Additional file 4: of DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines

Retreatment of the pooled surviving U-1810-clones from a first round of clonogenic survival, where the first treatment is indicated for cisplatin-surviving (10 μM, Cisplatin as 1st) or untreated (Untreated as 1st) clones. (A) The relative clonogenic survival in the first (1st) round is depicted in the first white bar, the grey bars are data from the retreated (2nd) experiment as described above, also using 10 μM cisplatin. (B) MTT cell viability data. Doses used for the retreatment were from 0.5-50 μM cisplatin and viability was analyzed after 72 h. Average ± SD from three experiments, MTT was performed in triplicate. (TIFF 54 kb

Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT – the Nordic experience

<div><p></p><p><b>Background.</b> Presentation of long term results of a phase II multicenter Nordic trial of medically inoperable stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).</p><p><b>Material and methods.</b> We report the extended outcome, focusing on long-term effects, of a prospective cohort of 57 evaluable patients with peripherally located T1N0M0 (72%) and T2N0M0 (28%) NSCLC, treated with SBRT 15 Gy × 3, prescribed to the 67% isodose line encompassing the PTV. The patients were inoperable due to chronic obstructive pulmonary disease (65%), cardiovascular disease (25%) or other illnesses (3%) or refused surgery (7%). Median Karnofsky score pre-treatment was 80% (70–100%). Late effects were defined as occurring > 36 months.</p><p><b>Results.</b> Thirty-eight patients (67%) were relapse free during their entire follow-up. Local control rate at four and five years were 79% (CI 95% 64–95%) and local relapses occurred at 10–76 months post-treatment. Seven local failures were noted, four occurring ≤ 36 months (all T2a-tumors; two isolated and two in combination with out-of-field relapses) and three occurring > 36 months (T1b-tumors n = 3). Thirteen patients had out-of-field failure only as first presentation of recurrence. Overall survival rate and lung cancer-specific survival rate at five years were 30% and 74%, respectively. Toxicity throughout the entire observation period was acceptable without any grade 5 toxicities. Seventeen grade 3–4 toxicities were noted, three presenting > 36 months (rib fracture, dyspnea and ventricle tachycardia). Median follow-up was 41.5 months (3.4–113.0) for the entire cohort and 59.3 months (36.4–113.0) for the 34 patients (60%) with a follow-up of > 36 months.</p><p><b>Conclusion.</b> Throughout the observation period local control was excellent and toxicity limited with no increase in late presenting local relapses or late treatment-related morbidity. This further supports SBRT as an efficient local treatment modality even in a medically impaired patient cohort.</p></div

Additional file 2: Figure S1. of Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells

TTFields effect on LN-18 glioma cells. Surviving fractions of LN-18 cells treated with TTFields (200 kHz, 1.0 V/cm) for 72 h either alone or immediately after irradiation with 4 Gy (A). Surviving fraction of LN-18 cells treated with RT alone or with RT at various doses followed by 200 kHz TTFields (1.0 V/cm RMS) for 72 h. Results of the combined treatments were normalized to the effect of TTFields alone (B). (PPTX 2783 kb

Additional file 3: Figure S2. of Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells

TTFields Delay Irradiation-Induced DNA Damage Repair in glioma cells. LN-18 cells were irradiated with 4 Gy RT and immediately treated with TTFields applied for 1 h, 2 h or 24 h (A-B). Effect on DNA repair was measured as tail moment in the comet assay. (PPTX 1940 kb

Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism

In this study, we have analyzed human primary lung adenocarcinoma tumors using global mass spectrometry to elucidate the biological mechanisms behind relapse post surgery. In total, we identified over 3000 proteins with high confidence. Supervised multivariate analysis was used to select 132 proteins separating the prognostic groups. Based on in-depth bioinformatics analysis, we hypothesized that the tumors with poor prognosis had a higher glycolytic activity and HIF activation. By measuring the bioenergetic cellular index of the tumors, we could detect a higher dependency of glycolysis among the tumors with poor prognosis. Further, we could also detect an up-regulation of HIF1α mRNA expression in tumors with early relapse. Finally, we selected three proteins that were upregulated in the poor prognosis group (cathepsin D, ENO1, and VDAC1) to confirm that the proteins indeed originated from the tumor and not from a stromal or inflammatory component. Overall, these findings show how in-depth analysis of clinical material can lead to an increased understanding of the molecular mechanisms behind tumor progression