EVALUACIÓN DEL COMPORTAMIENTO BIOLÓGICO DE LA ACETIL PODOFILOTOXINA, SOBRE LÍNEAS CELULARES DE CÁNCER ASOCIADO A VPH

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La información epidemiológica describe que la infección por el Virus del Papiloma Humano (VPH), se considera como factor etiológico del cáncer cervical, sustentado en que el 99,9% de las mujeres tienen o han tenido la infección con el virus ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.bpobgyn.2017.08.006","ISSN":"15216934","abstract":"Human papillomavirus (HPV) infection is recognized as one of the major causes of infection-related cancer in both men and women. High-risk HPV types are not only responsible for virtually all cervical cancer cases but also for a fraction of cancers of the vulva, vagina, penis, anus, and head and neck cancers. Furthermore, HPV is also the cause of anogenital warts and recurrent respiratory papillomatosis. Despite the availability of multiple preventative strategies, HPV-related cancer remains a leading cause of morbi-mortality in many parts of the world, particularly in less developed countries. Thus, in this review, we summarize the latest estimates of the global burden of HPV-related diseases, trends, the attributable fraction by HPV types, and the potential preventative fraction.","author":[{"dropping-particle":"","family":"Serrano","given":"Beatriz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brotons","given":"María","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bosch","given":"Francesc Xavier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bruni","given":"Laia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Best Practice & Research Clinical Obstetrics & Gynaecology","id":"ITEM-1","issued":{"date-parts":[["2018","2"]]},"page":"14-26","publisher":"Elsevier Ltd","title":"Epidemiology and burden of HPV-related disease","type":"article-journal","volume":"47"},"uris":["http://www.mendeley.com/documents/?uuid=77384179-bc96-4949-b935-97f35b03bdd0"]}],"mendeley":{"formattedCitation":"(1)","plainTextFormattedCitation":"(1)","previouslyFormattedCitation":"(1)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(1). Por otra parte, esta infección viral, también se encuentra relacionado con carcinomas en otras zonas anatómicas como pene (49%), ano (70%) y cabeza y cuello (30-60%) (CECC). ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/ans.13417","ISSN":"14452197","abstract":"The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed.","author":[{"dropping-particle":"","family":"Buckley","given":"Lisa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gupta","given":"Ruta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ashford","given":"Bruce","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jabbour","given":"Joe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clark","given":"Jonathan R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"ANZ Journal of Surgery","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2016"]]},"page":"442-447","title":"Oropharyngeal cancer and human papilloma virus: Evolving diagnostic and management paradigms","type":"article-journal","volume":"86"},"uris":["http://www.mendeley.com/documents/?uuid=d14e9078-4691-4f01-97b2-9739cf687c7f"]},{"id":"ITEM-2","itemData":{"DOI":"10.15446/rev.colomb.biote.v20n1.64114","ISSN":"0123-3475","abstract":"De acuerdo a la historia natural del cáncer del cuello uterino, en donde las lesiones preneoplásicas de bajo y alto grado pueden presentar fenómenos de regresión o progresión, existe gran interés en la búsqueda de biomarcadores que permita predecir la evolución de las lesiones preneoplásicas del cérvix hacia la progresión o regresión de la enfermedad. Estos biomarcadores pudieran ser de origen genético, o epigenético que alteren la expresión de los genes y que pudieran estar asociados con la carcinogénesis en diferentes tipos de tejido humano. El objetivo del estudio fue analizar la expresión del mARN de los genes SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 y HAND1 en muestras negativas para lesiones intraepiteliales cervicales (n=9), muestras con lesiones intraepiteliales de bajo grado (n=10) y alto grado (n=11). Se realizó análisis de expresión de los genes mencionados mediante qRT-PCR y el análisis de los datos se realizó mediante la prueba no paramétrica de ANOVA. La diferencia estadística se determinó en valores p< 0,05. Para los genes EDNRB y CDX2 se observó disminución 66,7% en las muestras sin alteraciones histológicas cervicales, comparado con una disminución en la expresión del 50% en muestras con LIEBG y para el grupo de LIEAG del 36,4% para el gen EDNRB y del 27,3% para el gen CDX2 dando una diferencia estadísticamente significativa p= 0,02. Sugiriendo que EDNRB y CDX2 podrían ser útiles como posibles biomarcadores en la carcinogénesis cervical.","author":[{"dropping-particle":"","family":"García Robayo","given":"Dabeiba Adriana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baena","given":"Juvenal Dario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Castañeda","given":"Diego Andres","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aristizabal","given":"Fabio Ancizar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cid Arregui","given":"Angel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Revista Colombiana de Biotecnología","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018"]]},"page":"6-15","title":"Expresión de EDNRB y CDX2 posibles biomarcadores en progresión al cáncer cervical","type":"article-journal","volume":"20"},"uris":["http://www.mendeley.com/documents/?uuid=8e5e5c08-5a55-4b44-95b4-b975ba18578d"]},{"id":"ITEM-3","itemData":{"DOI":"10.1093/infdis/jiu077","ISSN":"0022-1899","abstract":"Background. In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. Methods. A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. Results. The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. Conclusion. The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.","author":[{"dropping-particle":"","family":"Moreira","given":"Edson Duarte","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giuliano","given":"Anna R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Palefsky","given":"Joel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Flores","given":"Carlos Aranda","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldstone","given":"Stephen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ferris","given":"Daron","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hillman","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moi","given":"Harald","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoler","given":"Mark H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marshall","given":"Brooke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vuocolo","given":"Scott","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guris","given":"Dalya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haupt","given":"Richard M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Infectious Diseases","id":"ITEM-3","issue":"15 July","issued":{"date-parts":[["2014","7","15"]]},"page":"192-199","title":"Incidence, Clearance, and Disease Progression of Genital Human Papillomavirus Infection in Heterosexual Men","type":"article-journal","volume":"210"},"uris":["http://www.mendeley.com/documents/?uuid=2c206f19-c425-4352-a860-c587caf0eb7a"]},{"id":"ITEM-4","itemData":{"ISSN":"01208322","abstract":"Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000 and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines","author":[{"dropping-particle":"","family":"Muñoz, Nubia; Bravo","given":"Luis Eduardo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colombia Medica","id":"ITEM-4","issue":"4","issued":{"date-parts":[["2012"]]},"page":"298-304","title":"Epidemiology of cervical cancer in Colombia.","type":"article-journal","volume":"43"},"uris":["http://www.mendeley.com/documents/?uuid=ae32cb3a-debd-478c-8990-780df3044db1"]},{"id":"ITEM-5","itemData":{"DOI":"10.1016/j.bpobgyn.2017.08.006","ISSN":"15216934","abstract":"Human papillomavirus (HPV) infection is recognized as one of the major causes of infection-related cancer in both men and women. High-risk HPV types are not only responsible for virtually all cervical cancer cases but also for a fraction of cancers of the vulva, vagina, penis, anus, and head and neck cancers. Furthermore, HPV is also the cause of anogenital warts and recurrent respiratory papillomatosis. Despite the availability of multiple preventative strategies, HPV-related cancer remains a leading cause of morbi-mortality in many parts of the world, particularly in less developed countries. Thus, in this review, we summarize the latest estimates of the global burden of HPV-related diseases, trends, the attributable fraction by HPV types, and the potential preventative fraction.","author":[{"dropping-particle":"","family":"Serrano","given":"Beatriz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brotons","given":"María","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bosch","given":"Francesc Xavier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bruni","given":"Laia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Best Practice & Research Clinical Obstetrics & Gynaecology","id":"ITEM-5","issued":{"date-parts":[["2018","2"]]},"page":"14-26","publisher":"Elsevier Ltd","title":"Epidemiology and burden of HPV-related disease","type":"article-journal","volume":"47"},"uris":["http://www.mendeley.com/documents/?uuid=77384179-bc96-4949-b935-97f35b03bdd0"]}],"mendeley":{"formattedCitation":"(1–5)","plainTextFormattedCitation":"(1–5)","previouslyFormattedCitation":"(1–5)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(1–5) A la fecha se han descrito más de 100 tipos virales, de los cuales, 40 infectan la región ano-genital y de ellos 14 aproximadamente se relacionan con la presencia de cáncer (carcinogénicos). A nivel mundial los tipos de VPH más frecuentemente relacionados con cáncer en las distintas regiones anatómicas son el 16 y 18; sin embargo, estas frecuencias pueden variar de acuerdo con la región geográfica ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.23961/cimel.v22i1.749","ISSN":"1992-4240","abstract":"La infección genital por el Virus del Papiloma Humano (VPH), es una enfermedad de transmisión sexual (ETS) de alta incidencia mundial; desempeña un rol importante en la génesis de las lesiones pre-neoplásicas y del cáncer invasivo de cuello uterino. El VPH es un virus de tamaño pequeño, no encapsulado, virus ADN de doble cadena circular. Además del Cáncer Cérvico-Uterino (CCU), también produce cáncer de vagina, vulva, ano, pene y orofaríngeo;enfermedades benignas como las verrugas, condilomas genitales y patología de las vías aéreas superiores como la Papilomatosis respiratoria recurrente. El diagnóstico se realiza con: examen clínico, colposcopia y los estudios citológicos e histopatológicos, además existen otros métodos basados en la manipulación de ácidos nucleicos para detectar y tipificar VPH con alta sensibilidad y especificidad. La vacunación contra el VPH es una de las acciones que se están implementando para la erradicación del cáncer cérvico-uterino a nivel mundial, aunque faltan muchos años para evaluar la efectividad de las vacunas en todo el espectro de enfermedades relacionadas con el virus. En la actualidad no existe un fármaco específico contra el VPH, sin embargo, el tratamiento debe ser consensuado con el fin de dar una mejor calidad de vida, teniendo en cuenta siempre la morfología y la extensión de las lesiones.Palabras Clave: Infecciones por Papillomavirus; vacunas contra papillomavirus; neoplasias del cuello uterino; cáncer (Fuente DeCS BIREME)","author":[{"dropping-particle":"","family":"Vasquez-Bonilla","given":"WO","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rotela-Fisch","given":"Verónica","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz-Martínez","given":"Yeimer","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Ciencia e Investigación Medico Estudiantil Latinoamericana","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2017"]]},"page":"72-76","title":"Virus Del Papiloma Humano: Revisión De La Literatura","type":"article-journal","volume":"22"},"uris":["http://www.mendeley.com/documents/?uuid=24409e13-c4d0-412b-bc4f-e14fb51d02a3"]},{"id":"ITEM-2","itemData":{"ISSN":"01208322","abstract":"Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000 and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines","author":[{"dropping-particle":"","family":"Muñoz, Nubia; Bravo","given":"Luis Eduardo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colombia Medica","id":"ITEM-2","issue":"4","issued":{"date-parts":[["2012"]]},"page":"298-304","title":"Epidemiology of cervical cancer in Colombia.","type":"article-journal","volume":"43"},"uris":["http://www.mendeley.com/documents/?uuid=ae32cb3a-debd-478c-8990-780df3044db1"]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/j.bpobgyn.2017.08.006","ISSN":"15216934","abstract":"Human papillomavirus (HPV) infection is recognized as one of the major causes of infection-related cancer in both men and women. High-risk HPV types are not only responsible for virtually all cervical cancer cases but also for a fraction of cancers of the vulva, vagina, penis, anus, and head and neck cancers. Furthermore, HPV is also the cause of anogenital warts and recurrent respiratory papillomatosis. Despite the availability of multiple preventative strategies, HPV-related cancer remains a leading cause of morbi-mortality in many parts of the world, particularly in less developed countries. Thus, in this review, we summarize the latest estimates of the global burden of HPV-related diseases, trends, the attributable fraction by HPV types, and the potential preventative fraction.","author":[{"dropping-particle":"","family":"Serrano","given":"Beatriz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brotons","given":"María","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bosch","given":"Francesc Xavier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bruni","given":"Laia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Best Practice & Research Clinical Obstetrics & Gynaecology","id":"ITEM-3","issued":{"date-parts":[["2018","2"]]},"page":"14-26","publisher":"Elsevier Ltd","title":"Epidemiology and burden of HPV-related disease","type":"article-journal","volume":"47"},"uris":["http://www.mendeley.com/documents/?uuid=77384179-bc96-4949-b935-97f35b03bdd0"]}],"mendeley":{"formattedCitation":"(1,5,6)","plainTextFormattedCitation":"(1,5,6)","previouslyFormattedCitation":"(1,5,6)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(1,5,6). En la actualidad, se cuenta con la vacuna contra VPH como mecanismo de prevención para el cáncer de cuello uterino, estas vacunas son: bivalentes (tipos virales 16 y 18 - Cervarix® de Glaxo Smith Kline), tetravalentes (tipos virales 6, 11 “bajo riesgo”, 16 y 18 “alto riesgo” - GardasilTM de Merck) y nonavalente (tipos virales 6, 11, 16, 18, 31, 33, 45, 52 y 58 – Gardasil 9TM de Merck) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"El reconocimiento del Virus del Papiloma Humano VPH, como la principal causa asociada con el desarrollo de cáncer de cuello uterino y sus lesiones precursoras impulsó el desarrollo de vacunas profilácticas con el fin de pre- venir el desarrollo de lesiones pre-neoplásicas i ii . Luego de más de 20 años de investigación, vacunas eficaces con- tra la Infección por VPH lograron ser desarrolladas.","author":[{"dropping-particle":"","family":"Ministerio de Salud y Protección Social, Instituto Nacional de Cancerología ESE","given":"Instituto Nacional de Salud","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2012"]]},"number-of-pages":"1-5","publisher-place":"Colombia","title":"Vacunación contra el Virus Papiloma humano - VPH en Colombia, para la prevención del cáncer de cuello uterino y verrugas genitales","type":"report"},"uris":["http://www.mendeley.com/documents/?uuid=8d83b0ab-054a-4364-b897-deb701c05dae"]},{"id":"ITEM-2","itemData":{"abstract":"El virus del papiloma humano (VPH) es una familia de virus que, transmitidos a través del contacto sexual, pueden causar enfermedad anogenital y orofaríngea en hombres y mujeres (1). La persistencia de la infección viral con genotipos de VPH de alto riesgo se considera “causa necesaria” para la aparición de cáncer de cuello uterino. Los genotipos de VPH de alto riesgo 16 y 18 causan, aproximadamente, el 70% de todos los cánceres de cuello uterino alrededor del mundo, los tipos 31, 33, 45, 52 y 58 causan un 20% adicional de cánceres","author":[{"dropping-particle":"de","family":"Cancerología","given":"Instituto Nacional","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["2018"]]},"page":"1-6","publisher-place":"Colombia","title":"Evidencia sobre la seguridad de la vacuna contra el cáncer de cuello uterino","type":"article"},"uris":["http://www.mendeley.com/documents/?uuid=5c7b87fc-6544-406e-a8c8-7171ebd35955"]}],"mendeley":{"formattedCitation":"(7,8)","plainTextFormattedCitation":"(7,8)","previouslyFormattedCitation":"(7,8)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(7,8), las cuales son aplicadas en Colombia en el marco de la campaña “Que vivan las mujeres, que viva la vida” desde el año 2012, pero la cual sufrió de un importante revés debido a que en el año 2014 un grupo de estudiantes vacunadas en el municipio El Carmen de Bolívar, presentaron alteraciones de salud que fueron atribuidas por los habitantes de esta localidad a la aplicación de la segunda dosis de la vacuna, sumado a los movimientos anti-vacunas, la cobertura de la misma disminuyó en el país, pasando de 91.4% en el año 2013 a un 20.4% para finales del año 2014 manteniéndose esta cifra hasta en la actualidad ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"21459932","abstract":"HPV infection is considered one of the main causes of neoplasia and preneoplasia associated with infectious processes. It represents public health problems in developed countries, but especially in those which are developing. In response to this, since 2008, the HPV vaccine has been introduced in vaccination schemes and it is currently in more than 120 countries. Once the vaccine was implemented by the Immunization Program in Colombia, its coverage was the best in the world, nevertheless what occurred in 2014, in Bolivar Department it impacted negatively. This article, based on the use of the Theories of Decision and Perception, tackles the process performed by the parents for election of non-vaccination as the most beneficial action considered. The health authority must deal three facts that determine its acceptance by parents and adolescents: first, to manage the uncertainty generated by the vaccine because of doubts about its safety. Second, the impact of communication in the Information Age. Third, the inclusion of Gender equality in terms of beliefs, desires and interpretations about sexuality, reproduction, HPV and in general in daily life in order to end with the disparity between women and men in the exercise of power and decision making process at all levels. (English) [ABSTRACT FROM AUTHOR]","author":[{"dropping-particle":"","family":"Benavides","given":"Mónica","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Salazar","given":"Lida","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Reasons to explain the reduction in coverage of HPV vaccine in Colombia.","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2017"]]},"page":"82-93","title":"Razones que pueden explicar la reducción en la cobertura de vacunación contra VPH en Colombia.","type":"article-journal","volume":"8"},"uris":["http://www.mendeley.com/documents/?uuid=84c438ec-fd81-4369-9688-e99913f3fa67"]},{"id":"ITEM-2","itemData":{"abstract":"El virus del papiloma humano (VPH) es una familia de virus que, transmitidos a través del contacto sexual, pueden causar enfermedad anogenital y orofaríngea en hombres y mujeres (1). La persistencia de la infección viral con genotipos de VPH de alto riesgo se considera “causa necesaria” para la aparición de cáncer de cuello uterino. Los genotipos de VPH de alto riesgo 16 y 18 causan, aproximadamente, el 70% de todos los cánceres de cuello uterino alrededor del mundo, los tipos 31, 33, 45, 52 y 58 causan un 20% adicional de cánceres","author":[{"dropping-particle":"de","family":"Cancerología","given":"Instituto Nacional","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["2018"]]},"page":"1-6","publisher-place":"Colombia","title":"Evidencia sobre la seguridad de la vacuna contra el cáncer de cuello uterino","type":"article"},"uris":["http://www.mendeley.com/documents/?uuid=5c7b87fc-6544-406e-a8c8-7171ebd35955"]}],"mendeley":{"formattedCitation":"(8,9)","plainTextFormattedCitation":"(8,9)","previouslyFormattedCitation":"(8,9)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(8,9); Adicionalmente, aunque los estudios indican que la población masculina también se ve afectada por el VPH causando diversas lesiones benignas y malignas y que la vacunación también es una alternativa viable para controlar estas enfermedades ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/infdis/jiu077","ISSN":"0022-1899","abstract":"Background. In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. Methods. A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. Results. The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. Conclusion. The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.","author":[{"dropping-particle":"","family":"Moreira","given":"Edson Duarte","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giuliano","given":"Anna R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Palefsky","given":"Joel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Flores","given":"Carlos Aranda","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldstone","given":"Stephen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ferris","given":"Daron","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hillman","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moi","given":"Harald","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoler","given":"Mark H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marshall","given":"Brooke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vuocolo","given":"Scott","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guris","given":"Dalya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haupt","given":"Richard M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Infectious Diseases","id":"ITEM-1","issue":"15 July","issued":{"date-parts":[["2014","7","15"]]},"page":"192-199","title":"Incidence, Clearance, and Disease Progression of Genital Human Papillomavirus Infection in Heterosexual Men","type":"article-journal","volume":"210"},"uris":["http://www.mendeley.com/documents/?uuid=2c206f19-c425-4352-a860-c587caf0eb7a"]}],"mendeley":{"formattedCitation":"(4)","plainTextFormattedCitation":"(4)","previouslyFormattedCitation":"(4)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(4), en Colombia la vacunación para VPH es parte de una política pública enfocada exclusivamente en las mujeres, ya que el cáncer es más raro en hombres y la población masculina puede optar por su aplicación pero no de forma gratuita ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Secretaría de Salud /","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2015"]]},"page":"1-10","publisher":"Alcaldía Mayor de Bogotá D.C.","publisher-place":"Bogotá D.C. / Colombia","title":"Lo que debes saber sobre la vacuna contra el virus de papiloma humano (VPH)","type":"article"},"uris":["http://www.mendeley.com/documents/?uuid=d1b378d0-7902-4044-904a-a816ba2d2463"]}],"mendeley":{"formattedCitation":"(10)","plainTextFormattedCitation":"(10)","previouslyFormattedCitation":"(10)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(10). Se han planteado alternativas terapéuticas para el tratamiento de las lesiones VPH positivas, principalmente en lesiones verrugosas como el condiloma acuminado, entre las que destacan el uso de los derivados de la podofilotoxina ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/0002-9343(90)90424-c","ISSN":"00029343","abstract":"PURPOSE: Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy. Conventional ablative therapy requires repeated treatment, often for months or years. This study was undertaken to evaluate the safety and efficacy of 0.5% podofilox in patient-administered treatment of penile warts.\\n\\nPATIENTS AND METHODS: Thirty-eight men with penile warts were randomly assigned to double-blind, self-administration of 0.5% podofilox solution or placebo, twice daily for 3 days per week for 4 weeks. Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment.\\n\\nRESULTS: By the end of treatment, podofilox recipients had their mean wart number and area reduced to 15.9% and 5.1% of baseline values, compared to 97.4% and 92.9% in the placebo group (p = 0.0001). Local adverse reactions were more common in the podofilox group, but were transient. Complete disappearance of warts was observed in 25 (53.3%) of 45 treatment courses, including open-label treatment. Recurrences of warts after therapy were frequent. Only 21% of patients remained free of warts 2 weeks after completing treatment, and subsequent recurrences were noted in all patients available for long-term follow-up, which is a common limitation of ablative therapy for genital warts.\\n\\nCONCLUSION: Podofilox 0.5% solution is effective in treating penile warts and is well tolerated in a self-administered regimen. Podofilox 0.5% offers potential advantages in safety and cost over podophyllin resin therapy of genital warts.","author":[{"dropping-particle":"","family":"Kirby","given":"Philip","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunne","given":"Ardeth","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"King","given":"Dannie H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Corey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Medicine","id":"ITEM-1","issued":{"date-parts":[["1990"]]},"page":"465-469","publisher":"The American Journal of Medicine","title":"Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts","type":"article-journal","volume":"88"},"uris":["http://www.mendeley.com/documents/?uuid=fa9085a5-42b9-4283-ab4a-ac5cfc40f3ad"]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/0002-9343(94)90168-6","ISSN":"00029343","PMID":"8192173","abstract":"purpose: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. patients and methods: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. results: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. conclusion: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease. © 1994.","author":[{"dropping-particle":"","family":"Bonnez","given":"William","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Elswick","given":"Ronald K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bailey-Farchione","given":"Allyson","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hallahan","given":"Dawn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bell","given":"Renée","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Isenberg","given":"Ruth","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoler","given":"Mark H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reichman","given":"Richard C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Medicine","id":"ITEM-2","issue":"5","issued":{"date-parts":[["1994"]]},"page":"420-425","title":"Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts","type":"article-journal","volume":"96"},"uris":["http://www.mendeley.com/documents/?uuid=21b03711-10aa-45be-9de1-ce7df214f1c8"]},{"id":"ITEM-3","itemData":{"DOI":"10.2165/00128071-200506060-00004","abstract":"The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.","author":[{"dropping-particle":"","family":"Fox","given":"Paul A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tung","given":"Mun-Yee","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Am J Clin Dermatol","id":"ITEM-3","issue":"6","issued":{"date-parts":[["2005"]]},"page":"365-381","title":"Burden of Illness and Treatment Cost Considerations","type":"article-journal","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=f22fd976-fee0-4d62-8fa3-a29e742a5d1b"]}],"mendeley":{"formattedCitation":"(11–13)","plainTextFormattedCitation":"(11–13)","previouslyFormattedCitation":"(11–13)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(11–13). La podofilotoxina es un metabolito secundario de tipo lignano ariltetralino, el cual ha sido extraído principalmente de los rizomas de especies del género podophyllum y que ha mostrado resultados prometedores para el tratamiento de lesiones asociadas a VPH, aunque produzca severos efectos citotóxicos sobre el epitelio ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/0002-9343(94)90168-6","ISSN":"00029343","PMID":"8192173","abstract":"purpose: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. patients and methods: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. results: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. conclusion: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease. © 1994.","author":[{"dropping-particle":"","family":"Bonnez","given":"William","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Elswick","given":"Ronald K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bailey-Farchione","given":"Allyson","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hallahan","given":"Dawn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bell","given":"Renée","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Isenberg","given":"Ruth","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoler","given":"Mark H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reichman","given":"Richard C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Medicine","id":"ITEM-1","issue":"5","issued":{"date-parts":[["1994"]]},"page":"420-425","title":"Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts","type":"article-journal","volume":"96"},"uris":["http://www.mendeley.com/documents/?uuid=21b03711-10aa-45be-9de1-ce7df214f1c8"]},{"id":"ITEM-2","itemData":{"ISSN":"15320650","abstract":"External genital warts are a significant health problem particularly for young adults. This review summarizes the current literature on epidemiology, transmission, diagnosis, and treatment. Efficacy of all treatments is less than optimal, and multiple therapies may be necessary for complete resolution. Data on a new patient-applied therapy are presented. New vaccine therapy for prevention of infection should reduce the incidence of disease.","author":[{"dropping-particle":"","family":"Karnes","given":"Jonathan B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Usatine","given":"Richard P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Family Physician","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2014"]]},"page":"312-318","title":"Management of external genital warts","type":"article-journal","volume":"90"},"uris":["http://www.mendeley.com/documents/?uuid=13350f04-43a9-4538-8e47-03ae9ae31e46"]},{"id":"ITEM-3","itemData":{"DOI":"10.1371/journal. pone.0200509","ISBN":"1111111111","ISSN":"19326203","abstract":"Although human papillomavirus (HPV) positive oral and oropharyngeal cancers have distinct epidemiologic and molecular characteristics compared to HPV-negative cancers, all patients with oral and oropharyngeal cancers received same standard regimen regardless of HPV status. For these reasons, specific regimens for patients with HPV-positive oral and oropharyngeal cancer are needed. Differentially expressed genes (DEG) between HPV-positive and HPV-negative oropharyngeal cancers were re-analyzed and categorized from public database. Then, druggable targets to HPV-positive oral and oropharyngeal cancer were identified and were validated with E6/E7, which is oncogene of HPV, transfected oral and oropharyngeal cancer cell lines and HPV infected cell lines. In DEG analysis, HPV-positive oral and oropharyngeal cancer showed distinct disease entity from HPV-negative cancers. Unlike HPV-negative oral and oropharyngeal cancer, thymidylate synthase (TS) and topoisomerase II (Topo II) were overexpressed in HPV-positive cancers. Transfection of Lenti-virus containing E6/ E7 to HPV-negative oral and oropharyngeal cancer cells induced upregulation of TS and Topo II in those cells. Although cisplatin, which is standard regimen in head and neck cancers, showed more effectiveness in HPV-negative cells, 5-FU and pemetrexed, which are TS inhibitors, or etoposide, which is Topo II inhibitors, worked more effectively in HPV-positive cells. In addition, cisplatin/etoposide and cisplatin/pemetrexed combination regimens showed synergic effects in HPV-positive cells. Pemetrexed or etoposide alone, or in combination with other chemotherapeutic agents such as cisplatin, can be used as novel substitutes in a regimen of concurrent chemoradiotherapy or a palliative regimen for HPV-positive oral and oropharyngeal cancer patients. However, a well-designed clinical trial is needed.","author":[{"dropping-particle":"","family":"Kim","given":"Yi Rang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Bada","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Byun","given":"Mi Ran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Jong Kil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Choi","given":"Jin Woo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS ONE","id":"ITEM-3","issue":"7","issued":{"date-parts":[["2018"]]},"page":"1-16","title":"Evaluation of pemetrexed and etoposide as therapeutic regimens for human papillomavirus-positive oral and oropharyngeal cancer","type":"article-journal","volume":"13"},"uris":["http://www.mendeley.com/documents/?uuid=03063e16-f78e-4afb-ba0a-9db67d004fe1"]}],"mendeley":{"formattedCitation":"(12,14,15)","plainTextFormattedCitation":"(12,14,15)","previouslyFormattedCitation":"(12,14,15)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(12,14,15). Recientemente, el grupo de investigación (Fitometálica para el estudio de metabolitos secundarios y sus derivados UAN) encontró en la especie Bursera fagoroides var fagaroides, algunos lignanos derivados de la podofilotoxina con capacidad citotóxica, en líneas tumorales de próstata (PC3), seno (MCF7), nasofaringe (KB) y colon (HF6), de los cuales la acetil podofilotoxina presentó un comportamiento prometedor al inhibir la polimerización de la tubulina y la entrada de estas células en fase G2/M del ciclo celular ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/molecules17089506","abstract":"The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED50 = 9.6 × 10−2 μg/mL), PC-3 (ED50 = 2.5 × 10−1 μg/mL), MCF-7 (ED50 = 6.6 μg/mL), and HF-6 (ED50 = 7.1 × 10−3 μg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED50 = 1.0 × 10−5 μg/mL), and KB (ED50 = 1.0 × 10−5 μg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.","author":[{"dropping-particle":"","family":"Rojas-Sepúlveda","given":"Andrés M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mendieta-Serrano","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mojica","given":"Mayra Y. Antúnez","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Salas-Vida","given":"Enrique","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marquina","given":"Silvia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Villarrea","given":"María Luisa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Puebla","given":"Ana María","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delgado","given":"Jorge I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"Laura","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Molecules","id":"ITEM-1","issued":{"date-parts":[["2012"]]},"page":"9506-9519","title":"Cytotoxic Podophyllotoxin Type-Lignans from the Steam Bark of Bursera fagaroides var. fagaroides","type":"article-journal","volume":"17"},"uris":["http://www.mendeley.com/documents/?uuid=547f8d86-946c-4b7f-89d3-4d4c8df65dec"]},{"id":"ITEM-2","itemData":{"DOI":"10.1021/acs.jnatprod.6b00428","ISSN":"0163-3864","abstract":"Four natural analogues of podophyllotoxin obtained from the Mexican medicinal plant Bursera fagaroides, namely, acetyl podophyllotoxin (2), 5′-desmethoxy-β-peltatin A methyl ether (3), 7′,8′-dehydro acetyl podophyllotoxin (4), and burseranin (5), have been characterized, and their interactions with tubulin have been investigated. Cytotoxic activity measurements, followed by immunofluorescence microscopy and flow cytometry studies, demonstrated that these compounds disrupt microtubule networks in cells and cause cell cycle arrest in the G2/M phase in the A549 cell line. A tubulin binding assay showed that compounds 1−4 were potent assembly inhibitors, displaying binding to the colchicine site with Kb values ranging from 11.75 to 185.0 × 105 M−1. In contrast, burseranin (5) was not able to inhibit tubulin assembly. From the structural perspective, the ligand-binding epitopes of compounds 1−3 have been mapped using STD-NMR, showing that B and E rings are the major points for interaction with the protein. The obtained results indicate that the inhibition of tubulin assembly of this family of compounds is more effective when there are at least two methoxyl groups at the E ring, along with a trans configuration of the lactone ring in the aryltetralin lignan core. T","author":[{"dropping-particle":"","family":"Antúnez-Mojica","given":"Mayra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rodríguez-Salarichs","given":"Javier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Redondo-Horcajo","given":"Mariano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"León","given":"Alejandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barasoain","given":"Isabel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Canales","given":"Angeles","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cañada","given":"F. J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jiménez-Barbero","given":"Jesús","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"Laura","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Díaz","given":"J. Fernando","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Natural Products","id":"ITEM-2","issue":"8","issued":{"date-parts":[["2016"]]},"page":"2113-2121","title":"Structural and Biochemical Characterization of the Interaction of Tubulin with Potent Natural Analogues of Podophyllotoxin","type":"article-journal","volume":"79"},"uris":["http://www.mendeley.com/documents/?uuid=fced0008-4b56-4f56-a506-4946cdb9db48"]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/j.biopha.2014.12.038","ISSN":"19506007","abstract":"To develop a new radiosensitizer against non-small cell lung cancer cells, we screened a natural product library for growth-inhibitory compounds. PA was found to be cytotoxic toward NCI-H460 cells, and its IC50 value was determined. The radiosensitizer effects of PA were tested at its IC50 value in clonogenic and cell-counting assays. The intracellular mechanism underlying this effect was determined by immunoblotting and by measuring propidium iodide uptake and ROS generation. The radiosensitizer activity of PA in vivo was tested in nude mice by treating with PA and IR, and measuring tumor volume and assessing apoptosis. PA, tested at its experimentally determined IC50 value (12nM), enhanced IR-induced death of NCI-H460 cells by increasing apoptosis, yielding a mean calculated dose-enhancement ratio of 1.67. Combination with PA and IR also increased the production of ROS, which subsequently induced phosphorylation of p38, suppressed phosphorylation of ERK, and activated caspase-3, -8, and -9. Notably, inhibition of ROS production prevented p38 phosphorylation, and inhibition of ROS production or p38 activation blocked caspase activation and apoptosis. In a xenograft assay, combination with PA and IR delayed tumor growth by 11.4days compared with controls, yielding an enhancement factor of 1.48. Collectively, these results indicate that PA functions as a radiosensitizer by enhancing apoptosis through activation of a ROS/p38/caspase pathway and suppression of ERK.","author":[{"dropping-particle":"","family":"Choi","given":"Jae Yeon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"Hyun Ji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hwang","given":"Sang Gu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Wun Jae","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"Il","family":"Kim","given":"Jong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Um","given":"Hong Duck","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Jong Kuk","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedicine and Pharmacotherapy","id":"ITEM-3","issued":{"date-parts":[["2015"]]},"page":"111-118","publisher":"Elsevier Masson SAS","title":"Podophyllotoxin acetate enhances γ-ionizing radiation-induced apoptotic cell death by stimulating the ROS/p38/caspase pathway","type":"article-journal","volume":"70"},"uris":["http://www.mendeley.com/documents/?uuid=2d1f49c9-d2d3-4d11-bcda-4fb3a62f09b5"]}],"mendeley":{"formattedCitation":"(16–18)","plainTextFormattedCitation":"(16–18)","previouslyFormattedCitation":"(16–18)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(16–18). Estos resultados muestran que la acetil podofilotoxina podría ser eficiente como tratamiento de las lesiones generadas por el VPH, dado que éste sólo infecta células indiferenciadas y con alta rata proliferativa ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.ppat.1000318","ISSN":"15537366","PMID":"19247434","abstract":"Human papillomaviruses (HPVs) are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis) for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these results also have potentially important implications for HPV control.","author":[{"dropping-particle":"","family":"Pyeon","given":"Dohun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pearce","given":"Shane M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lank","given":"Simon M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahlquist","given":"Paul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lambert","given":"Paul F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS Pathogens","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2009"]]},"page":"e1000318","title":"Establishment of human papillomavirus infection requires cell cycle progression","type":"article-journal","volume":"5"},"uris":["http://www.mendeley.com/documents/?uuid=a7a7bc11-3cfb-47bb-9149-11eb70869306"]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/s13277-015-4548-y","ISBN":"1327701545","ISSN":"14230380","abstract":"Here, we report a new intracellular signaling pathway involved in gamma-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion and migration of A549 cells (a non-small cell lung cancer (NSCLC) cell line). Our results revealed that IR increased the invasion/migration of A549 cells, and this effect was decreased by 10 nM PA treatment. PA also inhibited the expressions/activities of matrix metalloprotase (MMP) -2, MMP-9, and vimentin, suggesting that PA could block the IR-induced epithelial-mesenchymal transition (EMT). The IR-induced increases in invasion/migration were associated with the activation of EGFR-AKT, and PA inhibited this effect. P38 and p44/42 ERK were also involved in IR-induced invasion/migration, and combined treatments with PA plus inhibitors of each MAPK synergistically blocked this invasion/migration. In terms of transcription factors (TFs), IR-induced increases in cyclic AMP response element-binding protein-1 (CREB-1) and signal transducer and activator of transcription 3 (STAT3) increased invasion/migration and EMT. PA also inhibited these transcription factors and then blocked IR-induced invasion/migration. Collectively, these results indicate that IR induces cancer cell invasion/migration by activating the EGFR-p38/ERK-CREB-1/STAT3-EMT pathway and that PA blocks this pathway to inhibit IR-induced invasion/migration.","author":[{"dropping-particle":"","family":"Cho","given":"Jeong Hyun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hong","given":"Wan Gi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jung","given":"Yu Jin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Jaeseok","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Eunah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hwang","given":"Sang Gu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Um","given":"Hong Duck","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Jong Kuk","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Tumor Biology","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2016"]]},"page":"7315-7325","title":"Γ-Ionizing radiation-induced activation of the EGFR–p38/ERK–STAT3/CREB-1–EMT pathway promotes the migration/invasion of non-small cell lung cancer cells and is inhibited by podophyllotoxin acetate","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=99f6a559-d157-49c7-a68c-d15bf812762d"]},{"id":"ITEM-3","itemData":{"DOI":"10.2165/00128071-200506060-00004","abstract":"The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.","author":[{"dropping-particle":"","family":"Fox","given":"Paul A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tung","given":"Mun-Yee","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Am J Clin Dermatol","id":"ITEM-3","issue":"6","issued":{"date-parts":[["2005"]]},"page":"365-381","title":"Burden of Illness and Treatment Cost Considerations","type":"article-journal","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=f22fd976-fee0-4d62-8fa3-a29e742a5d1b"]},{"id":"ITEM-4","itemData":{"DOI":"10.3892/ijo.2016.3471","ISSN":"17912423","abstract":"Podophyllotoxin acetate (PA) acts as a radiosensitizer against non-small cell lung cancer (NSCLC) in vitro and in vivo. In this study, we examined its potential role as a chemosensitizer in conjunction with the topoisomerase inhibitors etoposide (Eto) and camptothecin (Cpt). The effects of combinations of PA and Eto/Cpt were examined with CompuSyn software in two NSCLC cell lines, A549 and NCI-H1299. Combination index (CI) values indicated synergistic effects of PA and the topoisomerase inhibitors. The intracellular mechanism underlying synergism was further determined using propidium iodide uptake, immunoblotting and electrophoretic mobility shift assay (EMSA). Combination of PA with Eto/Cpt promoted disruption of the dynamics of actin filaments, leading to subsequent enhancement of apoptotic cell death via induction of caspase-3, -8, and -9, accompanied by increased phosphorylation of p38. Conversely, suppression of p38 phosphorylation blocked the apoptotic effect of the drug combinations. Notably, CREB-1, a transcription factor, was constitutively activated in both cell types, and synergistically inhibited upon combination treatment. Our results collectively indicate that PA functions as a chemosensitizer by enhancing apoptosis through activation of the p38/caspase axis and suppression of CREB-1.","author":[{"dropping-particle":"","family":"Hong","given":"Wan Gi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"Jeong Hyun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hwang","given":"Sang Gu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Eunah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Jaeseok","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"Il","family":"Kim","given":"Jong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Um","given":"Hong Duck","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Jong Kuk","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Oncology","id":"ITEM-4","issued":{"date-parts":[["2016"]]},"page":"2265-2276","title":"Chemosensitizing effect of podophyllotoxin acetate on topoisomerase inhibitors leads to synergistic enhancement of lung cancer cell apoptosis","type":"article-journal","volume":"48"},"uris":["http://www.mendeley.com/documents/?uuid=ecaa12a9-5b41-461c-b891-77e9eabcddd0"]}],"mendeley":{"formattedCitation":"(13,19–21)","plainTextFormattedCitation":"(13,19–21)","previouslyFormattedCitation":"(13,19–21)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(13,19–21). Sin embargo, dentro de las líneas celulares tumorales evaluadas con acetil podofilotoxina a la fecha, no se encuentran incluidos los modelos de cáncer asociados al VPH, como el cáncer cervicouterino (CCU) y carcinomas escamosos de cabeza y cuello (CECC), además de un modelo de células no tumorales. Adicionalmente, en un estudio reciente se compararon distintos quimioterapéuticos para posible uso en cáncer orofaríngeo asociado o no con VPH, encontrando que el etopósido, un derivado semisintético de la podofilotoxina presentó más efectividad en líneas celulares positivas para el virus, mientras que el cis-platino (agente quelante) era más eficaz para las líneas celulares negativas para VPH ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal. pone.0200509","ISBN":"1111111111","ISSN":"19326203","abstract":"Although human papillomavirus (HPV) positive oral and oropharyngeal cancers have distinct epidemiologic and molecular characteristics compared to HPV-negative cancers, all patients with oral and oropharyngeal cancers received same standard regimen regardless of HPV status. For these reasons, specific regimens for patients with HPV-positive oral and oropharyngeal cancer are needed. Differentially expressed genes (DEG) between HPV-positive and HPV-negative oropharyngeal cancers were re-analyzed and categorized from public database. Then, druggable targets to HPV-positive oral and oropharyngeal cancer were identified and were validated with E6/E7, which is oncogene of HPV, transfected oral and oropharyngeal cancer cell lines and HPV infected cell lines. In DEG analysis, HPV-positive oral and oropharyngeal cancer showed distinct disease entity from HPV-negative cancers. Unlike HPV-negative oral and oropharyngeal cancer, thymidylate synthase (TS) and topoisomerase II (Topo II) were overexpressed in HPV-positive cancers. Transfection of Lenti-virus containing E6/ E7 to HPV-negative oral and oropharyngeal cancer cells induced upregulation of TS and Topo II in those cells. Although cisplatin, which is standard regimen in head and neck cancers, showed more effectiveness in HPV-negative cells, 5-FU and pemetrexed, which are TS inhibitors, or etoposide, which is Topo II inhibitors, worked more effectively in HPV-positive cells. In addition, cisplatin/etoposide and cisplatin/pemetrexed combination regimens showed synergic effects in HPV-positive cells. Pemetrexed or etoposide alone, or in combination with other chemotherapeutic agents such as cisplatin, can be used as novel substitutes in a regimen of concurrent chemoradiotherapy or a palliative regimen for HPV-positive oral and oropharyngeal cancer patients. However, a well-designed clinical trial is needed.","author":[{"dropping-particle":"","family":"Kim","given":"Yi Rang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Bada","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Byun","given":"Mi Ran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Jong Kil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Choi","given":"Jin Woo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS ONE","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2018"]]},"page":"1-16","title":"Evaluation of pemetrexed and etoposide as therapeutic regimens for human papillomavirus-positive oral and oropharyngeal cancer","type":"article-journal","volume":"13"},"uris":["http://www.mendeley.com/documents/?uuid=03063e16-f78e-4afb-ba0a-9db67d004fe1"]}],"mendeley":{"formattedCitation":"(15)","plainTextFormattedCitation":"(15)","previouslyFormattedCitation":"(15)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(15). En este sentido, los hallazgos que hasta ahora han sido presentados permiten preguntar, ¿Cuál es el efecto biológico de la Acetil Podofilotoxina, sobre queratinocitos no tumorales y células tumorales de CCU y CECC (VPH + y VPH -)? El CCU y el CECC son entidades de interés creciente en Colombia, debido al alto costo económico, personal y social que implica el tratamiento de éstas. Las cifras epidemiológicas indican un incremento de la incidencia y mortalidad en el país. Dichos tumores están asociados a la infección por VPH y son prevenibles en estadios tempranos; Sin embargo, las alternativas terapéuticas son muy limitadas y poco eficientes y todos los esfuerzos se orientan a la vacunación en población femenina en edad fértil (en Colombia la edad de aplicación inicia a partir de los 9 años de edad) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"21459932","abstract":"HPV infection is considered one of the main causes of neoplasia and preneoplasia associated with infectious processes. It represents public health problems in developed countries, but especially in those which are developing. In response to this, since 2008, the HPV vaccine has been introduced in vaccination schemes and it is currently in more than 120 countries. Once the vaccine was implemented by the Immunization Program in Colombia, its coverage was the best in the world, nevertheless what occurred in 2014, in Bolivar Department it impacted negatively. This article, based on the use of the Theories of Decision and Perception, tackles the process performed by the parents for election of non-vaccination as the most beneficial action considered. The health authority must deal three facts that determine its acceptance by parents and adolescents: first, to manage the uncertainty generated by the vaccine because of doubts about its safety. Second, the impact of communication in the Information Age. Third, the inclusion of Gender equality in terms of beliefs, desires and interpretations about sexuality, reproduction, HPV and in general in daily life in order to end with the disparity between women and men in the exercise of power and decision making process at all levels. (English) [ABSTRACT FROM AUTHOR]","author":[{"dropping-particle":"","family":"Benavides","given":"Mónica","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Salazar","given":"Lida","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Reasons to explain the reduction in coverage of HPV vaccine in Colombia.","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2017"]]},"page":"82-93","title":"Razones que pueden explicar la reducción en la cobertura de vacunación contra VPH en Colombia.","type":"article-journal","volume":"8"},"uris":["http://www.mendeley.com/documents/?uuid=84c438ec-fd81-4369-9688-e99913f3fa67"]},{"id":"ITEM-2","itemData":{"DOI":"10.2165/00128071-200506060-00004","abstract":"The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.","author":[{"dropping-particle":"","family":"Fox","given":"Paul A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tung","given":"Mun-Yee","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Am J Clin Dermatol","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2005"]]},"page":"365-381","title":"Burden of Illness and Treatment Cost Considerations","type":"article-journal","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=f22fd976-fee0-4d62-8fa3-a29e742a5d1b"]},{"id":"ITEM-3","itemData":{"abstract":"E l Instituto Nacional de Cancerología ESE a través del Grupo de Evaluación y Seguimiento de Servicios On- cológicos, en el Marco del Sistema de Gestión de Tecnología cuenta con una unidad de vigilancia tecnológica e inteligencia competitiva la cual de forma periódica realiza la publicación del BOLETÍN DE VIGILANCIA TEC- NOLÓGICA. Este contiene información relevante respecto a políticas, avances científicos, patentes, publicaciones de los pro- yectos de investigación, entre otros, en los diferentes ámbitos de la salud, permitiendo para esta edición, ampliar la perspectiva frente a la evolución en la detección del Virus del Papiloma Humano (VPH) a nivel internacional y nacional. Una de las fases de la vigilancia tecnológica e inteligencia competitiva es la difusión de la información, que permite identificar las tendencias del desarrollo tecnológico mundial; proceso que favorece la toma de decisiones de las innovaciones frente a nuevas oportunidades de desarrollo a nivel institucional, local y nacional; la difusión motiva la innovación, alcanza un valor agregado en el mercado, incrementa la eficiencia en el diagnóstico, mejora la calidad del análisis de las muestras, aumentando la competitividad y sostenibilidad de las empresas. El objetivo de este boletín es proporcionar información específica y estructurada sobre las tendencias en publi- caciones científicas relacionadas con VPH, los avances de las pruebas de detección del VPH en Colombia y las patentes","author":[{"dropping-particle":"","family":"Ministerio de Salud y Protección Social, Instituto Nacional de Cancerología ESE","given":"Grupo de evaluación y Seguimiento de Servicios Oncológicos","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Boletín de Vigilancia Tecnológica","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2016"]]},"number-of-pages":"1-17","title":"Boletín de Vigilancia Tecnológica Sistema de Gestión de Tecnología","type":"report","volume":"2"},"uris":["http://www.mendeley.com/documents/?uuid=6bc40139-b723-4a7e-8fbe-9d1f0930474b"]},{"id":"ITEM-4","itemData":{"DOI":"10.23961/cimel.v22i1.749","ISSN":"1992-4240","abstract":"La infección genital por el Virus del Papiloma Humano (VPH), es una enfermedad de transmisión sexual (ETS) de alta incidencia mundial; desempeña un rol importante en la génesis de las lesiones pre-neoplásicas y del cáncer invasivo de cuello uterino. El VPH es un virus de tamaño pequeño, no encapsulado, virus ADN de doble cadena circular. Además del Cáncer Cérvico-Uterino (CCU), también produce cáncer de vagina, vulva, ano, pene y orofaríngeo;enfermedades benignas como las verrugas, condilomas genitales y patología de las vías aéreas superiores como la Papilomatosis respiratoria recurrente. El diagnóstico se realiza con: examen clínico, colposcopia y los estudios citológicos e histopatológicos, además existen otros métodos basados en la manipulación de ácidos nucleicos para detectar y tipificar VPH con alta sensibilidad y especificidad. La vacunación contra el VPH es una de las acciones que se están implementando para la erradicación del cáncer cérvico-uterino a nivel mundial, aunque faltan muchos años para evaluar la efectividad de las vacunas en todo el espectro de enfermedades relacionadas con el virus. En la actualidad no existe un fármaco específico contra el VPH, sin embargo, el tratamiento debe ser consensuado con el fin de dar una mejor calidad de vida, teniendo en cuenta siempre la morfología y la extensión de las lesiones.Palabras Clave: Infecciones por Papillomavirus; vacunas contra papillomavirus; neoplasias del cuello uterino; cáncer (Fuente DeCS BIREME)","author":[{"dropping-particle":"","family":"Vasquez-Bonilla","given":"WO","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rotela-Fisch","given":"Verónica","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ortiz-Martínez","given":"Yeimer","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Ciencia e Investigación Medico Estudiantil Latinoamericana","id":"ITEM-4","issue":"1","issued":{"date-parts":[["2017"]]},"page":"72-76","title":"Virus Del Papiloma Humano: Revisión De La Literatura","type":"article-journal","volume":"22"},"uris":["http://www.mendeley.com/documents/?uuid=24409e13-c4d0-412b-bc4f-e14fb51d02a3"]}],"mendeley":{"formattedCitation":"(6,9,13,22)","plainTextFormattedCitation":"(6,9,13,22)","previouslyFormattedCitation":"(6,9,13,22)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(6,9,13,22). Los anteriores antecedentes muestran la necesidad de generar nuevas alternativas terapéuticas, eficientes y específicas. Una alternativa ya evaluada en la literatura es la podofilotoxina, pero debido a sus niveles de citotoxicidad sobre tejidos sanos, no es usada en el tratamiento activo de lesiones carcinomatosas ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/chem.201602472","ISBN":"0365-6233","ISSN":"15213765","PMID":"27726183","abstract":"Abstract Podophyllotoxin and its related aryltetralin cyclolignans belong to a family of important products that exhibit various biological properties (e.g., cytotoxic, insecticidal, antifungal, antiviral, anti-inflammatory, neurotoxic, immunosuppressive, antirheumatic, antioxidative, antispasmogenic, and hypolipidemic activities). This Review provides a survey of podophyllotoxin and its analogues isolated from plants. In particular, recent developments in the elegant total chemical synthesis, structural modifications, biosynthesis, and biotransformation of podophyllotoxin and its analogues are summarized. Moreover, a deoxypodophyllotoxin-based chemosensor for selective detection of mercury ion is described. In addition to the most active podophyllotoxin derivatives in each series against human cancer cell lines and insect pests listed in the tables, the structure?activity relationships of podophyllotoxin derivatives as cytotoxic and insecticidal agents are also outlined. Future prospects and further developments in this area are covered at the end of the Review. We believe that this Review will provide necessary information for synthetic, medicinal, and pesticidal chemistry researchers who are interested in the chemistry and biology of podophyllotoxins.","author":[{"dropping-particle":"","family":"Yu","given":"Xiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Che","given":"Zhiping","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xu","given":"Hui","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Chemistry - A European Journal","id":"ITEM-1","issue":"19","issued":{"date-parts":[["2017"]]},"page":"4467-4526","title":"Recent Advances in the Chemistry and Biology of Podophyllotoxins","type":"article-journal","volume":"23"},"uris":["http://www.mendeley.com/documents/?uuid=d96d1784-db4a-42b1-8413-9c315786b3dc"]},{"id":"ITEM-2","itemData":{"DOI":"10.1177/095632029800900307","abstract":"Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4–6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC50 values of RD4–6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4–6277) and 5′-methoxy-podorhizol (RD4–6276), in which ring C is absent, did notinhibit HSV replication. Moreover, RD4–6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.","author":[{"dropping-particle":"","family":"Sudo","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Konno","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shigeta","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yokota","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Antiviral Chemestry & Chemotherapy","id":"ITEM-2","issued":{"date-parts":[["1998"]]},"page":"263-267","title":"Inhibitory effects of podophyllotoxin derivatives on","type":"article-journal","volume":"9"},"uris":["http://www.mendeley.com/documents/?uuid=406dcd0b-1a02-4351-a051-e081414e12d8"]}],"mendeley":{"formattedCitation":"(23,24)","plainTextFormattedCitation":"(23,24)","previouslyFormattedCitation":"(23,24)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(23,24), por lo que la Acetil Podofilotoxina, extraída de la Bursera fagoroides var fagaroides, se convierte en un importante blanco de investigación en el área de fármacos antitumorales ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/molecules24010008","ISSN":"1420-3049","abstract":"By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1–7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation.","author":[{"dropping-particle":"","family":"Antúnez-Mojica","given":"Mayra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gonzalez-Maya","given":"Leticia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rojas-Sepúlveda","given":"Andrés M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mendieta-Serrano","given":"Mario A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marquina","given":"Silvia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Salas-Vidal","given":"Enrique","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"Laura","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Molecules","id":"ITEM-1","issue":"8","issued":{"date-parts":[["2019"]]},"page":"1-13","title":"Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos","type":"article-journal","volume":"24"},"uris":["http://www.mendeley.com/documents/?uuid=5080f381-7015-407c-acc0-ecba01bd819a"]},{"id":"ITEM-2","itemData":{"DOI":"10.1021/acs.jnatprod.6b00428","ISSN":"0163-3864","abstract":"Four natural analogues of podophyllotoxin obtained from the Mexican medicinal plant Bursera fagaroides, namely, acetyl podophyllotoxin (2), 5′-desmethoxy-β-peltatin A methyl ether (3), 7′,8′-dehydro acetyl podophyllotoxin (4), and burseranin (5), have been characterized, and their interactions with tubulin have been investigated. Cytotoxic activity measurements, followed by immunofluorescence microscopy and flow cytometry studies, demonstrated that these compounds disrupt microtubule networks in cells and cause cell cycle arrest in the G2/M phase in the A549 cell line. A tubulin binding assay showed that compounds 1−4 were potent assembly inhibitors, displaying binding to the colchicine site with Kb values ranging from 11.75 to 185.0 × 105 M−1. In contrast, burseranin (5) was not able to inhibit tubulin assembly. From the structural perspective, the ligand-binding epitopes of compounds 1−3 have been mapped using STD-NMR, showing that B and E rings are the major points for interaction with the protein. The obtained results indicate that the inhibition of tubulin assembly of this family of compounds is more effective when there are at least two methoxyl groups at the E ring, along with a trans configuration of the lactone ring in the aryltetralin lignan core. T","author":[{"dropping-particle":"","family":"Antúnez-Mojica","given":"Mayra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rodríguez-Salarichs","given":"Javier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Redondo-Horcajo","given":"Mariano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"León","given":"Alejandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barasoain","given":"Isabel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Canales","given":"Angeles","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cañada","given":"F. J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jiménez-Barbero","given":"Jesús","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez","given":"Laura","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Díaz","given":"J. Fernando","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Natural Products","id":"ITEM-2","issue":"8","issued":{"date-parts":[["2016"]]},"page":"2113-2121","title":"Structural and Biochemical Characterization of the Interaction of Tubulin with Potent Natural Analogues of Podophyllotoxin","type":"article-journal","volume":"79"},"uris":["http://www.mendeley.com/documents/?uuid=fced0008-4b56-4f56-a506-4946cdb9db48"]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/j.biopha.2014.12.038","ISSN":"19506007","abstract":"To develop a new radiosensitizer against non-small cell lung cancer cells, we screened a natural product library for growth-inhibitory compounds. PA was found to be cytotoxic toward NCI-H460 cells, and its IC50 value was determined. The radiosensitizer effects of PA were tested at its IC50 value in clonogenic and cell-counting assays. The intracellular mechanism underlying this effect was determined by immunoblotting and by measuring propidium iodide uptake and ROS generation. The radiosensitizer activity of PA in vivo was tested in nude mice by treating with PA and IR, and measuring tumor volume and assessing apoptosis. PA, tested at its experimentally determined IC50 value (12nM), enhanced IR-induced death of NCI-H460 cells by increasing apoptosis, yielding a mean calculated dose-enhancement ratio of 1.67. Combination with PA and IR also increased the production of ROS, which subsequently induced phosphorylation of p38, suppressed phosphorylation of ERK, and activated caspase-3, -8, and -9. Notably, inhibition of ROS production prevented p38 phosphorylation, and inhibition of ROS production or p38 activation blocked caspase activation and apoptosis. In a xenograft assay, combination with PA and IR delayed tumor growth by 11.4days compared with controls, yielding an enhancement factor of 1.48. Collectively, these results indicate that PA functions as a radiosensitizer by enhancing apoptosis through activation of a ROS/p38/caspase pathway and suppression of ERK.","author":[{"dropping-particle":"","family":"Choi","given":"Jae Yeon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"Hyun Ji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hwang","given":"Sang Gu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Wun Jae","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"Il","family":"Kim","given":"Jong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Um","given":"Hong Duck","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Jong Kuk","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedicine and Pharmacotherapy","id":"ITEM-3","issued":{"date-parts":[["2015"]]},"page":"111-118","publisher":"Elsevier Masson SAS","title":"Podophyllotoxin acetate enhances γ-ionizing radiation-induced apoptotic cell death by stimulating the ROS/p38/caspase pathway","type":"article-journal","volume":"70"},"uris":["http://www.mendeley.com/documents/?uuid=2d1f49c9-d2d3-4d11-bcda-4fb3a62f09b5"]}],"mendeley":{"formattedCitation":"(17,18,25)","plainTextFormattedCitation":"(17,18,25)","previouslyFormattedCitation":"(17,18,25)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(17,18,25). Por lo anterior, es necesario profundizar en el estudio de los efectos biológicos de la Acetil Podofilotoxina en tejidos normales y tumorales asociados a la infección por VPH y de esta manera generar focos de estudio en el ámbito fito-farmacológico que conlleven a la generación de futuras estrategias terapéuticas que impacten en un mejor pronóstico en la salud del paciente oncológico.
StatusFinished
Effective start/end date01/10/2130/04/24

Project Status

  • Not defined

Project funding

  • Internal
  • Pontificia Universidad Javeriana

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