Medicine and Health Sciences Commons^™

Small Molecules Targeting Insm1 For The Treatment Of High-Risk Neuroblastoma, Michael S. Lan, Chiachen Chen

School of Medicine Faculty Publications

Human neuroblastoma (NB) is the most common childhood extracranial tumor arising from the sympathetic nervous system. It is also a clinically heterogeneous disease that ranges from spontaneous regression to high-risk stage 4 disease. The cause of this disease remains elusive. However, the amplification of NMYC oncogene occurred in roughly 30% of NB patients, which strongly correlated with the advanced stage of disease subtype and the worse prognosis status. We discovered that N-Myc oncoprotein binds and activates INSM1, a zinc-finger transcription factor of neuroendocrine tumors. We also found that INSM1 modulates N-Myc stability mediated through PI3K/AKT/GSK3β signaling pathway. Therefore, INSM1 emerges …

The Discovery Of Metarhizium Anisopliae (Metchnikoff) Sorokin Isolates From Arkansas And Their Pathogenicity To Amblyomma Americanum L., Austin Goldsmith

Graduate Theses and Dissertations

The lone star tick Amblyomma americanum L. is the most abundant tick in Arkansas and has been implicated as a vector of many important disease-causing pathogens. Many species of entomopathogenic fungi have been isolated from several species of ticks, with some of these fungi being utilized for tick biocontrol. However, few studies have assessed the pathogenicity of entomopathogenic fungi to A. americanum. The objectives of this study were to: isolate and identify native Arkansas isolates of entomopathogenic fungi from wild A. americanum ticks exposed to soil and to compare the pathogenicity of one isolate (Metarhizium anisopliae (Metchnikoff) Sorokin isolate Savoy …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

Effects Of Salinity On Plant Development Of In Vitro Sweet Potato (Ipomoea Batatas) Explants And Growth Of Pakchoi (Brassica Rapa Var. Chinensis) Seedlings, Tristan Paulino, Mari Marutani, Phd

Journal of Health Disparities Research and Practice

Climate change has affected the Pacific Islands with increased sea levels, and the contamination of freshwater with saltwater, which has become a serious problem for plant development. Bioassays were performed to examine the effects of salinity on root and shoot development of in-vitro sweet potato (Ipomoea batatas), and effects on the seedling growth of pakchoi (Brassica rapa var. chinensis).

Sterilized stems with one or two nodes of sweet potato cv. Liberty were placed in in-vitro Murashige & Skoog solid media with NaCl concentrations of 0%, 0.5%, 1.0% and 1.5%. Newly emerged roots and shoots were recorded …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

An Evaluation Of Porcine Epidemic Diarrhea Virus Survival In Individual Feed Ingredients In The Presence Or Absence Of A Liquid Antimicrobial, Scott Dee, Casey Neill, Travis Clement, Aaron Singrey, Jane Christopher-Hennings, Eric A. Nelson

Veterinary and Biomedical Sciences Faculty Publications

Background: Contaminated complete feed and porcine plasma are risk factors for PEDV introduction to farms and a liquid antimicrobial has been proven useful for reducing risk. This study provides information on the survivability of PEDV across common swine feed ingredients in the presence or absence of the liquid antimicrobial.
Results: Eighteen ingredients commonly included in commercial swine diets were selected, including 3 grain sources (corn, soybean meal (SBM), dried distillers grains with solubles (DDGS)), 5 porcine by-products (spray-dried plasma, purified plasma, intestinal mucosa, meat and bone meal and red blood cells (RBCs)), 3 vitamin/trace mineral (VTM) mixes (sow, nursery, finishing), …

Utilizing Feed Sequencing To Decrease The Risk Of Porcine Epidemic Diarrhea Virus (Pedv) Cross-Contamination During Feed Manufacturing, L. L. Schumacher, R. A. Cochrane, J. C. Woodworth, C. R. Stark, C. K. Jones, Rodger G. Main, Jianqiang Zhang, Phillip Charles Gauger, S. S. Dritz, M. D. Tokach

Kansas Agricultural Experiment Station Research Reports

Understanding key points of potential cross-contamination during the feed manufacturing process is important to developing efficacious methods to control or prevent transmission of pathogens into swine diets. In this study, an experiment was conducted involving 30 crossbred 10-d-old pigs that were used as a bioassay model for Porcine Epidemic Diarrhea Virus (PEDV) to determine the effects of feed batch sequencing on PEDV cross-contamination and subsequent infectivity. PEDV with a PCR cycle threshold value (Ct) of 11 was uniformly mixed into 4.5 kg of swine diet using a stainless steel bench top mixer validated for mixing efficiency. The inoculated feed was …

Experimental Approaches To Derive Cd34+ Progenitors From Human And Nonhuman Primate Embryonic Stem Cells, Qiang Shi, John L. Vandeberg

School of Medicine Publications and Presentations

Traditionally, CD34 positive cells are predominantly found in the umbilical cord and bone marrow, thus are considered as hematopoietic progenitors. Increasing evidence has suggested that the CD34+ cells represent a distinct subset of cells with enhanced progenitor activity; CD34 is a general marker of progenitor cells in a variety of cell types. Because the CD34 protein shows expression early on in hematopoietic and vascular-associated tissues, CD34+ cells have enormous potential as cellular agents for research and for clinical cell transplantation. Directed differentiation of embryonic stem cells will give rise to an inexhaustible supply of CD34+ cells, creating an exciting approach …

An Evaluation Of A Liquid Antimicrobial (Sal Curb®) For Reducing The Risk Of Porcine Epidemic Diarrhea Virus Infection Of Naïve Pigs During Consumption Of Contaminated Feed, Scott Dee, Casey Neill, Travis Clement, Jane Christopher-Hennings, Eric A. Nelson

Veterinary and Biomedical Sciences Faculty Publications

Background: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Recently, contaminated feed was confirmed as a vehicle for PEDV infection of naïve piglets. This research provides in vivo data supporting the ability of a liquid antimicrobial product to reduce this risk.
Results: Sal CURB® (Kemin Industries, Des Moines, IA, USA) is a FDA-approved liquid antimicrobial used to control Salmonella contamination in poultry and swine diets. To test its effect against PEDV, Sal CURB®-treated feed was spiked with a stock isolate of PEDV (Ct = 25.22), which PEDV-naïve piglets …

An Evaluation Of Contaminated Complete Feed As A Vehicle For Porcine Epidemic Diarrhea Virus Infection Of Naïve Pigs Following Consumption Via Natural Feeding Behavior: Proof Of Concept, Scott Dee, Travis Clement, Adam Schelkopf, Joel Nerem, David Knudsen, Jane Christopher-Hennings, Eric A. Nelson

Veterinary and Biomedical Sciences Faculty Publications

Background: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Initially, contaminated feed was proposed as a risk factor for PEDV; however, data were not available to support this theory. Here we provide proof of concept of this risk by describing a novel means for recovering PEDV-contaminated complete feed material from commercial swine sites and conducting an in vivo experiment to prove its infectivity.

Results: For on-farm detection of PEDV RNA in feed, paint rollers were used to collect material from at-risk feed bins from 3 clinically affected breeding …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Bioassay Guided Fractionation Of American Ginseng. A Hexane Fraction Of American Ginseng Suppresses Colitis And Associated Colon Cancer. Mechanism Of Action., Deepak Poudyal

Theses and Dissertations

Inflammatory Bowel Disease (IBD) [Ulcerative colitis (UC) and Crohn's Disease (CD)] is a group of chronic disorders of unknown etiology characterized by inflammation in the gastrointestinal tract associated with a high colon cancer risk. UC is characterized by periods of active disease ("flare-ups"), followed by periods when the disease is inactive ("remission"). The end result is an abnormal immune response with repeated episodes of colonic inflammation. Conventional treatment of UC by aminosalicylates, TNFα inhibitors, and steroids have modest effects, and come with a high risk of side effects including dyspeptic symptoms, gastric ulceration and sometimes hospitalization and deaths. Because of …

Complexity And Uncertainty In Human And Ecological Risk Assessment, Matthew Jordan Dellinger

Theses and Dissertations

Multiple interacting stressors in the environment present increasingly complex risks to human health. Too often, however, the data required for traditional risk assessment are either lacking or unavailable at the necessary spatial or temporal scale. In addition, assessment practices and management policies need to move away from single factor approaches in order to accommodate the reality of complex chemical mixtures and environmental stressors. Recent literature suggests that a paradigm shift is under way. This points to a need for the development of new techniques both for rapid data collection and flexible risk assessment strategies that can adapt to make use …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Lethal Chlorine Concentrations For The Pearl Oyster Pinctada Radiata (Leach, 1814), Müni̇r Zi̇ya Lugal Göksu, Fatma Çevi̇k, Özlem Findik

Turkish Journal of Veterinary & Animal Sciences

In this study, the lethal chlorine concentrations (LC) and residual chlorine concentrations in water for a fouling organism, the pearl oyster Pinctada radiata (Leach, 1814) [Avicula], were investigated during May 1999-April 2000. The study was carried out under laboratory conditions at 20ºC. Acute toxicity tests were conducted under a flow through system by using continuous application of chlorine according to bioassay test methods. Test solutions were made by using an appropriate amount of sodium hypochlorite (NaOCl^{-}). According to the results, the 24h-LC_{50} was 1.75 mgl^{-1} and the residual chlorine was 0.47 mgl^{-1} for LC_{50} of Pinctada radiata.