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Mouse Lung Tumor

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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.

Technical Report
Technical Report

Summary report: State-of-the-science workshop on chemically-induced mouse lung tumors: Applications to human health assessments

Author: U.S. EPA (2014) (600R14002). HERO ID: 3056779


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.

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

Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification

Authors: Travis, WD; Brambilla, E; Noguchi, M; Nicholson, AG; Geisinger, K; Yatabe, Y; Ishikawa, Y; Wistuba, I; Flieder, DB; Franklin, W; Gazdar, A; Hasleton, PS; Henderson, DW; Kerr, KM; Petersen, I; Roggli, V; Thunnissen, E; Tsao, M (2013) HERO ID: 2347035

[Less] The new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory . . . [More] The new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification provides, for the first time, standardized terminology for lung cancer diagnosis in small biopsies and cytology; this was not primarily addressed by previous World Health Organization classifications. Until recently there have been no therapeutic implications to further classification of NSCLC, so little attention has been given to the distinction of adenocarcinoma and squamous cell carcinoma in small tissue samples. This situation has changed dramatically in recent years with the discovery of several therapeutic options that are available only to patients with adenocarcinoma or NSCLC, not otherwise specified, rather than squamous cell carcinoma. This includes recommendation for use of special stains as an aid to diagnosis, particularly in the setting of poorly differentiated tumors that do not show clear differentiation by routine light microscopy. A limited diagnostic workup is recommended to preserve as much tissue for molecular testing as possible. Most tumors can be classified using a single adenocarcinoma marker (eg, thyroid transcription factor 1 or mucin) and a single squamous marker (eg, p40 or p63). Carcinomas lacking clear differentiation by morphology and special stains are classified as NSCLC, not otherwise specified. Not otherwise specified carcinomas that stain with adenocarcinoma markers are classified as NSCLC, favor adenocarcinoma, and tumors that stain only with squamous markers are classified as NSCLC, favor squamous cell carcinoma. The need for every institution to develop a multidisciplinary tissue management strategy to obtain these small specimens and process them, not only for diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, is emphasized.

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

Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification

Authors: Travis, WD; Brambilla, E; Noguchi, M; Nicholson, AG; Geisinger, K; Yatabe, Y; Ishikawa, Y; Wistuba, I; Flieder, DB; Franklin, W; Gazdar, A; Hasleton, PS; Henderson, DW; Kerr, KM; Nakatani, Y; Petersen, I; Roggli, V; Thunnissen, E; Tsao, M (2013) HERO ID: 2347036

[Less] A new lung adenocarcinoma classification has been published by the International Association for the . . . [More] A new lung adenocarcinoma classification has been published by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. This new classification is needed to provide uniform terminology and diagnostic criteria, most especially for bronchioloalveolar carcinoma. It was developed by an international core panel of experts representing all 3 societies with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons.This summary focuses on the aspects of this classification that address resection specimens. The terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced, such as adenocarcinoma in situ and minimally invasive adenocarcinoma for small solitary adenocarcinomas with either pure lepidic growth (adenocarcinoma in situ) and predominant lepidic growth with invasion of 5 mm or less (minimally invasive adenocarcinoma), to define the condition of patients who will have 100% or near 100% disease-specific survival, respectively, if they undergo complete lesion resection. Adenocarcinoma in situ and minimally invasive adenocarcinoma are usually nonmucinous, but rarely may be mucinous. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous bronchioloalveolar carcinoma), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid, fetal, and enteric adenocarcinoma.It is possible that this classification may impact the next revision of the TNM staging classification, with adjustment of the size T factor according to only the invasive component pathologically in adenocarcinomas with lepidic areas.

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

Radiologic implications of the 2011 classification of adenocarcinoma of the lung

Authors: Austin, JH; Garg, K; Aberle, D; Yankelevitz, D; Kuriyama, K; Lee, HJ; Brambilla, E; Travis, WD (2013) HERO ID: 2347037

[Less] Now the leading subtype of lung cancer, adenocarcinoma received a new classification in 2011. For tumors . . . [More] Now the leading subtype of lung cancer, adenocarcinoma received a new classification in 2011. For tumors categorized previously as bronchioloalveolar carcinoma (BAC), criteria and terminology had not been uniform, so the 2011 classification provided four new terms: (a) adenocarcinoma in situ (AIS), representing histopathologically a small (≤3-cm), noninvasive lepidic growth, which at computed tomography (CT) is usually nonsolid; (b) minimally invasive adenocarcinoma, representing histopathologically a small (≤3-cm) and predominantly lepidic growth that has 5-mm or smaller invasion, which at CT is mainly nonsolid but may have a central solid component of up to approximately 5 mm; (c) lepidic predominant nonmucinous adenocarcinoma, representing histopathologically invasive adenocarcinoma that shows predominantly lepidic nonmucinous growth, which at CT is usually part solid but may be nonsolid or occasionally have cystic components; and (d) invasive mucinous adenocarcinoma, histopathologically showing lepidic growth as its predominant component, which at CT varies widely from solid to mostly solid to part solid to nonsolid and may be single or multiple (when multifocal, it was formerly called multicentric BAC). In addition, new histopathologic subcategories of acinar, papillary, micropapillary, and solid predominant adenocarcinoma are now described, all as nonmucinous, predominantly invasive, may include a small lepidic component, and at CT are usually solid but may include a small nonsolid component. The micropapillary subtype has a poorer prognosis than the other subtypes. In addition, molecular genetic correlations for the subcategories of adenocarcinoma of the lung are now a topic of increasing interest. As the new classification enters common use, further descriptions of related correlations can be anticipated.