Expression of TLR4/MyD88 in CRC

BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15–4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31–4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67–5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27–3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64–5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99–3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01–3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17–4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC

50-60 Hz magnetic fields and cancer, forty years of research: it is time to reassure

In 1979, an epidemiological study carried out in Denver, Colorado first suggested that very weak alternating magnetic fields arising from electrical lines around houses was associated with an increased risk of cancer in children. The potential impact on public health was high, considering the fact that exposure to power-frequency magnetic fields is omnipresent. All power transmission and distribution networks, domestic and industrial wiring, and all kinds of electrical equipment give off magnetic fields. The hypothesis was taken seriously and substantial research budgets have been devoted not only to answering the important question raised by this study but more broadly to identify all other potential health effects of magnetic fields. Since 1979, an exceptional number of scientific studies have been published worldwide. In 2007, the World Health Organization published one of the most comprehensive review so far. The present article summarizes important facts regarding the interaction between a magnetic field and the human body and the key findings from this extensive research looking for a possible link with cancer.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctrico

Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation

The molecular pathogenesis of gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) remains to be elucidated. High-mobility group A (HMGA) proteins play important roles in the regulation of transcription, differentiation, and neoplastic transformation. In this study, the expression of HMGA1 and HMGA2 was studied in 55 GEP NETs. Overexpression of HMGA1 and 2 was frequently detected in GEP NETs compared with normal tissues. Nuclear immunostaining of HMGA1 and 2 was observed in GEP NETs (38 of 55, 69%; 40 of 55, 73%, respectively). High-mobility group A2 expression increased from well-differentiated NET (WNET) to well-differentiated neuroendocrine carcinoma (WNEC) and poorly differentiated NEC (PNEC) (P<0.005) and showed the highest level in stage IV tumours (P<0.01). In WNECs, the expression of HMGA1 and 2 was significantly higher in metastatic tumours than those without metastasis (P<0.05). Gastroenteropancreatic NETs in foregut showed the highest level of HMGA1 and 2 expressions. MIB-1 labelling index (MIB-1 LI) correlated with HMGA1 and 2 overexpression (R=0.28, P<0.05; R=0.434, P<0.001; respectively) and progressively increased from WNETs to WNECs and PNECs (P<0.001). Let-7 expression was addressed in 6 normal organs, 30 tumour samples, and 24 tumour margin non-tumour tissues. Compared with normal tissues, let-7 downregulation was frequent in NETs (19 of 30, 63%). Higher expression of HMGA1 and 2 was frequently observed in tumours with let-7 significant reduction (53, 42%, respectively). The reverse correlation could be detected between HMGA1 and let-7 (P<0.05). Our findings suggested that HMGA1 and 2 overexpression and let-7 downregulation might relate to pathogenesis of GEP NETs

50-60 Hz magnetic fields and cancer, forty years of research: it is time to reassure

In 1979, an epidemiological study carried out in Denver, Colorado first suggested that very weak alternating magnetic fields arising from electrical lines around houses was associated with an increased risk of cancer in children. The potential impact on public health was high, considering the fact that exposure to power-frequency magnetic fields is omnipresent. All power transmission and distribution networks, domestic and industrial wiring, and all kinds of electrical equipment give off magnetic fields. The hypothesis was taken seriously and substantial research budgets have been devoted not only to answering the important question raised by this study but more broadly to identify all other potential health effects of magnetic fields. Since 1979, an exceptional number of scientific studies have been published worldwide. In 2007, the World Health Organization published one of the most comprehensive review so far. The present article summarizes important facts regarding the interaction between a magnetic field and the human body and the key findings from this extensive research looking for a possible link with cancer.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctrico

Living with electric and magnetic fields (EMF)

As for back as 1972, a report was presented during a CIGRE session raised the possibility that exposure to power frequency (50/60 Hz) high electric fields might adversely affect workers’ health. In 1979, an epidemiological study in Denver, Colorado suggested that children’s exposure to power-frequency magnetic fields in the home might increase their risk of cancer. For nearly 40 years, substantial research budgets have been devoted worldwide to the question of possible health effects of power frequency electric and magnetic fields. Over 400 epidemiological studies have been carried out around the world not only to study cancer but also many other health outcomes. At the same time, thousands of laboratory studies on cells, tissues and whole animals have been carried out. The amount of data generated by this international research effort is exceptional. In general, studies have failed to establish a causal relationship between any particular adverse health outcome and electric or magnetic field exposure. CIGRE has always recognized the importance of this issue in terms of its potential impact on the health and safety of workers in the electricity industry, and on the general public. CIGRE Administrative Council has an Expert Group comprising occupational and public health physicians supported by other scientists and engineers. Their role is to keep the President, members and others regularly informed on the issue of powerfrequency electric and magnetic fields and health. No adverse health effects have been found with exposure to electric fields. This position deals mainly about concerns related to magnetic fields exposure.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos (IITREE