A signature of 14 immune-related gene pairs predicts overall survival in gastric cancer

Objective Increasing evidence demonstrates that immune signature plays an important role in the prognosis of gastric cancer (GC). We aimed to develop and validate a robust immune-related gene pair (IRGP) signature for predicting the prognosis of GC patients. Methods RNA-Seq data and corresponding clinical information of GC cohort were downloaded from the TCGA (The Cancer Genome Atlas Program) data portal. GSE84437 and GSE15459 microarray datasets were included as independent external cohorts. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to build the best prognostic signature. All patients were classified into the high immune-risk and low immune-risk groups via the optimal cut-off of the signature scores determined by time-dependent receiver-operating characteristic (ROC) curve analysis. The prognostic role of the signature was measured by a log-rank test and a Cox proportional hazard regression model. Results 14 immune gene pairs consisting of 25 unique genes were identified to construct the immune prognostic signature. High immune-risk groups showed poor prognosis in the TCGA datasets and GSE84437 datasets as well as in the GSE15459 datasets (all P < 0.001). The 14-IRGP signature was an independent prognostic factor of GC after adjusting for other clinical factors (P < 0.05). Functional analysis revealed that DNA integrity checkpoint, DNA replication, T-cell receptor signaling pathway, and B-cell receptor signaling pathway were enriched in the low immune-risk groups. B cells naive and Monocytes were significantly higher in the high-risk group, and B-cell memory and T-cell CD4 memory activated were significantly higher in the low-risk group. The prognostic signature based on IRGP reflected infiltration by several types of immune cells. Conclusion The novel proposed clinical-immune signature is a promising biomarker for prediction overall survival in patients with GC and providing new insights into the treatment strategies (AU)

Coordination between replication, segregation and cell division in multi-chromosomal bacteria: lessons from Vibrio cholera

Bacteria display a highly flexible cell cycle in which cell division can be temporally disconnected from the replication/segregation cycle of their genome. The accuracy of genetic transmission is enforced by restricting the assembly of the cell division apparatus to the low DNA-density zones that develop between the regularly spaced nucleoids originating from the concurrent replication and segregation of genomic DNA. In most bacteria, the process is simplified because the genome is encoded on a single chromosome. This is notably the case in Escherichia coli, the most well studied bacterial model organism. However, ~10% of bacteria have domesticated horizontally acquired mega-plasmids into extra-numerous chromosomes. Most of our current knowledge on the cell cycle regulation of multi-chromosomal species derives from the study of replication, segregation and cell division in Vibrio cholerae, the agent of the deadly epidemic human diarrheal disease cholera. A nicety of this model is that it is closely related to E. coli in the phylogenetic tree of bacteria. Here, we review recent findings on the V. cholerae cell cycle in the context of what was previously known on the E. coli cell cycle (AU)

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Carcinoma colorrectal con alteración de la vía reparadora. Claves para su identificación y relevancia clínica / Mismatch-repair deficiency colorrectal carcinoma. Identification keys and clinical relevance

Un 7,5% de los carcinomas colorrectales (CCR) en España presenta alteraciones del sistema de reparación de errores de replicación del ADN (mismatch repair, MMR). De ellos, un 20% se desarrolla en pacientes que presentan el síndrome de Lynch. Para identificar a estos pacientes se utilizan criterios clínicos, moleculares, histopatológicos e inmunohistoquímicos. El análisis inmunohistoquímico de las proteínas reparadoras (MLH1, MSH2, MSH6 y PMS2) ha demostrado ser una técnica válida para la detección de tumores con alteración del MMR. La generalización del uso de la inmunohistoquímica hace que actualmente el patólogo desempeñe un papel fundamental en la identificación de pacientes con síndrome de Lynch

Colorectal carcinoma (CRC) in Spain shows mismatchrepair deficiency (MMR+) reaching a 7.5%. Twenty percent of them presents in Lynch syndrome. Identification of these patients is based on clinical, molecular, histopathologic and immunohistochemical criteria. Immunohistochemical analysis of mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2) is a valid technique to detect MMR+ tumors. The generalized use of immunohistochemistry confers to pathologists a fundamental role in the identification of patients with Lynch syndrome

DNA repair inhibitors in cancer treatment

Chemotherapy and radiation are two important modalities for cancer treatment. Many agents in clinical used have the ability to induce DNA damage, however they may be highly cytotoxic as a secondary effect. Different mechanisms are involved both, in detection and repair of DNA damage. The modulation of these pathways, has a great impact on clinical outcome and is frequently responsible of therapeutic resistance. Therefore, pharmacological inhibition of DNA damage repair pathways has been explored as a useful strategy to enhance chemo and radiosensitivity, thus it could be used for reversing drug resistance. Different agents have shown excellent results in preclinical studies in combination with radiation or chemotherapy. Early phase clinical trials are now being carried out using different DNA repair inhibitors targeting several enzymes such as PARP, DNA-PK or MGMT (AU)

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

Cuantificación de ADN como factor pronóstico en un caso de Carcinoma de células Acinares de parótida diagnosticado por PAAF / DNA quantification as prognostic factor in a case of Acinar Cell Carcinoma of the parotid gland, diagnosed by FNA

Presentamos el caso de un varón de 43 años de edad que consulta por una tumoración preauricular derecha dolorosa a la palpación que, según refiere, tiene más de tres años de evolución. Se realiza punción aspiración con aguja fina que informa de compatible con carcinoma de células acinares, por lo que se realiza cuantificación de ADN por citometría de imagen. Los parámetros biológicos estudiados (ploidía, fase S, células por encima de 5c) indican que se trata de una lesión de bajo grado de malignidad.Con estos datos se practica parotidectomía total conservadora del facial, sin vaciamiento ganglionar. El paciente se encuentra, un año después, asintomático y libre de signos tumorales residuales

Hereby we present a case of a 43-years-old male who complained of a three years history preauricular painful mass. Fine needle aspiration cytology was performed, diagnosing of compatible with acinar cell carcinoma, thus DNA quantification by image cytometry was carried out. Biological parameters studied (ploidy, S-phase, 5-c exceeding rate) showed that it is a low grade of malignancy lesion. ;;Total parotidectomy conservative of facial nerve was recommended, without regional lymphadenectomy. Patient remains, one year later, asymptomatic and free of disease

Cáncer. Panorámica general. Aspectos básicos de la epidemiología, etiología, genética y diagnóstico / Cancer. General environment. Basic aspects of epydemiology, aetiology, genetics and diagnosis

El cáncer infantil es raro, representando menos del 1% de todas las enfermedades malignasdiagnosticadas anualmente, pero es la enfermedad que origina más muertes entre los0 y los 14 años de edad, con una incidencia de 140/1.000.000 niños. La supervivencia globalactual ha sobrepasado el 75%. Los principales avances en la investigación del cáncerhan tenido lugar en los campos de la Genética y la Biología Molecular, en el conocimientode los mecanismos moleculares que dan origen al cáncer a nivel celular. Eso ha contribuidoa un mejor diagnóstico y tratamiento. Se comentan las bases epidemiológicas de los diferentestipos de cáncer infantil, su etiología tanto en sus aspectos genético como medioambiental,así como las enfermedades familiares hereditarias que predisponen al cáncer. Finalmentese comentan aspectos prácticos sobre el diagnóstico del cáncer infantil en AtenciónPrimaria

Childhood cancer is rare, comprising less than 1% of all malignancies diagnosed eachyear, but it is the disease that originates more deaths in children 0-14 years of age, with anannual incidence of 140/1,000,000 children. Actual survival has surpassed 75%. The principaladvances in cancer research have taken place in Genetics and Molecular Biology, inthe knowledge of the molecular mechanisms that originate cancer at the cellular level. Thishas contributed to a better diagnosis and treatment. The epidemiological bases of the differenttypes of childhood cancer, its etiology both in its genetic and environmental aspectsand the familial hereditary cancer predisposing syndromes are discussed. Finally, practicalclues about childhood cancer diagnosis in paediatric primary care are commented

Tetraciclinas, sulfamidas y metronidazol / Tetracyclines, sulfonamides and metronidazole

Las tetraciclinas constituyen un grupo de productos naturales y semisintéticos que actúa inhibiendo la síntesis de las proteínas bacterianas. Son agentes bacteriostáticos, con actividad frente a una gran variedad de organismos, pero de limitado uso en la actualidad a causa de la resistencia adquirida. Doxiciclina es la más utilizada actualmente en medicina humana y constituye uno de los medicamentos esenciales de la Organización Mundial de la Salud. Las sulfamidas son antibióticos sintéticos, bacteriostáticos, de amplio espectro. Fueron los primeros agentes antimicrobianos sistémicos eficaces. Su mecanismo de acción se basa en la inhibición de la síntesis del ADN bacteriano. Debido a su toxicidad y elevada resistencia adquirida su uso actualmente es muy escaso. El metronidazol es el principal componente de la familia de los 5-nitroimidazoles. Es un antibiótico con gran actividad bactericida frente a anaerobios y algunos microaerófilos y continúa siendo muy útil en el tratamiento de infecciones bacterianas y parasitarias (AU)

Efecto antimitogénico de extractos de Pygeum africanum sobre líneas celulares de cáncer de próstata humana y explantes de hiperplasia benigna de próstata / Antimytogenic effect of Pygeum africanum extracts on human prostate cancer cell lines and benign prostatic hyperplasia explants

OBJETIVOS: Analizar el efecto de extractos de Pygeum africanum sobre la proliferación de células de próstata humana, in vitro. MÉTODOS: Líneas celulares tumorales prostáticas, así como células epiteliales derivadas de hiperplasia benigna de próstata fueron puestas en cultivo y tratadas con extractos de P. africanum. El efecto sobre la proliferación celular fue monitorizado mediante incorporación de (3H)-timidina o bromodesoxiuridina y ensayos de citometría de flujo. RESULTADOS: La incubación con extractos de P. africanum, con o sin adición de aminoácidos, inhibe significativamente y de forma dosis-dependiente la proliferación de las líneas celulares derivadas de cáncer de próstata LNCaP, PZ-HPV-7, y CA-HPV-10. En las células PZ-HPV-7, los extractos de P. africanum contrarrestan la acción mitogénica de EGF y bloquean la transición G1 a S del ciclo celular. Los extractos de P. africanum ejercen también una potente acción antimitogénica sobre células epiteliales que derivan de explantes de hiperplasia benigna de próstata. CONCLUSIONES: Los extractos etanólicos de P. africanum tienen un efecto antimitogénico sobre células tumorales prostáticas y sobre células epiteliales derivadas de hiperplasia benigna de próstata. Dicho efecto está asociado a la inhibición de la acción mitogénica de EGF y se acompaña de una disminución de la entrada de las células en la fase S del ciclo celular (AU)

Efecto diferencial de los análogos de la vitamina D en la proliferación de células de músculo liso vascular / Vascular and tissue calcifications in haemodialysis patients

Existen datos experimentales contradictorios respecto al comportamiento de las células de músculo liso vascular (CMLV) expuestas al calcitriol. Determinar el efecto del calcitriol y de sus análogos a nivel vascular tiene una considerable trascendencia clínica ya que la proliferación de las CMLV está implicada en el mecanismo patogénico de la arteriosclerosis y de la resistencia tras angioplastia. En este trabajo demostramos mediante incorporación de BrdU que el calcitriol estimula la proliferación en las CMLV. La proliferación es menor al añadir al medio de cultivo Paracalcitol o EB1089 a dosis equimolar. En concordancia con estos hechos, también observamos que el calcitriol induce la expresión del mRNA VDR mientras que no existe este efecto con ninguno de los análogos estudiados. En conclusión, el calcitriol tiene un efecto directo estimulador de la proliferación de las CMLV que no se observa con el Paracalcitol y EB1089 a concentración equimolar (AU)

Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. The excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion. The direct effect of calcitriol and vitamin D analogs on the VSMCs proliferation is not clear. In this study we have analysed if calcitriol, Paracalcitol (19-nor-1,25-dihydroxyvitamin D2) and EB1089 (experimental analog used as anticancerous) modify proliferation and the expression of vitamin D receptor (VDR) gene that is regulated at the transcriptional level by itself in the VSMCs. VSMCs proliferation was analysed by BrdU incorporation and VDR gene expression using RT-PCR. VSMCs proliferation was stimulated when calcitriol was added to the culture. VSMCs proliferation was significantly lower with analogs at the same dose. With regard to the functional study, the expression of VDR gene was upregulated by calcitriol at a concentration of 100 nM. There were no changes in this expression with the analogs. In conclusion, calcitriol, do not modify VSMCs proliferation. Therefore, Paracalcitol could have a minor proliferating effect on the wall of vessels that vitamin D (AU)