Arturo Valle-Mendiola | UNAM Universidad Nacional Autónoma de México (original) (raw)
Papers by Arturo Valle-Mendiola
International journal of molecular sciences, Jun 21, 2024
Genes
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway ... more The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway constitutes a rapid signaling module from the cell surface to the nucleus, and activates different cellular responses, such as proliferation, survival, migration, invasion, and inflammation. When the JAK/STAT pathway is altered, it contributes to cancer progression and metastasis. STAT proteins play a central role in developing cervical cancer, and inhibiting the JAK/STAT signaling may be necessary to induce tumor cell death. Several cancers show continuous activation of different STATs, including cervical cancer. The constitutive activation of STAT proteins is associated with a poor prognosis and overall survival. The human papillomavirus (HPV) oncoproteins E6 and E7 play an essential role in cervical cancer progression, and they activate the JAK/STAT pathway and other signals that induce proliferation, survival, and migration of cancer cells. Moreover, there is a crosstalk between the ...
BioDrugs, 2010
The high-risk types of human papillomavirus (HPV) have been found to be associated with most cerv... more The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, the E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines, since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus
This cross-sectional study was conducted to screen the presence of antibiotic residue in poultry.... more This cross-sectional study was conducted to screen the presence of antibiotic residue in poultry. A total of 60 samples (30 Muscle and 30 Liver) were taken from local meat shops from different parts of Kathmandu valley. Disc assay method was used. Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) were used as test organisms. The results revealed 8 positive samples (which is 13%). Among 30 Liver samples, 3 showed positive result, while only 2 muscle sample indicated positive result. Muscle has the highest percentage of positive results than liver. For S. aureus showed greater percentage of positive results than that of E. coli. The presence of antibiotic residue and its many pathological effects to public health demands the strict rules and regulations as well as surveillance from the concerned authorities.
Vertientes, 2003
El proceso por el cual las celulas normales se transforman en celulas malignas, requiere la adqui... more El proceso por el cual las celulas normales se transforman en celulas malignas, requiere la adquisicion secuencial de mutaciones,las cuales acarrean como consecuencia el dano al genoma. Este dano puede ser el resultado de un proceso endogeno, por ejemplopor errores en la replicacion de DNA, la inestabilidad inherente de ciertas bases o por el ataque de radicales libres, o por ataqueexogeno, como las radiaciones ionizantes o exposicion a agentes cancerigenos quimicos. Las celulas tienen mecanismos dereparacion, pero pueden ocurrir errores introduciendo mutaciones permanentes.Algunas mutaciones por inactivacion ocurren en genes importantes para el mantenimiento de la integridad genomica, facilitandola adquisicion de mutaciones adicionales que finalmente daran como resultado el proceso de transformacion maligna.
Cancers, 2020
A central characteristic of many types of cancer is altered energy metabolism processes such as e... more A central characteristic of many types of cancer is altered energy metabolism processes such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is an elaborate process involving regulatory proteins such as HIF (pro-metastatic protein), which reduces oxidative metabolism, and some other proteins such as tumour suppressors that promote oxidative phosphorylation. In recent years, it has been demonstrated that signal transducer and activator of transcription (STAT) proteins play a pivotal role in metabolism regulation. STAT3 and STAT5 are essential regulators of cytokine- or growth factor-induced cell survival and proliferation, as well as the crosstalk between STAT signalling and oxidative metabolism. Several reports suggest that the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of hypoxia-inducible factors and therefore, the alteration of mitochondrial activity. It seem...
Archives of Pharmacy and Pharmaceutical Sciences, 2018
Human cervical cancer tumours expressing the IL-2 receptor (IL-2R) were induced in the peritoneal... more Human cervical cancer tumours expressing the IL-2 receptor (IL-2R) were induced in the peritoneal cavity of nude mice. The tumours were signifi cantly reduced by the i.p. administration of either free IL-2 or liposomes containing this growth factor. No toxicity was observed in the mice even at the highest doses of IL-2 in liposomes. We did not detect any IL-2 in the blood plasma pointing to a strong retention of the liposomes on the cavity. We concluded that this preclinical study for the treatment of tumours expressing IL-2R in the peritoneal cavity is effective and safe. The liposomes were stable and their IL-2 active for up to one year when kept at-14 o C in a cryopreservation media approved by the FDA for human use.
Journal of Immunology Research, 2019
Cervical cancer is the second most frequent cancer in women in Mexico, and its development depend... more Cervical cancer is the second most frequent cancer in women in Mexico, and its development depends on the presence of human papillomaviruses in the uterine cervix. These oncogenic viruses transform cells where the control over cell cycle disappears, and the capacity to induce apoptosis is absent. On the other hand, some mutations confer to the transformed cells the ability to evade recognition by the immune system. The expression of markers of the immune system such as CD95, MICA/B, CD39, CD73, NKp30, NKp46, CD44, CD24, NKG2A, and CTLA-4 was analysed by flow cytometry on cervical cancer cells INBL (HPV 18, stage IVB), HeLa (HPV 18), CaSki (HPV 16), and C33A (HPV-). Our results showed the presence of atypical markers on cervical cancer cells; some of them are molecules involved in tumour cell recognition such as MICA/B and CD95. Other markers associated with immune system escape, such as CD39, CD73, and CTLA-4, were also present. Furthermore, we found that some cervical cancer cells ...
One of the most important characteristics of many types of cancer is the presence of an abnormal ... more One of the most important characteristics of many types of cancer is the presence of an abnormal metabolism such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is complex, some regulatory proteins, like HIF (pro-metastatic protein), decrease oxidative metabolism, whereas other proteins, like p53 (tumor suppressor), promote oxidative phosphorylation. These data indicate that one of the possible primary roles of activated oncogenes and inactivated tumor suppressors is the reprogramming of cell metabolism.
Biomarkers and Applications
To evaluate if CD16adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeate... more To evaluate if CD16adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeated them and measured its presence by flow cytometry. To determine if they can be induced to express CD16 on their cell membranes they were cultured with the receptor inducer LIPO-PI. We obtained that the great majority of the CD16cells had CD16 inter and that they became CD16 + after a short incubation with LIPO-PI. Our results thus hint that there might not exist different subgroups of CD16and CD16 + monocytes but leukocytes in different stages of activation. To evaluate if cervical cancer cells contain CD16 inter the cervical cell line INBL was permeated and CD16 presence determined by flow cytometry. We obtained that INBL cells had CD16 inter and in a similar way as with leukocytes they expressed CD16 in their membranes when cultured for short times with LIPO-PI. Taking into consideration that endocervical columnar epithelial cells express CD16 and not the exocervical ones our results hint to the endocervical origin of INBL. We propose CD16 inter as a new phenotype marker .
El ciclo celular es un proceso en el cual una celula crece y se divide para crear una copia de si... more El ciclo celular es un proceso en el cual una celula crece y se divide para crear una copia de si misma, permitiendo crecer y reemplazar las celulas a medida que se desgastan. En los animales, el ciclo de una celula normal toma alrededor de 24 horas de principio a fin para los diferentes tipos de celulas, aunque algunas, como las de la piel o las tumorales, estan constantemente pasando por este ciclo, mientras que otras pueden dividirse rara vez, o no hacerlo. La secuencia de eventos que se producen cuando se estimula una celula para crecer y dividirse constituye el ciclo celular. Inicia con celulas en reposo (fase G0), las cuales tienen que ser estimuladas por factores de crecimiento con el fin de entrar en el ciclo celular, lo que comienza con el primer periodo de crecimiento (fase G1) en el que se prepara para un periodo de sintesis de ADN (fase S). Hacia el final de G1, hay un punto de restriccion (R), en que se repara el ADN en caso de estar danado. De no ser asi, sigue adelant...
El receptor para el factor de crecimiento epidermico (EGFR) y los otros miembros de la familia Er... more El receptor para el factor de crecimiento epidermico (EGFR) y los otros miembros de la familia ErbB son receptores con actividadde cinasa de tirosina que juegan papeles esenciales tanto en condiciones fisiologicas normales como en condicionescancerosas. Al unirse a sus ligandos, se llevan a cabo cambios conformacionales tanto en los dominios extracelulares comointracelulares de las cinasas de tirosina, dando como resultado la transfosforilacion de residuos de tirosina en el dominio Cterminalregulador. Estas tirosinas se convierten en sitios de union para moleculas senalizadoras y pueden inducir una evasionde la apoptosis, proliferacion, hasta invasion y metastasis, procesos que son muy importantes para el fenotipo del cancer.Se han encontrado varias mutaciones en el gen EGFR, particularmente en el dominio de cinasa en diferentes tipos de cancer.El significado biologico de esas mutaciones y su relacion con otros genes activados en el cancer se discuten en este trabajo. EGFR, familia ...
Epigenetics is described as the changes that do not alter the DNA sequence but affect gene expres... more Epigenetics is described as the changes that do not alter the DNA sequence but affect gene expression. Many types of modifications do exist especially in the N-terminal domain of the histones that give structure to nucleosomes; these changes have direct implications in the expression or repression of genes, with different consequences at the cellular level. One such modification is the addition of an acetyl group on lysine residues (acetylation) which has been implicated in various processes such as wound healing, in diseases of the central nervous system and cancer. The development of drugs capable of controlling the generated epigenetic changes in various diseases is currently a broad field of study and where promising results have been found.
La via de transduccion de senales a traves de las Janus-cinasas-transductores de la senal y activ... more La via de transduccion de senales a traves de las Janus-cinasas-transductores de la senal y activadores de la transcripcion(Jak-STAT) es esencial para la senalizacion de muchas citocinas. Esta via transmite informacion que se recibe de senalespolipeptidicas extracelulares, a traves de receptores transmembranales, directamente a promotores blanco en el nucleo,generando en consecuencia un mecanismo para regular la transcripcion sin necesidad de segundos mensajeros. Unaalteracion en la regulacion de la via de senalizacion Jak-STAT esta asociada con varias enfermedades humanas. Estudiosrecientes han ayudado a entender los mecanismos reguladores que modifican la cantidad y calidad de la respuesta a estavia de senales. En esta revision se da una vision general de esta via, de la estructura de las JAKs y STATs, asi como de algunosfarmacos inhibidores de la via.
Biochemical Society Transactions, 2000
Journal of Oncology
Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express th... more Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express the IL-2 receptor (IL-2R). However, the effect of IL-2 on cervical cancer cells is unknown. IL-2R is present in normal cells of the immune system but not in the healthy cervix. We report that IL-2R is expressed in cervical cancer cells. IL-2 decreases cervical cancer cell proliferation via transient arrest of the G1 phase, which does not result in apoptosis or senescence. IL-2 upregulates the expression of p53 and p21 and downregulates cyclin D. In addition, we report the resistance of cervical cancer cells to treatments that induce apoptosis in HeLa and INBL cells. When arrested cells were treated with cisplatin, the cytokine protected cells from apoptosis induced by cisplatin. The effects of IL-2 on the cell cycle do not induce cellular senescence or activate the proapoptotic protein Bax. The cell arrest induced by IL-2 is conferring protection to cells against apoptosis.
Cellular signalling, 2004
Activation of the interleukin-2 receptor (IL-2R) induces signalling cascades promoting T cell pro... more Activation of the interleukin-2 receptor (IL-2R) induces signalling cascades promoting T cell proliferation. However, signal transduction pathways triggered in IL-2R-expressing solid tumours are unknown. This report shows that human papillomavirus (HPV)-associated cervical ...
Cancer Investigation, 2008
The HER family receptors have an important role controlling cell growth and differentiation. Alth... more The HER family receptors have an important role controlling cell growth and differentiation. Although the activity of the HER-2 receptor is strictly controlled in normal cells, its overexpression plays a pivotal role in transformation and tumorigenesis. Constitutive phosphorylation of HER-2 protein has been implicated in conferring uncontrolled growth to mammary cancer cells, and to a lesser extent, with adenocarcinoma of uterus, cervix, fallopian tube, and endometrium. This study addresses the role of HER-2 in cervical carcinoma. Firstly, we demonstrate the presence of HER-2 protein expression by flow cytometry in two new cervical carcinoma cell lines CALO and INBL. Secondly, we use the specific tyrosine kinase inhibitors, Tyrphostins to examine HER-2 regulation by the crystal violet assay. Thirdly, we use western blot analysis to assess the state of HER-2 phosphorylation. The most efficient agent, Tyrphostin B42, known as an inhibitor of epithelial growth factor receptor, arrested cervical carcinoma cell lines growth in vitro at micromolar concentrations within 72 h of application. Tyrphostin B42 inhibited the HER2 signal-regulated kinase pathway, as observed by the reduction in the phosphorylated forms of HER2. The loss of phosphorylated forms of HER2 at early time points after Tyrphostin B42 application was associated with suppression of cell growth. Thus, the inhibition of the proliferation of our cervical carcinoma cell lines by Tyrphostin B42 is associated with inhibition of HER2 protein kinase signal.
To evaluate if CD16-adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeat... more To evaluate if CD16-adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeated them and measured its presence by flow cytometry. To determine if they can be induced to express CD16 on their cell membranes they were cultured with the receptor inducer LIPO-PI. We obtained that the great majority of the CD16-cells had CD16 inter and that they became CD16 + after a short incubation with LIPO-PI. Our results thus hint that there might not exist different subgroups of CD16-and CD16 + monocytes but leukocytes in different stages of activation. To evaluate if cervical cancer cells contain CD16 inter the cervical cell line INBL was permeated and CD16 presence determined by flow cytometry. We obtained that INBL cells had CD16 inter and in a similar way as with leukocytes they expressed CD16 in their membranes when cultured for short times with LIPO-PI. Taking into consideration that endocervical columnar epithelial cells express CD16 and not the exocervical ones our results hint to the endocervical origin of INBL. We propose CD16 inter as a new phenotype marker .
International journal of molecular sciences, Jun 21, 2024
Genes
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway ... more The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway constitutes a rapid signaling module from the cell surface to the nucleus, and activates different cellular responses, such as proliferation, survival, migration, invasion, and inflammation. When the JAK/STAT pathway is altered, it contributes to cancer progression and metastasis. STAT proteins play a central role in developing cervical cancer, and inhibiting the JAK/STAT signaling may be necessary to induce tumor cell death. Several cancers show continuous activation of different STATs, including cervical cancer. The constitutive activation of STAT proteins is associated with a poor prognosis and overall survival. The human papillomavirus (HPV) oncoproteins E6 and E7 play an essential role in cervical cancer progression, and they activate the JAK/STAT pathway and other signals that induce proliferation, survival, and migration of cancer cells. Moreover, there is a crosstalk between the ...
BioDrugs, 2010
The high-risk types of human papillomavirus (HPV) have been found to be associated with most cerv... more The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, the E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines, since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus
This cross-sectional study was conducted to screen the presence of antibiotic residue in poultry.... more This cross-sectional study was conducted to screen the presence of antibiotic residue in poultry. A total of 60 samples (30 Muscle and 30 Liver) were taken from local meat shops from different parts of Kathmandu valley. Disc assay method was used. Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) were used as test organisms. The results revealed 8 positive samples (which is 13%). Among 30 Liver samples, 3 showed positive result, while only 2 muscle sample indicated positive result. Muscle has the highest percentage of positive results than liver. For S. aureus showed greater percentage of positive results than that of E. coli. The presence of antibiotic residue and its many pathological effects to public health demands the strict rules and regulations as well as surveillance from the concerned authorities.
Vertientes, 2003
El proceso por el cual las celulas normales se transforman en celulas malignas, requiere la adqui... more El proceso por el cual las celulas normales se transforman en celulas malignas, requiere la adquisicion secuencial de mutaciones,las cuales acarrean como consecuencia el dano al genoma. Este dano puede ser el resultado de un proceso endogeno, por ejemplopor errores en la replicacion de DNA, la inestabilidad inherente de ciertas bases o por el ataque de radicales libres, o por ataqueexogeno, como las radiaciones ionizantes o exposicion a agentes cancerigenos quimicos. Las celulas tienen mecanismos dereparacion, pero pueden ocurrir errores introduciendo mutaciones permanentes.Algunas mutaciones por inactivacion ocurren en genes importantes para el mantenimiento de la integridad genomica, facilitandola adquisicion de mutaciones adicionales que finalmente daran como resultado el proceso de transformacion maligna.
Cancers, 2020
A central characteristic of many types of cancer is altered energy metabolism processes such as e... more A central characteristic of many types of cancer is altered energy metabolism processes such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is an elaborate process involving regulatory proteins such as HIF (pro-metastatic protein), which reduces oxidative metabolism, and some other proteins such as tumour suppressors that promote oxidative phosphorylation. In recent years, it has been demonstrated that signal transducer and activator of transcription (STAT) proteins play a pivotal role in metabolism regulation. STAT3 and STAT5 are essential regulators of cytokine- or growth factor-induced cell survival and proliferation, as well as the crosstalk between STAT signalling and oxidative metabolism. Several reports suggest that the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of hypoxia-inducible factors and therefore, the alteration of mitochondrial activity. It seem...
Archives of Pharmacy and Pharmaceutical Sciences, 2018
Human cervical cancer tumours expressing the IL-2 receptor (IL-2R) were induced in the peritoneal... more Human cervical cancer tumours expressing the IL-2 receptor (IL-2R) were induced in the peritoneal cavity of nude mice. The tumours were signifi cantly reduced by the i.p. administration of either free IL-2 or liposomes containing this growth factor. No toxicity was observed in the mice even at the highest doses of IL-2 in liposomes. We did not detect any IL-2 in the blood plasma pointing to a strong retention of the liposomes on the cavity. We concluded that this preclinical study for the treatment of tumours expressing IL-2R in the peritoneal cavity is effective and safe. The liposomes were stable and their IL-2 active for up to one year when kept at-14 o C in a cryopreservation media approved by the FDA for human use.
Journal of Immunology Research, 2019
Cervical cancer is the second most frequent cancer in women in Mexico, and its development depend... more Cervical cancer is the second most frequent cancer in women in Mexico, and its development depends on the presence of human papillomaviruses in the uterine cervix. These oncogenic viruses transform cells where the control over cell cycle disappears, and the capacity to induce apoptosis is absent. On the other hand, some mutations confer to the transformed cells the ability to evade recognition by the immune system. The expression of markers of the immune system such as CD95, MICA/B, CD39, CD73, NKp30, NKp46, CD44, CD24, NKG2A, and CTLA-4 was analysed by flow cytometry on cervical cancer cells INBL (HPV 18, stage IVB), HeLa (HPV 18), CaSki (HPV 16), and C33A (HPV-). Our results showed the presence of atypical markers on cervical cancer cells; some of them are molecules involved in tumour cell recognition such as MICA/B and CD95. Other markers associated with immune system escape, such as CD39, CD73, and CTLA-4, were also present. Furthermore, we found that some cervical cancer cells ...
One of the most important characteristics of many types of cancer is the presence of an abnormal ... more One of the most important characteristics of many types of cancer is the presence of an abnormal metabolism such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is complex, some regulatory proteins, like HIF (pro-metastatic protein), decrease oxidative metabolism, whereas other proteins, like p53 (tumor suppressor), promote oxidative phosphorylation. These data indicate that one of the possible primary roles of activated oncogenes and inactivated tumor suppressors is the reprogramming of cell metabolism.
Biomarkers and Applications
To evaluate if CD16adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeate... more To evaluate if CD16adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeated them and measured its presence by flow cytometry. To determine if they can be induced to express CD16 on their cell membranes they were cultured with the receptor inducer LIPO-PI. We obtained that the great majority of the CD16cells had CD16 inter and that they became CD16 + after a short incubation with LIPO-PI. Our results thus hint that there might not exist different subgroups of CD16and CD16 + monocytes but leukocytes in different stages of activation. To evaluate if cervical cancer cells contain CD16 inter the cervical cell line INBL was permeated and CD16 presence determined by flow cytometry. We obtained that INBL cells had CD16 inter and in a similar way as with leukocytes they expressed CD16 in their membranes when cultured for short times with LIPO-PI. Taking into consideration that endocervical columnar epithelial cells express CD16 and not the exocervical ones our results hint to the endocervical origin of INBL. We propose CD16 inter as a new phenotype marker .
El ciclo celular es un proceso en el cual una celula crece y se divide para crear una copia de si... more El ciclo celular es un proceso en el cual una celula crece y se divide para crear una copia de si misma, permitiendo crecer y reemplazar las celulas a medida que se desgastan. En los animales, el ciclo de una celula normal toma alrededor de 24 horas de principio a fin para los diferentes tipos de celulas, aunque algunas, como las de la piel o las tumorales, estan constantemente pasando por este ciclo, mientras que otras pueden dividirse rara vez, o no hacerlo. La secuencia de eventos que se producen cuando se estimula una celula para crecer y dividirse constituye el ciclo celular. Inicia con celulas en reposo (fase G0), las cuales tienen que ser estimuladas por factores de crecimiento con el fin de entrar en el ciclo celular, lo que comienza con el primer periodo de crecimiento (fase G1) en el que se prepara para un periodo de sintesis de ADN (fase S). Hacia el final de G1, hay un punto de restriccion (R), en que se repara el ADN en caso de estar danado. De no ser asi, sigue adelant...
El receptor para el factor de crecimiento epidermico (EGFR) y los otros miembros de la familia Er... more El receptor para el factor de crecimiento epidermico (EGFR) y los otros miembros de la familia ErbB son receptores con actividadde cinasa de tirosina que juegan papeles esenciales tanto en condiciones fisiologicas normales como en condicionescancerosas. Al unirse a sus ligandos, se llevan a cabo cambios conformacionales tanto en los dominios extracelulares comointracelulares de las cinasas de tirosina, dando como resultado la transfosforilacion de residuos de tirosina en el dominio Cterminalregulador. Estas tirosinas se convierten en sitios de union para moleculas senalizadoras y pueden inducir una evasionde la apoptosis, proliferacion, hasta invasion y metastasis, procesos que son muy importantes para el fenotipo del cancer.Se han encontrado varias mutaciones en el gen EGFR, particularmente en el dominio de cinasa en diferentes tipos de cancer.El significado biologico de esas mutaciones y su relacion con otros genes activados en el cancer se discuten en este trabajo. EGFR, familia ...
Epigenetics is described as the changes that do not alter the DNA sequence but affect gene expres... more Epigenetics is described as the changes that do not alter the DNA sequence but affect gene expression. Many types of modifications do exist especially in the N-terminal domain of the histones that give structure to nucleosomes; these changes have direct implications in the expression or repression of genes, with different consequences at the cellular level. One such modification is the addition of an acetyl group on lysine residues (acetylation) which has been implicated in various processes such as wound healing, in diseases of the central nervous system and cancer. The development of drugs capable of controlling the generated epigenetic changes in various diseases is currently a broad field of study and where promising results have been found.
La via de transduccion de senales a traves de las Janus-cinasas-transductores de la senal y activ... more La via de transduccion de senales a traves de las Janus-cinasas-transductores de la senal y activadores de la transcripcion(Jak-STAT) es esencial para la senalizacion de muchas citocinas. Esta via transmite informacion que se recibe de senalespolipeptidicas extracelulares, a traves de receptores transmembranales, directamente a promotores blanco en el nucleo,generando en consecuencia un mecanismo para regular la transcripcion sin necesidad de segundos mensajeros. Unaalteracion en la regulacion de la via de senalizacion Jak-STAT esta asociada con varias enfermedades humanas. Estudiosrecientes han ayudado a entender los mecanismos reguladores que modifican la cantidad y calidad de la respuesta a estavia de senales. En esta revision se da una vision general de esta via, de la estructura de las JAKs y STATs, asi como de algunosfarmacos inhibidores de la via.
Biochemical Society Transactions, 2000
Journal of Oncology
Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express th... more Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express the IL-2 receptor (IL-2R). However, the effect of IL-2 on cervical cancer cells is unknown. IL-2R is present in normal cells of the immune system but not in the healthy cervix. We report that IL-2R is expressed in cervical cancer cells. IL-2 decreases cervical cancer cell proliferation via transient arrest of the G1 phase, which does not result in apoptosis or senescence. IL-2 upregulates the expression of p53 and p21 and downregulates cyclin D. In addition, we report the resistance of cervical cancer cells to treatments that induce apoptosis in HeLa and INBL cells. When arrested cells were treated with cisplatin, the cytokine protected cells from apoptosis induced by cisplatin. The effects of IL-2 on the cell cycle do not induce cellular senescence or activate the proapoptotic protein Bax. The cell arrest induced by IL-2 is conferring protection to cells against apoptosis.
Cellular signalling, 2004
Activation of the interleukin-2 receptor (IL-2R) induces signalling cascades promoting T cell pro... more Activation of the interleukin-2 receptor (IL-2R) induces signalling cascades promoting T cell proliferation. However, signal transduction pathways triggered in IL-2R-expressing solid tumours are unknown. This report shows that human papillomavirus (HPV)-associated cervical ...
Cancer Investigation, 2008
The HER family receptors have an important role controlling cell growth and differentiation. Alth... more The HER family receptors have an important role controlling cell growth and differentiation. Although the activity of the HER-2 receptor is strictly controlled in normal cells, its overexpression plays a pivotal role in transformation and tumorigenesis. Constitutive phosphorylation of HER-2 protein has been implicated in conferring uncontrolled growth to mammary cancer cells, and to a lesser extent, with adenocarcinoma of uterus, cervix, fallopian tube, and endometrium. This study addresses the role of HER-2 in cervical carcinoma. Firstly, we demonstrate the presence of HER-2 protein expression by flow cytometry in two new cervical carcinoma cell lines CALO and INBL. Secondly, we use the specific tyrosine kinase inhibitors, Tyrphostins to examine HER-2 regulation by the crystal violet assay. Thirdly, we use western blot analysis to assess the state of HER-2 phosphorylation. The most efficient agent, Tyrphostin B42, known as an inhibitor of epithelial growth factor receptor, arrested cervical carcinoma cell lines growth in vitro at micromolar concentrations within 72 h of application. Tyrphostin B42 inhibited the HER2 signal-regulated kinase pathway, as observed by the reduction in the phosphorylated forms of HER2. The loss of phosphorylated forms of HER2 at early time points after Tyrphostin B42 application was associated with suppression of cell growth. Thus, the inhibition of the proliferation of our cervical carcinoma cell lines by Tyrphostin B42 is associated with inhibition of HER2 protein kinase signal.
To evaluate if CD16-adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeat... more To evaluate if CD16-adherent blood leukocytes contain CD16 intracellulary (CD16 inter) we permeated them and measured its presence by flow cytometry. To determine if they can be induced to express CD16 on their cell membranes they were cultured with the receptor inducer LIPO-PI. We obtained that the great majority of the CD16-cells had CD16 inter and that they became CD16 + after a short incubation with LIPO-PI. Our results thus hint that there might not exist different subgroups of CD16-and CD16 + monocytes but leukocytes in different stages of activation. To evaluate if cervical cancer cells contain CD16 inter the cervical cell line INBL was permeated and CD16 presence determined by flow cytometry. We obtained that INBL cells had CD16 inter and in a similar way as with leukocytes they expressed CD16 in their membranes when cultured for short times with LIPO-PI. Taking into consideration that endocervical columnar epithelial cells express CD16 and not the exocervical ones our results hint to the endocervical origin of INBL. We propose CD16 inter as a new phenotype marker .