24 results on '"Obiorah I"'
Search Results
2. Nigerian Audience Views on Mainstream Media and Moulding of Public Opinion in the 21st Century.
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Edogor, Obiorah I., Odogwu, Emeka C., Chukwuemeka, Gloria N., Nworah, Uche, and Okoyeocha, Chinwe R.
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MASS media influence ,WEB 2.0 ,MASS media ,PUBLIC opinion ,PUBLIC communication - Abstract
The mass media have been long known to shape and mould public opinion in every human society. However, with the influence of web 2.0 technologies that have affected mainstream journalism practice in the 21st century, this study investigated the extent to which mainstream media still mould public opinion in Nigeria. The paper was anchored on agenda-setting and media dependency theories as it investigated journalism's ability to mould the views of people on issues of public concern. The survey research design was used where the multistage sampling technique was adopted and an online Australian Calculator was used to draw the sample size of 371, the questionnaire was deployed as the instrument for data collection. The results among other things revealed that, though social media and blogs' usage have influenced mass media and public communication generally, mainstream journalism still moulds public opinion in Nigeria. This was revealed as respondents disclosed that in making decisions, they believe and use more information they obtained from mainstream media platforms than information they got from blogs and social media sites. [ABSTRACT FROM AUTHOR] more...
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- 2024
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Catalog
3. Exploring ‘Omniscience Theory’ as a Theoretical Framework in Journalism Practice
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Obiorah I. Edogor, Olusola Oyero, and Mercy I. Obichili
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- 2023
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4. Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death
- Author
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Obiorah, I, Sengupta, S, Fan, P, and Jordan, V C
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- 2014
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5. Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol
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Obiorah, I E and Jordan, V C
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- 2014
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6. Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells
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Sengupta, S, Obiorah, I, Maximov, P Y, Curpan, R, and Jordan, V C
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- 2013
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7. Correction: Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death
- Author
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Obiorah, I, Sengupta, S, Fan, P, and Jordan, V C
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- 2016
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8. IgG4-related disease involving the esophagus: a clinicopathological study
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Obiorah, I., primary, Hussain, A., additional, Palese, C., additional, Azumi, N., additional, Benjamin, S., additional, and Ozdemirli, M., additional
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- 2017
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9. Erratum: Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death
- Author
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Obiorah, I, primary, Sengupta, S, additional, Fan, P, additional, and Jordan, V C, additional
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- 2016
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10. Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death.
- Author
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Obiorah, I, Sengupta, S, Fan, P, and Jordan, V C
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- 2016
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11. A-135 Challenges in differentiating among the primary cutaneous lymphoproliferative diseases with gamma-delta phenotype - a case report.
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Ali, S., Roberts, N., Cropley, T., Obiorah, I., Fan, J., Williams, E., Gru, A., and Marchi, E.
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CONFERENCES & conventions , *LYMPHOPROLIFERATIVE disorders , *CELL receptors , *PHENOTYPES - Published
- 2024
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12. Assessment for acceleration and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma using histologic and immunohistochemical features: a case series.
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Moore ME, Aguilera NS, Obiorah I, Williams E, and Courville E
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- Humans, Male, Female, Aged, Middle Aged, Biomarkers, Tumor metabolism, Biomarkers, Tumor genetics, Cell Transformation, Neoplastic pathology, Aged, 80 and over, Observer Variation, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Immunohistochemistry
- Abstract
Morphologic features of aggressive/ "accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (aCLL/SLL) have been described. Richter transformation (RT) also occurs in a subset of CLL/SLL cases. This case series examined inter-observer variability when assessing for aCLL/SLL and RT, with attention to how immunohistochemical (IHC) markers may assist in this evaluation. Twelve cases of CLL/SLL with available FFPE tissue were identified. H&E staining and IHC (CD3, CD20, CD5, CD23, LEF1, LAG3, C-MYC, PD-1, MUM1, Cyclin D1, BCL-6, p53, and Ki-67) were performed. Three hematopathologists reviewed each case. The pathologists provided a final interpretation of (1) CLL/SLL, (2) CLL/SLL with expanded and/or confluent proliferation centers or increased Ki-67 (aCLL/SLL), or (3) large cell transformation/DLBCL. The pathologists lacked consensus in the diagnosis in 6/12 cases (50%). The reviewers disagreed on the presence of expanded/confluent proliferation centers in 8/12 cases (67%). With the exception of Ki-67, no IHC marker showed a difference in the staining profile in aCLL/SLL or RT compared to low-grade cases. This series showed inter-observer variability in the evaluation for aCLL/SLL and RT. A study that serially examines genetic alterations in FFPE tissue and correlates the features with histology and IHC, at diagnosis and throughout the disease course, may help refine indicators of aggressive disease., (© 2024. The Author(s).) more...
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- 2024
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13. Tumor flare reaction in a patient with mycosis fungoides treated with a novel immune-epigenetic doublet.
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Dar N, Roberts N, Gru A, Obiorah I, Zheng J, Shields LK, Cropley T, and Marchi E
- Abstract
Competing Interests: Dr Gru reports participation on a Data Safety Monitoring Board or Advisory Board of StemLine, Seattle Genetics, and Innate Pharma; receives payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Kyowa Kyrin and StemLine Therapeutic. Dr Marchi is a scientific advisor for Kyowa Kirin, Seagen, and Acrotech. Author Dar and Drs Roberts, Obiorah, Zheng, Shields, and Cropley have no conflicts of interest to declare. more...
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- 2024
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14. Diagnostic Flow Cytometry in the Era of Targeted Therapies: Lessons from Therapeutic Monoclonal Antibodies and Chimeric Antigen Receptor T-cell Adoptive Immunotherapy.
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Obiorah I and Courville EL
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- Humans, Antibodies, Monoclonal therapeutic use, Flow Cytometry, Immunotherapy, T-Lymphocytes, Immunotherapy, Adoptive, Receptors, Chimeric Antigen genetics
- Abstract
Therapeutic monoclonal antibodies (therapeutic mAb) and adoptive immunotherapy have become increasingly more common in the treatment of hematolymphoid neoplasms, with practical implications for diagnostic flow cytometry. Their use can reduce the sensitivity of flow cytometry for populations of interest owing to downregulation/loss of the target antigen, competition for the target antigen, or lineage switch. Expanded flow panels, marker redundancy, and exhaustive gating strategies can overcome this limitation. Therapeutic mAb have been reported to cause pseudo-light chain restriction, and awareness of this potential artifact is key. Established guidelines do not yet exist for antigen expression by flow cytometry for therapeutic purposes., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...
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- 2023
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15. Dural Marginal Zone Lymphoma With Extensive Crystal Storing Histiocytosis: Spotting the Zebra Among the Horses.
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Morgan KM, Obiorah I, Sun H, David K, Chundury A, Jaffe E, Salaru G, Sojitra P, and Matsuda K
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- Humans, Histiocytosis pathology, Lymphoma, B-Cell, Marginal Zone pathology
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- 2022
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16. THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders.
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Guennewig B, Bitar M, Obiorah I, Hanks J, O'Brien EA, Kaczorowski DC, Hurd YL, Roussos P, Brennand KJ, and Barry G
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- Autistic Disorder genetics, Base Sequence, Gene Expression Profiling, Gene Expression Regulation, Glutamic Acid metabolism, Humans, Intellectual Disability genetics, Mitochondria drug effects, Mitochondria metabolism, Post-Synaptic Density metabolism, Schizophrenia genetics, Transcriptome, Dronabinol pharmacology, Induced Pluripotent Stem Cells drug effects, Induced Pluripotent Stem Cells metabolism, Mental Disorders genetics, Neurons drug effects, Neurons metabolism
- Abstract
There is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Δ
9 -tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC. more...- Published
- 2018
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17. An Unusual Posttransplant T-cell Lymphoma After Liver Transplantation: A Case Report.
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Obiorah IE and Ozdemirli M
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- Antineoplastic Agents therapeutic use, Humans, Lymphoma, T-Cell drug therapy, Male, Middle Aged, Postoperative Complications drug therapy, Graft vs Host Disease complications, Liver Transplantation adverse effects, Lymphoma, T-Cell immunology, Natural Killer T-Cells immunology, Postoperative Complications immunology
- Abstract
Posttransplantation lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities ranging from benign lymphocytic proliferations to high-grade malignant lymphomas. The majority of PTLDs are associated with reactivation of Epstein-Barr virus (EBV), which induces B-cell proliferation and occurs in the setting of severe immune suppression after solid organ or bone marrow transplantation. T-cell/natural killer cell PTLDs are relatively rare, constituting ∼15% of all cases. T-cell PTLDs are usually aggressive, and outcomes are poor. This article describes an unusual case of T-cell PTLD with a favorable outcome. The patient is a 57-year-old man who underwent a liver transplantation due to hepatitis C cirrhosis. He developed graft-versus-host disease with skin and gastrointestinal involvement and generalized lymphadenopathy 4 months after transplantation. Histologic sections of an excised axillary lymph node showed atypical medium and larger T-lymphocytes that were positive for CD3, CD5, CD43, and CD8 but were negative for B-cell antigens, CD56, and in situ hybridization for EBV-encoded RNA. Polymerase chain reaction analysis revealed monoclonal T-cell receptor gamma chain gene rearrangement. A diagnosis of high-grade T-cell PTLD was made. The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone and is currently in remission, 4 years after therapy. The rapid presentation of an EBV-negative T-cell PTLD with a nonaggressive course and complete response to treatment is an unusual presentation of posttransplantation T-cell lymphoma, which is usually associated with a high mortality rate., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...
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- 2017
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18. Evaluating Synthetic Activation and Repression of Neuropsychiatric-Related Genes in hiPSC-Derived NPCs, Neurons, and Astrocytes.
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Ho SM, Hartley BJ, Flaherty E, Rajarajan P, Abdelaal R, Obiorah I, Barretto N, Muhammad H, Phatnani HP, Akbarian S, and Brennand KJ
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- Calcium metabolism, Cell Differentiation, Cells, Cultured, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells metabolism, Molecular Imaging, Transcriptome, Astrocytes cytology, Astrocytes metabolism, Induced Pluripotent Stem Cells cytology, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neurons cytology, Neurons metabolism
- Abstract
Modulation of transcription, either synthetic activation or repression, via dCas9-fusion proteins is a relatively new methodology with the potential to facilitate high-throughput up- or downregulation studies of gene function. Genetic studies of neurodevelopmental disorders have identified a growing list of risk variants, including both common single-nucleotide variants and rare copy-number variations, many of which are associated with genes having limited functional annotations. By applying a CRISPR-mediated gene-activation/repression platform to populations of human-induced pluripotent stem cell-derived neural progenitor cells, neurons, and astrocytes, we demonstrate that it is possible to manipulate endogenous expression levels of candidate neuropsychiatric risk genes across these three cell types. Although proof-of-concept studies using catalytically inactive Cas9-fusion proteins to modulate transcription have been reported, here we present a detailed survey of the reproducibility of gRNA positional effects across a variety of neurodevelopmental disorder-relevant risk genes, donors, neural cell types, and dCas9 effectors., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2017
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19. Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.
- Author
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Leung W, Shaffer CD, Reed LK, Smith ST, Barshop W, Dirkes W, Dothager M, Lee P, Wong J, Xiong D, Yuan H, Bedard JE, Machone JF, Patterson SD, Price AL, Turner BA, Robic S, Luippold EK, McCartha SR, Walji TA, Walker CA, Saville K, Abrams MK, Armstrong AR, Armstrong W, Bailey RJ, Barberi CR, Beck LR, Blaker AL, Blunden CE, Brand JP, Brock EJ, Brooks DW, Brown M, Butzler SC, Clark EM, Clark NB, Collins AA, Cotteleer RJ, Cullimore PR, Dawson SG, Docking CT, Dorsett SL, Dougherty GA, Downey KA, Drake AP, Earl EK, Floyd TG, Forsyth JD, Foust JD, Franchi SL, Geary JF, Hanson CK, Harding TS, Harris CB, Heckman JM, Holderness HL, Howey NA, Jacobs DA, Jewell ES, Kaisler M, Karaska EA, Kehoe JL, Koaches HC, Koehler J, Koenig D, Kujawski AJ, Kus JE, Lammers JA, Leads RR, Leatherman EC, Lippert RN, Messenger GS, Morrow AT, Newcomb V, Plasman HJ, Potocny SJ, Powers MK, Reem RM, Rennhack JP, Reynolds KR, Reynolds LA, Rhee DK, Rivard AB, Ronk AJ, Rooney MB, Rubin LS, Salbert LR, Saluja RK, Schauder T, Schneiter AR, Schulz RW, Smith KE, Spencer S, Swanson BR, Tache MA, Tewilliager AA, Tilot AK, VanEck E, Villerot MM, Vylonis MB, Watson DT, Wurzler JA, Wysocki LM, Yalamanchili M, Zaborowicz MA, Emerson JA, Ortiz C, Deuschle FJ, DiLorenzo LA, Goeller KL, Macchi CR, Muller SE, Pasierb BD, Sable JE, Tucci JM, Tynon M, Dunbar DA, Beken LH, Conturso AC, Danner BL, DeMichele GA, Gonzales JA, Hammond MS, Kelley CV, Kelly EA, Kulich D, Mageeney CM, McCabe NL, Newman AM, Spaeder LA, Tumminello RA, Revie D, Benson JM, Cristostomo MC, DaSilva PA, Harker KS, Jarrell JN, Jimenez LA, Katz BM, Kennedy WR, Kolibas KS, LeBlanc MT, Nguyen TT, Nicolas DS, Patao MD, Patao SM, Rupley BJ, Sessions BJ, Weaver JA, Goodman AL, Alvendia EL, Baldassari SM, Brown AS, Chase IO, Chen M, Chiang S, Cromwell AB, Custer AF, DiTommaso TM, El-Adaimi J, Goscinski NC, Grove RA, Gutierrez N, Harnoto RS, Hedeen H, Hong EL, Hopkins BL, Huerta VF, Khoshabian C, LaForge KM, Lee CT, Lewis BM, Lydon AM, Maniaci BJ, Mitchell RD, Morlock EV, Morris WM, Naik P, Olson NC, Osterloh JM, Perez MA, Presley JD, Randazzo MJ, Regan MK, Rossi FG, Smith MA, Soliterman EA, Sparks CJ, Tran DL, Wan T, Welker AA, Wong JN, Sreenivasan A, Youngblom J, Adams A, Alldredge J, Bryant A, Carranza D, Cifelli A, Coulson K, Debow C, Delacruz N, Emerson C, Farrar C, Foret D, Garibay E, Gooch J, Heslop M, Kaur S, Khan A, Kim V, Lamb T, Lindbeck P, Lucas G, Macias E, Martiniuc D, Mayorga L, Medina J, Membreno N, Messiah S, Neufeld L, Nguyen SF, Nichols Z, Odisho G, Peterson D, Rodela L, Rodriguez P, Rodriguez V, Ruiz J, Sherrill W, Silva V, Sparks J, Statton G, Townsend A, Valdez I, Waters M, Westphal K, Winkler S, Zumkehr J, DeJong RJ, Hoogewerf AJ, Ackerman CM, Armistead IO, Baatenburg L, Borr MJ, Brouwer LK, Burkhart BJ, Bushhouse KT, Cesko L, Choi TY, Cohen H, Damsteegt AM, Darusz JM, Dauphin CM, Davis YP, Diekema EJ, Drewry M, Eisen ME, Faber HM, Faber KJ, Feenstra E, Felzer-Kim IT, Hammond BL, Hendriksma J, Herrold MR, Hilbrands JA, Howell EJ, Jelgerhuis SA, Jelsema TR, Johnson BK, Jones KK, Kim A, Kooienga RD, Menyes EE, Nollet EA, Plescher BE, Rios L, Rose JL, Schepers AJ, Scott G, Smith JR, Sterling AM, Tenney JC, Uitvlugt C, VanDyken RE, VanderVennen M, Vue S, Kokan NP, Agbley K, Boham SK, Broomfield D, Chapman K, Dobbe A, Dobbe I, Harrington W, Ibrahem M, Kennedy A, Koplinsky CA, Kubricky C, Ladzekpo D, Pattison C, Ramirez RE Jr, Wande L, Woehlke S, Wawersik M, Kiernan E, Thompson JS, Banker R, Bartling JR, Bhatiya CI, Boudoures AL, Christiansen L, Fosselman DS, French KM, Gill IS, Havill JT, Johnson JL, Keny LJ, Kerber JM, Klett BM, Kufel CN, May FJ, Mecoli JP, Merry CR, Meyer LR, Miller EG, Mullen GJ, Palozola KC, Pfeil JJ, Thomas JG, Verbofsky EM, Spana EP, Agarwalla A, Chapman J, Chlebina B, Chong I, Falk IN, Fitzgibbons JD, Friedman H, Ighile O, Kim AJ, Knouse KA, Kung F, Mammo D, Ng CL, Nikam VS, Norton D, Pham P, Polk JW, Prasad S, Rankin H, Ratliff CD, Scala V, Schwartz NU, Shuen JA, Xu A, Xu TQ, Zhang Y, Rosenwald AG, Burg MG, Adams SJ, Baker M, Botsford B, Brinkley B, Brown C, Emiah S, Enoch E, Gier C, Greenwell A, Hoogenboom L, Matthews JE, McDonald M, Mercer A, Monsma N, Ostby K, Ramic A, Shallman D, Simon M, Spencer E, Tomkins T, Wendland P, Wylie A, Wolyniak MJ, Robertson GM, Smith SI, DiAngelo JR, Sassu ED, Bhalla SC, Sharif KA, Choeying T, Macias JS, Sanusi F, Torchon K, Bednarski AE, Alvarez CJ, Davis KC, Dunham CA, Grantham AJ, Hare AN, Schottler J, Scott ZW, Kuleck GA, Yu NS, Kaehler MM, Jipp J, Overvoorde PJ, Shoop E, Cyrankowski O, Hoover B, Kusner M, Lin D, Martinov T, Misch J, Salzman G, Schiedermayer H, Snavely M, Zarrasola S, Parrish S, Baker A, Beckett A, Belella C, Bryant J, Conrad T, Fearnow A, Gomez C, Herbstsomer RA, Hirsch S, Johnson C, Jones M, Kabaso R, Lemmon E, Vieira CM, McFarland D, McLaughlin C, Morgan A, Musokotwane S, Neutzling W, Nietmann J, Paluskievicz C, Penn J, Peoples E, Pozmanter C, Reed E, Rigby N, Schmidt L, Shelton M, Shuford R, Tirasawasdichai T, Undem B, Urick D, Vondy K, Yarrington B, Eckdahl TT, Poet JL, Allen AB, Anderson JE, Barnett JM, Baumgardner JS, Brown AD, Carney JE, Chavez RA, Christgen SL, Christie JS, Clary AN, Conn MA, Cooper KM, Crowley MJ, Crowley ST, Doty JS, Dow BA, Edwards CR, Elder DD, Fanning JP, Janssen BM, Lambright AK, Lane CE, Limle AB, Mazur T, McCracken MR, McDonough AM, Melton AD, Minnick PJ, Musick AE, Newhart WH, Noynaert JW, Ogden BJ, Sandusky MW, Schmuecker SM, Shipman AL, Smith AL, Thomsen KM, Unzicker MR, Vernon WB, Winn WW, Woyski DS, Zhu X, Du C, Ament C, Aso S, Bisogno LS, Caronna J, Fefelova N, Lopez L, Malkowitz L, Marra J, Menillo D, Obiorah I, Onsarigo EN, Primus S, Soos M, Tare A, Zidan A, Jones CJ, Aronhalt T, Bellush JM, Burke C, DeFazio S, Does BR, Johnson TD, Keysock N, Knudsen NH, Messler J, Myirski K, Rekai JL, Rempe RM, Salgado MS, Stagaard E, Starcher JR, Waggoner AW, Yemelyanova AK, Hark AT, Bertolet A, Kuschner CE, Parry K, Quach M, Shantzer L, Shaw ME, Smith MA, Glenn O, Mason P, Williams C, Key SC, Henry TC, Johnson AG, White JX, Haberman A, Asinof S, Drumm K, Freeburg T, Safa N, Schultz D, Shevin Y, Svoronos P, Vuong T, Wellinghoff J, Hoopes LL, Chau KM, Ward A, Regisford EG, Augustine L, Davis-Reyes B, Echendu V, Hales J, Ibarra S, Johnson L, Ovu S, Braverman JM, Bahr TJ, Caesar NM, Campana C, Cassidy DW, Cognetti PA, English JD, Fadus MC, Fick CN, Freda PJ, Hennessy BM, Hockenberger K, Jones JK, King JE, Knob CR, Kraftmann KJ, Li L, Lupey LN, Minniti CJ, Minton TF, Moran JV, Mudumbi K, Nordman EC, Puetz WJ, Robinson LM, Rose TJ, Sweeney EP, Timko AS, Paetkau DW, Eisler HL, Aldrup ME, Bodenberg JM, Cole MG, Deranek KM, DeShetler M, Dowd RM, Eckardt AK, Ehret SC, Fese J, Garrett AD, Kammrath A, Kappes ML, Light MR, Meier AC, O'Rouke A, Perella M, Ramsey K, Ramthun JR, Reilly MT, Robinett D, Rossi NL, Schueler MG, Shoemaker E, Starkey KM, Vetor A, Vrable A, Chandrasekaran V, Beck C, Hatfield KR, Herrick DA, Khoury CB, Lea C, Louie CA, Lowell SM, Reynolds TJ, Schibler J, Scoma AH, Smith-Gee MT, Tuberty S, Smith CD, Lopilato JE, Hauke J, Roecklein-Canfield JA, Corrielus M, Gilman H, Intriago S, Maffa A, Rauf SA, Thistle K, Trieu M, Winters J, Yang B, Hauser CR, Abusheikh T, Ashrawi Y, Benitez P, Boudreaux LR, Bourland M, Chavez M, Cruz S, Elliott G, Farek JR, Flohr S, Flores AH, Friedrichs C, Fusco Z, Goodwin Z, Helmreich E, Kiley J, Knepper JM, Langner C, Martinez M, Mendoza C, Naik M, Ochoa A, Ragland N, Raimey E, Rathore S, Reza E, Sadovsky G, Seydoux MI, Smith JE, Unruh AK, Velasquez V, Wolski MW, Gosser Y, Govind S, Clarke-Medley N, Guadron L, Lau D, Lu A, Mazzeo C, Meghdari M, Ng S, Pamnani B, Plante O, Shum YK, Song R, Johnson DE, Abdelnabi M, Archambault A, Chamma N, Gaur S, Hammett D, Kandahari A, Khayrullina G, Kumar S, Lawrence S, Madden N, Mandelbaum M, Milnthorp H, Mohini S, Patel R, Peacock SJ, Perling E, Quintana A, Rahimi M, Ramirez K, Singhal R, Weeks C, Wong T, Gillis AT, Moore ZD, Savell CD, Watson R, Mel SF, Anilkumar AA, Bilinski P, Castillo R, Closser M, Cruz NM, Dai T, Garbagnati GF, Horton LS, Kim D, Lau JH, Liu JZ, Mach SD, Phan TA, Ren Y, Stapleton KE, Strelitz JM, Sunjed R, Stamm J, Anderson MC, Bonifield BG, Coomes D, Dillman A, Durchholz EJ, Fafara-Thompson AE, Gross MJ, Gygi AM, Jackson LE, Johnson A, Kocsisova Z, Manghelli JL, McNeil K, Murillo M, Naylor KL, Neely J, Ogawa EE, Rich A, Rogers A, Spencer JD, Stemler KM, Throm AA, Van Camp M, Weihbrecht K, Wiles TA, Williams MA, Williams M, Zoll K, Bailey C, Zhou L, Balthaser DM, Bashiri A, Bower ME, Florian KA, Ghavam N, Greiner-Sosanko ES, Karim H, Mullen VW, Pelchen CE, Yenerall PM, Zhang J, Rubin MR, Arias-Mejias SM, Bermudez-Capo AG, Bernal-Vega GV, Colon-Vazquez M, Flores-Vazquez A, Gines-Rosario M, Llavona-Cartagena IG, Martinez-Rodriguez JO, Ortiz-Fuentes L, Perez-Colomba EO, Perez-Otero J, Rivera E, Rodriguez-Giron LJ, Santiago-Sanabria AJ, Senquiz-Gonzalez AM, delValle FR, Vargas-Franco D, Velázquez-Soto KI, Zambrana-Burgos JD, Martinez-Cruzado JC, Asencio-Zayas L, Babilonia-Figueroa K, Beauchamp-Pérez FD, Belén-Rodríguez J, Bracero-Quiñones L, Burgos-Bula AP, Collado-Méndez XA, Colón-Cruz LR, Correa-Muller AI, Crooke-Rosado JL, Cruz-García JM, Defendini-Ávila M, Delgado-Peraza FM, Feliciano-Cancela AJ, Gónzalez-Pérez VM, Guiblet W, Heredia-Negrón A, Hernández-Muñiz J, Irizarry-González LN, Laboy-Corales ÁL, Llaurador-Caraballo GA, Marín-Maldonado F, Marrero-Llerena U, Martell-Martínez HA, Martínez-Traverso IM, Medina-Ortega KN, Méndez-Castellanos SG, Menéndez-Serrano KC, Morales-Caraballo CI, Ortiz-DeChoudens S, Ortiz-Ortiz P, Pagán-Torres H, Pérez-Afanador D, Quintana-Torres EM, Ramírez-Aponte EG, Riascos-Cuero C, Rivera-Llovet MS, Rivera-Pagán IT, Rivera-Vicéns RE, Robles-Juarbe F, Rodríguez-Bonilla L, Rodríguez-Echevarría BO, Rodríguez-García PM, Rodríguez-Laboy AE, Rodríguez-Santiago S, Rojas-Vargas ML, Rubio-Marrero EN, Santiago-Colón A, Santiago-Ortiz JL, Santos-Ramos CE, Serrano-González J, Tamayo-Figueroa AM, Tascón-Peñaranda EP, Torres-Castillo JL, Valentín-Feliciano NA, Valentín-Feliciano YM, Vargas-Barreto NM, Vélez-Vázquez M, Vilanova-Vélez LR, Zambrana-Echevarría C, MacKinnon C, Chung HM, Kay C, Pinto A, Kopp OR, Burkhardt J, Harward C, Allen R, Bhat P, Chang JH, Chen Y, Chesley C, Cohn D, DuPuis D, Fasano M, Fazzio N, Gavinski K, Gebreyesus H, Giarla T, Gostelow M, Greenstein R, Gunasinghe H, Hanson C, Hay A, He TJ, Homa K, Howe R, Howenstein J, Huang H, Khatri A, Kim YL, Knowles O, Kong S, Krock R, Kroll M, Kuhn J, Kwong M, Lee B, Lee R, Levine K, Li Y, Liu B, Liu L, Liu M, Lousararian A, Ma J, Mallya A, Manchee C, Marcus J, McDaniel S, Miller ML, Molleston JM, Diez CM, Ng P, Ngai N, Nguyen H, Nylander A, Pollack J, Rastogi S, Reddy H, Regenold N, Sarezky J, Schultz M, Shim J, Skorupa T, Smith K, Spencer SJ, Srikanth P, Stancu G, Stein AP, Strother M, Sudmeier L, Sun M, Sundaram V, Tazudeen N, Tseng A, Tzeng A, Venkat R, Venkataram S, Waldman L, Wang T, Yang H, Yu JY, Zheng Y, Preuss ML, Garcia A, Juergens M, Morris RW, Nagengast AA, Azarewicz J, Carr TJ, Chichearo N, Colgan M, Donegan M, Gardner B, Kolba N, Krumm JL, Lytle S, MacMillian L, Miller M, Montgomery A, Moretti A, Offenbacker B, Polen M, Toth J, Woytanowski J, Kadlec L, Crawford J, Spratt ML, Adams AL, Barnard BK, Cheramie MN, Eime AM, Golden KL, Hawkins AP, Hill JE, Kampmeier JA, Kern CD, Magnuson EE, Miller AR, Morrow CM, Peairs JC, Pickett GL, Popelka SA, Scott AJ, Teepe EJ, TerMeer KA, Watchinski CA, Watson LA, Weber RE, Woodard KA, Barnard DC, Appiah I, Giddens MM, McNeil GP, Adebayo A, Bagaeva K, Chinwong J, Dol C, George E, Haltaufderhyde K, Haye J, Kaur M, Semon M, Serjanov D, Toorie A, Wilson C, Riddle NC, Buhler J, Mardis ER, and Elgin SC more...
- Subjects
- Animals, Codon, Computational Biology, DNA Transposable Elements, Drosophila melanogaster genetics, Exons, Gene Rearrangement, Heterochromatin, Introns, Molecular Sequence Annotation, Polytene Chromosomes, Repetitive Sequences, Nucleic Acid, Selection, Genetic, Species Specificity, Drosophila genetics, Drosophila Proteins genetics, Evolution, Molecular, Genome, Genomics
- Abstract
The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.) more...
- Published
- 2015
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20. Defining the conformation of the estrogen receptor complex that controls estrogen-induced apoptosis in breast cancer.
- Author
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Obiorah I, Sengupta S, Curpan R, and Jordan VC
- Subjects
- Apoptosis drug effects, Breast Neoplasms chemically induced, Crystallography, X-Ray, Dose-Response Relationship, Drug, Estrogen Receptor alpha agonists, Estrogens chemistry, Estrogens pharmacology, Female, Humans, MCF-7 Cells, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Stilbenes chemistry, Stilbenes metabolism, Stilbenes pharmacology, Apoptosis physiology, Breast Neoplasms metabolism, Estrogen Receptor alpha chemistry, Estrogen Receptor alpha metabolism, Estrogens metabolism
- Abstract
Development of acquired antihormone resistance exposes a vulnerability in breast cancer: estrogen-induced apoptosis. Triphenylethylenes (TPEs), which are structurally similar to 4-hydroxytamoxifen (4OHT), were used for mechanistic studies of estrogen-induced apoptosis. These TPEs all stimulate growth in MCF-7 cells, but unlike the planar estrogens they block estrogen-induced apoptosis in the long-term estrogen-deprived MCF7:5C cells. To define the conformation of the TPE:estrogen receptor (ER) complex, we employed a previously validated assay using the induction of transforming growth factor α (TGFα) mRNA in situ in MDA-MB 231 cells stably transfected with wild-type ER (MC2) or D351G ER mutant (JM6). The assays discriminate ligand fit in the ER based on the extremes of published crystallography of planar estrogens or TPE antiestrogens. We classified the conformation of planar estrogens or angular TPE complexes as "estrogen-like" or "antiestrogen-like" complexes, respectively. The TPE:ER complexes did not readily recruit the coactivator steroid receptor coactivator-3 (SRC3) or ER to the PS2 promoter in MCF-7 and MCF7:5C cells, and molecular modeling showed that they prefer to bind to the ER in an antagonistic fashion, i.e., helix 12 not sealing the ligand binding domain (LBD) effectively, and therefore reduce critical SRC3 binding. The fully activated ER complex with helix 12 sealing the LBD is suggested to be the appropriate trigger to initiate rapid estrogen-induced apoptosis. more...
- Published
- 2014
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21. Scientific rationale for postmenopause delay in the use of conjugated equine estrogens among postmenopausal women that causes reduction in breast cancer incidence and mortality.
- Author
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Obiorah I and Jordan VC
- Subjects
- Aged, Animals, Apoptosis drug effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cardiovascular Diseases, Drug Resistance, Neoplasm, Estrogen Replacement Therapy adverse effects, Estrogen Replacement Therapy methods, Female, Humans, Middle Aged, Progestins administration & dosage, Progestins adverse effects, Risk Factors, Tamoxifen therapeutic use, Treatment Failure, Women's Health, Breast Neoplasms prevention & control, Estrogens, Conjugated (USP) therapeutic use, Postmenopause
- Abstract
High-dose synthetic estrogens were the first successful chemical therapy used in the treatment of metastatic breast cancer in postmenopausal women, and this approach became the standard of care in postmenopausal women with metastatic breast cancer between the 1950s and the end of the 1970s. The most recent analysis of the Women's Health Initiative estrogen-alone trial in hysterectomized women revealed a persistently significant decrease in the incidence of breast cancer and breast cancer mortality. Although estrogens are known to induce the proliferation of breast cancer cells, we have shown that physiologic concentrations induce apoptosis in breast cancer cells with long-term estrogen deprivation. We have developed laboratory models that illustrate the new biology of estrogen-induced apoptosis or growth to explain the effects of estrogen therapy. The key to the success of estrogen therapy lies in a sufficient period of withdrawal of physiologic estrogens (5-10 y) and the subsequent regrowth of nascent breast tumor cells that survive under estrogen-deprived conditions. These nascent tumors are now vulnerable to estrogen-induced apoptosis. more...
- Published
- 2013
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22. Progress in endocrine approaches to the treatment and prevention of breast cancer.
- Author
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Obiorah I and Jordan VC
- Subjects
- Antineoplastic Agents, Hormonal therapeutic use, Aromatase Inhibitors therapeutic use, Chemotherapy, Adjuvant, Drug Therapy, Combination, Female, Humans, Selective Estrogen Receptor Modulators therapeutic use, Tamoxifen therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms prevention & control
- Abstract
Tamoxifen had been the only available hormonal option for the systemic treatment for breast cancer from 1973 to 2000. Enormous efforts have led to the development of potent and selective third generation aromatase inhibitors including anastrozole, letrozole and exemestane. Due to their superior efficacy to tamoxifen, aromatase inhibitors are presently approved as first line agents for the treatment of advanced estrogen receptor (ER) positive breast cancer and adjuvant therapy in early ER positive early breast cancer in postmenopausal women. Selective ER Modulators (SERMS), tamoxifen and raloxifene are the only agents presently used in breast cancer prevention in high risk women and their use has increased substantially over the last decade. Third generations SERMS, lasofoxifene and bazedoxifene have shown significant reduction in bone loss compared to placebo in postmenopausal women and are currently approved in the European Union for the treatment of postmenopausal osteoporosis. This review outlines the current strategies employed in the use of endocrine therapy in the management and prevention of breast cancer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.) more...
- Published
- 2011
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23. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.
- Author
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Jordan VC, Obiorah I, Fan P, Kim HR, Ariazi E, Cunliffe H, and Brauch H
- Subjects
- Breast Neoplasms surgery, Chemotherapy, Adjuvant, Disease-Free Survival, Drug Administration Schedule, Estrogen Antagonists adverse effects, Female, Humans, Long-Term Care, Prognosis, Quality of Life, Receptors, Estrogen drug effects, Receptors, Estrogen metabolism, Risk Assessment, Survival Rate, Switzerland, Tamoxifen adverse effects, United States, Awards and Prizes, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Estrogen Antagonists therapeutic use, Tamoxifen therapeutic use
- Abstract
The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence., (Copyright © 2011 Elsevier Ltd. All rights reserved.) more...
- Published
- 2011
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24. Concomitant use of nonnucleoside analogue reverse transcriptase inhibitors and rifampicin in TB/HIV type 1-coinfected patients.
- Author
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Sathia L, Obiorah I, Taylor G, Kon O, O'Donoghue M, Gibbins S, Walsh J, and Winston A
- Subjects
- Adult, Alkynes, Antiretroviral Therapy, Highly Active, Benzoxazines pharmacokinetics, Chemical and Drug Induced Liver Injury prevention & control, Cyclopropanes, Drug Administration Schedule, Drug Monitoring, Female, HIV Infections complications, HIV Infections metabolism, Humans, Male, Nevirapine pharmacokinetics, Prospective Studies, Reverse Transcriptase Inhibitors pharmacokinetics, Treatment Outcome, Antibiotics, Antitubercular therapeutic use, Benzoxazines therapeutic use, HIV Infections drug therapy, HIV-1, Nevirapine therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Rifampin therapeutic use, Tuberculosis drug therapy
- Abstract
Pharmacokinetic interactions between rifampicin and nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) pose challenges in the treatment of TB/HIV coinfection. We describe NNRTI plasma concentrations (PC) and treatment outcomes in TB/HIV coinfected patients receiving rifampicin and NNRTIs concomitantly. Single center prospective data were collected on all TB/HIV-coinfected patients who received concomitant NNRTI and rifampicin between 2001 and 2005. Of 103 TB/HIV coinfected patients, 26 received concomitant rifampicin with efavirenz (EFV) and 17 with nevirapine (NVP). NNRTIs were commenced after rifampicin in 18/26 (69%) and 7/17 (41%) subjects treated with EFV and NVP, respectively. Of these 88% completed antituberculosis therapy. There were two (5%) deaths, both due to lymphoproliferative malignancy. Three (7%) patients transferred care or discontinued therapy. Of subjects 83% had normal liver function tests (LFTs) and 11% had Grade 1-2 and 6% Grade 3-4 LFT abnormalities during concomitant therapy. PCs were measured in 31 patients. The first PCs were within the therapeutic range in 5/7 on NVP 200 mg bd, 2/4 on NVP 300 mg bd, 3/7 EFV 600 mg od, and 7/13 on EFV 800 mg od. PCs were subtherapeutic in 4/11 (36%) and 3/20 (20%) subjects on NVP and EFV, respectively. No virological rebounds were observed. Of subjects receiving concomitant NVP or EFV with rifampicin, 64% and 80%, respectively, had therapeutic NNRTI PCs. Subtherapeutic PCs were not associated with virological failure. Good clinical outcomes and a low incidence of hepatotoxicity were observed. more...
- Published
- 2008
- Full Text
- View/download PDF
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