2012 — 2016 |
Ignatenko, Natalia A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Role of Kallikrein 6 Expression and Secretion in Colon Cancer
DESCRIPTION (provided by applicant): This proposal will test the hypothesis that kallikrein 6 (KLK6) protein is functionally involved in, and may be a useful marker of, colon carcinogenesis. We have shown that: 1) KLK6 protein can be detected at the adenomas in the mouse colon, and in human colon tumors; 2) KLK6 function blocking antibody attenuates invasion of colon cancer cells; and 3) colon cancer cells with knockdown of KLK6 do not form distant metastases in SCID mouse model and increase animal survival rates. To test the overall hypothesis, we propose the following specific aims: 1) determine the role of KLK6 in the colon cancer progression in vivo; 2) determine the role of KLK6 in colon cancer metastasis; 3) evaluate KLK6 protein expression and enzymatic activity in the colon. The major objectives of this proposal are to determine the role of KLK6 in colon tumor and metastasis formation, develop an imaging modality for measuring of KLK6 enzymatic activity in the colon and correlate it with disease progression. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the third most common cancer in the United States. Screening for colon cancer has the ability to reduce mortality from this disease. Many kallikreins have been identified as promising diagnostic and/or prognostic biomarkers for several cancer sites, including ovarian, breast and prostate. In colon cancer, KLK6 expression is likely to be involved in tumor progression and metastasis through degradation of the extracellular matrix. This proposal will generate data on KLK6 functions and enzymatic activity in colon cancer. It will evaluate KLK6 as a specific molecular marker for colon cancer progression, metastasis and targeted therapy.
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2014 |
Ignatenko, Natalia A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Research Supplement to Promote Diversity in Health-Related Research
DESCRIPTION (provided by applicant): This proposal will test the hypothesis that kallikrein 6 (KLK6) protein is functionally involved in, and may be a useful marker of, colon carcinogenesis. We have shown that: 1) KLK6 protein can be detected at the adenomas in the mouse colon, and in human colon tumors; 2) KLK6 function blocking antibody attenuates invasion of colon cancer cells; and 3) colon cancer cells with knockdown of KLK6 do not form distant metastases in SCID mouse model and increase animal survival rates. To test the overall hypothesis, we propose the following specific aims: 1) determine the role of KLK6 in the colon cancer progression in vivo; 2) determine the role of KLK6 in colon cancer metastasis; 3) evaluate KLK6 protein expression and enzymatic activity in the colon. The major objectives of this proposal are to determine the role of KLK6 in colon tumor and metastasis formation, develop an imaging modality for measuring of KLK6 enzymatic activity in the colon and correlate it with disease progression.
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1 |
2016 — 2021 |
Ignatenko, Natalia A |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Experimental Mouse
Project Summary / Abstract: Experimental Mouse Shared Resource (EMSR) The goal of the Experimental Mouse Shared Resource (EMSR) is to enhance the productivity and capabilities of Members of the University of Arizona Cancer Center (UACC) by providing access to in vivo models, including immunocompromised and genetically engineered mouse (GEM) models, and to provide comprehensive support of experimentation in rodents (mouse and rat). The EMSR is dedicated to effective and efficient service that allows UACC Members to avoid duplication of equipment and training that would occur without such a Resource and to ensure the reproducibility of technical interventions and provide the rigorous quality control required for informative analyses of animal studies. EMSR personnel process tissues and perform procedures for experimental endpoints, including gross pathologic examinations with cryopreservation of organs/tissues and preparation of tissues for microscopic examination for further analysis by other UACC Shared Resources. The EMSR is divided into two sections: 1) the GEM Production Unit which utilizes the University of Arizona's Genetically Engineered Mouse Modeling (GEMM) core to generate the GEMs through ?sequence-to-whiskers? services, and 2) the Rodent Experimentation Unit which provides ?whiskers-to-data? services. These two units are complimentary and interactive, sharing animals, techniques, equipment and reagents. The EMSR maintains two blanket protocols for GEM generation and pilot work. The Unit is in compliance with the University's Biosafety Committee rules and is GLP-certified.
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2021 |
Besselsen, David G Ignatenko, Natalia A |
UG3Activity Code Description: As part of a bi-phasic approach to funding exploratory and/or developmental research, the UG3 provides support for the first phase of the award. This activity code is used in lieu of the UH2 activity code when larger budgets and/or project periods are required to establish feasibility for the project. |
Targeting Polyamines to Suppress Sars-Cov-2 Related Disease
ABSTRACT The pandemic COronaVIrus disease 2019 (COVID-19) is an infectious disease, which is caused by a novel and highly pathogenic virus strain SARS-CoV-2 (Severe acute respiratory virus syndrome coronavirus 2). The infection may cause severe lower respiratory tract infection with acute respiratory distress and extrapulmonary organ disfunctions in infected individuals. Treatment strategy that both limits SARS-CoV-2 replication and reduce inflammation associated with COVID-19 would provide the greatest therapeutic benefit. Polyamines are naturally occurring organic cations that are essential for growth and development of both prokaryotic and eukaryotic cells. Many viruses require host polyamines for replication in the infected cells and targeting polyamine metabolism during viral infection showed promising results in in vitro and in vivo animal studies. The goal of this proposal is to test the applicability of two currently FDA approved drugs, eflornithine (other name ?-difluoromethylornithine or DFMO) and sulindac, and their combination for prevention or treatment of COVID-19 disease. Eftornithine is an irreversible inhibitor of a key polyamine biosynthetic enzyme ornithine decarboxylase (ODC). Sulindac is a common non-steroidal anti-inflammatory drug (NSAIDs), which also induces polyamine catabolism. Eflornithine and sulindac work in a complementary manner to reduce intracellular polyamine levels. The safety doses of eflornithine/sulindac combination have been established for prevention of recurrence of high-risk adenomas (ClinicalTrials.gov Identifier NCT00118365). In this proposal we will test the hypothesis that eflornithine and sulindac combination will reduce both the intracellular polyamine availability for coronavirus replication, and inflammation associated with COVID-19. We will test this hypothesis using cell culture models (Specific Aim 1) and mouse models of COVID-19 disease (Specific Aim 2). Planning activities in preparation for clinical trials for eflornithine/sulindac combination for antiviral indication in collaboration with Cancer Prevention Pharmaceuticals (CPP) (www.canprevent.com) are also included. The translational goal of this project is to develop the effective approach for prevention COVID-19 infection as well as decreasing severity of the viral infection in the COVID-19 patients. It is essential to develop new approaches to prevention and treatment of virus outbreaks.
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