AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer

Background Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs. Methods Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot. Results The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C. Conclusion This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells (AU)

NIMA-related kinase-6 (NEK6) as an executable target in cancer

Cancer is a disease that develops when cells begin to divide uncontrollably and spreads to other parts of the body. Proliferation and invasion of cancerous cells are generally known to be influenced by cell cycle-related proteins in human malignancies. Therefore, in this review, we have emphasized on the serine/threonine kinase named NEK6. NEK6 is been deliberated to play a critical role in mitosis progression that includes mitotic spindle formation, metaphase to anaphase transition, and centrosome separation. Moreover, it has a mechanistic role in DNA repair and can cause apoptosis when inhibited. Past studies have connected NEK6 protein expression to cancer cell senescence. Besides, there are reports relating NEK6 to a range of malignancies including breast, lung, ovarian, prostate, kidney, liver, and others. Given its significance, this review attempts to describe the structural and functional aspects of NEK6 in various cellular processes, as well as how it is linked to different forms of cancer. Lastly, we have accentuated, on some of the plausible inhibitors that have been explored against NEK6 overexpression (AU)

CDC7 as a novel biomarker and druggable target in cancer

Due to the bottlenecks encountered in traditional treatment for tumor, more effective drug targets need to be developed. Cell division cycle 7 kinase plays an important role in DNA replication, DNA repair and recombination signaling pathways. In this review, we first describe recent studies on the role of CDC7 in DNA replication in normal human tissues, and then we integrate new evidence focusing on the important role of CDC7 in replication stress tolerance of tumor cells and its impact on the prognosis of clinical oncology patients. Finally, we comb through the CDC7 inhibitors identified in recent studies as a reference for further research in clinical practice. (AU)

The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway

PurposeThe long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC.MethodsLINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay.ResultsLINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC.ConclusionLINC00261 regulates PC cell metastasis through the “KLF13-LINC00261-mTOR-P70S6K1-S6” signaling pathway, which provides a significant set of potential PC therapeutic targets.

Síndrome de Joubert: incidencia y descripción clinicorradiológica de una serie genotipada de siete casos / Joubert syndrome: incidence and clinicoradiological description of a genotyped series of seven cases

Introducción: El síndrome de Joubert se produce por una alteración de las proteínas ciliares esenciales para la estructura y la función de neuronas y órganos como los riñones, el hígado, la retina y el oído. Se conocen unas 34 mutaciones en la actualidad. Objetivo: Calcular la incidencia/prevalencia y describir el fenotipo/genotipo y las alteraciones clinicorradiológicas de esta ciliopatía en nuestra área de salud. Pacientes y métodos: Revisamos las historias clínicas con diagnóstico de síndrome de Joubert en los últimos 10 años para recoger el fenotipo, las características radiológicas y las manifestaciones extraneurológicas en relación con la alteración genética detectada. Resultados: Se incluyeron siete casos, de los cuales cinco eran varones (6-17 años). Presentaban seis mutaciones diferentes. Fue constante la hipotonía, los dedos finos/largos y el retraso en el desarrollo psicomotor. Presentaban rasgos dismórficos, retraso mental, apraxia ocular y nistagmo indistintamente, 3/7; apnea/hiperpnea neonatal, 2/7; hipoplasia de vermis, 7/7; síndrome del molar, 6/7; elongación-adelgazamiento de los pedúnculos cerebelosos, 2/7; estrechez en la unión pontomesencefálica, 6/7, y fastigio del IV ventrículo alto, 4/7. Entre las complicaciones somáticas había: retinopatía, 2/7; coloboma retiniano, 1/7; fibrosis hepática, 1/7; nefronoptisis, 1/7, y quiste renal 1/7. Conclusiones: La incidencia del síndrome de Joubert fue de al menos 1/20.000 recién nacidos/año. Las alteraciones radiológicas pontomesencefálicas y pedunculares fueron constantes. La hipotonía, el retraso psicomotor y los dedos finos/largos afectaron a todos los casos.(AU)

Introduction: Joubert syndrome is produced by an alteration of the ciliary proteins essential for the structure and function of neurons and organs such as the kidneys, liver, sight, and hearing. Some 34 mutations are currently known. Objective: Calculate the incidence / prevalence, describe the phenotype / genotype and radiological alterations of this ciliopathy in our health area. Patients and methods: We reviewed the medical records with a diagnosis of Joubert Syndrome in the last 10 years to collect phenotype, radiological characteristics, and extra-neurological manifestations in relation to the genetic alteration detected. Results: 7 cases were included: 5 children (6 -17 years). They had 6 different mutations. Hypotonia, thin / long fingers and delayed psychomotor development were constant. They presented dysmorphic features, mental retardation, ocular apraxia, and nystagmus indistinctly in 3/7; Neonatal apnea/hyperpnea 2/7; hypoplasia of vermis 7/7; Molar syndrome was evident in 6/7 and in 2/7 there was elongation-thinning of cerebellar peduncles. Pontomesencephalic junction tightness 6/7; fastigium of the IV ventricle high in 4/7. Among the somatic complications, retinopathy 2/7, retinal coloboma 1/7, liver fibrosis 1/7, nephronoptysis 1/7 and renal cyst 1/7. Conclusions: The incidence of Joubert syndrome was at least 1 / 20,000 newborns / year. The pontomesencephalic and peduncular radiological alterations were constant. Hypotonia, psychomotor retardation, and thin / long fingers affected all cases.(AU)

Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética / Megalencephalic leukoencephalopathy with cysts -the clinical importance in the genetic era

INTRODUCCIÓN: La leucoencefalopatía megalencefálica con quistes es una leucodistrofia de origen genético que produce una alteración de la homeostasis del agua e iones en el cerebro, generando formas vacuolares y edema crónico en la sustancia blanca con deterioro neurológico progresivo. Debe sospecharse en los lactantes que presentan macrocefalia progresiva durante el primer año de vida, retraso motor y hallazgos característicos en la resonancia magnética cerebral. CASO CLÍNICO: Niña en seguimiento desde los 9 meses por macrocefalia progresiva y retraso del desarrollo psicomotor con presencia en la resonancia magnética cerebral de hallazgos compatibles con leucoencefalopatía megalencefálica con quistes, y aparición de epilepsia en su evolución. Los estudios genéticos habituales (secuenciación de nueva generación y array) fueron negativos, pero, al cumplir los criterios diagnósticos, se procedió al estudio del ARN mensajero y el ADN complementario, que confirmó la presencia de dos variantes patogénicas en MLC1. CONCLUSIONES: La leucoencefalopatía megalencefálica con quistes es una entidad infrecuente. Es característica la macrocefalia progresiva en el primer año de vida, la ausencia de deterioro o deterioro lento, y la posibilidad de desarrollar epilepsia, espasticidad y ataxia en su evolución. Cobra importancia en dichos pacientes la realización de una prueba de imagen que muestre hallazgos propios de la entidad, lo que, junto con la clínica, permite diferenciarla de otras leucodistrofias y establecer un diagnóstico confirmatorio. Los estudios genéticos pueden constatar la mutación asociada que posibilita predecir el fenotipo clinicorradiológico

INTRODUCTION: Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans. CASE REPORT: We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development. The usual genetic studies (new generation sequencing and array) were negative, but as the diagnostic criteria were met, a complementary messenger RNA and DNA study was conducted, which confirmed the presence of two pathogenic variants in MLC1. CONCLUSIONS: Megalencephalic leukoencephalopathy with cysts is a rare condition. Progressive macrocephaly in the first year of life, the absence of deterioration or slow deterioration, and the possibility of developing epilepsy, spasticity and ataxia are characteristic signs in its course. It is important for these patients to undergo an imaging test that shows findings that characterise this condition, which, together with the clinical features, makes it possible to differentiate it from other leukodystrophies and to establish a confirmatory diagnosis. Genetic studies can confirm the associated mutation that makes it possible to predict the clinicoradiological phenotype

Phosphate: from stardust to eukaryotic cell cycle control

Phosphorus is a pivotal element in all biochemical systems: it serves to store metabolic energy as ATP, it forms the backbone of genetic material such as RNA and DNA, and it separates cells from the environment as phospholipids. In addition to this 'big hits', phosphorus has recently been shown to play an important role in other important processes such as cell cycle regulation. In the present review, we briefly summarize the biological processes in which phosphorus is involved in the yeast Saccharomyces cerevisiae before discussing our latest findings on the role of this element in the regulation of DNA replication in this eukaryotic model organism. We describe both the role of phosphorus in the regulation of G1 progression by means of the Cyclin Dependent Kinase (CDK) Pho85 and the stabilization of the cyclin Cln3, as well as the role of other molecule composed of phosphorus-the polyphosphate-in cell cycle progression, dNTP synthesis, and genome stability. Given the eminent role played by phosphorus in life, we outline the future of phosphorus in the context of one of the main challenges in human health: cancer treatment (AU)

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The expression of Nek7, FoxM11, and Plk1 in gallbladder cancer and their relationships to clinicopathologic features and survival

PURPOSE: Gallbladder carcinoma (GC) is generally considered as a relatively rare malignancy with poor prognosis. In order to guide clinicians in selecting suitable treatment for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the expression of Polo-like kinase 1 (Plk1), Nima related kinases 7 (Nek7) and Forkhead box M1 (FoxM1) in GC tissues and their relationship to clinicopathologic features and survival. METHODS: We immunohistochemically investigated the 76 specimens of gallbladder carcinoma, pericarcinoma and normal tissues using Nek7, FoxM1 and Plk1 antibodies and analyzed the overall survival time of these 76 patients. RESULTS: There were significant correlations between the high level expression of Nek7, FoxM1 and Plk1 and the tumor differentiation, Nevin staging and metastasis. The high level expression of Nek7, FoxM1 and Plk1 was significantly associated with shorter overall survival time in univariate analysis (log-rank test), also identified as an independent prognostic factor in multivariate analysis. CONCLUSION: Nek7, FoxM1 and Plk1 were significantly associated with certain clinicopathologic indices in GC. Evaluation of Nek7, FoxM1 and Plk1 expression may be an important factor in identifying a group of poor GC prognosis (AU)

Bases moleculares de la hiperplexia hereditaria / Molecular bases of hereditary hyperekplexia

Introducción. La hiperplexia es un síndrome clínico poco común caracterizado por sobresaltos enérgicos y generalizados en respuesta a estímulos triviales generalmente acústicos o táctiles. La hiperplexia hereditaria se manifiesta justo despuésdel nacimiento y los afectados tienen, durante el período perinatal, un alto riesgo de sufrir muerte súbita, debido a episodios de espasmos laríngeos y fallos cardiorrespiratorios. Objetivo. Revisar las bases genéticas y moleculares, conocidas hasta el momento, subyacentes a la hiperplexia hereditaria. Desarrollo. Aproximadamente en el 30% de los pacientes con hiperplexia hereditaria se ha identificado una mutación génica en el cromosoma 5q32. Este gen codifica la subunidad alfa del receptor de glicina sensible a estricnina, el cual regula el tono muscular en el tallo cerebral y la médula espinal, zonas donde desempeñan un papel fundamental las interneuronas inhibidoras glicinérgicas. El 70% de los pacientes con hiperplexia hereditaria no tiene mutaciones en el receptor de glicina, lo que sugiere que otros genes podrían estar implicados en la enfermedad. Recientemente se han encontrado mutaciones en el gen humano del transportador neuronal de glicina GLYT2 en familias con miembros diagnosticados de hiperplexia. Conclusiones. La hiperplexia hereditaria es una enfermedad genética compleja, en la que intervienen diferentes genes que codifican proteínas de vías glicinérgicas inhibidoras. Las proteínas más importantes implicadas en la hiperplexia son el receptor de glicina (GlyR) y el transportador neuronal de glicina GLYT2. No sedescarta la implicación en la enfermedad de otras proteínas que interaccionen con GlyR o con GLYT2, tales como proteínas asociadas, proteínas de andamiaje o proteínas reguladoras

Introduction. Hereditary hyperekplexia is a rare clinical syndrome typically characterized by sudden and generalized startle in response to trivial but unexpected tactile or acoustic stimulations. Typically it is accompanied by a temporally but complete muscular rigidly, and usually it manifests shortly after birth. Some affected infants die suddenly from lapses incardiorespiratory function. Mental development usually is normal. Aim. To summarize and update the molecular bases underlying the hereditary hyperekplexia syndrome. Development. Approximately 30% of the individuals suffering hereditary hyperekplexia show mutations on a gene located on chromosome 5q32 with a dominant or recessive trait. This gene encodes the alpha subunit of the strychnine-sensitive glycine receptor, which plays a crucial role in inhibitory glycinergic neurotransmissionthat process sensory and motor information. About 70% of the patients with hyperekplexia do not show geneticdefects in the glycine receptor gene; this suggested that additional genes might be affected in this disease. Recent studies have reveals that mutations in the neuronal glycine transporter GLYT2 are a second major cause of hyperekplexia. Conclusions. Hereditary hyperekplexia is a complex genetic disease in which several genes can be implicated, all of them directly orindirectly involved in inhibitory glycinergic neurotransmission. Two major proteins involved in hyperekplexia are the strychninesensitive glycine receptor (GlyR) and the neuronal glycine transporter GLYT2. Implication of secondary additional accompanyingor interacting proteins in glycinergic terminals are not ruled out

Biología molecular de los glioblastomas / Biology molecular of glioblastomas

La formación de los glioblastomas es muy diversa, pudiendo presentarse de “novo” o provenir de recidivas de astrocitomas que van progresando hacia mayores grados de malignidad. La alteración molecular más frecuente que se encuentra en estos tipos tumorales es la pérdida de heterocigocidad del cromosoma 10en el que se han identificado varios genes supresores de tumores. Las vías genéticas TP53/MDM2/ P14arf yCDK4/RB1/P16ink4 implicadas en división celular, se encuentran desreguladas en la mayoría de los gliomas así como los genes que promueven la división celular, entre ellos EGFR. Por último el aumento de factores decrecimiento y angiogénicos también está involucrado en el desarrollo de estos tipos tumorales. Uno de los objetivos de la biología molecular en tumores de estirpeglial es intentar encontrar marcadores o alteraciones genéticas que permitan abordar mejor la clasificación de los glioblastomas, su evolución y pronóstico así como su tratamiento. La diversidad y la cantidad de las alteraciones moleculares presentes en glioblastomas probablemente sea el motivo por el que todavía no se han encontrado fármacos efectivos para combatirlos. En la actualidad, con la aparición de nuevas técnicas de biología molecular, se puede intentar individualizar y clasificara los pacientes en función de su expresión génica. Esto abre una ventana esperanzadora a la aparición de nuevos fármacos que tengan como diana exclusiva a los genes y/o proteínas alterados de las células tumorales en función de su patrón de expresión génica individualizado para cada tumor. En este artículo revisamos los mecanismos moleculares más frecuentes en la patogénesis de los glioblastomas

Glioblastomas, the most frequent and malignant human brain tumors, may develop de novo (primaryglioblastoma) or by progression from low-grade or anapalsic astrocytoma (secondary glioblastoma). The molecular alteration most frequent in these tumor like types is the loss of heterozygosity on chromosome 10,in wich several genes have been identified as tumors suppressor. The TP53/MDM2/P14arf and CDK4/RB1/P16ink4 genetic pathways involved in cycle control are deregulated in the majority of gliomas as well as genes that promote the cellular division, EGFR. Finally the increase of growth and angiogenics factors is also involved in the development of glioblastomas. One of the objetives of molecular biology in tumors of glial an cestryis to try to find the genetic alterations that allow to approach better the classification of glioblastomas, its evolution prediction and treatment. The new path molecular classification of gliomas should improve the old one, especially being concerned about the oncogenesis and heterogenity of these tumors. It is desirable that this classification had clinical applicability and integrates new molecular findings with some known histological features with prognostic value. In this paper we review the most frequent molecular mechanisms involved in the patogenesis of glioblastomas

Therapeutic opportunities to control tumor cell cycles

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Tumor cell proliferation is frequently associated togenetic or epigenetic alterations in key cell cycleregulators. Most human tumors deregulate thispathway to sustain proliferation with independenceof external mitogenic factors. In addition, the alterationof cell cycle proteins may confer genomic instabilitythat results in additional mutations inthese tumor cells. The frequent alteration of the cellcycle in tumor cells has launched the identificationfor critical cell cycle regulators as anticancer targets.The inhibition of some cell cycle kinases suchas cyclin-dependent kinases (CDKs) or the Auroraand Polo mitotic kinases is currently under study inseveral preclinical and clinical trials. Similarly, theclinical success of microtubule poisons such as taxolhas promoted new applied research in mitosisregulation. Recent investigations have suggestednew targets of interest including additional kinases,phosphatases and other mitotic regulators such asmicrotubule motor proteins (kinesins). Currrent researchin this area will undoubtedly result in newand improved targeted therapies for cancer treatment

Valor pronóstico de progresión de las moléculas reguladoras del ciclo celular en tumores vesicales T1G3 / Prognostic value for progression of the regulating proteins of the cellular cycle in PT1G3 bladder tumours

Introducción y Objetivos: El tumor vesical T1G3 constituye el grupo de tumores superficiales más agresivo. Nuevos factores pronósticos en el campo de la citogenética y la biología molecular han sido analizados, con resultados a menudo contradictorios, siendo escasos los trabajos específicos en tumores T1G3. Nuestro objetivo es determinar si en este grupo de tumores los marcadores inmunohistoquímicos presentan valor predictivo de progresión clínicamente útil, y por tanto con validez para indicar una actitud terapéutica precoz más idónea. Material y Métodos: Estudio retrospectivo de una serie de 83 pacientes afectos de tumor vesical T1G3, sobre los que analizamos un total de 14 variables; entre los nuevos factores predictivos: la determinación inmunohistoquímica de las proteínas reguladoras del ciclo celular: p53, p21 y bcl-2, así como la proteína Ki-67 como marcador de proliferación celular. Mediante análisis de regresión logística establecemos las variables pronósticas independientes para progresión tumoral. Resultados: El punto de corte establecido para Ki67 y p53 fue el 40% de células inmunomarcadas, 20% para p21 y10% para Bcl-2. El análisis univariante puso de manifiesto diferentes tasas de progresión y tiempos libres de progresión en función de la inmunotinción de Ki67 y p53; sin embargo, la regresión logística demostró que solo la inmunohistoquímica de p53 presentaba valor predictivo independiente. Conclusiones: La determinación inmunohistoquímica de p53 presenta valor predictivo de progresión clínicamente útil en tumores vesicales T1G3, de manera que su determinación puede constituir un factor fundamental en las estrategias de tratamiento de estos tumores (AU)

Introduction and objective: Bladder tumor T1G3 constitutes the group of superficial tumors more aggressive. New prognostic factors in the field of the cytogenetics and molecular biology have been analyzed, with often contradictory results, being little the specific works in tumors T1G3. Our objective is to determine if in this group of tumors the immunohistochemical markers present predictive value of clinically useful progression, and therefore with validity to indicate more suitable a precocious therapeutic attitude. Material and methods: Retrospective study of a series of 83 patients affected of bladder tumor T1G3, on which we analyzed a total of 14 variables; between the new predictive factors: the immunohistochemical determination of regulating proteins of the cellular cycle: p53, p21 and bcl-2, as well as the Ki-67 protein like marker of cellular proliferation. By means of logistic regression analisys we establish the independent prognostic variables for tumor like progression. Results: The cut point established for Ki67 and p53 was 40% of inmmunomarked cells, 20% for p21 and 10% forBcl-2. The univariant analysis showed different rates from progression and free times of progression based on the immunohistochemistry of Ki67 and p53; nevertheless, the logistic regression demonstrated that single the immunohistochemistry of p53 presented independent predictive value. Conclusions: The determination of p53 presents predictive value of clinically useful progression in bledder tumorsT1G3, so that its determination can constitute a essential factor in the strategies of treatment of these tumors (AU)

Valor pronóstico de la expresión inmunohistoquímica de la proteina p21WAF1 en cáncer de laringe / Prognosis value of the immunohystochemical expression of the P21WAF1 in the larynx cancer

En este trabajo hemos estudiado la expresión inmunohistoquímica de la proteína p21WAF1 (EA10) en una serie de 195 pacientes con cáncer de laringe que fueron diagnosticados, tratados y seguidos durante al menos 5 años en el servicio de ORL del Hospital “Virgen de la Salud” (Toledo). En los casos que presentaron metástasis ganglionares analizamos también la expresión de p21WAF1 a dicho nivel. Además se ha analizado el valor pronóstico de la expresión de p21WAF1 en este tipo de tumores (desarrollo de recidivas, mortalidad por cáncer de laringe y supervivencia) y estudiamos la posible relación de dicha expresión con otros parámetros clínicopatológicos

In this paper we carried out an immunohistochemical study of protein p21WAF1 (EA 10) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at «Virgen de la Salud» Hospital (Toledo, Spain). In the cases with lymph node metastasis; we also studied p21WAF1 expression at this level. Furthermore we have analysed the value of protein p21WAF1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival (and we evaluate the relationship between p21WAF1 expression and other clinic and pathologic parameters. Keywords: p21WAFl Protein. Larynx cancerIn this paper we carried out an immunohistochemical study of bcl-2 protein expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at «Virgen de la Salud» Hospital (Toledo. Spain). In the cases with lymphonode metastasis we also analysed bcl-2 protein expression at this level. Furthermore we have studied the value of bcl-2 protein expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we analysed the relationship between bcl-2 protein expression and other clinic and pathologic parametersIn this paper we carried out an immunohistochemical study of protein Rb (G3-245) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at «Virgen de la Salud» Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied Rb expression at this level. Furthermore we have analysed the value of Rb expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between Rb expression and other clinic and pathologic parameters

Diferentes fenotipos del síndrome de Charcot-Marie-Tooth causados por mutaciones del mismo gen: ¿siguen siendo útiles los criterios de clasificación clásicos? / Different phenotypes of Charcot-Marie-Tooth disease caused by mutations in the same gene. Are classical criteria for classification still valid?

La investigación genética molecular de las neuropatías hereditarias está descubriendo continuamente nuevos genes y proteínas implicados en el funcionamiento de los nervios periféricos. Paralelamente, al profundizar en la investigación clínica, neurofisiológica y patológica y establecerse correlaciones genotipo-fenotipo en la enfermedad de Charcot-Marie-Tooth (CMT) se ha permitido conocer que algunos genes son capaces de causar indistintamente fenotipos desmielinizantes (CMT1) y axonales (CMT2). Este fenómeno cuestiona la utilidad de algunos criterios de clasificación vigentes y suscita la conveniencia de plantear nuevas estrategias para el diagnóstico. Descubrir el funcionamiento de la unidad axón-célula de Schwann será un reto para los próximos años. En esta revisión se realiza un análisis pormenorizado de las mutaciones de los genes que pueden dar lugar a fenotipos CMT1 y CMT2. Están documentadas tres formas de variabilidad genética. Mutaciones de gen MPZ originan un alelismo real, es decir, fenotipos CMT1 o CMT2 dependientes de mutaciones específicas por su localización o calidad. Mutaciones del gen GADP-1 y probablemente el gen NF-L manifiestan diferentes fenotipos, pero sólo con respecto al parámetro de la velocidad de conducción (VC). Se aportan pruebas de que la reducción de la VC en los pacientes con neuropatía GADP-1 puede ser el resultado de la pérdida axonal. Una última forma de variabilidad acontece en el CMTX, que obedece al grado de expresión clínica en mujeres relacionada con la inactivación del cromosoma X (AU)

Tumor del estroma gastrointestinal de localización anorrectal / Gastrointestinal stromal tumor located in the rectum

Los tumores del estroma gastrointestinal forman un grupo infrecuente de neoplasias. Representan únicamente el 1-2 por ciento del total de tumores del tracto digestivo y la localización anorrectal es una de las menos descritas en la bibliografía. Se presenta un caso de tumor del estroma gastrointestinal situado en la parte distal del recto y el canal anal en un varón de 44 años de edad. Se revisan los datos clínicos y de tratamiento más significativos de este tipo de neoplasias (AU)

Papel del inhibidor del ciclo celular p27durante el remodelado vascular / Role of cell cycle inhibitor p27 during vascular remodeling

Las células de la pared arterial presentan normalmente una tasa de proliferación celular muy reducida. Sin embargo, la hiperplasia de células vasculares es una característica del remodelado vascular inducido por diversos estímulos fisiopatológicos (por ejemplo, neovascularización, arteriosclerosis y re-estenosis post-angioplastia). El avance en el conocimiento de los mecanismos moleculares que controlan el crecimiento celular en la pared vascular puede facilitar el desarrollo de terapias anti-proliferativas para el tratamiento de la patología vascular obstructiva. En esta revisión se discuten estudios recientes que demuestran el papel de la proteína supresora de crecimiento p27 durante el remodelado vascular (AU)

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