Endothelial NOX5 overexpression induces changes in the cardiac gene profile: potential impact in myocardial infarction?

Cardiovascular diseases and the ischemic heart disease specifically constitute the main cause of death worldwide. The ischemic heart disease may lead to myocardial infarction, which in turn triggers numerous mechanisms and pathways involved in cardiac repair and remodeling. Our goal in the present study was to characterize the effect of the NADPH oxidase 5 (NOX5) endothelial expression in healthy and infarcted knock-in mice on diverse signaling pathways. The mechanisms studied in the heart of mice were the redox pathway, metalloproteinases and collagen pathway, signaling factors such as NFκB, AKT or Bcl-2, and adhesion molecules among others. Recent studies support that NOX5 expression in animal models can modify the environment and predisposes organ response to harmful stimuli prior to pathological processes. We found many alterations in the mRNA expression of components involved in cardiac fibrosis as collagen type I or TGF-β and in key players of cardiac apoptosis such as AKT, Bcl-2, or p53. In the heart of NOX5-expressing mice after chronic myocardial infarction, gene alterations were predominant in the redox pathway (NOX2, NOX4, p22phox, or SOD1), but we also found alterations in VCAM-1 and β-MHC expression. Our results suggest that NOX5 endothelial expression in mice preconditions the heart, and we propose that NOX5 has a cardioprotective role. The correlation studies performed between echocardiographic parameters and cardiac mRNA expression supported NOX5 protective action. (AU)

Bcl-2 pathway inhibition in solid tumors: a review of clinical trials

Due to their key role in the pathogenesis of cancer through the regulation of apoptosis, the B-cell leukemia/lymphoma-2 (BCL-2) family proteins have been an attractive target for cancer therapy for the past decades. Throughout the years, many Bcl-2 family inhibitors have been developed, with Venetoclax being now successfully used in treating hematological malignancies. Although their effectiveness in the treatment of solid tumors is yet to be established, some preclinical evidence indicates their possible clinical application. This review aims to summarize current data from completed clinical trials that used Bcl-2 protein family inhibitors as monotherapy or in combination with other agents for the treatment of solid malignancies. We managed to include clinical trials of various phases which analyze the pharmacokinetics and pharmacodynamics of the drugs, as well as the effectiveness and adverse effects. Active and recruiting clinical trials are also briefly presented and future prospects and challenges are discussed (AU)

The microRNA-520a-3p inhibits invasion and metastasis by targeting NF-kappaB signaling pathway in non-small cell lung cancer

Purpose: To identify the expression of miR-520a-3p and AKT1 in non-small cell lung cancer cells (NSCLC) and the mechanism in inhibiting cell invasion and metastasis by targeting NF-kappaB signaling pathway.Methods: Bioinformatics analysis and dual luciferase reporter gene assay were used to predict and verify the targeting relationship between miR-520a-3p and AKT1. EdU assay was used to detect the proliferation of NSCLC cells. Flow cytometry detected the apoptosis of NSCLC cells. Transwell assay tested the invasion ability of NSCLC cells. qRT-PCR measured the expression of miR-520a-3p and AKT1 mRNA in NSCLC cells; while western blotting was adopted to detect the protein expressions of AKT1, Ki67, CyclinD1, Bax, Bcl-2, MMP-2, MMP-9, NF-kB p65, IkBs kinase (IKK), NF-kB inducing kinase (NIK).Results: Bioinformatics analysis suggested that miR-520a-3p could target AKT1. miR-520a-3p could regulate the expression of AKT1 negatively. Compared to mimic-NC group, miR-520a-3p mimic group had increased expressions of miR-520a-3p and Bax, while decreased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, reduced cell proliferation, invasion, and increased cell apoptosis rate (all P < 0.05). Compared to inhibitor NC group, miR-520a-3p inhibitor group had decreased expressions of miR-520a-3p and Bax, but increased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, promoted cell proliferation, invasion, and suppressed cell apoptosis rate (all P < 0.05).Conclusion: Overexpression of miR-520a-3p can target and downregulate the expression of AKT1 to inhibit the invasion and metastasis of NSCLC via suppressing the activation of NF-kappaB signaling pathway. (AU)

Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Background: To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patientswith oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredictable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax,E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition.Material and Methods: A cross-sectional study using genomic DNA and biopsy samples extracted from the oralmucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, UniversidadNacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test wasapplied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance).Results: GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation toCC “healthy” genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis(p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherinmarkers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, andBax immunomarker was diminished in OSCC.Conclusions: We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, whichmodifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G ofGJA1rs12197797 could be at risk of developing OSCC. (AU)

Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2

Purpose This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. Methods qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. Results Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. Conclusions In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer (AU)

Circulating Bcl-2 concentrations and septic patient mortality / Concentraciones sanguíneas de Bcl-2 y mortalidad de los pacientes con sepsis

Introduction: There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction. Methods: Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable. Results: We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-2<4.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406–7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55–68%; p=0.003). Conclusions: In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.(AU)

Introducción: No hemos encontrado datos publicados sobre las concentraciones sanguíneas de B-cell lymphoma 2 (Bcl-2) (una de las moléculas antiapoptóticas de la familia Bcl-2 de la vía intrínseca de la apoptosis) en pacientes con sepsis. Por lo cual, este estudio se realizó con los propósitos de explorar las concentraciones sanguíneas de Bcl-2 en el momento del diagnóstico de la sepsis en los pacientes supervivientes y fallecidos, analizar si se asocian con la supervivencia y determinar si son útiles para predecir el fallecimiento. Métodos: Las unidades de Cuidados Intensivos de 3 hospitales españoles participaron en este estudio observacional y prospectivo de pacientes con sepsis, y se determinaron las concentraciones sanguíneas de Bcl-2 al diagnosticar la sepsis. La mortalidad a 30 días fue nuestra variable resultado. Resultados: Los pacientes que fallecían en los primeros 30 días (n=81) presentaron menores concentraciones sanguíneas de Bcl-2 (p=0,003) que los supervivientes (n=140). Encontramos que las concentraciones sanguíneas de Bcl-2<4,4 ng/ml se asociaban con la mortalidad en el análisis de regresión logística múltiple (OR=3,228; IC del 95%=1,406-7,415; p=0,006). Encontramos que las concentraciones sanguíneas de Bcl-2 tenían un área bajo la curva del 62% (IC del 95%=55%-68%; p=0,003) para la predicción del fallecimiento. Conclusiones: En nuestro estudio aparecieron nuevos hallazgos como que las concentraciones sanguíneas de Bcl-2 fueron superiores en los supervivientes, se asociaban con la supervivencia y podían predecir la mortalidad.(AU)

Long intergenic non-coding RNA-p21 is associated with poor prognosis in chronic lymphocytic leukemia

Long non-coding RNAs (LncRNAs) are RNA transcripts longer than 200 nucleotides. They are new players in transcriptional regulation and cancer research. LincRNA-p21 is a p53-regulated lncRNA involved in the p53 transcriptional network. It has an important role in regulating cellular proliferation and apoptosis. Chronic lymphocytic leukemia is derived by a typical defect in apoptosis and characterized by clonal proliferation and accumulation of mature B cells. The aim of the present study was to assess the expression pattern of the lincRNA-p21 and investigate its potential role as a new prognostic marker in CLL. Methods The study was conducted on 80 newly diagnosed CLL patients and 80 age- and sex-matched controls. The analysis of LincRNA-p21 and the p53 downstream proapoptotic target genes (MDM2, PUMA, BAX, and NOXA) was performed by real-time PCR. The cytogenetic abrasions and expression of ZAP70 and CD38 were detected by FISH and Flow cytometry, respectively. Results LincRNA-p21 was significantly downregulated in CLL patients compared to controls. The downstream proapoptotic targets were significantly downregulated in CLL patients and positively correlated with lincRNA-p21. Low expression of lincRNA-p21 was associated with poor prognostic markers (advanced stages of CLL, del 17p13, ZAP70, and CD38 expression), failure of complete remission, shorter progression free survival, and overall survival. Low lincRNA-p21 expression was independently prognostic for shorter time to treatment. Conclusion Low expression of lincRNA-p21 demarcates a more aggressive form of CLL with poor prognosis. Therefore, it could be considered as a new prognostic marker to predict disease outcome in CLL (AU)

SOX2 and BCL-2 Expressions in Odontogenic Keratocyst and Ameloblastoma

BACKGROUND: The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB) specimens, and to identify a possible correlation in their expression.MATERIAL AND METHODS: Immunohistochemical analysis was performed to evaluate SOX2 and BCL-2 expression in OKC (n = 20) and AB (n = 20). The immunoexpression was analyzed by a quantitative and qualitative scoring system. The comparison between the immunoexpression of SOX 2 and BCL-2 was assessed by the Mann-Whitney U-test. Spearman's correlation coefficient evaluated the correlation between SOX2 and BCL-2 expressions.RESULTS: SOX2 and BCL-2 expression was observed in all specimens of OKC in the full thickness of the epithelium lining. SOX2 immunostaining was higher in OKC, in comparison with AB samples (P<0.05). BCL-2 immunostaining between OKC and AB was not statistically significant. There was no significant correlation between SOX2 and BCL-2 in OKC and AB specimens.CONCLUSIONS: SOX2 and BCL-2 expressions in OKC may suggest their relationship with the biological behavior of this lesion, and the higher expression of SOX2 might be an upstream influence on the Hh signaling pathway

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Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats

In recent years, the beneficial impact of targeted gut microbiota manipulation in various neurological disorders has become more evident. Therefore, probiotics have been considered as a promising approach to modulate brain gene expression and neuronal pathways even in some neurodegenerative diseases. The purpose of this study was to determine the effect of probiotic biotherapy with combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the expression levels of proteins critical to neuronal apoptosis in hippocampus of lipopolysaccharide (LPS)-exposed rats. Four groups of animals (Control, LPS, Probiotic + LPS, and Probiotic) were treated with maltodextrin (placebo) or probiotic (109 CFU/ml/rat) for 2 weeks by gavage. On the 15th day, a single intraperitoneal dose of saline or LPS (1 mg/kg) was injected and 4 h later, protein assessment was performed by western blotting in hippocampal tissues. LPS significantly increased the Bax, Bax/Bcl-2 ratio, and cleaved caspase-3 expression along with decreased the Bcl-2 and procaspase-3 protein levels. However, probiotic pretreatment (L. helveticus R0052 + B. longum R0175) significantly downregulated the Bax and Bax/Bcl-2 ratio accompanied with upregulated Bcl-2 expression. Prophylactic treatment with these bacteria also attenuated LPS-induced caspase-3 activation by remarkably increasing the expression of procaspase-3 while reducing the level of cleaved caspase-3 in target tissues. Our data indicate that probiotic formulation (L. helveticus R0052 + B. longum R0175) alleviated hippocampal apoptosis induced by LPS in rats via the gut-brain axis and suggest that this probiotic could play a beneficial role in some neurodegenerative conditions

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Apoptosis and cell cycle aberrations in epithelial odontogenic lesions: An evidence by the expression of p53, Bcl-2 and Bax

Background: Ameloblastoma (AMB), odontogenic keratocyst (OKC) and adenomatoid odontogenic tumor (AOT) are epithelial odontogenic lesions with diverse biologic profiles. Defects in regulation of apoptosis and cell cycle may be involved in the development and progression of those lesions, therefore we aimed to investigate the expression of Bcl-2, Bax and p53 to better understand the possible role of these proteins in AMBs, OKCs and AOTs. Material and Methods: The studied sample consisted of 20 AMBs, 20 OKCs and 20 AOTs. Immunohistochemistry technique was performed for the antibodies p53, Bcl-2 and Bax. Immunoreactivity was observed in the epithelial component and positive cells were counted in five fields (100x magnification). Statistical analysis was performed with Kruskal-Wallis and Spearman tests (p< 0.05). Results: All lesions exhibited staining for the three studied proteins. There was no statistically significant associations between the expression of proteins and the lesions, however we identified a positive correlation between the expression of p53 and Bcl-2 (r = 0.200) and a negative correlation between p53 and Bax expressions (r = -0.100). In addition, p53 and Bax were similarly expressed between AMBs and OKCs. Bcl-2 was similarly expressed in AMBs and AOTs. Conclusions: Apoptosis regulatory proteins, as well as cell cycle proteins, are differently expressed in epithelial odontogenic lesions and their expression is possibly related to the biological behavior of AMB, OKC and AOT (AU)

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Actualización de las guías nacionales de consenso del Grupo Español de Leucemia Linfocítica Crónica para el tratamiento y seguimiento de la leucemia linfocítica crónica / Update of the Grupo Español de Leucemia Linfocítica Crónica clinical guidelines of the management of chronic lymphocytic leukemia

Antecedentes y objetivo: El amplio arsenal terapéutico junto con la heterogeneidad biológica de los pacientes hace que sea difícil estandarizar el tratamiento de la leucemia linfocítica crónica (LLC) en la práctica clínica. Estas consideraciones han motivado la preparación del presente documento de consenso, que se trata de una actualización de la versión publicada en 2013, prestando especial atención a las estrategias de tratamiento que han aparecido en los últimos 5 años, como los inhibidores del receptor de células B (ibrutinib e idelalisib), los nuevos anticuerpos monoclonales anti-CD20 (ofatumumab y obinutuzumab) y los inhibidores de Bcl-2 (venetoclax). Material y métodos: Un grupo de expertos del Grupo Español de Leucemia Linfocítica Crónica ha revisado la bibliografía publicada entre 2010 y 2016 para poder establecer una serie de recomendaciones basadas en la evidencia clínica. En aquellas áreas donde no se encontró una evidencia científica, el grupo de expertos estableció recomendaciones por consenso con base en sus experiencias clínicas. Resultados: Como resultado del proyecto se ha establecido un conjunto de recomendaciones de carácter práctico que facilitarán el diagnóstico, el tratamiento y el seguimiento de los pacientes con LLC. Conclusiones: Existen muchos aspectos del tratamiento de la LLC que resultan ser temas controvertidos sobre los que no hay estudios apropiados para generar recomendaciones de forma consensuada (AU)

Background and objective: The broad therapeutic arsenal and the biological heterogeneity of patients with chronic lymphocytic leukemia (CLL) makes it difficult to standardize treatment for CLL patients with specific clinical settings in routine clinical practice. These considerations prompted us to elaborate the present consensus document, which constitutes an update of the previous version published in 2013, mainly focusing on novel treatment strategies that have been developed over last 5 years, namely B-cell receptor inhibitors (ibrutinib and idelalisib), anti-CD20 monoclonal antibodies (ofatumumab and obinutuzumab), and Bcl-2 inhibitors (venetoclax). Material and methods: A group of experts from the Spanish Chronic Lymphocytic Leukemia Group reviewed all published literature from January 2010 to January 2016, in order to provide recommendations based on clinical evidence. For those areas without strong scientific evidence, the panel of experts established consensus criteria based on their clinical experience. Results: The project has resulted in several practical recommendations that will facilitate the diagnosis, treatment, and follow-up of patients with CLL. Conclusions: There are many controversial issues in the management of CLL with no appropriate studies for making consensus recommendations (AU)

A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line

The prostate gland is a part of the male reproductive tract which produces both angiotensin II (Ang II) and relaxin 2 (RLN2). The present study analyzes the effect of both these peptide hormones at concentration 10−8M on viability, proliferation, adhesion, migration, and invasion of normal prostate epithelial cells (PNT1A). Improved survival in two- and three-dimensional cell cultures was noted as well as visual changes in colony size and structure in Geltrex™. Stimulatory influence on cell viability of each peptide applied single was lower than in combination. Enhanced survival of PNT1A cells appears to be associated with increased BCL2/BAX messenger RNA (mRNA) expression ratio. Modulation of cell spreading and cell-extracellular matrix adhesion dynamics were also altered as an influence of tested hormone application. However, long-term Ang II and RLN2 effects may lead to an increase of normal prostate cell migration and invasion abilities. Moreover, gelatin zymography revealed that both gelatinases A and B were augmented by Ang II treatment, whereas RLN2 significantly stimulated only MMP-9 secretion. These results support the hypothesis that deregulation of locally secreted peptide hormones such as Ang II and RLN2 may take part in the development of certain cancers, including prostate cancer. Moreover, the observed ability of relaxin 2 to act as a regulator of mRNA expression levels not only LGR7 but also classic angiotensin receptors suggested that renin-angiotensin system and relaxin family peptide system are functionally linked (AU)

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Chain elongation analog of resveratrol as potent cancer chemoprevention agent

Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism (AU)

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Procesos linfoproliferativos múltiples en un paciente / Multiple lymphoprolipherative disorders in a patient

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Immunohistochemical expression of Bcl-2 in benign andmalignant salivary gland tumors

Objectives: The present study was undertaken to assess and compare the immunohistochemical expression ofBcl-2 in selected benign and malignant salivary gland tumors.Study Design: A total of 50 cases of buffered formalin-fixed, paraffin embedded tissues of previously diagnosedcases of benign and malignant salivary gland tumors from the archives of Department of Oral and MaxillofacialPathology and Microbiology, SDM College of Dental Sciences and Hospital, Dharwad, India, were taken for thestudy. The immunohistochemical staining procedure was performed using monoclonal anti Bcl-2 antibody, asdirected by the manufacturer.Results: Thirty six cases (72%) out of 50 cases showed a positive expression for Bcl-2. Benign salivary glandtumors showed a positive expression in 8 out of 14 cases (~57%) and malignant salivary gland tumors in 28 outof 36 cases (~78%). The staining was intense in the normal lymph node, which is used as a positive control. Bcl-2expression was seen in both benign and in malignant salivary gland tumors taken for the study except in “canalicularadenoma”.Conclusion: The immunohistochemical expression of Bcl-2 was greater and more intense in malignant salivarygland neoplasms, suggesting a high survival rate of tumor cells in malignant neoplasms (AU)

Tumor fibroso solitario del paladar blando / Solitary fibrous tumour of the smooth palate

El tumor fibroso solitario de la cavidad oral es una entidad extremadamente infrecuente y difícil de diagnosticar por su amplia diversidad morfológica, especialmente cuando se trata de biopsias de pequeño tamaño por su similitud con numerosas lesiones mesenquimales como el hemangiopericitoma. Su pronóstico es reservado por los pocos casos reportados, debiéndo basarse en la localización y tamaño del tumor (AU)

The solid fibrous solitary tumour of the oral cavity is an extremely rare entity. It is also of complicated diagnosis because of its extensive morphologic diversity (especially when there is a small amount of biopsied tissue) and because of its similarity to many mesenchymal injuries, mostly with hemangiopericytoma. The prognosis is reserved because of the few cases reported, mainly depending on tumour location and size (AU)

Utilidad del análisis inmunohistoquímico de diversos marcadores moleculares en la caracterización del carcinoma papilar de tiroides con metástasis linfáticas iniciales / Usefulness of the immunohistochemical analysis of several molecular markers in the characterization of papillary thyroid carcinoma with initial lymph node metastasis

Introducción y objetivo En el carcinoma papilar de tiroides, la detección de metástasis linfáticas (ML) en la región cervical es frecuente, observándose en cerca de la mitad de los casos en el momento del diagnóstico. El objetivo del estudio es analizar mediante técnica inmunohistoquímica la expresión combinada de diversas moléculas con el fin de establecer las características de aquellos casos con mayor tendencia a desarrollar ML. Pacientes y métodos Treinta y cinco pacientes con carcinoma papilar de tiroides fueron distribuidos en 2 grupos. El grupo i incluyó 19 pacientes que no presentaron ML al diagnóstico. En el grupo ii se incluyeron 16 pacientes en los cuales se había demostrado la presencia de ML. En todos los casos se practicó tinción inmunohistoquímica para RET/PTC, receptor del factor de crecimiento epidérmico (EGFR), p16INk4a, p21cip1, p27kip1, BCL2 y pAKT. Resultados No se apreciaron diferencias en ambos grupos en relación a p21cip1, p27kip1, p16INk4a, Bcl-2 y pAKT. No obstante, se observaron diferencias de expresión para RET/PTC y para EGFR, siendo ambas más frecuentes en los pacientes con ML. Asimismo se vio que la doble positividad de RET/PTC y el EGFR discriminaba de manera significativa los casos con ML. Finalmente, la triple combinación: RET/PTC negativo, EGFR negativo y p16INk4a negativo no se daba en ningún paciente del grupo ii y en casi la mitad del grupo i. Conclusiones El estudio de la expresión de diversas moléculas de manera combinada puede resultar eficaz en la caracterización fenotípica del carcinoma papilar de tiroides. Con ello se podría mejorar el manejo de los pacientes con cáncer de tiroides (AU)

Introduction and objective Regional lymph node metastases (LNM) are a common finding in papillary thyroid cancer (PTC). Approximately half of patients have LNM at diagnosis. The aim of this study was to analyze immunohistochemically the combined expression of different PTC-related molecules in order to identify cases with a tendency to show LNM. Patients and methods Thirty-five patients were included in the study. The patients were distributed in two groups. Group I included 19 patients with no histological evidence of LNM at diagnosis. Group II included 16 patients with histological evidence of cervical LNM. Samples were stained for RET/PTC, EGFR, p16INk4a, p21cip1, p27kip1, BCL2, and pAKT. Results Expression of p21cip1, p27kip1, p16INk4a, Bcl-2, and pAKT showed no differences between the two groups. However, RET/PTC and EGFR expression showed significant differences: in both cases, staining was more frequent in patients with LNM. Simultaneous positivity of RET/PTC and EGFR was a discriminative marker in patients with LNM. Finally, the combination of RET/PTC negative, EGFR negative and p16INk4a negative was found in none of the patients with LNM but in nearly half of those in group I. ConclusionsI mmunohistochemical analysis of several molecular markers could be useful in the phenotypic characterization of PTC. Application of these markers could enhance diagnosis and improve the management of patients with thyroid cancer (AU)

Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras / Idiotype vaccines in the treatment of follicular lymphoma: current status and future perspectives

El linfoma folicular (LF) está considerado como elsegundo tipo de linfoma no-Hodgkin más común, representandomás del 20% del total de los linfomas. Es unaenfermedad de progresión lenta y curso indolente enla que, a pesar de la buena respuesta al tratamiento,las recaídas son muy frecuentes y cada vez es más difícilconseguir respuestas completas. Por ello, se puedeconsiderar que hasta el momento, el LF es incurable.La búsqueda continua de nuevas estrategias terapéuticasen enfermedades neoplásicas, junto con un mejorconocimiento del sistema inmunitario, ha llevado ala aparición de una nueva disciplina, conocida con elnombre de inmunoterapia, que aprovecha la capacidaddel sistema inmunitario de atacar lo extraño sin dañarlo propio. El LF es un tumor muy apropiado para estetipo de tratamiento por presentar un antígeno específicode tumor: el idiotipo de la inmunoglobulina monoclonalexpresada en la membrana de todas las célulastumorales. Se han realizado diversos estudios en losque se ha probado la inmunoterapia como tratamientocomplementario al tratamiento convencional. Recientemente,nuestro grupo ha publicado un estudio en el quese observa claramente que los resultados que se obtienentras la vacunación idiotípica, cuando se consigue lainmunización adecuada del paciente, son mejores quelos obtenidos con quimioterapia sola. En este sentido,es necesario seguir investigando para aclarar si la vacunaciónidiotípica pudiera no sólo mantener remisionescompletas duraderas en los pacientes vacunados, sinoincluso conseguir la curación de los mismos. Por ello,resulta interesante abordar un mejor planteamiento delos ensayos clínicos, la mejora de la producción de lavacuna y el estudio de mecanismos de la célula tumoralcapaces de modificar la inmunoglobulina específica del tumor(AU)

Follicular lymphoma is the second most prevalentnon-Hodgkin lymphoma, representing 20% of all lymphomas.Follicular lymphoma is an indolent diseasewith a slow progression in which, although exhibitinga good response to treatment, relapse is very frequentand complete remission is not easy to maintain. Therefore,the disease is regarded as incurable. The searchfor new therapeutic strategies, together with a betterunderstanding of the immune system, has led to theemergence of a new treatment named immunotherapy.Follicular lymphoma is a malignancy suitable for thiskind of treatment given the fact that it is characterizedby presenting a unique tumour-specific antigen: theidiotype of the monoclonal immunoglobulin displayedon the membrane of tumour cells. Several studies havebeen conducted to test immunotherapy as complementaryto conventional treatment. In a previous study byour group, a clear benefit was evident is obtained afteridiotypic vaccination, when an adequate immunizationof the patient is obtained, in comparison to chemotherapyalone. In this sense, analysis is needed of whetheridiotypic vaccination can produce not only long-lastingand complete remission, but even cure. It would be ofgreat interest to consider an optimisation of the experimentaldesign of clinical trials, an improvementof vaccine production, and the study of the molecularmechanisms of the tumour cell which modify the targetimmunoglobulin(AU)

Apoptosis y liquen plano oral. Situación actual / Apoptosis and oral lichen planus. Actual state

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria crónica, con una etiología aún desconocida, de base autoinmune, que suele cursar con manifestaciones orales, con una clínica e histología características y de curso evolutivo benigno, pero susceptible de transformación maligna. En los últimos años se ha investigado la relación entre su patogenia y los mecanismos apoptóticos de destrucción celular. Material y método: Búsqueda bibliográfica en el servidor de la U.S. National Library of Medicine and the National Institutes of Health (Pubmed) con las palabras clave “apoptosis AND oral lichen planus”. Discusión: Existen diferentes estudios que evalúan la relación de los diferentes marcadores apoptóticos (TNF-α, bcl-2, Fas, p53, BMP-4, granzima B, MMP…) con la patogenia, evolución, clínica y malignización del LPO. Para la determinación de estos factores se emplean técnicas de anatomía patológica e inmunohistoquímica(TUNEL, PCR,…).Conclusión: no existe consenso en los resultados y las consiguientes conclusiones obtenidas en los diferentes estudios sobre la influencia de cada uno de los marcadores apoptóticos en el desarrollo de las lesiones de LPO. Es necesaria una mayor y más profunda investigación en búsqueda de un factor siempre asociado a las formas clínicas agresivas con mayor tendencia a la malignización (AU)

Oral lichen planus (OLP) is a mucocutaneous inflammatory chronic disease, with unknown etiology, autoinmune, usually associated with characteristical oral manifestations. Despite it has a benign evolution, is possible to become malign. Lately, relation between the pathogenesis and apoptotic cells destroy has been investigated. Methods: A bibliography survey was carried out with the U.S. National Library of Medicine and the National Institutes of Health (Pubmed) with the keywords “apoptosis AND oral lichen planus”. Discussion: Several trials evaluate the relationship among several apoptotic markers (TNF-α, bcl-2, Fas, p53,BMP-4, granzyme B, MMP…) and OLP pathogenesis, evolution, clinic and malignization. These studies employed histology and immunohistochemistry (TUNEL, PCR)Conclusion: Lack of consensus on results and conclusions about the influence of each apoptotic marker in the OLP development. Further investigation is required to obtain an apoptotic marker strongly associated with aggressive clinic and high-risk of malignancy (AU)

Mecanismos de muerte celular y su relevancia clínica / No disponible

No disponible