The tissues were homogenized and passed through a 70 μm cell strainer to remove clumps. No, Is the Subject Area "Colorectal cancer" applicable to this article? Analgesics (meloxicam or carprofen) are administered as needed to manage suspected pain. Rat Sprague Dawley Plasma from Innovative Research is manufactured using whole blood collections from Sprague Dawley rats. The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. Try out the SAS Sprague Dawley rat with our animal model evaluation program→ Article Snippet: Male Sprague-Dawley rats weighing 275–300 g were procured from Envigo and used in … A) Tumor kinetics in the SRG rat vs. SCID/NCr mouse. In addition, SRG rats can also greatly reduce the time needed to establish a PDX bank and can produce sufficient tumor tissue in the first in vivo generation (P1) to make a full preclinical study possible in the subsequent passage (P2). Since the rat is often the preferred rodent species for preclinical studies due to size and robust nature, particularly for pharmacokinetic and toxicology assessments, a severely immunodeficient rat model could be highly advantageous for oncology studies. If ulceration occurs, antibiotic ointment, which may include an analgesic, is applied topically at the onset of ulceration to prevent infection after consultation and approval by veterinarians. Then, sampling was done from rats … SDR rats demonstrated high efficiency and desirable uniformity in a variety of human tumor growth profiles and grew tumors to nearly ten times the volume (or double the diameter) allowed in mice. Strikingly, circulating NK cells in the peripheral blood of the SRG rat are significantly reduced (0.5%) relative to wild-type levels (10.1%) (Fig 2I–2K). These data demonstrate that SRG rats support the growth of human cancer cell lines with favorable take rates and growth kinetics for preclinical efficacy studies. SCID/NCr mice and SRG rats were inoculated with 5x106 and 10x106 VCaP cells, respectively, subcutaneously in the hind flank. The adult body weight is 250-300g for females, and 450-520g for males. Citation: Noto FK, Sangodkar J, Adedeji BT, Moody S, McClain CB, Tong M, et al. https://doi.org/10.1371/journal.pone.0240169.s003, https://doi.org/10.1371/journal.pone.0240169.s004, https://doi.org/10.1371/journal.pone.0240169.s005. Ns for Sprague-Dawley rats, respectively, were 5, 8, 10, 6, 9, 5, 14 and 6. Dr. Innis acknowledges support from the Morton S. and Henrietta K. Sellner Professorship in Human Genetics. These rats have proven to be extremely helpful in reproductive endocrinology research. Taken together, SRG rats are a valuable addition to the existing mouse models for use in preclinical oncology research. Tumor diameter was measured using digital calipers 3 times a week. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. G-I) NK cells in G) wild-type rat spleen and H) SRG rat spleen. Patient derived lung tumor was implanted into SRG rats. Litter average: 11.0. Formal analysis, and prepared for stereotaxic infusion of drug (0–10 nmol ferrous citrate and/or 0–16.8 nmol GSNO in 1 μl sterilized Ringer's solution or 0–33.6 nmol peroxynitrite in 1.05 μl 0.3 M NaOH solution) into right or left substantia nigra compacta area (i.n. Primary patient NSCLC tissue and NSCLC-PDX tissue collected from mouse and rat were fixed in 10% neutral buffered formalin, processed, paraffin embedded, and sectioned. Footshock could be avoided by pressing a lever during a danger period prior to onset of shock. Division of Genetic Medicine, Department of Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles MIA-PaCa-2, HCC1954, and 786-O were gifted to Hera BioLabs in June 2018. Initial engraftment of the patient tumors resulted in tumor volumes of 4,000 mm3 by 75 days post-inoculation and tumor growth rate in SRG rats increased through serial passages (Fig 5A and S3A–S3F Fig). Molecular characterization and histological analyses were performed for three PDX lines and showed high concordance between passages 1, 2 and 3 (P1, P2, P3), and the original patient sample. Tissues were stained with H&E, P40, and TTF1. The typical life span is 2.5 - 3.5 years.. Correlation measurements were obtained by Pearson Correlation. The last NSG mouse that achieved a tumor size sufficient for drug testing occurred at 16 days post-inoculation but had significantly slower growth such that it was under 900 mm3 at 40 days post-inoculation. Nurul Iftitah Musameh, Siti Rosmani Md Zin, Normadiah M. Kassim Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Abstract Genistein (Gen), is commonly consumed phytoestrogen among Asian and known to exert weak estrogenic effects. Each graph depicts tumor volumes for individual animals for 6 different NSCLC patient samples (A-F). Compared to NK cells in the wild-type rat (I; 10.1% CD161a+), the SRG rat has significantly reduced circulating NK cells (J; 0.5% CD161a+). Regional Medical Center, San Jose, California, United States of America, Affiliation Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America, The caveat to using the rat for efficacy studies is the need for larger amounts of dosing materials. Yes Blood was allowed to clot at room temperature for at least 30 minutes, then centrifuged at 6000xg for 3 minutes at room temperature to separate serum. We further demonstrated that SRG rats have high engraftment rates, favorable growth kinetics for efficacy studies, and can support large tumor volumes, providing ample tissue for molecular characterization and PDX bank establishment. VCaP tumors grown in SCID/NCr mice or SRG rats were collected, fixed in 10% neutral buffered formalin, processed, paraffin embedded, sectioned, and stained for AR (ab108341, abcam) or PSA (A056201-2, Dako). Yes This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. VCaP cells are difficult to maintain in vitro and display variable growth kinetics in vivo between published research groups . (Unpaired t-test, p-values: ** <0.01). Body condition score was also assessed for mice and rats as previously described [17, 18]. Tumors were monitored once daily for signs of ulceration. To SASCO from ARS/Sprague Dawley in 1979. The Sprague Dawley rat was first produced at Sprague Dawley farms, now a corporation called Harlan Sprague Dawley, and is widely used due in part to its calmness and ability to be handled easily. The rats are maintained as an outbred closed colony. While patient derived xenograft (PDX) models are a valuable cancer model, there are some limitations in employing such model systems for precision medicine approaches. For all staining, tissue slides were incubated with primary antibody overnight at 4°C. The chart below indicates specific parameters that are monitored (Table 1). Writing – original draft, Affiliation If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). Mouse models therefore are not always ideal for drug efficacy testing and downstream analyses such as pharmacokinetics, pharmacodynamics, and toxicology. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. (Unpaired t-test, p-values: * < 0.05). For transplantation, 5-10x106 VCaP cells, 2x106 HCT-116 cells, 5 x106 MIA-PaCa-2, 10 x106 786-O cells, or 5x106 HCC1954 cells were injected in each animal. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. The Sprague Dawley (SD) rat is often used as a general multipurpose rat model, including safety and efficacy testing, aging, nutrition, diet-induced obesity, oncology, and for surgical procedures. Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America, Affiliation https://doi.org/10.1371/journal.pone.0240169.t001. The wild-type Sprague Dawley rat thymus was comprised mostly of CD4/CD8 double positive cells whereas in the SRG rat, the viable cells recovered were CD4-/CD8- (Fig 1A–1C). Sprague Dawley rat: The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. We further demonstrated that SRG rats have high engraftment rates, favorable growth kinetics for efficacy studies, and can support … In addition, we can perform serial blood collection from the rat within humane guidelines to allow for pharmacokinetic and biomarker analysis following a single animal’s progression throughout the study. https://doi.org/10.1371/journal.pone.0240169.g001. HCT-116 cells were grown in McCoy’s 5a Medium Modified (ATCC #30–2007) supplemented with 10% fetal bovine serum (Atlanta Biologicals # S12450) and 1% penicillin and streptomycin solutions (Cat# 15140–122, Themofisher). Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan, United States of America, Blood was collected from SRG rats in Clot activator SST microtainers prior to inoculation of VCaP cells and then weekly throughout the study. A : Relative retroperitoneal fat weight. Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) Hera BioLabs Inc., Lexington, Kentucky, United States of America, Roles Conceptualization, https://doi.org/10.1371/journal.pone.0240169, Editor: Francesco Bertolini, European Institute of Oncology, ITALY, Received: July 6, 2020; Accepted: September 22, 2020; Published: October 7, 2020. In contrast, all 6 tumor HCT116 xenografts in SRG rats reached 150–250 mm3 in volume by 10 days post-inoculation and exhibited faster growth kinetics compared with the mouse, with all tumors in the SRG rats reaching endpoints for size between 26 and 33 days after inoculation. Two tailed t-tests (for two group comparisons) was used for experiments. By 10 days post-inoculation, tumor take rate was 100% in both NSG mice and SRG rats. These developed into a large tumor volume, over 20,000 mm3 in the first passage, which would provide an ample source of tissue for characterization and/or subsequent passage into NSG mice for drug efficacy studies. The Sprague Dawley® outbred model was developed by Sprague Dawley, Inc. NIH received stock from Sprague Dawley, Inc in 1945. Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America, Affiliations Tumor growth was monitored by externally measuring the greatest longtitudinal diameter (length) and the greatest transverse diameter (width) using digital calipers (Fowler #54-100-067-1) 3 times a week. The suspension of cells and Cultrex/Matrigel was injected subcutaneously into the hindflank. In addition to the colorectal cell line HCT-116, we also assessed the growth of several other cell lines in SRG rats (Fig 3B–3D): pancreatic cancer cell line MIA-PaCa-2, breast cancer cell line HCC1954, and renal cancer cell line 786-O. Each line represents tumor growth in an individual SRG rat or SCID/NCr mouse. The NSG mice had tumor volumes of 1000–2700 mm3 by 30 days post-inoculation and SRG rats had tumor volumes of 1800 mm3 to over 12,000 mm3 by 24 days post-inoculation (Fig 3A). (Unpaired t-test, p-values: * < 0.05). Compared to B cells in a wild-type spleen, the SRG spleen contains no mature B cells as demonstrated by lack of CD45R (B220)+/IgM+ cells. A) Tumor growth curve in NSG mice and SRG rats inoculated with 2x106 HCT-116 cells subcutaneously in the hind flank. We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. In summary, we have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B and T cells and circulating NK cells. Molecular analysis of VCaP tumors confirmed expression of the androgen receptor (AR) in both the SCID/NCr mouse and SRG rat models (Fig 4B and 4C). Also, some compounds display low systemic exposures in mice making it difficult to perform efficacy studies; for these compounds an alternative model is available using SRG rats. Subsequent passages from mouse/rat to mouse/rat are annotated as PDX passage 2, 3 or P2, P3, etc, to establish a bank of tissues. It was for this reason, together with the growing use of APM in industrialized countries, that we designed and performed a mega-experiment using seven groups of Sprague-Dawley rats (100-150 per sex per group) treated with APM in feed at various dose levels (including one very close to the ADI for humans), from 8 weeks of age until natural death (Belpoggi et al. The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. Serum PSA analysis was not performed for SCID/NCr mice since the procedure would require a terminal blood draw due to the much lower blood volume in the mice. This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley … Writing – original draft, Affiliation K) Quantification of data, n = 3, error ± SD. NK cells in the SRG rat spleen (H) are similar to or less than the amount of NK cells in the wild-type rat. All animal studies were conducted under the authorities of University of Kentucky’s and Icahn School of Medicine at Mount Sinai’s IACUCs, who specifically reviewed and approved these protocols. The processed soybean meal was added to formulated rodent diets at 20% (w/w) and fed to rats for 90 days.  This model has been tested and validated for use in oncology (SRG OncoRat®) with different human cancer cell lines and PDXs. These include cell lines that have poor take rates or variable growth kinetics in mice. T cells are significantly reduced in peripheral blood of the SRG rat (B; 1.6% CD4+, 5.3% CD8+, 1.2% CD4+/CD8+) compared to wild-type rat (A; 37.4% CD4+, 36.6% CD8+, 3.5% CD4+/CD8+). Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. (2020) The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. Flow cytometry dot plots show representative data from one WT and one SRG rat each. Sprague Dawley Rat High Fat T Increases Pain Behaviors In Rats With Or Without Nutrients full text calorie restriction modulates 1209 s7 article 03 sprague dawley rats a model of successful heart aging sciencedirect an weights of sprague dawley rats and age table safety essment and single dose toxiiics of the flavouring Change trends of organ weight background data in sprague dawley rats at different ages J Toxicol Pathol. Department of Pediatrics, The University of Michigan, Ann Arbor, Michigan, United States of America, Affiliations L) Quantitative comparison of wild-type Sprague Dawley versus SRG spleen and thymus at 8 weeks of age. Despite these advances, some important human cancer cell lines, such as the VCaP prostate model, exhibit high variability and poor tumor growth in both SDR rats and NSG mice, hindering the ability to run efficacy studies . here. Genetic analyses were performed for three of the PDX lines at multiple passages for each line in addition to the original patient sample. These measurements were used to calculate tumor volume by the modified ellipsoidal formula [19, 20]: Tumor volume = (L x W2)/2. Data represent average of 3 from each strain with SEM (Unpaired t-test, p-values: **** < 0.0001). Discover a faster, simpler path to publishing in a high-quality journal. Index, The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. PLOS ONE promises fair, rigorous peer review, Surgically resected NSCLC tissue from nine patients were implanted in SRG rats, seven of which engrafted and grew for an overall success rate of 78%. All of the pathogenic SNPs identified in our analysis were conserved across all passages. 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