432 results on '"Marincola, Francesco"'
Search Results
2. Shifting the paradigm: engaging multicellular networks for cancer therapy
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Hu, Joyce, Ascierto, Paolo, Cesano, Alessandra, Herrmann, Volker, and Marincola, Francesco M.
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- 2024
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3. Tyrosine kinase signaling-independent MET-targeting with CAR-T cells
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Qin, Anna, Qin, Yuan, Lee, Joseph, Musket, Anna, Ying, Mingyao, Krenciute, Giedre, Marincola, Francesco M., Yao, Zhi Q., Musich, Phillip R., and Xie, Qian
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- 2023
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4. Advancing personalized medicine in brain cancer: exploring the role of mRNA vaccines
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Lin, Feng, Lin, Emma Z., Anekoji, Misa, Ichim, Thomas E., Hu, Joyce, Marincola, Francesco M., Jones, Lawrence D., Kesari, Santosh, and Ashili, Shashaanka
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- 2023
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5. Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions
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Myint, Melissa, Oppedisano, Francesca, De Giorgi, Valeria, Kim, Byeong-Moo, Marincola, Francesco M., Alter, Harvey J., and Nesci, Salvatore
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- 2023
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6. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances
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Maalej, Karama Makni, Merhi, Maysaloun, Inchakalody, Varghese P., Mestiri, Sarra, Alam, Majid, Maccalli, Cristina, Cherif, Honar, Uddin, Shahab, Steinhoff, Martin, Marincola, Francesco M., and Dermime, Said
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- 2023
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7. Immunogenic cell death in cancer: concept and therapeutic implications
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Galluzzi, Lorenzo, Kepp, Oliver, Hett, Erik, Kroemer, Guido, and Marincola, Francesco M.
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- 2023
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8. Nanoscale, antigen encounter-dependent, IL-12 delivery by CAR T cells plus PD-L1 blockade for cancer treatment
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Yang, Zhifen, Pietrobon, Violena, Bobbin, Maggie, Stefanson, Ofir, Yang, Jin, Goswami, Angshumala, Alphson, Bennett, Choi, Hana, Magallanes, Khristina, Cai, Qi, Barrett, David, Wang, Bing, Qi, Lei S., and Marincola, Francesco M.
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- 2023
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9. Current strategies employed in the manipulation of gene expression for clinical purposes
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Tsai, Hsing-Chuan, Pietrobon, Violena, Peng, Maoyu, Wang, Suning, Zhao, Lihong, Marincola, Francesco M., and Cai, Qi
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- 2022
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10. Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma
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Sumner, Whitney, Ray, Xenia, Sutton, Leisa, Rebibo, Daniel, Marincola, Francesco, Sanghvi, Parag, Moiseenko, Vitali, and Deichaite, Ida
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- 2021
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11. Hypoxia and the phenomenon of immune exclusion
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Pietrobon, Violena and Marincola, Francesco M.
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- 2021
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12. Contextual reprogramming of CAR-T cells for treatment of HER2+ cancers
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Yang, Zhifen, Li, Lingyu, Turkoz, Ahu, Chen, Pohan, Harari-Steinfeld, Rona, Bobbin, Maggie, Stefanson, Ofir, Choi, Hana, Pietrobon, Violena, Alphson, Bennett, Goswami, Angshumala, Balan, Vitaly, Kearney, Alper, Patel, Dharmesh, Yang, Jin, Inel, Damla, Vinod, Veena, Cesano, Alessandra, Wang, Bing, Roh, Kyung-Ho, Qi, Lei S., and Marincola, Francesco M.
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- 2021
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13. Lentiviral delivery of combinatorial CAR/CRISPRi circuit into human primary T cells is enhanced by TBK1/IKKɛ complex inhibitor BX795
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Li, Lingyu, Gao, Yuan, Srivastava, Richa, Wang, Wei, Xiong, Qinghui, Fang, Zhiming, Pelayo, Alejandra, Denson, Carolyn, Goswami, Angshumala, Harari-Steinfeld, Rona, Yang, Zhifen, Weng, Lihong, Qi, Lei Stanley, and Marincola, Francesco M.
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- 2020
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14. Differential responsiveness to BRAF inhibitors of melanoma cell lines BRAF V600E-mutated
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Al Hashmi, Muna, Sastry, Konduru S., Silcock, Lee, Chouchane, Lotfi, Mattei, Valentina, James, Nicola, Mathew, Rebecca, Bedognetti, Davide, De Giorgi, Valeria, Murtas, Daniela, Liu, Wei, Chouchane, Aouatef, Temanni, Ramzi, Seliger, Barbara, Wang, Ena, Marincola, Francesco M., and Tomei, Sara
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- 2020
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15. A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
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Mirandola, Leonardo, Chiriva-Internati, Maurizio, Bresalier, Robert, Piccotti, Lucia, Grizzi, Fabio, and Marincola, Francesco M.
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- 2019
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16. Preliminary report of a novel formulation of clinical-grade, fully matured, tumor-associated peptide-loaded dendritic cells for cancer immunotherapy
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Mirandola, Leonardo, Chiriva-Internati, Maurizio, Bresalier, Robert, Marincola, Francesco M., Figueroa, Jose A., and Dahlbeck, Scott
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- 2019
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17. First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells
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Minev, Boris R., Lander, Elliot, Feller, John F., Berman, Mark, Greenwood, Bernadette M., Minev, Ivelina, Santidrian, Antonio F., Nguyen, Duong, Draganov, Dobrin, Killinc, Mehmet O., Vyalkova, Anna, Kesari, Santosh, McClay, Edward, Carabulea, Gabriel, Marincola, Francesco M., Butterfield, Lisa H., and Szalay, Aladar A.
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- 2019
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18. Perspectives in melanoma: meeting report from the Melanoma Bridge (November 29th–1 December 1st, 2018, Naples, Italy)
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Ascierto, Paolo A., Agarwala, Sanjiv S., Botti, Gerardo, Budillon, Alfredo, Davies, Michael A., Dummer, Reinhard, Ernstoff, Marc, Ferrone, Soldano, Formenti, Silvia, Gajewski, Thomas F., Garbe, Claus, Hamid, Omid, Lo, Roger S., Luke, Jason J., Michielin, Oliver, Palmieri, Giuseppe, Zitvogel, Laurence, Marincola, Francesco M., Masucci, Giuseppe, Caracò, Corrado, Thurin, Magdalena, and Puzanov, Igor
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- 2019
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19. Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop
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Bedognetti, Davide, Ceccarelli, Michele, Galluzzi, Lorenzo, Lu, Rongze, Palucka, Karolina, Samayoa, Josue, Spranger, Stefani, Warren, Sarah, Wong, Kwok-Kin, Ziv, Elad, Chowell, Diego, Coussens, Lisa M., De Carvalho, Daniel D., DeNardo, David G., Galon, Jérôme, Kaufman, Howard L., Kirchhoff, Tomas, Lotze, Michael T., Luke, Jason J., Minn, Andy J., Politi, Katerina, Shultz, Leonard D., Simon, Richard, Thórsson, Vésteinn, Weidhaas, Joanne B., Ascierto, Maria Libera, Ascierto, Paolo Antonio, Barnes, James M., Barsan, Valentin, Bommareddy, Praveen K., Bot, Adrian, Church, Sarah E., Ciliberto, Gennaro, De Maria, Andrea, Draganov, Dobrin, Ho, Winson S., McGee, Heather M., Monette, Anne, Murphy, Joseph F., Nisticò, Paola, Park, Wungki, Patel, Maulik, Quigley, Michael, Radvanyi, Laszlo, Raftopoulos, Harry, Rudqvist, Nils-Petter, Snyder, Alexandra, Sweis, Randy F., Valpione, Sara, Zappasodi, Roberta, Butterfield, Lisa H., Disis, Mary L., Fox, Bernard A., Cesano, Alessandra, Marincola, Francesco M., and Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups
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- 2019
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20. Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop
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Bedognetti, Davide, Ceccarelli, Michele, Galluzzi, Lorenzo, Lu, Rongze, Palucka, Karolina, Samayoa, Josue, Spranger, Stefani, Warren, Sarah, Wong, Kwok-Kin, Ziv, Elad, Chowell, Diego, Coussens, Lisa M., De Carvalho, Daniel D., DeNardo, David G., Galon, Jérôme, Kaufman, Howard L., Kirchhoff, Tomas, Lotze, Michael T., Luke, Jason J., Minn, Andy J., Politi, Katerina, Shultz, Leonard D., Simon, Richard, Thórsson, Vésteinn, Weidhaas, Joanne B., Ascierto, Maria Libera, Ascierto, Paolo Antonio, Barnes, James M., Barsan, Valentin, Bommareddy, Praveen K., Bot, Adrian, Church, Sarah E., Ciliberto, Gennaro, De Maria, Andrea, Draganov, Dobrin, Ho, Winson S., McGee, Heather M., Monette, Anne, Murphy, Joseph F., Nisticò, Paola, Park, Wungki, Patel, Maulik, Quigley, Michael, Radvanyi, Laszlo, Raftopoulos, Harry, Rudqvist, Nils-Petter, Snyder, Alexandra, Sweis, Randy F., Valpione, Sara, Zappasodi, Roberta, Butterfield, Lisa H., Disis, Mary L., Fox, Bernard A., Cesano, Alessandra, Marincola, Francesco M., and Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups
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- 2019
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21. Monoallelic expression in melanoma
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Silcock, Lee, Almabrazi, Hakeem, Mokrab, Younes, Jithesh, Puthen, Al-Hashmi, Muna, James, Nicola, Mathew, Rebecca, Mattei, Valentina, Bedognetti, Davide, Lessi, Francesca, Temanni, Ramzi, Seliger, Barbara, Al-Ali, Rashid, Marincola, Francesco M., Wang, Ena, and Tomei, Sara
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- 2019
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22. Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28–29 2017, Doha, Qatar)
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Deola, Sara, Guerrouahen, Bella S., Sidahmed, Heba, Al-Mohannadi, Anjud, Elnaggar, Muhammad, Elsadig, Ramaz, Abdelalim, Essam M., Petrovski, Goran, Gadina, Massimo, Thrasher, Adrian, Wels, Winfried S., Hunger, Stephen P., Wang, Ena, Marincola, Francesco M., ATH Consortium, Maccalli, Cristina, and Cugno, Chiara
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- 2018
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23. Unleashing endogenous TNF-alpha as a cancer immunotherapeutic
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Josephs, Steven F., Ichim, Thomas E., Prince, Stephen M., Kesari, Santosh, Marincola, Francesco M., Escobedo, Anton Rolando, and Jafri, Amir
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- 2018
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24. Perspectives in melanoma: Meeting report from the Melanoma Bridge (30 November–2 December, 2017, Naples, Italy)
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Ascierto, Paolo A., Puzanov, Igor, Agarwala, Sanjiv S., Bifulco, Carlo, Botti, Gerardo, Caracò, Corrado, Ciliberto, Gennaro, Davies, Michael A., Dummer, Reinhard, Ferrone, Soldano, Gajewski, Thomas F., Garbe, Claus, Luke, Jason J., Marincola, Francesco M., Masucci, Giuseppe, Mehnert, Janice M., Mozzillo, Nicola, Palmieri, Giuseppe, Postow, Michael A., Schoenberger, Stephen P., Wang, Ena, and Thurin, Magdalena
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- 2018
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25. Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA)
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Danaher, Patrick, Warren, Sarah, Lu, Rongze, Samayoa, Josue, Sullivan, Amy, Pekker, Irena, Wallden, Brett, Marincola, Francesco M., and Cesano, Alessandra
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- 2018
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26. Immune oncology, immune responsiveness and the theory of everything
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Turan, Tolga, Kannan, Deepti, Patel, Maulik, Matthew Barnes, J., Tanlimco, Sonia G., Lu, Rongze, Halliwill, Kyle, Kongpachith, Sarah, Kline, Douglas E., Hendrickx, Wouter, Cesano, Alessandra, Butterfield, Lisa H., Kaufman, Howard L., Hudson, Thomas J., Bedognetti, Davide, Marincola, Francesco, and Samayoa, Josue
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- 2018
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27. The influence of diet on anti-cancer immune responsiveness
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Soldati, Laura, Di Renzo, Laura, Jirillo, Emilio, Ascierto, Paolo A., Marincola, Francesco M., and De Lorenzo, Antonino
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- 2018
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28. The need for a network to establish and validate predictive biomarkers in cancer immunotherapy
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Masucci, Giuseppe V., Cesano, Alessandra, Eggermont, Alexander, Fox, Bernard A., Wang, Ena, Marincola, Francesco M., Ciliberto, Gennaro, Dobbin, Kevin, Puzanov, Igor, Taube, Janis, Wargo, Jennifer, Butterfield, Lisa H., Villabona, Lisa, Thurin, Magdalena, Postow, Michael A., Sondel, Paul M., Demaria, Sandra, Agarwala, Sanjiv, and Ascierto, Paolo A.
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- 2017
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29. Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration
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Panelli, Monica C, Wang, Ena, Phan, Giao, Puhlmann, Markus, Miller, Lance, Ohnmacht, Galen A, Klein, Harvey G, and Marincola, Francesco M
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- 2002
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30. World-Wide Immunoscore Task Force: meeting report from the "Melanoma Bridge", Napoli, November 30th-December 3rd, 2016.
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Galon, Jerome, Lugli, Alessandro, Bifulco, Carlo, Pages, Franck, Masucci, Giuseppe, Marincola, Francesco M., and Ascierto, Paolo A.
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DISEASE progression ,PROGRESSION-free survival ,MELANOMA ,TUMOR necrosis factors ,CARCINOMA ,IMMUNOLOGY ,IMMUNOSUPPRESSION ,T cells - Abstract
The predictive accuracy of the traditional staging system is based on disease progression as a tumour cell-autonomous process, but it fails to incorporate the effects of the host immune response. A precise analysis of the immune component of the tumour microenvironment by computer-based analysis may be essential to managing patients better, opening the road to an expertise in this new emerging field. The Immunoscore as a new possible approach in the classification of cancer, designated TNM-Immune, studied in colon cancer patients with predictive and prognostic value. This new scoring system is derived from the immune contexture, and is based on the numeration of lymphocyte populations, both in the core of the tumour and in the invasive margin of tumours. The Immunoscore demonstrated to be quantitative, reproducible and robust. The usefulness of Immunoscore in advanced melanoma cancer patients has been as well demonstrated; the correlation of marker expression profile with clinical outcome is ongoing. More recently, the Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. A multivariable Cumulative "Suppression Index" scoring system has been also studied in Oral Squamous Cell Carcinoma patients: it evaluates both the tumor and stromal microcompartments at the invasive margin and summarizes them into the score, providing an accurate stratification, independent of stage, tumour classification. The introduction of Immunoscore requires a redefinition of the Laboratory system according to the LEAN Management process, which has been already implemented in referral research labs. The definition and test of hundreds of biomarkers, in the tumour contexture represents a definitive scientific progression. However, there is still a need of substantial body of work to reach the end of the tunnel to assure a personalize treatment. [ABSTRACT FROM AUTHOR]
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- 2017
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31. Inaugural Charles River World Congress on Animal Models in Drug Discovery and Development.
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Berzofsky, Jay, Koch, Lauren, Britton, Steven, Chen, Shaochen, Zhu, Wei, Ma, Xuanyi, Comuzzie, Anthony, Devy-Dimanche, Laetitia, Feaver, Ryan, Grimm, Jan, Hock, Christoph, Nitsch, Roger, Hoying, James, Lusis, Aldons, Marincola, Francesco, Samayoa, Josue, Turan, Tolga, Pearce, David, Nurmi, Antti, and Huhtala, Tuulia
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CANCER vaccines ,LABORATORY mice ,CLINICAL trials ,MEDICATION safety ,MOORE'S law ,BIOPRINTING ,CARDIOVASCULAR diseases - Published
- 2017
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32. Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.
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Bagga, Puneet, Haris, Mohammad, D'Aquilla, Kevin, Wilson, Neil E., Marincola, Francesco M., Schnall, Mitchell D., Hariharan, Hari, and Reddy, Ravinder
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SUCRALOSE ,NONNUTRITIVE sweeteners ,MAGNETIC resonance imaging ,CROSS-sectional imaging ,GLIOMAS ,ANIMAL experimentation ,BLOOD-brain barrier ,BRAIN tumors ,CELL lines ,DIAGNOSTIC imaging ,HYDROGEN-ion concentration ,MOLECULAR diagnosis ,IMAGING phantoms ,RATS ,RESEARCH funding ,SWEETENERS ,TUMORS ,CONTRAST media - Abstract
Background: Image contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies.Methods: High-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor.Results: The sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood-brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast.Conclusions: We show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications. [ABSTRACT FROM AUTHOR]- Published
- 2017
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33. Diagnosis implications of the whole genome sequencing in a large Lebanese family with hyaline fibromatosis syndrome.
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Haidar, Zahraa, Temanni, Ramzi, Chouery, Eliane, Jitesh, Puthen, Wei Liu, Al-Ali, Rashid, Ena Wang, Marincola, Francesco M., Jalkh, Nadine, Haddad, Soha, Haidar, Wassim, Chouchane, Lotfi, and Mégarbané, André
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SOFT tissue tumors ,LEBANESE ,GENETIC mutation ,ANTHRAX toxin ,GINGIVAL hyperplasia ,HEALTH - Abstract
Background: Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions. Methods: We describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents. Results: A mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted. Conclusions: The main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases. [ABSTRACT FROM AUTHOR]
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- 2017
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34. Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype.
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Fadda, Abeer, Butt, Fiza, Tomei, Sara, Deola, Sara, Lo, Bernice, Robay, Amal, Al-Shakaki, Alya, Al-Hajri, Noor, Crystal, Ronald, Kambouris, Marios, Wang, Ena, Marincola, Francesco M., Fakhro, Khalid A., and Cugno, Chiara
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GENETIC disorders ,HUMAN phenotype ,NUCLEOTIDE sequencing ,PHENOTYPES ,GENOMES - Abstract
Background: Ligase IV syndrome, a hereditary disease associated with compromised DNA damage response mechanisms, and Urofacial syndrome, caused by an impairment of neural cell signaling, are both rare genetic disorders, whose reports in literature are limited. We describe the first case combining both disorders in a specific phenotype. Case presentation: We report a case of a 7-year old girl presenting with a complex phenotype characterized by multiple congenital abnormalities and dysmorphic features, microcephaly, short stature, combined immunodeficiency and severe vesicoureteral reflux. Whole Genome Sequencing was performed and a novel ligase IV homozygous missense c.T1312C/p.Y438H mutation was detected, and is believed to be responsible for most of the clinical features of the child, except vesicoureteral reflux which has not been previously described for ligase IV deficiency. However, we observed a second rare damaging (nonsense) homozygous mutation (c.C2125T/p.R709X) in the leucine-rich repeats and immunoglobulin-like domains 2 gene that encodes a protein implicated in neural cell signaling and oncogenesis. Interestingly, this mutation has recently been reported as pathogenic and causing urofacial syndrome, typically displaying vesicoureteral reflux. Thus, this second mutation completes the missing genetic explanation for this intriguing clinical puzzle. We verified that both mutations fit an autosomal recessive inheritance model due to extensive consanguinity. Conclusions: We successfully identified a novel ligase IV mutation, causing ligase IV syndrome, and an additional rare leucine-rich repeats and immunoglobulin-like domains 2 gene nonsense mutation, in the context of multiple autosomal recessive conditions due to extensive consanguinity. This work demonstrates the utility of Whole Genome Sequencing data in clinical diagnosis in such cases where the combination of multiple rare phenotypes results in very intricate clinical pictures. It also reports a novel causative mutation and a clinical phenotype, which will help in better defining the essential features of both ligase IV and leucine-rich repeats and immunoglobulin-like domains 2 deficiency syndromes. [ABSTRACT FROM AUTHOR]
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- 2016
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35. Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?
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Mégarbané, André, Al-Ali, Rashid, Choucair, Nancy, Lek, Monko, Ena Wang, Ladjimi, Moncef, Rose, Catherine M., Hobeika, Remy, Macary, Yvette, Temanni, Ramzi, Jithesh, Puthen V., Chouchane, Aouatef, Sastry, Konduru S., Thomas, Remy, Tomei, Sara, Wei Liu, Marincola, Francesco M., MacArthur, Daniel, and Chouchane, Lotfi
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TREATMENT of rare diseases ,GENETIC disorder treatment ,NUCLEOTIDE sequencing ,VOLTAGE-gated ion channels ,GENETIC mutation ,CENTRAL nervous system diseases - Abstract
Background: KCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann-Laband syndrome (ZLS). Methods: Here, we report a new case of TMBTS diagnosed in a Lebanese child. Whole genome sequencing was carried out on DNA samples of the proband and his parents to identify mutations associated with this disease. Sanger sequencing was performed to confirm the presence of detected variants. Results: Whole genome sequencing revealed three missense mutations in TMBTS patient: c.1042G > A in KCNH1, c. 2131 T > C in STK36, and c.726C > A in ZNF517. According to all predictors, mutation in KCNH1 is damaging de novo mutation that results in substitution of Glycine by Arginine, i.e., p.(Gly348Arg). This mutation was already reported in a patient with ZLS that could affect the connecting loop between helices S4-S5 of KCNH1 with a gain of function effect. Conclusions: Our findings demonstrate that KCNH1 mutations cause TMBTS and expand the mutational spectrum of KCNH1 in TMBTS. In addition, all cases of TMBTS were reviewed and compared to ZLS. We suggest that the two syndromes are a continuum and that the variability in the phenotypes is the result of the involvement of genetic modifiers. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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36. Characterization of viscosupplementation formulations using chemical exchange saturation transfer (ViscoCEST).
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Haris, Mohammad, Singh, Anup, Reddy, Sanjana, Bagga, Puneet, Kneeland, J. Bruce, Tjoumakaris, Fotios P., Hariharan, Hari, Marincola, Francesco M., and Reddy, Ravinder
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OSTEOARTHRITIS treatment ,HYALURONIC acid ,MAGNETIC resonance imaging ,CONTRAST media ,INTRA-articular injections ,KNEE anatomy ,ARTICULAR cartilage ,COMPARATIVE studies ,GLYCOSAMINOGLYCANS ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,EVALUATION research ,ANATOMY - Abstract
Background: Osteoarthritis (OA) is characterized by progressive loss of cartilage in joints, and is a major cause of pain and disability, and imposes significant health care expense. New therapies are being developed to treat the symptomatic effect of OA, one of which is intra-articular injection of viscosupplementations of different forms of hyaluronic acid (HA). The current study evaluates the chemical exchange saturation transfer (CEST) effect from two popular viscosupplementations [Hylan gf-20 (Synvisc) and hyaluronan (Orthovisc)] by targeting the exchangeable hydroxyl protons present on these molecules (ViscoCEST).Methods: ViscoCEST imaging from two viscosupplementations (Synvisc and Orthovisc) was performed on a 7T Siemens whole body MRI scanner. ViscoCEST images were collected with different combination of saturation pulse power and saturation duration. Z spectra were acquired at B1rms of 3.6 μT and 1 s saturation duration by varying the frequency from -4 to +4 ppm in step size of 0.1 ppm. Field inhomogeneity (B0) and radiofrequency (B1) maps were also acquired to correct ViscoCEST contrast map for any inhomogeneity.Results: Both viscosupplementations showed broad CEST effect (ViscoCEST), which peaked ~0.8 ppm from down field of water resonance. Orthovisc showed 20 % higher ViscoCEST contrast than Synvisc suggestive of more HA component in Orthovisc. Increased ViscoCEST contrast was observed from both viscosupplementations with increase in B1rms and saturation pulse duration.Conclusion: ViscoCEST has a potential to image the spatial distribution of viscosupplements in vivo in patients' intra-articular space as well as temporal variation in their spatial distribution. [ABSTRACT FROM AUTHOR]- Published
- 2016
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37. Reduced cortical thickness in patients with acute-on-chronic liver failure due to non-alcoholic etiology.
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Yadav, Santosh K., Gupta, Rakesh K., Saraswat, Vivek A., Rangan, Murali, Thomas, Michael A., Rutella, Sergio, Danese, Silvio, Ena Wang, Marincola, Francesco M., Haris, Mohammad, and Wang, Ena
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ASPARTIC acid metabolism ,GLUTAMINE metabolism ,GLUTAMIC acid metabolism ,ASPARTIC acid ,BRAIN ,COGNITION ,COGNITION disorders ,COMPUTER software ,INOSITOL ,LIVER ,LIVER failure ,LONGITUDINAL method ,MAGNETIC resonance imaging ,NEUROPSYCHOLOGICAL tests ,NUCLEAR magnetic resonance spectroscopy ,TREATMENT effectiveness ,CASE-control method ,DISEASE complications - Abstract
Background: Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers.Methods: For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy ((1)H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls.Results: Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls.Conclusions: Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment. [ABSTRACT FROM AUTHOR]- Published
- 2015
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38. Molecular magnetic resonance imaging in cancer.
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Haris, Mohammad, Yadav, Santosh K., Rizwan, Arshi, Singh, Anup, Ena Wang, Hariharan, Hari, Reddy, Ravinder, and Marincola, Francesco M.
- Abstract
The ability to identify key biomolecules and molecular changes associated with cancer malignancy and the capacity to monitor the therapeutic outcome against these targets is critically important for cancer treatment. Recent developments in molecular imaging based on magnetic resonance (MR) techniques have provided researchers and clinicians with new tools to improve most facets of cancer care. Molecular imaging is broadly described as imaging techniques used to detect molecular signature at the cellular and gene expression levels. This article reviews both established and emerging molecular MR techniques in oncology and discusses the potential of these techniques in improving the clinical cancer care. It also discusses how molecular MR, in conjunction with other structural and functional MR imaging techniques, paves the way for developing tailored treatment strategies to enhance cancer care. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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39. Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma.
- Author
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Johnson, Jennifer, Ascierto, Maria Libera, Mittal, Sandeep, Newsome, David, Liang Kang, Briggs, Michael, Tanner, Kirk, Marincola, Francesco M., Berens, Michael E., Vande Woude, George F., Qian Xie, Kang, Liang, and Xie, Qian
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ANIMAL experimentation ,BIOLOGICAL models ,CANCER invasiveness ,CELL lines ,CELL physiology ,DRUG therapy ,CYTOKINES ,EPIDERMAL growth factor ,GENES ,GLIOMAS ,MICE ,RESEARCH funding ,GENOMICS ,TREATMENT effectiveness ,GENE expression profiling ,PHARMACODYNAMICS ,PROTEIN kinase inhibitors ,THERAPEUTICS - Abstract
Background: Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM.Methods: Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p ≤ 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p ≤ 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p ≤ 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance.Results: We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors.Conclusions: Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors. Human and mouse microarrays maybe used to dissect the tumor-host interactions. Targeting MET in EGFR (amp) GBM may delay the acquired resistance developed during treatment with erlotinib. [ABSTRACT FROM AUTHOR]- Published
- 2015
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40. What's new in melanoma? Combination!
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Ascierto, Paolo A., Marincola, Francesco M., and Atkins, Michael B.
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MELANOMA , *IMMUNOTHERAPY , *PROGRESSION-free survival , *BRAF genes , *TUMORS - Abstract
Melanoma was again a focus of attention at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, in particular the use of combination treatment strategies involving immunotherapies and/or targeted agents. New data on targeted therapies confirmed previous findings, with combined BRAF inhibitor (vemurafenib) plus MEK inhibitor (cobimetinib) improving progression-free survival (PFS) compared to vemurafenib monotherapy in patients with BRAFV600 mutation-positive tumors (CoBRIM trial). Positive results were also seen with combined dabrafenib and trametinib in patients with BRAF V600E/K metastatic melanoma and encorafenib plus binimetinib in BRAFV600- mutant cutaneous melanoma. Even more interesting news centered on the use of combination immunotherapy, in particular the randomized, double-blind CheckMate 067 study in which median PFS with nivolumab plus ipilimumab was 11.5 months, compared to 2.9 months with ipilimumab alone (HR 0.42) and 6.9 months with nivolumab alone (HR 0.57). Of interest, in patients with ≥5% PD-L1 expression, median PFS was 14 months with the combination or with nivolumab alone compared with 3.9 months in the ipilimumab group, while in the PD-L1 negative cohort, the combination remained superior to both monotherapies. Given that combination therapy was accompanied by a high occurrence of side-effects, this raises the suggestion that combination therapy might be reserved for PD-L1 negative patients only, with PD-L1 positive patients achieving the same benefit from nivolumab monotherapy. However, overall survival data are awaited and the equivalence of single agent to the combination remains unconvincing. Interesting data were also reported on the combination of T-VEC (talimogene laherparepvec) with ipilimumab, and the anti-PD-1 agent MEDI4736 (durvolumab) combined with dabrafenib plus trametinib. Emerging data also suggested that predictive markers based on immunoprofiling and mismatch repair deficiency may be of clinical use. In conclusion, the use of combination approaches to treat patients with melanoma, as well as other cancers, is no longer a just a wish for the future but is today a clinical reality with a rapidly growing evidence-base. Moreover, the most exciting consideration is that this is far from the end of the story, but rather a fantastic introduction. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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41. Different maturation cocktails provide dendritic cells with different chemoattractive properties.
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Massa, Chiara, Thomas, Carolin, Ena Wang, Marincola, Francesco, Seliger, Barbara, and Wang, Ena
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COCKTAILS ,DENDRITIC cells ,DEVELOPMENTAL biology ,IMMUNOTHERAPY ,TUMOR immunology ,ANTISENSE DNA ,INTERFERONS - Abstract
Background: Dendritic cells (DC) are currently implemented as immunotherapeutic strategy for the treatment of tumor patients based on their central role in the immune system. Despite good results were obtained in vitro and in animal models, their clinical use has provided limited success suggesting the requirement to optimise the protocol for their production.Methods: A cDNA array was performed on FastDC obtained from the differentiation of human peripheral blood monocytes stimulated with the clinical gold standard or with two alternative maturation cocktails combining interferon (IFN)γ and ligands for different toll like receptors (TLR).Results: A stronger modulation of the DC transcriptome with respect to immature DC was found in alternatively stimulated DC when compared to DC stimulated with the clinical gold standard. A major class of molecules differentially expressed using distinct DC stimulation protocols were chemokines. Validation of their differential expression pattern at the mRNA and protein level confirmed the secretion of inflammatory chemokines by the alternative DC. Functional analyses of the chemotactic properties of DC "wash out" supernatants highlighted the ability of alternative, but not of gold standard DC to efficiently recruit immune cells with a prevalence of monocytes. Effector cells belonging to the innate as well as adaptive immunity were also attracted and the interaction with alternative DC resulted in enhanced secretion of IFNγ and induction of cytotoxic activity. Using leukocytes from cancer patients, it was demonstrated that the monocyte-attracting activity targeted cells with an inflammatory phenotype characterised by high levels of HLA-DR expression.Conclusions: Despite other classes of immune modulatory genes differently expressed in the alternative DC require to be investigated and characterised regarding their functional consequences, the reduced maturation state and chemoattractive properties of the gold standard versus alternative DC clearly promote the necessity to change the clinically used maturation cocktail of DC in order to improve the outcome of patients treated with DC-based vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2015
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42. Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus.
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Ascierto, Maria Libera, Bozzano, Federica, Bedognetti, Davide, Marras, Francesco, Schechterly, Cathy, Kentaro Matsuura, Picciotto, Antonino, Marenco, Simona, Yingdong Zhao, DeGiorgi, Valeria, Sommariva, Michele, Moretta, Lorenzo, Ena Wang, Alter, Harvey J., Marincola, Francesco M., and De Maria, Andrea
- Subjects
KILLER cells ,COMMUNICABLE diseases ,FLAVIVIRAL diseases ,LIVER diseases ,MEDICAL records - Abstract
Background: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNα/RBV in patients chronically infected with HCV. Methods: To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNα/RBV. Results were further correlated with divergent clinical response obtained after treatment. Results: The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. Conclusions: Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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43. Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection
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Panelli, Monica C, Stashower, Mitchell E, Slade, Herbert B, Smith, Kina, Norwood, Christopher, Abati, Andrea, Fetsch, Patricia, Filie, Armando, Walters, Shelley-Ann, Astry, Calvin, Aricó, Eleonora, Zhao, Yingdong, Selleri, Silvia, Wang, Ena, and Marincola, Francesco M
- Subjects
Imiquimod ,Research ,CD8 Antigens ,Gene Expression Profiling ,Interferon-alpha ,Antineoplastic Agents ,Polymerase Chain Reaction ,CD56 Antigen ,Gene Expression Regulation, Neoplastic ,Placebos ,Interferon-gamma ,Carcinoma, Basal Cell ,Aminoquinolines ,Humans ,RNA, Messenger ,Genes, Neoplasm - Abstract
An analysis of basal cell carcinoma subjected to local application of imiquimod revealed that most transcripts stimulated by imiquimod involve the activation of cellular innate and adaptive immune-effector mechanisms., Background Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. Results We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 × 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-α involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. Conclusion This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction.
- Published
- 2007
44. Forecasting the cytokine storm following systemic interleukin (IL)-2 administration
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Panelli Monica C, White Richard, Foster Mareva, Martin Brian, Wang Ena, Smith Kina, and Marincola Francesco M
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Research ,lcsh:R ,lcsh:Medicine - Abstract
Extensive clinical experience has shown that systemic interleukin (IL)-2 administration can induce complete or partial regression of renal cell cancer (RCC) metastases in 15 to 20 % of patients. Since IL-2 has no direct anti-cancer effects, it is believed that cancer regression is mediated either by a direct modulation of immune cell effector functions or through the mediation of soluble factors released as a result of IL-2 administration. We previously observed that transcriptional and protein changes induced by systemic IL-2 administration affect predominantly mononuclear phagocytes with little effect, particularly within the tumor microenvironment, on T cell activation, localization and proliferation. It further appeared that mononuclear phagocyte activation could be best explained by the indirect mediation of a secondary release of cytokines by IL-2 responsive cells either in the circulation or in peripheral tissues. To better characterize the cytokine outburst that follows systemic IL-2 administration we followed the serum levels of 68 soluble factors in ten patients with RCC undergoing high dose (720,000 IU/kg intravenously every 8 hours) IL-2 therapy. Serum was collected before therapy, 3 hours after the 1st and 4th dose and assayed on a multiplexed protein array platform. This study demonstrated that 1) the serum concentration of more than half the soluble factors studied changed significantly during therapy; 2) changes became more dramatic with increasing doses; 3) subclasses of soluble factors displayed different kinetics and 4) cytokine patterns varied quantitatively among patients. This study shows that the cytokine storm that follows systemic IL-2 administration is complex and far-reaching inclusive of soluble factors with disparate, partly redundant and partly contrasting effects on immune function. Therefore comparing in parallel large number of soluble factors, it sets a comprehensive foundation for further elucidation of "cytokine storm" in larger patient pools. Based on this analysis, we propose a prospective collection of serum samples in a larger cohort of patients undergoing IL-2 administration with the purpose of discerning patterns predictive of clinical outcome and toxicity.
- Published
- 2004
45. Synopsis of the 6th Walker's Cay Colloquium on Cancer Vaccines and Immunotherapy
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Marincola Francesco M, Levitsky Hyam, and Kast W Martin
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lcsh:R ,Commentary ,lcsh:Medicine - Abstract
The 6th annual Cancer Vaccines and Immunotherapy Colloquium at Walker's Cay was held under the auspices of the Albert B. Sabin Vaccine Institute on March 10–13, 2004. The Colloquium consisted of a select group of 34 scientists representing academia, biotechnology and pharmaceutical industry. The main goal of this gathering was to promote in a peaceful and comfortable environment exchanges between basic and clinical science. The secondary benefit was to inspire novel bench to bedside ventures and at the same time provide feed back about promising and/or disappointing clinical results that could help re-frame some scientific question or guide the design of future trials. Several topics were covered that included tumor antigen discovery and validation, platforms for vaccine development, tolerance, immune suppression and tumor escape mechanisms, adoptive T cell therapy and dendritic cell-based therapies, clinical trials and assessment of response. Here we report salient points raised by speakers or by the audience during animated discussion that followed each individual presentation.
- Published
- 2004
46. A strategy for detection of known and unknown SNP using a minimum number of oligonucleotides applicable in the clinical settings
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Klein Harvey, Simon Richard, Panelli Monica, Zhao Yingdong, Adams Sharon, Wang Ena, and Marincola Francesco M
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lcsh:R ,Methodology ,lcsh:Medicine - Abstract
Detection of unknown single nucleotide polymorphism (SNP) relies on large scale sequencing expeditions of genomic fragments or complex high-throughput chip technology. We describe a simplified strategy for fluorimetric detection of known and unknown SNP by proportional hybridization to oligonucleotide arrays based on optimization of the established principle of signal loss or gain that requires a drastically reduced number of matched or mismatched probes. The array consists of two sets of 18-mer oligonucleotide probes. One set includes overlapping oligos with 4-nucleotide tiling representing an arbitrarily selected "consensus" sequence (consensus-oligos), the other includes oligos specific for known SNP within the same genomic region (variant-oligos). Fluorescence-labeled DNA amplified from a homozygous source identical to the consensus represents the reference target and is co-hybridized with a differentially-labeled test sample. Lack of hybridization of the test sample to consensus- with simultaneous hybridization to variant-oligos designates a known allele. Lack of hybridization to consensus- and variant-oligos indicates a new allele. Detection of unknown variants in heterozygous samples depends upon fluorimetric analysis of signal intensity based on the principle that homozygous samples generate twice the amount of signal. This method can identify unknown SNP in heterozygous conditions with a sensitivity of 82% and specificity of 90%. This strategy should dramatically increase the efficiency of SNP detection throughout the human genome and will decrease the cost and complexity of applying genomic wide analysis in the context of clinical trials.
- Published
- 2003
47. Translational Medicine: A two-way road
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Marincola Francesco M
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Editorial ,lcsh:R ,education ,lcsh:Medicine ,health care economics and organizations - Abstract
The purpose of translational research is to test, in humans, novel therapeutic strategies developed through experimentation. Translational research should be regarded as a two-way road: Bench to Bedside and Bedside to Bench. However, Bedside to Bench efforts have regrettably been limited because the scientific aspects are poorly understood by full time clinicians and the difficulty of dealing with humans poorly appreciated by basic scientists. Translational research would be most useful to the scientific community at large if journals would foster specific interest for the publication of ex vivo human observation. The review process for such work should be assigned to clinical scientists competent not only in the intricacies of molecular or cell biology but also intimate with the reality of Internal Review Boards, ethics committees, Governmental Regulatory Agencies and most importantly the humane aspects of dealing with sick individuals and their families. This approach may focus both basic and clinical scientists and those struggling to fill the gap between them on the effective treatment of diseases affecting women, men and children making translational research more than an interesting concept.
- Published
- 2003
48. High-dimensional analysis of the aging immune system: Verification of age-associated differences in immune signaling responses in healthy donors.
- Author
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Longo, Diane M., Louie, Brent, Ptacek, Jason, Friedland, Greg, Evensen, Erik, Putta, Santosh, Atallah, Michelle, Spellmeyer, David, Ena Wang, Pos, Zoltan, Marincola, Francesco M., Schaeffer, Andrea, Lukac, Suzanne, Railkar, Radha, Beals, Chan R., Cesano, Alessandra, Carayannopoulos, Leonidas N., and Hawtin, Rachael E.
- Subjects
IMMUNE system ,FLOW cytometry ,AGING ,CANCER immunotherapy ,VACCINATION - Abstract
Background Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. Methods In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. Results Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. Conclusions These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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49. What have we learned from cancer immunotherapy in the last 3 years?
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Ascierto, Paolo A. and Marincola, Francesco M.
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IMMUNOLOGY , *IMMUNE system , *CANCER immunotherapy , *IMMUNE response , *MEDICAL sciences - Abstract
Until recently, most immunotherapeutic approaches used to fight cancer were ineffective, counteracted by the tumour's ability to evade immune attack. However, extensive research has improved our understanding of tumour immunology and enabled the development of novel treatments that can harness the patient's immune system and prevent immune escape. Over the last few years, through numerous clinical trials and real-world experience, we have accumulated a large amount of evidence regarding the potential for long-term survival with immunotherapy agents in various types of malignancy. The results of these studies have also highlighted a number of recurring observations with immuno-oncology agents, including their potential for clinical application across a broad patient population and for both conventional and unconventional response patterns. Furthermore, given the numerous immune checkpoints that exist and the multiple mechanisms used by tumours to escape the immune system, targeting distinct checkpoint pathways using combination approaches is an attractive therapeutic strategy with the potential to further enhance the antitumour immune response. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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50. Impact of carbon nanotubes and graphene on immune cells.
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Orecchioni, Marco, Bedognetti, Davide, Sgarrella, Francesco, Marincola, Francesco, Bianco, Alberto, and Delogu, Lucia Gemma
- Subjects
CARBON nanotubes ,GRAPHENE ,LYMPHOCYTES ,LEUCOCYTES ,DENDRITIC cells - Abstract
It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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