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Nude mice

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Sourced in France, United States

Nude mice are a type of laboratory mouse that lack a functional immune system. They are commonly used in medical research and drug development as hosts for human tumor xenografts or to study the effects of new treatments on human diseases.

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9 protocols using nude mice

1

Compound C Inhibits Uveal Melanoma Tumor Growth

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Example 16

Procedure: Nude mice (Envigo) were engrafted subcutaneously in the axillary region with 5×106 92-1 uveal melanoma cells in 50% Matrigel. Tumors were grown to a mean of ˜200 mm3, at which point mice were grouped and dosing was initiated. Mice were dosed once daily by oral gavage with vehicle (20% 2-Hydroxypropyl-8-Cyclodextrin) or increasing doses of Compound C. Tumor volumes and body weights were measured over the course of 3 weeks, and doses were adjusted by body weight to achieve the proper dose in terms of mg/kg. At this time, animals were sacrificed, and tumors were dissected and imaged.

Results: As shown in FIG. 11 and FIG. 12, treatment with Compound C led to tumor growth inhibition in a dose-dependent manner with tumor regression observed at the highest (50 mg/kg) dose. As shown in FIG. 13, all treatments were well tolerated with no body weight loss observed (FIG. 13).

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2

Combination Immunotherapy in Murine Tumor Models

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Male or female BALB/c, C57BL-6 and nude mice were purchased from Envigo and housed under specific pathogen free conditions at the CRUK Cambridge institute animal facility. All procedures were carried out in accordance with UK home office regulations and with approved institutional guidelines.
CT-26 (5x106 cells/mouse) or MC-38 (5x106 cells/mouse) tumour cells were implanted subcutaneously (s.c.) in the left flank of female mice. Four days (CT-26) or one day (MC-38) after implantation mice were randomised by body weight and dosed dosed at 15 mg/kg daily p.o. with vistusertib in 1% Polysorbate and 20 mg/kg 2 times a week, i.p. with anti- CTLA-4 (9D9) IgG1, or 10 mg/kg 2 times a week with anti-PD-L1 (D265A) IgG1 in PBS. At end of study tumour tissues were then transferred into the gentleMACS C Tube containing RPMI. Tumour samples were processed using the mouse tumour dissociation kit from Miltenyi Biotec. Cells were liberated from tumours for downstream application using a mouse tumour dissociation kit and octodissociator (Miltenyi) according to manufacturer's instructions.
Plasma pharmacokinetic analysis of vistusertib concentrations was performed as previously described.6
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3

Subcutaneous Tumor Growth Assay

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All animal experiments were performed according to the guidelines of the Institutional Animal Care and Use Committee and the regional ethics committee (approval references PEA-503 and PEA-673). All experiments used age-matched five-week-old female littermates. WT syngeneic BALB/c and C57BL/6 mice as well as Nude mice were obtained from ENVIGO and housed in our animal facility (C3M-Nice, France). When specified, mice were fed isocaloric diets purchased from ENVIGO: either the Control (CTR: TD.130931) or the Low Protein diet (Low PROT −25%: TD.130933). The caloric composition of these diets (% of energy provided by carbohydrate: protein: fat content) was the following: CTR – (70.9%: 19.5%: 9.6%) and Low PROT −25% – (73.7%: 14.9%: 11.5%), see.6 (link) Mice were fed the specified diets for 7 days prior to subcutaneous engraftment of tumor cells. WT syngeneic BALB/c and Nude mice were subcutaneously engrafted with 0.75 × 106 CT26 cells while C57BL/6 mice were subcutaneously engrafted with 0.5 × 106 LLC1. After subcutaneous engraftment of CT26 and LLC1 cells, mice were inspected every two days for tumor development. Tumor growth was monitored by caliper measurement following the equation (width2 x length)/2. Animals were sacrificed when a tumor reached at least 1000 mm3.
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4

Nude Mice Xenograft of Uveal Melanoma

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Example 18

Procedure: Nude mice (Envigo) were engrafted subcutaneously in the axillary region with 5×106 92-1 uveal melanoma cells in 50% Matrigel. Tumors were grown to a mean of ˜200 mm3, at which point mice were grouped and dosing was initiated. Mice were dosed once daily by oral gavage with vehicle (20% 2-Hydroxypropyl-β-Cyclodextrin) or increasing doses of N—((S)-1-((4-(6-(cis-2,6-dimethylmorpholino)pyridin-2-yl)thiazol-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-1-(methylsulfonyl)-1H-pyrrole-3-carboxamide. Tumor volumes and body weights were measured over the course of 3 weeks, and doses were adjusted by body weight to achieve the proper dose in terms of mg/kg.

Results: As shown in FIG. 15, treatment with N—((S)-1-((4-(6-(cis-2,6-dimethylmorpholino)pyridin-2-yl)thiazol-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-1-(methylsulfonyl)-1H-pyrrole-3-carboxamide led to tumor growth inhibition in a dose-dependent manner with tumor regression observed at the highest (1.5 mg/kg) dose. As shown in FIG. 16, all treatments were well tolerated based on % body weight change observed.

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5

Organoid Generation and Transplantation Assays

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For organoid generation, 8–12 weeks old DsRed.T3 mice of both sexes were used. This strain was purchased from the Jackson Laboratory. Mice were maintained in virus-free conditions and were housed in groups. All mouse experiments were approved by the BCH Animal Care and Use Committee, accredited by AAALAC, and were performed in accordance with relevant institutional and national guidelines and regulations.
For injury and transplantation assays, 8–12 weeks old Rag1 KO and Nude mice of both sexes were used. Rag1 KO mice are available from The Jackson Laboratory and Nude mice are available from ENVIGO. Mice were maintained in virus-free conditions and were housed in groups. Littermates were randomly assigned to experimental groups. All mouse experiments were approved by the BCH Animal Care and Use Committee, accredited by AAALAC, and were performed in accordance with relevant institutional and national guidelines and regulations.
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6

Organoid Generation and Transplantation Assays

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For organoid generation, 8–12 weeks old DsRed.T3 mice of both sexes were used. This strain was purchased from the Jackson Laboratory. Mice were maintained in virus-free conditions and were housed in groups. All mouse experiments were approved by the BCH Animal Care and Use Committee, accredited by AAALAC, and were performed in accordance with relevant institutional and national guidelines and regulations.
For injury and transplantation assays, 8–12 weeks old Rag1 KO and Nude mice of both sexes were used. Rag1 KO mice are available from The Jackson Laboratory and Nude mice are available from ENVIGO. Mice were maintained in virus-free conditions and were housed in groups. Littermates were randomly assigned to experimental groups. All mouse experiments were approved by the BCH Animal Care and Use Committee, accredited by AAALAC, and were performed in accordance with relevant institutional and national guidelines and regulations.
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7

Generating Pancreatic Tumor Mouse Models

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Tumor mouse models were created by orthotopic pancreatic injections of 5 × 105 LM-PmC cells into nude mice purchased from Envigo (Indianapolis, IN) and 105 KPC-derived PDAC organoids into C57BL6/129 F1 hybrid mice (Jackson, Bar Harbor, ME). In some cases, luciferase-labeled KPC-derived PDAC organoids were used, and their growth was monitored by luminescence imaging of the mice using a Xenogen IVIS Spectrum Imaging System (PerkinElmer, Waltham, MA). The p48-CRE, LSL-KrasG12D, INK4aflox mice required for the experiments were kindly provided by Dr. Douglas Hanahan (current affiliation: Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland). KPC mice were maintained as previously described52 (link).
The mice were maintained at a maximum of 5 mice per cage with 12 h-light/dark cycles, 20 °C, and 50% humidity. All animal experiments were performed according to procedures approved by the Animal Research Committees at Sanford–Burnham–Prebys (SBP) Medical Discovery Institute (La Jolla, CA) and University of California San Diego (UCSD, La Jolla, CA).
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8

Osteosarcoma Tumor Xenograft Model

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Tumors were established by subcutaneously implanting 5 x 106 F420 osteosarcoma cells or K7M2 osteosarcoma cells into the flanks of 6-week-old C57BL/6 or BALB/c mice, respectively. To compare tumor growth without treatment, tumors as above were established in the flanks of 6-week-old nude mice (Envigo).
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9

Evaluating Napabucasin and Radiation Therapy Against Colorectal Cancer

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Nude mice were purchased from Envigo (Indianapolis, IN, USA) and maintained according to IACUC protocols at Emory University. HCT 116 cells (1 × 106) mixed with 15% matrigel and were subcutaneously inserted into mice. The animals were randomized into 4 groups when the tumor reached 100 mm3 in size. Group 1 received water orally and served as a control group. Group 2 received napabucasin orally (100mg per kg) for 11 days daily. Group 3 received 5-FU (30mg/kg IV) + a single fraction of radiation at 4Gy once a week for two weeks. Finally, group 4 received napabucasin + 5FU + radiation. The tumor volumes were measured once every 4 days using veneal caliber scales. Mice were euthanized via CO2 asphyxiation followed by dissected to peel the skin covering tumors over the inserted matrigel. This was then was photographed under visible light to evaluate angiogenesis.
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