Health & Environmental Research Online (HERO)


Mouse Lung Tumor

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47 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Epigenetic biomarkers in lung cancer

Authors: Liloglou, T; Bediaga, NG; Brown, BR; Field, JK; Davies, MP (In Press) Cancer Letters. HERO ID: 1597197

[Less] Lung cancer mortality is strongly associated with the predominant diagnosis of late stage lesions that . . . [More] Lung cancer mortality is strongly associated with the predominant diagnosis of late stage lesions that hampers effective therapy. Molecular biomarkers for early lung cancer detection is an unmet public health need and the lung cancer research community worldwide is putting a lot of effort to utilise major lung cancer population programmes in order to develop such molecular tools. The study of cancer epigenetics in the last decade has radically altered our views in cancer pathogenesis, providing new insights in biomarker development for risk assessment, early detection and therapeutic stratification. DNA methylation and miRNAs have rapidly emerged as potential biomarkers in body fluids showing promise to assist the clinical management of lung cancer. These new developments are exemplified in this review, demonstrating the huge potential of clinical cancer epigenetics, but also critically discussing the necessary validation steps to bring epigenetic biomarkers towards clinical implementation and the weaknesses of current biomarker studies.

Technical Report
Technical Report

Cancer facts & figures 2014

Author: American Cancer Society (2014) Atlanta, GA: American Cancer Society. HERO ID: 2347019


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Induction of multiciliated cells from induced pluripotent stem cells

Author: Gomperts, BN (2014) HERO ID: 2347031


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Transcriptomic architecture of the adjacent airway field cancerization in non-small cell lung cancer

Authors: Kadara, H; Fujimoto, J; Yoo, SY; Maki, Y; Gower, AC; Kabbout, M; Garcia, MM; Chow, CW; Chu, Z; Mendoza, G; Shen, L; Kalhor, N; Hong, WK; Moran, C; Wang, J; Spira, A; Coombes, KR; Wistuba, II (2014) HERO ID: 2347032

[Less] BACKGROUND: Earlier work identified specific tumor-promoting abnormalities that are . . . [More] BACKGROUND: Earlier work identified specific tumor-promoting abnormalities that are shared between lung cancers and adjacent normal bronchial epithelia. We sought to characterize the yet unknown global molecular and adjacent airway field cancerization (FC) in early-stage non-small cell lung cancer (NSCLC).

METHODS: Whole-transcriptome expression profiling of resected early-stage (I-IIIA) NSCLC specimens (n = 20) with matched tumors, multiple cytologically controlled normal airways with varying distances from tumors, and uninvolved normal lung tissues (n = 194 samples) was performed using the Affymetrix Human Gene 1.0 ST platform. Mixed-effects models were used to identify differentially expressed genes among groups. Ordinal regression analysis was performed to characterize site-dependent airway expression profiles. All statistical tests were two-sided, except where noted.

RESULTS: We identified differentially expressed gene features (n = 1661) between NSCLCs and airways compared with normal lung tissues, a subset of which (n = 299), after gene set enrichment analysis, statistically significantly (P < .001) distinguished large airways in lung cancer patients from airways in cancer-free smokers. In addition, we identified genes (n = 422) statistically significantly and progressively differentially expressed in airways by distance from tumors that were found to be congruently modulated between NSCLCs and normal lung tissues. Furthermore, LAPTM4B, with statistically significantly increased expression (P < .05) in airways with shorter distance from tumors, was upregulated in human immortalized cells compared with normal bronchial epithelial cells (P < .001) and promoted anchorage-dependent and -independent lung cancer cell growth.

CONCLUSIONS: The adjacent airway FC comprises both site-independent profiles as well as gradient and localized airway expression patterns. Profiling of the airway FC may provide new insights into NSCLC oncogenesis and molecular tools for detection of the disease.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Exposure-Response Estimates for Diesel Engine Exhaust and Lung Cancer Mortality Based on Data from Three Occupational Cohorts

Authors: Vermeulen, R; Silverman, DT; Garshick, E; Vlaanderen, J; Portengen, L; Steenland, K (2014) Environmental Health Perspectives 122:172-177. HERO ID: 2215191

[Less] BACKGROUND: Diesel engine exhaust (DEE) has recently been classified as a known human . . . [More] BACKGROUND: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen.

OBJECTIVE: To derive a meta-exposure-response curve (ERC) for DEE and lung cancer mortality and estimate lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios.

METHODS: We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios, and also calculated the fractions of annual lung cancer deaths attributable to DEE.

RESULTS: We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m(3)-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through age 80 for lifetime occupational exposures of 1, 10, and 25 μg/m(3) EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m(3) EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures we estimate that approximately 6% of annual lung cancer deaths may be due to DEE exposure.

CONCLUSIONS: Combined data from three US occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above usually acceptable limits in the US and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review

Authors: Lee, PN; Forey, BA (2013) BMC Cancer 13:189. [Review] HERO ID: 2347016

[Less] BACKGROUND: National smoking-specific lung cancer mortality rates are unavailable, . . . [More] BACKGROUND: National smoking-specific lung cancer mortality rates are unavailable, and studies presenting estimates are limited, particularly by histology. This hinders interpretation. We attempted to rectify this by deriving estimates indirectly, combining data from national rates and epidemiological studies.

METHODS: We estimated study-specific absolute mortality rates and variances by histology and smoking habit (never/ever/current/former) based on relative risk estimates derived from studies published in the 20th century, coupled with WHO mortality data for age 70-74 for the relevant country and period. Studies with populations grossly unrepresentative nationally were excluded. 70-74 was chosen based on analyses of large cohort studies presenting rates by smoking and age. Variations by sex, period and region were assessed by meta-analysis and meta-regression.

RESULTS: 148 studies provided estimates (Europe 59, America 54, China 22, other Asia 13), 54 providing estimates by histology (squamous cell carcinoma, adenocarcinoma). For all smoking habits and lung cancer types, mortality rates were higher in males, the excess less evident for never smokers. Never smoker rates were clearly highest in China, and showed some increasing time trend, particularly for adenocarcinoma. Ever smoker rates were higher in parts of Europe and America than in China, with the time trend very clear, especially for adenocarcinoma. Variations by time trend and continent were clear for current smokers (rates being higher in Europe and America than Asia), but less clear for former smokers. Models involving continent and trend explained much variability, but non-linearity was sometimes seen (with rates lower in 1991-99 than 1981-90), and there was regional variation within continent (with rates in Europe often high in UK and low in Scandinavia, and higher in North than South America).

CONCLUSIONS: The indirect method may be questioned, because of variations in definition of smoking and lung cancer type in the epidemiological database, changes over time in diagnosis of lung cancer types, lack of national representativeness of some studies, and regional variation in smoking misclassification. However, the results seem consistent with the literature, and provide additional information on variability by time and region, including evidence of a rise in never smoker adenocarcinoma rates relative to squamous cell carcinoma rates.

Archival Material
Archival Material

Surveillance, epidemiology, and end results program: turning cancer data into discovery

Author: NCI (2013) HERO ID: 2347020


Journal Article
Journal Article

Enriching the molecular definition of the airway "field of cancerization:" establishing new paradigms for the patient at risk for lung cancer

Authors: Gomperts, BN; Walser, TC; Spira, A; Dubinett, SM (2013) HERO ID: 2347030

[Less] The "field of cancerization" refers to histologically normal-appearing tissue adjacent to . . . [More] The "field of cancerization" refers to histologically normal-appearing tissue adjacent to neoplastic tissue that displays molecular abnormalities, some of which are the same as those of the tumor. Improving our understanding of these molecular events is likely to increase our understanding of carcinogenesis. Kadara and colleagues attempt to characterize the molecular events occurring temporally and spatially within the field of cancerization of patients with early-stage non-small cell lung cancer (NSCLC) following definitive surgery. They followed patients with bronchoscopies annually after tumor resection and extracted RNA from the serial brushings from different endobronchial sites. They then conducted microarray analysis to identify gene expression differences over time and in different sites in the airway. Candidate genes were found that may have biologic relevance to the field of cancerization. For example, expression of phosphorylated AKT and ERK1/2 was found to increase in the airway epithelium with time. Although there are limitations in the study design, this investigation demonstrates the utility of identifying molecular changes in histologically normal airway epithelium in lung cancer. In addition to increasing our understanding of lung cancer biology, studying the field of cancerization has the potential to identify biomarkers from samples obtained in a minimally invasive manner.

Journal Article
Journal Article

Characterizing the molecular spatial and temporal field of injury in early-stage smoker non-small cell lung cancer patients after definitive surgery by expression profiling

Authors: Kadara, H; Shen, L; Fujimoto, J; Saintigny, P; Chow, CW; Lang, W; Chu, Z; Garcia, M; Kabbout, M; Fan, YH; Behrens, C; Liu, DA; Mao, L; Lee, JJ; Gold, KA; Wang, J; Coombes, KR; Kim, ES; Hong, WK; Wistuba, II (2013) HERO ID: 2347033

[Less] Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing . . . [More] Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing bronchial epithelium of healthy smokers, and it has been suggested that adjacent histologically normal tissue displays tumor-associated molecular abnormalities. We sought to delineate the spatial and temporal molecular lung field of injury in smoker patients with early-stage non-small cell lung cancer (NSCLC; n = 19) who were accrued into a surveillance clinical trial for annual follow-up and bronchoscopies within 1 year after definitive surgery. Bronchial brushings and biopsies were obtained from six different sites in the lung at the time of inclusion in the study and at 12, 24, and 36 months after the first time point. Affymetrix Human Gene 1.0 ST arrays were used for whole-transcript expression profiling of airways (n = 391). Microarray analysis identified gene features (n = 1,165) that were nonuniform by site and differentially expressed between airways adjacent to tumors relative to more distant samples as well as those (n = 1,395) that were significantly altered with time up to 3 years. In addition, gene interaction networks mediated by phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK)1/2 were modulated in adjacent compared with contralateral airways and the latter network with time. Furthermore, phosphorylated AKT and ERK1/2 immunohistochemical expression were significantly increased with time (nuclear pAKT, P = 0.03; cytoplasmic pAKT, P < 0.0001; pERK1/2, P = 0.02) and elevated in adjacent compared with more distant airways (nuclear pAKT, P = 0.04; pERK1/2, P = 0.03). This study highlights spatial and temporal cancer-associated expression alterations in the molecular field of injury of patients with early-stage NSCLCs after definitive surgery that warrant further validation in independent studies.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

New pathologic classification of lung cancer: relevance for clinical practice and clinical trials

Authors: Travis, WD; Brambilla, E; Riely, GJ (2013) HERO ID: 2347034

[Less] We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 . . . [More] We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. The classification was developed by an international core panel of experts representing IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. Because 70% of patients with lung cancer present with advanced stages, a new approach to small biopsies and cytology with specific terminology and criteria focused on the need for distinguishing squamous cell carcinoma from adenocarcinoma and on molecular testing for EGFR mutations and ALK rearrangement. Tumors previously classified as non-small-cell carcinoma, not otherwise specified, because of the lack of clear squamous or adenocarcinoma morphology should be classified further by using a limited immunohistochemical workup to preserve tissue for molecular testing. The terms "bronchioloalveolar carcinoma" and "mixed subtype adenocarcinoma" have been discontinued. For resected adenocarcinomas, new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma define patients who, if they undergo complete resection, will have 100% disease-free survival. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype with poor prognosis. Former mucinous bronchioloalveolar carcinomas are now called "invasive mucinous adenocarcinoma." Because the lung cancer field is now rapidly evolving with new advances occurring on a frequent basis, particularly in the molecular arena, this classification provides a much needed standard for pathologic diagnosis not only for patient care but also for clinical trials and TNM classification.