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2. Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation

Author

Boidin, Léa, Moinard, Morgane, Moussaron, Albert, Merlier, Margaux, Moralès, Olivier, Grolez, Guillaume Paul, Baydoun, Martha, Mohd-Gazzali, Amirah, Tazizi, Mohammad Hafizie Dianel Mohd, Allah, Hassan Hadi Abd, Kerbage, Yohan, Arnoux, Philippe, Acherar, Samir, Frochot, Céline, and Delhem, Nadira

Published
2024
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3. Photodynamic Therapy Using a Rose-Bengal Photosensitizer for Hepatocellular Carcinoma Treatment: Proposition for a Novel Green LED-Based Device for In Vitro Investigation.

Author

Lefebvre, Anthony, Marhfor, Smail, Baert, Gregory, Deleporte, Pascal, Grolez, Guillaume Paul, Boileau, Marie, Morales, Olivier, Vignoud, Séverine, Delhem, Nadira, Mortier, Laurent, and Dewalle, Anne-Sophie

Subjects
PHOTODYNAMIC therapy, ROSE bengal, HEPATOCELLULAR carcinoma, TUMOR treatment, SURGICAL margin
Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite new treatments, the HCC rate remains important, making it necessary to develop novel therapeutic strategies. Photodynamic therapy (PDT) using a Rose-Bengal (RB) photosensitizer (RB-PDT) could be a promising approach for liver tumor treatment. However, the lack of standardization in preclinical research and the diversity of illumination parameters used make comparison difficult across studies. This work presents and characterizes a novel illumination device based on one green light-emitting diode (CELL-LED-550/3) dedicated to an in vitro RB-PDT. The device was demonstrated to deliver a low average irradiance of 0.62 mW/cm2 over the 96 wells of a multi-well plate. Thermal characterization showed that illumination does not cause cell heating and can be performed inside an incubator, allowing a more rigorous assessment of cell viability after PDT. An in vitro cytotoxic study of the RB-PDT on an HCC cell line (HepG2) demonstrated that RB-PDT induces a significant decrease in cell viability: almost all the cells died after a light dose irradiation of 0.3 J/cm2 using 75 µM of RB (<10% of viability). In conclusion, the RB-PDT could be a therapeutic option to treat unresectable liver lesions and subclinical disease remaining in the post-resection tumor surgical margin. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Sperm kinematic subpopulations of the American crocodile (Crocodylus acutus)

Author

Tecnológico de Costa Rica, Ministerio de Economía y Competitividad (España), CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI), Valverde, Anthony, Castro-Morales, Olivier, Madrigal-Valverde, Mónica, Camacho, Marlen, Banquero, Vinicio, Soler, Carles, Roldán, Eduardo R. S., Tecnológico de Costa Rica, Ministerio de Economía y Competitividad (España), CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI), Valverde, Anthony, Castro-Morales, Olivier, Madrigal-Valverde, Mónica, Camacho, Marlen, Banquero, Vinicio, Soler, Carles, and Roldán, Eduardo R. S.

Abstract

There has been very limited use of computer assisted semen analysis (CASA) to evaluate reptile sperm. The aim of this study was to examine sperm kinematic variables in American crocodile (Crocodylus acutus) semen samples and to assess whether sperm subpopulations could be characterized. Eight ejaculates (two ejaculates/male) from four sexually mature captive crocodiles were obtained. An ISAS®v1 CASA-Mot system, with an image acquisition rate of 50 Hz, and ISAS®D4C20 counting chambers were used for sperm analyses. The percentages of motile and progressively motile spermatozoa did not differ among animals (P > 0.05) but there was a significant animal effect with regards to kinematic variables (P < 0.05). Principal component (PC) analysis revealed that kinematic variables grouped into three components: PC1, related to velocity; PC2 to progressiveness and PC3 to oscillation. Subpopulation structure analysis identified four groups (P < 0.05), which represented, on average, 9.8%, 32.1%, 26.8%, and 31.3% of the total sperm population. Males differed in the proportion of sperm in each of the kinematic subpopulations. This new approach for the analysis of reptile sperm kinematic subpopulations, reflecting quantifiable parameters generated by CASA system technology, opens up possibilities for future assessments of crocodile sperm and will be useful in the future development of assisted reproduction for these species.

Published
2021

10. Tamaño corporal de cuatro especies de mariposas del género Heliconius (Lepidoptera: Nymphalidae) producidas en zoocriaderos del Caribe de Costa Rica

Author

Castro Morales, Olivier, Gadea Rivas, Arnoldo, and Madrigal Valverde, Mónica

Subjects
Lepidoptera, biometrics, biometría, butterfly farms, zoocriadero, cría de mariposas, Heliconius, breeding of butterflies, Lepidóptera
Abstract

Introduction: The production of butterflies is an important socioeconomic activity and has become an option to generate income for rural microenterprises. Objective: To see how farming affects the body size of Heliconius butteflies in Costa Rican farms. Methods: We measured adults and pupae of Heliconius cydno, H. erato, H. hecale and H. melpomene in 10 butterfly farms, in the Huetar Atlantic Region of Costa Rica. Results: In some farms, adult Heliconius erato and H. hecale are heavier (p≤ 0.05), and have a longer abdomen and larger forewings. The weight did not differ among farms, and the sex ratio is close to 0,5. Conclusion: All farms sampled produce butterflies of fit for commercialization. Introducción: La producción de mariposas es una actividad socioeconómica importante y se ha convertido en una opción para generar ingresos en las microempresas rurales. Objetivo: Observar como los zoocriaderos afectan el tamaño corporal de mariposas Heliconius, producidas en zoocriaderos de Costa Rica. Métodos: Medimos adultos y pupas de Heliconius cydno, H. erato, H. hecale y H. melpomene de 10 zoocriaderos de mariposas, ubicados en el la zona Huetar Atlántica de Costa Rica. Resultados: En algunos zoocriaderos las mariposas adultas de Heliconius erato y H. hecale son significativamente más pesadas (p ≤ 0,05), poseen un abdomen más largo y el ala anterior más grande. El peso no difiere entre zoocriaderos, las relaciones de sexos son cercanas a 0,5. Conclusiones: Todos los zoocriaderos muestreados producen mariposas con calidad para su comercialización.

Published
2019

11. Sperm kinematics and morphometric subpopulations analysis with CASA systems: a review

Author

Valverde, Anthony, Castro-Morales, Olivier, Madrigal-Valverde, Mónica, and Soler, Carles

Subjects
multivariate analysis, motility, movilidad, reproduction, semen, andrology, análisis multivariado, andrología, reproducción
Abstract

Resumen La valoración subjetiva de la calidad seminal ha dado paso al uso de las técnicas objetivas de valoración por medio de la tecnología CASA (computer-assisted semen analysis). Se pueden aplicar una serie de pruebas cinéticas, morfométricas, morfológicas o de integridad del ADN para caracterizar y entender la biología reproductiva del espermatozoide. En los últimos años, se ha dado un cambio significativo de paradigma conceptual respecto de qué es un eyaculado. Cabe decir que, hasta tiempos recientes, se consideró que una población representativa (miles de millones) de espermatozoides estaba formada por células "equivalentes" con un objetivo común: ser el que finalmente pudiese fecundar el ovocito. La comprobación de que el conjunto de espermatozoides se agrupa en subpoblaciones bien definidas de acuerdo con sus características cinéticas y/o morfométricas, ha abierto el camino hacia una visión más cooperativa. Además, se ha visto que la distribución subpoblacional es diferente entre individuos, lo que parece indicar diferentes estrategias que se pueden entender dentro de otro paradigma: el de la competencia espermática entre diferentes eyaculados. A pesar de que aún no se conoce el papel de las diferentes subpoblaciones, se deben continuar los trabajos en esa dirección. En esta revisión, se caracterizó la evaluación de la fertilidad con la tecnología CASA y se examinaron los principales métodos multivariados en la evaluación de subpoblaciones de espermatozoides analizados mediante un sistema CASA. Abstract: In recent years, there has been a substantive change in the conceptual paradigm regarding what an ejaculate is. Until recently, it was considered that a representative population (billions) of sperm was made up of "equivalent" cells with a common goal: to be the one that could finally fertilize the oocyte. New data suggesting that a set of spermatozoa is grouped in distinct subpopulations, according to their kinematic and morphometric characteristics, has opened the way towards a more cooperative vision. In addition, recently, it has been established that the subpopulation distribution is different among males, which seems to indicate that there are different strategies that can be understood within another paradigm: sperm competition between different ejaculates. These heterogeneous subpopulations of spermatozoa in the ejaculate, that show kinematics and morphometric patterns, has been widely known for a while, but the biological meaning of these different sperm subpopulations is still not clear. For this reason, the subjective evaluation of seminal quality is being displaced by objective assessment techniques using CASA technology (computer-assisted semen analysis). Also, the application of principal components (PC) and clustering methods to reveal subpopulations of spermatozoa are complementary tools used to characterize raw semen and processed cell suspensions. Despite the advances in such powerful tools, researchers are not well versed on such techniques and its advantages. For instance, PC analysis is a multivariate statistical method that reduces the number of variables used in subsequent calculations for describing the data. By integrating the original data into new complex mathematical variables, homogenous subpopulations of spermatozoa can define clearly. Furthermore, kinematic, morphometric, morphological or DNA integrity tests can be also applied to characterize and understand the reproductive biology of the spermatozoon. Although the role of the different subpopulations of spermatozoa remains unknown, the work should continue by implementing novel technologies and coordinated tools. In this review, we characterize the fertility evaluation with CASA technology and examine the main multivariate methods in the assessment of sperm subpopulations analyzed by CASA systems.

Published
2019

14. 5-aminolevulinic acid mediated photodynamic therapy: pathing the way towards a new therapeutic modality for hepatocellular carcinoma

Author

Kumar, Abhishek, primary, Morales, Olivier, additional, Baydoun, Martha, additional, Leroux, Bertrand, additional, Ziane, Laurine, additional, Aoudjehane, Lynda, additional, Quilbe, Alexandre, additional, Frochot, Celine, additional, Conti, Filomena, additional, Mordon, Serge, additional, Boleslawski, Emmanuel, additional, and Delhem, Nadira, additional

Published
2020
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16. Caracterización de sistemas productivos de pupas de mariposas (lepidoptera: nymphalidae) para la exportación en la región Huetar caribe de Costa Rica

Author

Castro-Morales, Olivier and Madrigal-Valverde, Mónica

Subjects
Agroecosistemas, Acidity, Agronomic analysis, Uso del suelo, FORESTRY, AGRICULTURAL SCIENCES and LANDSCAPE PLANNING::Plant production [Research Subject Categories], Plantas, Lepidoptera, Insects, Lepidópteros, Exports, Exportaciones, Insectos, Agroecosystems, Análisis agronómico, Acidez, Butterflies, Mariposas, Calidad
Abstract

Proyecto de Investigación (Código: 215107 VIE) Instituto Tecnológico de Costa Rica. Vicerrectoría de Investigación y Extensión (VIE), 2018 La producción de mariposas es una actividad socioeconómica importante, la cual requiere apoyo gubernamental, académico y profesional para mejorar sus procesos. Este estudio es el comienzo de un grupo de investigaciones dirigidas a optimizar los agroecosistemas productivos de mariposas a nivel nacional, para la mejora de la calidad de los productos que los agricultores ofrecen al mercado internacional. Se incluyeron 10 zoocriaderos de mariposas. En este estudio se realizó análisis de suelo en cada zoocriadero de mariposas y un análisis foliar para cuatro especies de plantas de la familia Passifloracea. Se realizó una biometría a cuatro especies de mariposas adultas y a las pupas. Mediante un instrumento de preguntas y respuestas, se analizó la situación socioeconómica de los productores apoyados con visitas de campo. La edad promedio de los productores es de 42 años, 80% han completado la educación primaria, el mismo porcentaje tiene seguridad social. Las áreas de producción en promedio miden 821 m2, producen un promedio 450 pupas por semana. Se encontró diferencias significativas en los tamaños de adultos y pupas entre los productores. Las condiciones del suelo son ácidas, no tienen sistemas de drenaje y riego ni un programa de fertilización, no se determinó deficiencias nutricionales en las plantas hospederas. Las estructuras de los zoocriaderos están hechas de postes de madera, con estructuras de alambre y cubiertas con mallas de nylon (sarán) de segundo uso y existe una deficiencia en la capacitación para mantener registros de sus sistemas de producción.

Published
2018

18. Effect of a vitamin supplement and three species of food plants (Fabaceae) on the production of Morpho helenor butterflies (Nymphalidae:Lepidoptera)

Author

Morales, Olivier Castro, Arias-Reverón, Julio M., Gadea-Rivas, Arnoldo, and Camero Rey, Luis Alberto

Subjects
Morpho helenor, nutritional supplement, producción de mariposas, pupae, Planta hospedera, mariposa, butterfly, lepidóptera, suplemento nutricional, caterpillar, production butterflies, pupa, lepidoptera, oruga, Host plant
Abstract

Resumen El uso de dietas artificiales en la producción de mariposas ha sido poco estudiado en la familia Nymphalidae, en este experimento evaluamos el efecto de un suplemento vitamínico comercial llamado Farvital - 18, compuesto por aminoácidos, vitaminas y electrolitos, en la producción de mariposas Morpho helenor, el suplemento se aplicó en tres plantas hospederas de la familia Fabaceae: Lonchocarpus oliganthus, Erythrina berteroana y Arachis pintoi, el tamaño de la muestra fue de 25 orugas para cada uno de los seis tratamientos, realizamos cuatro repeticiones, analizamos el tiempo del ciclo larval, la tasa de crecimiento de las orugas en cada estadio, la tasa de supervivencia de las orugas y en las pupas analizamos el peso, calidad y cantidad obtenida. La planta de Lonchocarpus oliganthus sin y con la adición del suplemento vitamínico produjo orugas de mayor tamaño, mayor tasa de sobrevivencia, el ciclo larval fue más corto, produjo pupas más pesadas y de mejor calidad. La planta de Arachis pintoi con y sin suplemento vitamínico, produjo pupas de menor peso. Los machos alimentados con Lonchocarpus oliganthus eclosionaron más rápido y en las hembras el alimento no causó ninguna diferencia. Independiente de la dieta utilizada, de las 600 larvas iniciales, se produjeron 371 pupas, con un rendimiento del 61,83%. Del total de las pupas formadas el 3,63% no eclosionó y el 88% de las pupas fueron calidad A. La mayor eclosión de adultos fue entre los días 14 y 15 de formada la pupa. Las pupas de las hembras son más pesadas que los machos. La planta nativa Lonchocarpus oliganthus dio mejores rendimientos en la producción de mariposas Morpho helenor. Abstract Little has been published on the use of artificial diets for the production of butterflies in the Nymphalidae family. We evaluated the effect of a commercial vitamin supplement called Farvital - 18, composed of amino acids, vitamins and electrolytes, on the production of the butterfly Morpho helenor. This supplement was applied on three host plants from the family Fabaceae: Lonchocarpus oliganthus, Erythrina berteroana and Arachis pintoi. We analyzed the duration of the larval stages, the growth rate of the caterpillars at each stage, the survival rate of the caterpillars, pupal weight, and quality and quantity of pupae obtained. Lonchocarpus oliganthus without and with the addition of vitamin supplement produced larger caterpillars, higher survival rate, shorter larval stage duration, and produced heavier and better quality pupae. Arachis pintoi with and without vitamin supplement produced pupae of lower weight. Males fed on Lonchocarpus oliganthus hatched faster but for females the food did not make any difference. Independent of the diet used for the 600 initial larvae, 371 pupae were produced (61,83%). Of the total pupae obtained, 3,63% did not emerge and 88% of the pupae were A quality. The greatest adult emergence occurred between days 14 and 15 of the pupa formation. The pupae of females were heavier than males. The native plant Lonchocarpus oliganthus gave better yields in the production of butterflies Morpho helenor.

Published
2017

19. Characterization of neutralizing antibodies reacting with the 213-224 amino-acid segment of human galectin-9

Author

Lhuillier, Claire, primary, Barjon, Clément, additional, Baloche, Valentin, additional, Niki, Toshiro, additional, Gelin, Aurore, additional, Mustapha, Rami, additional, Claër, Laetitia, additional, Hoos, Sylviane, additional, Chiba, Yoichi, additional, Ueno, Masaki, additional, Hirashima, Mitsuomi, additional, Wei, Ming, additional, Morales, Olivier, additional, Raynal, Bertrand, additional, Delhem, Nadira, additional, Dellis, Olivier, additional, and Busson, Pierre, additional

Published
2018
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20. Se fortalece cultura ambiental y manejo de residuos sólidos

Author

Castro-Morales, Olivier

Abstract

La iniciativa de fortalecimiento de la cultura ambiental y el manejo de residuos sólidos seviene ejecutando desde el segundo semestre del 2014, en el distrito de La Cureña, cantón de Sarapiquí.

Published
2016

21. Proceedings of the 7th Biannual International Symposium on Nasopharyngeal Carcinoma 2015

Author

Tan, IB, Chang, Ellen T., Chen, Chien-Jen, Hsu, Wan-Lun, Chien, Yin-Chu, Hildesheim, Allan, McKay, James D., Gaborieau, Valerie, Kaderi, Mohamed Arifin Bin, Purnomosari, Dewajani, Voegele, Catherine, LeCalvez-Kelm, Florence, Byrnes, Graham, Brennan, Paul, Devi, Beena, Li, L., Zhang, Y., Fan, Y., Sun, K., Du, Z., Sun, H., Chan, A. T., Tsao, S. W., Zeng, Y. X., Tao, Q., Busson, Pierre, Lhuillier, Claire, Morales, Olivier, Mrizak, Dhafer, Gelin, Aurore, Kapetanakis, Nikiforos, Delhem, Nadira, Mansouri, Sheila, Cao, Jennifer, Vaidya, Anup, Frappier, Lori, Wai, Lo Kwok, Chen, Sui-Hong, Du, Jin-lin, Ji, Ming-Fang, Huang, Qi-Hong, Liu, Qing, Cao, Su-Mei, Doolan, Denise L., Coghill, Anna, Mulvenna, Jason, Proietti, Carla, Lekieffre, Lea, Bethony, Jeffrey, Hildesheim, and Allan, Fles, Renske, Indrasari, Sagung Rai, Herdini, Camelia, Martini, Santi, Isfandiari, Atoillah, Rhomdoni, Achmad, Adham, Marlinda, Mayangsari, Ika, van Werkhoven, Erik, Wildeman, Maarten, Hariwiyanto, Bambang, Hermani, Bambang, Kentjono, Widodo Ario, Haryana, Sofia Mubarika, Schmidt, Marjanka, O’Sullivan, Brian, Ozyar, Enis, Lee, Anne W. M., Zeng, Mu-Sheng, Gao, Xiaojiang, Tang, Minzhong, Martin, Pat, Zeng, Yi, Carrington, Mary, Coghill, Anna E., Bu, Wei, Nguyen, Hanh, Yu, Kelly J., Lou, Pei-Jen, Wang, Cheng-Ping, Cohen, Jeffrey I., King, Ann D., Chen, Tseng-Cheng, Lin, Ching-Yuan, Tsou, Yung-An, Leu, Yi-Shing, Laio, Li-Jen, Chang, Yen-Liang, Hua, Chun-Hun, Wu, Ming-Shiang, Hsiao, Chu-Hsing Kate, Lee, Jehn-Chuan, Tsai, Ming-Hsui, Cheng, Skye Hung-Chun, Liao, Li-Jen, Yang, Tsung-Lin, Ko, Jenq-Yuh, Ko, Josephine Mun Yee, Dai, Wei, Kwong, Dora, Ng, Wai Tong, Lee, Anne, Ngan, Roger Kai Cheong, Yau, Chun Chung, Tung, Stewart, Lung, Maria Li, Ji, Mingfang, Sheng, Wei, Ng, Mun Hon, Cheng, Weimin, Yu, Xia, Wu, Biaohua, Wei, Kuangrong, Zhan, Jun, Zeng, Yi Xin, Cao, Su Mei, Xia, Ningshao, Yuan, Yong, Cui, Qian, Xu, Miao, Bei, Jin-Xin, Zeng, Yi-Xin, Şahin, B, Dizman, A, Esassolak, M, İkizler, A Saran, Yıldırım, HC, Çaloğlu, M, Atalar, B, Akman, F, Demiroz, C, Atasoy, BM, Canyilmaz, E, Igdem, S, Ugurluer, G, Kütük, T, Akmansoy, M, Ozyar, E, Sommat, Kiattisa, Wang, Fu Qiang, Kwok, Li-Lian, Tan, Terence, Fong, Kam Weng, Soong, Yoke Lim, Cheah, Shie Lee, Wee, Joseph, Casanova, M, Özyar, E, Patte, C, Orbach, D, Ferrari, A, Cristine, VF, Errihani, H, Pan, J, Zhang, L, Liji, S, Grzegorzewski, K, Gore, L, Varan, A, Hutajulu, Susanna Hilda, Khuzairi, Guntara, Kusumo, Henry, Hardianti, Mardiah Suci, Taroeno-Hariadi, Kartika Widayati, Purwanto, Ibnu, Kurnianda, Johan, Messick, Troy E., Malecka, Kimberly, Tolvinski, Lois, Soldan, Samantha, Deakyne, Julianna, Song, Hui, van den Heuvel, Antonio, Gu, Baiwei, Cassel, Joel, McDonnell, Mark, Smith, Garry R., Velvadapu, Venkata, Bian, Haiyan, Zhang, Yan, Carlsen, Marianne, Chen, Shuai, Donald, Alastair, Lemmen, Christian, Reitz, Allen B., Lieberman, Paul M., Chan, King Chi, Chan, Lai Sheung, Lo, Kwok Wai, Yip, Timothy Tak Chun, Kahn, Michael, Mak, Nai Ki, Liu, Fei-Fei, Khaali, Wafa, Thariat, Juliette, Fantin, Laurence, Spirito, Flavia, Khyatti, Meriem, Driss, El Khalil Ben, Olivero, Sylvain, Maryanski, Janet, Doglio, Alain, Xia, Mengxue, Xia, Yunfei, Chang, Hui, Shaw, Rachel, Rahaju, Pudji, Wisesa, Sindhu, Taroeno-Harijadi, Kartika Widayati, Dhamiyati, Wigati, Tan, Sang-Nee, Sim, Sai-Peng, Yusuf, Muhtarum, Romdhoni, Ahmad C., K, Widodo Ario, Rantam, Fedik Abdul, Sugiyanto, Aryati, Lina, Adi-Kusumo, Fajar, Bintoro, SY, Oktriani, R., Herawati, C., Surono, A., Haryana, Sofia M., Zhong, L., Ma, B. B., Kalra, M., Ngo, M., Perna, S., Leen, A., Lapteva, N., Rooney, C. M., Gottschalk, S., Mustikaningtyas, Elida, Herawati, Sri, Romdhoni, Achmad C., Xu, Yarui, Ge, Shengxiang, Li, Fugui, Ng, M. H., Tan, Louise SY, Wong, Benjamin, Lim, C. M., Rantam, Fedik A., Madani, Deasy Z., Akbar, Nur, Permana, Agung Dinasti, Fachiroh, Jajah, Hartati, Dwi, Rahayudjati, T. Baning, Darwis, Iswandi, Anwar, Khoirul, Dwidanarti, Sri Retna, Pramana, Dominicus Wendhy, Safitri, Diah Ari, Danarti, Sri Retna Dwi, Taroeno, Suryo A, Wijaya, I., Oehadian, A., Prasetya, D., Yu, Kelly J, Rahman, Sukri, Budiman, Bestari J., Novialdi, Rahmadona, Lestari, Dewi Yuri, Yin, C., Foussadier, A., Blein, E., Chen, C., Ammour, N. Bournet, Khiatti, M., Cao, S., Marzaini, Dewi Syafriyetti Soeis, Rahayujati, Baning, Gunawan, L., Mubarika Haryana, S., Hartono, Michael, Intansari, Umi, Paramita, Dewi Kartikawati, Akbar, Akmal, Hermawan, Benny, Paramita, Dewi K., Argy, Gabriella, Sihotang, Theodora Caroline, Wahyono, Daniel Joko, Soeharso, Purnomo, Suryandari, Dwi Anita, Lisnawati, Musa, Zanil, Daker, Maelinda, Tzen, Yeo Jiun, Bakar, Norhasimah, Rahman, Asma’ Saiyidatina Aishah Abdul, Ahmad, Munirah, Chia, Yeo Tiong, Beng, Alan Khoo Soo, Sasikirana, Widyandani, Wardana, Tirta, Radifar, Muhammad, Herawati, Cita, Surono, Agus, and Çocuk Sağlığı ve Hastalıkları

Subjects
Meeting Abstracts
Abstract

A1 Hope and despair in the current treatment of nasopharyngeal cancer, IB Tan, I1 NPC international incidence and risk factors, Ellen T Chang, I2 Familial nasopharyngeal carcinoma and the use of biomarkers, Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien, I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings, Allan Hildesheim, I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia, James D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena Devi, I6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylation, Li L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao Q, I7 Tumor exosomes and translational research in NPC, Pierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira Delhem, I8 Host manipulations of the Epstein-Barr virus EBNA1 protein, Sheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori Frappier, I9 Somatic genetic changes in EBV-associated nasopharyngeal carcinoma, Lo Kwok Wai, I10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern China, Sui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei Cao, I11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disorders, Denise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan Hildesheim, I12 The nasopharyngeal carcinoma awareness program in Indonesia, Renske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB Tan, I13 Current advances and future direction in nasopharyngeal cancer management, Brian O’Sullivan, I14 Management of juvenile nasopharyngeal cancer, Enis Ozyar, I15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapy, Anne WM Lee, I16 The predictive/prognostic biomarker for nasopharyngeal carcinoma, Mu-Sheng Zeng, I17 Effect of HLA and KIR polymorphism on NPC risk, Xiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary Carrington, I18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal Carcinoma, Anna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I Cohen, I19 Advances in MR imaging in NPC, Ann D King, O1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Yin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, O2 Familial tendency and environmental co-factors of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Kelly J Yu, Yin-Chu Chien, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang, Tsung-Lin Yang, Chun-Hun Hua, Ming-ShiangWu, Chu-Hsing Kate Hsiao, Jehn-ChuanLee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Jenq-Yuh Ko, Allan Hildesheim, Chien-Jen Chen, O3 The genetic susceptibility and prognostic role of TERT-CLPTM1L and genes in DNA damage pathways in NPC, Josephine Mun Yee Ko, Wei Dai, Dora Kwong, Wai Tong Ng, Anne Lee, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Maria Li Lung, O4 Long term effects of NPC screening, Mingfang Ji, Wei Sheng, Mun Hon Ng, Weimin Cheng, Xia Yu, Biaohua Wu, Kuangrong Wei, Jun Zhan, Yi Xin Zeng, Su Mei Cao, Ningshao Xia, Yong Yuan, O5 Risk prediction of nasopharyngeal carcinoma by detecting host genetic and Epstein-Barr virus variation in saliva, Qian Cui, Miao Xu, Jin-Xin Bei, Yi-Xin Zeng, O6 Patterns of care study in Turkish nasopharyngeal cancer patients (NAZOTURK): A Turkish Radiation Oncology Association Head and Neck Cancer Working Group Study, B Şahin, A Dizman, M Esassolak, A Saran İkizler, HC Yıldırım, M Çaloğlu, B Atalar, F Akman, C Demiroz, BM Atasoy, E Canyilmaz, S Igdem, G Ugurluer, T Kütük, M Akmansoy, E Ozyar, O7 Long term outcome of intensity modulated radiotherapy in nasopharyngeal carcinoma in National Cancer Centre Singapore, Kiattisa Sommat, Fu Qiang Wang, Li-Lian Kwok, Terence Tan, Kam Weng Fong, Yoke Lim Soong, Shie Lee Cheah, Joseph Wee, O8 International phase II randomized study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents, M Casanova, E Özyar, C Patte, D Orbach, A Ferrari, VF Cristine, H Errihani, J Pan, L Zhang, S Liji, K Grzegorzewski, L Gore, A Varan, O9 Prognostic impact of metastatic status in patients with nasopharyngeal carcinoma, Susanna Hilda Hutajulu, Guntara Khuzairi, Camelia Herdini, Henry Kusumo, Mardiah Suci Hardianti, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Johan Kurnianda, O10 Development of small molecule inhibitors of latent Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma, Troy E. Messick, Kimberly Malecka, Lois Tolvinski, Samantha Soldan, Julianna Deakyne, Hui Song, Antonio van den Heuvel, Baiwei Gu, Joel Cassel, Mark McDonnell, Garry R Smith, Venkata Velvadapu, Haiyan Bian, Yan Zhang, Marianne Carlsen, Shuai Chen, Alastair Donald, Christian Lemmen, Allen B Reitz, Paul M Lieberman, O11 Therapeutic targeting of cancer stem-like cells using a Wnt modulator, ICG-001, enhances the treatment outcome of EBV-positive nasopharyngeal carcinoma, King Chi Chan, Lai Sheung Chan, Kwok Wai Lo, Timothy Tak Chun Yip, Roger Kai Cheong Ngan, Michael Kahn, Maria Li Lung, Nai Ki Mak, O12 Role of micro-RNA in NPC biology, Fei-Fei Liu, O13 Expansion of EBNA1- and LMP2-specific effector T lymphocytes from patients with nasopharyngeal carcinoma without enhancement of regulatory T cells, Wafa Khaali; Juliette Thariat; Laurence Fantin; Flavia Spirito; Meriem Khyatti; El Khalil Ben Driss; Sylvain Olivero; Janet Maryanski; Alain Doglio, O14 The experience of patients’ life after amifostine radiotherapy treatment (ART) for nasopharyngeal carcinoma (NPC), Mengxue Xia, Yunfei Xia, Hui Chang, Rachel Shaw, O15 Analysis of mitochondrial DNA mutation in latent membrane protein-1 positive nasopharyngeal carcinoma, Pudji Rahaju, O16 Factors influencing treatment adherence of nasopharyngeal cancer and the clinical outcomes: a hospital-based study, Mardiah Suci Hardianti, Sindhu Wisesa, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, O17 Chromosomal breaks mediated by bile acid-induced apoptosis in nasopharyngeal epithelial cells: in relation to matrix association region/scaffold attachment region, Sang-Nee Tan, Sai-Peng Sim, O18 Expression of p53 (wild type) on nasopharyngeal carcinoma stem cell that resistant to radiotherapy, Muhtarum Yusuf, Ahmad C Romdhoni, Widodo Ario K, Fedik Abdul Rantam, O19 Mathematical model of nasopharyngeal carcinoma in cellular level, Sugiyanto, Lina Aryati, Fajar Adi-Kusumo, Mardiah Suci Hardianti, O20 Differential expression of microRNA-21 on nasopharyngeal carcinoma plasma patient, SY Bintoro, R Oktriani, C. Herawati, A Surono, Sofia M. Haryana, O21 Therapeutic targeting of an oncogenic fibroblast growth factor-FGF19, which promotes proliferation and induces EMT of carcinoma cells through activating ERK and AKT signaling, L. Zhong, L. Li, B. B. Ma, A. T. Chan, Q. Tao, O22 Resist nasopharyngeal carcinoma (NPC): next generation T cells for the adoptive immunotherapy of NPC, M. Kalra, M. Ngo, S. Perna, A. Leen, N. Lapteva, C. M. Rooney, S. Gottschalk, O23 The correlation of heat shock protein 70 expressions and staging of nasopharyngeal carcinoma, Elida Mustikaningtyas, Sri Herawati, Achmad C Romdhoni, O24 Epstein-Barr virus serological profiles of nasopharyngeal carcinoma - A tribute to Werner Henle, Mingfang Ji, YaruiXu, Weimin Cheng, ShengxiangGe, Fugui Li, M. H. Ng, O25 Targeting the apoptosis pathway using combination TLR3 agonist with anti-survivin molecule (YM-155) in nasopharyngeal carcinoma, Louise SY Tan, Benjamin Wong, CM Lim, O26 The resistance mechanism of nasopharyngeal cancer stem cells to cisplatin through expression of CD44, Hsp70, p53 (wild type), Oct-4, and ß-catenin encoded-genes, Achmad C Romdhoni, Fedik A. Rantam, Widodo Ario Kentjono, P1 Prevalence of nasopharyngeal carcinoma patients at Departement of Otorhinolaringology-Head and Neck Surgery, Dr. Hasan Sadikin general hospital, Bandung, Indonesia in 2010-2014, Deasy Z Madani, Nur Akbar, Agung Dinasti Permana, P2 Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito Hospital, Yogyakarta, Camelia Herdini, Sagung Rai Indrasari, Jajah Fachiroh, Dwi Hartati, T. Baning Rahayudjati, P3 Report on loco regionally advanced nasopharyngeal cancer patients treated with induction chemotherapy followed by concurrent chemo-radiation therapy, Iswandi Darwis, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P4 Sex and age differences in the survival of patients with nasopharyngeal carcinoma, Sindhu Wisesa, Mardiah Suci Hardianti, Susanna Hilda Hutajulu, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Camelia Herdini, Wigati Dhamiyati, Johan Kurnianda, P5 Impact of delayed diagnosis and delayed therapy in the treatment outcome of patients with nasopharyngeal carcinoma, Khoirul Anwar, Susanna Hilda Hutajulu, Sagung Rai Indrasari, Sri Retna Dwidanarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P6 Anaysis of pretreatment anemia in nasopharyngeal cancer patients undergoing neoadjuvant therapy, Dominicus Wendhy Pramana, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P7 Results of treatment with neoadjuvant cisplatin-5FU in locally advanced nasopharyngeal carcinoma: a local experience, Diah Ari Safitri, Susanna Hilda Hutajulu, Camelia Herdini, Sri Retna Dwi Danarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P8 Geriatrics with nasopharyngeal cancer, Suryo A Taroeno, Sindhu Wisesa, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, P9 Correlation of lymphocyte to monocyte and neutrophil to lymphocyte ratio to the response of cisplatin chemoradiotheraphy in locally advance nasopharyngeal carcinoma, I. Wijaya, A. Oehadian, D. Prasetya, P10 Prediction of nasopharyngeal carcinoma risk by Epstein-Barr virus seromarkers and environmental co-factors: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Yin-Chu Chien, Kelly J Yu, Cheng-Ping Wang, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang191,192, Jenq-Yuh Ko, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, P11 Non-viral risk factors for nasopharyngeal carcinoma in West Sumatra, Indonesia, Sukri Rahman, Bestari J. Budiman, Novialdi, Rahmadona, Dewi Yuri Lestari, P12 New prototype Vidas EBV IgA quick: performance on Chinese and Moroccan populations, C. Yin, A. Foussadier, E. Blein, C. Chen, N. Bournet Ammour, M. Khiatti, S. Cao, P13 The expression of EBV-LMP1 and VEGF as predictors and plasma EBV-DNA levels as early marker of distant metastasis after therapy in nasopharyngeal cancer, Dewi Syafriyetti Soeis Marzaini, P14 Characteristics and factors influencing subjects refusal for blood samples retrieval: lesson from NPC case control study in Yogyakarta – Indonesia, Dwi Hartati, Baning Rahayujati, Camelia Herdini, Jajah Fachiroh, P15 Expression of microRNA BART-7-3p and mRNA PTEN on blood plasma of patients with nasopharyngeal carcinoma, L. Gunawan, S. Mubarika Haryana, A. Surono, C. Herawati, P16 IgA response to native early antigen (IgA-EAext) of Epstein-Barr virus (EBV) in healthy population and nasopharyngeal carcinoma (NPC) patients: the potential for diagnosis and screening tools, Michael Hartono, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P17 IgA responses against Epstein-Barr Virus Early Antigen (EBV-EA) peptides as potential candidates of nasopharyngeal carcinoma detection marker, Akmal Akbar, Jajah Fachiroh, Dewi Kartikawati Paramita, P18 Association between smoking habit and IgA-EBV titer among healthy individuals in Yogyakarta, Indonesia, Benny Hermawan, T Baning Rahayudjati, Dewi K Paramita, Jajah Fachiroh, P19 Epstein-Barr virus IgA titer comparison of healthy non-family individuals and healthy first degree family of NPV patients, Gabriella Argy, Jajah Fachiroh, Dewi Kartikawati Paramita, Susanna Hilda Hutajulu, P20 Identification of EBV Early Antigen (EA) derived peptides for NPC diagnosis, Theodora Caroline Sihotang, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P21 Host-pathogen study: relative expression of mRNA BRLF1 Epstein-Barr virus as a potential biomarker for tumor progressivity and polymorphisms of TCRBC and TCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma, Daniel Joko Wahyono, Purnomo Soeharso, Dwi Anita Suryandari, Lisnawati, Zanil Musa, Bambang Hermani, P22 In vitro efficacy of silvestrol and episilvestrol, isolated from Borneo, on nasopharyngeal carcinoma, a major cancer in Borneo, Maelinda Daker, Yeo Jiun Tzen, Norhasimah Bakar, Asma’ Saiyidatina Aishah Abdul Rahman, Munirah Ahmad, Yeo Tiong Chia, Alan Khoo Soo Beng, P23 The expression of mir-141 in patients with nasopharyngeal cancer, Widyandani Sasikirana, Tirta Wardana, Muhammad Radifar, Cita Herawati, Agus Surono, Sofia Mubarika Haryana

Published
2016

23. Impact of Exogenous Galectin-9 on Human T Cells: CONTRIBUTION OF THE T CELL RECEPTOR COMPLEX TO ANTIGEN-INDEPENDENT ACTIVATION BUT NOT TO APOPTOSIS INDUCTION*

Author

Lhuillier, Claire, Barjon, Clément, Niki, Toshiro, Gelin, Aurore, Praz, Françoise, Morales, Olivier, Souquere, Sylvie, Hirashima, Mitsuomi, Wei, Ming, Dellis, Olivier, and Busson, Pierre

Subjects
stomatognathic diseases, animal structures, CD3 Complex, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Galectins, T-Lymphocytes, Immunology, otorhinolaryngologic diseases, Receptors, Antigen, T-Cell, Cytokines, Humans, Apoptosis, Calcium
Abstract

Galectin-9 (gal-9) is a multifunctional β-galactoside-binding lectin, frequently released in the extracellular medium, where it acts as a pleiotropic immune modulator. Despite its overall immunosuppressive effects, a recent study has reported bimodal action of gal-9 on human resting blood T cells with apoptosis occurring in the majority of them, followed by a wave of activation and expansion of Th1 cells in the surviving population. Our knowledge of the signaling events triggered by exogenous gal-9 in T cells remains limited. One of these events is cytosolic calcium (Ca(2+)) release reported in some murine and human T cells. The aim of this study was to investigate the contribution of Ca(2+) mobilization to apoptotic and nonapoptotic effects of exogenous gal-9 in human T cells. We found that the T cell receptor (TCR)-CD3 complex and the Lck kinase were required for Ca(2+) mobilization but not for apoptosis induction in Jurkat cells. These data were confirmed in human CD4(+) T cells from peripheral blood as follows: a specific Lck chemical inhibitor abrogated Ca(2+) mobilization but not apoptosis induction. Moreover, Lck activity was also required for the production of Th1-type cytokines, i.e. interleukin-2 and interferon-γ, which resulted from gal-9 stimulation in peripheral CD4(+) T cells. These findings indicate that gal-9 acts on T cells by two distinct pathways as follows: one mimicking antigen-specific activation of the TCR with a mandatory contribution of proximal elements of the TCR complex, especially Lck, and another resulting in apoptosis that is independent of this complex.

Published
2015

25. CD49b, a Major Marker of Regulatory T-Cells Type 1, Predicts the Response to Antiviral Therapy of Recurrent Hepatitis C after Liver Transplantation

Author

Aoudjehane Lynda, Delhem Nadira, Conti Filomena, Stenard Fabien, Goormachtigh Gautier, Ouaguia Laurissa, Calmus Yvon, Viallon Vivian, Ghazal Khaldoun, Morales Olivier, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Unité de biostatistique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL UPMC, Gestionnaire, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Biopsy, medicine.medical_treatment, Integrin alpha2, lcsh:Medicine, Liver transplantation, T-Lymphocytes, Regulatory, CD49b, Polyethylene Glycols, 0302 clinical medicine, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prospective cohort study, 0303 health sciences, medicine.diagnostic_test, FOXP3, General Medicine, Middle Aged, Hepatitis C, Recombinant Proteins, 3. Good health, Treatment Outcome, Liver, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, 030211 gastroenterology & hepatology, Research Article, Adult, Article Subject, Antiviral Agents, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, Virus, 03 medical and health sciences, Immune system, Ribavirin, medicine, Humans, Aged, Demography, 030304 developmental biology, General Immunology and Microbiology, business.industry, lcsh:R, Interferon-alpha, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Transplantation, Gene Expression Regulation, Immunology, business, Biomarkers
Abstract

The TRANSPEG study was a prospective study to assess the efficacy of antiviral therapy in patients with a recurrent hepatitis C virus (HCV) after liver transplantation. The influence of regulatory T-cells (Tregs) on the response to antiviral therapy was analyzed. Patients were considered as a function of their sustained virological response (SVR) at 18 months after treatment initiation. A transcriptomic analysis was performed to assess Treg markers (Tr1 and FoxP3+) in serum, PBMC, and liver biopsies. 100 patients had been included in the TRANSPEG study. Data from 27 of these patients were available. The results showed that the expression of CD49b (a predominant marker of Tr1) before the introduction of antiviral therapy was significantly associated with SVR. Responders displayed lower serum levels of CD49b than nonresponders (P<0.02). These findings were confirmed in PBMC and liver biopsies even if in a nonsignificant manner for the limited number of samples. The assessment of CD49b levels is thus predictive of the response to antiviral therapy. This data suggests that CD49b may be a marker of the failure of the immune response and antiviral therapy during HCV recurrence. The assessment of CD49b could help to select patients who require earlier and more intensive antiviral therapy.

Published
2014

26. Impact of Exogenous Galectin-9 on Human T Cells

Author

Lhuillier, Claire, primary, Barjon, Clément, additional, Niki, Toshiro, additional, Gelin, Aurore, additional, Praz, Françoise, additional, Morales, Olivier, additional, Souquere, Sylvie, additional, Hirashima, Mitsuomi, additional, Wei, Ming, additional, Dellis, Olivier, additional, and Busson, Pierre, additional

Published
2015
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27. Evaluation of a new therapeutic strategy in Nasopharyngeal carcinoma: Photodynamic Therapy using 5-aminolevulinic acid.

Author

TRIOEN, Camille, LEFEBVRE, Anthony, LEROUX, Bertrand, DELHEM, Nadira, and MORALES, Olivier

Abstract

Nasopharyngeal carcinoma (NPC) is a chemo-radiosensitive cancer leading to an effective control of the primary tumor with a 10-year disease-free survival rate of 67-71%. However, due to late diagnosis and extensive metastatic formation, the survival rate decreases drastically to 29-54%. Thus, for recurrent or persistent local tumors, there are few treatment options left. Photodynamic Therapy (PDT) could be a relevant candidate by inducing direct cell death and the activation of a systemic immune response. Indeed, NPC is characterized by an immunosuppressive environment dominated by regulatory T lymphocytes and tumor-derived exosomes (NPC-Exo). We demonstrated that NPC-Exo induce dendritic cells with tolerogenic properties favouring the suppressive microenvironment [1]. Moreover, the team's work has established the ability of PDT to induce the release of ovarian tumor derived extracellular vesicles capable of activating immune cells [2]. In this context, the objective of this study is to evaluate, on one hand, the effectiveness of a new therapeutic strategy in the NPC namely a photodynamic therapy using 5-aminolevulinc acid (5-ALA) and on the other hand to assess the impact of PDT on the deleterious function of NPC-Exo. Two NPC cell lines, C17 and C666-1 were used. First, we evaluate the capacity of the cell to metabolize the photosensitizer PpIX. And then, we validated the effectiveness of PDT using an ATP-based viability assay. After the determination of the optimal lighting protocol, we will assess the ability of the PDT strategy to modulate the secretome (ELISA) and NPC-Exo phenotype and properties (Suppressive test). This strategy will be confirmed in vivo in a humanized mouse model of NPC. We have shown that C17 and C666-1 cell lines are able to incorporate 5-ALA and to metabolize the photosensitizer PpIX in a dose and time dependent manner. C17 cells appear receptive to PDT treatment with significant cell death. We expected that photodynamic therapy strategy could allow a modification in cytokines production, NPC-Exo fonction and could induce tumor regression in mouse model. Taken together, these results seem to indicate that 5-ALA-mediated PDT could be a promising treatment of NPCs as an adjuvant therapy to conventional anti-cancer therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Targeted PDT for intraperitoneal ovarian cancer, a novel way to stimulate anti-tumoral immune response.

Author

BOIDIN, Léa, BAYDOUN, Martha, LEROUX, Bertrand, MORALES, Olivier, ACHERAR, Samir, FROCHOT, Céline, and DELHEM, Nadira

Abstract

Ovarian cancer is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. The Photodynamic treatment (PDT) available data have shown improvements in the uptake in small tumors and in the induction of a proper anti-tumoral immune response. Herein we propose PDT using a PS coupled with folate receptor for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFN γ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFN γ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Targeted PDT, a novel way to induce immunoactivating properties and stimulate anti-tumoral immune response: Illustration in human Pancreatic Adenocarcinoma and Peritoneal Ovarian Cancer models.

Author

QUILBE, Alexandre, BOIDIN, Léa, BAYDOUN, Martha, MORALES, Olivier, MURAKAMI, Takashi, LEROUX, Bertrand, ZIANE, Laurine, FROCHOT, Céline, MORDON, Serge, and DELHEM, Nadira

Abstract

Otherwise, the use of Photodynamic Therapy (PDT), based on the use of a photosensitizer (PS) and a light with a specific wavelength, has already proved its worth and has prompted a growing interest in the field of oncology. The combination of these factors will generate cytotoxic reactive oxygen species capable of inducing cancer cell death and very importantly, to close the tumor-associated vasculature and trigger the host immune system. More specifically, the damage induced by the PDT generates various alarm signals that could be detected by effectors of innate and adaptative immunity. Nevertheless, the effect of PDT on the regulation of the immune system remains poorly investigated. Although PDT appears to be more selective than other cancer treatment procedures, cancers such as pancreatic adenocarcinoma (ADKP) and intraperitoneal ovarian cancers (OVC) are more problematic and, therefore, the PS used must be much more selective for these tumors. Our previous study described the specificity of a new patented PS coupled with folate receptor (FR) and capable of targeting specifically cancer cells which overexpresses FR. In this context, the aim of this study was (i) to evaluate in vitro and in vivo the efficacy of this new-patented photosensitizer on ADKP and ovarian cancer, which expressed FR in 100% of ADKP and OVC or over-expressed in almost 50% of cases and (ii) to analyze the consequences of this treatment on the regulation of the human immune cells (PBMC). For this purpose, we first evaluated the viability and proliferation rate of these two different human cancer cell lines after targeted PDT treatment. We have also evaluated the secretion of cancer cells subjected to PDT, in particular by analyzing the cytokines and the effects of extracellular vesicles (EVs) secreted by the treated cancer cells. We then examined the effect of this secretome on human peripheral blood mononuclear cells (PBMC) to define the profile of the induced immune response. Finally, we have evaluated in vivo the efficacy of this targeted PDT in a humanized SCID mice model of PDAC and OVC, without and with human PBMC reconstitution. We showed that this PS upon illumination could induce cell death of different ovarian tumor and ADKP cell lines. Furthermore, PDT using this new PS seems to favor an activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing EVs prone to activate immune cells. We also showed that PDT can activate CD4+ and CD8+ T cells resulting in a potential immunostimulating process. All the results therefore indicate that PDT treatment with this new PS would not only be effective in rapidly and directly destroying target tumor cells, but would also promote the activation of effective immune response notably by EVs and promote the development of a protective long-term antitumor immune response. Finally, after fractionized PDT protocol, a significant decrease in the tumor volume was noticed in both in vivo models (PDAC and OVC-SCID mice). An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease with a subsequent inhibition in the cytokine TGFβ. An immune response was activated resulting in an increase in NK, CD3 +T cells, and both helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of PDAC and Ovarian cancer These data thus open up good prospects for the treatment of PDAC and micrometastases of intraperitoneal ovarian carcinosis that are currently inoperable. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Vectorized photosensitizers to target, detect and treat peritoneal metastases by photodynamic therapy.

Author

MOINARD, Morgane, BOIDIN, Léa, MORALES, Olivier, ACHERAR, Samir, ARNOUX, Philippe, DELHEM, Nadira, and FROCHOT, Céline

Abstract

60% of women with epithelial ovarian cancer relapse after conventional treatment, which combines complete macroscopic cytoreduction surgery (CRS) with platinum salt-based chemotherapy. This high recurrence rate is believed to be strongly related to the presence of microscopic residues at the end of surgery. It is essential to detect and treat these microscopic peritoneal metastases after macroscopic CRS, in order to limit their occurrence and thus increase the survival of the patients after treatment. Folate Receptor α (FR) shows promising prospects in targeting ovarian cancerous cells. Folic acid (FA) targeted photosensitizer could be used in intraperitoneal PDT that could be an innovative add-on therapy to macroscopic cytoreductive surgery to treat microscopic peritoneal metastasis. A disadvantage of FA is that it undergoes structure decomposition upon illumination. In order to avoid this decomposition, we designed and developed modified FA. We performed rational changes based on our own expertise and on systematic molecular docking in parallel. These modifications are also considered based on the known interactions between folic acid and FRα. A first FA analog was synthesized and coupled with pyropheophorbide a. The final product was obtained after 9 synthesis steps and with an overall yield of 10%. The study of its photophysical properties was performed and showed similarity with those of free pyropheophorbide a. The first biological analyses showed an absence of dark toxicity of this new analogue for various ovarian cancer cell lines. Moreover, its efficiency in PDT was demonstrated by the induction of cell death at a concentration of 1.8 μM, with 5 min illumination we could observe 60% cell death 24h after PDT and with a concentration of 9 μM, with 60 min illumination, 100 % cell death 24h after PDT. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Development of a light emitting device for the treatment of peritoneal carcinomatosis of ovarian origin by intracavitary photodynamic therapy.

Author

ZIANE, Laurine, BAERT, Grégory, MORALES, Olivier, VIGNION-DEWALLE, Anne-Sophie, and DELHEM, Nadira

Abstract

Peritoneal carcinomatosis of ovarian origin (PCO) is an evolution of ovarian cancer, which is the fourth leading cause of death by cancer in women in France. PCO is defined by dissemination of cancerous cells from ovarian cancer to the peritoneal cavity. Photodynamic therapy (PDT) has been proposed in complement to the standard of care, consisting of surgery and chemotherapy. However, litterature has highlighted the lack of selectivity of available photosensitizers (PS) leading to inconclusive results [1, 2]. In this context, PRODYNOV project, initiated by our research team INSERM U1189 ONCOTHAI, has enabled the development of a patented PS. The high selectivity of this PS makes possible to carry out relevant PDT for PCO provided that an adequate illumination device would exist. In this study, we developed and assessed such a device. First, a test bench aiming to evaluate quantity and homogeneity of the delivered illumination has been developed. It is composed of a fantom of peritoneal cavity in which seven optical probes connected to a power-meter were placed in strategic zones characterised by high recurrence risk. Then, three illumination devices were implemented and assessed. The first one consisted of six fixed light emitting fabrics (LEF), the second one was a moving luminous wand, and the last one, a hybrid one, combined a fixed luminous wand and six fixed LEF. Light doses received by the probes have been calculated by integrating measured powers over illumination time. Each of the seven optical probes received a mean light dose of 0.68 mJ with the first illumination device (minimum: 18.37 10−3 mJ, maximum: 2.66 mJ), 0.11 mJ with the second one (minimum: 5.25 10−3 mJ, maximum: 0.35 mJ) and 0.65 mJ with the third one (minimum: 48.19 10−3 mJ, maximum: 1.27 mJ). With a variation coefficient of 77.1% (versus 93.1% for the first device and 119.5% for the second one), the hybrid device enabled to homogeneously illuminate the largest part of the cavity. For these reasons, the hybrid method has been selected as illumination process for PDT of PCO. Illumination solutions for PDT of PCO have been proposed and tested. One of these solutions has been approved. The light dose necessary for an effective treatment remains to be determined and first feasability tests will be led on mini-pig by the end of the year. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Intraperitoneal targeted photodynamic therapy for advanced epithelial ovarian cancer.

Author

AZAÏS, Henri, BAYDOUN, Martha, MOINARD, Morgane, MORALES, Olivier, COLOMBEAU, Ludovic, LEROUX, Bertrand, ZIANE, Laurine, MORDON, Serge, DELHEM, Nadira, and FROCHOT, Céline

Abstract

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist and be the cause of peritoneal recurrence that occur in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve the patient survival. Therapeutic targeting method, such as photodynamic therapy (PDT), would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origin including ovarian cancer cells, is a good target to address photosensitizing molecules. Long limited by the absence of a sufficiently specific photosensitizer to allow its application in the peritoneal cavity, the development of intraperitoneal PDT is based on the synthesis of a patent protected drug candidate. We have shown that PDT with a folate-targeted photosensitizer could induce in vitro cell death of different ovarian tumor cells and in vivo tumor growth limitation in a humanized mouse model of ovarian peritoneal carcinosis. The results obtained also underline the positive impact of PDT on the activation of the immune response by inducing the secretion of effective cytokines and by inhibiting that of pro-inflammatory and immunosuppressive cytokines, as well as by releasing extracellular vesicles likely to activate the immune cells, leading to an immunostimulation process. These data must be confirmed in vivo. They require a redefinition of the position of PDT as a potential treatment with a systemic effect to be considered as an immunotherapy, and its coherent integration in the current management proposed to patients. The objective of this presentation is to present recent results concerning our research on photodynamic therapy using a photosensitizer coupled to folate and to discuss the modalities of an application of this strategy in human medical practice. [ABSTRACT FROM AUTHOR]

Published
2023
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33. The chemokine CCL18 generates adaptive regulatory T cells from memory CD4+ T cells of healthy but not allergic subjects.

Author

Chang, Ying, De Nadai, Patricia, Azzaoui, Imane, Morales, Olivier, Delhem, Nadira, Vorng, Han, Tomavo, Stanislas, Ait Yahia, Saliha, Zhang, Guizhen, Wallaert, Benoît, Chenivesse, Cécile, Tsicopoulos, Anne, Chang, Ying, De Nadai, Patricia, Azzaoui, Imane, Morales, Olivier, Delhem, Nadira, Vorng, Han, Tomavo, Stanislas, Ait Yahia, Saliha, Zhang, Guizhen, Wallaert, Benoît, Chenivesse, Cécile, and Tsicopoulos, Anne

Abstract

The purpose of this study was to assess the direct effect of CCL18, a chemokine elevated in allergic diseases and induced by Th2 cytokines, on the polarization of human CD4(+) T cells. Purified human T cells from healthy subjects were pretreated or not with CCL18, and evaluated for cytokine production. CCL18-pretreated memory but not naive CD4(+) T cells exhibited an increased production of IL-10 (12.3 ± 2.6 vs. 5.6 ± 0.9 ng/ml for medium) and TGF-β1 but not IL-4, IFN-γ, and IL-17 compared with control cells. Pretreatment of highly purified CD4(+)CD25(-) memory T cells with CCL18 led to their conversion to CD4(+)CD25(+)Foxp3(+) regulatory T cells able to inhibit the proliferation of CD4(+)CD25(-) effector T cells by both cytokine and cell contact-dependent mechanisms. However, this regulatory effect of CCL18 was lost when T cells originated from allergic subjects in relation with a decreased binding of CCL18 to these cells [0.7 ± 0.3 mean fluorescence intensity (MFI)] as compared to those from healthy subjects (6.0 ± 1.7 MFI). This study is the first to define a chemokine that generates adaptive regulatory T cells from CD4(+)CD25(-) memory T cells. This mechanism appears defective in allergic patients and may underlie the decreased tolerance observed in allergic diseases., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2010

34. Rôle des Lymphocytes T régulateurs dans la progression de la fibrose hépatique associée à l'infection par le VHC.

Author

Delhem, Nadira, Cottrez, Françoise, Carpentier, Arnaud, Miroux, Céline, Morales, Olivier, Francois, Violaine, Groux, Hervé, Auriault, Claude, Pancré, Véronique, Delhem, Nadira, Cottrez, Françoise, Carpentier, Arnaud, Miroux, Céline, Morales, Olivier, Francois, Violaine, Groux, Hervé, Auriault, Claude, and Pancré, Véronique

Abstract

Hepatitis C virus (HCV) becomes chronic in about 85 % of infected individuals, whereas only 15 % of infected people clear spontaneously the virus. The progression of hepatitis C to chronic status is associated to a profound down-regulation of CD4 and CD8 multispecific immune response. This immune defect may participate to the immune tolerance of VHC and consequently to its persistence. Recent findings indicate that T regulatory cells as Tr1 play an inhibitory role on T helper responses notably in the context of auto-immune or inflammatory disorders. The existence of immunosuppressive mechanisms supported by Tr1 lymphocytes and their IL-10 production represent an attractive hypothesis. We have previously evaluated the existence of regulatory T cells (Tr1) via high production of IL-10, in liver biopsies of three well-defined cohorts of HCV-1b infected patients. To this purpose, we compared liver biopsies of chronically infected patients including patients without liver lesions, with cirrhosis and with hepatocellular carcinoma (HCC). Using quantitative real time PCR, the results obtained demonstrate, an increased expression of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta)_, in liver biopsies with more severe fibrosis. This observation was correlated with an increased expression during the pathogenesis progression, of the three specific markers of the Tr1 cells sub-population, recently described and confirming the Tr1 phenotype. Evidence of regulatory T cells installation in the liver of chronically infected patient and increased frequency in cirrhosis and HCC suggest a main role of these cells in the aggravation of the liver pathology. This study should bring insight of T regulatory cell implications in VHC persistence and in the pathology progression., English Abstract, Journal Article, info:eu-repo/semantics/published

Published
2008

36. Determination of a HLA II promiscuous peptide cocktail as potential vaccine against EBV latency II malignancies.

Author

Depil, Stéphane, Morales, Olivier, Castelli, Florence A, Delhem, Nadira, Francois, Violaine, Georges, Bertrand, Dufossé, Françoise, Morschhauser, F, Hammer, Juergen, Maillère, Bernard, Auriault, Claude, Pancré, Véronique, Depil, Stéphane, Morales, Olivier, Castelli, Florence A, Delhem, Nadira, Francois, Violaine, Georges, Bertrand, Dufossé, Françoise, Morschhauser, F, Hammer, Juergen, Maillère, Bernard, Auriault, Claude, and Pancré, Véronique

Abstract

The Epstein-Barr virus (EBV) is associated with several malignant diseases, which can be distinguished by their patterns of viral latent gene expression. The latency II program is limited to the expression of the nonimmunodominant antigens EBNA1, LMP1 and LMP2 and is seen in EBV-positive Hodgkin disease, nasopharyngeal carcinomas, and peripheral T/NK-cell lymphomas. CD4 T cells may play a crucial role in controlling these EBV latency II malignancies. In this study, we used the prediction software TEPITOPE to predict promiscuous major histocompatibility complex class II epitopes derived from the latency II antigens EBNA1, LMP1, and LMP2. The predicted peptides were then submitted to peptide-binding assays on HLA II purified molecules, which allowed the selection of 6 peptides (EBNA1: 3; LMP1: 1; and LMP2: 2) with a highly promiscuous capability of binding. This peptide cocktail was immunogenic in a model of HLA-DR1 transgenic mice, leading to a specific cellular and humoral TH1 response. The peptides were also recognized by human CD4 T cells from individuals expressing various HLA II genotypes. This promiscuous peptide cocktail could be immunogenic in the majority of the population and may be used as a peptide-based vaccine in EBV latency II malignancies., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2007

37. Peptide-binding assays and HLA II transgenic Abeta degrees mice are consistent and complementary tools for identifying HLA II-restricted peptides.

Author

Depil, Stéphane, Angyalosi, Gerhild, Morales, Olivier, Delacre, Myriam, Delhem, Nadira, Francois, Violaine, Georges, Bertrand, Hammer, Juergen, Maillère, Bernard, Auriault, Claude, Pancré, Véronique, Depil, Stéphane, Angyalosi, Gerhild, Morales, Olivier, Delacre, Myriam, Delhem, Nadira, Francois, Violaine, Georges, Bertrand, Hammer, Juergen, Maillère, Bernard, Auriault, Claude, and Pancré, Véronique

Abstract

The identification of MHC class II-restricted peptides has become a priority for the development of peptide-based prophylactic and therapeutic vaccines. The aim of this study was to assess the correlations between peptide-binding assays on purified HLA II molecules and immunization of human HLA II transgenic mice deficient in murine class II molecules (Abeta degrees ). We used as models two MHC class II-restricted peptides, one derived from the HIV Nef regulatory protein (Nef (56-68)) and the other from the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST (190-211)). High correlations were found between the two approaches, which showed that the Nef (56-68) and Sm28GST (190-211) peptides may represent promiscuous ligands for HLA-DQ and for HLA-DR molecules, respectively. We suggest a rational method based on the combination of peptide-binding assays and HLA II transgenic mice experiments as consistent and complementary tools for selecting T helper epitopes., Journal Article, info:eu-repo/semantics/published

Published
2006

38. Pulmonary CCL18 Recruits Human Regulatory T Cells

Author

Chenivesse, Cécile, primary, Chang, Ying, additional, Azzaoui, Imane, additional, Ait Yahia, Saliha, additional, Morales, Olivier, additional, Plé, Coline, additional, Foussat, Arnaud, additional, Tonnel, André-Bernard, additional, Delhem, Nadira, additional, Yssel, Hans, additional, Vorng, Han, additional, Wallaert, Benoit, additional, and Tsicopoulos, Anne, additional

Published
2012
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39. Inhibition of Latent Membrane Protein 1 Impairs the Growth and Tumorigenesis of Latency II Epstein-Barr Virus-Transformed T Cells

Author

Ndour, Papa Alioune, primary, Brocqueville, Guillaume, additional, Ouk, Tan-Sothéa, additional, Goormachtigh, Gautier, additional, Morales, Olivier, additional, Mougel, Alexandra, additional, Bertout, Julie, additional, Melnyk, Oleg, additional, Fafeur, Véronique, additional, Feuillard, Jean, additional, Coll, Jean, additional, and Adriaenssens, Eric, additional

Published
2012
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41. The chemokine CCL18 generates adaptive regulatory T cells from memory CD4+ T cells of healthy but not allergic subjects

Author

Chang, Ying, primary, de Nadai, Patricia, additional, Azzaoui, Imane, additional, Morales, Olivier, additional, Delhem, Nadira, additional, Vorng, Han, additional, Tomavo, Stanislas, additional, Ait Yahia, Saliha, additional, Zhang, Guizhen, additional, Wallaert, Benoît, additional, Chenivesse, Cécile, additional, and Tsicopoulos, Anne, additional

Published
2010
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42. The Pulmonary Chemokine CCL18 Recruits Human Regulatory T Cells

Author

Chenivesse, Cécile, primary, Chang, Ying, additional, Azzaoui, Imane, additional, Morales, Olivier, additional, Foussat, Arnaud, additional, Delhem, Nadira, additional, Kemper, Claudia, additional, Tonnel, André-Bernard, additional, Yssel, Hans, additional, Wallaert, Benoit, additional, Lassalle, Philippe, additional, and Tsicopoulos, Anne, additional

Published
2010
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46. The chemokine CCL18 generates adaptive regulatory T cells from memory CD4+ T cells of healthy but not allergic subjects.

Author

Chang, Ying, De Nadai, Patricia, Azzaoui, Imane, Morales, Olivier, Delhem, Nadira, Vorng, Han, Tomavo, Stanislao, Yahia, Saliha Ait, Zhang, Guizhen, Wallaert, Benoît, Chenivesse, Cécile, and Tsicopoulos, Anne

Subjects
BIOLOGICAL research, CHEMOKINES, T cells, CD4 antigen, ALLERGIES
Abstract

The purpose of this study was to assess the direct effect of CCL18, a chemokine elevated in allergic diseases and induced by Th2 cytokines, on the polarization of human CD4+ T cells. Purified human T cells from healthy subjects were pretreated or not with CCL18, and evaluated for cytokine production. CCL18-pretreated memory but not naive CD4 T cells exhibited an increased production of IL10 (12.3±2.6 vs. 5.6±0.9 ng/ml for medium) and TGF-β1 but not HA, IFNγ, and IL-17 compared with control cells. Pretreatment of highly purified CD4+CD25- memory T cells with CCL18 led to their CD4+CD25-FoxP3+ conversion to CIM regulatory T cells able to inhibit the proliferation of CD4+CD25- effector T cells by both cytokine and cell contact-dependent mechanisms. However, this regulatory effect of CCL18 was lost when T cells originated from allergic subjects in relation with a decreased binding of CCL18 to these cells [0.7±0.3 mean fluorescence intensity (MFI)] as compared to those from healthy subjects (6.0±1.7 MFI). This study is the first to define a chemokine CD25- that generates adaptive regulatory T cells from CD4+ memory T cells. This mechanism appears defective in allergic patients and may underlie the decreased tolerance observed in allergic diseases. [ABSTRACT FROM AUTHOR]

Published
2010
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