A5022932721- Microtubule and mitosis dynamics
- Liver physiology and pathology
- Muscle Physiology and Disorders
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Skin and Cellular Biology Research
- Hair Growth and Disorders
- Glutathione Transferases and Polymorphisms
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Chemical Reactions and Isotopes
- Nitrogen and Sulfur Effects on Brassica
- Celiac Disease Research and Management
- Hepatocellular Carcinoma Treatment and Prognosis
- Wnt/β-catenin signaling in development and cancer
- Chemokine receptors and signaling
- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Dermatology and Skin Diseases
- Angiogenesis and VEGF in Cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
Eli Lilly (United States)
2014-2024
Indianapolis Zoo
2014
University of Pennsylvania
2014
Texas A&M University
2001-2009
Pfizer (United States)
2004
Mitchell Institute
2003
Cornell University
1993-1997
New York State College of Veterinary Medicine
1993-1996
Royal Liverpool University Hospital
1996
University of Liverpool
1996
Abstract Emerging evidence demonstrates that stromal cell-derived factor 1 (SDF-1) and CXCR4, a chemokine receptor pair, play important roles in tumorigenesis. In this report, we describe small cyclic peptide, LY2510924, which is potent selective CXCR4 antagonist currently phase II clinical studies for cancer. LY2510924 specifically blocked SDF-1 binding to with IC50 value of 0.079 nmol/L, inhibited SDF-1–induced GTP Kb 0.38 nmol/L. human lymphoma U937 cells expressing endogenous cell...
MET, the receptor for hepatocyte growth factor (HGF), has been implicated in driving tumor proliferation and metastasis. High MET expression is correlated with poor prognosis multiple cancers. Activation of can be induced either by HGF-independent mechanisms such as gene amplification, specific genetic mutations, transcriptional upregulation or HGF-dependent autocrine paracrine mechanisms.Here, we report on LY2875358, a novel humanized bivalent anti-MET antibody that high neutralization...
ObjectiveHigh-grade serous ovarian cancer, the most frequent type of has a poor prognosis and novel treatments are needed for patients with platinum resistant/refractory disease. New therapeutic strategies targeting cell cycle checkpoints, including CHK1 inhibition prexasertib, may help improve clinical response overcome resistance.MethodsPatients cancer (N = 169) were assigned to 4 cohorts as part Phase 2 multicenter trial (NCT03414047): Cohort 1: resistant, BRCA-wildtype ≥3 lines prior...
Abstract Purpose: Lung cancer is the leading cause of cancer-related death worldwide. Sustained activation, overexpression, or mutation MET pathway associated with a poor prognosis in variety tumors, including non–small cell lung (NSCLC), implicating as potential therapeutic target for cancer. Previously, we reported on development LY2801653: novel, orally bioavailable oncokinase inhibitor one its targets. Here, discuss evaluation LY2801653 both preclinical vitro and vivo NSCLC models....
Abstract The Hedgehog (Hh) pathway is a highly conserved signaling system that plays an important role in embryonic development and tissue homeostasis through regulation of cell differentiation proliferation, deregulated Hh has been implicated variety cancers. Two distinct mechanisms are responsible for inappropriate uncontrolled activation human malignancies: ligand-dependent, due to over-expression ligand, ligand-independent, resulting from genetic mutations components such as Patched...
// Bruce W. Konicek 1 , Andrew R. Capen Kelly M. Credille Philip J. Ebert Beverly L. Falcon Gary Heady Bharvin K.R. Patel Victoria Peek Jennifer Stephens Julie A. Stewart Stephanie Stout David E. Timm Suzane Um Melinda D. Willard Isabella H. Wulur Yi Zeng Yong Wang Richard Walgren and Sau-Chi Betty Yan Lilly Research Laboratories, Eli Company, Indianapolis, IN 46285, USA Correspondence to: Konicek, email: konicek_bruce_w@lilly.com Keywords: NTRK fusion; merestinib; LY2801653; inhibitor; type...
The microgravity conditions of prolonged spaceflight are known to result in skeletal muscle atrophy that leads diminished functional performance. To assess if inhibition the growth factor myostatin has potential reverse these effects, mice were treated with a antibody while housed on International Space Station. Grip strength ground control increased 3.1% compared baseline values over 6 weeks study, whereas grip measured for first time space showed flight animals be -7.8% decreased values....
Summary A severe myopathy leading to death or euthanasia was identified in 4 Belgian and Percheron draught horses age 2–21 years. Clinical signs ranged from overt weakness muscle atrophy 2 3 years, recumbency with inability rise 6 4–21 In 5 there mild increases enzyme levels. diagnoses included equine motor neuron disease (2 horses), post anaesthetic exertional due unknown (one horse), protozoal myelitis horse). Characteristic histopathology of affected the presence excessive complex...
The biomechanical holding strength and histological characteristics of a laparoscopic stapled gastropexy (LG) adhesion were compared with that an incisional (IG) adhesion. An LG was performed in 14 dogs IG six dogs. During the procedure, abdomen insufflated carbon dioxide three cannulae placed caudal aspect right side abdomen. A 35 mm stapler used to staple gastric antrum adjacent lateral abdominal wall. procedure through ventral midline celiotomy. made by apposing wall two continuous rows...
Fatty acid binding protein 3 (Fabp3) has been used as a serological biomarker of cardiac injury, but its utility preclinical injury to skeletal muscle is not well described. Fabp3 concentrations were determined for tissues from Sprague–Dawley rats and found occur at highest in muscles containing an abundance type I fibers, such the soleus muscle. Soleus also primary site (SKM) caused by lipid-lowering peroxisome proliferator–activated receptor alpha (PPAR-α) agonists. In administered repeat...
Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions.To describe an recessive, severe lamellar (LI) JRT due insertion a long interspersed nucleotide element (LINE-1) the transglutaminase 1 (TGM1) gene.Dogs were evaluated clinically, skin samples examined by light...
Skeletal muscle wasting occurs in a great majority of cancer patients with advanced disease and is associated poor prognosis decreased survival. Myostatin functions as negative regulator skeletal mass has recently become therapeutic target for reducing the loss strength clinical myopathies. We generated neutralizing antibodies to myostatin test their potential use agents attenuate due cancer. show that our antimyostatin significantly increase body weight, mass, non-tumor-bearing mice...
Serum cardiac troponin-I (cTnI) has been validated as a biomarker for cardiotoxicity in numerous animal models; however, owing to sensitivity issues cTnI concentrations healthy, resting animals used toxicology studies have not established. from healthy and isoproterenol hydrochloride (iso)-treated rats, dogs, monkeys were assayed using the Erenna system. The assay provided < 1 ng/L across human, rat, dog, monkey cTnI. Linear responses ( R 2 = 0.99) observed all species. Precision yielded...
Intervention of cancer cell mitosis by antitubulin drugs is among the most effective chemotherapies. However, have dose-limiting side effects due to important functions microtubules in resting normal cells and are often rendered ineffective rapid emergence resistance. Antimitotic agents with different mechanisms action improved safety profiles needed as new treatment options. Mitosis-specific kinesin Eg5 represents an attractive anticancer target for discovering such antimitotic agents,...
An 8‐year‐old Trakehner mare developed fulminant pulmonary edema following suspected upper airway obstruction 50 minutes into an otherwise unremarkable anesthetic recovery after surgery for left cricoarytenoideus dorsalis muscle reinnervation and ventriculocordectomy. Establishing a patent by orotracheal reintubation cardiopulmonary resuscitation attempts were unsuccessful. Gross, histological, electron microscopic postmortem examination showed severe hemorrhagic edema. Laryngeal swelling or...
Background Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations suprabasal epidermal keratins 1 and 10. However, spontaneous keratin have not been confirmed a species other than human. Objectives To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating extended pedigree of Norfolk terrier dogs due to splice-site mutation the gene encoding 10 (KRT10). Methods Dogs were evaluated clinically, skin samples examined light electron...
Chronic treatment with suprapharmacologic doses of peroxisome proliferator–activated receptor (PPAR) agonists has a known potential for causing left ventricular hypertrophy (LVH). The mechanism by which LVH develops is not well understood nor are biomarkers it characterized. Natriuretic peptides important regulators cardiac growth, blood volume, and arterial pressure may be useful hemodynamic changes that precede it. We measured amino-terminal pro-atrial natriuretic peptide (NTproANP),...
LY573636-sodium (tasisulam) is a small molecule antitumor agent with novel mechanism of action currently being investigated in variety human cancers. In vitro, tasisulam induced apoptosis via the intrinsic pathway, resulting cytochrome c release and caspase-dependent cell death. Using high content cellular imaging subpopulation analysis wide range vitro vivo cancer models, increased proportion cells 4N DNA phospho-histone H3 expression, leading to G(2)-M accumulation subsequent apoptosis....
A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 ( ICHTHYIN). This protein plays a role epidermal lipid metabolism, although the mechanism is unknown. The study describes moderate form ARCI an extended pedigree American Bulldogs that linked to gene encoding ichthyin. gross phenotype was manifest as disheveled pelage shortly after birth, generalized scaling, and adherent brown scale erythema abdominal skin. Pedigree analysis...
Ninety-seven pure-bred Akitas were examined clinically and histologically for sebaceous adenitis. The diagnosis was established in 23 by demonstrating an inflammatory reaction targeted against the glands or a reduction number of glands. clinical course adenitis Akita similar to that seen other breeds. first skin lesions occurred mainly on dorsal midline ears. Compared with Poodle, age at onset disease more variable hair loss affected undercoat. progression gland destruction varied between...
Abstract: A 13–year‐old neutered male Jack Russell Terrier (Parson Terrier) was presented to the Texas Veterinary Medical Center with a history of lethargy, depression, vomiting, and fever. The dog had mildly regenerative anemia, severe thrombocytopenia low antithrombin activity. Marked splenomegaly found on physical examination imaging studies, malignant round cell neoplasia marked extramedullary hematopoiesis were diagnosed aspirates spleen. underwent exploratory laporatomy splenectomy....
The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in biopsy samples from 3 groups age‐ gender‐matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid administration 131 I; (3) maintained a state treatment with synthetic thyroxine. After 10 months observation, there was slower regrowth 2 after clipping the untreated‐hypothyroid dogs. Untreated‐hypothyroid had greater number follicles telogen fewer shafts...
Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring impact investigational therapies. While Marsh-Oberhuber classification has been used to categorize histologic findings into discrete stages (i.e., Type 0-3c), significant variability documented between observers using this ordinal scoring system. Therefore, we evaluated whether pathologist-trained machine learning classifiers can be developed...