34 results on '"Chacon JA"'
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2. Levantamiento de ácaros de hojarasca en el agroecosistema de yuca en Yopal, Casanare
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Chacón Jaramillo, Liliana
- Published
- 2021
3. Sarna sarcóptica y salud: impactos en fauna silvestre y ganadería
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Chacón Jaramillo, Liliana
- Published
- 2021
4. Introducción
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Chacón Jaramillo, Liliana
- Published
- 2021
5. Importancia de la adaptación de sistemas automáticos para la aplicación de plaguicidas en cultivos de flores de invernadero
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Chacón Jaramillo, Liliana
- Published
- 2021
6. Página legal
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Chacón Jaramillo, Liliana
- Published
- 2021
7. Frontasunto
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Chacón Jaramillo, Liliana
- Published
- 2021
8. Recorrido hasta el Alto Chicamocha, Boyacá: contexto y conceptos aplicables al manejo del agua y del riego
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Chacón Jaramillo, Liliana
- Published
- 2021
9. Biorremediación ambiental: los microorganismos en el saneamiento del suelo
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Chacón Jaramillo, Liliana
- Published
- 2021
10. Índice de cuadros
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Chacón Jaramillo, Liliana
- Published
- 2021
11. Índice de figuras
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Chacón Jaramillo, Liliana
- Published
- 2021
12. Haemophagocytic lymphohistiocytosis in kidney transplant recipients
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Nieto Ríos, John Fredy, Morales Contreras, Carol Lisbeth, Chacón Jaimes, Diana Carolina, Benavides Henao, Diego Armando, Bello Márquez, Diana Carolina, and Serna Higuita, Lina María
- Subjects
hemophagocytic lymphohistiocytosis ,histoplasmosis ,ferritins ,kidney transplantation ,Medicine ,Medicine (General) ,R5-920 - Abstract
Hemophagocytic lymphohistiocytosis (HLH) in renal transplant recipients is a life-threatening hyper-inflammatory syndrome; associated with uncontrolled activation of cytotoxic T-lymphocytes and macrophages due to infections or immunosuppressive therapy. Histoplasmosis, tuberculosis and herpes virus infection are among the leading infectious causes. It is characterized by fever, organomegaly, cytopenia, hyperferritinemia, hypertrigiceridemia and/or hypofibrinogenemia; which may be accompanied by hemophagocytosis in bone marrow, liver or other organs. LH can follow a rapidly fatal course, with progression to multisystemic failure and death. The treatment is based on early control of the triggering cause, reducing immunosuppression and stop the inflammatory process. In some cases, is necessary to use other immunosuppressant, chemotherapy and in a very few cases, a bone marrow transplant may be required.
- Published
- 2019
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13. Mercado de trabajo en información y documentación y crisis económica en España : una aproximación a partir de las ofertas publicadas en IweTel entre 2008 y 2013
- Author
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Tejada Artigas, Carlos, Chacón Jarén, Sandra, and Moreiro González, José Antonio
- Subjects
Spain ,Mailing lists ,Information professionals ,Labour market ,Bibliography. Library science. Information resources ,Communication. Mass media ,P87-96 - Abstract
Objetivos: analizar las ofertas de empleo publicadas en la lista de correo IweTel desde el inicio de la crisis en 2008 hasta diciembre de 2013, para ver las características de dichas convocatorias, en cuanto a su número, los puestos que demandan y los requisitos para los candidatos. -- Metodología: análisis estadístico de diferentes aspectos de las ofertas de empleo que, en muchas ocasiones, se han tenido que normalizar y sistematizar para ser tratados. -- Resultados: la caída del empleo en estos seis años estudiados (2008–2013) se hace patente, ya que pasa de 190 ofertas publicadas en el primer año a 35 del último. Otras características que se han detectado es la precariedad de dichas convocatorias, sobre todo en lo que respecta a la duración de los empleos ofertados. El organismo tipo convocante es una empresa de servicios documentales con sede en Madrid que pide catalogadores. El estudio tiene la fortaleza de que IweTel es la lista de distribución más importante en información y documentación en España, pero también tiene la debilidad de que los organismos convocantes, que generalmente acuden a este medio de difusión, son generalmente privados y conocen el sector, por lo que no aparecen, o si lo hacen es en menor medida, otras ofertas de otros tipos de empresas.Objective: This paper analyses the number, nature and conditions of job offers in the job listings published by the internet forum IweTel during the period January 2008–December 2013. -- Methodology: The characteristics of job offers were analysed using statistical analysis. In many cases, the data had to be normalized before it could be used. -- Results: Employment in information and documentation clearly fell during the six-year period studied, from 2008 when a total of 190 job offers were listed, to 2013 when that figure had dropped to 35. The precarity of the labour market was also noted, especially in the length of employment time offered. The organization that most frequently used the forum was typically a document service company with headquarters in Madrid, and the jobs most frequently advertised were for professionals in cataloguing. The IweTel forum was considered a valuable source of data because it has the largest mailing list for information professionals in Spain; its disadvantage was that IweTel is most frequently used by private ventures who are familiar with the sector, while other types of company advertise there less frequently or not at all.
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- 2014
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14. Mercat de treball en informació i documentació i crisi econòmica a Espanya : una aproximació a partir de les ofertes publicades a la IweTel entre 2008 i 2013
- Author
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Tejada Artigas, Carlos, Chacón Jarén, Sandra, and Moreiro González, José Antonio
- Subjects
Spain ,Mailing lists ,Information professionals ,Labour market ,Bibliography. Library science. Information resources ,Communication. Mass media ,P87-96 - Abstract
Objectiu: analitzar les ofertes d'ocupació publicades a la llista de correu IweTel des de l'inici de la crisi el 2008 fins a desembre de 2013, per veure les característiques d'aquestes convocatòries, quant al nombre, els llocs que demanen i els requisits per als candidats. -- Metodologia: anàlisi estadística de diferents aspectes de les ofertes d'ocupació que, en moltes ocasions, s'han hagut de normalitzar i sistematitzar perquè es puguin tractar. -- Resultats: la caiguda de l'ocupació en aquests sis anys estudiats (2008–2013) es fa evident, ja que passa de 190 ofertes publicades en el primer any a 35 de l'últim. Una altra característica que s'ha detectat és la precarietat d'aquestes convocatòries, sobretot pel que fa a la durada de les feines ofertes. L'organisme tipus convocant és una empresa de serveis documentals amb seu a Madrid que demana catalogadors. L'estudi té la fortalesa que la IweTel és la llista de distribució més important en informació i documentació a Espanya, però també té la debilitat que els organismes convocants, que generalment utilitzen aquest mitjà de difusió, són generalment privats i coneixen el sector, motiu pel qual no apareixen, o si ho fan és en menor mesura, ofertes d'altres tipus d'empreses.Objective: This paper analyses the number, nature and conditions of job offers in the job listings published by the internet forum IweTel during the period January 2008–December 2013. -- Methodology: The characteristics of job offers were analysed using statistical analysis. In many cases, the data had to be normalized before it could be used. -- Results: Employment in information and documentation clearly fell during the six-year period studied, from 2008 when a total of 190 job offers were listed, to 2013 when that figure had dropped to 35. The precarity of the labour market was also noted, especially in the length of employment time offered. The organization that most frequently used the forum was typically a document service company with headquarters in Madrid, and the jobs most frequently advertised were for professionals in cataloguing. The IweTel forum was considered a valuable source of data because it has the largest mailing list for information professionals in Spain; its disadvantage was that IweTel is most frequently used by private ventures who are familiar with the sector, while other types of company advertise there less frequently or not at all.
- Published
- 2014
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15. Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages.
- Author
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Veerapandian R, Ramos EI, Vijayaraghavan M, Sedano MJ, Carmona A, Chacon JA, Gadad SS, and Dhandayuthapani S
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- Animals, Mice, Methionine metabolism, Oxidative Stress, Reactive Oxygen Species metabolism, Tumor Necrosis Factor-alpha metabolism, Macrophages microbiology, Methionine Sulfoxide Reductases genetics, Methionine Sulfoxide Reductases metabolism, Mycobacterium smegmatis enzymology, Mycobacterium smegmatis genetics
- Abstract
Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). Its pivotal role in the cellular processes has been well established by overexpressing, silencing, and knocking down MsrA or deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA in bacterial pathogens. To elucidate this, we infected mouse bone marrow-derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM), secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-α than BMDMs infected with MSC. The increased ROS and TNF-α levels in MSM-infected BMDMs correlated with elevated necrotic cell death in this group. Further, RNA-seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial-delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified the down-regulation of cancer-related signaling genes in MSM-infected cells, indicating that MsrA can potentially regulate the development and progression of cancer., Competing Interests: Declaration of competing interest “The authors declare no conflict of interest.”, (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
- Published
- 2023
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16. Quantum Dot-Doped Electrospun Polymer Fibers for Explosive Vapor Sensors.
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Ennis D, Golden D, Curtin MC, Cooper A, Sun C, Riegner K, Johnson CC, Nolletti JL, Wallace KB, Chacon JA, Bethune H, Ritchie TS, Schnee V, DeNeve DR, and Riegner DE
- Abstract
This research seeks to support reconnaissance efforts against homemade explosives (HMEs) and improvised explosive devices (IEDs), which are leading causes of combat casualties in recent conflicts. The successful deployment of a passive sensor to be developed for first responders and military must take expense, training requirements, and physical burden all into consideration. By harnessing the size-dependent luminescence of quantum dots (QDs) being electrospun into polymer fibers, the authors of this work hope to progress toward the development of lightweight, multivariable, inexpensive, easy to use and interpret, field-applicable sensors capable of detecting explosive vapors. The data demonstrate that poly(methyl methacrylate) (PMMA), polystyrene (PS), and polyvinyl chloride (PVC) fibers doped with Fort Orange cadmium selenide (CdSe) QDs, Birch Yellow CdSe QDs, or carbon (C) QDs will quench in the presence of explosive vapors (DNT, TNT, TATP, and RDX). In all cases, the fluorescent signal of the doped fiber continuously quenched upon sustained exposure to the headspace vapors. The simple method for the integration of QDs into the fibers' structure combined with their straightforward visual response, reusability, and durability all present characteristics desired for a field-operable and multimodal sensor with the ability to detect explosive threats., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
- Published
- 2023
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17. Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells.
- Author
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Ramos EI, Veerapandian R, Das K, Chacon JA, Gadad SS, and Dhandayuthapani S
- Abstract
Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with Mycoplasma genitalium (Mg) and Mycoplasma penumoniae (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis. HeLa cells infected with these species showed up-and-down regulation of lncRNAs expression, indicating that both species can modulate host lncRNAs. However, the number of upregulated (200 for Mg and 112 for Mp) and downregulated lncRNAs (30 for Mg and 62 for Mp) differ widely between these two species. GREAT analysis of the noncoding regions associated with differentially expressed lncRNAs showed that Mg and Mp regulate a discrete set of lncRNA plausibly related to transcription, metabolism, and inflammation. Further, signaling network analysis of the differentially regulated lncRNAs exhibited diverse pathways such as neurodegeneration, NOD-like receptor signaling, MAPK signaling, p53 signaling, and PI3K signaling, suggesting that both species primarily target signaling mechanisms. Overall, the study's results suggest that Mg and Mp modulate lncRNAs to promote their survival within the host but in distinct manners., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)
- Published
- 2023
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18. Bioinductive collagen implants facilitate tendon regeneration in rotator cuff tears.
- Author
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Camacho-Chacon JA, Cuenca-Espierrez J, Roda-Rojo V, Martin-Martinez A, Calderon-Meza JM, Alvarez-Alegret R, and Martin-Hernandez C
- Abstract
Purpose: To evaluate the clinical outcomes, MRI imaging and histological characteristics of biopsy samples of the tendon from patients in whom rotator cuff repair was previously performed with a bioinductive type I bovine collagen implants., Methods: Prospective study of 30 patients with partial or complete rotator cuff tears who underwent arthroscopic repair and augmentation with a resorbable type I bovine collagen implant. Preoperatively and at 6 and 12 months after surgery, the VAS, ASES and Constant-Murley scores were evaluated and an MRI study was performed. At 6 months, biopsies of the resulting tissue were obtained and examined histologically., Results: Patients experienced statistically significant and sustained improvement from baseline for all scores and the mean tendon thickness increased by 1.84 mm. Magnetic resonance imaging evidence of complete healing was found in 27 patients and a considerable reduction in defect size, greater than 50%, was shown in 3. In all samples obtained, the new tissue generated had the histological appearance of a tendon, and was indistinguishable from the native tendon. There was no evidence of any remaining collagen implant., Conclusions: Biopsies of tissue formed from bioinductive type I bovine collagen implants showed, six months after surgery, the generation of a neotendon indistinguishable from the native one. Histology and MRI imaging, revealed complete integration of the implant and absence of inflammatory or foreign body reactions. The clinical parameters, thickness and MRI signal of the tendon improved significantly at 6 months, regardless of the type and size of the tear, and remained unchanged until 12 months., Level of Evidence: Level IV, case series., (© 2022. The Author(s).)
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- 2022
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19. Systematic analysis of CD39, CD103, CD137, and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs.
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Eiva MA, Omran DK, Chacon JA, and Powell DJ Jr
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- Female, Humans, Interferon-gamma immunology, Antigens, CD immunology, Apyrase immunology, Biomarkers, Tumor immunology, Integrin alpha Chains immunology, Lymphocytes, Tumor-Infiltrating immunology, Ovarian Neoplasms immunology, Programmed Cell Death 1 Receptor immunology, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
- Abstract
The detection of tumor-specific T cells in solid tumors is integral to interrogate endogenous antitumor responses and to advance downstream therapeutic applications. Multiple biomarkers are reported to identify endogenous tumor-specific tumor-infiltrating lymphocytes (TILs), namely CD137, PD-1, CD103, and CD39; however, a direct comparison of these molecules has yet to be performed. We evaluated these biomarkers in primary human ovarian tumor samples using single-cell mass cytometry to compare their relative phenotypic profiles, and examined their response to autologous tumor cells ex vivo. PD-1
+ , CD103+ , and CD39+ TILs all contain a CD137+ cell subset, while CD137+ TILs highly co-express the aforementioned markers. CD137+ TILs exhibit the highest expression of cytotoxic effector molecules compared to PD-1+ , CD103+ , or CD39+ TILs. Removal of CD137+ cells from PD-1+ , CD103+ , or CD39+ TILs diminish their IFN-γ secretion in response to autologous tumor cell stimulation, while CD137+ TILs maintain high HLA-dependent IFN-γ secretion. CD137+ TILs exhibited an exhausted phenotype but with CD28 co-expression, suggesting possible receptiveness to reinvigoration via immune checkpoint blockade. Together, our findings demonstrate that the antitumor abilities of PD-1+ , CD103+ , and CD39+ TILs are mainly derived from a subset of CD137-expressing TILs, implicating CD137 as a more selective biomarker for naturally occurring tumor-specific TILs., (© 2021 Wiley-VCH GmbH.)- Published
- 2022
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20. Teaching Critical Thinking and Problem-Solving Skills to Healthcare Professionals.
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Chacon JA and Janssen H
- Abstract
Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest.
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- 2020
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21. Personalized Medicine in Undergraduate Medical Education: a Spiral Learning Model.
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Chacon JA, Cervantes JL, Perry CN, Pfarr CM, and Ayoubieh H
- Abstract
Educational strategies to introduce medical students to scientific advances are needed as evidence continues to evolve regarding their clinical application in personalized medicine. Our overall project goal is to design an evidence-based, clinically relevant, personalized medicine curriculum spanning the 4 years of undergraduate medical education., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2020.)
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- 2020
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22. 4-1BB-Enhanced Expansion of CD8 + TIL from Triple-Negative Breast Cancer Unveils Mutation-Specific CD8 + T Cells.
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Harao M, Forget MA, Roszik J, Gao H, Babiera GV, Krishnamurthy S, Chacon JA, Li S, Mittendorf EA, DeSnyder SM, Rockwood KF, Bernatchez C, Ueno NT, Radvanyi LG, Vence L, Haymaker C, and Reuben JM
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- Antibodies, Monoclonal pharmacology, Female, Humans, Mutation, Triple Negative Breast Neoplasms genetics, Tumor Cells, Cultured, CD8-Positive T-Lymphocytes immunology, Lymphocytes, Tumor-Infiltrating immunology, Triple Negative Breast Neoplasms immunology, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
- Abstract
Triple-negative breast cancer (TNBC) highly infiltrated with CD8
+ tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439-45. ©2017 AACR ., (©2017 American Association for Cancer Research.)- Published
- 2017
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23. The Impact of Chemotherapy, Radiation and Epigenetic Modifiers in Cancer Cell Expression of Immune Inhibitory and Stimulatory Molecules and Anti-Tumor Efficacy.
- Author
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Chacon JA, Schutsky K, and Powell DJ
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Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression. While administration of immunomodulatory antibodies that block the interactions between inhibitory receptors on immune cells and their ligands on tumor cells can mediate cancer regression in a subset of treated patients, it is crucial to understand how genomic destabilizers alter the immune system and malignant cells, including which inhibitory molecules, receptors and/or ligands are upregulated in response to genotoxic stress. Knowledge gained in this area will aid in the rational design of trials that combine genomic destabilizers, epigenetic modifiers and immunotherapeutic agents that may be synergized to improve clinical responses and prevent tumor escape from the immune system. Our review article describes the impact genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers have on anti-tumor immunity and the tumor microenvironment. Although genomic destabilizers cause DNA damage on cancer cells, these therapies can also have diverse effects on the immune system, promote immunogenic cell death or survival and alter the cancer cell expression of immune inhibitor molecules., Competing Interests: The authors declare no potential conflicts of interest with regard to this paper.
- Published
- 2016
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24. Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level.
- Author
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Song DG, Ye Q, Poussin M, Chacon JA, Figini M, and Powell DJ Jr
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- Animals, Cells, Cultured, Female, Folate Receptor 1 immunology, Heterografts, Humans, Immunotherapy, Adoptive standards, Mice, Ovarian Neoplasms chemistry, Receptors, Antigen, T-Cell genetics, T-Lymphocytes immunology, T-Lymphocytes transplantation, Triple Negative Breast Neoplasms chemistry, Folate Receptor 1 analysis, Immunotherapy, Adoptive methods, Ovarian Neoplasms therapy, Triple Negative Breast Neoplasms therapy
- Abstract
Background: The poor prognosis and the limited efficacy of targeted therapy in patients with triple-negative breast cancer (TNBC) have raised the need for alternative therapies. Recent studies have demonstrated that folate receptor-alpha (FRα) may represent an ideal tumor-associated marker for immunotherapy for TNBC., Methods: The aim of the present study was to apply a chimeric antigen receptor (CAR) approach for the targeting of FRα expressed on TNBC cells and evaluate the antitumor activity of CAR-engineered T cells in vitro and in vivo., Results: We found that human T cells expressing a FRα-specific CAR were potent and specific killers of TNBC cells that express moderate levels of FRα in vitro and significantly inhibited tumor outgrowth following infusion into immunodeficient mice bearing an MDA-MB-231 tumor xenograft. However, the antitumor activity of the FRα CAR T cells was modest when compared to the same CAR T cells applied in an ovarian tumor xenograft model where FRα expression is more abundant. Notably, FRα CAR T cells induced superior tumor regression in vivo against MDA-MB-231 that was engineered for overexpression of FRα., Conclusions: Taken together, our results show that FRα CAR T cells can mediate antitumor activity against established TNBC tumor, particularly when FRα is expressed at higher levels. These results have significant implications for the pre-selection of patients with high antigen expression levels when utilizing CAR-based adoptive T cell therapies of cancer in future clinical trials.
- Published
- 2016
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25. Triggering co-stimulation directly in melanoma tumor fragments drives CD8 + tumor-infiltrating lymphocyte expansion with improved effector-memory properties.
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Chacon JA, Sarnaik AA, Pilon-Thomas S, and Radvanyi L
- Abstract
TIL from solid tumors can express activation/co-stimulatory molecules like 4-1BB/CD137, a sign of recent antigenic stimulation in the tumor microenvironment (TME). This activated state can be exploited ex vivo to enhance the expansion of tumor-reactive CD8
+ TIL for adoptive cell therapy through direct addition of immunomodulators to tumor fragments in culture.- Published
- 2015
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26. Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy.
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Chacon JA, Sarnaik AA, Chen JQ, Creasy C, Kale C, Robinson J, Weber J, Hwu P, Pilon-Thomas S, and Radvanyi L
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- Active Transport, Cell Nucleus drug effects, Antibodies, Monoclonal pharmacology, Dendritic Cells drug effects, Dendritic Cells immunology, Humans, Immunophenotyping, Lymphocytes, Tumor-Infiltrating drug effects, Lymphocytes, Tumor-Infiltrating metabolism, Melanoma immunology, Melanoma pathology, Melanoma therapy, NF-kappa B metabolism, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Phenotype, Signal Transduction drug effects, Tumor Microenvironment genetics, Tumor Necrosis Factor Receptor Superfamily, Member 9 agonists, Tumor Necrosis Factor Receptor Superfamily, Member 9 genetics, Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism, Immunotherapy, Adoptive methods, Lymphocytes, Tumor-Infiltrating immunology, Neoplasms immunology, Neoplasms therapy, Tumor Microenvironment immunology
- Abstract
Purpose: Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8(+) T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8(+) T cells recently found to constitute the majority of tumor-specific T cells., Experimental Design: We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB costimulation., Results: We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8(+) TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8(+) T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8(+) T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8(+) TIL outgrowth., Conclusions: Our results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics., (©2014 American Association for Cancer Research.)
- Published
- 2015
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27. Hemodialysis catheter implantation in the axillary vein by ultrasound guidance versus palpation or anatomical reference.
- Author
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Valencia CA, Villa CA, and Cardona JA
- Abstract
Background: WE COMPARED THE RESULTS OF FOUR DIFFERENT METHODS OF HEMODIALYSIS CATHETER INSERTION IN THE MEDIAL SEGMENT OF THE AXILLARY VEIN: ultrasound guidance, palpation, anatomical reference, and prior transient catheter., Methods: All patients that required acute or chronic hemodialysis and for whom it was determined impossible or not recommended either to place a catheter in the internal jugular vein (for instance, those patients with a tracheostomy), or to practice arteriovenous fistula or graft; it was then essential to obtain an alternative vascular access. When the procedure of axillary vein catheter insertion was performed in the Renal Care Facility (RCF), ultrasound guidance was used, but in the intensive care unit (ICU), this resource was unavailable, so the palpation or anatomical reference technique was used., Results: Two nephrologists with experience in the technique performed 83 procedures during a period lasting 15 years and 8 months (from January 1997-August 2012): 41 by ultrasound guidance; 19 by anatomical references; 15 by palpation of the contiguous axillary artery; and 8 through a temporary axillary catheter previously placed. The ultrasound-guided patients had fewer punctures than other groups, but the value was not statistically significant. Arterial punctures were infrequent in all techniques. Analyzing all the procedure-related complications, such as hematoma, pneumothorax, brachial-plexus injury, as well as the reasons for catheter removal, no differences were observed among the groups. The functioning time was longer in the ultrasound-guided and previous catheter groups. In 15 years and 8 months of surveillance, no clinical or image evidence for axillary vein stenosis was found., Conclusion: The ultrasound guide makes the procedure of inserting catheters in the axillary veins easier, but knowledge of the anatomy of the midaxillary region and the ability to feel the axillary artery pulse (for the palpation method) also allow relatively easy successful implant of catheters in the axillary veins.
- Published
- 2013
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28. Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.
- Author
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Chacon JA, Pilon-Thomas S, Sarnaik AA, and Radvanyi LG
- Abstract
Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.
- Published
- 2013
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29. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy.
- Author
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Chacon JA, Wu RC, Sukhumalchandra P, Molldrem JJ, Sarnaik A, Pilon-Thomas S, Weber J, Hwu P, and Radvanyi L
- Subjects
- CD28 Antigens genetics, CD28 Antigens immunology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes transplantation, Cell Proliferation drug effects, Cell Survival drug effects, Gene Expression drug effects, Humans, Immunologic Memory drug effects, Inhibitor of Apoptosis Proteins genetics, Inhibitor of Apoptosis Proteins immunology, Lymphocyte Activation drug effects, Lymphocytes, Tumor-Infiltrating drug effects, Lymphocytes, Tumor-Infiltrating transplantation, Melanoma genetics, Melanoma immunology, Melanoma pathology, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 immunology, Signal Transduction drug effects, Skin Neoplasms genetics, Skin Neoplasms immunology, Skin Neoplasms pathology, Survivin, Tumor Cells, Cultured, Tumor Necrosis Factor Receptor Superfamily, Member 9 agonists, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology, CD8-Positive T-Lymphocytes immunology, Immunoglobulin G pharmacology, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating immunology, Melanoma therapy, Skin Neoplasms therapy, Tumor Necrosis Factor Receptor Superfamily, Member 9 genetics
- Abstract
Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the "rapid expansion protocol" (REP) were not designed to enhance the generation of optimal effector-memory CD8(+) T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8(+) effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8(+) T cells, on the yield, phenotype, and functional activity of expanded CD8(+) T cells during the REP. We found that CD8(+) TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the REP significantly enhanced the frequency and total yield of CD8(+) T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8(+) post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8(+) T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients.
- Published
- 2013
- Full Text
- View/download PDF
30. Detection and characterization of a novel subset of CD8⁺CD57⁺ T cells in metastatic melanoma with an incompletely differentiated phenotype.
- Author
-
Wu RC, Liu S, Chacon JA, Wu S, Li Y, Sukhumalchandra P, Murray JL, Molldrem JJ, Hwu P, Pircher H, Lizée G, and Radvanyi LG
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, CD57 Antigens metabolism, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes pathology, Female, Flow Cytometry, Humans, Immunologic Memory, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating metabolism, Lymphocytes, Tumor-Infiltrating pathology, Male, Melanoma metabolism, Middle Aged, Neoplasm Staging, Phenotype, Receptors, Antigen, T-Cell metabolism, T-Lymphocyte Subsets metabolism, T-Lymphocyte Subsets pathology, Transforming Growth Factor beta1 pharmacology, Tumor Cells, Cultured, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, Young Adult, CD8-Positive T-Lymphocytes immunology, Cell Differentiation, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Melanoma secondary, T-Lymphocyte Subsets immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Purpose: Tumor-specific T cells are frequently induced naturally in melanoma patients and infiltrate tumors. It is enigmatic why these patients fail to experience tumor regression. Given that CD8(+) T cells mediate antigen-specific killing of tumor cells, the focus of this study was to identify alterations in the differentiation of CD8(+) residing at the tumor site, with emphasis on a population expressing CD57, a marker for terminal differentiation., Experimental Design: We conducted flow cytometric analysis of CD8(+) tumor-infiltrating lymphocytes (TIL) isolated from 44 resected melanoma metastases with known T-cell differentiation markers. For comparison, peripheral blood mononuclear cells were isolated from matched melanoma patients. We sorted different CD8(+) subsets found in TIL and determined their effector functions. In addition, we carried out Vβ clonotype expression analysis of T-cell receptors to determine lineage relationship between the CD8(+) TIL subsets., Results: The majority of CD8(+) TIL was in the early-effector memory stage of differentiation. A significant population consisted of an oligoclonal subset of cells coexpressing CD27, CD28, CD57, and Granzyme B, with little or no perforin. These cells could be induced to proliferate, produce a high level of IFN-γ, and differentiate into CD27(-)CD57(+), perforin(high) mature CTL in vitro. Addition of TGF-β1 prevented further differentiation., Conclusions: Our studies identified a novel subset of incompletely differentiated CD8(+) CTL coexpressing early effector memory and late CTL markers. This population resembles that found in patients with uncontrolled chronic viral infections. TGF-β1, frequently produced by melanoma tumors, may be a key cytokine inhibiting further maturation of this subset., (©2012 AACR.)
- Published
- 2012
- Full Text
- View/download PDF
31. Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function.
- Author
-
Hernandez-Chacon JA, Li Y, Wu RC, Bernatchez C, Wang Y, Weber JS, Hwu P, and Radvanyi LG
- Subjects
- Animals, Antilymphocyte Serum pharmacology, Antilymphocyte Serum therapeutic use, CD28 Antigens immunology, CD28 Antigens metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes metabolism, Cell Death drug effects, Cell Death immunology, Cell Proliferation drug effects, Cytotoxicity, Immunologic drug effects, Cytotoxicity, Immunologic immunology, Humans, Immunotherapy, Adoptive methods, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Lymphocytes, Tumor-Infiltrating metabolism, Melanoma pathology, Melanoma therapy, Mice, Muromonab-CD3 pharmacology, Neoplasms pathology, Neoplasms therapy, Receptors, OX40 immunology, Receptors, OX40 metabolism, Signal Transduction drug effects, Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism, CD8-Positive T-Lymphocytes immunology, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Neoplasms immunology, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
- Abstract
Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.
- Published
- 2011
- Full Text
- View/download PDF
32. Preadenoid space size and its relationship to the vertical facial type.
- Author
-
Gomez CE, Gomez LC, and Chacon JA
- Subjects
- Adolescent, Cephalometry statistics & numerical data, Child, Facial Bones anatomy & histology, Humans, Face anatomy & histology, Maxillofacial Development, Mouth Breathing physiopathology, Nasopharynx anatomy & histology, Vertical Dimension
- Abstract
The purpose of this study of 103 patients was to present a statistical analysis of the relationship between the size of the preadenoid space and the measurements that determine the vertical and anterior-posterior relationship between the maxilla and the mandible, which could disturb the facial type. This study also analyzes the relationship of mouth breathing with the measurements that determine the vertical facial type in the human cranium. No statistically significant relationship was found between the size of the preadenoid space and the vertical characteristics of the sample, nor was there a statistically significant relationship between the mouth-breathing pattern and its facial type in the vertical plane.
- Published
- 2006
33. Reliability and validity of a computer-based Little irregularity index.
- Author
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Tran AM, Rugh JD, Chacon JA, and Hatch JP
- Subjects
- Humans, Mandible, Models, Dental, Reproducibility of Results, Diagnosis, Computer-Assisted, Incisor pathology, Malocclusion diagnosis
- Published
- 2003
- Full Text
- View/download PDF
34. Adapting a parallel flow dialyser to the Travenol RSP machine.
- Author
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Chacon JA, Yañez A, Lampreabe I, Sangrador M, Escubi N, and Damborenea RG
- Subjects
- Blood Volume, Kidneys, Artificial
- Published
- 1972
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