Ítem
Acceso Abierto

Tratamiento antitumoral basado en la expresión de la proteína NIS: Análisis del microambiente tumoral en un modelo in vitro

dc.contributor.advisorPourcher, Thierry
dc.contributor.advisorOndo Méndez, Alejandro Oyono
dc.creatorCastillo-Rivera, Fabio
dc.creator.degreeDoctor en Ciencias Biomédicas y Biológicasspa
dc.creator.degreetypeFull timespa
dc.date.accessioned2021-01-14T21:32:18Z
dc.date.available2021-01-14T21:32:18Z
dc.date.created2020-06-04
dc.descriptionEl co-transportador de sodio/yoduro (NIS) media la captación de yoduro en la tiroides. Desde hace décadas, la captación de yoduro mediada por NIS es una herramienta muy útil para la ablación radiactiva de las células de cáncer de tiroides. La terapia génica basada en NIS es una herramienta prometedora para el tratamiento de células tumorales de origen extratiroideo. Algunos estudios preclínicos sobre este enfoque produjeron resultados muy prometedores, pero otros estudios concluyeron que las administraciones de yodo radioactivo requeridas eran demasiado altas, o se presentaba resistencia al tratamiento. La razón de esta variabilidad no está bien definida. Este trabajo parte de las observaciones realizadas por el grupo TIRO de la Universidad de Niza en Francia quienes inocularon subcutáneamente células HT29NIS, células de adenocarcinoma de colon (línea HT29) que expresaban mNIS exógena de forma estable en ratones desnudos para inducir tumores. Usando imágenes SPECT e inmunohistoquímica, encontraron una distribución heterogénea inesperada de la capacidad captadora de yoduro y de la expresión de NIS localizada en el borde de los xenoinjertos. En este estudio, el objetivo fue analizar factores del microambiente tumoral como la hipoxia y la heterogeneidad celular (este término hace referencia a la presencia de células en estado proliferativo o quiescente) sobre la actividad de la proteína NIS. Se estudiaron las células HT29NIS in vitro en condiciones que inducen estados proliferativo o quiescente en normoxia o hipoxia. En este modelo in vitro, se analizaron la expresión, función y localización de la proteína NIS y se estudiaron los cambios en el proteoma y el metaboloma de HT29NIS inducidos por la quiescencia y/o hipoxia. También se analizaron cambios a nivel del estado redox celular y sus incidencias en el metabolismo glucolítico y oxidativo en condiciones de quiescencia e hipoxia y su efecto en la expresión de la proteína NIS. Finalmente se analizaron los posibles cambios en el comportamiento 14 celular como la viabilidad, el estado redox y el metabolismo glucolítico y oxidativo de las células HT29 silvestres cuando son transfectadas con el gen de NIS. Se encontró que la captación de yoduro, el nivel de expresión de NIS y la localización de NIS en la membrana plasmática se redujeron por quiescencia e hipoxia. Los resultados proteómicos indican que los estados de quiescencia e hipoxia están asociados a una disminución en la expresión de proteínas involucradas en la localización de proteínas en la membrana y se detectan cambios en las proteínas asociadas al metabolismo energético, adicionalmente se encontró que la transfección de la proteína NIS en las células HT29WT reduce el metabolismo glucolítico e incrementa el metabolismo oxidativo. En conclusión, los resultados aquí reportados mostraron que la hipoxia y la quiescencia perjudican la expresión y la localización celular de la proteína NIS y, en consecuencia, la captación de yoduro. Estos hallazgos también indican que el uso de líneas celulares para la evaluación preclínica de la terapia génica basada en NIS podría conducir a subestimar la eficiencia del método. También es importante tener en cuenta los posibles cambios en el comportamiento celular cuando se introduce un gen exógeno, en líneas celulares que son sometidas a condiciones como hipoxia y quiescencia. De manera más general, este estudio muestra que el microambiente tumoral es un parámetro importante en el uso de NIS en el tratamiento de células cancerosas. Resolver algunas limitaciones del uso de NIS en la terapia génica, dada por factores del microambiente tumoral, como la heterogeneidad celular, las variaciones en la disponibilidad de oxígeno y nutrientes, el pH y la producción ROS permitirán en el futuro delimitar áreas del tumor, dosis de radioisótopos, disminución de los efectos secundarios en tejidos sanos, aumentando la radiosensibilidad del tumor y mejorando el pronóstico del paciente con cáncer.spa
dc.description.abstractThe sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid. Since decades, NIS-mediated iodide uptake is a very useful tool for radioactive ablation of thyroid cancer cells. NIS-based gene therapy is a promising tool for the treatment of tumor cells of extrathyroidal origin. Some preclinical studies on this approach produced very promising results, but other studies concluded that the required radioactive iodine administrations were too high or resistance to treatment occurs. The reason of this variability was not well-defined. This work is based on the observations made by the TIRO group from the University of Nice in France. They inoculated subcutaneously HT29NIS cells, colon adenocarcinoma cells (HT29 line) stably expressing exogenous mNIS to induce tumors in nude mice. Using SPECT imaging and immunohistochemistry, they found an unexpected heterogeneous distribution of iodide uptake capacity and NIS expression localized at the border of the xenografts. In this study, the aim was to analyze factors of the tumor microenvironment such as hypoxia and cellular heterogeneity (this term refers to the presence of cells in a proliferative or quiescent state) on the activity of the NIS protein. We studied HT29NIS cells in vitro in conditions that induce quiescent and/or hypoxic states. In this in vitro model, the expression, function and localization of NIS protein were analyzed. Changes in the proteome and metabolome of HT29NIS induced by quiescence and / or hypoxia were also analyzed. Also, change at the cellular redox state level and its effects on glycolytic and oxidative metabolism under quiescence and hypoxia conditions and its effect on the expression of the NIS protein were analyzed. Finally, possible changes in cellular behavior such as viability, redox status, and glycolytic and oxidative metabolism of wild type HT29 cells when transfected with the NIS gene were analyzed. We found that the iodide uptake, NIS-expression level and NIS localization at the plasma membrane were reduced by quiescence and hypoxia. Our proteomics results indicate that quiescent and hypoxic states are associated to a 16 decrease in the expression of proteins involved in protein localization to membrane and changes in protein linked to energy metabolism. In addition, transfection of the NIS protein in HT29WT cells was found to reduce glycolytic metabolism and increase oxidative metabolism. In conclusion, the results showed that hypoxia and quiescence impair NIS expression and NIS cellular localization, and consequently iodide uptake. These findings also indicate that the use of cell lines for preclinical evaluation of NIS-based gene therapy could lead to underestimate the efficiency of the approach. It is also important to consider possible changes in cellular behavior when an exogenous gene is introduced into cell lines that are subjected to conditions such as hypoxia and quiescence. More generally, our study show that tumor microenvironment is an important parameter in the use of NIS in the treatment of cancer cells. Resolving some limitations of the use of NIS in gene therapy, given by factors of the tumor microenvironment such as cellular heterogeneity, variations in the availability of oxygen and nutrients, pH and ROS production will allow in the future to delimit areas of the tumor, dosage of radioisotopes, decrease of side effects in healthy tissues, increasing the radiosensitivity of the tumor and improving the prognosis of the cancer patient.spa
dc.description.sponsorshipECOS-Nord, Colcienciasspa
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.48713/10336_30751
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/30751
dc.language.isospaspa
dc.publisherUniversidad del Rosariospa
dc.publisher.departmentFacultad de Ciencias Naturales y Matemáticasspa
dc.publisher.programDoctorado en Ciencias Biomédicas y Biológicasspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.licenciaPARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe.
dc.source.bibliographicCitationDohan O, Baloch Z, Banrevi Z, Livolsi V, Carrasco N. Rapid communication: predominant intracellular overexpression of the Na(+)/I(-) symporter (NIS) in a large sampling of thyroid cancer cases. The Journal of clinical endocrinology and metabolism. 2001;86(6):2697-700. Epub 2001/06/09.spa
dc.source.bibliographicCitationDai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379(6564):458-60. Epub 1996/02/01.spa
dc.source.bibliographicCitationSmanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, et al. Cloning of the human sodium lodide symporter. Biochemical and biophysical research communications. 1996;226(2):339-45. Epub 1996/09/13.spa
dc.source.bibliographicCitationPerron B, Rodriguez AM, Leblanc G, Pourcher T. Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. The Journal of endocrinology. 2001;170(1):185-96. Epub 2001/06/30.spa
dc.source.bibliographicCitationRavera S, Reyna-Neyra A, Ferrandino G, Amzel LM, Carrasco N. The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annual review of physiology. 2017;79:261-89. Epub 2017/02/14.spa
dc.source.bibliographicCitationDarrouzet E, Lindenthal S, Marcellin D, Pellequer JL, Pourcher T. The sodium/iodide symporter: state of the art of its molecular characterization. Biochimica et biophysica acta. 2014;1838(1 Pt B):244-53. Epub 2013/08/31.spa
dc.source.bibliographicCitationPortulano C, Paroder-Belenitsky M, Carrasco N. The Na+/I- symporter (NIS): mechanism and medical impact. Endocrine reviews. 2014;35(1):106-49. Epub 2013/12/07.spa
dc.source.bibliographicCitationChoudhury PS, Gupta M. Differentiated thyroid cancer theranostics: radioiodine and beyond. The British journal of radiology. 2018;91(1091):20180136. Epub 2018/09/28.spa
dc.source.bibliographicCitationMartin M, Modenutti CP, Peyret V, Geysels RC, Darrouzet E, Pourcher T, et al. A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter. Endocrinology. 2019;160(1):156-68. Epub 2018/11/30.spa
dc.source.bibliographicCitationYin HY, Zhou X, Wu HF, Li B, Zhang YF. Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy. World journal of gastroenterology. 2010;16(42):5367-74. Epub 2010/11/13.spa
dc.source.bibliographicCitationTazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, et al. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nature medicine. 2000;6(8):871-8. Epub 2000/08/10.spa
dc.source.bibliographicCitationHonour AJ, Myant NB, Rowlands EN. Secretion of radioiodine in digestive juices and milk in man. Clinical science. 1952;11(4):449-62. Epub 1952/11/01.spa
dc.source.bibliographicCitationKilbane MT, Ajjan RA, Weetman AP, Dwyer R, McDermott EW, O'Higgins NJ, et al. Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer. The Journal of clinical endocrinology and metabolism. 2000;85(3):1245-50. Epub 2000/03/17spa
dc.source.bibliographicCitationCho JY, Leveille R, Kao R, Rousset B, Parlow AF, Burak WE, Jr., et al. Hormonal regulation of radioiodide uptake activity and Na+/I- symporter expression in mammary glands. The Journal of clinical endocrinology and metabolism. 2000;85(8):2936-43. Epub 2000/08/18.spa
dc.source.bibliographicCitationDong L, Lu J, Zhao B, Wang W, Zhao Y. Review of the possible association between thyroid and breast carcinoma. World journal of surgical oncology. 2018;16(1):130. Epub 2018/07/07.spa
dc.source.bibliographicCitationPoole VL, McCabe CJ. Iodide transport and breast cancer. The Journal of endocrinology. 2015;227(1):R1-R12. Epub 2015/08/20.spa
dc.source.bibliographicCitationElliyanti A, Putra AE, Sribudiani Y, Noormartany N, Masjhur JS, Achmad TH, et al. Epidermal Growth Factor and Adenosine Triphosphate Induce Natrium Iodide Symporter Expression in Breast Cancer Cell Lines. Open access Macedonian journal of medical sciences. 2019;7(13):2088-92. Epub 2019/08/29.spa
dc.source.bibliographicCitationCarvalho DP, Ferreira AC. The importance of sodium/iodide symporter (NIS) for thyroid cancer management. Arquivos brasileiros de endocrinologia e metabologia. 2007;51(5):672-82. Epub 2007/09/25.spa
dc.source.bibliographicCitationDohan O, Carrasco N. Advances in Na(+)/I(-) symporter (NIS) research in the thyroid and beyond. Molecular and cellular endocrinology. 2003;213(1):59-70. Epub 2004/04/06.spa
dc.source.bibliographicCitationKim SH, Chung HK, Kang JH, Kim KI, Jeon YH, Jin YN, et al. Tumor-targeted radionuclide imaging and therapy based on human sodium iodide symporter gene driven by a modified telomerase reverse transcriptase promoter. Human gene therapy. 2008;19(9):951-7. Epub 2008/09/24.spa
dc.source.bibliographicCitationLiu RS, Hsieh YJ, Ke CC, Chen FD, Hwu L, Wang FH, et al. Specific activation of sodium iodide symporter gene in hepatoma using alpha-fetoprotein promoter combined with hepatitis B virus enhancer (EIIAPA). Anticancer research. 2009;29(1):211-21. Epub 2009/04/01.spa
dc.source.bibliographicCitationBarton KN, Stricker H, Brown SL, Elshaikh M, Aref I, Lu M, et al. Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate. Molecular therapy : the journal of the American Society of Gene Therapy. 2008;16(10):1761-9. Epub 2008/08/21.spa
dc.source.bibliographicCitationHart IR. Tissue specific promoters in targeting systemically delivered gene therapy. Seminars in oncology. 1996;23(1):154-8. Epub 1996/02/01.spa
dc.source.bibliographicCitationLindencrona U, Nilsson M, Forssell-Aronsson E. Similarities and differences between free 211At and 125I- transport in porcine thyroid epithelial cells cultured in bicameral chambers. Nuclear medicine and biology. 2001;28(1):41-50. Epub 2001/02/22.spa
dc.source.bibliographicCitationVan Sande J, Massart C, Beauwens R, Schoutens A, Costagliola S, Dumont JE, et al. Anion selectivity by the sodium iodide symporter. Endocrinology. 2003;144(1):247-52. Epub 2002/12/19.spa
dc.source.bibliographicCitationDadachova E, Bouzahzah B, Zuckier LS, Pestell RG. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS). Nuclear medicine and biology. 2002;29(1):13-8. Epub 2002/01/12.spa
dc.source.bibliographicCitationHingorani M, Spitzweg C, Vassaux G, Newbold K, Melcher A, Pandha H, et al. The biology of the sodium iodide symporter and its potential for targeted gene delivery. Current cancer drug targets. 2010;10(2):242-67. Epub 2010/03/06.spa
dc.source.bibliographicCitationSon SH, Gangadaran P, Ahn BC. A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity. International journal of nanomedicine. 2019;14:1779-87. Epub 2019/03/19.spa
dc.source.bibliographicCitationColler HA, Sang L, Roberts JM. A new description of cellular quiescence. PLoS biology. 2006;4(3):e83. Epub 2006/03/03.spa
dc.source.bibliographicCitationKyle AH, Baker JH, Minchinton AI. Targeting quiescent tumor cells via oxygen and IGF-I supplementation. Cancer research. 2012;72(3):801-9. Epub 2011/12/14.spa
dc.source.bibliographicCitationCheung TH, Rando TA. Molecular regulation of stem cell quiescence. Nature reviews Molecular cell biology. 2013;14(6):329-40. Epub 2013/05/24.spa
dc.source.bibliographicCitationZhang X, de Milito A, Olofsson MH, Gullbo J, D'Arcy P, Linder S. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors. International journal of molecular sciences. 2015;16(11):27313-26. Epub 2015/11/19.spa
dc.source.bibliographicCitationBrown J. Extra-thyroidal iodide metabolism in the rat. Endocrinology. 1956;58(1):68-78. Epub 1956/01/01.spa
dc.source.bibliographicCitationDenef JF, Bjorkman U, Ekholm R. Structural and functional characteristics of isolated thyroid follicles. Journal of ultrastructure research. 1980;71(2):185-202. Epub 1980/05/01.spa
dc.source.bibliographicCitationUtiger RD. Therapy of hypothyroidism--when are changes needed? The New England journal of medicine. 1990;323(2):126-7. Epub 1990/07/12.spa
dc.source.bibliographicCitationEskandari S, Loo DD, Dai G, Levy O, Wright EM, Carrasco N. Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. The Journal of biological chemistry. 1997;272(43):27230-8. Epub 1997/10/27.spa
dc.source.bibliographicCitationWatabe T, Kaneda-Nakashima K, Liu Y, Shirakami Y, Ooe K, Toyoshima A, et al. Enhancement of (211)At Uptake via the Sodium Iodide Symporter by the Addition of Ascorbic Acid in Targeted alpha-Therapy of Thyroid Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;60(9):1301-7. Epub 2019/02/24.spa
dc.source.bibliographicCitationhttp://www.cancer.gov/about-cancer/treatment. National Cancer Institute; 2015 [cited 2016 March 2016].spa
dc.source.bibliographicCitationBarton MB, Frommer M, Shafiq J. Role of radiotherapy in cancer control in low-income and middle-income countries. The Lancet Oncology. 2006;7(7):584-95. Epub 2006/07/04.spa
dc.source.bibliographicCitationJemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011;61(2):69-90. Epub 2011/02/08.spa
dc.source.bibliographicCitationBonnema SJ, Hegedus L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocrine reviews. 2012;33(6):920-80. Epub 2012/09/11spa
dc.source.bibliographicCitationReiners C, Hanscheid H, Luster M, Lassmann M, Verburg FA. Radioiodine for remnant ablation and therapy of metastatic disease. Nature reviews Endocrinology. 2011;7(10):589-95. Epub 2011/08/10spa
dc.source.bibliographicCitationKondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nature reviews Cancer. 2006;6(4):292-306. Epub 2006/03/25.spa
dc.source.bibliographicCitationChung JK, Cheon GJ. Radioiodine therapy in differentiated thyroid cancer: the first targeted therapy in oncology. Endocrinol Metab (Seoul). 2014;29(3):233-9. Epub 2014/10/14.spa
dc.source.bibliographicCitationXing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nature reviews Cancer. 2013;13(3):184-99. Epub 2013/02/23.spa
dc.source.bibliographicCitationDurante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. The Journal of clinical endocrinology and metabolism. 2006;91(8):2892-9. Epub 2006/05/11.spa
dc.source.bibliographicCitationMazzaferri EL, Kloos RT. Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. The Journal of clinical endocrinology and metabolism. 2001;86(4):1447-63. Epub 2001/04/12.spa
dc.source.bibliographicCitationKebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005;103(7):1330-5. Epub 2005/03/02.spa
dc.source.bibliographicCitationCaillou B, Troalen F, Baudin E, Talbot M, Filetti S, Schlumberger M, et al. Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study. The Journal of clinical endocrinology and metabolism. 1998;83(11):4102-6. Epub 1998/11/14.spa
dc.source.bibliographicCitationJhiang SM, Cho JY, Ryu KY, DeYoung BR, Smanik PA, McGaughy VR, et al. An immunohistochemical study of Na+/I- symporter in human thyroid tissues and salivary gland tissues. Endocrinology. 1998;139(10):4416-9. Epub 1998/09/29.spa
dc.source.bibliographicCitationCastro MR, Bergert ER, Beito TG, Roche PC, Ziesmer SC, Jhiang SM, et al. Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer. The Journal of endocrinology. 1999;163(3):495-504. Epub 1999/12/10.spa
dc.source.bibliographicCitationJung MY, Offord CP, Ennis MK, Kemler I, Neuhauser C, Dingli D. In Vivo Estimation of Oncolytic Virus Populations within Tumors. Cancer research. 2018;78(20):5992-6000. Epub 2018/08/18.spa
dc.source.bibliographicCitationWarner SG, Kim SI, Chaurasiya S, O'Leary MP, Lu J, Sivanandam V, et al. A Novel Chimeric Poxvirus Encoding hNIS Is Tumor-Tropic, Imageable, and Synergistic with Radioiodine to Sustain Colon Cancer Regression. Molecular therapy oncolytics. 2019;13:82-92. Epub 2019/05/08spa
dc.source.bibliographicCitationMsaouel P, Opyrchal M, Dispenzieri A, Peng KW, Federspiel MJ, Russell SJ, et al. Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects. Current cancer drug targets. 2018;18(2):177-87. Epub 2017/02/24.spa
dc.source.bibliographicCitationSchlumberger M, Lacroix L, Russo D, Filetti S, Bidart JM. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nature clinical practice Endocrinology & metabolism. 2007;3(3):260-9. Epub 2007/02/23.spa
dc.source.bibliographicCitationKim YH, Youn H, Na J, Hong KJ, Kang KW, Lee DS, et al. Codon-optimized human sodium iodide symporter (opt-hNIS) as a sensitive reporter and efficient therapeutic gene. Theranostics. 2015;5(1):86-96. Epub 2015/01/02.spa
dc.source.bibliographicCitationKogai T, Brent GA. The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics. Pharmacology & therapeutics. 2012;135(3):355-70. Epub 2012/07/04.spa
dc.source.bibliographicCitationLiu J, Liu Y, Lin Y, Liang J. Radioactive Iodine-Refractory Differentiated Thyroid Cancer and Redifferentiation Therapy. Endocrinol Metab (Seoul). 2019;34(3):215-25. Epub 2019/10/01.spa
dc.source.bibliographicCitationAashiq M, Silverman DA, Na'ara S, Takahashi H, Amit M. Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies. Cancers. 2019;11(9). Epub 2019/09/20.spa
dc.source.bibliographicCitationRusso D, Damante G, Puxeddu E, Durante C, Filetti S. Epigenetics of thyroid cancer and novel therapeutic targets. Journal of molecular endocrinology. 2011;46(3):R73-81. Epub 2011/02/18spa
dc.source.bibliographicCitationSmith VE, Sharma N, Watkins RJ, Read ML, Ryan GA, Kwan PP, et al. Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors. The Journal of clinical endocrinology and metabolism. 2013;98(7):2876-86. Epub 2013/05/17.spa
dc.source.bibliographicCitationHo AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. The New England journal of medicine. 2013;368(7):623-32. Epub 2013/02/15.spa
dc.source.bibliographicCitationFeng F, Yehia L, Ni Y, Chang YS, Jhiang SM, Eng C. A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling. Cancer research. 2018;78(21):6121-33. Epub 2018/09/16.spa
dc.source.bibliographicCitationFeng F, Yehia L, Eng C. Pro-tumorigenic non-pump function of sodium iodide symporter: A reimagined Trojan horse? Oncotarget. 2019;10(7):688-9. Epub 2019/02/19.spa
dc.source.bibliographicCitationRibeiro Franco PI, Rodrigues AP, de Menezes LB, Pacheco Miguel M. Tumor microenvironment components: Allies of cancer progression. Pathology, research and practice. 2020;216(1):152729. Epub 2019/11/19.spa
dc.source.bibliographicCitationWeis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nature medicine. 2011;17(11):1359-70. Epub 2011/11/09.spa
dc.source.bibliographicCitationde Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nature reviews Cancer. 2006;6(1):24-37. Epub 2006/01/07.spa
dc.source.bibliographicCitationKalluri R, Zeisberg M. Fibroblasts in cancer. Nature reviews Cancer. 2006;6(5):392-401. Epub 2006/03/31.spa
dc.source.bibliographicCitationOhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS, Ponz-Sarvise M, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. The Journal of experimental medicine. 2017;214(3):579-96. Epub 2017/02/25.spa
dc.source.bibliographicCitationJena MK, Janjanam J. Role of extracellular matrix in breast cancer development: a brief update. F1000Research. 2018;7:274. Epub 2018/07/12.spa
dc.source.bibliographicCitationCorrea LH, Correa R, Farinasso CM, de Sant'Ana Dourado LP, Magalhaes KG. Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression. Frontiers in immunology. 2017;8:1129. Epub 2017/10/04.spa
dc.source.bibliographicCitationLu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. The Journal of cell biology. 2012;196(4):395-406. Epub 2012/02/22.spa
dc.source.bibliographicCitationLobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annual review of cell and developmental biology. 2007;23:675-99. Epub 2007/07/25spa
dc.source.bibliographicCitationAl-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(7):3983-8. Epub 2003/03/12.spa
dc.source.bibliographicCitationSingh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741-51. Epub 2010/06/10spa
dc.source.bibliographicCitationAponte PM, Caicedo A. Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment. Stem cells international. 2017;2017:5619472. Epub 2017/05/06.spa
dc.source.bibliographicCitationCreighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(33):13820-5. Epub 2009/08/12.spa
dc.source.bibliographicCitationCheung TH, Quach NL, Charville GW, Liu L, Park L, Edalati A, et al. Maintenance of muscle stem-cell quiescence by microRNA-489. Nature. 2012;482(7386):524-8. Epub 2012/02/24.spa
dc.source.bibliographicCitationArnold CP, Tan R, Zhou B, Yue SB, Schaffert S, Biggs JR, et al. MicroRNA programs in normal and aberrant stem and progenitor cells. Genome research. 2011;21(5):798-810. Epub 2011/04/01.spa
dc.source.bibliographicCitationLa T, Liu GZ, Farrelly M, Cole N, Feng YC, Zhang YY, et al. A p53-Responsive miRNA Network Promotes Cancer Cell Quiescence. Cancer research. 2018;78(23):6666-79. Epub 2018/10/12.spa
dc.source.bibliographicCitationZalatnai A. Molecular aspects of stromal-parenchymal interactions in malignant neoplasms. Current molecular medicine. 2006;6(6):685-93. Epub 2006/10/07.spa
dc.source.bibliographicCitationLaconi E. The evolving concept of tumor microenvironments. BioEssays : news and reviews in molecular, cellular and developmental biology. 2007;29(8):738-44. Epub 2007/07/11.spa
dc.source.bibliographicCitationSwanton C. Intratumor heterogeneity: evolution through space and time. Cancer research. 2012;72(19):4875-82. Epub 2012/09/25.spa
dc.source.bibliographicCitationJustus CR, Sanderlin EJ, Yang LV. Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment. International journal of molecular sciences. 2015;16(5):11055-86. Epub 2015/05/20.spa
dc.source.bibliographicCitationHuang Y, Lin D, Taniguchi CM. Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe? Science China Life sciences. 2017;60(10):1114-24. Epub 2017/10/19.spa
dc.source.bibliographicCitationPaolicchi E, Gemignani F, Krstic-Demonacos M, Dedhar S, Mutti L, Landi S. Targeting hypoxic response for cancer therapy. Oncotarget. 2016;7(12):13464-78. Epub 2016/02/10.spa
dc.source.bibliographicCitationLendahl U, Lee KL, Yang H, Poellinger L. Generating specificity and diversity in the transcriptional response to hypoxia. Nature reviews Genetics. 2009;10(12):821-32. Epub 2009/11/04.spa
dc.source.bibliographicCitationGatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nature reviews Cancer. 2004;4(11):891-9. Epub 2004/11/02.spa
dc.source.bibliographicCitationSilva-Filho AF, Sena WLB, Lima LRA, Carvalho LVN, Pereira MC, Santos LGS, et al. Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;41(5):1801-29. Epub 2017/04/05.spa
dc.source.bibliographicCitationWarburg O. On respiratory impairment in cancer cells. Science. 1956;124(3215):269-70. Epub 1956/08/10.spa
dc.source.bibliographicCitationWarburg O. On the origin of cancer cells. Science. 1956;123(3191):309-14. Epub 1956/02/24.spa
dc.source.bibliographicCitationJones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes & development. 2009;23(5):537-48. Epub 2009/03/10.spa
dc.source.bibliographicCitationDeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell metabolism. 2008;7(1):11-20. Epub 2008/01/08.spa
dc.source.bibliographicCitationKennedy KM, Dewhirst MW. Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation. Future Oncol. 2010;6(1):127-48. Epub 2009/12/22.spa
dc.source.bibliographicCitationFeron O. Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2009;92(3):329-33. Epub 2009/07/17.spa
dc.source.bibliographicCitationSemenza GL. Tumor metabolism: cancer cells give and take lactate. The Journal of clinical investigation. 2008;118(12):3835-7. Epub 2008/11/27.spa
dc.source.bibliographicCitationHardee ME, Dewhirst MW, Agarwal N, Sorg BS. Novel imaging provides new insights into mechanisms of oxygen transport in tumors. Current molecular medicine. 2009;9(4):435-41. Epub 2009/06/13.spa
dc.source.bibliographicCitationParks SK, Chiche J, Pouyssegur J. pH control mechanisms of tumor survival and growth. Journal of cellular physiology. 2011;226(2):299-308. Epub 2010/09/22.spa
dc.source.bibliographicCitationOdunewu A, Fliegel L. Acidosis-mediated regulation of the NHE1 isoform of the Na(+)/H(+) exchanger in renal cells. American journal of physiology Renal physiology. 2013;305(3):F370-81. Epub 2013/05/17.spa
dc.source.bibliographicCitationUllah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. The Journal of biological chemistry. 2006;281(14):9030-7. Epub 2006/02/03spa
dc.source.bibliographicCitationSedlakova O, Svastova E, Takacova M, Kopacek J, Pastorek J, Pastorekova S. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors. Frontiers in physiology. 2014;4:400. Epub 2014/01/11.spa
dc.source.bibliographicCitationFolkerts H, Hilgendorf S, Vellenga E, Bremer E, Wiersma VR. The multifaceted role of autophagy in cancer and the microenvironment. Medicinal research reviews. 2019;39(2):517-60. Epub 2018/10/12spa
dc.source.bibliographicCitationCho RW, Clarke MF. Recent advances in cancer stem cells. Current opinion in genetics & development. 2008;18(1):48-53. Epub 2008/03/22.spa
dc.source.bibliographicCitationKumari S, Badana AK, G MM, G S, Malla R. Reactive Oxygen Species: A Key Constituent in Cancer Survival. Biomarker insights. 2018;13:1177271918755391. Epub 2018/02/17spa
dc.source.bibliographicCitationWeinberg F, Ramnath N, Nagrath D. Reactive Oxygen Species in the Tumor Microenvironment: An Overview. Cancers. 2019;11(8). Epub 2019/08/21.spa
dc.source.bibliographicCitationKobayashi M, Yamamoto M. Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Advances in enzyme regulation. 2006;46:113-40. Epub 2006/08/05.spa
dc.source.bibliographicCitationLin W, Shen G, Yuan X, Jain MR, Yu S, Zhang A, et al. Regulation of Nrf2 transactivation domain activity by p160 RAC3/SRC3 and other nuclear co-regulators. Journal of biochemistry and molecular biology. 2006;39(3):304-10. Epub 2006/06/08.spa
dc.source.bibliographicCitationCopple I.M. GCE, Kitteringham N.R., Park B.K. he Keap1-Nrf2 Cellular Defense Pathway: Mechanisms of Regulation and Role in Protection Against Drug-Induced Toxicity. Berlin, Heidelberg Springer; 2010.spa
dc.source.bibliographicCitationMcMahon M, Thomas N, Itoh K, Yamamoto M, Hayes JD. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. The Journal of biological chemistry. 2006;281(34):24756-68. Epub 2006/06/23.spa
dc.source.bibliographicCitationTong KI, Kobayashi A, Katsuoka F, Yamamoto M. Two-site substrate recognition model for the Keap1-Nrf2 system: a hinge and latch mechanism. Biological chemistry. 2006;387(10-11):1311-20. Epub 2006/11/04.spa
dc.source.bibliographicCitationItoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and biophysical research communications. 1997;236(2):313-22. Epub 1997/07/18.spa
dc.source.bibliographicCitationHagiya Y, Adachi T, Ogura S, An R, Tamura A, Nakagawa H, et al. Nrf2-dependent induction of human ABC transporter ABCG2 and heme oxygenase-1 in HepG2 cells by photoactivation of porphyrins: biochemical implications for cancer cell response to photodynamic therapy. Journal of experimental therapeutics & oncology. 2008;7(2):153-67. Epub 2008/09/06.spa
dc.source.bibliographicCitationChanas SA, Jiang Q, McMahon M, McWalter GK, McLellan LI, Elcombe CR, et al. Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice. The Biochemical journal. 2002;365(Pt 2):405-16. Epub 2002/05/07.spa
dc.source.bibliographicCitationSajadimajd S, Khazaei M. Oxidative Stress and Cancer: The Role of Nrf2. Current cancer drug targets. 2018;18(6):538-57. Epub 2017/10/04.spa
dc.source.bibliographicCitationRomero R, Sayin VI, Davidson SM, Bauer MR, Singh SX, LeBoeuf SE, et al. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nature medicine. 2017;23(11):1362-8. Epub 2017/10/03.spa
dc.source.bibliographicCitationLignitto L, LeBoeuf SE, Homer H, Jiang S, Askenazi M, Karakousi TR, et al. Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1. Cell. 2019;178(2):316-29 e18. Epub 2019/07/02.spa
dc.source.bibliographicCitationeong Y, Hellyer JA, Stehr H, Hoang NT, Niu X, Das M, et al. Role of KEAP1/NFE2L2 Mutations in the Chemotherapeutic Response of Patients with Non-Small Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;26(1):274-81. Epub 2019/09/25.spa
dc.source.bibliographicCitationArbour KC, Jordan E, Kim HR, Dienstag J, Yu HA, Sanchez-Vega F, et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2018;24(2):334-40. Epub 2017/11/02.spa
dc.source.bibliographicCitationKitamura H, Onodera Y, Murakami S, Suzuki T, Motohashi H. IL-11 contribution to tumorigenesis in an NRF2 addiction cancer model. Oncogene. 2017;36(45):6315-24. Epub 2017/07/18.spa
dc.source.bibliographicCitationKitamura H, Motohashi H. NRF2 addiction in cancer cells. Cancer science. 2018;109(4):900-11. Epub 2018/02/17.spa
dc.source.bibliographicCitationStacy DR, Ely K, Massion PP, Yarbrough WG, Hallahan DE, Sekhar KR, et al. Increased expression of nuclear factor E2 p45-related factor 2 (NRF2) in head and neck squamous cell carcinomas. Head & neck. 2006;28(9):813-8. Epub 2006/04/26spa
dc.source.bibliographicCitationShibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology. 2008;135(4):1358-68, 68 e1-4. Epub 2008/08/12.spa
dc.source.bibliographicCitationShibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(36):13568-73. Epub 2008/09/02.spa
dc.source.bibliographicCitationLister A, Nedjadi T, Kitteringham NR, Campbell F, Costello E, Lloyd B, et al. Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy. Molecular cancer. 2011;10:37. Epub 2011/04/15.spa
dc.source.bibliographicCitationRodriguez AE, Ducker GS, Billingham LK, Martinez CA, Mainolfi N, Suri V, et al. Serine Metabolism Supports Macrophage IL-1beta Production. Cell metabolism. 2019;29(4):1003-11 e4. Epub 2019/02/19.spa
dc.source.bibliographicCitationMitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer cell. 2012;22(1):66-79. Epub 2012/07/14.spa
dc.source.bibliographicCitationMcDonald JT, Kim K, Norris AJ, Vlashi E, Phillips TM, Lagadec C, et al. Ionizing radiation activates the Nrf2 antioxidant response. Cancer research. 2010;70(21):8886-95. Epub 2010/10/14.spa
dc.source.bibliographicCitationTsukimoto M, Tamaishi N, Homma T, Kojima S. Low-dose gamma-ray irradiation induces translocation of Nrf2 into nuclear in mouse macrophage RAW264.7 cells. Journal of radiation research. 2010;51(3):349-53. Epub 2010/04/23.spa
dc.source.bibliographicCitationLau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacological research. 2008;58(5-6):262-70. Epub 2008/10/08.spa
dc.source.bibliographicCitationRichard-Fiardo P, Franken PR, Lamit A, Marsault R, Guglielmi J, Cambien B, et al. Normalisation to blood activity is required for the accurate quantification of Na/I symporter ectopic expression by SPECT/CT in individual subjects. PloS one. 2012;7(3):e34086. Epub 2012/04/04.spa
dc.source.bibliographicCitationGengenbacher N, Singhal M, Augustin HG. Preclinical mouse solid tumour models: status quo, challenges and perspectives. Nature reviews Cancer. 2017;17(12):751-65. Epub 2017/10/28.spa
dc.source.bibliographicCitationSabit H, Samy MB, Said OA, El-Zawahri MM. Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells. Genetics research international. 2016;2016:8348450. Epub 2016/11/16.spa
dc.source.bibliographicCitationDayem M, Basquin C, Navarro V, Carrier P, Marsault R, Chang P, et al. Comparison of expressed human and mouse sodium/iodide symporters reveals differences in transport properties and subcellular localization. The Journal of endocrinology. 2008;197(1):95-109. Epub 2008/03/29.spa
dc.source.bibliographicCitationKim KI, Kang JH, Chung JK, Lee YJ, Jeong JM, Lee DS, et al. Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2007;48(9):1553-61. Epub 2007/08/21.spa
dc.source.bibliographicCitationD'Ignazio L, Bandarra D, Rocha S. NF-kappaB and HIF crosstalk in immune responses. The FEBS journal. 2016;283(3):413-24. Epub 2015/10/30.spa
dc.source.bibliographicCitationWendland K, Thielke M, Meisel A, Mergenthaler P. Intrinsic hypoxia sensitivity of the cytomegalovirus promoter. Cell death & disease. 2015;6:e1905. Epub 2015/10/16.spa
dc.source.bibliographicCitationLeung CO, Wong CC, Fan DN, Kai AK, Tung EK, Xu IM, et al. PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma. Oncotarget. 2015;6(13):10880-92. Epub 2015/04/03.spa
dc.source.bibliographicCitationLi XF, Ma Y, Sun X, Humm JL, Ling CC, O'Donoghue JA. High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2010;51(4):632-8. Epub 2010/03/31.spa
dc.source.bibliographicCitationBedessem B, Stephanou A. A mathematical model of HiF-1alpha-mediated response to hypoxia on the G1/S transition. Mathematical biosciences. 2014;248:31-9. Epub 2013/12/19.spa
dc.source.bibliographicCitationPark HJ, Lyons JC, Ohtsubo T, Song CW. Acidic environment causes apoptosis by increasing caspase activity. British journal of cancer. 1999;80(12):1892-7. Epub 1999/09/02.spa
dc.source.bibliographicCitationSemenza GL. HIF-1: upstream and downstream of cancer metabolism. Current opinion in genetics & development. 2010;20(1):51-6. Epub 2009/11/28.spa
dc.source.bibliographicCitationHayashi M, Sakata M, Takeda T, Yamamoto T, Okamoto Y, Sawada K, et al. Induction of glucose transporter 1 expression through hypoxia-inducible factor 1alpha under hypoxic conditions in trophoblast-derived cells. The Journal of endocrinology. 2004;183(1):145-54. Epub 2004/11/05.spa
dc.source.bibliographicCitationDenko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature reviews Cancer. 2008;8(9):705-13. Epub 2009/01/15.spa
dc.source.bibliographicCitationRodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, et al. p53 mutations in colorectal cancer. Proceedings of the National Academy of Sciences of the United States of America. 1990;87(19):7555-9. Epub 1990/10/01.spa
dc.source.bibliographicCitationZhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, et al. Tumour-associated mutant p53 drives the Warburg effect. Nature communications. 2013;4:2935. Epub 2013/12/18.spa
dc.source.bibliographicCitationFiletti S, Vetri M, Damante G, Belfiore A. Thyroid autoregulation: effect of iodine on glucose transport in cultured thyroid cells. Endocrinology. 1986;118(4):1395-400. Epub 1986/04/01.spa
dc.source.bibliographicCitationRehab El nour Omer, Omer Musa Izz eldin and Reem Hassan Ahmed Rehab. Effect of potassium iodide on glucose, cholesterol and triglycerides levels in glucose loaded rats. International Journal of Pharmacy and Biological Sciences. 2015;5:96-9.spa
dc.source.bibliographicCitationZhang Z, Deng X, Liu Y, Sun L, Chen F. PKM2, function and expression and regulation. Cell & bioscience. 2019;9:52. Epub 2019/08/09.spa
dc.source.bibliographicCitationMazurek S. Pyruvate kinase type M2: a key regulator within the tumour metabolome and a tool for metabolic profiling of tumours. Ernst Schering Foundation symposium proceedings. 2007(4):99-124. Epub 2008/09/25.spa
dc.source.bibliographicCitationWarburg O, Wind F, Negelein E. The Metabolism of Tumors in the Body. The Journal of general physiology. 1927;8(6):519-30. Epub 1927/03/07.spa
dc.source.bibliographicCitationMathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. The Journal of biological chemistry. 2001;276(46):43407-12. Epub 2001/09/15.spa
dc.source.bibliographicCitationVander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-33. Epub 2009/05/23.spa
dc.source.bibliographicCitationChesnelong C, Chaumeil MM, Blough MD, Al-Najjar M, Stechishin OD, Chan JA, et al. Lactate dehydrogenase A silencing in IDH mutant gliomas. Neuro-oncology. 2014;16(5):686-95. Epub 2013/12/25.spa
dc.source.bibliographicCitationSemenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, et al. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. The Journal of biological chemistry. 1996;271(51):32529-37. Epub 1996/12/20.spa
dc.source.bibliographicCitationKoukourakis MI, Giatromanolaki A, Panteliadou M, Pouliliou SE, Chondrou PS, Mavropoulou S, et al. Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy. British journal of cancer. 2014;110(9):2217-23. Epub 2014/04/10.spa
dc.source.bibliographicCitationMarchiq I, Pouyssegur J. Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H(+) symporters. J Mol Med (Berl). 2016;94(2):155-71. Epub 2015/06/24.spa
dc.source.bibliographicCitationChen JL, Lucas JE, Schroeder T, Mori S, Wu J, Nevins J, et al. The genomic analysis of lactic acidosis and acidosis response in human cancers. PLoS genetics. 2008;4(12):e1000293. Epub 2008/12/06.spa
dc.source.bibliographicCitationXie J, Wu H, Dai C, Pan Q, Ding Z, Hu D, et al. Beyond Warburg effect--dual metabolic nature of cancer cells. Scientific reports. 2014;4:4927. Epub 2014/05/14.spa
dc.source.bibliographicCitationFeine U, Lietzenmayer R, Hanke JP, Held J, Wohrle H, Muller-Schauenburg W. Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1996;37(9):1468-72. Epub 1996/09/01.spa
dc.source.bibliographicCitationMatsuzu K, Segade F, Matsuzu U, Carter A, Bowden DW, Perrier ND. Differential expression of glucose transporters in normal and pathologic thyroid tissue. Thyroid : official journal of the American Thyroid Association. 2004;14(10):806-12. Epub 2004/12/14.spa
dc.source.bibliographicCitationMatsuzu K, Segade F, Wong M, Clark OH, Perrier ND, Bowden DW. Glucose transporters in the thyroid. Thyroid : official journal of the American Thyroid Association. 2005;15(6):545-50. Epub 2005/07/21.spa
dc.source.bibliographicCitationRuan M, Liu M, Dong Q, Chen L. Iodide- and glucose-handling gene expression regulated by sorafenib or cabozantinib in papillary thyroid cancer. The Journal of clinical endocrinology and metabolism. 2015;100(5):1771-9. Epub 2015/03/15.spa
dc.source.bibliographicCitationRizwan H, Pal S, Sabnam S, Pal A. High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes. Life sciences. 2020;241:117148. Epub 2019/12/13.spa
dc.source.bibliographicCitationHolynska-Iwan I, Wroblewski M, Olszewska-Slonina D, Tyrakowski T. [The application of N-acetylcysteine in optimization of specific pharmacological therapies]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2017;43(255):140-4. Epub 2017/10/08. Zastosowanie N-acetylocysteiny do optymalizacji specyficznych terapii farmakologicznych.spa
dc.source.bibliographicCitationSerrano-Nascimento C, da Silva Teixeira S, Nicola JP, Nachbar RT, Masini-Repiso AM, Nunes MT. The acute inhibitory effect of iodide excess on sodium/iodide symporter expression and activity involves the PI3K/Akt signaling pathway. Endocrinology. 2014;155(3):1145-56. Epub 2014/01/16.spa
dc.source.bibliographicCitationMa Q. Role of nrf2 in oxidative stress and toxicity. Annual review of pharmacology and toxicology. 2013;53:401-26. Epub 2013/01/09.spa
dc.source.bibliographicCitationSeagroves TN, Ryan HE, Lu H, Wouters BG, Knapp M, Thibault P, et al. Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Molecular and cellular biology. 2001;21(10):3436-44. Epub 2001/04/21.spa
dc.source.bibliographicCitationShi X, Zhang Y, Zheng J, Pan J. Reactive oxygen species in cancer stem cells. Antioxidants & redox signaling. 2012;16(11):1215-28. Epub 2012/02/10.spa
dc.source.bibliographicCitationAmmon HP, Muller PH, Eggstein M, Wintermantel C, Aigner B, Safayhi H, et al. Increase in glucose consumption by acetylcysteine during hyperglycemic clamp. A study with healthy volunteers. Arzneimittel-Forschung. 1992;42(5):642-5. Epub 1992/05/01spa
dc.source.bibliographicCitationFalach-Malik A, Rozenfeld H, Chetboun M, Rozenberg K, Elyasiyan U, Sampson SR, et al. N-Acetyl-L-Cysteine inhibits the development of glucose intolerance and hepatic steatosis in diabetes-prone mice. American journal of translational research. 2016;8(9):3744-56. Epub 2016/10/12.spa
dc.source.bibliographicCitationDe la Vieja A, Santisteban P. Role of iodide metabolism in physiology and cancer. Endocrine-related cancer. 2018;25(4):R225-R45. Epub 2018/02/14.spa
dc.source.bibliographicCitationZhang L, Sharma S, Zhu LX, Kogai T, Hershman JM, Brent GA, et al. Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. Cancer research. 2003;63(16):5065-72. Epub 2003/08/28.spa
dc.source.bibliographicCitationSarkar D, Chakraborty A, Saha A, Chandra AK. Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well as histomorphometric changes in associated organs. Journal of basic and clinical physiology and pharmacology. 2018;29(6):631-43. Epub 2018/08/02.spa
dc.source.bibliographicCitationLiemburg-Apers DC, Willems PH, Koopman WJ, Grefte S. Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Archives of toxicology. 2015;89(8):1209-26. Epub 2015/06/07.spa
dc.source.bibliographicCitationLorenz MA, Burant CF, Kennedy RT. Reducing time and increasing sensitivity in sample preparation for adherent mammalian cell metabolomics. Analytical chemistry. 2011;83(9):3406-14. Epub 2011/04/05.spa
dc.source.bibliographicCitationHolman JD, Tabb DL, Mallick P. Employing ProteoWizard to Convert Raw Mass Spectrometry Data. Current protocols in bioinformatics. 2014;46:13 24 1-9. Epub 2014/06/19.spa
dc.source.bibliographicCitationPluskal T, Castillo S, Villar-Briones A, Oresic M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC bioinformatics. 2010;11:395. Epub 2010/07/24.spa
dc.source.bibliographicCitationWishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, et al. HMDB 3.0--The Human Metabolome Database in 2013. Nucleic acids research. 2013;41(Database issue):D801-7. Epub 2012/11/20.spa
dc.source.bibliographicCitationChong J, Soufan O, Li C, Caraus I, Li S, Bourque G, et al. MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic acids research. 2018;46(W1):W486-W94. Epub 2018/05/16.spa
dc.source.bibliographicCitationChong J, Wishart DS, Xia J. Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis. Current protocols in bioinformatics. 2019;68(1):e86. Epub 2019/11/23.spa
dc.source.bibliographicCitationNam SO, Yotsumoto F, Miyata K, Fukagawa S, Yamada H, Kuroki M, et al. Warburg effect regulated by amphiregulin in the development of colorectal cancer. Cancer medicine. 2015;4(4):575-87. Epub 2015/02/04.spa
dc.source.bibliographicCitationBosch EH, van Doorne H, de Vries S. The lactoperoxidase system: the influence of iodide and the chemical and antimicrobial stability over the period of about 18 months. Journal of applied microbiology. 2000;89(2):215-24. Epub 2000/09/06.spa
dc.source.bibliographicCitationHuang YY, Choi H, Kushida Y, Bhayana B, Wang Y, Hamblin MR. Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide. Antimicrobial agents and chemotherapy. 2016;60(9):5445-53. Epub 2016/07/07.spa
dc.source.bibliographicCitationIhalin R, Loimaranta V, Tenovuo J. Origin, structure, and biological activities of peroxidases in human saliva. Archives of biochemistry and biophysics. 2006;445(2):261-8. Epub 2005/08/23.spa
dc.source.bibliographicCitationFischer AJ, Lennemann NJ, Krishnamurthy S, Pocza P, Durairaj L, Launspach JL, et al. Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. American journal of respiratory cell and molecular biology. 2011;45(4):874-81. Epub 2011/03/29.spa
dc.source.bibliographicCitationSoriano O, Delgado G, Anguiano B, Petrosyan P, Molina-Servin ED, Gonsebatt ME, et al. Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production. Endocrine-related cancer. 2011;18(4):529-39. Epub 2011/06/22.spa
dc.source.bibliographicCitationRosner H, Moller W, Groebner S, Torremante P. Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines. Oncology letters. 2016;12(3):2159-62. Epub 2016/09/08.spa
dc.source.bibliographicCitationGreen WL. Further studies of the effects of inorganic iodide on thyroidal intermediary metabolism in vitro. Endocrinology. 1966;79(1):1-9. Epub 1966/07/01.spa
dc.source.bibliographicCitationGuzy RD, Schumacker PT. Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Experimental physiology. 2006;91(5):807-19. Epub 2006/07/22.spa
dc.source.bibliographicCitationKim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell metabolism. 2006;3(3):177-85. Epub 2006/03/07.spa
dc.source.bibliographicCitationMaciewicz RA, Wotton SF, Etherington DJ, Duance VC. Susceptibility of the cartilage collagens types II, IX and XI to degradation by the cysteine proteinases, cathepsins B and L. FEBS letters. 1990;269(1):189-93. Epub 1990/08/20.spa
dc.source.bibliographicCitationBuck MR, Karustis DG, Day NA, Honn KV, Sloane BF. Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. The Biochemical journal. 1992;282 ( Pt 1):273-8. Epub 1992/02/15.spa
dc.source.bibliographicCitationOstad M, Weiss R, Droller M, Liu B. Ha-ras oncogene induction of invasion and metastasis is associated with the activation and redistribution of protease(s) in rat-kidney cells. International journal of oncology. 1992;1(7):765-71. Epub 1992/12/01.spa
dc.source.bibliographicCitationPark HJ, Makepeace CM, Lyons JC, Song CW. Effect of intracellular acidity and ionomycin on apoptosis in HL-60 cells. Eur J Cancer. 1996;32A(3):540-6. Epub 1996/03/01.spa
dc.source.bibliographicCitation195. Rahmani S, Defferrari MS, Wakarchuk WW, Antonescu CN. Energetic adaptations: Metabolic control of endocytic membrane traffic. Traffic. 2019;20(12):912-31. Epub 2019/10/18.spa
dc.source.bibliographicCitation196. Lee HJ, Jedrychowski MP, Vinayagam A, Wu N, Shyh-Chang N, Hu Y, et al. Proteomic and Metabolomic Characterization of a Mammalian Cellular Transition from Quiescence to Proliferation. Cell reports. 2017;20(3):721-36. Epub 2017/07/21.spa
dc.source.bibliographicCitationWapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, et al. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. The Journal of clinical endocrinology and metabolism. 2003;88(4):1880-8. Epub 2003/04/08.spa
dc.source.bibliographicCitationPeyrottes I, Navarro V, Ondo-Mendez A, Marcellin D, Bellanger L, Marsault R, et al. Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers. European journal of endocrinology. 2009;160(2):215-25. Epub 2008/11/26.spa
dc.source.bibliographicCitationWang Y, Ohh M. Oxygen-mediated endocytosis in cancer. Journal of cellular and molecular medicine. 2010;14(3):496-503. Epub 2010/01/20.spa
dc.source.bibliographicCitationDada LA, Chandel NS, Ridge KM, Pedemonte C, Bertorello AM, Sznajder JI. Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-zeta. The Journal of clinical investigation. 2003;111(7):1057-64. Epub 2003/04/03.spa
dc.source.bibliographicCitationDada LA, Novoa E, Lecuona E, Sun H, Sznajder JI. Role of the small GTPase RhoA in the hypoxia-induced decrease of plasma membrane Na,K-ATPase in A549 cells. Journal of cell science. 2007;120(Pt 13):2214-22. Epub 2007/06/07.spa
dc.source.bibliographicCitationKiang JG, Wang XD, Ding XZ, Gist ID, Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid : official journal of the American Thyroid Association. 1996;6(5):475-83. Epub 1996/10/01.spa
dc.source.bibliographicCitationVadysirisack DD, Chen ES, Zhang Z, Tsai MD, Chang GD, Jhiang SM. Identification of in vivo phosphorylation sites and their functional significance in the sodium iodide symporter. The Journal of biological chemistry. 2007;282(51):36820-8. Epub 2007/10/05spa
dc.source.bibliographicCitationChung T, Youn H, Yeom CJ, Kang KW, Chung JK. Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake. PloS one. 2015;10(11):e0142984. Epub 2015/11/26.spa
dc.source.bibliographicCitationWang Y, Roche O, Yan MS, Finak G, Evans AJ, Metcalf JL, et al. Regulation of endocytosis via the oxygen-sensing pathway. Nature medicine. 2009;15(3):319-24. Epub 2009/03/03.spa
dc.source.bibliographicCitationSzul T, Sztul E. COPII and COPI traffic at the ER-Golgi interface. Physiology (Bethesda). 2011;26(5):348-64. Epub 2011/10/21.spa
dc.source.bibliographicCitationMatsuoka K, Orci L, Amherdt M, Bednarek SY, Hamamoto S, Schekman R, et al. COPII-coated vesicle formation reconstituted with purified coat proteins and chemically defined liposomes. Cell. 1998;93(2):263-75. Epub 1998/05/06.spa
dc.source.bibliographicCitationBarroso M, Nelson DS, Sztul E. Transcytosis-associated protein (TAP)/p115 is a general fusion factor required for binding of vesicles to acceptor membranes. Proceedings of the National Academy of Sciences of the United States of America. 1995;92(2):527-31. Epub 1995/01/17.spa
dc.source.bibliographicCitationRoyle SJ. The cellular functions of clathrin. Cellular and molecular life sciences : CMLS. 2006;63(16):1823-32. Epub 2006/05/16.spa
dc.source.bibliographicCitationPedersen NB, Carlsson MC, Pedersen SF. Glycosylation of solute carriers: mechanisms and functional consequences. Pflugers Archiv : European journal of physiology. 2016;468(2):159-76. Epub 2015/09/19.spa
dc.source.bibliographicCitationHuet G, Gouyer V, Delacour D, Richet C, Zanetta JP, Delannoy P, et al. Involvement of glycosylation in the intracellular trafficking of glycoproteins in polarized epithelial cells. Biochimie. 2003;85(3-4):323-30. Epub 2003/05/29.spa
dc.source.bibliographicCitationLevy O, Dai G, Riedel C, Ginter CS, Paul EM, Lebowitz AN, et al. Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus antibody. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(11):5568-73. Epub 1997/05/27.spa
dc.source.bibliographicCitationZhou F, Xu W, Hong M, Pan Z, Sinko PJ, Ma J, et al. The role of N-linked glycosylation in protein folding, membrane targeting, and substrate binding of human organic anion transporter hOAT4. Molecular pharmacology. 2005;67(3):868-76. Epub 2004/12/04.spa
dc.source.bibliographicCitationLevy O, De la Vieja A, Ginter CS, Riedel C, Dai G, Carrasco N. N-linked glycosylation of the thyroid Na+/I- symporter (NIS). Implications for its secondary structure model. The Journal of biological chemistry. 1998;273(35):22657-63. Epub 1998/08/26.spa
dc.source.bibliographicCitationChai W, Ye F, Zeng L, Li Y, Yang L. HMGB1-mediated autophagy regulates sodium/iodide symporter protein degradation in thyroid cancer cells. Journal of experimental & clinical cancer research : CR. 2019;38(1):325. Epub 2019/07/25.spa
dc.source.bibliographicCitationPlantinga TS, Tesselaar MH, Morreau H, Corssmit EP, Willemsen BK, Kusters B, et al. Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer. Autophagy. 2016;12(7):1195-205. Epub 2016/04/23.spa
dc.source.bibliographicCitationRavanan P, Srikumar IF, Talwar P. Autophagy: The spotlight for cellular stress responses. Life sciences. 2017;188:53-67. Epub 2017/09/04.spa
dc.source.bibliographicCitationLazar V, Bidart JM, Caillou B, Mahe C, Lacroix L, Filetti S, et al. Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. The Journal of clinical endocrinology and metabolism. 1999;84(9):3228-34. Epub 1999/09/16.spa
dc.source.bibliographicCitationXu XD, Shao SX, Jiang HP, Cao YW, Wang YH, Yang XC, et al. Warburg effect or reverse Warburg effect? A review of cancer metabolism. Oncology research and treatment. 2015;38(3):117-22. Epub 2015/03/21.spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectQuiescenciaspa
dc.subjectHipoxiaspa
dc.subjectMicroambiente tumoralspa
dc.subjectMetabolismospa
dc.subjectCélulas HT29spa
dc.subjectTratamiento alternativo al cáncerspa
dc.subjectTerapia génica basada en NISspa
dc.subjectCáncer de tiroidesspa
dc.subject.ddcFarmacología & terapéuticaspa
dc.subject.ddcMedicina experimentalspa
dc.subject.keywordNISspa
dc.subject.keywordQuiescencespa
dc.subject.keywordHypoxiaspa
dc.subject.keywordTumor microenvironmentspa
dc.subject.keywordMetabolismspa
dc.subject.keywordHT29 cellsspa
dc.subject.keywordAlternative cancer treatmentspa
dc.subject.keywordNIS-based gene therapyspa
dc.subject.keywordThyroid cancerspa
dc.titleTratamiento antitumoral basado en la expresión de la proteína NIS: Análisis del microambiente tumoral en un modelo in vitrospa
dc.title.TranslatedTitleAntitumor treatment based on the expression of NIS protein: Analysis of the tumor microenvironment in an in vitro modeleng
dc.typedoctoralThesiseng
dc.type.documentEnsayo clínicospa
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaTesis de doctoradospa
local.department.reportEscuela de Medicina y Ciencias de la Saludspa
Archivos
Bloque original
Mostrando1 - 2 de 2
Cargando...
Miniatura
Nombre:
Tesis doctorado-Fabio Castillo-26-11-2020-Repositorio.pdf
Tamaño:
3.35 MB
Formato:
Adobe Portable Document Format
Descripción:
Tesis de Doctorado Fabio Castillo Rivera
Cargando...
Miniatura
Nombre:
Articulo-1-Publicado-Translational oncology.pdf
Tamaño:
4.97 MB
Formato:
Adobe Portable Document Format
Descripción:
Artículo Principal Publicado en Translational oncology