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31 results on '"Cornea, Virgilius"'

1. Efficacy and Safety of Ravulizumab in IgA Nephropathy: A Phase 2 Randomized Double-Blind Placebo-Controlled Trial

Author

Lafayette, Richard, Tumlin, James, Fenoglio, Roberta, Kaufeld, Jessica, Pérez Valdivia, Miguel Angel, Wu, Mai-Szu, Susan Huang, Shih-Han, Alamartine, Eric, Kim, Sung Gyun, Yee, Min, Kateifides, Andreas, Rice, Kara, Garlo, Katherine, Barratt, Jonathan, Ranganathan, Dwarakanathan, Wolley, Martin, Tan, Sven-Jean, Chow, Kevin, Tin Law, Mandy Man, Nichols, Kathleen, See, Emily Jan, Steinberg, Adam Glenn, Tiong, Mark, Susan Huang, Shih-Han, Jain, Arsh, Laurin, Louis-Phillipe, Lafrance, Jean-Phillipe, Lamarche, Caroline, Philibert, David, Agharazii, Mohsen, Mac-Way, Fabrice, Alamartine, Eric, Maillard, Nicolas, Mariat, Christophe, Masson, Ingrid, Boffa, Jean-Jacques, Cez, Alexandre, Esteve, Emmanuel, Marchal, Armance, Chauveau, Dominique, Belliere, Julie, Monrozeis, Pauline Bernadet, Colliou, Eloise, Faguer, Stanislas, Huart, Antoine, Ribes, David, Garrouste, Cyril, Heng, Anne-Elisabeth, Mayet, Valentin, Philipponnet, Carole, Moulin, Bruno, Parvez, Laura Braun, Vargas, Gabriela Gautier, Perrin, Peggy, Ohlmann, Sophie, Olagne, Jerome, Haller, Herman, Schmidt-Ott, Kai, Bahlmann-Kroll, Elisabeth, Kaufeld, Jessica, Reinhardt, Martin, Gaeckler, Anja, Dolff, Sebastian, Wilde, Benjamin, Schreiber, Adrian, Koch, Nadine, Seelow, Evelyn, Alberici, Federico, Affatato, Stefania, Mainardi, Allesandro, Mescia, Federica, Scolari, Francesco, Tedesco, Martina, Venturini, Margherita, Cirami, Calogero Lino, Antognoli, Giulia, Caroti, Leonardo, Gualtiero, Gabriele, Moscato, Marcos, Trivioli, Giorgio, La Manna, Gaetano, Baraldi, Olga, Campus, Anita, Stefanini, Carlo, Vischini, Gisella, Roccatello, Dario, Fenoglio, Roberta, Lalloni, Stefania, Sciascia, Savino, Nowicki, Michal, Holub, Tomasz, Kieszek, Błażej, Makówka, Agnieszka, Masajtis, Anna, Piechota, Piotr, Tylski, Maciej, Han, Seung Hyeok, Lee, Sang-Won, Lim, Beon Jin, Pyo, Jung Yoon, Kim, Sung Gyun, An, Jung Nam, Chung, Byung Ha, Kim, Jwa-Kyung, Lee, Hyung Seok, Seo, Young Il, Song, Young Rim, Lee, Hajeong, Park, Sehoon, Han, Seung Seok, Kim, Dong Ki, Kim, Yong Chul, Ryu, Hyunjin, Agraz, Irene, Bolufer, Monica, Hernandez, Josefina Cortés, Gabaldon, Maria Alejandra, Soler, Maria José, Arroyo, David, Carbayo, Javier, Diezhandino, Marian Goicoechea, Perez de Jose, Ana, Guzman, Ursula Verdalles, Moreno, Eduardo Verde, García, Olga Gracia, Albines Fiestas, Zoila Stany, Aladren Gonzalvo, Daniel Joaquin, Gonzalez, Andrea Bernal, Lou Arnal, Luis Miguel, Villarroya, Cristina Medrano, Lopez, Paula Mora, Moncasi, Eduardo Parra, Martin Conde, Maria Luisa, Gonzalez, Jorge, Jatem, Elias, Estor, Aida Moroba, Medrano, Alfons Segarra, Moreno, Antolina Rodriguez, Sanchez de la Nieta, Dolores, Garcia, Clara, Velo, Mercedes, Rocha Castilla, Jose Luis, Bermejo, Sheila, Mendoza, Manuel Lopez, Pérez Valdivia, Miguel Angel, Rojas, Remedios Toledo, Hidalgo, Pilar, Sanchez, Teresa Vazquez, Uriol Rivera, Miguel Giovanni, Fuentes, Mario Lado, Chiu, Yi-Wen, Chang, Jer-Ming, Chen, Hung-Chun, Hsiao, Mei-Ju, Hung, Chi-Chih, Hwang, Shang-Jih, Kuo, Mei Chuan, Kuo, Hung-Tien, Lim, Lee-Moay, Lee, Jia-Jung, Lai, Ping Chin, Chang, David Ray, Chang, Yun-Lun, Chen, I-Ru, Hsieh, Ming-Han, Huang, Chiu-Ching, Kuo, Huey-Liang, Wang, I-Kuan, Wu, Mai-Szu, Chen, Yu-Wei, Chiu, I-Jen, Hsu, Yung-Ho, Hung, Lie-Yee, Laio, Chia-Te, Lin, Gua-Hong, Lin, Yuh-Feng, Wu, Mei-Yi, Zheng, Cai-Mei, Lightstone, Elizabeth, Cairns, Tommy, Mcadoo, Stephen, Medjeral-Thomas, Nicholas, Pickering, Matthew, Robson, Michael, Sinha, Smeeta, Chukwu, Chukwuma, Storrar, Joshua, Ahmed, Sadiq, Cornea, Virgilius, Nadim, Amina, Sims, Tyler, Awad, Ahmed, Aldahan, Mohammed, Clark, Laurie, Lustig, Ryan, Niles, John, Jeyabalan, Anushya, Zonozi, Reza, Tumlin, James, and Paxton, William

Published
2024
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2. Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis

Author

Barbour, Sean J., Coppo, Rosanna, Er, Lee, Pillebout, Evangeline, Russo, Maria Luisa, Alpers, Charles E., Fogo, Agnes B., Ferrario, Franco, Jennette, J. Charles, Roberts, Ian S.D., Cook, H. Terence, Ding, Jie, Su, Baige, Zhong, Xuhui, Fervenza, Fernando C., Zand, Ladan, Peruzzi, Licia, Lucchetti, Laura, Katafuchi, Ritsuko, Shima, Yuko, Yoshikawa, Norishige, Ichikawa, Daisuke, Suzuki, Yusuke, Murer, Luisa, Wyatt, Robert J., Park, Catherine, Nelson, Raoul D., Narus, JoAnn H., Wenderfer, Scott, Geetha, Duvuru, Daugas, Eric, Monteiro, Renato C., Nakatani, Shinya, Mastrangelo, Antonio, Nuutinen, Matti, Koskela, Mikael, Weber, Lutz T., Hackl, Agnes, Pohl, Martin, Pecoraro, Carmine, Tsuboi, Nobuo, Yokoo, Takashi, Takafumi, Ito, Fujimoto, Shouichi, Conti, Giovanni, Santoro, Domenico, Materassi, Marco, Zhang, Hong, Shi, Sufang, Liu, Zhi-Hong, Tesar, Vladimir, Maixnerova, Dita, Avila-Casado, Carmen, Bajema, Ingeborg, Barreca, Antonella, Becker, Jan U., Comstock, Jessica M., Cornea, Virgilius, Eldin, Karen, Hernandez, Loren Herrera, Hou, Jean, Joh, Kensuke, Lin, Mercury, Messias, Nidia, Muda, Andrea Onetti, Pagni, Fabio, Diomedi-Camassei, Francesca, Tokola, Heikki, DʼArmiento, Maria, Seidl, Maximilian, Rosenberg, Avi, Sannier, Aurélie, Soares, Maria Fernanda, Wang, Suxia, Zeng, Caihong, and Haas, Mark

Published
2024
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5. Anti-neoplastic sulfonamides alter the metabolic homeostasis and disrupt the suppressor activity of regulatory T cells

Author

Gedaly, Roberto, Cornea, Virgilius, Turcios, Lilia, Edmisson, Jacob S., Harris, Dwight D., Watt, David S., Chapelin, Fanny, Khurana, Aman, Mei, Xiaonan, Liu, Chunming, Taylor, Isaac, Gonzalez-Valdivieso, Juan, Mitchel, Hunter, Ruffing, Alexis, Chishti, Asir, Orozco, Gabriel, Zwischenberger, Joseph, Evers, B. Mark, and Marti, Francesc

Published
2022
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7. Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis

Author

Barbour, S, Coppo, R, Er, L, Pillebout, E, Russo, M, Alpers, C, Fogo, A, Ferrario, F, Jennette, J, Roberts, I, Cook, H, Ding, J, Su, B, Zhong, X, Fervenza, F, Zand, L, Peruzzi, L, Lucchetti, L, Katafuchi, R, Shima, Y, Yoshikawa, N, Ichikawa, D, Suzuki, Y, Murer, L, Wyatt, R, Nelson, R, Narus, J, Wenderfer, S, Geetha, D, Daugas, E, Monteiro, R, Nakatani, S, Mastrangelo, A, Nuutinen, M, Koskela, M, Weber, L, Hackl, A, Pohl, M, Pecoraro, C, Tsuboi, N, Yokoo, T, Takafumi, I, Fujimoto, S, Conti, G, Santoro, D, Materassi, M, Zhang, H, Shi, S, Liu, Z, Tesar, V, Maixnerova, D, Avila-Casado, C, Bajema, I, Barreca, A, Becker, J, Comstock, J, Cornea, V, Eldin, K, Hernandez, L, Hou, J, Joh, K, Lin, M, Messias, N, Muda, A, Pagni, F, Diomedi-Camassei, F, Tokola, H, D’Armiento, M, Seidl, M, Rosenberg, A, Sannier, A, Soares, M, Wang, S, Zeng, C, Haas, M, Barbour, Sean J., Coppo, Rosanna, Er, Lee, Pillebout, Evangeline, Russo, Maria Luisa, Alpers, Charles E., Fogo, Agnes B., Ferrario, Franco, Jennette, J. Charles, Roberts, Ian S. D., Cook, H. Terence, Ding, Jie, Su, Baige, Zhong, Xuhui, Fervenza, Fernando C., Zand, Ladan, Peruzzi, Licia, Lucchetti, Laura, Katafuchi, Ritsuko, Shima, Yuko, Yoshikawa, Norishige, Ichikawa, Daisuke, Suzuki, Yusuke, Murer, Luisa, Wyatt, Robert J., Nelson, Raoul D., Narus, JoAnn H., Wenderfer, Scott, Geetha, Duvuru, Daugas, Eric, Monteiro, Renato C., Nakatani, Shinya, Mastrangelo, Antonio, Nuutinen, Matti, Koskela, Mikael, Weber, Lutz T, Hackl, Agnes, Pohl, Martin, Pecoraro, Carmine, Tsuboi, Nobuo, Yokoo, Takashi, Takafumi, Ito, Fujimoto, Shouichi, Conti, Giovanni, Santoro, Domenico, Materassi, Marco, Zhang, Hong, Shi, Sufang, Liu, Zhi-Hong, Tesar, Vladimir, Maixnerova, Dita, Avila-Casado, Carmen, Bajema, Ingeborg, Barreca, Antonella, Becker, Jan U., Comstock, Jessica M., Cornea, Virgilius, Eldin, Karen, Hernandez, Loren Herrera, Hou, Jean, Joh, Kensuke, Lin, Mercury, Messias, Nidia, Muda, Andrea Onetti, Pagni, Fabio, Diomedi-Camassei, Francesca, Tokola, Heikki, D’Armiento, Maria, Seidl, Maximilian, Rosenberg, Avi, Sannier, Aurélie, Soares, Maria Fernanda, Wang, Suxia, Zeng, Caihong, Haas, Mark, Barbour, S, Coppo, R, Er, L, Pillebout, E, Russo, M, Alpers, C, Fogo, A, Ferrario, F, Jennette, J, Roberts, I, Cook, H, Ding, J, Su, B, Zhong, X, Fervenza, F, Zand, L, Peruzzi, L, Lucchetti, L, Katafuchi, R, Shima, Y, Yoshikawa, N, Ichikawa, D, Suzuki, Y, Murer, L, Wyatt, R, Nelson, R, Narus, J, Wenderfer, S, Geetha, D, Daugas, E, Monteiro, R, Nakatani, S, Mastrangelo, A, Nuutinen, M, Koskela, M, Weber, L, Hackl, A, Pohl, M, Pecoraro, C, Tsuboi, N, Yokoo, T, Takafumi, I, Fujimoto, S, Conti, G, Santoro, D, Materassi, M, Zhang, H, Shi, S, Liu, Z, Tesar, V, Maixnerova, D, Avila-Casado, C, Bajema, I, Barreca, A, Becker, J, Comstock, J, Cornea, V, Eldin, K, Hernandez, L, Hou, J, Joh, K, Lin, M, Messias, N, Muda, A, Pagni, F, Diomedi-Camassei, F, Tokola, H, D’Armiento, M, Seidl, M, Rosenberg, A, Sannier, A, Soares, M, Wang, S, Zeng, C, Haas, M, Barbour, Sean J., Coppo, Rosanna, Er, Lee, Pillebout, Evangeline, Russo, Maria Luisa, Alpers, Charles E., Fogo, Agnes B., Ferrario, Franco, Jennette, J. Charles, Roberts, Ian S. D., Cook, H. Terence, Ding, Jie, Su, Baige, Zhong, Xuhui, Fervenza, Fernando C., Zand, Ladan, Peruzzi, Licia, Lucchetti, Laura, Katafuchi, Ritsuko, Shima, Yuko, Yoshikawa, Norishige, Ichikawa, Daisuke, Suzuki, Yusuke, Murer, Luisa, Wyatt, Robert J., Nelson, Raoul D., Narus, JoAnn H., Wenderfer, Scott, Geetha, Duvuru, Daugas, Eric, Monteiro, Renato C., Nakatani, Shinya, Mastrangelo, Antonio, Nuutinen, Matti, Koskela, Mikael, Weber, Lutz T, Hackl, Agnes, Pohl, Martin, Pecoraro, Carmine, Tsuboi, Nobuo, Yokoo, Takashi, Takafumi, Ito, Fujimoto, Shouichi, Conti, Giovanni, Santoro, Domenico, Materassi, Marco, Zhang, Hong, Shi, Sufang, Liu, Zhi-Hong, Tesar, Vladimir, Maixnerova, Dita, Avila-Casado, Carmen, Bajema, Ingeborg, Barreca, Antonella, Becker, Jan U., Comstock, Jessica M., Cornea, Virgilius, Eldin, Karen, Hernandez, Loren Herrera, Hou, Jean, Joh, Kensuke, Lin, Mercury, Messias, Nidia, Muda, Andrea Onetti, Pagni, Fabio, Diomedi-Camassei, Francesca, Tokola, Heikki, D’Armiento, Maria, Seidl, Maximilian, Rosenberg, Avi, Sannier, Aurélie, Soares, Maria Fernanda, Wang, Suxia, Zeng, Caihong, and Haas, Mark

Abstract

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classificatio

Published
2024

10. Ki-67 Testing in Breast Cancer: Assessing Variability With Scoring Methods and Specimen Types and the Potential Subsequent Impact on Therapy Eligibility

Author

Bocklage, Therese, Cornea, Virgilius, Hickey, Caylin, Miller, Justin, Moss, Jessica, Chambers, Mara, and Bachert, S. Emily

Abstract

Abemaciclib was originally FDA approved for patients with ER-positive/HER2-negative breast cancer with Ki-67 expression ≥20%. However, there were no guidelines provided on which specimen to test or which scoring method to use. We performed a comprehensive study evaluating the variation in Ki-67 expression in breast specimens from 50 consecutive patients who could have been eligible for abemaciclib therapy. Three pathologists with breast expertise each performed a blinded review with 3 different manual scoring methods [estimated (EST), unweighted (UNW), and weighted (WT) (WT recommended by the International Ki-67 in Breast Cancer Working Group)]. Quantitative image analysis (QIA) using the HALO platform was also performed. Three different specimen types [core needle biopsy (CNB) (n=63), resection (RES) (n=52), and axillary lymph node metastasis (ALN) (n=50)] were evaluated for each patient. The average Ki-67 for all specimens was 14.68% for EST, 14.46% for UNW, 14.15% for WT, and 11.15% for QIA. For the manual methods, the range between the lowest and highest Ki-67 for each specimen between the 3 pathologists was 8.44 for EST, 5.94 for WT, and 5.93 for UNW. The WT method limited interobserver variability with ICC1=0.959 (EST ICC1=0.922 and UNW=0.949). Using the aforementioned cutoff of Ki-67 ≥20% versus <20% to determine treatment eligibility, the averaged EST method yields 20 of 50 patients (40%) who would have been treatment-eligible, versus 15 (30%) for the UNW, 17 (34%) for the WT, and 12 (24%) for the QIA. There was no statistically significant difference in Ki-67 among the 3 specimen types. The average Ki-67 difference was 4.36 for CNB vs RES, 6.95 for CNB versus ALN, and RES versus ALN (P=0.93, 0.99, and 0.94, respectively). Our study concludes that further refinement in Ki-67 scoring is advisable to reduce clinically significant variation.

Published
2024
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17. Cytopathological characteristics of solitary fibrous tumour involving the pancreas by fine needle aspiration: Making an accurate preoperative diagnosis in an uncommon location.

Author

Jones, Victoria M., Wangsiricharoen, Sintawat, Cornea, Virgilius, Bocklage, Therese J., Ali, Syed Z., and Allison, Derek B.

Subjects
NEEDLE biopsy, PLEURA, PANCREAS, PLASMACYTOMA, ANATOMICAL pathology, GENE fusion, SURGICAL diagnosis, CYTOLOGY
Abstract

Background: Solitary fibrous tumour (SFT) is a unique mesenchymal neoplasm with classic features on histology and is characterised by the NAB2‐STAT6 gene fusion. There are rare reports of SFTs with pancreatic involvement and only two cases in the literature reporting its features by preoperative fine needle aspiration (FNA). Herein, we characterise the cytomorphological features of four SFTs involving the pancreas by FNA to establish a preoperative diagnostic approach. Methods: The anatomic pathology archives of two academic medical centres were searched to identify patients with a pancreatic FNA cytology specimen and a confirmed diagnosis of SFT by surgical resection. The clinical history, pathological diagnosis, cytomorphological findings, and results of immunohistochemistry (IHC) were reviewed. Results: Four SFTs were identified from four patients with a median age of 59 years. The morphological features were variable but most frequently showed a bland spindled‐to‐epithelioid proliferation in fragments and single cells with small, oval, elongated, and hypochromatic nuclei in a haphazard arrangement with or without dense collagen. One tumour presented with a concurrent metastasis and showed a pure epithelioid component with necrosis and enlarged, hyperchromatic nuclei with conspicuous nucleoli and scattered mitoses. IHC was necessary for all diagnoses which were confirmed by surgical resection. Conclusions: SFTs with pancreatic involvement are rare, and non‐specific features and tumour heterogeneity can pose a diagnostic challenge on FNA; however, IHC can be used to make a definitive diagnosis. As a result, FNA is a simple, safe, cost‐effective, and accurate approach that can be used to diagnose SFT in the pancreas. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Prevalence, Risk Factors, Treatment, and Overall Impact of BK Viremia on Kidney Transplantation

Author

Malik, Omar, primary, Saleh, Sherif, additional, Suleiman, Belal, additional, Ashqar, Bilal, additional, Maibam, Amita, additional, Yaseen, Maria, additional, Elrefaei, Amro, additional, Hines, Abigail, additional, Cornea, Virgilius, additional, El-Husseini, Amr, additional, Mei, Xiaonan, additional, Gedaly, Roberto, additional, Castellanos, Ana Lia, additional, and Waid, Thomas, additional

Published
2019
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19. Impact of human leukocyte antigen and calculated panel reactive antibody on BK viremia in kidney transplant recipients: A single‐center experience and literature review

Author

El‐Husseini, Amr, primary, Hassan, Waleed, additional, Yaseen, Maria, additional, Suleiman, Belal, additional, Saleh, Sherif, additional, Malik, Omar, additional, Ashqar, Hasan, additional, Maibam, Amita, additional, Mei, Xiaonan, additional, Castellanos, Ana L., additional, Cornea, Virgilius, additional, Gedaly, Roberto, additional, and Waid, Thomas, additional

Published
2019
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22. Fulminant Necrotizing Eosinophilic Myocarditis

Author

George, Bennet, Hager, Matthew, Cornea, Virgilius, O'Connor, William, and Guglin, Maya

Subjects
Medical Pathology
Abstract

Acute eosinophilic myocarditis is a relatively rare disorder with serious morbidity and mortality. Due to its infrequency, standardized management guidelines are wanting. We present a case of acute, necrotizing eosinophilic myocarditis requiring several levels of critical care. We reviewed similar cases reported in the literature to highlight common clinical features, describe natural disease course and associated complications, and review varying approaches to medical therapy.

Published
2016
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23. Adequate histologic sampling of breast magnetic resonance imaging--guided core needle biopsy

Author

Cornea, Virgilius, Jaffer, Shabnam, Bleiweiss, Ira J., and Nagi, Chandandeep

Subjects
Magnetic resonance imaging -- Usage, Mammography -- Usage, Breast examination
Abstract

* Context.--The increasing use of contrast-enhanced magnetic resonance imaging (MRI) of the breast as a valuable adjunct to mammography and ultrasound in the detection of breast lesions, in association with needle core biopsy taken from the suspicious areas, has major workload implications for histopathology laboratories wherever breast MRI is practiced. Objective.--To establish the number of histologic levels necessary for the evaluation of breast MRI-guided needle core biopsy specimens taken from suspicious areas on breast MRI examination. Design.--Retrospective histologic review of a series of breast MRI-guided core needle biopsies, initially examined routinely at 4 levels, in the Pathology Department at Mount Sinai School of Medicine in New York, New York. Results.--Accurate diagnostic classification was possible after examination of the first level in 95.4% of cases. For a small group of patients (4.4%), 4 levels were considered to provide additional useful information, although this information did not alter the diagnosis. In only a single case (0.2%) was it likely that routine examination of 4 levels could have led to an incidental finding of a very small intraductal papilloma (0.15 cm) present only at the second histologic level. However, this incidental finding would have not changed the patient outcome. Conclusions.--Needle core biopsies for MRI-detected abnormalities should be routinely examined at only 1 level. Further levels may be needed in occasional cases to identify more conclusively an associated pathologic abnormality and may be of particular value when assessing atypical intraductal proliferative epithelial lesions., Within the last 10 years, contrast-enhanced magnetic resonance imaging (MRI) of the breast has gained recognition as a valuable adjunct to mammography and ultrasound in the detection of breast lesions [...]

Published
2009

29. Evidence of the immunomodulatory role of dual PI3K/ mTOR inhibitors in transplantation: an experimental study in mice.

Author

Vilchez, Valery, Turcios, Lilia, Coquillard, Cristin L., Gedaly, Roberto, Marti, Francesc, Mitov, Mihail I., Butterfield, David A., Brandon, Ja Anthony, and Cornea, Virgilius

Subjects
T cells, TRANSPLANTATION of organs, tissues, etc., LABORATORY mice, RAPAMYCIN, IMMUNOSUPPRESSION
Abstract

The PI3K/ mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/ mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/ mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/ mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/ mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation. [ABSTRACT FROM AUTHOR]

Published
2017
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