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1. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, de Garibay, G Ruiz, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Català, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, AM, de Weerd, V, Look, MP, Puertas, S, García, N, Perkins, AS, Bonifaci, N, Skowron, M, Gómez-Baldó, L, Hernández, V, Martínez-Aranda, A, Martínez-Iniesta, M, Serrat, X, Cerón, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernández, A, Morilla, I, Pernas, S, Plà, MJ, Andreu, X, Seguí, MA, Ballester, R, Castellà, E, Nellist, M, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sánchez-Mut, JV, Sánchez-Céspedes, M, Cordero, A, Gómez-Miragaya, J, Palomero, L, Gómez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, López-Bigas, N, Valdés-Mas, R, Puente, XS, Viñals, F, Casanovas, O, Graupera, M, Hernández-Losa, J, Ramón y Cajal, S, García-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martín-Martín, N, Matheu, A, Carracedo, A, González-Suárez, E, Nanjundan, M, Cortés, J, Lázaro, C, Odero, MD, Martens, JWM, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, and Pujana, MA

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Stem Cell Research, Adaptor Proteins, Signal Transducing, Adult, Aged, Breast Neoplasms, Carrier Proteins, Cell Proliferation, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, MCF-7 Cells, MDS1 and EVI1 Complex Locus Protein, Microfilament Proteins, Middle Aged, Neoplasm Metastasis, Osteonectin, Proto-Oncogenes, Regulatory-Associated Protein of mTOR, SOX9 Transcription Factor, Signal Transduction, TOR Serine-Threonine Kinases, Transcription Factors, Xenograft Model Antitumor Assays, Clinical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017

4. Microbial control of seawater by microfiltration

Author

Wilmer Soler T, Juan P. Soler A, and Harold Durango

Subjects
seawater disinfection, seawater drinking, coastal water pollution, Public aspects of medicine, RA1-1270
Abstract

Recent scientific literature presents seawater as a potential aid to solve a variety of health diseases in animals and human beings because by means of its mineral and trace elements content. In Colombia, Nicaragua and Spain it is collected in a natural way from de shore and drunk; however, this can represent a health risk because of the problems related to chemical and microbiological contamination. Microbial control of seawater allows the improvement of its microbiological quality. Objective: to compare the efficiency of three microbial control methods: microfiltration, solar exposition and quarantine. Methodology: 30 samples were collected in 20-liter high density polyethylene containers in three different places in the Colombian Atlantic coast. Results: 15 samples out of 30 showed the presence of bacteria such as E. coli and halophiles bacteria like Vibrio and Aeromonas. Microfiltration through ceramic filters of 0.5 µm produces disinfection in 100% of the samples but the quarantine for five months and solar disinfection are effective in 66 and 21% respectively. The latter requires certain weather conditions to achieve disinfection and it only allows managing small quantities of water. Dicussion: Considering chemical contamination in some places which cannot be controlled through disinfection methods, the collection of water offshore in clean places is suggested and then microfiltration treatment should be performed.

Published
2010

5. BAJA GENOTOXICIDAD DE EXTRACTO ORGÁNICO DE AGUA DE MAR DE COVEÑAS (SUCRE, COLOMBIA) LOW GENOTOXICITY OF ORGANIC SEA WATER EXTRACTS FROM COVEÑAS (SUCRE, COLOMBIA)

Author

Wilmer SOLER T, Nelly D VELÁSQUEZ E, and Juan P SOLER A

Subjects
agua de mar, extracto orgánico, genotoxicidad, citotoxicidad, ensayo cometa, sea water, organic extract, genotoxicity, cytotoxicity, comet assay, Food processing and manufacture, TP368-456, Pharmaceutical industry, HD9665-9675
Abstract

El agua de mar natural se utiliza en algunos países iberoamericanos como elemento nutritivo y terapéutico, y en los países desarrollados se usa como complemento nutricional de forma refinada y comercial. Los estudios de ingesta de agua de mar tratada muestran que no hay toxicidad; sin embargo, el uso de agua cercana a las playas representa un riesgo para la salud debido a la polución de los centros urbanos. En este estudio se emplearon linfocitos humanos y la electroforesis de células individuales (ensayo cometa), para comparar la genotoxicidad de un extracto orgánico de agua de mar tomada de la orilla respecto a muestras obtenidas mar adentro en el pequeño municipio de Coveñas-Sucre, Colombia, que vierte sus aguas domésticas directamente al mar o a pozos sépticos. Se observa genotoxicidad a 37 ºC pero no a 4 ºC, este efecto es dependiente de la concentración del extracto (pNatural sea water is used as a nutritive and therapeutic element in Ibero-American countries, and commercial, refined sea water as a nutritional complement in developed countries. Although treated sea water has no toxicity, as demonstrated by previous sea water ingestion studies, consumption of near-shore seawater poses a health risk due to pollution of nearby urban centers. In this study, human lymphocytes and single cell gel electrophoresis (comet assay) were used to compare the genotoxicity of an organic sea water extract taken near shore with that of sea water samples taken offshore in the small municipality of Coveñas (Sucre, Colombian), where domestic waters are flushed directly into the sea or into septic tanks. Genotoxicity was observed at 37°C, but not at 4°C. This effect depends on the concentration of extract (p

Published
2008

6. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, K., Haynes, H. R., Blackley, E., Fineberg, S., Shear, J., Turner, S., de Freitas, J. R., Sur, D., Amendola, L. C., Gharib, M., Kallala, A., Arun, I., Azmoudeh-Ardalan, F., Fujimoto, L., Sua, L. F., Liu, S. -W., Lien, H. -C., Kirtani, P., Balancin, M., El Attar, H., Guleria, P., Yang, W., Shash, E., Chen, I. -C., Bautista, V., Do Prado Moura, J. F., Rapoport, B. L., Castaneda, C., Spengler, E., Acosta-Haab, G., Frahm, I., Sanchez, J., Castillo, M., Bouchmaa, N., Md Zin, R. R., Shui, R., Onyuma, T., Husain, Z., Willard-Gallo, K., Coosemans, A., Perez, E. A., Provenzano, E., Ericsson, P. G., Richardet, E., Mehrotra, R., Sarancone, S., Ehinger, A., Rimm, D. L., Bartlett, J. M. S., Viale, G., Denkert, C., Hida, A. I., Sotiriou, C., Loibl, S., Hewitt, S. M., Badve, S., Symmans, W. F., Kim, R. S., Pruneri, G., Goel, S., Francis, P. A., Inurrigarro, G., Yamaguchi, R., Garcia-Rivello, H., Horlings, H., Afqir, S., Salgado, R., Adams, S., Kok, M., Dieci, M. V., Michiels, S., Demaria, S., Loi, S., Schelfhout, V., Arbzadeh, E., Bondanar, A., Reyes, S. A. G., Ruz, J. R., Kang, J., Xiang, L., Zimovjanova, M., Togores, P., Ozturk, T., Patil, A., Corpa, M., Whitehouse, A., Tan, B., de Paula, A., Rossetti, C., Lang-Schwarz, C., Mahon, S., Giacometti, C., Linderholm, B., Deman, F., Montagna, G., Gong, G., Pavcovich, M., Chaer, Y., Cabrero, I. A., de Brito, M. L., Ilieva, N., Fulop, A., Souza, M., Bilancia, D., Idowu, M., Johri, R., Szpor, J., Bachani, L., Schmitt, F., Giannotti, M., Kurebayashi, Y., Ramirez, B. E. A., Salido, E., Bortesi, L., Bonetto, S., Elomina, K., Lopez, P., Sharma, V., Edirisinghe, A., Mathur, D., Sahay, A., Mouloud, M. A., Giang, C. H., Mukolwe, E., Kiruka, E., Samberg, N., Abe, N., Brown, M., Millar, E., X. B., Li, Yuan, Z., Pasupathy, A., Miele, R., Luff, R., e Porfirio, M. M. A., Ajemba, O., Soni, R., Orvieto, E., Dimaio, M., Thomas, J., Merard, R., Subramaniam, M. M., Apolinario, T., Preda, O., Preda, R., Makanga, A., Maior, M. S., Li, L., Saghatchian, M., Saurine, T., Janssen, E., Cochran, J., Vlada, N., Cappellesso, R., Elfer, K., Hollick, M., Desai, S., Oner, G., Schreurs, A., Liu, S., Perera, R., Mercurio, P., Garcia, F., Hosny, K., Matsumoto, H., van Deurzen, C., Bianchini, G., Coban, I., Jahangir, A., Rahman, A., Stover, D., Luz, P., Martel, A., Waumans, Y., Stenzinger, A., Cortes, J., Dimitrova, P., Nauwelaers, I., Velasco, M., Fan, F., Akturk, G., Firer, M., Roxanis, I., Schneck, M., Wen, H., Cockenpot, V., Konstantinov, A., Calatrava, A., Vidya, M. N., Choi, H. J., Jank, P., Ciinen, A. H., Sabanathan, D., Floris, G., Hoeflmayer, D., Hamada, T., Laudus, N., Grigoriadis, A., Porcellato, I., Acs, B., Miglietta, F., Parrodi, J., Clunie, D., Calhoun, B., F. -I., Lu, Lefevre, A., Tabbarah, S., Tran, W., Garcia-murillas, I., Jelinic, P., Boeckx, C., Souza, S., Cebollero, M. C., Felip, E., Rendon, J. L. S., El Gabry, E., Saltz, J., Bria, E., Garufi, G., Hartman, J., Sebastian, M., Olofsson, H., Kooreman, L., Cucherousset, J., Mathieu, M. -C., Ballesteros-Merino, C., Siziopikou, P., Fong, J., Klein, M., Qulis, I. R. I., Wesseling, J., Bellolio, E., Araya, J. C., Naber, S., Cheang, M., Castellano, I., Ales, A., Laenkholm, A. -V., Kulka, J., Quinn, C., Sapino, A., Amendoeira, I., Marchio, C., Braybrooke, J., Vincent-Salomon, A., Korski, K. P., Sofopoulos, M., Stovgaard, E. I. S., Bianchi, S., Bago-Horvath, Z., Yu, C., Regitnig, P., Hall, S., Kos, Z., Sant, S., Tille, J. -C., Gallas, B., Bethmann, D., Savas, P., Mendes, L., Soler, T., van Seijen, M., Gruosso, T., Quintana, A., Giltnane, J., Van den Eynden, G., Duregon, E., de Cabo, R., Recamo, P. C., Gaboury, L., Zimmerman, J., Pop, C. S., Wernicke, A., Williams, D., Gill, A., Solomon, B., Thapa, B., Farshid, G., Gilham, L., Christie, M., O'Toole, S., Hendry, S., Fox, S. B., Luen, S. J., Lakhani, S. R., Fuchs, T., John, T., Brcic, I., Hainfellner, J., Sigurd, L., Preusser, M., Poortmans, P., Decaluwe, A., Carey, C., Colpaert, C., Larsimont, D., Peeters, D., Broeckx, G., van de Vijver, K., Buisseret, L., Dirix, L., Hertoghs, M., Piccart, M., Ignatiadis, M., Van Bockstal, M., Sirtaine, N., Vermeulen, P., de Wind, R., Declercq, S., Gevaert, T., Haibe-Kans, B., Nelson, B. H., Watson, P. H., Leung, S., Nielsen, T., Shi, L., Balslev, E., Thagaard, J., Almangush, A., Makitie, A., Joensuu, H., Lundin, J., Drubay, D., Roblin, E., Andre, F., Penault-Llorca, F., Lemonnier, J., Adam, J., Lacroix-Triki, M., Ternes, N., Radosevic-Robin, N., Klaushen, F., Weber, K., Harbeck, N., Gluz, O., Wienert, S., Cserni, G., Vingiani, A., Criscitiello, C., Solinas, C., Curigliano, G., Konishi, E., Suzuki, E., Yoshikawa, K., Kawaguchi, K., Takada, M., Toi, M., Ishida, M., Shibata, N., Saji, S., Kogawa, T., Sakatani, T., Okamoto, T., Moriya, T., Kataoka, T., Shimoi, T., Sugie, T., Mukohara, T., Shu, Y., Kikawa, Y., Kozuka, Y., Sayed, S., Rahayu, R., Ramsaroop, R., Senkus-Konefka, E., Chmielik, E., Cardoso, F., Ribeiro, J., Chan, J., Dent, R., Martin, M., Hagen, C., Guerrero, A., Rojo, F., Comerma, L., Nuciforo, P., Serrano, V. V., Camaea, V. P., Steenbruggen, T., Ciompi, F., Nederlof, I., Jan, Hudecek, van der Laak, J., van den Berg, J., Voorwerk, L., van de Vijver, M., de Maaker, M., Linn, S., Mckenzie, H., Somaiah, N., Tutt, A., Swanton, C., Hiley, C., Moore, D. A., Hall, J. A., Le Quesne, J., Jabbar, K. A., al Bakir, M., Hills, R., Irshad, S., Yuan, Y., Li, Z., Liu, M., Klein, J., Fadare, O., Thompson, A., Lazar, A. J., Gown, A., Lo, A., Garrido Castro, A. C., Madabhushi, A., Moreira, A., Richardson, A., Beck, A. H., Bellizzi, A. M., Wolff, A., Harbhajanka, A., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Singh, B., Chennubhotla, C. S., Chauhan, C., Dillon, D. A., Zardavas, D., Johnson, D. B., Thompson, A. E., Brogi, E., Reisenbichler, E., Huang, E., Hirsch, F. R., Mcarthur, H., Ziai, J., Brock, J., Kerner, J., Zha, J., Lennerz, J. K., Carter, J. M., Reis-Filho, J., Sparano, J., Balko, J. M., Pogue-Geile, K., Steele, K. E., Blenman, K. R. M., Allison, K. H., Pusztai, L., Cooper, L., Estrada, V. M., Flowers, M., Robson, M., Rebelatto, M. C., Hanna, M. G., Goetz, M. P., Khojasteh, M., Sanders, M. E., Regan, M. M., Misialek, M., Amgad, M., Tung, N., Singh, R., Huang, R., Pierce, R. H., Leon-Ferre, R., Swain, S., Ely, S., Kim, S. -R., Bedri, S., Paik, S., Schnitt, S., D'Alfons, T., Kurkure, U., Bossuyt, V., Tong, W., Wang, Y., Dos Anjos, C. H., Gaire, F., Van Diest, P. J., El Bairi, Khalid [0000-0002-8414-4145], de Freitas, Juliana Ribeiro [0000-0003-4978-7273], Sur, Daniel [0000-0002-0926-4614], Amendola, Luis Claudio [0000-0002-6404-450X], Azmoudeh-Ardalan, Farid [0000-0003-4701-0532], Kirtani, Pawan [0000-0002-2343-7016], Yang, Wenxian [0000-0002-5349-9680], Castillo, Miluska [0000-0002-0111-3176], Provenzano, Elena [0000-0003-3345-3965], Mehrotra, Ravi [0000-0001-9453-1408], Ehinger, Anna [0000-0001-9225-7396], Rimm, David L [0000-0001-5820-4397], Bartlett, John MS [0000-0002-0347-3888], Denkert, Carsten [0000-0002-2249-0982], Hida, Akira I [0000-0002-4486-8819], Sotiriou, Christos [0000-0002-5745-9977], Hewitt, Stephen M [0000-0001-8283-1788], Badve, Sunil [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Goel, Shom [0000-0001-8329-9084], Francis, Prudence A [0000-0002-7207-9286], Horlings, Hugo [0000-0003-4782-8828], Salgado, Roberto [0000-0002-1110-3801], Demaria, Sandra [0000-0003-4426-0499], Loi, Sherene [0000-0001-6137-9171], Apollo - University of Cambridge Repository, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), and UNICANCER

Subjects
Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], TRASTUZUMAB, Improved survival, MICROENVIRONMENT, Review Article, SUBTYPES, NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, Breast cancer, Ecology,Evolution & Ethology, PROGNOSTIC-SIGNIFICANCE, Medicine and Health Sciences, Pharmacology (medical), TUMOR-INFILTRATING LYMPHOCYTES, Stage (cooking), RC254-282, Chemical Biology & High Throughput, 0303 health sciences, Human Biology & Physiology, Genome Integrity & Repair, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ASSOCIATION, 3. Good health, 030220 oncology & carcinogenesis, Biomarker (medicine), Life Sciences & Biomedicine, Genetics & Genomics, medicine.medical_specialty, chemical and pharmacologic phenomena, International Immuno-Oncology Biomarker Working Group, Predictive markers, 03 medical and health sciences, Signalling & Oncogenes, SDG 3 - Good Health and Well-being, Internal medicine, 692/53/2423, medicine, Radiology, Nuclear Medicine and imaging, In patient, 030304 developmental biology, Computational & Systems Biology, Science & Technology, IDENTIFICATION, business.industry, review-article, Cancer, 03.01. Általános orvostudomány, Immunotherapy, Tumour Biology, medicine.disease, PREDICTIVE-VALUE, 692/4028/67/1347, Programmed death 1, business, FREE SURVIVAL
Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

Published
2021
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10. Geometric combination of multiple terrestrial network solutions

Author

Han, J.Y., van Gelder, B.H.W., Soler, T., and Snay, R.A.

Subjects
Geodetic satellites -- Usage, Numerical analysis -- Methods, Artificial satellites in surveying -- Methods, Artificial satellites in surveying -- Buildings and facilities, Engineering and manufacturing industries, Science and technology
Abstract

Terrestrial network solutions prepared by different institutes and/or at different epochs imply different reference frame definitions, since various reference stations and processing strategies may be involved. A combination procedure, utilizing a time-variant similarity transformation model, enables a geometric integration of multiple solutions into a common reference frame definition. Additional benefits, including an elimination of systematic bias and a cross check on the quality of each individual network solution, could also be achieved. In this study, a combination approach which takes into account complete geometric interrelations between multiple solutions is developed. With the observable dependency analysis procedure, the proposed approach guarantees a self-consistent, more meaningful, combination solution regardless of the choice of a reference solution. Numerical tests have been performed on actual International Global Navigation Satellite System (GNNS) Service (IGS) and National Geodetic Survey (NGS) solutions using the Geodetic Network Analysis Tool software developed along with this study. Results reveal potential problems if the proposed analysis procedure is not implemented in a combination solution. DOI: 10.1061/(ASCE)0733-9453(2008)134:4(126) CE Database subject headings: Geodetic surveys; Satellites; Numerical analysis.

Published
2008

12. 14P Immunomodulatory effect of denosumab in early breast cancer: Preliminary results of a randomized window-opportunity clinical trial D-Biomark

Author

Vethencourt, A.C., primary, Trinidad, E.M., additional, Gómez Aleza, C., additional, Pernas Simon, S., additional, Petit, A., additional, Soler, T., additional, Urruticoechea, A., additional, Gumà Martinez, A., additional, García-Tejedor, A., additional, Pla, M.J., additional, Capó, C., additional, Gil, M. Gil, additional, Stradella, A., additional, Fernádez, A., additional, Recalde Penabad, S., additional, Cejuela, M., additional, Vazquez, S., additional, Iserte, A., additional, Falo, C., additional, and Gonzalez-Suarez, E., additional

Published
2021
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13. LOW GENOTOXICITY OF ORGANIC SEA WATER EXTRACTS FROM COVEÑAS (SUCRE, COLOMBIA)

Author

Wilmer SOLER T., Nelly D. VELÁSQUEZ E., and Juan P. SOLER A.

Subjects
sea water, organic extract, genotoxicity, cytotoxicity, comet assay, Food processing and manufacture, TP368-456, Pharmaceutical industry, HD9665-9675
Abstract

Natural sea water is used as a nutritive and therapeutic element in Ibero-American countries, and commercial, refined sea water as a nutritional complement in developed countries. Although treated sea water has no toxicity, as demonstrated by previous sea water ingestion studies, consumption of near-shore seawater poses a health risk due to pollution of nearby urban centers. In this study, human lymphocytes and single cell gel electrophoresis (comet assay) were used to compare the genotoxicity of an organic sea water extract taken near shore with that of sea water samples taken offshore in the small municipality of Coveñas (Sucre, Colombian), where domestic waters are flushed directly into the sea or into septic tanks. Genotoxicity was observed at 37°C, but not at 4°C. This effect depends on the concentration of extract (p

Published
2009

20. Enantioselective Synthesis, DFT Calculations, and Preliminary Antineoplastic Activity of Dibenzo 1-Azaspiro[4.5]decanes on Drug-Resistant Leukemias

Author

Mendes, J.A., Merino, P., Soler, T., Salustiano, E.J., Costa, P.R.R., Yus, M., Foubelo, F., and Buarque, C.D.

Subjects
inorganic chemicals
Abstract

The addition of 2-bromobenzylmagnesium bromide to chiral N- tert-butanesulfinyl imines derived from tetralone-type ketones proceeds with high levels of diastereocontrol. The resulting sulfinamide derivatives were transformed into dibenzoazaspiro compounds after a palladium-catalyzed intramolecular N-arylation. DFT calculations have been performed to rationalize the stereochemical course of the reaction. Similar results have been obtained considering either diethyl ether or toluene as a solvent, in both cases in an excellent agreement with experimental findings. NCI topological calculations have also been used to evidence crucial noncovalent interactions. In addition, the azaspiro compounds reduced the viability of chronic myeloid leukemia cells in the micromolar range. Notably, both the halogen-substituted ( R)- and ( S)-8g and -8h as well as ( R)-8j were at least two times more effective on a multidrug-resistant derivative than on the parental cell line, exerting a collateral sensitivity effect.

Published
2020

21. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Author

Hudecek, J., Voorwerk, L., van Seijen, M., Nederlof, I., de Maaker, M., van den Berg, J., van de Vijver, K. K., Sikorska, K., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Michiels, S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S. M., Denkert, C., Loibl, S., Loi, S., Bartlett, J. M. S., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kos, Z., Salgado, R., Kok, M., Horlings, H. M., Hyytiainen, A., Hida, A. I., Thompson, A., Lefevre, A., Lazar, A. J., Gown, A., Lo, A., Sapino, A., Madabhushi, A., Moreira, A., Richardson, A., Vingiani, A., Beck, A. H., Bellizzi, A. M., Guerrero, A., Grigoriadis, A., Ehinger, A., Garrido-Castro, A., Vincent-Salomon, A., Laenkholm, A. -V., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Acs, B., Singh, B., Calhoun, B., Haibe-Kans, B., Solomon, B., Thapa, B., Nelson, B. H., Gallas, B. D., Castaneda, C., Ballesteros-Merino, C., Criscitiello, C., Boeckx, C., Colpaert, C., Quinn, C., Chennubhotla, C. S., Swanton, C., Solinas, C., Hiley, C., Drubay, D., Bethmann, D., Moore, D. A., Larsimont, D., Sabanathan, D., Peeters, D., Zardavas, D., Hoflmayer, D., Johnson, D. B., Thompson, E. A., Brogi, E., Perez, E., Elgabry, E. A., Stovgaard, E. S., Blackley, E. F., Roblin, E., Reisenbichler, E., Bellolio, E., Balslev, E., Chmielik, E., Gaire, F., Andre, F., F. -I., Lu, Azmoudeh-Ardalan, F., Rojo, F., Gruosso, T., Ciompi, F., Peale, F., Hirsch, F. R., Klauschen, F., Penault-Llorca, F., Acosta Haab, G., Farshid, G., van den Eynden, G., Curigliano, G., Floris, G., Broeckx, G., Gonzalez-Ericsson, Koeppen, H., Haynes, H. R., Mcarthur, H., Joensuu, H., Olofsson, H., Lien, H. -C., Chen, I. -C., Cree, I., Frahm, I., Brcic, I., Chan, J., Ziai, J., Brock, J., Wesseling, J., Giltnane, J., Kerner, J. K., Thagaard, J., Braybrooke, J. P., van der Laak, J. A. W. M., Lemonnier, J., Zha, J., Ribeiro, J., Lennerz, J. K., Carter, J. M., Saltz, J., Hartman, J., Hainfellner, J., Quesne, J. L., Juco, J. W., Reis-Filho, J., Sanchez, J., Sparano, J., Cucherousset, J., Araya, J. C., Adam, J., Balko, J. M., Saeger, K., Siziopikou, K., Willard-Gallo, K., Weber, K., Pogue-Geile, K. L., Steele, K. E., Emancipator, K., Abduljabbar, K., El Bairi, K., Blenman, K. R. M., Allison, K. H., Korski, K., Pusztai, L., Comerma, L., Buisseret, L., Cooper, L. A. D., Shi, L., Kooreman, L. F. S., Molinero, L., Estrada, M. V., Lacroix-Triki, M., Al Bakir, M., Sebastian, M. M., van de Vijver, M., Balancin, M. L., Dieci, M. V., Mathieu, M. -C., Rebelatto, M. C., Piccart, M., Hanna, M. G., Goetz, M. P., Preusser, M., Khojasteh, M., Sanders, M. E., Regan, M. M., Barnes, M., Christie, M., Misialek, M., Ignatiadis, M., van Bockstal, M., Castillo, M., Amgad, M., Harbeck, N., Tung, N., Laudus, N., Sirtaine, N., Burchardi, N., Ternes, N., Radosevic-Robin, N., Gluz, O., Grimm, O., Nuciforo, P., Jank, P., Gonzalez-Ericsson, P., Kirtani, P., Jelinic, P., Watson, P. H., Savas, P., Francis, P. A., Russell, P. A., Singh, R., Kim, R. S., Pierce, R. H., Hills, R., Leon-Ferre, R., de Wind, R., Shui, R., De Clercq, S., Leung, S., Tabbarah, S., Souza, S. C., O'Toole, S., Swain, S., Dudgeon, S., Willis, S., Ely, S., Kim, S. -R., Bedri, S., Irshad, S., Liu, S. -W., Goel, S., Hendry, S., Bianchi, S., Braganca, S., Paik, S., Wienert, S., Fox, S. B., Luen, S. J., Naber, S., Schnitt, S. J., Sua, L. F., Lakhani, S. R., Fineberg, S., Soler, T., Gevaert, T., D'Alfonso, T., John, T., Sugie, T., Kurkure, U., Bossuyt, V., Manem, V., Camara, V. P., Tong, W., Chen, W., Yang, W., Tran, W. T., Wang, Y., Yuan, Y., Allory, Y., Husain, Z., Bago-Horvath, Z., Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Charité, Institute of Pathology, Translational Tumorpathology Unit, German Breast Group, Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), University of the Sunshine Coast (USC), European Institute of Oncology [Milan] (ESMO), Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Pathology, The Netherlands Cancer Institute, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hudeček, Jan [0000-0003-1071-5686], van de Vijver, Koen K [0000-0002-2026-9790], Demaria, Sandra [0000-0003-4426-0499], Badve, Sunil S [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Rimm, David L [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hall, Jacqueline A [0000-0003-0708-1360], Horlings, Hugo M [0000-0003-4782-8828], Apollo - University of Cambridge Repository, van de Vijver, Koen K. [0000-0002-2026-9790], Badve, Sunil S. [0000-0001-8861-9980], Rimm, David L. [0000-0001-5820-4397], Hall, Jacqueline A. [0000-0003-0708-1360], Horlings, Hugo M. [0000-0003-4782-8828], Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, German Breast Group (GBG), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review Article, lcsh:RC254-282, 631/67/1857, Tumour biomarkers, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 692/53, Internal medicine, Medicine and Health Sciences, medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, 692/4028/67/580, Stromal tumor, Biomarkers, Tumour immunology, business.industry, Risk management framework, review-article, Médecine pathologie humaine, 631/67/1347, Immunotherapy, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Review article, Clinical trial, Cancérologie, 030104 developmental biology, 030220 oncology & carcinogenesis, Biomarker (medicine), business
Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting., info:eu-repo/semantics/published

Published
2020
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25. Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals

Author

Recalde, S., primary, Quiroga, V., additional, del Barco, S., additional, Falo, C., additional, Dorca, J., additional, Margeli, M., additional, Stradella, A., additional, Soler, T., additional, Te García, I ruel, additional, Viñas, G., additional, Fernandez, A., additional, Vázquez, R Villanueva, additional, Vethencourt, A., additional, Marin, M Romeo, additional, and Gil-Gil, M., additional

Published
2019
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26. Residual cancer burden as a prognostic factor in a large series of neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes

Author

Falo, C., primary, Fernández, S., additional, Garrigós, E., additional, Casado, A C Vethencourt, additional, Vázquez, S., additional, Stradella, A., additional, Recalde, S., additional, Pla, M.J., additional, Campos, M., additional, Gumà, A., additional, Ortega, R., additional, Petit, A., additional, Soler, T., additional, Perez, J., additional, Fernandez, E., additional, Bergamino, M.S., additional, Simon, S Pernas, additional, Gil, M.J., additional, Ponce, J., additional, and Tejedor, A Garcia, additional

Published
2019
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27. Abstract P5-15-09: Impact of oncotype dx genetic signature used in early breast cancer. Clinical and economic analisys of a 110 patient cohort treated in the Catalan Oncologic Institute (ICO), Spain

Author

Ferrer, M, primary, Dorcas, J, additional, Quiroga, V, additional, Margelí, M, additional, del Barco, S, additional, Stradella, A, additional, Petit, A, additional, Falo, C, additional, Viñas, G, additional, Romeo, M, additional, Villanueva, R, additional, Cirauqui, B, additional, Vázquez, S, additional, Fernández, A, additional, Recalde, S, additional, Vethencourt, A, additional, Soler, T, additional, Pérez-Martín, X, additional, and Gil-Gil, M, additional

Published
2019
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29. Abstract P3-13-07: Is radiofrequency ablation better than lumpectomy for margin status in breast cancer? Results of a randomized clinical trial

Author

Garcia-Tejedor, A, primary, Guma, A, additional, Soler, T, additional, Valdivieso, A, additional, Petit, A, additional, Contreras, N, additional, Chappuis, CG, additional, Falo, C, additional, Pernas, S, additional, Anselem, A, additional, Fernandez-Montoli, E, additional, Pla, MJ, additional, Burdio, F, additional, and Ponce, J, additional

Published
2019
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31. Diagnosis of fibroepithelial lesions and Pyllodes tumors by core biopsy: Correlation with the surgical specimen

Author

Soler, T., primary, Dorca, E., additional, Fernandez-Calvo, D., additional, Bosch, J., additional, Petit, A., additional, Taco, M.D.R., additional, Guerra, E., additional, Zanca, A., additional, Baixeras, N., additional, Perez Tapia, L., additional, Ortega, R., additional, Perez-Sidelnikova, D., additional, Fernandez Montoli, M.E., additional, Tena, G., additional, and Matias-Guiu, X., additional

Published
2018
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33. Microbial control of seawater by microfiltration

Author

Soler T, Wilmer, Durango, Harold, and Soler A, Juan P

Subjects
ingestión de agua de mar, seawater disinfection, lcsh:Public aspects of medicine, coastal water pollution, seawater drinking, lcsh:RA1-1270, agua costera, desinfección
Abstract

El agua de mar refinada aparece en la literatura científica reciente como una potencial ayuda terapéutica en el tratamiento de varias enfermedades en humanos y animales por su contenido de minerales y oligoelementos. En Colombia, Nicaragua y España se utiliza de forma natural por recogida de la orilla e ingesta; sin embargo, esto puede representar un riesgo para la salud por los problemas de contaminación microbiológica y química. Los tratamientos de control microbiano del agua de mar permiten mejorar su calidad microbiológica. OBJETIVO: comparar la eficiencia de tres métodos de control microbiano: microfiltración, exposición solar y cuarentena. METODOLOGIA: se recolectaron 30 muestras de agua de mar en recipientes de polietileno de alta densidad con capacidad de 20 litros, en tres lugares diferentes de la costa atlántica colombiana. RESULTADOS: de 30 muestras recolectadas, 15 resultaron con enterobacterias como E. coli y bacterias halófilas como Vibrio y Aeromonas. La microfiltración a través de cerámica de 0,5 µm produce una desinfección de 100% de las muestras, mientras que la cuarentena por cinco meses y la desinfección solar son efectivas en 66 y 21% respectivamente. Esta última requiere de ciertas condiciones climáticas para alcanzar la desinfección y solo permite el manejo de pequeños volúmenes. DISCUSION: Respecto de la contaminación química en ciertos lugares, que no es controlable por los métodos de desinfección, se recomienda recoger el agua en altamar, en lugares limpios, y realizar la microfiltración. Recent scientific literature presents seawater as a potential aid to solve a variety of health diseases in animals and human beings because by means of its mineral and trace elements content. In Colombia, Nicaragua and Spain it is collected in a natural way from de shore and drunk; however, this can represent a health risk because of the problems related to chemical and microbiological contamination. Microbial control of seawater allows the improvement of its microbiological quality. OBJECTIVE: to compare the efficiency of three microbial control methods: microfiltration, solar exposition and quarantine. METHODOLOGY: 30 samples were collected in 20-liter high density polyethylene containers in three different places in the Colombian Atlantic coast. RESULTS: 15 samples out of 30 showed the presence of bacteria such as E. coli and halophiles bacteria like Vibrio and Aeromonas. Microfiltration through ceramic filters of 0.5 µm produces disinfection in 100% of the samples but the quarantine for five months and solar disinfection are effective in 66 and 21% respectively. The latter requires certain weather conditions to achieve disinfection and it only allows managing small quantities of water. DISCUSSION: Considering chemical contamination in some places which cannot be controlled through disinfection methods, the collection of water offshore in clean places is suggested and then microfiltration treatment should be performed.

Published
2010

34. Abstract P6-15-06: SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety

Author

Gil-Gil, M, primary, Bellet, M, additional, Morales, S, additional, Barnadas, A, additional, Manso, L, additional, Morilla Ruiz, I, additional, Azaro, A, additional, Ciruelos Gil, E, additional, Garcia Martínez, E, additional, Marínez, N, additional, Melé, M, additional, Soler, T, additional, Villagrasa, P, additional, and Pernas, S, additional

Published
2018
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35. Abstract P4-08-08: Biomarkers to predict distant recurrence free survival after neoadjuvant endocrine therapy in breast cancer. A long follow up retrospective study

Author

Gil-Gil, M, primary, Morilla, I, additional, Petit, A, additional, Soler, T, additional, Perez-Martin, X, additional, Guma, A, additional, Pla, MJ, additional, Ortega, R, additional, Garcia-Tejedor, A, additional, Falo, C, additional, Montal, R, additional, Perez-Casanova, L, additional, Loayza, C, additional, and Pernas, S, additional

Published
2018
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36. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F. (F.), Arenas, E.J. (E. J.), Aguilar, H. (Helena), Serra-Musach, J. (Jordi), De Garibay, G.R. (G. Ruiz), Boni, J. (J.), Maicas, M. (M.), Du, S. (S.), Iorio, F. (F.), Herranz-Ors, C. (C.), Islam, A. (A.), Prado, X. (X.), Llorente, A. (A.), Petit, A. (Anna), Vidal, A. (A.), Català, I. (Isabel), Soler, T. (T.), Venturas, G. (G.), Rojo-Sebastian, A. (A.), Serra, H. (H.), Cuadras, D. (Daniel), Blanco, I. (I.), Lozano, J. (J.), Canals, F. (F.), Sieuwerts, A.M. (Anieta), Weerd, V. (Vanja) de, Look, M.P. (Maxime), Puertas, S. (S.), García, N. (Nadia), Perkins, A.S. (A. S.), Bonifaci, N. (Núria), Skowron, M. (Margaretha), Gómez-Baldó, L. (Laia), Hernández, V. (V.), Martínez-Aranda, A. (A.), Martínez-Iniesta, M. (M.), Serrat, X. (X.), Cerón, J. (Julián), Brunet, J. (Joan), Barretina, M.P. (M. P.), Gil, M. (Miguel), Falo, C. (C.), Fernández, A. (A.), Morilla, I. (I.), Pernas, S. (S.), Plà, M.J. (M. J.), Andreu, X. (X.), Seguí, M.A. (M. A.), Ballester, R. (R.), Castellà, E. (E.), Nellist, M.D. (Mark), Morales, S. (S.), Valls, J. (J.), Velasco, A. (A.), Matias-Guiu, X. (Xavier), Figueras, J., Sánchez-Mut, J.V. (J. V.), Sánchez-Céspedes, M. (M.), Cordero, A. (A.), Gómez-Miragaya, J. (J.), Palomero, L. (L.), Gómez, A. (A.), Gajewski, T.F. (T. F.), Cohen, E.E.W. (E. E.W.), Jesiotr, M. (M.), Bodnar, L. (L.), Quintela-Fandino, M. (M.), López-Bigas, N. (Núria), Valdés-Mas, R. (Rafael), Puente, X.S. (Xose), Viñals, F. (F.), Casanovas, O. (O.), Graupera, M. (M.), Hernandez-Losa, J. (Javier), Ramóny Cajal, S. (S.), García-Alonso, L. (L.), Saez-Rodriguez, J. (J.), Esteller, M. (Manel), Sierra, A. (A.), Martín-Martín, N. (N.), Matheu, A. (A.), Carracedo, A. (A.), González-Suárez, E. (E.), Nanjundan, M. (M.), Cortés, J. (J.), Lázaro, C. (C.), Odero, M.D. (Maria), Martens, J.W.M. (John), Moreno-Bueno, G. (G.), Barcellos-Hoff, M.H., Villanueva, A. (Alberto), Gomis, R.R. (R. R.), Pujana, M.A. (M. A.), Mateo, F. (F.), Arenas, E.J. (E. J.), Aguilar, H. (Helena), Serra-Musach, J. (Jordi), De Garibay, G.R. (G. Ruiz), Boni, J. (J.), Maicas, M. (M.), Du, S. (S.), Iorio, F. (F.), Herranz-Ors, C. (C.), Islam, A. (A.), Prado, X. (X.), Llorente, A. (A.), Petit, A. (Anna), Vidal, A. (A.), Català, I. (Isabel), Soler, T. (T.), Venturas, G. (G.), Rojo-Sebastian, A. (A.), Serra, H. (H.), Cuadras, D. (Daniel), Blanco, I. (I.), Lozano, J. (J.), Canals, F. (F.), Sieuwerts, A.M. (Anieta), Weerd, V. (Vanja) de, Look, M.P. (Maxime), Puertas, S. (S.), García, N. (Nadia), Perkins, A.S. (A. S.), Bonifaci, N. (Núria), Skowron, M. (Margaretha), Gómez-Baldó, L. (Laia), Hernández, V. (V.), Martínez-Aranda, A. (A.), Martínez-Iniesta, M. (M.), Serrat, X. (X.), Cerón, J. (Julián), Brunet, J. (Joan), Barretina, M.P. (M. P.), Gil, M. (Miguel), Falo, C. (C.), Fernández, A. (A.), Morilla, I. (I.), Pernas, S. (S.), Plà, M.J. (M. J.), Andreu, X. (X.), Seguí, M.A. (M. A.), Ballester, R. (R.), Castellà, E. (E.), Nellist, M.D. (Mark), Morales, S. (S.), Valls, J. (J.), Velasco, A. (A.), Matias-Guiu, X. (Xavier), Figueras, J., Sánchez-Mut, J.V. (J. V.), Sánchez-Céspedes, M. (M.), Cordero, A. (A.), Gómez-Miragaya, J. (J.), Palomero, L. (L.), Gómez, A. (A.), Gajewski, T.F. (T. F.), Cohen, E.E.W. (E. E.W.), Jesiotr, M. (M.), Bodnar, L. (L.), Quintela-Fandino, M. (M.), López-Bigas, N. (Núria), Valdés-Mas, R. (Rafael), Puente, X.S. (Xose), Viñals, F. (F.), Casanovas, O. (O.), Graupera, M. (M.), Hernandez-Losa, J. (Javier), Ramóny Cajal, S. (S.), García-Alonso, L. (L.), Saez-Rodriguez, J. (J.), Esteller, M. (Manel), Sierra, A. (A.), Martín-Martín, N. (N.), Matheu, A. (A.), Carracedo, A. (A.), González-Suárez, E. (E.), Nanjundan, M. (M.), Cortés, J. (J.), Lázaro, C. (C.), Odero, M.D. (Maria), Martens, J.W.M. (John), Moreno-Bueno, G. (G.), Barcellos-Hoff, M.H., Villanueva, A. (Alberto), Gomis, R.R. (R. R.), and Pujana, M.A. (M. A.)

Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017
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41. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, primary, Arenas, E J, additional, Aguilar, H, additional, Serra-Musach, J, additional, de Garibay, G Ruiz, additional, Boni, J, additional, Maicas, M, additional, Du, S, additional, Iorio, F, additional, Herranz-Ors, C, additional, Islam, A, additional, Prado, X, additional, Llorente, A, additional, Petit, A, additional, Vidal, A, additional, Català, I, additional, Soler, T, additional, Venturas, G, additional, Rojo-Sebastian, A, additional, Serra, H, additional, Cuadras, D, additional, Blanco, I, additional, Lozano, J, additional, Canals, F, additional, Sieuwerts, A M, additional, de Weerd, V, additional, Look, M P, additional, Puertas, S, additional, García, N, additional, Perkins, A S, additional, Bonifaci, N, additional, Skowron, M, additional, Gómez-Baldó, L, additional, Hernández, V, additional, Martínez-Aranda, A, additional, Martínez-Iniesta, M, additional, Serrat, X, additional, Cerón, J, additional, Brunet, J, additional, Barretina, M P, additional, Gil, M, additional, Falo, C, additional, Fernández, A, additional, Morilla, I, additional, Pernas, S, additional, Plà, M J, additional, Andreu, X, additional, Seguí, M A, additional, Ballester, R, additional, Castellà, E, additional, Nellist, M, additional, Morales, S, additional, Valls, J, additional, Velasco, A, additional, Matias-Guiu, X, additional, Figueras, A, additional, Sánchez-Mut, J V, additional, Sánchez-Céspedes, M, additional, Cordero, A, additional, Gómez-Miragaya, J, additional, Palomero, L, additional, Gómez, A, additional, Gajewski, T F, additional, Cohen, E E W, additional, Jesiotr, M, additional, Bodnar, L, additional, Quintela-Fandino, M, additional, López-Bigas, N, additional, Valdés-Mas, R, additional, Puente, X S, additional, Viñals, F, additional, Casanovas, O, additional, Graupera, M, additional, Hernández-Losa, J, additional, Ramón y Cajal, S, additional, García-Alonso, L, additional, Saez-Rodriguez, J, additional, Esteller, M, additional, Sierra, A, additional, Martín-Martín, N, additional, Matheu, A, additional, Carracedo, A, additional, González-Suárez, E, additional, Nanjundan, M, additional, Cortés, J, additional, Lázaro, C, additional, Odero, M D, additional, Martens, J W M, additional, Moreno-Bueno, G, additional, Barcellos-Hoff, M H, additional, Villanueva, A, additional, Gomis, R R, additional, and Pujana, M A, additional

Published
2016
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42. Lipoma Arborescens of the Knee: MR Characteristics in 13 Joints

Author

Bargiela A, Da Riba M, Rodríguez E, and Soler T

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Adolescent, Knee Joint, Synovitis, Pigmented Villonodular, Fat mass, Diagnosis, Differential, Lesion, Clinical history, Synovitis, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, business.industry, Synovial Membrane, Anatomy, Lipoma arborescens, Middle Aged, Lipoma, medicine.disease, Magnetic Resonance Imaging, Female, Joint Diseases, medicine.symptom, Signal intensity, business, Mixed pattern
Abstract

Purpose: Lipoma arborescens (LA) is a rare, poorly understood intraarticular lesion, with few cases reported in the imaging literature. Our purpose was to describe on MR the different morphologic appearances of LA of the knee and to investigate the incidence of associated anomalies. Method: The medical records and MR findings of 12 patients with proven LA in 13 knee joints were retrospectively reviewed with particular emphasis on the shape of the lesion, location, signal intensity, and past clinical history. Results: We found three common morphological patterns of presentation: multiple villous lipomatous synovial proliferations (n = 6), isolated frond-like fat subsynovial mass (n = 2), and mixed pattern (n = 5). Multiple villous lipomatous synovial proliferations and mixed pattern were usually associated with a history of trauma and/or chronic inflammatory diseases. However. the least frequent isolated frond-like fat subsynovial mass appears to originate without antecedent. The durations of symptoms were 1-7 months (multiple villous lipomatous synovial proliferations). 1-20 years (mixed pattern). and 6-7 years (isolated frond-like subsynovial fat mass). Conclusion: Our study suggests that LA can present with a variety of morphological appearances on MR that may depend on the previous clinical history and duration of the disease.

Published
1998
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47. BAJA GENOTOXICIDAD DE EXTRACTO ORGÁNICO DE AGUA DE MAR DE COVEÑAS (SUCRE, COLOMBIA)

Author

SOLER T, Wilmer, VELÁSQUEZ E, Nelly D, and SOLER A, Juan P

Subjects
organic extract, comet assay, genotoxicity, genotoxicidad, sea water, extracto orgánico, cytotoxicity, agua de mar, citotoxicidad, ensayo cometa
Abstract

El agua de mar natural se utiliza en algunos países iberoamericanos como elemento nutritivo y terapéutico, y en los países desarrollados se usa como complemento nutricional de forma refinada y comercial. Los estudios de ingesta de agua de mar tratada muestran que no hay toxicidad; sin embargo, el uso de agua cercana a las playas representa un riesgo para la salud debido a la polución de los centros urbanos. En este estudio se emplearon linfocitos humanos y la electroforesis de células individuales (ensayo cometa), para comparar la genotoxicidad de un extracto orgánico de agua de mar tomada de la orilla respecto a muestras obtenidas mar adentro en el pequeño municipio de Coveñas-Sucre, Colombia, que vierte sus aguas domésticas directamente al mar o a pozos sépticos. Se observa genotoxicidad a 37 ºC pero no a 4 ºC, este efecto es dependiente de la concentración del extracto (p

Published
2008

48. Parasitological versus molecular diagnosis of strongyloidiasis in serial stool samples: how many?

Author

Dacal, E., Saugar, J. M., Soler, T., Azcárate, J. M., Jiménez, M. S., Merino, F. J., and Rodríguez, E.

Subjects
STRONGYLOIDIASIS, PARASITOLOGY, FECAL analysis, IMMUNOCOMPROMISED patients, POLYMERASE chain reaction, DIAGNOSIS
Abstract

Strongyloidiasis is usually an asymptomatic disease in immunocompetent patients, caused by Strongyloides stercoralis. However, in immunocompromised patients it can produce a severe clinical profile. Therefore, a correct diagnosis is necessary in these cases and in those chronic asymptomatic patients. The low sensitivity of classical parasitological techniques requires the analysis of multiple serial stool samples. Molecular diagnostic techniques represent an improvement in the detection of the parasite. The objective of this study was to evaluate the minimum number of samples necessary to achieve maximum sensitivity by real-time polymerase chain reaction (PCR). A total of 116 stool samples from 39 patients were analysed by direct microscopic observation, agar culture, Harada-Mori and real-time PCR, in one, two, three and four or more consecutive samples. After two serial samples, 6 out of 39 patients were positive by parasitological and molecular techniques, while 16 of them were real-time PCR positive, and all the patients detected by parasitology were also detected by the molecular technique, reaching 100.00% sensitivity versus 83.00% when analysing a single sample. These data also reflect apparently low specificity (51.52%) and positive predictive value (PPV) (27.27 %) values, due to the high number of cases detected by real-time PCR and not by parasitological techniques. These cases were confirmed as true positives when analysing three, four or more samples from the same patient. In conclusion, the application of molecular techniques decreases the number of serial stool samples necessary to give a diagnosis with the maximum sensitivity. [ABSTRACT FROM AUTHOR]

Published
2018
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49. Absence of genotoxicity of sea water from Coveñas: In vitro study on human leukocytes and erythrocytes

Author

Soler T, Wilmer, Velásquez E, Nelly del Carmen, Miranda R, Luis Francisco, and Zuluaga G, Diana Cristina

Subjects
Sea water, actividad antioxidante, comet assay, genotoxicity, genotoxicidad, antioxidant activity, Agua de mar, ensayo cometa
Abstract

En Colombia y América latina se ha iniciado recientemente el uso nutricional y terapéutico del agua de mar natural, por su contenido de minerales y oligoelementos, práctica ya reconocida en Europa desde hace más de un siglo. Objetivo: evaluar la posible toxicidad del agua de mar de Coveñas (costa atlántica colombiana). Materiales y métodos: se incubaron células humanas en agua de mar recogida en Coveñas para determinar fragilidad osmótica de eritrocitos, viabilidad celular y daño en el ADN de linfocitos (ensayo cometa); además, se determinó su capacidad antioxidante. Resultados: los eritrocitos en agua de mar presentaron hemólisis significativamente mayor respecto a la observada en amortiguador PBS hipertónico de concentración similar (4,3 y 2,8% respectivamente, P = 0,00001); sin embargo, la diferencia de los promedios fue muy pequeña. La viabilidad celular de los linfocitos en agua de mar fue de 95%, similar a la observada en PBS isotónico. Dicha agua de mar tampoco produjo daño en el ADN de linfocitos humanos, según los resultados de los promedios del momento de Olive del ensayo cometa. Tampoco presentó actividad antioxidante ni prooxidante. Conclusiones: según estos ensayos, el agua de mar obtenida en Coveñas presentó bioseguridad para el consumo humano; sin embargo, se deberá evaluar en el futuro la toxicidad de su componente orgánico concentrado y la genotoxicidad en personas que la consuman. In Latin America, Colombia included, the use of natural sea water has been recently introduced for nutritional and therapeutics purposes due to its high content of minerals and oligoelements. This practice has also been used in Europe during the last century. Objective: to evaluate potential toxicity in sea water from Coveñas (Colombian Atlantic coast). Methods: erythrocytes and leukocytes were incubated in sea water samples collected in Coveñas to evaluate osmotic fragility, viability, and DNA damage (by comet technique). Atioxidant properties of this water were additionally studied. Results: erythrocytes presented a higher index of hemolysis in sea water compared with phosphate buffer (PBS) with a similar hypertonic concentration (4,3% y 2,8% respectively, P=0,00001); however, median differences were very low. Lymphocytes viability Absence of genotoxicity of sea water from Coveñas: in vitro study on human leukocytes and erythrocytes in sea water was 95% after one hour of incubation at 4°C and it was similar to the percentage observed in isotonic PBS. Sea water did not cause damage on DNA as tested one hour after treatment of lymphocytes according to the "Olive moment" averages. Sea water did not present any pro-oxidant or antioxidant capacity as tested with the ABTS+ technique. Conclusions: these results suggest that sea water from this area in the Colombian Atlantic cast is bio-safe for human consumption but it is necessary to test concentrated organic fraction and determine in vivo toxic effects.

Published
2005

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