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Author Paraic Kenny

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Melanomagenesis driven by a kinase-dead mutant BRAF lacking codons 600-618

Megan Girtman, Craig Richmond, Meagan Campbell, William Rehrauer, Paraic Kenny,

<h4>ABSTRACT</h4> While considerable success has been achieved with treating BRAF-V600E mutant tumors in several organ systems, tumors expressing non-V600E BRAF mutations remain a significant clinical challenge. Such atypical BRAF mutations are classified based on their kinase activity, RAS-dependence and their requirement for dimerization to function. We identified an unusually large ... Read more >>

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Outbreak or pseudo-outbreak? Integrating SARS-CoV-2 sequencing to validate infection control practices in a dialysis facility.

Bridget L Pfaff, Craig S Richmond, Arick P Sabin, Deena M Athas, Jessica C Adams, Megan E Meller, Kumari Usha, Sarah A Schmitz, Brian J Simmons, Andrew J Borgert, Paraic A Kenny,

<h4>Background</h4>The COVID-19 pandemic poses a particularly high risk for End Stage Renal Disease (ESRD) patients so rapid identification of case clusters in ESRD facilities is essential. Nevertheless, with high community prevalence, a series of ESRD patients may test positive contemporaneously for reasons unrelated to their shared ESRD facility. Here we ... Read more >>

Am J Infect Control (American journal of infection control)
[2021, :]

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The MKRN1-BRAF exon4-exon9 fusion is a targetable oncogenic driver

Megan Girtman, Craig Richmond, Paraic Kenny,

<h4>ABSTRACT</h4> <h4>Background</h4> BRAF, when mutated at V600E, is a potent oncogenic driver in melanoma, lung and colorectal cancer with well understood signaling mechanisms and established treatment guidelines. Non-V600E mutations are less common, more functionally diverse and do not yet have clear treatment guidelines. One class of non-V600E mutations are BRAF ... Read more >>

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Anti-tumor efficacy of an MMAE conjugated antibody targeting cell surface TACE/ADAM17-cleaved Amphiregulin in breast cancer

Kristopher Lofgren, Sreeja Sreekumar, Charles Jenkins, Kyle Ernzen, Paraic Kenny,

The Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is ... Read more >>

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Outbreak or pseudo-outbreak? Integrating SARS-CoV-2 sequencing to validate infection control practices in an end stage renal disease facility

Bridget Pfaff, Craig Richmond, Arick Sabin, Deena Athas, Jessica Adams, Megan Meller, Kumari Usha, Sarah Schmitz, Brian Simmons, Andrew Borgert, Paraic Kenny,

<h4>ABSTRACT</h4> <h4>Background</h4> The COVID-19 pandemic of 2020 poses a particularly high risk for End Stage Renal Disease (ESRD) patients and led to a need for facility-wide control plans to prevent introduction and spread of infection within ESRD facilities. Rapid identification of clusters of contemporaneous cases is essential, as these may ... Read more >>

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SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations

Craig Richmond, Arick Sabin, Dean Jobe, Steven Lovrich, Paraic Kenny,

<h4>ABSTRACT</h4> College reopening decisions during the SARS-CoV-2 pandemic represent a trade-off between competing risks to students, faculty and staff, and college finances. Additionally, risks taken in reopening colleges can impose significant burdens on individuals living in surrounding communities. Many colleges that reopened for in-person instruction have reported frequent SARS-CoV-2 outbreaks. ... Read more >>

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Interregional SARS-CoV-2 spread from a single introduction outbreak in a meat-packing plant in northeast Iowa

Craig Richmond, Arick Sabin, Dean Jobe, Steven Lovrich, Paraic Kenny,

<h4>ABSTRACT</h4> SARS-CoV-2 spread has proven to be especially difficult to mitigate in high risk settings, including nursing homes, cruises, prisons and various industrial settings. Among industrial settings, meat processing facilities in the United States have experienced particularly challenging outbreaks. We have sequenced SARS-CoV-2 whole viral genomes from individuals testing positive ... Read more >>

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Acquisition of Cabozantinib-Sensitive MET D1228N Mutation During Progression on Crizotinib in MET-Amplified Triple-Negative Breast Cancer.

Benjamin M Parsons, David R Meier, Craig S Richmond, Grzegorz T Gurda, Kristopher A Lofgren, Mark E Burkard, Dustin A Deming, Paraic A Kenny,

<h4>Background</h4>Targeting of somatic MET mutations using crizotinib has led to strong clinical responses, most frequently in patients with lung cancer, raising the possibility of adopting similar treatment strategies in patients with MET alterations in other cancer types.<h4>Patient and methods</h4>We describe a patient with advanced triple-negative breast cancer with a 30-fold ... Read more >>

Clin Breast Cancer (Clinical breast cancer)
[2020, 20(4):e433-e438]

Cited: 3 times

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Amphiregulin deletion strongly attenuates the development of estrogen receptor-positive tumors in p53 mutant mice.

David R Meier, Megan A Girtman, Kristopher A Lofgren, Paraic A Kenny,

PURPOSE:The epidermal growth factor receptor ligand, Amphiregulin, is a transcriptional target of estrogen receptor alpha and is required for pubertal mammary gland development. Previous studies using immortalized human breast cancer cell line xenografts have suggested that Amphiregulin may be an important effector of estrogen receptor alpha during breast cancer development, ... Read more >>

Breast Cancer Res Treat (Breast cancer research and treatment)
[2020, 179(3):653-660]

Cited: 1 time

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Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells.

Natasha Emmanuel, Kristopher A Lofgren, Esther A Peterson, David R Meier, Eric H Jung, Paraic A Kenny,

<h4>Background/aim</h4>GATA3, a transcription factor expressed in luminal breast epithelial cells, is required for mammary gland development. Heterozygous GATA3 mutations occur in up to 15% of estrogen receptor (ER)-positive breast tumors and have been proposed to be null alleles resulting in haploinsufficiency; however, the mutation spectrum of GATA3 in breast cancer ... Read more >>

Anticancer Res (Anticancer research)
[2018, 38(8):4435-4441]

Cited: 5 times

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InferAMP, a python web app for copy number inference from discrete gene-level amplification signals noted in clinical tumor profiling reports

Paraic Kenny,

As somatic next-generation sequencing gene panel analysis in advanced cancer patients is becoming more routine, oncologists are frequently presented with reports containing lists of genes with increased copy number. Distinguishing which of these amplified genes, if any, might be driving tumor growth and might thus be worth considering targeting can ... Read more >>

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InferAMP, a python web app for copy number inference from discrete gene-level amplification signals noted in clinical tumor profiling reports.

Paraic A Kenny,

As somatic next-generation sequencing gene panel analysis in advanced cancer patients is becoming more routine, oncologists are frequently presented with reports containing lists of genes with increased copy number. Distinguishing which of these amplified genes, if any, might be driving tumor growth and might thus be worth considering targeting can ... Read more >>

F1000Res (F1000Research)
[2019, 8:807]

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Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma.

Craig S Richmond, Yazhini Vallatharasu, Jake A Deviley, Cullen R Vos, Benjamin M Parsons, Paraic A Kenny,

Although the treatment of metastatic melanoma has been significantly improved by both anti-BRAF/MEK and checkpoint immunotherapies, resistance to these treatment modalities remains a substantial clinical problem. Multiple clinical studies are addressing the optimal sequencing of these agents in larger patient cohorts, but successful long-term individualized treatment will likely require the ... Read more >>

Exp Mol Pathol (Experimental and molecular pathology)
[2019, 110:104260]

Cited: 2 times

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SAT-331 Elucidating the Role of Breast Cancer Specific GATA3 Mutation in Estrogen Receptor Positive Breast Cancer

Kristopher Lofgren, Natasha Emmanuel, David Meier, Paraic Kenny,

Abstract Approximately 266,000 women will be newly diagnosed with invasive breast cancer in the US this year, making it the most prevalent cancer in females, resulting in a 1 in 8 lifetime risk. Many of these tumors are of the hormone receptor positive luminal subtype, with 60-80% expressing the estrogen ... Read more >>

J Endocr Soc (Journal of the Endocrine Society)
[2019, 3(Suppl 1):]

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MTORC1/2 Inhibition as a Therapeutic Strategy for PIK3CA Mutant Cancers.

Stephanie L Fricke, Susan N Payne, Peter F Favreau, Jeremy D Kratz, Cheri A Pasch, Tyler M Foley, Alexander E Yueh, Dana R Van De Hey, Mitchell G Depke, Demetra P Korkos, Gioia Chengcheng Sha, Rebecca A DeStefanis, Linda Clipson, Mark E Burkard, Kayla K Lemmon, Benjamin M Parsons, Paraic A Kenny, Kristina A Matkowskyj, Michael A Newton, Melissa C Skala, Dustin A Deming,

<i>PIK3CA</i> mutations are common in clinical molecular profiling, yet an effective means to target these cancers has yet to be developed. MTORC1 inhibitors are often used off-label for patients with <i>PIK3CA</i> mutant cancers with only limited data to support this approach. Here we describe a cohort of patients treated with ... Read more >>

Mol Cancer Ther (Molecular cancer therapeutics)
[2019, 18(2):346-355]

Cited: 8 times

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Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth.

Serena P H Mao, Minji Park, Ramon M Cabrera, John R Christin, George S Karagiannis, Maja H Oktay, Dietmar M W Zaiss, Scott I Abrams, Wenjun Guo, John S Condeelis, Paraic A Kenny, Jeffrey E Segall,

<h4>Background</h4>Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, is not only essential for proper mammary ductal development, but also associated with breast cancer proliferation and growth. In the absence of AREG, mammary ductal growth is stunted and fails to expand. Furthermore, suppression of AREG expression in estrogen receptor-positive ... Read more >>

Breast Cancer Res (Breast cancer research : BCR)
[2018, 20(1):131]

Cited: 1 time

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The RUNX1/IL-34/CSF-1R axis is an autocrinally regulated modulator of resistance to BRAF-V600E inhibition in melanoma.

Orsi Giricz, Yongkai Mo, Kimberly B Dahlman, Xiomaris M Cotto-Rios, Chiara Vardabasso, Hoa Nguyen, Bernice Matusow, Matthias Bartenstein, Veronika Polishchuk, Douglas B Johnson, Tushar D Bhagat, Rafe Shellooe, Elizabeth Burton, James Tsai, Chao Zhang, Gaston Habets, John M Greally, Yiting Yu, Paraic A Kenny, Gregg B Fields, Kith Pradhan, E Richard Stanley, Emily Bernstein, Gideon Bollag, Evripidis Gavathiotis, Brian L West, Jeffrey A Sosman, Amit K Verma,

Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexpression of the ... Read more >>

JCI Insight (JCI insight)
[2018, 3(14):]

Cited: 7 times

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Adaptation of an amplicon-based human cancer next-generation sequencing panel assay for murine tumors.

David R Meier, Kristopher A Lofgren, Grzegorz T Gurda, Paraic A Kenny,

Unlike humans, inbred genetically engineered mice have minimal inter-individual variation and, consequently, offer substantially increased statistical power for robust definition of recurrent cooperating cancer mutations. While technically feasible, whole exome sequencing is expensive and extremely data-intensive. Somatic mutation analysis using panels of 25-75 genes now provides detailed insight into the ... Read more >>

Anal Biochem (Analytical biochemistry)
[2018, 551:26-28]

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Assessment of the TRPM8 inhibitor AMTB in breast cancer cells and its identification as an inhibitor of voltage gated sodium channels.

Kunsala T D S Yapa, Jennifer Deuis, Amelia A Peters, Paraic A Kenny, Sarah J Roberts-Thomson, Irina Vetter, Gregory R Monteith,

To assess levels of the calcium permeable transient receptor potential cation channel, subfamily melastatin, member 8 (TRPM8) in breast cancer molecular subtypes and to assess the consequences of TRPM8 pharmacological inhibition with AMTB (an inhibitor of TRPM8) on breast cancer cell lines.Cell viability and migration of breast cancer cells was ... Read more >>

Life Sci (Life sciences)
[2018, 198:128-135]

Cited: 12 times

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Genomic analysis of melanoma evolution following a 30-year disease-free interval.

Jerry J Miller, Kristopher A Lofgren, Sarah R Hughes, Steven E Cash, Paraic A Kenny,

Ultra-late melanoma recurrence is infrequent, poorly understood and, in most cases, difficult to unambiguously distinguish from a new primary melanoma. We identified a patient with a second melanoma diagnosed after a 30-year disease-free interval, and sought to determine if this new lesion was a recurrence of the original melanoma. Here ... Read more >>

J Cutan Pathol (Journal of cutaneous pathology)
[2017, 44(9):805-808]

Cited: 1 time

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Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board.

Mark E Burkard, Dustin A Deming, Benjamin M Parsons, Paraic A Kenny, Marissa R Schuh, Ticiana Leal, Nataliya Uboha, Joshua M Lang, Michael A Thompson, Ruth Warren, Jordan Bauman, Mary S Mably, Jennifer Laffin, Catherine R Paschal, Angela M Lager, Kristy Lee, Kristina A Matkowskyj, Darya G Buehler, William M Rehrauer, Jill Kolesar,

<h4>Purpose</h4>Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region.<h4>Materials and methods</h4>We developed a statewide molecular tumor board that integrates ... Read more >>

JCO Precis Oncol (JCO precision oncology)
[2017, 1:]

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Altered purinergic receptor-Ca²⁺ signaling associated with hypoxia-induced epithelial-mesenchymal transition in breast cancer cells.

Iman Azimi, Hannah Beilby, Felicity M Davis, Daneth L Marcial, Paraic A Kenny, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith,

Hypoxia is a feature of the microenvironment of many cancers and can trigger epithelial-mesenchymal transition (EMT), a process by which cells acquire a more invasive phenotype with enriched survival. A remodeling of adenosine 5'-triphosphate (ATP)-induced Ca(2+) signaling via purinergic receptors is associated with epidermal growth factor (EGF)-induced EMT in MDA-MB-468 ... Read more >>

Mol Oncol (Molecular oncology)
[2016, 10(1):166-178]

Cited: 41 times

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Amphiregulin Is a Critical Downstream Effector of Estrogen Signaling in ERα-Positive Breast Cancer.

Esther A Peterson, Edmund C Jenkins, Kristopher A Lofgren, Natasha Chandiramani, Hui Liu, Evelyn Aranda, Maryia Barnett, Paraic A Kenny,

Estrogen stimulation promotes epithelial cell proliferation in estrogen receptor (ERα)-positive breast cancer. Many ERα target genes have been enumerated, but the identities of the key effectors mediating the estrogen signal remain obscure. During mouse mammary gland development, the estrogen growth factor receptor (EGFR) ligand amphiregulin acts as an important stage-specific ... Read more >>

Cancer Res (Cancer research)
[2015, 75(22):4830-4838]

Cited: 18 times

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Comparative analysis of GATA3 mutation profiles between Asian and Western patients with breast cancer. Is there really a difference?

Natasha Chandiramani, Paraic A Kenny,

Cancer (Cancer)
[2014, 120(17):2778-2779]

Cited: 0 times

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PI3K-AKT signaling is a downstream effector of retinoid prevention of murine basal cell carcinogenesis.

Po-Lin So, Grace Y Wang, Kevin Wang, Mindy Chuang, Venice Calinisan Chiueh, Paraic A Kenny, Ervin H Epstein,

Basal cell carcinoma (BCC) is the most common human cancer. We have demonstrated previously that topical application of the retinoid prodrug tazarotene profoundly inhibits murine BCC carcinogenesis via retinoic acid receptor γ-mediated regulation of tumor cell transcription. Because topical retinoids can cause adverse cutaneous effects and because tumors can develop ... Read more >>

Cancer Prev Res (Phila) (Cancer prevention research (Philadelphia, Pa.))
[2014, 7(4):407-417]

Cited: 7 times

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