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      Evaluation of FTIR Spectroscopy as a diagnostic tool for lung cancer using sputum

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          Abstract

          Background

          Survival time for lung cancer is poor with over 90% of patients dying within five years of diagnosis primarily due to detection at late stage. The main objective of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) as a high throughput and cost effective method for identifying biochemical changes in sputum as biomarkers for detection of lung cancer.

          Methods

          Sputum was collected from 25 lung cancer patients in the Medlung observational study and 25 healthy controls. FTIR spectra were generated from sputum cell pellets using infrared wavenumbers within the 1800 to 950 cm -1 "fingerprint" region.

          Results

          A panel of 92 infrared wavenumbers had absorbances significantly different between cancer and normal sputum spectra and were associated with putative changes in protein, nucleic acid and glycogen levels in tumours. Five prominent significant wavenumbers at 964 cm -1, 1024 cm -1, 1411 cm -1, 1577 cm -1 and 1656 cm -1 separated cancer spectra from normal spectra into two distinct groups using multivariate analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal components analysis revealed that these wavenumbers were also able to distinguish lung cancer patients who had previously been diagnosed with breast cancer. No patterns of spectra groupings were associated with inflammation or other diseases of the airways.

          Conclusions

          Our results suggest that FTIR applied to sputum might have high sensitivity and specificity in diagnosing lung cancer with potential as a non-invasive, cost-effective and high-throughput method for screening.

          Trial Registration

          ClinicalTrials.gov: NCT00899262

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          Most cited references25

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          Smoking and lung cancer: the role of inflammation.

          Worldwide over 1 million people die due to lung cancer each year. It is estimated that cigarette smoking explains almost 90% of lung cancer risk in men and 70 to 80% in women. Clinically evident lung cancers have multiple genetic and epigenetic abnormalities. These abnormalities may result in activation of oncogenes and inactivation of tumor-suppressor genes. Chronic inflammation, which is known to promote cancer, may result both from smoking and from genetic abnormalities. These mediators in turn may be responsible for increased macrophage recruitment, delayed neutrophil clearance, and increase in reactive oxygen species (ROS). Thus, the pulmonary environment presents a unique milieu in which lung carcinogenesis proceeds in complicity with the host cellular network. The pulmonary diseases that are associated with the greatest risk for lung cancer are characterized by abundant and deregulated inflammation. Pulmonary disorders such as chronic obstructive pulmonary disease (COPD)/emphysema are characterized by profound abnormalities in inflammatory and fibrotic pathways. The cytokines and growth factors aberrantly produced in COPD and the developing tumor microenvironment have been found to have deleterious properties that simultaneously pave the way for both epithelial-mesenchymal transition (EMT) and destruction of specific host cell-mediated immune responses. Full definition of these pathways will afford the opportunity to intervene in specific inflammatory events mediating lung tumorigenesis and resistance to therapy.
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            A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial.

            Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. To explore the effect of screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability. Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only. A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively. The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.
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              Mie-type scattering and non-Beer-Lambert absorption behavior of human cells in infrared microspectroscopy.

              We report infrared microspectral features of nuclei in a completely inactive and contracted (pyknotic) state, and of nuclei of actively dividing cells. For pyknotic nuclei, the very high local concentration of DNA leads to opaqueness of the chromatin and, consequently, the absence of DNA signals in the IR spectra of very small nuclei. However, these nuclei can be detected by their scattering properties, which can be described by the Mie theory of scattering from dielectric spheres. This scattering depends on the size of the nucleus; consequently, quite different scattering cross-sections are calculated and observed for pyknotic and mitotic nuclei.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2010
                23 November 2010
                : 10
                : 640
                Affiliations
                [1 ]School of Medicine, Swansea University, Swansea, SA2 8PP, UK
                [2 ]Department of Respiratory Medicine, Prince Phillip Hospital, Llanelli, SA14 8LY, UK
                [3 ]Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, SY23 2AX, UK
                Article
                1471-2407-10-640
                10.1186/1471-2407-10-640
                3000851
                21092279
                df947333-f475-48e1-babe-d31a90cd3a13
                Copyright ©2010 Lewis et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 March 2010
                : 23 November 2010
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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