Occupational Exposures and Risk of Adenocarcinoma of the Lung in Uruguay

Objectives: To investigate occupational risks of lung adenocarcinoma in Uruguay and to confirm a previously reported increased risk among butchers.Methods: We conducted a case–control study among men in four major hospitals in Montevideo, based on interviews to 338 cases of lung adenocarcinoma and 1014 hospital-based controls. We calculated odds ratios (ORs) of lung adenocarcinoma for employment in 22 jobs, after adjustment for tobacco smoking and other potential confounders.Results: The OR was increased for employment as farmer, tractor driver, painter and medical worker, but no trend was suggested for duration of employment. Long-term employment as mason, glass worker or textile worker resulted in an increased OR. The OR for employment as butcher was 1.2 (95% confidence interval 0.7–2.1). The OR increased with increasing duration of self-reported exposure to formaldehyde.Conclusions: Occupational exposures seem to play a limited role in causing lung adenocarcinoma among men in Uruguay. Employment as butcher was not confirmed as an important risk factor.     

Prognostic factors in localized invasive cutaneous melanoma: high value of mitotic rate, vascular invasion and microscopic satellitosis

The aim of this study was to determine independent clinical and pathological prognostic factors for overall and disease-free survival in Spanish melanoma patients. Eight hundred and twenty-three patients with localized melanoma and complete clinical and pathological information were evaluated. The age at diagnosis, gender, location, tumour thickness, invasion level, ulceration, histological subtype, inflammatory infiltrate, mitotic rate, vascular invasion, microscopic satellitosis, regression and cell type were all included. Univariate and multivariate Cox regression analyses were performed for overall and disease-free survival. Gender, histological subtype, tumour thickness, invasion level, ulceration, inflammatory infiltrate, microscopic satellitosis, vascular invasion and mitotic rate were related to overall and disease-free survival in univariate analysis. Age and location were only related to disease-free survival. Only tumour thickness, vascular invasion and gender exhibited independent significance for overall survival in multivariate analysis. For disease-free survival, tumour thickness, location, mitotic rate, vascular invasion and microscopic satellitosis were the sole independent factors. It can be concluded that the Breslow thickness remains the most significant prognostic factor for the survival of patients with localized cutaneous melanoma. Our results support the inclusion of microscopic satellitosis and vascular invasion in the current American Joint Committee on Cancer (AJCC) staging system, although further studies evaluating their separate influence are needed. Mitotic rate is confirmed as an objective and independent predictor of disease-free survival for melanoma patients that should be considered in further revisions of the mentioned staging system.     

Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients

Based on the assumption that proteins can emanate from tumour to serum, we investigated whether serum low molecular weight proteins (LMW) can discriminate lung cancer patients from healthy donors. Pooled sera from 20 lung cancer patients matched in sex (men), histological type (adenocarcinoma) and stage (IIIB and IV) and from 20 healthy donors (men) were submitted to 2-DE coupled to MALDI-TOF peptide mass fingerprinting. Results of 2D-E/ MALDI-TOF showed five up regulated proteins (immunoglobulin lambda chain, transthyretin monomer, haptoglobin-alfa 2 and two isoforms of serum amyloid protein) and one down regulated (fragment of apolipoprotein A-I) in patients. All differentially expressed proteins, except immunoglobulin, may be acting as a non-specific sign of inflammation in cancer and transthyretin monomer may act as a possible blood marker to CSF barrier disruption that occurs, e.g., in cerebral metastasis. In conclusion, this work shows the usefulness of 2D-gel electrophoresis and mass spectrometry proteomic techniques for the identification of up- and down-regulated proteins in serum from adenocarcinoma lung cancer patients.     

The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation

There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in cells of the immune system, as well as in brain glial cells. In the present review it is summarized the effects of cannabinoids on immune reactivity and on the regulation of neuroinflammatory processes associated with brain disorders with special attention to chronic inflammatory demyelinating diseases such as multiple sclerosis.     

Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes

We tested the hypothesis that activation Jak2, which is prominently involved in the up-regulation of the renin-angiotensin system (RAS), constitutes a focal point in relaying signals triggered by a Angiotensin II (Ang II) and hypoxia/reoxygenation separately to cause an enhanced susceptibility of cardiac myocyte to apoptotic cell death. Ang II-treated adult cardiomyocytes in culture exhibited an increased level of apoptosis that accompanied activation of pro-apoptotic as well as anti-apoptotic signaling pathways. We observed increased phosphorylation of Jak2 kinase, Stat1, JNK, with increased expression of Bax protein, followed by an increase in caspase-1 and caspase-3 activity. Activation of these pro-apoptotic pathways was blocked by the Jak2 pharmacological inhibitor, Tyrphostin AG490. We also observed an increase in phosphorylation of cardioprotective pathway components, namely S6 ribosomal protein, and heat shock protein 27 (HSP27). Likewise, the oxidative stress, via the hypoxia/reoxygenation treatment of rat adult cardiomyocytes, produced apoptosis that was dependent upon activation of Jak2. The apoptotic response was not only reduced by Losartan, an inverse agonist of the AT1, receptor, but by treatment with AG490 as well. Taken together, these observations provide clear evidence in favor of Jak2 signaling as mediator of the apoptotic response in cardiomyocytes. However, there was a concomitant induction of cytoprotective signaling that presumably provides a negative feed-back to the deleterious effects of the agonist.     

A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads

This was a 12-month extension of a randomized, investigator-blinded, multicenter, 8-week trial with triple combination (TC) cream in facial melasma. A total of 585 patients were enrolled in the study and 569 patients received study medication. Three hundred eighty-nine patients completed 6 months of treatment and 327 patients completed 12 months of treatment. TC cream demonstrated a favorable safety profile: only 14 patients (2.5%) discontinued the study due to treatment-related adverse events (AEs). The 2 cases of skin atrophy were mild and did not lead to withdrawal. From the 23 cases of mild telangiectasia, only 2 resulted in discontinuation. All others were transient. Results confirmed those of a previous smaller study, with both physicians and patients reporting clinically significant improvements in melasma. By month 12, 80% of patients had lesions completely cleared or nearly cleared. Once daily application of TC cream applied intermittently over a long period is a safe, tolerable, and effective treatment for moderate to severe melasma of the face.