Generation of human acute lymphoblastic leukemia xenografts for use in oncology drug discovery.
Authors: Holmfeldt L, Mullighan CG
Abstract
The establishment of reproducible mouse models of acute lymphoblastic leukemia (ALL) is necessary to provide in vivo therapeutic test systems that recapitulate human ALL, and for amplification of limited amounts of primary tumor material. A popular assay is the primary xenograft model that utilizes immunocompromised mice. The protocol includes injection of primary patient tumor specimens into mice with subsequent serial passaging of the tumors by retransplants of cells harvested from the mouse bone marrow and spleen. The tumors generated are then used for genomic...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Arrestin-3-Dependent Activation of c-Jun N-Terminal Kinases (JNKs).
Authors: Zhan X, Kook S, Kaoud TS, Dalby KN, Gurevich EV, Gurevich VV
Abstract
Only one out of four mammalian arrestin subtypes, arrestin-3, facilitates the activation of JNK family kinases. Here we describe two different protocols used for elucidating the mechanisms involved. One is based on reconstitution of signaling modules from purified proteins: arrestin-3, MKK4, MKK7, JNK1, JNK2, and JNK3. The main advantage of this method is that it unambiguously establishes which effects are direct because only intended purified proteins are present in these assays. The key drawback is that the upstream-most kinas...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Overview of KRAS-Driven Genetically Engineered Mouse Models of Non-Small Cell Lung Cancer.
Authors: Sheridan C, Downward J
Abstract
KRAS, the most frequently mutated oncogene in non-small cell lung cancer, has been utilized extensively to model human lung adenocarcinomas. The results from such studies have enhanced considerably an understanding of the relationship between KRAS and the development of lung cancer. Detailed in this overview are the features of various KRAS-driven genetically engineered mouse models (GEMMs) of non-small cell lung cancer, their utilization, and the potential of these models for the study of lung cancer biology. © 2015 by John Wiley & Sons, Inc.
PMID: 26...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Overview of Genetically Engineered Mouse Models of Breast Cancer Used in Translational Biology and Drug Development.
Authors: Greenow KR, Smalley MJ
Abstract
Breast cancer is a heterogeneous condition with no single standard of treatment and no definitive method for determining whether a tumor will respond to therapy. The development of murine models that faithfully mimic specific human breast cancer subtypes is critical for the development of patient-specific treatments. While the artificial nature of traditional in vivo xenograft models used to characterize novel anticancer treatments has limited clinical predictive value, the development of genetically engineered mouse models (GEMMs) makes it possible to study the the...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Using Bioluminescence Resonance Energy Transfer (BRET) to Characterize Agonist-Induced Arrestin Recruitment to Modified and Unmodified G Protein-Coupled Receptors.
Authors: Donthamsetti P, Quejada JR, Javitch JA, Gurevich VV, Lambert NA
Abstract
G protein-coupled receptors (GPCRs) represent ∼25% of current drug targets. Ligand binding to these receptors activates G proteins and arrestins, which are involved in differential signaling pathways. Because functionally selective or biased ligands activate one of these two pathways, they may be superior medications for certain diseases states. The identification of such ligands requires robust drug screening assays for both G protein and arrestin activity. This unit describes protocols for two bioluminescence resonance en...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.
Authors: McCarson KE
Abstract
Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory ...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Streptozotocin-Induced Diabetic Models in Mice and Rats.
Authors: Furman BL
Abstract
Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition. © 2015 by John Wiley & Sons, Inc.
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Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Overview of Genetically Engineered Mouse Models of Papillary and Anaplastic Thyroid Cancers: Enabling Translational Biology for Patient Care Improvement.
Authors: Charles RP
Abstract
The prognosis from thyroid cancer subtypes in humans covers a spectrum from "cured at almost 90%" to "100% lethal." Invasive and poorly differentiated forms of thyroid cancer are among the most aggressive human cancers, and there are few effective therapeutic options. Genetically engineered mice, based on mutations observed in patients, can accurately recapitulate the human disease and its progression, providing invaluable tools for the preclinical evaluation of novel therapeutic approaches. This overview details models developed to date as well as their uses for identifying no...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Murine Models of Helicobacter (pylori or felis)-associated Gastric Cancer.
Authors: Duckworth CA, Burkitt MD, Williams JM, Parsons BN, Tang JM, Pritchard DM
Abstract
Gastric adenocarcinoma is the fifth most common cancer and third most common cause of cancer-related death in the world. The majority of these cancers develop in genetically susceptible individuals who are chronically infected with the Gram-negative bacterium Helicobacter pylori. Often these individuals have also been exposed to certain environmental factors that increase susceptibility, such as dietary components. Murine models of Helicobacter-induced gastric cancer are valuable tools for investigating the mechanism...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Determination of GPCR Phosphorylation Status: Establishing a Phosphorylation Barcode.
Authors: Prihandoko R, Bradley SJ, Tobin AB, Butcher AJ
Abstract
G protein-coupled receptors (GPCRs) are rapidly phosphorylated following agonist occupation in a process that mediates receptor uncoupling from its cognate G protein, a process referred to as desensitization. In addition, this process provides a mechanism by which receptors can engage with arrestin adaptor molecules and couple to downstream signaling pathways. The importance of this regulatory process has been highlighted recently by the understanding that ligands can direct receptor signaling along one pathway in preference to another, the p...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
Rodent Models of Amyotrophic Lateral Sclerosis.
Authors: Philips T, Rothstein JD
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼40% to 50% of fALS and ∼10% of sALS). Studies suggest t...
Source: Current Protocols in Pharmacology - November 18, 2015 Category: Drugs & Pharmacology Tags: Curr Protoc Pharmacol Source Type: research
