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A. Miller



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    P2.01 - Poster Session 2 - Cancer Biology (ID 145)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.01-001 - Deregulated Interleukin-6 Signaling Suppresses Lung Tumourigenesis in Mice Induced by Nicotine-derived Nitrosamine Ketone (ID 1404)

      09:30 - 09:30  |  Author(s): A. Miller

      • Abstract

      Background
      Serum levels of the potent immune-modulatory cytokine interleukin (IL)-6, which signals via the shared gp130 co-receptor, are elevated in smokers, and are higher still in those with lung cancer, the leading cause of cancer death worldwide. However, the precise role that IL-6 plays in the pathogenesis of lung cancer remains to be elucidated. To utilize in vivo molecular dissection of gp130 signaling to identify specific molecular components of the IL-6 cytokine family network which facilitate tobacco-related lung carcinogenesis.

      Methods
      Nicotine-derived Nitrosamine Ketone (NNK) is a potent tobacco carcinogen and reliably induces lung tumours in mice. We therefore examined the effect of deregulated IL-6 signaling on NNK-induced lung carcinogenesis by using gp130[F/F] mice which carry a knock-in mutation in the endogenous gene for gp130, the critical co-receptor for the IL-6 cytokine family.

      Results
      The lungs of these mice display IL-6-induced hyperactivation of the latent transcription factor Stat3 via gp130 in the absence of gp130-mediated PI3K/Akt and Mapk signaling. The gp130[F/F] and control gp130[+/+] (wild-type) mice were injected with NNK or PBS and observed over 16 weeks prior to the evaluation of lung tumourigenesis at the cellular (immunohistochemistry, histology) and molecular (qPCR) levels. In response to NNK, the absolute number of lung lesions in gp130[F/F] mice (3.81 ± 0.84; mean ± SEM) was significantly reduced compared to gp130[+/+ ](6.43 ± 1.72; p<0.05) mice. In addition, we also observed a significant reduction in the size of lesions in gp130[F/F] compared to gp130[+/+] mice (1.00 ± 0.05mm vs 0.69 ± 0.05; p<0.0001). Notably, the number and size of lesions in the lungs of NNK-treated gp130[F/F]:Stat3[-/+] mice displaying genetically-reduced Stat3 hyperactivation were comparable to gp130[F/F] mice.

      Conclusion
      Collectively, our data suggest that IL-6/gp130-mediated activation of the PI3K/Akt and/or Mapk pathways, but not Stat3, plays an important role in promoting NNK-induced lung carcinogenesis.

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    P3.20 - Poster Session 3 - Early Detection and Screening (ID 174)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P3.20-005 - Cardiac CT and pulmonary nodules; Incidental findings and incidence of malignancy in an Australian population (ID 1838)

      09:30 - 09:30  |  Author(s): A. Miller

      • Abstract

      Background
      Background: CT Coronary Angiography provides accurate non-invasive evaluation of coronary arteries but also images lung parenchyma and other mediastinal structures. Little is known about the range and incidence of non-cardiac findings in the Australian population and while CT screening has been shown to reduce mortality in high risk individuals the significance of identified pulmonary nodules in this mixed risk population is unknown. A lack of data regarding the malignant potential of these incidentally identified nodules makes evaluation of the relative risk/benefit of both initial imaging of the lung and subsequent surveillance scanning is difficult.

      Methods
      Methods: A retrospective analysis was performed on reports of all cardiac CT scans done in the calendar year 2012. Descriptive data was collected including baseline patient characteristics, type of nodule and smoking history, as well as whether a full field or restricted field view was performed. Surveillance radiological data and pathology was collected on a sub-group of the population.

      Results
      Results: 2500 Cardiac CT scans analysed with 48% females. Reports analysed for presence of lung nodules and type of nodule with most common nodule granuloma. Total lung nodules 14% (355) with follow up recommended by specialist radiologists; significant variation from recommendation in practice was noted. 39% of population positive for smoking exposure placing them in high risk population. No episodes of malignancy within follow up CT scans with the majority of nodules being stable over the follow up period. Majority of nodules were <4mm making up 60% of the total nodules described, 4-8mm 20% nodules of described nodules, >8mm making up 12% of nodules. Pulmonary Cysts represented 4% of nodules. Subpleural nodules described separately and making up a minority of nodules.

      Conclusion
      Conclusion: Cardiac CTs are an increasingly common modality used to evaluate coronary artery disease. Pulmonary nodules are a common finding with a prevalence in this study of 14%; this contributes significantly to a economic burden as well as exposure of the community to ionising radiation which there is growing community and professional concern around. The findings of this audit are in line with published data of a low risk of de novo malignancy in pulmonary nodules as well as a high prevalence of pulmonary nodules across the cohort.