The significance of the EGFR pathway in malignant pleural mesothelioma

IntroductionEGFR, MTOR and COX2 are up regulated in malignant pleural mesothelioma (MPM). In this study we aimed to determine the expression of Lipoxygenase enzymes (LOX), absence of PTEN protein expression and the cytotoxic effect of EGFR, MTOR and COX2 inhibitors in MPM.Materials and MethodsImmunohistochemical analysis was performed in 93 archival MPM tissue samples to determine the expression of 5-LOX and 12-LOX and PTEN protein. The COX-2 positive cell lines MSTO-211H, NCI-H2052, NCI-H2452 (mesothelioma) and A549 (lung cancer) were utilised. All cell lines were tested for EGFR, KRAS and BRAF mutations. Cells were incubated with Cetuximab, Gefitinib, Rapamycin, Ku0063794 (MTOR kinase inhibitor) and Celecoxib as single agents and in combinations and analysed using the MTS assay.ResultsPositive 5-LOX expression was seen in 73% and positive 12-LOX expression was seen in 83% of MPM samples. PTEN protein expression was absent in 27% of the samples. A549 cells had a KRAS missense mutation at codon 12. No other EGFR, KRAS and BRAF mutations were identified in any of the cell lines. Cetuximab showed 50% cell growth inhibition in MSTO-211H cells at a concentration of 1.6 μM. All other cell lines were resistant to Cetuximab. All cell lines were resistant to Gefitinib. Rapamycin and Ku0063794 demonstrated 50% cell growth inhibition in NCI-H2052, NCI-H2452 and A549. Celecoxib demonstrated 50% cell growth inhibition in all cell lines. Cetuximab and Gefitinib were combined in turn with Rapamycin, Ku0063794 and Celecoxib. Cetuximab when combined with Celecoxib (NCI-H2052, NCI-H2452 and A549 cells) and Ku0063794 (MSTO-211H cells) demonstrated significant growth inhibition.ConclusionsOur study suggests that 5LOX and 12LOX are expressed in the majority and PTEN protein expression is absent is a significant proportion of MPM tissue samples. Inhibition of MTOR pathway may be an important therapeutic strategy in patients with MPM

Wallenbergs jubileumsfond.

S6K1, S6K2 and 4EBP1 in breast cance

ORIGINAL ARTICLE Childhood Malignancy and Cardiotoxicity of Anthracyclines

ABSTRACT Background: Anthracyclines are antitumor agents with broad spectrum activity against many childhood malignancies. An important side effect of these drugs is cardiotoxicity which may happen even years after discontinuation. Our objective was tried to determine the incidence of Anthracycline induced chronic cardiotoxicity and its risk factors in an Iranian cohort. Methods: we carried out a prospective analytic descriptive study at Children's Medical hospital, Tabriz, Iran, from 2009 to 2010. To evaluate cardiotoxicity (early or late onset), echocardiographic investigation was carried out on 80 persons who had received anthracyclines to treat lymphohematopoietic (Acute lymphoblastic Leukemia [ALL] and Lymphoma) malignancy before the echocardiographic examination. All patients were off treatment. Results: Mean age ± SD was 9.74±3.79 years old .66.25 % (53) was male and 33.75% (27) was female. M/F ratio was 1.96. 60(75%) had ALL and 20 (25%) had lymphoma. 12.50% (10 cases) had left ventricular systolic dysfunction, 25% (20 cases) had left ventricular diastolic dysfunction, and 27.5 % (22 cases) had arrhythmias. Conclusion: In the current study among survivors of childhood cancer, finding show that, incidence of arrhythmias due to Anthracyclines cardiotoxicity was greater than other side effects

Colombo South Teaching Hospital, Kalubowila. Corresponding author:

A fourteen year old girl presented to us with persistent left hypochondrial and left loin pain for several months, associated with loss of weight and dyspeptic symptoms. Physical examination did no