-moment changes in pupillary size and converted into an Index of Cognitive Activity (ICA). Mann-Whitney U and independent t tests were used to compare group differences.ResultsEmergency response times were similar between drivers with preclinical AD and controls in scenario 1 (20.85 s ± 1.08 vs. 20.52 s ± 3.18; p = 0.83) and scenario 2 (14.83 s ± 7.37 vs. 13.45 s ± 10.43; p = 0.92). Likewise, no differences were found in ICA between drivers with preclinical AD and controls in scenario 1 (0.34 ± 0.08 vs. 0.33 ± 0.17; p = 0.74) or scenario 2 (0.30 ± 0.07 vs. 0.29 ± 0.17; p = 0.93).ConclusionsOlder drivers with preclinical AD may safely operate AV technology, without increased response times or cognitive workload. Future on-road studies with AV technology should confirm these preliminary results in drivers with preclinical AD.
| S-EPMC10843675 | biostudies-literature
Project description:Background and purposeSmall cell lung cancer (SCLC) is an aggressive disease with median survival of <2 years. Tumour biopsies for research are scarce, especially from extensive-stage patients, with repeat sampling at disease progression rarely performed. We overcame this limitation for relevant preclinical models by developing SCLC circulating tumour cell derived explants (CDX), which mimic the donor tumour pathology and chemotherapy response. To facilitate compound screening and identification of clinically relevant biomarkers, we developed short-term ex vivo cultures of CDX tumour cells.Experimental approachCDX tumours were disaggregated, and the human tumour cells derived were cultured for a maximum of 5 weeks. Phenotypic, transcriptomic and pharmacological characterization of these cells was performed.Key resultsCDX cultures maintained a neuroendocrine phenotype, and most changes in the expression of protein-coding genes observed in cultures, for up to 4 weeks, were reversible when the cells were re-implanted in vivo. Moreover, the CDX cultures exhibited a similar sensitivity to chemotherapy compared to the corresponding CDX tumour in vivo and were able to predict in vivo responses to therapeutic candidates.Conclusions and implicationsShort-term cultures of CDX provide a tractable platform to screen new treatments, identify predictive and pharmacodynamic biomarkers and investigate mechanisms of resistance to better understand the progression of this recalcitrant tumour.
| S-EPMC6329630 | biostudies-literature
Project description:Adipogenesis is essential in in vitro experimentation to assess differentiation capability of stem cells, and therefore, its accurate measurement is important. Quantitative analysis of adipogenic levels, however, is challenging and often susceptible to errors due to non-specific reading or manual estimation by observers. To this end, we developed a novel adipocyte quantification algorithm, named Fast Adipogenesis Tracking System (FATS), based on computer vision libraries. The FATS algorithm is versatile and capable of accurately detecting and quantifying percentage of cells undergoing adipogenic and browning differentiation even under difficult conditions such as the presence of large cell clumps or high cell densities. The algorithm was tested on various cell lines including 3T3-L1 cells, adipose-derived mesenchymal stem cells (ASCs), and induced pluripotent stem cell (iPSC)-derived cells. The FATS algorithm is particularly useful for adipogenic measurement of embryoid bodies derived from pluripotent stem cells and was capable of accurately distinguishing adipogenic cells from false-positive stains. We then demonstrate the effectiveness of the FATS algorithm for screening of nuclear receptor ligands that affect adipogenesis in the high-throughput manner. Together, the FATS offer a universal and automated image-based method to quantify adipocyte differentiation of different cell lines in both standard and high-throughput workflows.
| S-EPMC6341617 | biostudies-literature
Project description:Rhabdomyosarcoma (RMS) is the most common highly malignant pediatric soft tissue sarcoma. While recent multidisciplinary treatments have improved the 5‑year survival rate of low/intermediate‑risk patients to 70‑90%, there are various complications that arise due to treatment‑related toxicities. Immunodeficient mice‑derived xenograft models have been widely used in cancer drug research; however, these models have some limitations, including i) they are time‑consuming and expensive, ii) their use needs to be approved by animal experimental ethics committees, and iii) the inability to visualize where tumor cells or tissues were engrafted. The present study performed a chorioallantoic membrane (CAM) assay in fertilized chicken eggs, which is time‑saving, simple, and easy to standardize and handle because of the high vascularization and the immature immune system of the fertilized eggs. The present study aimed to examine the usability of the CAM assay as a novel therapeutic model for the development of precision medicine for pediatric cancer. A protocol was developed for constructing cell line‑derived xenograft (CDX) models using a CAM assay by transplanting RMS cells on the CAM. It was then examined as to whether these CDX models could be used as therapeutic drug evaluation models using vincristine (VCR) and human RMS cell lines. After grafting and culturing the RMS cell suspension on the CAM, three‑dimensional proliferation over time was observed visually and by comparing volumes. VCR reduced the size of the RMS tumor on the CAM in a dose‑dependent manner. Currently, treatment strategies based on patient‑specific oncogenic backgrounds have not been adequately developed in the field of pediatric cancer. The establishment of a CDX model with the CAM assay may lead to the advancement of precision medicine and help formulate novel therapeutic strategies for intractable pediatric cancer.
| S-EPMC10018452 | biostudies-literature
Project description:BackgroundGlioblastoma multiforme (GBM) is a fatal malignant primary brain tumor in adults. The therapeutic efficacy of chemotherapeutic drugs is limited due to the blood-brain barrier (BBB), poor drug targeting, and short biological half-lives. Multifunctional biomimetic nanodrugs have great potential to overcome these limitations of chemotherapeutic drugs.MethodsWe synthesized and characterized a biomimetic nanodrug CMS/PEG-DOX-M. The CMS/PEG-DOX-M effectively and rapidly released DOX in U87 MG cells. Cell proliferation and apoptosis assays were examined by the MTT and TUNEL assays. The penetration of nanodrugs through the BBB and anti-tumor efficacy were investigated in the orthotopic glioblastoma xenograft models.ResultsWe showed that CMS/PEG-DOX-M inhibited cell proliferation of U87 MG cells and effectively induced cell apoptosis of U87 MG cells. Intracranial antitumor experiments showed that free DOX hardly penetrated the BBB, but CMS/PEG-DOX-M effectively reached the orthotopic intracranial tumor through the BBB and significantly inhibited tumor growth. Immunofluorescence staining of orthotopic tumor tissue sections confirmed that nanodrugs promoted apoptosis of tumor cells. This study developed a multimodal nanodrug treatment system with the enhanced abilities of tumor-targeting, BBB penetration, and cancer-specific accumulation of chemotherapeutic drugs by combining chemotherapy and photothermal therapy. It can be used as a flexible and effective GBM treatment system and it may also be used for the treatment of other central nervous systems (CNS) tumors and extracranial tumors.
| S-EPMC9717509 | biostudies-literature
Project description:Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR), we evaluated Curcumin-Pyrogallol (CUR-PYR) cocrystal and Curcumin-Artemisinin (CUR-ART) coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose). Moreover, in simulated gastric and intestinal fluids (SGF and SIF), CUR-ART is stable up to 3 and 12 h, respectively. In addition, CUR-PYR and CUR-ART showed no adverse effects in toxicology studies (10 times higher dose at 2000 mg/kg). CUR-ART showed higher therapeutic effect and inhibited approximately 62% of tumor growth at 100 mg/kg oral dosage of CUR in xenograft models, which is equal to the positive control drug, doxorubicin (2 mg/kg) by i.v. administration.
| S-EPMC5874820 | biostudies-other