Analysis of labour risks in the Spanish industrial aerospace sector

Labour risk prevention is an activity integrated within Safety and Hygiene at Work in Spain. In 2003, the Electronic Declaration for Accidents at Work, Delt@ (DELTA) was introduced. The industrial aerospace sector is subject to various risks. Our objective is to analyse the Spanish Industrial Aerospace Sector (SIAS) using the ACSOM methodology to assess its labour risks and to prioritise preventive actions. The SIAS and the Services Subsector (SS) were created and the relevant accident rate data were obtained. The ACSOM method was applied through double contrast (deviation and translocation) of the SIAS or SS risk polygon with the considered pattern, accidents from all sectors (ACSOM G) or the SIAS. A list of risks was obtained, ordered by action phases. In the SIAS vs. ACSOM G analysis, radiation risks were the worst, followed by overstrains. Accidents caused by living beings were also significant in the SS vs. SIAE, which will be able to be used to improve Risk Prevention. Radiation is the most significant risk in the SIAS and the SS. Preventive actions will be primary and secondary. ACSOM has shown itself to be a valid tool for the analysis of labour risks

Review: mitochondrial defects in breast cancer

Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe a variety of mitochondrial DNA alterations present in breast cancer. In this review article, we to provide a summary of the mitochondrial genomic alterations reported in breast cancer and their functional consequences

Growth and growth hormone secretion in children with cancer treated with chemotherapy

To evaluate the effect of chemotherapy on growth and growth hormone (GH) secretion. METHODS: We analyzed growth and GH secretion in 60 children in complete remission after treatment by chemotherapy and surgery for malignant solid tumors. None of them received cranial radiotherapy. Growth hormone reserve was assessed by at least two stimulation tests (clonidine, L-dopa, growth hormone-releasing hormone). In 12 children the reserve of GH pretreatment was also evaluated. RESULTS: Growth hormone deficiency (GHD) was observed in 27 of 60 patients (45%). At diagnosis, mean standing height was +0.23 +/- 0.11 standard deviation score (SDS) in the GHD group and +0.16 +/- 0.10 SDS in the non-GHD group. After chemotherapy, mean standing height in the GHD group was -0.28 +/- 0.15 SDS and -0.14 +/- 0.11 in the non-GHD group (p < 0.05), and the growth rate was +0.13 +/- 0.07 SDS in the GHD group and +0.22 +/- 0.18 SDS in the non-GHD group. For a mean follow-up of 30 months, the mean standing height was -0.46 +/- 0.29 SDS in the GHD group and -0.24 +/- 0.16 SDS for the non-GHD group (p < 0.05), and the growth rate was -0.27 +/- 0.19 SDS in the GHD group and -0.16 +/- 0.12 SDS in the non-GHD group (p < 0.05). The GH response to clonidine was significantly less than that found with the other stimuli. There was correlation between the dose intensity of some drugs and the subsequent GH response to stimulation tests. The GHD group was found to have received significantly higher doses of actinomycin D than the non-GHD group (p < 0.05). Growth impairment and GHD were not found to be correlated with duration of treatment and follow-up, tumor type, sex, or age. CONCLUSIONS: Chemotherapy as the sole form of treatment in children with cancer interferes with growth. The observed impairment of growth depends, at least in part, on a GHD related to chemotherapy. The growth rate in conjunction with the GH response to clonidine provides a sensitive measure of GHD associated with chemotherapy

Differential modulation of IL-8 and TNF-α expression in human keratinocytes by buflomedil chlorhydrate and pentoxifylline

Pentoxifylline (PTX) is a methylxanthine derivative used in a wide range of dermatoses. As well as its hemorrheologic activity, PTX has anti-inflammatory properties. Buflomedil chlorhydrate (BC) is another hemorrheological drug with peripheral vasodilatory action, whose clinical uses are similar to those of PTX. Both drugs increase intracellular levels of cAMP, either secondary to phosphodiesterase inhibition (PTX) or adenyl-cyclase stimulation (BC). Long-term cultures of normal human keratinocytes were prepared in a free-serum medium, and stimulated with 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC (100-1000 micrograms/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1 using ELISA and Northern blot or RT-PCR techniques were measured. TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA did not induce IL-1 alpha or IL-1 beta release of keratinocytes. TPA increased RNA expression of the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1. BC diminished TPA-induced TNF-alpha and IL-8 release from keratinocytes; in the case of IL-8 it is possible that this inhibition occur to transcriptional level. Moreover PTX was unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced TPA-induced IL-1 alpha and beta expression. It is possible that BC action is specifically exerted on keratinocytes, because we did not find similar results with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells

A case of capecitabine-induced coronary microspasm in a patient with rectal cancer

5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed

Dose-finding study and pharmacogenomic analysis of fixed-rate infusion of gemcitabine, irinotecan and bevacizumab in pretreated metastatic colorectal cancer patients

BACKGROUND: To determine the dose-limiting toxicity (DLT), maximum tolerated dose, recommended dose (RD) and preliminary evidence of activity of escalating doses of irinotecan (CPT-11) fixed-dose-rate infusional gemcitabine (FDR-GMB) and bevacizumab in pretreated metastatic colorectal cancer (mCRC) patients. Pharmacogenomic analysis was performed to investigate the association between VEGF single-nucleotide polymorphisms and clinical outcome. PATIENTS AND METHODS: A total of 89 mCRC patients were recruited in a two-step study design; 28 were included in the dose-finding study and 59 in the pharmacogenomic analysis. The FDR-GMB of 1000 mg m⁻², bevacizumab 5 mg kg⁻¹ and CPT-11 doses ranging from 100 to 160 mg m⁻² were explored. The VEGF protein serum levels were quantified by EIA. Allelic discrimination was performed to genotype polymorphisms in the VEGF gene. RESULTS: CPT-11 RD was 150 mg m⁻². Diarrhoea and neutropenia were the DLT. After a median follow-up of 42 months, the median time to progression (TTP) and overall survival were 5.2 and 19.9 months, respectively. VEGF levels were significantly correlated with VEGF-2578AA and VEGF-460CC genotypes, and a trend was observed with VEGF+405GG genotype. The presence of any of these genotypes correlated with a longer median TTP (8.8 vs 4.5 months, P=0.04). CONCLUSION: The triplet combination tested in this study is effective and well tolerated. A possible predictive role for VEGF gene polymorphisms and baseline VEGF circulating levels is suggested

Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy

AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys /Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients

Combining chemotherapy and targeted therapies in metastatic colorectal cancer

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer