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Search Results: 1 - 10 of 224673 matches for " Kimberly R. Kalli "
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Functional Folate Receptor Alpha Is Elevated in the Blood of Ovarian Cancer Patients
Eati Basal, Guiti Z. Eghbali-Fatourechi, Kimberly R. Kalli, Lynn C. Hartmann, Karin M. Goodman, Ellen L. Goode, Barton A. Kamen, Philip S. Low, Keith L. Knutson
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006292
Abstract: Background Despite low incidence, ovarian cancer is the fifth leading cause of cancer deaths and it has the highest mortality rate of all gynecologic malignancies among US women. The mortality rate would be reduced with an early detection marker. The folate receptor alpha (FRα) is one logical choice for a biomarker because of its prevalent overexpression in ovarian cancer and its exclusive expression in only a few normal tissues. In prior work, it was observed that patients with ovarian cancer had elevated serum levels of a protein that bound to a FRα-specific monoclonal antibody relative to healthy individuals. However, it was not shown that the protein detected was intact functional FRα. In the current study, the goal was to determine whether ovarian cancer patients (n = 30) had elevated serum levels of a fully functional intact FRα compared to matched healthy controls (n = 30). Methodology/Principal Findings FRα levels in serum were analyzed by two methods, immunoblotting analysis and a radiolabeled folic acid-based microfiltration binding assay. Using the immunoassay, we observed that levels of FRα were higher in serum of ovarian cancer patients as compared to controls. Similar results were also observed using the microfiltration binding assay, which showed that the circulating FRα is functional. Importantly, we also found that the levels of FRα were comparable between early and advanced stage patients. Conclusions Our results demonstrate that ovarian cancer patients have elevated levels of functional intact FRα. These findings support the potential use of circulating FRα as a biomarker of early ovarian cancer.
The Ratios of CD8+ T Cells to CD4+CD25+ FOXP3+ and FOXP3- T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer
Claudia C. Preston, Matthew J. Maurer, Ann L. Oberg, Daniel W. Visscher, Kimberly R. Kalli, Lynn C. Hartmann, Ellen L. Goode, Keith L. Knutson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080063
Abstract: Ovarian cancer is an immune reactive malignancy with a complex immune suppressive network that blunts successful immune eradication. This suppressive microenvironment may be mediated by recruitment or induction of CD4+ regulatory T cells (Tregs). Our study sought to investigate the association of tumor-infiltrating CD4+CD25+FOXP3+ Tregs, and other immune factors, with clinical outcome in serous ovarian cancer patients. We performed immunofluorescence and quantification of intraepithelial tumor-infiltrating triple positive Tregs (CD4+CD25+FOXP3+), as well as CD4+CD25+FOXP3-, CD3+ and CD8+ T cells in tumor specimens from 52 patients with high stage serous ovarian carcinoma. Thirty-one of the patients had good survival (i.e. > 60 months) and 21 had poor survival of < 18 months. Total cell counts as well as cell ratios were compared among these two outcome groups. The total numbers of CD4+CD25+FOXP3+ Tregs, CD4+CD25+FOXP3-, CD3+ and CD8+ cells were not significantly different between the groups. However, higher ratios of CD8+/CD4+CD25+FOXP3+ Treg, CD8+/CD4+ and CD8/CD4+CD25+FOXP3- cells were seen in the good outcome group when compared to the patients with poor outcome. These data show for the first time that the ratios of CD8+ to both CD4+CD25+FOXP3+ Tregs and CD4+CD25+FOXP3- T cells are associated with disease outcome in ovarian cancer. The association being apparent in ratios rather than absolute count of T cells suggests that the effector/suppressor ratio may be a more important indicator of outcome than individual cell count. Thus, immunotherapy strategies that modify the ratio of CD4+CD25+FOXP3+ Tregs or CD4+CD25+FOXP3- T cells to CD8+ effector cells may be useful in improving outcomes in ovarian cancer.
Risk of Ovarian Cancer and Inherited Variants in Relapse-Associated Genes
Abraham Peedicayil,Robert A. Vierkant,Lynn C. Hartmann,Brooke L. Fridley,Zachary S. Fredericksen,Kristin L. White,Elaine A. Elliott,Catherine M. Phelan,Ya-Yu Tsai,Andrew Berchuck,Edwin S. Iversen Jr,Fergus J. Couch,Prema Peethamabaran,Melissa C. Larson,Kimberly R. Kalli,Matthew L. Kosel,Vijayalakshmi Shridhar,David N. Rider,Mark Liebow,Julie M. Cunningham,Joellen M. Schildkraut,Thomas A. Sellers,Ellen L. Goode
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008884
Abstract: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk.
Research at the University of Kent and subsequent research activities
Kyriacos Kalli
Photonic Sensors , 2011, DOI: 10.1007/s13320-011-0039-y
Abstract: The author’s research activities undertaken at the Applied Optics Group, the University of Kent at Canterbury are reviewed, during his time there from 1988–1992 and 1994–1996, followed by a summary of recent research. The areas of interest are high finesse ring resonators, tunable optical filters, novel optical fiber grating sensors in glass and polymer, femtosecond laser inscription and micromachining, environmental pollution monitoring, hydrogen activated Pd films on silicon and impurity measurement on silicon wafers.
Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer
Ellen L. Goode, Melissa DeRycke, Kimberly R. Kalli, Ann L. Oberg, Julie M. Cunningham, Matthew J. Maurer, Brooke L. Fridley, Sebastian M. Armasu, Daniel J. Serie, Priya Ramar, Krista Goergen, Robert A. Vierkant, David N. Rider, Hugues Sicotte, Chen Wang, Boris Winterhoff, Catherine M. Phelan, Joellen M. Schildkraut, Rachel P. Weber, Ed Iversen, Andrew Berchuck, Rebecca Sutphen, Michael J. Birrer, Shalaka Hampras, Leah Preus, Simon A. Gayther, Susan J. Ramus, Nicolas Wentzensen, Hannah P. Yang, Montserrat Garcia-Closas, Honglin Song, Jonathan Tyrer, Paul P. D. Pharoah, Gottfried Konecny, Thomas A. Sellers, Roberta B. Ness, Lara E. Sucheston, Kunle Odunsi, Lynn C. Hartmann, Kirsten B. Moysich, Keith L. Knutson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053903
Abstract: Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10?5), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10?4, and rs3753348, p = 9.0×10?4, respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10?4). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10?4) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies.
Preparing Leaders in Public Health for Success in a Flatter, More Distributed and Collaborative World
John R. Kimberly
Public Health Reviews , 2011,
Abstract: In a world that is rapidly changing, what are the challenges for which leaders in public health in the future need to be prepared, what are the qualities and skills they will need for success, and where will they get the training they require? Addressing each of these questions in succession, this article contends that success in a flatter, more distributed and collaborative world will require a new generation of leaders in public health with new mindsets, an appetite for innovation and interdisciplinary collaboration and a strong dose of political savvy. Faculty, curricula and com-petencies in academic centers play an important role in this equation.
The Goldilocks Model for TCR—Too Much Attraction Might Not Be Best for Vaccine Design
Jill E. Slansky,Kimberly R. Jordan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000482
Abstract:
Implementación del precursor del procedimiento de evaluación relacional en el establecimiento de marcos relacionales de igualdad, oposición y diferencia
Mark R. Dixon,Kimberly M. Zlomke
Revista Latinoamericana de Psicología , 2005,
Abstract: El propósito del estudio fue examinar la eficiencia del procedimiento de evaluación relacional (pPER) en la emergencia de respuestas relacionales de igualdad, oposición y diferencia. Quince adultos fueron expuestos a ensayos de entrenamiento y de prueba en discriminaciones condicionales. En primera instancia, los participantes observaron dos objetos- estímulo en la pantalla de un computador, después el sistema mostraba dos opciones de respuesta coloreadas que servían para describir de manera arbitraria la relación entre los dos objeto-estímulo (que podía ser de igualdad, oposición o diferencia). Seguidamente, los participantes fueron expuestos a ensayos de prueba de relaciones simétricas con pares de objetos-estímulo conocidos (del entrenamiento inicial) y otros novedosos. Los resultados evidencian que todos los participantes tuvieron niveles altos de precisión al relacionar tanto los pares de objetos-estímulo conocidos como los novedosos. Los datos en conjunto sugieren que es posible la emergencia de respuestas relacionales a través de procedimientos distintos al de igualación a la muestra
The Goldilocks Model for TCR—Too Much Attraction Might Not Be Best for Vaccine Design
Jill E. Slansky ,Kimberly R. Jordan
PLOS Biology , 2010, DOI: 10.1371/journal.pbio.1000482
Abstract:
Oncomorphic TP53 Mutations in Gynecologic Cancers Lose the Normal Protein:Protein Interactions with the microRNA Microprocessing Complex  [PDF]
Pavla Brachova, Samuel R. Mueting, Eric J. Devor, Kimberly K. Leslie
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.56058
Abstract:

Mutations in the tumor suppressor TP53 occur in almost all advanced ovarian cancers and in many advanced serous endometrial cancers. Mutations in TP53 can alter the function of the p53 protein, and some mutations result in a mutated protein with oncogenic activity. Previously referred to as gain of function (GOF) p53 proteins, we now term these “oncomorphic” mutations to better describe their function as oncogenes. We reviewed the data from The Cancer Genome Atlas (TCGA) and demonstrate that of the patients diagnosed with endometrial cancer that harbor TP53 mutations, approximately 30% of these mutations are oncomorphic. In ovarian cancer, approximately 20% are oncomorphic. The wild type (WT) p53 protein transactivates genes and micro-RNAs (miRNAs) necessary in the response to cellular stress, which turn off growth and induce apoptosis. In addition to direct transcriptional activation, WT p53 also acts through protein:protein interactions with Drosha and the miRNA processing complex to mediate rapid, enhanced processing of a subset of anti-growth miRNAs. We validated the interaction of WT p53 with the Drosha complex in the cell line UCI-107. We observed that miRNAs that inhibit the expression of oncogenes were induced. Specifically, some miRNAs were induced very rapidly over minutes, consistent with enhanced processing, while others required hours, consistent with transcriptional activation. In contrast, the most common oncomorphic TP53 mutations failed to interact with the Drosha complex and lost the ability to rapidly induce

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