10 research outputs found
Melanoma de la mucosa oral: casos clínicos y revisión de la literatura
La aparición de melanomas primarios de la mucosa oral es
infrecuente. La agresividad de esta entidad y la ausencia de
protocolos de tratamiento estandarizado, hacen que el pronóstico
sea infausto. Se han relacionado la dificultad de la resección
quirúrgica con márgenes libres, la tendencia elevada a la invasión
en profundidad y las metástasis hematógenas tempranas,
como consideraciones que justifican un peor pronóstico en
relación al melanoma cutáneo. Sin embargo, no existen series
clínicas grandes, y las series de casos clínicos constituyen la
fuente principal de información en el momento actual. Ante la
ausencia de modalidades de tratamiento que aumenten substancialmente
la supervivencia a largo plazo, sugerimos el empleo
de cirugía de resección con márgenes amplios y el diagnóstico
precoz mediante la biopsia de lesiones pigmentadas melánicas
sospechosas. En el presente trabajo presentamos 2 nuevos casos
de melanoma primario de mucosa oral, con un seguimiento de
72 y 12 meses respectivamente, y realizamos una revisión de
la literatura en relación con esta rara neoplasia.The appearance of primary melanomas of the oral mucosa is
uncommon. The aggressiveness of this entity and the absence
of any standardized treatment protocol make the prognostic unfortunate.
The difficulty to obtain free surgical margins, the elevated
tendency to invade in depth and the early haematogenous
metastasis have been referred as features which may explain its
bad prognosis, even in comparison with cutaneous melanoma.
However, no large clinical series exist and actually, clinical cases
are the main source of information. Due to the absence of
any treatment modality which may substantially increase longterm
survival, we suggest the use of resective surgery with wide
margins and early diagnosis by means of biopsy for suspicious
melanotic-pigmented lesions. In this work we present 2 new
cases of primary melanoma of the oral mucosa, with a follow-up
period of 72 and 12 months respectively, and we make a review
of the literature in relation with this rare entity
Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis
Objectives: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. Material and methods: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables. A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable. Results: The study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014). Conclusions: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages
ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology
ERK5; Leiomyosarcoma; Soft tissue sarcomaERK5; Leiomiosarcoma; Sarcoma de tejido blandoERK5; Leiomiosarcoma; Sarcoma dels teixits tousSarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)
ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma
Hi ha quatre pàgines de material suplementari sense numeracióExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas
ERK5 Is a major determinant of chemical sarcomagenesis: implications in human pathology
Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)
ERK5 Is a Major Determinant of Chemical Sarcomagenesis : Implications in Human Pathology
Sarcoma is a heterogeneous group of tumors poorly studied with few therapeutic opportunities. Interestingly, the role of MAPKs still remains unclear in sarcomatous pathology. Here, we describe for the first time the critical role of ERK5 in the biology of soft tissue sarcoma by using in vitro and in vivo approaches in a murine experimental model of chemical sarcomagenesis. Indeed, our observations were extrapolated to a short series of human leiomyosarcoma and rhabdomyosarcomas. Furthermore, transcriptome analysis allows us to demonstrate the critical role of KLF2 in the biological effects of ERK5. Therefore, the data presented here open new windows in the diagnosis and therapy of soft tissue sarcomas. Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology
ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma
Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas
ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma
Hi ha quatre pàgines de material suplementari sense numeracióExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas