Identification of redox-sensitive transcription factors as markers of malignant pleural mesothelioma.

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer

Cooperative role of thrombopoietin and vascular endothelial growth factor-a in the progression of liver cirrhosis to hepatocellular carcinoma

Primary thrombopoietic mediator thrombopoietin (THPO) is mainly produced by the liver; it may act as a growth factor for hepatic progenitors. Principal angiogenesis inducer vascular endothelial growth factor-A (VEGF-A) is critical for the complex vascular network within the liver architecture. As a cross-regulatory loop between THPO and VEGF-A has been demonstrated in the hematopoietic system, the two growth factors were hypothesized to cooperatively contribute to the progression from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). The mRNA and protein expression levels of THPO, VEGF-A, and their receptors were examined, compared, and correlated in paired cancerous and LC tissues from 26 cirrhosis-related HCC patients, using qRT-PCR and immunohistochemistry. THPO and VEGF-A were alternatively silenced by small interfering RNA (siRNA) in human liver cancer cell lines Huh7 and HepG2. THPO and VEGF-A expressions significantly increased in tumor versus LC tissues. HCC and paired LC cells expressed similar levels of THPO receptor (R), whereas vascular endothelial growth factor receptor (VEGFR) -1 and VEGFR-2 levels were higher in HCC than in corresponding LC tissue samples. A significant linear correlation emerged between THPO and VEGF-A transcripts in HCC and, at the protein level, THPO and THPOR were significantly correlated with VEGF-A in tumor tissues. Both HCC and LC expressed similar levels of gene and protein hypoxia inducible factor (HIF)-1α. Positive cross-regulation occurred with the alternative administration of siRNAs targeting THPO and those targeting VEGF-A in hypoxic liver cancer cell lines. These results suggest THPO and VEGF-A might act as interdependently regulated autocrine and/or paracrine systems for cellular growth in HCC. This might be clinically interesting, since new classes of THPOR agonistic/antagonistic drugs may provide novel therapeutic options to correct the frequent hemostatic abnormality seen in HCC patients

Abnormal Vertical Pump Suction Recirculation Problems Due To Pump-System Interaction

Lecturepg. 18It is well documented that the proper operation of vertical centrifugal pumps is greatly dependent upon the entire pump/piping system, which includes the piping geometry and the system operating conditions. Oftentimes, pump operate satisfactorily during shop tests but experience problems after they are installed in the field. Here, three large vertical pumps that operated satisfactorily on the test stand experienced excessive vibration after installation. Additionally, pulsation in the system piping was found to be causing unexpected vibration in downstream equipment. It was discovered that the problems were the result of complex interaction between several phenomena. Improper inlet conditions caused suction recirculation that generated broadband turbulence. The turbulent energy excited acoustical resonances of the pump/piping system, resulting in pulsation at several discrete frequencies. This energy subsequently excited mechanical natural frequencies of the motor/pump/piping system causing high amplitude nonsynchronous vibration of the pump and other structurers far downstream from the pump. Field data are presented. Diagnostic techniques and instrumentation needed to obtain the field data required to solve these problems are discussed. Also, additional data from pump hydraulic analysis and sump model tests are presented. Further, the solution strategy with two-step field changes (sump and pump) is shown. Following these modifications, the pumps have operated satisfactorily for more than four years

Mucociliary flow in the nose during general and epidural anesthesia.

By means of the coloured indicator transport test (phenol red 3% in calcium-hydrogen-phosphate), mucociliary function in nose and pharynx was studied in 50 patients who underwent general or ocular surgery and in 10 healthy adult subjects. Patients were anesthetized with halothane, enflurane, NLA, and epidural analgesia. At the end of surgery, mucociliary function was significantly depressed (p less than 0.001) after halothane or enflurane anesthesia, but not after NLA or epidural analgesia. Six hours following enflurane anesthesia we still found a significant depression (p less than 0.001) of mucociliary function. No difference between halothane or enflurane was noted