Transición epitelio-mesenquimática (TEM): Principios e impacto clínico en la terapia contra el cáncer

The epithelial-mesenchymal transition (EMT) is a biological phenomenon responsible for the formation of different tissues and organs during normal metazoan development. Because of the connection of the EMT with the pathogenesis of certain diseases, such as cancer, the attention of the scientific community has been directed towards the search for and identification of effective therapeutic targets. These targets include signal transduction in cancerous stem cells and the use of microRNAs, which would inhibit EMT-associated phenotypic changes and tumoral progression. In an attempt to compile relevant and current information, this work addresses concepts that define the EMT and the advances in this field. The wealth of knowledge gained from areas such as the loss of cell polarity and intracellular adhesion complexes, the signaling pathways implicated, microRNA participation in this process, and stemness acquisition in embryonic and cancerous cells, all of which allow for the visualization of promising perspectives, particularly, methods for targeting advanced malignancies, are presented herein

Transición epitelio-mesenquimática (TEM): Principios e impacto clínico en la terapia contra el cáncer

The epithelial-mesenchymal transition (EMT) is a biological phenomenon responsible for the formation of different tissues and organs during normal metazoan development. Because of the connection of the EMT with the pathogenesis of certain diseases, such as cancer, the attention of the scientific community has been directed towards the search for and identification of effective therapeutic targets. These targets include signal transduction in cancerous stem cells and the use of microRNAs, which would inhibit EMT-associated phenotypic changes and tumoral progression. In an attempt to compile relevant and current information, this work addresses concepts that define the EMT and the advances in this field. The wealth of knowledge gained from areas such as the loss of cell polarity and intracellular adhesion complexes, the signaling pathways implicated, microRNA participation in this process, and stemness acquisition in embryonic and cancerous cells, all of which allow for the visualization of promising perspectives, particularly, methods for targeting advanced malignancies, are presented herein

Pigment epithelium-derived factor: Clinical significance in estrogen-dependent tissues and its potential in cancer therapy

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of noninhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and antimetastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF. © 2015, Mashhad University of Medical Sciences. All rights reserved

Pigment epithelium-derived factor: Clinical significance in estrogen-dependent tissues and its potential in cancer therapy

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of noninhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and antimetastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF. © 2015, Mashhad University of Medical Sciences. All rights reserved

p53 y su papel en el epitelio superficial del ovario. Revisión

The ovarian surface epithelium (OSE) is a single layer of cells subject to a high rate of turnover at he site of follicular rupture at ovulation and this results in a higher risk of malignant cell transformation. Findings like cancer derived from OSE, that accounts for approximately 90% of all human ovarian malignancies and the frequent mutations of the p53 gen in most of them, are the basis for reviewing OSE structure and histogenesis related to p53, as well as some aspects associated with p53 stabilization and regulation, its involvement in key events like cell cycle arrest, induction of apoptosis, etiology and pathogenesis of epithelial ovarian cancer. Finally, this review takes into account recent farmacogenetics advances in order to use p53 as a target. in the therapy against cancer

p53 y su papel en el epitelio superficial del ovario. Revisión

The ovarian surface epithelium (OSE) is a single layer of cells subject to a high rate of turnover at he site of follicular rupture at ovulation and this results in a higher risk of malignant cell transformation. Findings like cancer derived from OSE, that accounts for approximately 90% of all human ovarian malignancies and the frequent mutations of the p53 gen in most of them, are the basis for reviewing OSE structure and histogenesis related to p53, as well as some aspects associated with p53 stabilization and regulation, its involvement in key events like cell cycle arrest, induction of apoptosis, etiology and pathogenesis of epithelial ovarian cancer. Finally, this review takes into account recent farmacogenetics advances in order to use p53 as a target. in the therapy against cancer

Actividad de la ?-galactosidasa como marcador de senescencia en cultivos primarios del epitelio superficial del ovario

La actividad de la -galactosidasa refleja la tasa de envejecimiento celular in vitro. Mediante quimioluminiscencia se cuantificó dicha actividad a pH 6 en células epiteliales ováricas provenientes de 28 donantes sin antecedentes de cáncer. Las células fueron cultivadas en forma seriada hasta alcanzar el estado de detención permanente de crecimiento. Durante la fase de crecimiento exponencial, todos los cultivos mostraron un patrón semejante de crecimiento y una baja actividad -galactosidasa. Sin embargo, el inicio de la disminución de la capacidad replicativa que caracteriza el final de dicha fase, así como el inicio de la fase estacionaria o senescente presentaron un aumento significativo en la actividad enzimática. Nuestros resultados mostraron que la actividad -galactosidasa puede ser considerada como marcador de senescencia replicativa del epitelio superficial del ovario a pH 6.?-galactosidase activity reflects the rate of cellular aging in vitro. Such activity was quantified at pH 6 in ovarian epithelial cells from 28 donors without a history of cancer, by the chemoluminiscent method. The cells were serially cultured until they achieved the state of permanent growth arrest. During the exponential growth phase, all cultures showed a similar pattern of growth and low ?-galactosidase activity. However, both in the onset of decrease replicative activity, as well as in the onset of the stationary phase, there was a significant rise in the enzyme activity. Our results showed that ?-galactosidase activity can be considered as a replicative senescence marker of the ovarian surface epithelium at pH 6

Aberraciones citogenéticas en cultivos primarios del epitelio superficial del ovario

Our objective was to determine the presence of chromosomal abnormalities in primary cultures of ovarian surface epithelial cells in women of different ages with no history of cancer. Throughout conventional cytogenetic techniques, we analyzed chromosome spreads of cultured ovarian epithelial cells from 10 donors who were 50 or more years old (B) and 16 controls between 20 and 49 years old (A), belonging to the mestizo population in Bogota DC, Colombia. Of the 26 cultures that were analyzed in passage 1, 61.5% had an abnormal chromosome complement (62.5% in A, and 60% in B). Abnormalities included polyploidies, endoduplications and monosomies. Deletions in chromosomes 3 and 11 were found in just one metaphase. None of the samples showed weaknesses or breakpoints. After transforming and applying the exact student's t-test for variance heterogeneity, we found significant differences in the frequency of metaphases, that were higher in A than in B (p=0.05), and in the frequency of polyploidies, which were higher in B than in A (p=0.044). Through the application of the Mann-Whitney test, we determined that the frequency of endoduplications was higher in A than in B (p=0.126), without reaching significant differences. There were no significant differences in the frequency of monosomies. The level of significance was set at p ? 0.05. Taking into account that polyploidization is a marker of chromosomal instability and that the risk of cancer arising from the ovarian surface epithelium augments substantially after menopause, the increase in the frequency of age-associated polyploidies could be used as a predictor of ovarian cancer in women from an ethnically homogeneous population as the mestizo one in Bogota DC

Actividad de la ?-galactosidasa como marcador de senescencia en cultivos primarios del epitelio superficial del ovario

La actividad de la -galactosidasa refleja la tasa de envejecimiento celular in vitro. Mediante quimioluminiscencia se cuantificó dicha actividad a pH 6 en células epiteliales ováricas provenientes de 28 donantes sin antecedentes de cáncer. Las células fueron cultivadas en forma seriada hasta alcanzar el estado de detención permanente de crecimiento. Durante la fase de crecimiento exponencial, todos los cultivos mostraron un patrón semejante de crecimiento y una baja actividad -galactosidasa. Sin embargo, el inicio de la disminución de la capacidad replicativa que caracteriza el final de dicha fase, así como el inicio de la fase estacionaria o senescente presentaron un aumento significativo en la actividad enzimática. Nuestros resultados mostraron que la actividad -galactosidasa puede ser considerada como marcador de senescencia replicativa del epitelio superficial del ovario a pH 6.?-galactosidase activity reflects the rate of cellular aging in vitro. Such activity was quantified at pH 6 in ovarian epithelial cells from 28 donors without a history of cancer, by the chemoluminiscent method. The cells were serially cultured until they achieved the state of permanent growth arrest. During the exponential growth phase, all cultures showed a similar pattern of growth and low ?-galactosidase activity. However, both in the onset of decrease replicative activity, as well as in the onset of the stationary phase, there was a significant rise in the enzyme activity. Our results showed that ?-galactosidase activity can be considered as a replicative senescence marker of the ovarian surface epithelium at pH 6

Aberraciones citogenéticas en cultivos primarios del epitelio superficial del ovario

Our objective was to determine the presence of chromosomal abnormalities in primary cultures of ovarian surface epithelial cells in women of different ages with no history of cancer. Throughout conventional cytogenetic techniques, we analyzed chromosome spreads of cultured ovarian epithelial cells from 10 donors who were 50 or more years old (B) and 16 controls between 20 and 49 years old (A), belonging to the mestizo population in Bogota DC, Colombia. Of the 26 cultures that were analyzed in passage 1, 61.5% had an abnormal chromosome complement (62.5% in A, and 60% in B). Abnormalities included polyploidies, endoduplications and monosomies. Deletions in chromosomes 3 and 11 were found in just one metaphase. None of the samples showed weaknesses or breakpoints. After transforming and applying the exact student's t-test for variance heterogeneity, we found significant differences in the frequency of metaphases, that were higher in A than in B (p=0.05), and in the frequency of polyploidies, which were higher in B than in A (p=0.044). Through the application of the Mann-Whitney test, we determined that the frequency of endoduplications was higher in A than in B (p=0.126), without reaching significant differences. There were no significant differences in the frequency of monosomies. The level of significance was set at p ? 0.05. Taking into account that polyploidization is a marker of chromosomal instability and that the risk of cancer arising from the ovarian surface epithelium augments substantially after menopause, the increase in the frequency of age-associated polyploidies could be used as a predictor of ovarian cancer in women from an ethnically homogeneous population as the mestizo one in Bogota DC