Elevating CDCA3 Levels Enhances Tyrosine Kinase Inhibitor Sensitivity in TKI-Resistant EGFR Mutant Non-Small-Cell Lung Cancer.

Tyrosine kinase inhibitors (TKIs) are the first-line therapy for non-small-cell lung cancers (NSCLC) that harbour sensitising mutations within the epidermal growth factor receptor (EGFR). However, resistance remains a key issue, with tumour relapse likely to occur. We have previously identified that cell division cycle-associated protein 3 (CDCA3) is elevated in adenocarcinoma (LUAD) and correlates with sensitivity to platinum-based chemotherapy.

Comparison of radiobiological parameters for Y radionuclide therapy (RNT) and external beam radiotherapy (EBRT) in vitro.

Background: Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Relatively few studies to date have investigated the dose rate effect in RNT. Therefore, the aim of this study was to benchmark Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes.

Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma.

Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats.

Health-related quality of life and inflammatory markers in malignant pleural mesothelioma.

Purpose: Malignant pleural mesothelioma (MPM) is a highly aggressive and symptomatic disease. We examined the relationship between health-related quality of life (HRQoL) and inflammatory markers, and the prognostic role of HRQoL in MPM patients.

Methods: MPM patients from two parallel phase II studies (thalidomide alone or thalidomide with chemotherapy) were included.

The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine.

There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed.

High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy.

Purpose: Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients.

Experimental Design: Patients with MM who had systemic therapy at participating institutes were studied.

Predicting the clonogenic survival of A549 cells after modulated x-ray irradiation using the linear quadratic model.

In this study we present two prediction methods, mean dose and summed dose, for predicting the number of A549 cells that will survive after modulated x-ray irradiation. The prediction methods incorporate the dose profile from the modulated x-ray fluence map applied across the cell sample and the linear quadratic (LQ) model. We investigated the clonogenic survival of A549 cells when irradiated using two different modulated x-ray fluence maps.

A preliminary investigation of cell growth after irradiation using a modulated x-ray intensity pattern.

In this study we have investigated a spatial distribution of cell growth after their irradiation using a modulated x-ray intensity pattern. An A549 human non-small cell lung cancer cell line was grown in a 6-well culture. Two of the wells were the unirradiated control wells, whilst another two wells were irradiated with a modulated x-ray intensity pattern and the third two wells were uniformly irradiated.

Changes in gene expression associated with stable drug and radiation resistance in small cell lung cancer cells are similar to those caused by a single X-ray dose.

Small cell lung cancer (SCLC) initially responds well to chemotherapy and fractionated radiotherapy, but resistance to these treatments eventually develops in the vast majority of cases. To understand how resistance develops in the H69 SCLC cell line, we compared the changes in gene expression associated with 37.5 Gy fractionated X-ray treatment that produced the stable radiation- and drug-resistant H69/R38 cell subline to the changes associated with a single 4- or 8-Gy X-ray treatment.

Cellular models of drug- and radiation-resistant small cell lung cancer.

Background: The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the classic small cell lung cancer (SCLC) line have proven useful in studies of resistance and its circumvention with paclitaxel.

Materials And Methods: The suppressor/oncogene profile of these sublines determined by Western and Northern blot was compared to the variant H82 SCLC cell profile. Two-dimensional electrophoresis/mass spectrometry was used to determine the effect of paclitaxel on protein expression.

Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIalpha expression.

Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance.

Methods And Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.