Definitive Chemoradiotherapy for Non–Small Cell Lung Cancer with N2 Disease

Patel, Shilpen; Sanborn, Rachel E.; Thomas, Charles R.

doi:10.1016/j.thorsurg.2008.07.003

Cited by 7 publications

(5 citation statements)

References 47 publications

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“…Early-stage NSCLC is potentially curable by surgery, but its long-term survival after resection is limited by local or distal recurrences. The best therapy available for inoperable and/or late-stage NSCLC is radiation with or without chemotherapy (2, 3). In addition, anti-angiogenic therapy targeting VEGF prolongs survival in lung cancer patients (4).…”

Section: Introductionmentioning

confidence: 99%

PPARα Activation Can Help Prevent and Treat Non–Small Cell Lung Cancer

Skrypnyk

Chen

et al. 2014

Cancer Research

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Non-small cell lung cancer (NSCLC) not amenable to surgical resection has a high mortality rate, due to the ineffectiveness and toxicity of chemotherapy. Thus, there remains an urgent need of efficacious drugs that can combat this disease. In this study, we show that targeting the formation of pro-angiogenic epoxyeicosatrienoic acids (EETs) by the cytochrome P450 arachidonic acid epoxygenases (Cyp2c) represents a new and safe mechanism to treat NSCLC growth and progression. In the transgenic murine K-Ras model and human orthotopic models of NSCLC, we found that Cyp2c44 could be downregulated by activating the transcription factor PPARα with the ligands bezafibrate and Wyeth-14,643. Notably, both treatments reduced primary and metastatic NSCLC growth, tumor angiogenesis, endothelial Cyp2c44 expression and circulating EET levels. These beneficial effects were independent of the time of administration, whether before or after the onset of primary NSCLC, and they persisted after drug withdrawal, suggesting the benefits were durable. Our findings suggest that strategies to downregulate Cyp2c expression and/or its enzymatic activity may provide a safer and effective strategy to treat NSCLC. Moreover, as bezafibrate is a well-tolerated clinically approved drug used for managing lipidemia, our findings provide an immediate cue for clinical studies to evaluate the utility of PPARα ligands as safe agents for the treatment of lung cancer in humans.

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Section: Introductionmentioning

confidence: 99%

PPARα Activation Can Help Prevent and Treat Non–Small Cell Lung Cancer

Skrypnyk

Chen

et al. 2014

Cancer Research

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“…Thermotherapy is a new treatment of tumors, which plays an important role in comprehensive treatment of tumors. Thermotherapy in combination with chemotherapy is able to improve tumor treatment efficiency (18). Initially thermo- Compared with control group and chemotherapy group, phosphorylation of Akt decreased significantly in thermo-chemotherapy group.…”

Section: Discussionmentioning

confidence: 96%

Involvement of ROS in the inhibitory effect of thermotherapy combined with chemotherapy on A549 human lung adenocarcinoma cell growth through the Akt pathway

Wang

Liu

et al. 2012

Oncology Reports

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Mechanisms of synergistic effect of thermotherapy and chemotherapy on human lung adenocarcinoma cell growth are unclear. The purpose of this study was to investigate these effects and explore the function of ROS, Akt and caspase-3 in relation to these. A549 cells were subjected to different thermochemotherapy treatments: 43˚C heat+50 µg/l paclitaxel (thermochemotherapy group), 43˚C heat+50 µg/l paclitaxel+1 µmol/l wortmannin (wortmannin group), 43˚C heat+50 µg/l paclitaxel+30 µmol/l NAC (NAC group) and 50 µg/l paclitaxel (chemotherapy group). The cells without any treatment were regarded as controls. Cell proliferation rates were measured with MTT assay and intracellular ROS levels were detected with fluorescence labeling technologies. Phosphorylation of Akt and caspase-3 expression were determined by western blotting and the cell apoptosis rates were examined by flow cytometry. Tests in vivo were carried out at the same time. It was found that the cell proliferation rates of the thermochemotherapy group were significantly lower compared to those of the controls or the chemotherapy group (P<0.05). The intracellular ROS levels of the thermochemotherapy group were elevated significantly compared with those of other groups, and these changes could be reversed using the ROS inhibitor NAC but not a PI3K inhibitor (wortmannin). Phosphorylation of Akt was significantly decreased in the thermochemotherapy group (P<0.05), which could be blocked by wortmannin, but increased by NAC (P<0.05). The caspase-3 expression levels and cell apoptosis rates of the thermochemotherapy group were higher compared to those of the other groups (P<0.05). All results have been confirmed by in vivo tests. Thus, the combination of thermotherapy with chemotherapy showed a stronger inhibitory effect on A549 cell growth compared to chemotherapy alone, which may be able to cause additional cell apoptosis through inhibition of Akt phosphorylation and activation of caspases by increased intracellular ROS production.

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“…4,5 Approximately one-third of patients are diagnosed at a locally advanced stage, ranging from large tumors invading the mediastinum with no lymph node involvement (T4N0) to tumors with bulky multi-station nodal involvement centrolateral (N3) to the side of the primary neoplasm. 6 The best therapeutic alternative for this group of patients is still debated, in particular, the role and the benefit of surgery after induction therapy are not yet clearly defined. 7 Nevertheless, induction therapy followed by surgical resection is generally accepted, and is now being adopted in patients with earlier stages of NSCLC.…”

Section: Discussionmentioning

confidence: 99%