<i>Objectives</i>. Environmental factors expose an individual to heavy metals that may stimulate cancer growth preclinically including non-small cell lung cancer (NSCLC) cells. Here, we examine the prevalence of four heavy metals present in postsurgical tissues from individuals with and without NSCLC. <i> Materials and Methods</i>. Thoracic tissue samples from two separate sample sets were analyzed for cadmium (Cd), arsenic (As), mercury (Hg), and lead (Pb) content. <i> Results</i>. In the first sample set, there was no significant measurable amount of Pb and Hg found in either NSCLC tissue or nonmalignant lung tissue samples. Cd was the most prevalent heavy metal and As was present in moderate amounts. In the second sample set, Cd was measurable across all tissue types taken from 28 NSCLC patients and significantly higher Cd was measurable in noncancer benign lung (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.27588pt;width:36.237499px;" id="M1" height="11.175" version="1.1" viewBox="0 0 36.237499 11.175" width="36.237499">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x1D45B" d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2&#xA;q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z"></path></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z"></path></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x39" d="M244 635q90 0 143 -72t53 -177q0 -133 -65 -229.5t-171 -139.5q-79 -32 -140 -32l-5 30q109 18 185 91t101 186l-68 -36q-29 -16 -60 -16q-79 0 -129 51.5t-50 130.5q0 80 57 146.5t149 66.5zM228 602q-52 0 -78 -45.5t-26 -98.5q0 -69 36.5 -115.5t97.5 -46.5&#xA;q53 0 90 28q4 31 4 66q0 51 -9.5 95.5t-39 80.5t-75.5 36z"></path></g>

		
	
</svg>). In the NSCLC samples, As was measurable in moderate amounts, while Hg and Pb amounts were negligible. <i> Conclusion</i>. Cd and As are present in lung tissues for patients with NSCLC. With existing preclinical evidence of their tumorigenecity, it is plausible that Cd and/or As may have an impact on NSCLC development. Additional studies examining the prevalence and association between smokers and nonsmokers are suggested.

Jessica Q. Tran

Alexandra Dranikov

Anita Iannucci

Walter P. Wagner

Janine LoBello

Jeffrey Allen

Glen J. Weiss

Heavy Metal Content in Thoracic Tissue Samples from Patients with and without NSCLC

The role of alveolar macrophages in lung cancer is multifaceted and conflicting. Alveolar macrophage secretion of proinflammatory cytokines has been found to enhance antitumour functions, cytostasis (inhibition of tumour growth), and cytotoxicity (macrophage-mediated killing). In contrast, protumour functions of alveolar macrophages in lung cancer have also been indicated. Inhibition of antitumour function via secretion of the anti-inflammatory cytokine IL-10 as well as reduced secretion of proinflammatory cytokines and reduction of mannose receptor expression on alveolar macrophages may contribute to lung cancer progression and metastasis. Alveolar macrophages have also been found to contribute to angiogenesis and tumour growth via the secretion of IL-8 and VEGF. This paper reviews the evidence for a dual role of alveolar macrophages in lung cancer progression.

Saleh A. Almatroodi

Christine F. McDonald

Dodie S. Pouniotis

Alveolar Macrophage Polarisation in Lung Cancer

<i>Background</i>. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. <i>Methods</i>. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. <i>Results</i>. The median survival was 5.6 months (IQR 4.8&#x2013;6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. <i>Discussion</i>. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer.

Derek Grose

Graham Devereux

Louise Brown

Richard Jones

Dave Sharma

Colin Selby

David S. Morrison

Kirsty Docherty

David McIntosh

Penny McElhinney

Marianne Nicolson

Donald C. McMillan

Robert Milroy

Simple and Objective Prediction of Survival in Patients with Lung Cancer: Staging the Host Systemic Inflammatory Response

<i  >Objectives</i>. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1<i  >&#x3b1;</i>) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1<i  >&#x3b1;</i> and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. <i  >Methodology</i>. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1<i  >&#x3b1;</i> was performed through real-time quantitative polymerase chain reaction (qRT-PCR). <i  >Results</i>. Mean age was 64.7 and  86.5&#x25; of patients were male. Stage IA represented 23.1&#x25; and stage IB 76.9&#x25;. Histology classification was 42.3&#x25; adenocarcinoma, 34.6&#x25; squamous cell carcinoma, and 23.1&#x25; others. Median survival was 81.0 months and 5-year survival 67.2&#x25;. There was correlation between HIF-1<i  >&#x3b1;</i>  and VEGF-A (<svg     style="vertical-align:-0.17555pt;width:66.875px;" id="M1" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g>

		
	
</svg>). Patients with overexpression of HIF-1<i  >&#x3b1;</i> had a tendency to better survival with marginal statistical significance (<svg     style="vertical-align:-0.17555pt;width:66.875px;" id="M2" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x36"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g>

		
	
</svg>). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (<svg     style="vertical-align:-0.17555pt;width:66.875px;" id="M3" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x31"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><use xlink:href="#x33"/></g>

		
	
</svg>). <i  >Conclusion</i>. The present study revealed that VEGF-A showed correlation with HIF-1<i  >&#x3b1;</i>. HIF-1<i  >&#x3b1;</i> had a tendency to protective effect with a <svg     style="vertical-align:-0.0pt;width:10.9375px;" id="M4" height="11.175" version="1.1" viewBox="0 0 10.9375 11.175" width="10.9375"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.113)"><use xlink:href="#x1D443"/></g>

		
	
</svg> value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance. 



Antonio Francisco Honguero Mart&#xed;nez

Antonio Arnau Obrer

Santiago Figueroa Alm&#xe1;nzar

Pablo Le&#xf3;n Atance

Ricardo Guijarro Jorge

Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer

We studied argyrophilic proteins associated with nucleolar organizer regions (AgNOR) in non-small-cell cancer. We determined the area index (AI) and coefficient of variation (CV) of AgNOR. AI is associated with the key clinicomorphological parameters within the TNM system: <svg     style="vertical-align:-0.0pt;width:11.45px;" id="M1" height="11.6125" version="1.1" viewBox="0 0 11.45 11.6125" width="11.45"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.55)"><path id="x1D447" d="M649 676l-22 -187l-33 -2q3 56 -12 94q-8 20 -31.5 26.5t-86.5 6.5h-74l-90 -491q-4 -23 -6 -36.5t1 -25t7 -16.5t18 -9t27 -5t41 -3l-6 -28h-286l4 28q68 5 84 18.5t28 76.5l94 491h-55q-74 0 -100.5 -6t-41.5 -23q-24 -29 -54 -98l-32 1q32 98 53 188h22q7 -18 15 -22&#xA;t37 -4h417q23 0 33.5 5t25.5 21h23z" /></g>

		
	
</svg> and <svg     style="vertical-align:-0.1092pt;width:14.9875px;" id="M2" height="11.3125" version="1.1" viewBox="0 0 14.9875 11.3125" width="14.9875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.113)"><path id="x1D441" d="M857 650l-6 -28q-44 -4 -61.5 -16.5t-29.5 -48.5q-11 -32 -37 -166l-78 -399h-29l-351 537h-4l-56 -276q-24 -120 -24 -164q0 -35 17.5 -46t75.5 -15l-6 -28h-245l7 28q41 2 62 14t31 44q10 30 41 171l53 245q8 44 6.5 60.5t-14.5 33.5q-10 15 -27 19.5t-64 6.5l6 28h153&#xA;l350 -516h5l48 257q25 131 25 171q0 34 -17.5 45t-77.5 15l7 28h240z" /></g>

		
	
</svg> values, greatest tumor dimension up to 3&#x2009;cm and more, disease stage, histogenesis, and tumor differentiation. CV is associated with <svg     style="vertical-align:-0.0pt;width:11.45px;" id="M3" height="11.6125" version="1.1" viewBox="0 0 11.45 11.6125" width="11.45"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.55)"><use xlink:href="#x1D447"/></g>

		
	
</svg> value, greatest tumor dimension up to 3&#x2009;cm and more, histogenesis, and tumor differentiation. Survival of patients is longer in low AI or CV values versus high AI or CV values, longer in low AI and CV values (&#x2212;AI/&#x2212;CV type), shorter in high AI and CV values (+AI/+CV type), and intermediate in opposite AI and CV values (&#x2212;AI/+CV and +AI/&#x2212;CV types). Independent predictors in non-small-cell lung cancer include <svg     style="vertical-align:-0.1092pt;width:14.9875px;" id="M4" height="11.3125" version="1.1" viewBox="0 0 14.9875 11.3125" width="14.9875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.113)"><use xlink:href="#x1D441"/></g>

		
	
</svg> value, greatest tumor dimension, histogenesis, and CV. Assessment of quantitative values and heterogeneity of AgNOR is important for differential diagnosis and prognosis of non-small-cell lung cancer.

Dmitriy Kobyakov

Vladimir Klimachev

Ashot Avdalyan

Igor Bobrov

Elena Bychkova

Natalia Kruglova

Aleksandr Lazarev

Elena Lushnikova

Lev Nepomnyashchikh

Association between Argyrophilic Proteins of Nucleolar Organizer Regions, Clinicomorphological Parameters, and Survival in Non-Small-Cell Lung Cancer

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Lung Cancer International