Identificación del polimorfismo en la MMP-7-181A>G en mujeres potosinas con neoplasia intraepitelial cervical
DOI:
https://doi.org/10.33064/iycuaa2021822452Palabras clave:
Polimorfismo, MMP-7, Neoplasia Intraepitelial Cervical, Cáncer CervicouterinoResumen
Las metaloproteasas están implicadas en la regulación del crecimiento, diferenciación, apoptosis, invasión, migración, metástasis, angiogénesis y regulan el microambiente del tumor. El polimorfismo -181A>G
del gen MMP-7 produce una sobreexpresión de la proteína y se ha asociado a diversos cánceres: hígado, pulmón, boca y cáncer cervicouterino (CaCu). En este estudio se recolectaron 103 muestras de células bucales descamadas de pacientes con diferentes grados de neoplasia intraepitelial cervical (NIC) y se aplicó el instrumento (30 preguntas) para la identificación de factor de riesgo y cofactores para el desarrollo de NIC y CaCu. Se amplificó por PCR un fragmento de 159pb del gen MMP-7 para la identificación del polimorfismo -181A>G a través de análisis de restricción.
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Campos-Romero, A., Anderson, K. S., Longatto-Filho, A., Esparza, M. A. L.-R., Morán-Portela, D. J., Castro-Menéndez, J. A., . . . Meynard-Mejía, F. A. (2019). The burden of 14 hr-HPV genotypes in women attending routine cervical cancer screening in 20 states of Mexico: a cross-sectional study. Scientific reports, 9(1), 1-10. https://www.nature.com/articles/s41598-019-46543-8
Caratachea, M. A. C. (2007). Polimorfismos genéticos: Importancia y aplicaciones. Revista del Instituto Nacional de Enfermedades Respiratorias, 20(3), 213-221. https://www.medigraphic.com/pdfs/iner/in-2007/in073h.pdf
Castellsagué, X., Bosch, F. X., Munoz, N., Meijer, C. J. L. M., Shah, K. V., De Sanjosé, S., . . . Smith, J. S. (2002). Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. New England journal of medicine, 346(15), 1105-1112. https://www.nejm.org/doi/full/10.1056/NEJMoa011688
Chatterjee, N., & Walker, G. C. (2017). Mechanisms of DNA damage, repair, and mutagenesis. Environmental and molecular mutagenesis, 58(5), 235-263.
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Jormsjö, S., Whatling, C., Walter, D. H., Zeiher, A. M., Hamsten, A., & Eriksson, P. (2001). Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arteriosclerosis, thrombosis, and vascular biology, 21(11), 1834-1839. https://www.ahajournals.org/doi/full/10.1161/hq1101.098229?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Kastelijn, E. A., van Moorsel, C. H., Ruven, H. J., Karthaus, V., Kwakkel-van Erp, J. M., van de Graaf, E. A., . . . van den Bosch, J. M. (2010). Genetic polymorphisms in MMP7 and reduced serum levels associate with the development of bronchiolitis obliterans syndrome after lung transplantation. The Journal of Heart and Lung Transplantation, 29(6), 680-686. https://www.jhltonline.org/article/S1053-2498(10)00040-9/fulltext
Kubben, F., Sier, C. F. M., Meijer, M. J. W., Van Den Berg, M., Van der Reijden, J. J., Griffioen, G., . . . Verspaget, H. W. (2006). Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. British journal of cancer, 95(6), 744. https://www.nature.com/articles/6603307
Li, Y., Jia, J.-H., Kang, S., Zhang, X.-J., Zhao, J., Wang, N., . . . Wang, D.-J. (2009). The functional polymorphisms on promoter region of matrix metalloproteinase-12,-13 genes may alter the risk of epithelial ovarian carcinoma in Chinese. International Journal of Gynecologic Cancer, 19(1), 129-133. https://www.ncbi.nlm.nih.gov/pubmed/19258954
Malik, M. A., Sharma, K. L., Zargar, S. A., & Mittal, B. (2011). Association of matrix metalloproteinase-7 (-181A> G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association, 17(5), 301. http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2011;volume=17;issue=5;spage=301;epage=306;aulast=Malik
Medina-Villaseñor, E., Oliver-Parra, P., Neyra-Ortiz, E., Pérez-Castro, J., Sánchez-Orozco, J., & Contreras-González, N. (2014). Neoplasia intraepitelial cervical, análisis de las características clínico patológicas. GAMO, 13(1), 12-25. https://www.elsevier.es/es-revista-gaceta-mexicana-oncologia-305-articulo-neoplasia-intraepitelial-cervical-analisis-caracteristicas-X166592011427863X
Mogulkoc, U., Coskunpinar, E., Aynaci, E., Cağlar, E., Ortakoylu, M. G., Ozkan, G., . . . Eraltan, I. Y. (2012). Is MMP-7 gene polymorphism a possible risk factor for chronic obstructive pulmonary disease in Turkish patients. Genetic testing and molecular biomarkers, 16(6), 519-523. https://www.liebertpub.com/doi/abs/10.1089/gtmb.2011.0271?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=gtmb
Moreno-Ortiz, J. M., Gutierrez-Angulo, M., Partida-Perez, M., Peregrina-Sandoval, J., Ramirez-Ramirez, R., Muniz-Mendoza, R., . . . Cabrales-Vazquez, J. E. (2014). Association of MMP7-181A/Gand MMP13-77A/G polymorphisms with colorectal cancer in a Mexican population. Genetics and Molecular Research, 13(2), 3537-3544. https://www.geneticsmr.com/articles/2869
Qiu, W., Zhou, G., Zhai, Y., Zhang, X., Xie, W., Zhang, H., . . . Zhang, X. (2008). No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population. Cancer Epidemiology and Prevention Biomarkers, 17(9), 2514-2518. https://cebp.aacrjournals.org/content/17/9/2514.long
Ramírez-Bello, J., Vargas-Alarcón, G., Tovilla-Zárate, C., & Fragoso, J. M. (2013). Polimorfismos de un solo nucleótido (SNP): implicaciones funcionales de los SNP reguladores (rSNP) y de los SNP-ARN estructurales (srSNP) en enfermedades complejas. Gaceta medica de Mexico, 149(2), 220-228. https://www.anmm.org.mx/GMM/2013/n2/GMM_149_2013_2_220-228.pdf
Singh, H., Jain, M., & Mittal, B. (2008). MMP-7 (− 181A> G) promoter polymorphisms and risk for cervical cancer. Gynecologic oncology, 110(1), 71-75. https://www.gynecologiconcology-online.net/article/S0090-8258(08)00199-6/fulltext
Subramanian, L., Maghajothi, S., Singh, M., Kesh, K., Kalyani, A., Sharma, S., . . . Asthana, S. (2019). A Common Tag Nucleotide Variant in MMP7 Promoter Increases Risk for Hypertension via Enhanced Interactions With CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor. Hypertension, 74(6), 1448-1459. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.12960
Sugawara, Y., Tsuji, I., Mizoue, T., Inoue, M., Sawada, N., Matsuo, K., . . . Kitamura, Y. (2018). Cigarette smoking and cervical cancer risk: An evaluation based on a systematic review and meta-analysis among Japanese women. Japanese journal of clinical oncology, 49(1), 77-86. https://academic.oup.com/jjco/article/49/1/77/5165106
Sánchez, A. A., Grimaldo, J. F., & Alarcón, C. E. S. (2009). Factores de riesgo para el desarrollo de la displasia leve cervical. Revista de la Facultad de Medicina UNAM, 52(2), 69-72. https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=19577
Tacheva, T., Dimov, D., Anastasov, A., Zhelyazkova, Y., Kurzawski, M., Gulubova, M., . . . Vlaykova, T. (2017). Association of the MMP7–181A> G promoter polymorphism with early onset of chronic obstructive pulmonary disease. Balkan Journal of Medical Genetics, 20(2), 59-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972504/
Wu, J., Guan, X., Zhang, K., Li, Y. T., & Bai, P. (2013). A/G polymorphism of matrix metalloproteinase 7 gene promoter region and cancer risk: A meta‑analysis. Biomedical reports, 1(5), 792-796. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917052/
Yari, K., Rahimi, Z., Payandeh, M., & Rahimi, Z. (2015). MMP-7 A-181G polymorphism in breast cancer patients from western Iran. Breast Care, 10(6), 398-402. https://www.karger.com/Article/Fulltext/442231
Ye, S. (2000). Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biology, 19(7), 623-629. https://www.sciencedirect.com/science/article/pii/S0945053X00001025
Yoshimoto, M., Itoh, F., Yamamoto, H., Hinoda, Y., Imai, K., & Yachi, A. (1993). Expression of MMP‐7 (PUMP‐1) mRNA in human colorectal cancers. International journal of cancer, 54(4), 614-618. https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.2910540415?sid=nlm%3Apubmed
Yu, W.-H., Woessner, J. F., McNeish, J. D., & Stamenkovic, I. (2002). CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes & development, 16(3), 307-323. http://genesdev.cshlp.org/content/16/3/307.long
Zhang, J., Jin, X., Fang, S., Wang, R., Li, Y., Wang, N., . . . Wei, L. (2005). The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma. Carcinogenesis, 26(10), 1748-1753. https://academic.oup.com/carcin/article/26/10/1748/2390750
Zhang, X.-J., Guo, W., Wang, N., Zhou, R.-M., Dong, X.-J., & Li, Y. (2006). The association of MMP-13 polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. Yi chuan= Hereditas, 28(12), 1500-1504. https://www.ncbi.nlm.nih.gov/pubmed/17138534
Baltazar-Rodriguez, L. M., Anaya-Ventura, A., Andrade-Soto, M., Monrroy-Guizar, E. A., Bautista-Lam, J. R., Jonguitud-Olguin, G., . . . Soriano-Hernández, A. D. (2008). Polymorphism in the matrix metalloproteinase-2 gene promoter is associated with cervical neoplasm risk in Mexican women. Biochemical genetics, 46(3-4), 137-144. https://link.springer.com/article/10.1007%2Fs10528-007-9136-4
Beeghly‐Fadiel, A., Shu, X. o., Long, J., Li, C., Cai, Q., Cai, H., . . . Zheng, W. (2009). Genetic polymorphisms in the MMP‐7 gene and breast cancer survival. International journal of cancer, 124(1), 208-214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597698/
Bosch, F. X., & Muñoz, N. (2002). The viral etiology of cervical cancer. Virus research, 89(2), 183-190. https://www.sciencedirect.com/science/article/abs/pii/S0168170202001879?via%3Dihub
Campos-Romero, A., Anderson, K. S., Longatto-Filho, A., Esparza, M. A. L.-R., Morán-Portela, D. J., Castro-Menéndez, J. A., . . . Meynard-Mejía, F. A. (2019). The burden of 14 hr-HPV genotypes in women attending routine cervical cancer screening in 20 states of Mexico: a cross-sectional study. Scientific reports, 9(1), 1-10. https://www.nature.com/articles/s41598-019-46543-8
Caratachea, M. A. C. (2007). Polimorfismos genéticos: Importancia y aplicaciones. Revista del Instituto Nacional de Enfermedades Respiratorias, 20(3), 213-221. https://www.medigraphic.com/pdfs/iner/in-2007/in073h.pdf
Castellsagué, X., Bosch, F. X., Munoz, N., Meijer, C. J. L. M., Shah, K. V., De Sanjosé, S., . . . Smith, J. S. (2002). Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. New England journal of medicine, 346(15), 1105-1112. https://www.nejm.org/doi/full/10.1056/NEJMoa011688
Chatterjee, N., & Walker, G. C. (2017). Mechanisms of DNA damage, repair, and mutagenesis. Environmental and molecular mutagenesis, 58(5), 235-263.
Coronato, S., Laguens, G., & Di Girolamo, V. (2012). ROL DE LAS METALOPROTEINASAS Y SUS INHIBIDORES EN PATOLOGÍA TUMORAL. Medicina (Buenos Aires), 72(6). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474181/
Enríquez, S. O. G., Donjuan, L. F. M., Figueroa, Y. T., Hernández, D. G., Ovalle, C. O., & Oviedo, A. D. (2017). Impacto de la aplicación de una estrategia de aprendizaje para mejorar la calidad de la muestra en el tamizaje cervical en personal de enfermería en servicio social. Invest. educ. enferm, 35(3), 340-347. https://pesquisa.bvsalud.org/portal/resource/pt/biblio-878969
Ghilardi, G., Biondi, M. L., Erario, M., Guagnellini, E., & Scorza, R. (2003). Colorectal carcinoma susceptibility and metastases are associated with matrix metalloproteinase-7 promoter polymorphisms. Clinical chemistry, 49(11), 1940-1942. http://clinchem.aaccjnls.org/content/49/11/1940.long
Gunnell, A. S., Tran, T. N., Torrång, A., Dickman, P. W., Sparén, P., Palmgren, J., & Ylitalo, N. (2006). Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development. Cancer Epidemiology and Prevention Biomarkers, 15(11), 2141-2147. https://cebp.aacrjournals.org/content/15/11/2141.long
Jormsjö, S., Whatling, C., Walter, D. H., Zeiher, A. M., Hamsten, A., & Eriksson, P. (2001). Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arteriosclerosis, thrombosis, and vascular biology, 21(11), 1834-1839. https://www.ahajournals.org/doi/full/10.1161/hq1101.098229?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Kastelijn, E. A., van Moorsel, C. H., Ruven, H. J., Karthaus, V., Kwakkel-van Erp, J. M., van de Graaf, E. A., . . . van den Bosch, J. M. (2010). Genetic polymorphisms in MMP7 and reduced serum levels associate with the development of bronchiolitis obliterans syndrome after lung transplantation. The Journal of Heart and Lung Transplantation, 29(6), 680-686. https://www.jhltonline.org/article/S1053-2498(10)00040-9/fulltext
Kubben, F., Sier, C. F. M., Meijer, M. J. W., Van Den Berg, M., Van der Reijden, J. J., Griffioen, G., . . . Verspaget, H. W. (2006). Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. British journal of cancer, 95(6), 744. https://www.nature.com/articles/6603307
Li, Y., Jia, J.-H., Kang, S., Zhang, X.-J., Zhao, J., Wang, N., . . . Wang, D.-J. (2009). The functional polymorphisms on promoter region of matrix metalloproteinase-12,-13 genes may alter the risk of epithelial ovarian carcinoma in Chinese. International Journal of Gynecologic Cancer, 19(1), 129-133. https://www.ncbi.nlm.nih.gov/pubmed/19258954
Malik, M. A., Sharma, K. L., Zargar, S. A., & Mittal, B. (2011). Association of matrix metalloproteinase-7 (-181A> G) polymorphism with risk of esophageal squamous cell carcinoma in Kashmir Valley. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association, 17(5), 301. http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2011;volume=17;issue=5;spage=301;epage=306;aulast=Malik
Medina-Villaseñor, E., Oliver-Parra, P., Neyra-Ortiz, E., Pérez-Castro, J., Sánchez-Orozco, J., & Contreras-González, N. (2014). Neoplasia intraepitelial cervical, análisis de las características clínico patológicas. GAMO, 13(1), 12-25. https://www.elsevier.es/es-revista-gaceta-mexicana-oncologia-305-articulo-neoplasia-intraepitelial-cervical-analisis-caracteristicas-X166592011427863X
Mogulkoc, U., Coskunpinar, E., Aynaci, E., Cağlar, E., Ortakoylu, M. G., Ozkan, G., . . . Eraltan, I. Y. (2012). Is MMP-7 gene polymorphism a possible risk factor for chronic obstructive pulmonary disease in Turkish patients. Genetic testing and molecular biomarkers, 16(6), 519-523. https://www.liebertpub.com/doi/abs/10.1089/gtmb.2011.0271?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=gtmb
Moreno-Ortiz, J. M., Gutierrez-Angulo, M., Partida-Perez, M., Peregrina-Sandoval, J., Ramirez-Ramirez, R., Muniz-Mendoza, R., . . . Cabrales-Vazquez, J. E. (2014). Association of MMP7-181A/Gand MMP13-77A/G polymorphisms with colorectal cancer in a Mexican population. Genetics and Molecular Research, 13(2), 3537-3544. https://www.geneticsmr.com/articles/2869
Qiu, W., Zhou, G., Zhai, Y., Zhang, X., Xie, W., Zhang, H., . . . Zhang, X. (2008). No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population. Cancer Epidemiology and Prevention Biomarkers, 17(9), 2514-2518. https://cebp.aacrjournals.org/content/17/9/2514.long
Ramírez-Bello, J., Vargas-Alarcón, G., Tovilla-Zárate, C., & Fragoso, J. M. (2013). Polimorfismos de un solo nucleótido (SNP): implicaciones funcionales de los SNP reguladores (rSNP) y de los SNP-ARN estructurales (srSNP) en enfermedades complejas. Gaceta medica de Mexico, 149(2), 220-228. https://www.anmm.org.mx/GMM/2013/n2/GMM_149_2013_2_220-228.pdf
Singh, H., Jain, M., & Mittal, B. (2008). MMP-7 (− 181A> G) promoter polymorphisms and risk for cervical cancer. Gynecologic oncology, 110(1), 71-75. https://www.gynecologiconcology-online.net/article/S0090-8258(08)00199-6/fulltext
Subramanian, L., Maghajothi, S., Singh, M., Kesh, K., Kalyani, A., Sharma, S., . . . Asthana, S. (2019). A Common Tag Nucleotide Variant in MMP7 Promoter Increases Risk for Hypertension via Enhanced Interactions With CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor. Hypertension, 74(6), 1448-1459. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.12960
Sugawara, Y., Tsuji, I., Mizoue, T., Inoue, M., Sawada, N., Matsuo, K., . . . Kitamura, Y. (2018). Cigarette smoking and cervical cancer risk: An evaluation based on a systematic review and meta-analysis among Japanese women. Japanese journal of clinical oncology, 49(1), 77-86. https://academic.oup.com/jjco/article/49/1/77/5165106
Sánchez, A. A., Grimaldo, J. F., & Alarcón, C. E. S. (2009). Factores de riesgo para el desarrollo de la displasia leve cervical. Revista de la Facultad de Medicina UNAM, 52(2), 69-72. https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=19577
Tacheva, T., Dimov, D., Anastasov, A., Zhelyazkova, Y., Kurzawski, M., Gulubova, M., . . . Vlaykova, T. (2017). Association of the MMP7–181A> G promoter polymorphism with early onset of chronic obstructive pulmonary disease. Balkan Journal of Medical Genetics, 20(2), 59-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972504/
Wu, J., Guan, X., Zhang, K., Li, Y. T., & Bai, P. (2013). A/G polymorphism of matrix metalloproteinase 7 gene promoter region and cancer risk: A meta‑analysis. Biomedical reports, 1(5), 792-796. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917052/
Yari, K., Rahimi, Z., Payandeh, M., & Rahimi, Z. (2015). MMP-7 A-181G polymorphism in breast cancer patients from western Iran. Breast Care, 10(6), 398-402. https://www.karger.com/Article/Fulltext/442231
Ye, S. (2000). Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biology, 19(7), 623-629. https://www.sciencedirect.com/science/article/pii/S0945053X00001025
Yoshimoto, M., Itoh, F., Yamamoto, H., Hinoda, Y., Imai, K., & Yachi, A. (1993). Expression of MMP‐7 (PUMP‐1) mRNA in human colorectal cancers. International journal of cancer, 54(4), 614-618. https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.2910540415?sid=nlm%3Apubmed
Yu, W.-H., Woessner, J. F., McNeish, J. D., & Stamenkovic, I. (2002). CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes & development, 16(3), 307-323. http://genesdev.cshlp.org/content/16/3/307.long
Zhang, J., Jin, X., Fang, S., Wang, R., Li, Y., Wang, N., . . . Wei, L. (2005). The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma. Carcinogenesis, 26(10), 1748-1753. https://academic.oup.com/carcin/article/26/10/1748/2390750
Zhang, X.-J., Guo, W., Wang, N., Zhou, R.-M., Dong, X.-J., & Li, Y. (2006). The association of MMP-13 polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. Yi chuan= Hereditas, 28(12), 1500-1504. https://www.ncbi.nlm.nih.gov/pubmed/17138534
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2021-03-31
Cómo citar
Gallegos-García, V., Medina de la Cruz, O., Escoto Chávez, S. E., Gaytán Hernández, D., Villegas Hinojosa, E. ., & Terán Figuera, Y. (2021). Identificación del polimorfismo en la MMP-7-181A>G en mujeres potosinas con neoplasia intraepitelial cervical. Investigación Y Ciencia De La Universidad Autónoma De Aguascalientes, (82), 33–41. https://doi.org/10.33064/iycuaa2021822452
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Derechos de autor 2021 Verónica Gallegos-García, Medina- de la Cruz Omar, ESCOTO- CHÁVEZ SAÚL E., Gaytán- Hernández Dario, Villegas- Hinojosa Edgar, Terán- Figueroa Yolanda
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.
Las obras publicadas en versión electrónica de la revista están bajo la licencia Creative Commons Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
