Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients

Background: Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients. Methods: 104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated. Results: Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03). Conclusions: The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites. Our results suggest that detection of tumour emboli and assessment of global vessel density using the D2-40 antibody, may be useful in the clinical practice, as predictors of reduced survival among pN0 laryngeal carcinoma patients

Estimates of the Prevalence and Number of Fibromyalgia Syndrome Patients and Their Alpha-1 Antitrypsin Phenotypic Distributionin Ten Countries

During the last few years, clinical, epidemiological, and pathological evidence has suggested that inherited alpha-1 antitrypsin [AAT] deficiency might play a role in the development of the fibromyalgia syndrome [FMS], probably because of the loss of AAT anti-inflammatory efficacy. The objective of this study was to estimate the prevalence and number of FMS patients, and their AAT phenotypic distribution worldwide. Methods: A critical review selecting reliable studies on the subject. Results: Studies on AAT gene frequencies and FMS prevalence were retrieved for ten countries worldwide, namely Canada, the United States of America [USA], Denmark, Finland, Germany, Italy, the Netherlands, Spain, Sweden, and Pakistan. The severe deficiency Z allele was found in all these countries, with very high frequencies in Denmark and Sweden [23 and 27 per 1,000, respectively], high frequencies in Italy and Spain [16 and 17], intermediate frequencies in Germany, the Netherlands, Canada, and the USA [10 to 14], and a low frequency in Pakistan [nine per 1,000]. The calculated prevalence of AAT deficiency and the number of FMS patients with AAT deficiency were 1/10 and 25,408 in Canada, 1/11 and 478,681 in the US, 1/9 and 3,124 in Denmark, 1/ 36 and 726 in Finland, 1/16 and 48,523 in Germany, 1/13 and 84,876 in Italy, 1/15 and 9,639 in the Netherlands, 1/4 and 114,359 in Spain, 1/11 and 9,065 in Sweden, and 1/25 and 85,965 in Pakistan. Our calculations predict that AAT deficiency would remain undetected in around nine percent of FMS patients, with about eight percent of them carrying moderate deficiency phenotypes [MS, SS, and MZ], and less than one percent with severe deficiency phenotypes [SZ and ZZ]. Conclusions: Therefore, AAT phenotype characterization should be recommended in FMS patients and the possible efficacy of AAT replacement therapy in severe deficiency FMS patients should warrant further studie

Identifying the most suitable endogenous control for determining gene expression in hearts from organ donors

BACKGROUND: Quantitative real-time reverse transcription PCR (qRT-PCR) is a useful tool for assessing gene expression in different tissues, but the choice of adequate controls is critical to normalise the results, thereby avoiding differences and maximizing sensitivity and accuracy. So far, many genes have been used as a single reference gene, without having previously verified their value as controls. This practice can lead to incorrect conclusions and recent evidence indicates a need to use the geometric mean of data from several control genes. Here, we identified an appropriate set of genes to be used as an endogenous reference for quantifying gene expression in human heart tissue. RESULTS: Our findings indicate that out of ten commonly used reference genes (GADPH, PPIA, ACTB, YWHAZ, RRN18S, B2M, UBC, TBP, RPLP and HPRT), PPIA, RPLP and GADPH show the most stable gene transcription levels in left ventricle specimens obtained from organ donors, as assessed using geNorm and Normfinder software. The expression of TBP was found to be highly regulated. CONCLUSION: We propose the use of PPIA, RPLP and GADPH as reference genes for the accurate normalisation of qRT-PCR performed on heart tissue. TBP should not be used as a control in this type of tissue

Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

This work was supported in part by the Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (grant PI051564). The University Institute of Oncology of Asturias is supported by Obra Social Cajastur, Asturias, Spain

Genomic analyses of microdissected Hodgkin and Reed-Sternberg cells: mutations in epigenetic regulators and p53 are frequent in refractory classic Hodgkin lymphoma

This work was supported by grants from the Plan Nacional de I + D + I cofinanced by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), PI12/1832, the Spanish Association for Cancer Research (AECC), and Programas para Grupos de Investigación de la Comunidad Autónoma de Madrid (Biomedicina 2017)

Genetic Inactivation of ADAMTS15 Metalloprotease in Human Colorectal Cancer

Grant support: Ministerio de Ciencia e Innovacón-Spain, Fundación M. Botín, and the European Union (FP7 MicroEnviMet). The Instituto Universitario de Oncología is supported by Obra Social Cajastur and Acción Transversal del Cáncer-RTICC

Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury

Supported by Instituto de Salud Carlos III (FIS-PI07/0597 and FIS-PI10/0606). AGL is the recipient of a grant from Universidad de Oviedo (UNOV-09-pf). AA and ILA are the recipients of grants from Instituto Universitario de Oncología del Principado de Asturias (IUOPA). EBS is the recipient of a grant from FICYT (COF-11-40). GMA is the recipient of a grant from Instituto de Salud Carlos III (Intensificación de la Actividad Investigadora-INT 11/14)