ERG mediates the inhibition of NK cell cytotoxicity through the HLX/STAT4/Perforin signaling pathway, thereby promoting the progression of myocardial infarction

This study aimed to investigate the role of ERG in the HLX/STAT4/Perforin signaling axis, impacting natural killer (NK) cell cytotoxicity and myocardial infarction (MI) progression. NK cell cytotoxicity was assessed via co-culture and 51Cr release assays. Datasets GSE34198 and GSE97320 identified common differentially expressed genes in MI. NK cell gene expression was analyzed in MI patients and healthy individuals using qRT-PCR and Western blotting. ERG's regulation of HLX and STAT4's regulation of perforin were studied through computational tools (MEM) and ChIP experiments. HLX's influence on STAT4 was explored with the MG132 proteasome inhibitor. Findings were validated in a mouse MI model. ERG, a commonly upregulated gene, was identified in NK cells from MI patients and mice. ERG upregulated HLX, leading to STAT4 proteasomal degradation and reduced Perforin expression. Consequently, NK cell cytotoxicity decreased, promoting MI progression. ERG mediates the HLX/STAT4/Perforin axis to inhibit NK cell cytotoxicity, fostering MI progression. These results provide vital insights into MI's molecular mechanisms. (AU)

ERG mediates the inhibition of NK cell cytotoxicity through the HLX/STAT4/Perforin signaling pathway, thereby promoting the progression of myocardial infarction

This study aimed to investigate the role of ERG in the HLX/STAT4/Perforin signaling axis, impacting natural killer (NK) cell cytotoxicity and myocardial infarction (MI) progression. NK cell cytotoxicity was assessed via co-culture and 51Cr release assays. Datasets GSE34198 and GSE97320 identified common differentially expressed genes in MI. NK cell gene expression was analyzed in MI patients and healthy individuals using qRT-PCR and Western blotting. ERG's regulation of HLX and STAT4's regulation of perforin were studied through computational tools (MEM) and ChIP experiments. HLX's influence on STAT4 was explored with the MG132 proteasome inhibitor. Findings were validated in a mouse MI model. ERG, a commonly upregulated gene, was identified in NK cells from MI patients and mice. ERG upregulated HLX, leading to STAT4 proteasomal degradation and reduced Perforin expression. Consequently, NK cell cytotoxicity decreased, promoting MI progression. ERG mediates the HLX/STAT4/Perforin axis to inhibit NK cell cytotoxicity, fostering MI progression. These results provide vital insights into MI's molecular mechanisms. (AU)

LncRNA CASC19: a novel oncogene involved in human cancer

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial–mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers (AU)

Comprehensive analysis of novel cancer prediction genes and tumor microenvironment infiltration in colon cancer

Background Colon cancer with high incidence and mortality is a severe public health problem. As an emerging therapy, immunotherapy has played an active clinical role in tumor treatment, but only a small number of patients respond. Methods By univariate Cox regression analysis of 165 novel cancer prediction genes (NCPGs), 29 NCPGs related to prognosis were screened. Based on these 29 NCPGs and 336 differentially expressed genes, we constructed two colon cancer subgroups and three gene clusters and analyzed prognosis, activation pathways, and immune infiltration characteristics under various modification patterns. Then each patient was scored and divided into high or low NCPG_score groups. A comprehensive evaluation between NCPG_score and clinical characteristics, tumor microenvironment (TME), tumor somatic mutations, and the potential for immunotherapy was conducted. Results Patients with high NCPG_score were characterized by high tumor mutation burden and high microsatellite instability and were more suitable for immunotherapy. Conclusions This study screened 29 NCPGs as independent prognostic markers in colon cancer patients, demonstrating their TME, clinicopathological features, and potential roles in immunotherapy, helping to assess prognosis and guiding more personalized immunotherapy (AU)

Roles of oncogenes in esophageal squamous cell carcinoma and their therapeutic potentials

sophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer (EC) in Asia. It is a malignant digestive tract tumor with abundant gene mutations. Due to the lack of specific diagnostic markers and early cancer screening markers, most patients are diagnosed at an advanced stage. Genetic and epigenetic changes are closely related to the occurrence and development of ESCC. Here, We review the activation of proto-oncogenes into oncogenes through gene mutation and gene amplification in ESCC from a genetic and epigenetic genome perspective, We also discuss the specific regulatory mechanisms through which these oncogenes mainly affect the biological function and occurrence and development of ESCC through specific regulatory mechanisms. In addition, we summarize the clinical application value of these oncogenes is summarized, and it provides a feasible direction for clinical use as potential therapeutic and diagnostic markers (AU)

FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p

Purpose: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.MethodsThe biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.ResultsThrough bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.ConclusionsIn general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients. (AU)

Phenotypical screening on metastatic PRCC-TFE3 fusion translocation renal cell carcinoma organoids reveals potential therapeutic agents

PurposeTranslocation renal cell carcinoma (tRCC) is a subtype that occurs predominantly in children and young individuals. Metastatic tRCC occurring in young patients is more aggressive than that occurring in older patients, and there are still no effective therapies. Organoids can mimic original tissues and be assessed by high-throughput screening (HTS). We aimed to utilize patient-derived organoids and HTS to screen drugs that can be repurposed for metastatic tRCC with PRCC-TFE3 fusion.MethodsTumor tissues were obtained from treatment-naïve metastatic tRCC patients who underwent surgery. Histopathology and fluorescence in situ hybridization (FISH) confirmed the tRCC. Organoids derived from the dissected tissues were cultured and verified by FISH and RNA-seq. HTS was performed to seek promising drugs, and potential mechanisms were explored by RNA-seq and cell-based studies.ResultsWe successfully established a metastatic tRCC organoid with PRCC-TFE3 fusion, a common fusion subtype, and its characteristics were verified by histopathology, FISH, and RNA-seq. An HTS assay was developed, and the robustness was confirmed. A compound library of 1816 drugs was screened. Eventually, axitinib, crizotinib, and JQ-1 were selected for further validation and were found to induce cell cycle arrest and apoptosis. RNA-seq analyses of posttreatment organoids indicated that crizotinib induced significant changes in autophagy-related genes, consistent with the potential pathogenesis of tRCC.ConclusionsWe established and validated organoids derived from tissues dissected from a patient with metastatic tRCC with PRCC-TFE3 fusion and achieved the HTS process for the first time. Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion. Such organoid and HTS assays may represent a promising model system in translational research assisting in the development of clinical strategies.

Diagnóstico microbiológico de la infección por virus del papiloma humano / Microbiological diagnosis of human papilloma virus infection

La infección por el virus del papiloma humano (VPH) es la infección de transmisión sexual más frecuente en el mundo. Este virus ocasiona generalmente lesiones benignas, como verrugas genitales, pero también su persistencia ocasiona procesos malignos, como cáncer de cuello de útero (CCU) y, menos frecuentemente, anal, vaginal y de la cavidad orofaríngea. El CCU es una enfermedad muy severa, con alta mortalidad en muchos países. El cribado de CCU con citología ha tenido mucho éxito en estos últimos años, pero hay innumerable evidencia científica para que sea sustituida por la detección del VPH como prueba inicial. Para esto, hay en el mercado gran cantidad de técnicas, siendo aconsejable utilizar sistemas automáticos y pruebas aprobadas por la FDA. Un nuevo algoritmo basado en la detección individualizada de los genotipos 16 y 18 presentes en el 70% de los CCU ha sido propuesto por expertos y su implantación será inmediata en algunos países (AU)

Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future (AU)

RAS status in Korean patients with stage III and IV colorectal cancer

Background. KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship to clinical, pathologic, and molecular features remains unclear. Methods. We evaluated 130 colorectal tumors for mutations in KRAS and NRAS gene. We tested for mutations in codons 61 and 146 of KRAS and codons 12, 13, 59, 61 and 146 of NRAS. Mutation status was determined by targeted dideoxy sequencing. Results. Among the analyzed primary tumors, 36.2 % had KRAS mutation. Of the 83 KRAS codon 12 and 13 wild-type patients, 7.2 % had KRAS codon 61, 146 or NRAS. 40.7 % harbored any RAS mutation. Conclusion. The frequency of other RAS (NRAS and KRAS exon 3, 4) activating mutations in colorectal cancers is relatively low in Korean colorectal cancer patients (AU)

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Cáncer oral: Genética, prevención, diagnóstico y tratamiento. Revisión de la literatura / Oral cancer: Genetics, prevention, diagnosis and treatment. Literature review

El objetivo de esta revisión es actualizar la situación actual del cáncer oral, así como de otros aspectos en general de esta enfermedad y del mecanismo genético y tumorogénesis del cáncer. Para ello hemos revisado los trabajos publicados de los últimos diez años sobre todos los aspectos generales del cáncer oral, destacando, entre otros, los referentes a factores de riesgo, diagnóstico y tratamiento. Las conclusiones más importantes de esta revisión han sido que, el cáncer oral, es un problema que aumenta con la edad, a partir de los 50 años en adelante, y que el 90% de los tumores que aparecen en boca son carcinomas mucoepidermoides de células escamosas. Es una enfermedad multifactorial, pero dentro de los factores de riesgo, se destacan el papel del tabaco y el alcohol. La prevalencia del cáncer oral sigue en aumento, por lo que el papel del odontólogo es primordial para la detección precoz de estos procesos, realizando una correcta historia clínica y exploración extra e intraoral, consiguiendo disminuir su morbimortalidad (AU)

The aim of this revision was to update the actual situation of oral cancer, and other important aspects of this illness explaining how the genetic mechanism and tumorogenesis in cancer works. We have reviewed the articles published in the last ten years about the general aspects of oral cancer, distinguishing the risk factors, diagnosis and treatment. The most important conclusions of this review, in relation to oral cancer, have been that this illness is a problem which increases with age, from 50 years old onwards, and that around 90% of the tumours that appear in the oral cavity are squamous cell carcinomas. Oral cancer is multifactorial, but the two most important risk factors are tobacco and alcohol. The prevalence of oral cancer continues to rise, that is why the role of the dentist is very important in detecting this illness in its early stages, by doing a correct anamnesis and a correct extraoral and intraoral inspection, decreasing the morbility and mortality (AU)

The NanoString-based multigene assay as a novel platform to screen EGFR, HER2, and MET in patients with advanced gastric cancer

Introduction: Molecular targets are emerging rapidly and the development of clinical tests that simultaneously screen for multiple targets has become especially important. We assessed the gene expression levels of three known targets in advanced gastric cancer, epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and N-methyl-N-nitrosoguanidine human osteosarcoma transforming gene (MET), using the nCounter assay (NanoString Technologies, Seattle, WA, USA) and compared these results with protein overexpression, detected by immunohistochemistry, to evaluate the performance of this new technology. Methods: We investigated 42 formalin-fixed, paraffinembedded tumor samples from patients with gastric cancer. A NanoString-based assay containing a 522 kinase gene panel was investigated. We analyzed the correlations between immunohistochemical findings and kinase gene expression levels of EGFR, HER2 and MET to validate this assay. Results EGFR, HER2, and MET overexpression were observed in 7 (16.6 %), 5 (11.9 %), and 3 (7.1 %) cases, respectively. For EGFR, HER2, and MET, the concordance rates between the NanoString-based assay results and the immunohistochemistry methods were 83.3, 97.6, and 100 %, respectively. Relative to immunohistochemistry findings, the NanoString-based assay sensitivities and specificities were 85.7 and 82.8 % for EGFR, 100 and 97.2 % for HER2, and 100 and 100 % for MET, respectively. Conclusions: We found a high concordance between immunohistochemistry- and nCounter-based assessments of EGFR, HER2, and MET in advanced gastric cancer. Judged against immunohistochemistry results, the NanoString assay had high sensitivities and high specificities. These results suggest that the nCounter assay provides a reliable, high-throughput assay to simultaneously screen for the overexpression of several target proteins (AU)

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Papel de los micro-RNA en el cribado del cáncer colorrectal / Role of micro-RNA in colorectal cancer screening

Los micro-RNAs son responsables de la regulación de múltiples procesos biológicos de índole metabólica, de proliferación, de diferenciación, de apoptosis, del desarrollo y de la oncogénesis. En la carcinogénesis, los micro-RNA pueden ejercer su función a través de la alteración de los genes supresores de tumores o mediante la interacción con los oncogenes. Se ha determinado la presencia de diferentes micro-RNA en distintas enfermedades neoplásicas como cáncer de colon, próstata, mama, estómago, páncreas, pulmón, etc. Existen datos prometedores sobre la utilidad de cuantificar los micro-RNA en diferentes fluidos orgánicos y tejidos. Se ha realizado una revisión sobre las determinaciones de los micro-RNA en el diagnóstico del cáncer colorrectal

MicroRNAs are involved in carcinogenesis through postranscriptional gene regulatory activity. These molecules are involved in various physiological and pathological functions, such as apoptosis, cell proliferation and differentiation, which indicates their functionality in carcinogenesis as tumour suppressor genes or oncogenes. Several studies have determined the presence of microRNAs in different neoplastic diseases such as colon, prostate, breast, stomach, pancreas, and lung cancer. There are promising data on the usefulness of quantifying microRNAs in different organic fluids and tissues. We have conducted a review of the determinations of microRNAs in the diagnosis of colorectal cancer

CHD1L is a novel independent prognostic factor for gastric cancer

BACKGROUND: Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is involved in malignancies. However, the role of CHD1L in gastric cancer (GC) has not been elucidated. The aim of this study is to explore the clinical role of CHD1L in GC. METHODS: The gene and protein expression levels of CHD1L were detected by quantitative real-time PCR and Western blot analysis in fresh samples of GC and paired adjacent noncancerous tissue (n = 34). We evaluated the CHD1L expression by immunohistochemistry in a large number of GC patients (n = 616) and paired adjacent noncancerous tissues from December 1, 2004 to December 1, 2008. The correlations of CHD1L expression with clinicopathological features and clinical outcome were analyzed. RESULTS: The gene and protein expression levels of CHD1L were higher in fresh samples of GC than in paired adjacent noncancerous tissues as determined by quantitative real-time PCR and Western blot analysis. Immunohistochemical analysis showed that positive expression rates of CHD1L in GC and paired adjacent noncancerous tissues were 58.7 % (361/616) and 7.3 % (45/616), respectively. CHD1L positivity was significantly associated with clinical stage and distant metastasis. GC patients with positive CHD1L expression had shorter overall survival than those with negative CHD1L expression. Multivariate analysis showed that CHD1L was an independent prognostic marker for overall survival [Hazard Ratio (HR) = 5.952, 95 % confidence interval (CI) = 3.194-11.187, P = 0.0043]. CONCLUSION: These results indicated that CHD1L could serve as a prognostic marker for GC (AU)

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Biomarcadores proteómicos en la enfermedad de Parkinson / Proteomic biomarkers in Parkinson's disease

La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo que afecta al movimiento, cuya causa es la muerte de las neuronas dopaminérgicas de la parte compacta de la sustancia negra. El diagnóstico es fundamentalmente clínico, pero, a pesar de que los signos y síntomas de la EP se conocen bien, el error diagnóstico es relativamente alto. Se calcula que un 10-30% de los pacientes inicialmente diagnosticados de EP se reclasifican posteriormente. Esta enfermedad tiene una alta prevalencia a partir de los 60 años, y uno de los mayores problemas que tiene es que su diagnóstico se hace cuando el proceso degenerativo está muy avanzado. Por tanto, es necesaria la búsqueda de biomarcadores que permitan un diagnóstico precoz de la EP, seguir su progresión, diferenciarla de otras patologías relacionadas (parkinsonismos) y que ayuden a monitorizar el efecto de nuevas terapias. El hecho de que existan mutaciones que conducen a la EP, así como combinaciones poligénicas que pueden actuar como factores de riesgo, sugiere que es posible analizar las proteínas resultantes de la expresión de estos genes en tejidos periféricos, que, una vez demostrada su sensibilidad y especificidad, podrían utilizarse como biomarcadores de la EP, incluso en fases iniciales de la enfermedad. El objetivo del presente trabajo es centrarse en una revisión detallada de los principales biomarcadores proteómicos candidatos investigados hasta el momento, discutiendo la literatura más reciente (AU)

Parkinson’s disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature (AU)

Pituitary tumor transforming gene and insulin-like growth factor 1receptor expression and immunohistochemical measurement ofKi-67 as potential prognostic markers of pituitary tumorsaggressiveness

Introducción y objetivo La capacidad de predecir recurrencia en los adenomas hipofisarios (AH) tras la cirugía puede ser útil para determinar la frecuencia de seguimiento y la necesidad de tratamientos adyuvantes. El objetivo del presente estudio fue valorar la capacidad pronóstica de gen transformador de tumores hipofisarios (pituitary tumor transforming gene [PTTG]), del receptor del factor de crecimiento insulinoide 1 (insulin-like growth factor 1 receptor [IGF1R]) y de Ki-67. Material y métodos En este estudio retrospectivo determinamos el número de copias normalizadas de ARNm (Cnn) de PTTG e IGF1R mediante RT-PCR y el índice Ki-67 mediante inmunohistoquímica en 46 muestras de AH. Los datos clínicos, el subtipo histológico y las características radiológicas se recogieron para determinar asociaciones entre las variables y el comportamiento tumoral. Además, estudiamos la progresión de los restos tumorales y su asociación con los marcadores en 14 pacientes sin tratamiento adyuvante posquirúrgico seguidos durante 46 ± 36 meses. Resultados Los tumores extraselares mostraron una expresión de PTTG menor que los intraselares (0,065 [1.er-3.er cuartil: 0,000-0,089] Cnn frente a 0,135 [0,105–0,159] Cnn, p = 0,04). La expresión de IGF1R varió en función del subtipo histológico (p = 0,014), siendo mayor en los tumores que presentaron crecimiento de los restos mayor del 20% durante el seguimiento (10,69 ± 3,84 Cnn frente a 5,44 ± 3,55 Cnn, p = 0,014). Conclusiones Nuestros resultados indican que IGF1R, en mayor medida que PTTG, es un marcador molecular útil en el manejo de los AH. Ki-67 no mostró asociación con el comportamiento tumoral. Sin embargo, el potencial de estos marcadores debe ser establecido en futuros estudios con una metodología estandarizada y una muestra mayor (AU)

Introduction and objective The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. Materials and methods In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46 ± 36 months. Results Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st–3rd quartile: 0.000–0.089] NCN vs. 0.135 [0.105–0.159] NCN, p = 0.04). IGF1R expression changed depending on histological subtype (p = 0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69 ± 3.84 NCN vs. 5.44 ± 3.55 NCN, p = 0.014). Conclusions Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples(AU)

Implicaciones clínicas de la determinación histológica de los micrornas en el cáncer colorrectal / Clinical implication of histological determination of micrornas in colorectal cancer

Los microRNAs son estructuras moleculares con actividad post-transcripcional que están implicados en la regulación de la expresión genética. Diversos estudios ponen de manifiesto la participación de los microRNAs con distintas funciones fisiológicas, así como con el proceso de la oncogénesis. La expresión de los microRNAs puede verse alterada en las neoplasias por su interacción bien con los genes supresores de tumores, bien con los oncogenes. Se ha llevado a cabo una revisión bibliográfica en PubMed acerca de la evidencia publicada sobre la determinación histológica de los microRNAs y la relación existente con el diagnóstico y el pronóstico del cáncer colorrectal. A pesar de ser preciso nuevos estudios clínicos que especifiquen la relación de los microRNAs con el cáncer colorrectal, se ha evidenciado una relación de estas estructuras con el diagnóstico y pronóstico de esta neoplasia (AU)

MicroRNAs are short non-coding RNA molecules involved in the regulation of gene expression. Several studies demonstrate the involvement of microRNAs with different physiological functions and oncogenesis. The expression of microRNAs may be altered in tumors by their interaction with tumor suppressor genes or with oncogenes. A literature review in PubMed was made about the evidence on the histological determination of microRNAs and the relationship with the diagnosis and prognosis of colorectal cancer. Although further clinical studies focusing on serum microRNAs are required to determine the relationship of microRNAs in colorectal cancer, the relationship of these structures with the diagnosis and prognosis of this neoplasm has been shown (AU)

Implicaciones del nuevo enfoque etiopatogénico en la clasificación de las enfermedades constitucionales y genéticas del hueso / Implications of the new etiophatogenic approach in the classification of constitutional and genetic bone diseases

El avance en el conocimiento de las alteraciones bioquímicas que causan las enfermedades constitucionales óseas no tiene precedentes. La constatación de que su característica esencial es el trasfondo genético común a todas ellas ha dado lugar a una propuesta de alcance: sustituir el término «constitucionales» por «genéticas» para referirse a estas entidades. La comprensión de los mecanismos fisiopatológicos implicados, identificando el punto exacto de la vía metabólica alterada y sus sistemas de regulación y control, facilita realizar un diagnóstico preciso, basado en la colaboración interdisciplinar, en un tiempo muy inferior del que requería el enfoque tradicional. Además, aunque la correcta valoración de las manifestaciones clínicas y radiológicas sigue siendo crucial, el diagnóstico de certeza se basa cada vez con mayor frecuencia en la aplicación de las nuevas técnicas de análisis genético y molecular. Por último, el esclarecimiento de las complejas alteraciones subyacentes a estos trastornos descubre unas dianas moleculares de gran utilidad potencial en la investigación terapéutica de unas enfermedades que a menudo limitan de manera notable la calidad de vida y que, casi sin excepciones, todavía carecen de un tratamiento eficaz (AU)

Recent years have seen an unprecedented increase in the knowledge and understanding of biochemical disturbances involved on constitutional bone disorders. Recognition of the genetic background as the common cause of these diseases prompted the substitution of the term «constitutional» by «genetic», in referring to them. Understanding physiopathological bases by finding out the altered metabolic pathways as well as their regulatory and control systems, favours an earlier and more accurate diagnosis based on interdisciplinary collaboration. Although clinical and radiological assessment remains crucial in the study of these disorders, ever more often the diagnosis is achieved by molecular and genetic analysis. Elucidation of the damaged underlying molecular mechanisms offers targets potentially useful for therapeutic research in these complex and often disabling diseases (AU)

Hipoxia tumoral. Papel del factor inducible por hipoxia / Tumor hypoxia: the role of HIF

Los tumores sólidos, por lo general, existen y progresan en un ambiente de hipoxia; así se observa que las células tumorales son resistentes a la apoptosis y se acompañan de un aumento de la angiogénesis, volviéndose más agresivas, con capacidad invasora y resistentes al tratamiento. La genética y los mecanismos biológicos subyacentes a este fenómeno son todavía poco claros, pero muchos estudios sugieren un papel del factor inducible por hipoxia (hipoxia inducible factor [HIF]) en este proceso. En condiciones de hipoxia, la subunidad alfa no es destruida y activará la transcripción de un conjunto de genes que contribuyen a la agresividad del tumor. Su expresión está asociada a un aumento del potencial metastásico que se verifica tanto en estudios animales, como en tumores humanos. La hipoxia tumoral se ha convertido en un factor clave en la progresión tumoral y se asocia a un mal pronóstico, sobre todo en tumores de riñón y próstata. Este trabajo tiene por objetivo revisar la importancia de la hipoxia en la carcinogénesis y en la progresión tumoral, presentando una revisión de los conocimientos actuales sobre el tema, mecanismos de acción y la activación del HIF-1α (AU)

Solid tumors usually occur and progress in a hypoxic enviroment, suggesting that tumor cells are resistant to apoptosis and are associated to an increased angiogenesis, which makes them more aggressive, with invasive capacity and resistant to treatment. The genetic and biological mechanisms underlying this phenomenon are still unclear, but many studies suggest a role of HIF in this process. Under hypoxic conditions, the alpha subunit is not destroyed, and will activate transcription of a set of genes contributing to tumor aggressiveness. Its expression is associated to an increased metastatic potential that has been shown in both animal studies and human tumors. Tumor hypoxia has emerged as a key factor in tumor progression and is associated to a poor prognosis, particularly in kidney and prostate tumors. The purpose of this study was to review the significance of hypoxia in carcinogeneses and tumor progression by reviewing the current knowledge on the subject and the mechanisms of action and activation of HIF-1a (AU)

Bases moleculares de la cancerización de cavidad oral / Molecular basis on oral cavity cancerization

Se presenta una revisión bibliográfica breve sobre los principales aspectos moleculares de interés en la cancerización de cavidad oral. Se hace referencia a los conocimientos más recientes sobre las aberraciones cromosómicas más comunes y las alteraciones de los oncogenes y genes supresores tumorales que están implicados en la carcinogénesis oral. Así mismo, se resume la teoría molecular actual que explica el proceso de cancerización de campo (AU)

A review about the main molecular aspects on oral cavity cancerization is presented, with special reference to the common chromosomal aberration, oncogenes and tumour suppressor genes implied in oral carcinogenesis. A summary about molecular theory explaining the field cancerization process is also presented (AU)