Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

PubMed

Nguyen-Kim, Thi Dan Linh; Frauenfelder, Thomas; Strobel, Klaus; Veit-Haibach, Patrick; Huellner, Martin W

2015-03-01

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer.

PubMed

Castellanos, Emily; Feld, Emily; Horn, Leora

2017-04-01

EGFR-mutated NSCLC is a genetically heterogeneous disease that includes more than 200 distinct mutations. The implications of mutational subtype for both prognostic and predictive value are being increasingly understood. Although the most common EGFR mutations-exon 19 deletions or L858R mutations-predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), it is now being recognized that outcomes may be improved in patients with exon 19 deletions. Additionally, 10% of patients will have an uncommon EGFR mutation, and response to EGFR TKI therapy is highly variable depending on the mutation. Given the growing recognition of the genetic and clinical variation seen in this disease, the development of comprehensive bioinformatics-driven tools to both analyze response in uncommon mutation subtypes and inform clinical decision making will be increasingly important. Clinical trials of novel EGFR TKIs should prospectively account for the presence of uncommon mutation subtypes in study design. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

NASA Astrophysics Data System (ADS)

Ashkani, Jahanshah; Naidoo, Kevin J.

2016-05-01

Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

Survival in patients with metachronous second primary lung cancer.

PubMed

Ha, Duc; Choi, Humberto; Chevalier, Cory; Zell, Katrina; Wang, Xiao-Feng; Mazzone, Peter J

2015-01-01

Four to 10% of patients with non-small cell lung cancer subsequently develop a metachronous second primary lung cancer. The decision to perform surveillance or screening imaging for patients with potentially cured lung cancer must take into account the outcomes expected when detecting metachronous second primaries. To assess potential survival differences between patients with metachronous second primary lung cancer compared to matched patients with first primary lung cancer. We retrospectively reviewed patients diagnosed with lung cancer at the Cleveland Clinic (2006-2010). Metachronous second primary lung cancer was defined as lung cancer diagnosed after a 4-year, disease-free interval from the first lung cancer, or if there were two different histologic subtypes diagnosed at different times. Patients with first primary lung cancer diagnosed in the same time period served as control subjects. Propensity score matching was performed using age, sex, smoking history, histologic subtype, and collaborative stage, with a 1:3 case-control ratio. Survival analyses were performed by Cox proportional hazards modeling and Kaplan-Meier estimates. Forty-four patients met criteria for having a metachronous second primary lung cancer. There were no statistically significant differences between case subjects and control subjects in prognostic variables. The median survival time and 2-year overall survival rate for the metachronous second primary group, compared with control subjects, were as follows: 11.8 versus 18.4 months (P = 0.18) and 31.0 versus 40.9% (P = 0.28). The survival difference was largest in those with stage I metachronous second primaries (median survival time, 26.8 vs. 60.4 mo, P = 0.09; 2-year overall survival, 56.3 vs. 71.2%, P = 0.28). Patients with stage I metachronous second primary lung cancer may have worse survival than those who present with a first primary lung cancer. This could influence the benefit-risk balance of screening the high-risk cohort with

Predicting Survival within the Lung Cancer Histopathological Hierarchy Using a Multi-Scale Genomic Model of Development

PubMed Central

Liu, Hongye; Kho, Alvin T; Kohane, Isaac S; Sun, Yao

2006-01-01

Background The histopathologic heterogeneity of lung cancer remains a significant confounding factor in its diagnosis and prognosis—spurring numerous recent efforts to find a molecular classification of the disease that has clinical relevance. Methods and Findings Molecular profiles of tumors from 186 patients representing four different lung cancer subtypes (and 17 normal lung tissue samples) were compared with a mouse lung development model using principal component analysis in both temporal and genomic domains. An algorithm for the classification of lung cancers using a multi-scale developmental framework was developed. Kaplan–Meier survival analysis was conducted for lung adenocarcinoma patient subgroups identified via their developmental association. We found multi-scale genomic similarities between four human lung cancer subtypes and the developing mouse lung that are prognostically meaningful. Significant association was observed between the localization of human lung cancer cases along the principal mouse lung development trajectory and the corresponding patient survival rate at three distinct levels of classical histopathologic resolution: among different lung cancer subtypes, among patients within the adenocarcinoma subtype, and within the stage I adenocarcinoma subclass. The earlier the genomic association between a human tumor profile and the mouse lung development sequence, the poorer the patient's prognosis. Furthermore, decomposing this principal lung development trajectory identified a gene set that was significantly enriched for pyrimidine metabolism and cell-adhesion functions specific to lung development and oncogenesis. Conclusions From a multi-scale disease modeling perspective, the molecular dynamics of murine lung development provide an effective framework that is not only data driven but also informed by the biology of development for elucidating the mechanisms of human lung cancer biology and its clinical outcome. PMID:16800721

Diagnosing lung cancer using coherent anti-Stokes Raman scattering microscopy

NASA Astrophysics Data System (ADS)

Gao, Liang; Yang, Yaliang; Xing, Jiong; Thrall, Michael J.; Wang, Zhiyong; Li, Fuhai; Luo, Pengfei; Wong, Kelvin K.; Zhao, Hong; Wong, Stephen T. C.

2011-03-01

Lung carcinoma is the most prevalent type of cancer in the world, and it is responsible for more deaths than other types of cancer. During diagnosis, a pathologist primarily aims to differentiate small cell carcinoma from non-small cell carcinoma on biopsy and cytology specimens, which is time consuming due to the time required for tissue processing and staining. To speed up the diagnostic process, we investigated the feasibility of using coherent anti-Stokes Raman scattering (CARS) microscopy as a label-free strategy to image lung lesions and differentiate subtypes of lung cancers. Different mouse lung cancer models were developed by injecting human lung cancer cell lines, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, into lungs of the nude mice. CARS images were acquired from normal lung tissues and different subtypes of cancer lesions ex vivo using intrinsic contrasts from symmetric CH2 bonds. These images showed good correlation with the hematoxylin and eosin (H&E) stained sections from the same tissue samples with regard to cell size, density, and cell-cell distance. These features are routinely used in diagnosing lung lesions. Our results showed that the CARS technique is capable of providing a visualizable platform to differentiate different kinds of lung cancers using the same pathological features without histological staining and thus has the potential to serve as a more efficient examination tool for diagnostic pathology. In addition, incorporating with suitable fiber-optic probes would render the CARS technique as a promising approach for in vivo diagnosis of lung cancer.

Combining Cell Type-Restricted Adenoviral Targeting with Immunostaining and Flow Cytometry to Identify Cells-of-Origin of Lung Cancer.

PubMed

Best, Sarah A; Kersbergen, Ariena; Asselin-Labat, Marie-Liesse; Sutherland, Kate D

2018-01-01

Lung cancers display considerable intertumoral heterogeneity, leading to the classification of distinct tumor subtypes. Our understanding of the genetic aberrations that underlie tumor subtypes has been greatly enhanced by recent genomic sequencing studies and state-of-the-art gene targeting technologies, highlighting evidence that distinct lung cancer subtypes may be derived from different "cells-of-origin". Here, we describe the intra-tracheal delivery of cell type-restricted Ad5-Cre viruses into the lungs of adult mice, combined with immunohistochemical and flow cytometry strategies for the detection of lung cancer-initiating cells in vivo.

Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992-2013.

PubMed

Noone, Anne-Michelle; Cronin, Kathleen A; Altekruse, Sean F; Howlader, Nadia; Lewis, Denise R; Petkov, Valentina I; Penberthy, Lynne

2017-04-01

Background: Cancers are heterogeneous, comprising distinct tumor subtypes. Therefore, presenting the burden of cancer in the population and trends over time by these tumor subtypes is important to identify patterns and differences in the occurrence of these subtypes, especially to generalize findings to the U.S. general population. Methods: Using SEER Cancer Registry Data, we present incidence rates according to subtypes for diagnosis years (1992-2013) among men and women for five major cancer sites: breast (female only), esophagus, kidney and renal pelvis, lung and bronchus, and thyroid. We also describe estimates of 5-year relative survival according to subtypes and diagnosis year (1992-2008). We used Joinpoint models to identify years when incidence rate trends changed slope. Finally, recent 5-year age-adjusted incidence rates (2009-2013) are presented for each subtype by race and age. Results: Hormone receptor-positive and HER2-negative was the most common subtype (about 74%) of breast cancers. Adenocarcinoma made up about 69% of esophagus cases among men. Adenocarcinoma also is the most common lung subtype (43% in men and 52% in women). Ninety percent of thyroid subtypes were papillary. Distinct incidence and survival patterns emerged by these subtypes over time among men and women. Conclusions: Histologic or molecular subtype revealed different incidence and/or survival trends that are masked when cancer is considered as a single disease on the basis of anatomic site. Impact: Presenting incidence and survival trends by subtype, whenever possible, is critical to provide more detailed and meaningful data to patients, providers, and the public. Cancer Epidemiol Biomarkers Prev; 26(4); 632-41. ©2016 AACR . ©2016 American Association for Cancer Research.

Maternal lung cancer and testicular cancer risk in the offspring.

PubMed

Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Alectinib Approved for ALK+ Lung Cancer.

PubMed

2016-02-01

The FDA has approved a third ALK inhibitor, alectinib, for advanced ALK-positive non-small cell lung cancer. Two phase II studies show that patients who have become resistant to crizotinib respond well to alectinib; the drug is also effective against brain metastases, which are common in this disease subtype. ©2016 American Association for Cancer Research.

Lung Cancer in HIV Infection

PubMed Central

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2011-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the HAART era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is 2–4 times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the commonest histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Since pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies for this population frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. PMID:21802373

A global view of regulatory networks in lung cancer: An approach to understand homogeneity and heterogeneity.

PubMed

Lu, Jiapei; Wang, William; Xu, Menglin; Li, Yuping; Chen, Chengshui; Wang, Xiangdong

2017-02-01

A number of new biotechnologies are used to identify potential biomarkers for the early detection of lung cancer, enabling a personalized therapy to be developed in response. The combinatorial cross-regulation of hundreds of biological function-specific transcription factors (TFs) is defined as the understanding of regulatory networks of molecules within the cell. Here we integrated global databases with 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without cancer with the understanding of TF functions. The present review aims at the homogeneity or heterogeneity of gene expression profiles among subtypes of lung cancer. About 5, 136, 52, or 16 up-regulated or 19, 24, 122, or 97down-regulated type-special TF genes were identified in ADC, SCC, LCC or SCLC, respectively. DNA-binding and transcription regulator activity associated genes play a dominant role in the differentiation of subtypes in lung cancer. Subtype-specific TF gene regulatory networks with elements should be an alternative for diagnostic and therapeutic targets for early identification of lung cancer and can provide insightful clues to etiology and pathogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

Cancer.gov

In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to

[Value of liquid-based cytology of brushing specimens obtained via fiberoptic bronchoscopy for the diagnosis of lung cancer].

PubMed

Zhao, Huan; Guo, Huiqin; Zhang, Chuanxin; Zhao, Linlin; Cao, Jian; Pan, Qinjing

2015-06-01

To investigate the value of the liquid-based cytology (LBC) of brushing specimens obtained via fiberoptic bronchoscopy for clinical diagnosis of lung cancer. We retrospectively analyzed the LBC cases in our hospital from January 2011 to May 2012, and evaluate its role in the diagnosis of lung cancer. The clinical data of a total of 4 380 cases were reviewed and 3 763 of them had histopathological or clinical follow-up results (including 3 306 lung cancer cases and 457 benign lesion cases). The sensitivity, specificity, and accuracy of LBC diagnosis for lung cancer were 72.4% (2 392/3 306), 99.3% (454/457) and 75.6% (2 846/3 763), respectively. Of the 1 992 lung cancer cases diagnosed by brushing LBC, 528 cases (26.5%) were failed to take forceps biopsy and 113 cases (5.7%) showed negative forceps biopsy results. The accurate rate of subtyping of LBC for non-small cell carcinoma and small cell carcinoma was 99.0% (1 487/1 502) (P < 0.001). Take the resection histopathology as gold standard, the accurate rates of subtyping squamous cell carcinoma, adenocarcinoma and small cell carcinoma by LBC were 95.6% (351/367), 95.6% (351/367) and 100% (367/367), respectively, (P < 0.001). The accurate rates of subtyping of squamous cell carcinoma, adenocarcinoma and small cell carcinoma by forceps biopsy were 97.0% (293/302), 97.4% (294/302) and 99.7% (301/302), respectively, (Kappa = 0.895, P < 0.001). There was no significant difference in subtyping respectively between forceps biopsy and brushing LBC (P > 0.05). Fiberoptic bronchoscopic brushing liquid-based cytology can significantly improve the detection rate of lung cancer, and have a high specificity and accurate rate of subtyping. It is an effective tool for the diagnosis and subtyping of lung cancer.

Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

PubMed Central

Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

2013-01-01

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

Lung cancer in HIV Infection.

PubMed

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2012-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the highly active antiretroviral therapy era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is two to four times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the most common histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Because pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early-stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies because this population is frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. Copyright © 2012 Elsevier Inc. All rights reserved.

Patterns of breast cancer relapse in accordance to biological subtype.

PubMed

Ignatov, Atanas; Eggemann, Holm; Burger, Elke; Ignatov, Tanja

2018-04-19

To evaluate the pattern of recurrence of breast cancer according to its biological subtype in a large cohort of patients treated with therapy representative of current practice. Patients treated between 2000 and 2016 with known biological subtype were eligible. Data were prospectively collected. Primary endpoint was the subtype-dependent pattern and time of recurrence. Loco-regional and distant site and time of recurrence were assessed. Median follow-up time was 80.8 months. For 12,053 (82.5%) of 14,595 patients with primary non-metastatic invasive breast cancer a subtype classification was possible. The luminal A subtype had the highest 10-year survival followed by luminal B and luminal/HER2. The worst survival demonstrated HER2 enriched and TNBC. HER2 and TNBC had the highest rate of recurrence in the first 5 years, whereas the rate of recurrence for luminal A and luminal B tumors was initially low, but remained continuously even after 10 years of follow-up. Luminal A tumors demonstrated the lowest rate of distant metastases predominantly in bone. So did luminal B tumors. HER2 enriched subtype was characterized with increased rate of loco-regional recurrence and distant metastases in bone, liver and brain. Luminal/HER2 had pattern of relapse similar to HER2 enriched tumors, with exception of loco-regional relapse and brain metastases. TNBC had higher rate of lung, bone and brain metastases as well as loco-regional relapse. Breast cancer subtypes are associated with different time and pattern of recurrence and it should be considered during treatment decision.

Added prognostic value of CT characteristics and IASLC/ATS/ERS histologic subtype in surgically resected lung adenocarcinomas.

PubMed

Suh, Young Joo; Lee, Hyun-Ju; Kim, Young Tae; Kang, Chang Hyun; Park, In Kyu; Jeon, Yoon Kyung; Chung, Doo Hyun

2018-06-01

Our study investigates the added value of computed tomography (CT) characteristics, histologic subtype classification of the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS), and genetic mutation for predicting postoperative prognoses of patients who received curative surgical resections for lung adenocarcinoma. We retrospectively enrolled 988 patients who underwent curative resection for invasive lung adenocarcinoma between October 2007 and December 2013. Cox's proportional hazard model was used to explore the risk of recurrence-free survival, based on the combination of conventional prognostic factors, CT characteristics, IASLC/ATS/ERS histologic subtype, and epidermal growth factor receptor (EGFR) mutations. Incremental prognostic values of CT characteristics, histologic subtype, and EGFR mutations over conventional risk factors were measured by C-statistics. During median follow-up period of 44.7 months (25th to 75th percentile 24.6-59.7 months), postoperative recurrence occurred in 248 patients (25.1%). In univariate Cox proportion hazard model, female sex, tumor size and stage, CT characteristics, and predominant histologic subtype were associated with tumor recurrence (P < 0.05). In multivariate Cox regression model adjusted for tumor size and stage, both CT characteristics and histologic subtype were independent tumor recurrence predictors (P < 0.05). Cox proportion hazard models combining CT characteristics or histologic subtype with size and tumor stage showed higher C-indices (0.763 and 0.767, respectively) than size and stage-only models (C-index 0.759, P > 0.05). CT characteristics and histologic subtype have relatively limited added prognostic values over tumor size and stage in surgically resected lung adenocarcinomas. Copyright © 2018 Elsevier B.V. All rights reserved.

Number of circulating endothelial progenitor cells and intratumoral microvessel density in non-small cell lung cancer patients: differences in angiogenic status between adenocarcinoma histologic subtypes.

PubMed

Maeda, Ryo; Ishii, Genichiro; Ito, Masami; Hishida, Tomoyuki; Yoshida, Junji; Nishimura, Mitsuyo; Haga, Hironori; Nagai, Kanji; Ochiai, Atsushi

2012-03-01

Angiogenesis plays a significant role in tumor progression. This study examined the association between the number of circulating endothelial progenitor cells (EPCs), intratumoral microvessel density (MVD) (both of which may be markers for neovascularization), and lung cancer histological types, particularly adenocarcinoma histological subtypes. A total of 83 stage I non-small cell lung cancer (NSCLC) patients underwent complete tumor resection between November 2009 and July 2010. The number of EPCs from the pulmonary artery of the resected lungs was measured by assaying CD34/vascular endothelial growth factor receptor 2 positive cells, and the MVD was assessed immunohistochemically in tumor specimens by staining for CD34. A statistically significant correlation between the number of EPCs from pulmonary artery and intratumoral MVD was found (p < 0.001). No statistically significant differences in the number of EPCs and the MVD were observed between the adenocarcinomas and the squamous cell carcinomas. Among the adenocarcinoma histological subtypes, a higher number of EPCs and MVD were found significantly more frequently in solid adenocarcinomas than in nonsolid adenocarcinomas (p < 0.001 and p = 0.011, respectively). In addition, solid adenocarcinomas showed higher levels of vascular endothelial growth factor using quantitative real-time polymerase chain reaction in the tumor tissue samples than in the nonsolid adenocarcinomas (p = 0.005). The higher number of circulating EPCs and the MVD of solid adenocarcinoma may indicate the presence of differences in the tumor angiogenic status between early-stage adenocarcinoma histological subtypes. Among adenocarcinoma patients, patients with solid adenocarcinoma may be the best candidates for antiangiogenic therapies.

Overexpression of K-p21Ras play a prominent role in lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Peng-bo; Zhou, Xin-liang; Yang, Ju-lun

2018-06-01

The proto-oncogene ras product, p21Ras, has been found overexpression in many human tumors. However, the subtypes of overexpressed p21Ras still remain unclear. The purpose of this study was to investigate overexpressed isoforms of p21Ras and their roles in the progress of lung cancer. Method: The expression of total p21Ras in normal lung tissues and lung cancers was determined by immunohistochemically staining with monoclonal antibody (Mab) KGHR-1 which could recognize and broad spectrum reaction with the (K/H/N) ras protein. Then, the isoforms of p21Ras was examined by specific Mab for each p21Ras subtypes. Results: Low expression of total p21Ras was found in 26.67% (8/30) of normal lung tissues, and 81.31% (87/107) of adenocarcinoma harbored overexpressed total p21Ras. Besides, 70.00% (35/50) of squamous cell carcinoma were detected overexpressed total p21Ras. In addition, 122 lung cancer tissues from overexpression of total p21Ras protein were selected to detect the expression of each subtype. And all the 122 lung cancer tissues were K-p21Ras overexpression. Moreover, there was a statistical significance difference between the expression level of total p21Ras and differentiation, and the same results were observed between the expression level of total p21Ras and lymph node metastasis (P<0.05). However, there was no correlation between the expression level of total p21Ras and gender, age, tumor size (P>0.05). Conclusions: Overexpression of K-p21Ras plays a prominent role in the progress of lung cancer and it is suggested that the p21Ras could serve as a promising treatment target in lung cancer.

Three-Dimensional Gene Map of Cancer Cell Types: Structural Entropy Minimisation Principle for Defining Tumour Subtypes

PubMed Central

Li, Angsheng; Yin, Xianchen; Pan, Yicheng

2016-01-01

In this study, we propose a method for constructing cell sample networks from gene expression profiles, and a structural entropy minimisation principle for detecting natural structure of networks and for identifying cancer cell subtypes. Our method establishes a three-dimensional gene map of cancer cell types and subtypes. The identified subtypes are defined by a unique gene expression pattern, and a three-dimensional gene map is established by defining the unique gene expression pattern for each identified subtype for cancers, including acute leukaemia, lymphoma, multi-tissue, lung cancer and healthy tissue. Our three-dimensional gene map demonstrates that a true tumour type may be divided into subtypes, each defined by a unique gene expression pattern. Clinical data analyses demonstrate that most cell samples of an identified subtype share similar survival times, survival indicators and International Prognostic Index (IPI) scores and indicate that distinct subtypes identified by our algorithms exhibit different overall survival times, survival ratios and IPI scores. Our three-dimensional gene map establishes a high-definition, one-to-one map between the biologically and medically meaningful tumour subtypes and the gene expression patterns, and identifies remarkable cells that form singleton submodules. PMID:26842724

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

Cancer.gov

In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to generate an animal model of lung SCC, which is critical for understanding the biology of the disease and for identifying novel therapeutic targets.

Occupational Exposures and Lung Cancer Risk among Minnesota Taconite Mining Workers

PubMed Central

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-01-01

Objective To examine the association between employment duration, elongate mineral particle (EMP) exposure, and silica exposure and the risk of lung cancer in the taconite mining industry. Methods We conducted a nested case control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers’ cumulative exposures. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP and silica exposure by quartile of the exposure distribution. Results A total of 1,706 cases and 3,381 controls were included in the analysis. After adjusting for work in hematite mining, asbestos exposure, and sex, the OR for total duration of employment was 0.99 (95% CI: 0.96–1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI: 0.57–1.19) and 0.97 (95% CI: 0.70–1.35) respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. Conclusions This study suggests that the estimated taconite mining exposures do not increase the risk for the development of lung cancer. PMID:25977445

FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.

PubMed

Wang, Rui; Wang, Lei; Li, Yuan; Hu, Haichuan; Shen, Lei; Shen, Xuxia; Pan, Yunjian; Ye, Ting; Zhang, Yang; Luo, Xiaoyang; Zhang, Yiliang; Pan, Bin; Li, Bin; Li, Hang; Zhang, Jie; Pao, William; Ji, Hongbin; Sun, Yihua; Chen, Haiquan

2014-08-01

The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions. Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected. Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095). FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation. ©2014 American Association for Cancer Research.

Lung tumor diagnosis and subtype discovery by gene expression profiling.

PubMed

Wang, Lu-yong; Tu, Zhuowen

2006-01-01

The optimal treatment of patients with complex diseases, such as cancers, depends on the accurate diagnosis by using a combination of clinical and histopathological data. In many scenarios, it becomes tremendously difficult because of the limitations in clinical presentation and histopathology. To accurate diagnose complex diseases, the molecular classification based on gene or protein expression profiles are indispensable for modern medicine. Moreover, many heterogeneous diseases consist of various potential subtypes in molecular basis and differ remarkably in their response to therapies. It is critical to accurate predict subgroup on disease gene expression profiles. More fundamental knowledge of the molecular basis and classification of disease could aid in the prediction of patient outcome, the informed selection of therapies, and identification of novel molecular targets for therapy. In this paper, we propose a new disease diagnostic method, probabilistic boosting tree (PB tree) method, on gene expression profiles of lung tumors. It enables accurate disease classification and subtype discovery in disease. It automatically constructs a tree in which each node combines a number of weak classifiers into a strong classifier. Also, subtype discovery is naturally embedded in the learning process. Our algorithm achieves excellent diagnostic performance, and meanwhile it is capable of detecting the disease subtype based on gene expression profile.

Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

PubMed

Wei, Shi; Siegal, Gene P

2017-03-01

It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

Occupational exposures and lung cancer risk among Minnesota taconite mining workers.

PubMed

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-09-01

To examine the association between employment duration, elongate mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in the taconite mining industry. We conducted a nested case-control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers' cumulative exposures. ORs and 95% CIs were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP, and silica exposure by quartile of the exposure distribution. A total of 1706 cases and 3381 controls were included in the analysis. After adjusting for work in haematite mining, asbestos exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96 to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. This study suggests that the estimated taconite mining exposures do not increase the risk of developing lung cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study.

PubMed

Schulpen, Maya; van den Brandt, Piet A

2018-03-01

The evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55-69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6-8) v. low (0-3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

University of Texas Southwestern Medical Center: Lung Cancer Oncogenotype-Selective Drug Target Discovery (Natural Products Focus) | Office of Cancer Genomics

Cancer.gov

The goal of this project is to use small molecules and RNAi to functionally define subtypes of non-small cell lung cancer (NSCLC) using a panel of cell lines prepared and molecularly annotated by Drs. John Minna and Adi Gazdar. Experimental Approaches Lung Cancer Natural Products Screening/Chemical Library Screening

Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

DTIC Science & Technology

2015-08-01

better understand critical molecular alterations in non -small cell lung cancer (NSCLC) which may lead to the identification of effective therapies...Program Official: Email: kimke@mail.nih.gov; Phone: 301-496-8639; Fax: 301-402-7819 EGFR Mutations in Non Small Cell Lung Cancer The aims of the study...forryscs@mail.nih.gov; Phone: (301) 435-9147; Fax: 301-402-5200 Protein Kinase Therapeutic Targets for Non Small Cell Lung Carcinoma The overall goal

EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk

PubMed Central

Wilson, Ian M.; Vucic, Emily A.; Enfield, Katey S.S.; Thu, Kelsie L.; Zhang, Yu-An; Chari, Raj; Lockwood, William W.; Radulovich, Niki; Starczynowski, Daniel T.; Banáth, Judit P.; Zhang, May; Pusic, Andrea; Fuller, Megan; Lonergan, Kim M.; Rowbotham, David; Yee, John; English, John C.; Buys, Timon P.H.; Selamat, Suhaida A.; Laird-Offringa, Ite A.; Liu, Pengyuan; Anderson, Marshall; You, Ming; Tsao, Ming-Sound; Brown, Carolyn J.; Bennewith, Kevin L.; MacAulay, Calum E.; Karsan, Aly; Gazdar, Adi F.; Lam, Stephen; Lam, Wan L.

2015-01-01

In an effort to identify novel biallelically inactivated tumor suppressor genes (TSG) in sporadic invasive and pre-invasive non-small cell lung cancer (NSCLC) genomes, we applied a comprehensive integrated multi-‘omics approach to investigate patient matched, paired NSCLC tumor and non-malignant parenchymal tissues. By surveying lung tumor genomes for genes concomitantly inactivated within individual tumors by multiple mechanisms, and by the frequency of disruption in tumors across multiple cohorts, we have identified a putative lung cancer TSG, Eyes Absent 4 (EYA4). EYA4 is frequently and concomitantly deleted, hypermethylated and underexpressed in multiple independent lung tumor data sets, in both major NSCLC subtypes, and in the earliest stages of lung cancer. We find not only that decreased EYA4 expression is associated with poor survival in sporadic lung cancers, but EYA4 SNPs are associated with increased familial cancer risk, consistent with EYA4’s proximity to the previously reported lung cancer susceptibility locus on 6q. Functionally, we find that EYA4 displays TSG-like properties with a role in modulating apoptosis and DNA repair. Cross examination of EYA4 expression across multiple tumor types suggests a cell type-specific tumorigenic role for EYA4, consistent with a tumor suppressor function in cancers of epithelial origin. This work shows a clear role for EYA4 as a putative TSG in NSCLC. PMID:24096489

Cytology-based treatment decision in primary lung cancer: is it accurate enough?

PubMed

Sakr, Lama; Roll, Patrice; Payan, Marie-José; Liprandi, Agnès; Dutau, Hervé; Astoul, Philippe; Robaglia-Schlupp, Andrée; Loundou, Anderson; Barlesi, Fabrice

2012-03-01

Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007-2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Different EGFR gene mutations in two patients with synchronous multiple lung cancers: A case report

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Tsuda, Masataka; Wakiyama, Yoichi; Miyazawa, Tomoyuki; Marushima, Hideki; Kojima, Koji; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Haruhiko

2017-01-01

Routine clinical and pathological evaluations to determine the relationship between different lesions are often not completely conclusive. Interestingly, detailed genetic analysis of tumor samples may provide important additional information and identify second primary lung cancers. In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma. The present report highlights the clinical importance of molecular cancer biomarkers to guide management decisions in cases involving multiple lung tumors. PMID:29090842

Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

PubMed

Maddison, Paul

2017-04-01

Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

University of Texas Southwestern Medical Center (UTSW): Lung Cancer Oncogenotype-Selective Drug Target Discovery (Natural Products Focus) | Office of Cancer Genomics

Cancer.gov

The goal of this project is to use small molecules and RNAi to functionally define subtypes of non-small cell lung cancer (NSCLC) using a panel of cell lines prepared and molecularly annotated by Drs. John Minna and Adi Gazdar. Experimental Approaches Lung Cancer Natural Products Screening/Chemical Library Screening

Lack of any association between blood groups and lung cancer, independent of histology.

PubMed

Oguz, Arzu; Unal, Dilek; Tasdemir, Arzu; Karahan, Samet; Aykas, Fatma; Mutlu, Hasan; Cihan, Yasemin Benderli; Kanbay, Mehmet

2013-01-01

Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. The files of 307 pathologically confirmed lung cancer patients were were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-06-01

Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Minimally Invasive Lung Adenocarcinoma; Squamous Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7

On-the-spot lung cancer differential diagnosis by label-free, molecular vibrational imaging and knowledge-based classification

NASA Astrophysics Data System (ADS)

Gao, Liang; Li, Fuhai; Thrall, Michael J.; Yang, Yaliang; Xing, Jiong; Hammoudi, Ahmad A.; Zhao, Hong; Massoud, Yehia; Cagle, Philip T.; Fan, Yubo; Wong, Kelvin K.; Wang, Zhiyong; Wong, Stephen T. C.

2011-09-01

We report the development and application of a knowledge-based coherent anti-Stokes Raman scattering (CARS) microscopy system for label-free imaging, pattern recognition, and classification of cells and tissue structures for differentiating lung cancer from non-neoplastic lung tissues and identifying lung cancer subtypes. A total of 1014 CARS images were acquired from 92 fresh frozen lung tissue samples. The established pathological workup and diagnostic cellular were used as prior knowledge for establishment of a knowledge-based CARS system using a machine learning approach. This system functions to separate normal, non-neoplastic, and subtypes of lung cancer tissues based on extracted quantitative features describing fibrils and cell morphology. The knowledge-based CARS system showed the ability to distinguish lung cancer from normal and non-neoplastic lung tissue with 91% sensitivity and 92% specificity. Small cell carcinomas were distinguished from nonsmall cell carcinomas with 100% sensitivity and specificity. As an adjunct to submitting tissue samples to routine pathology, our novel system recognizes the patterns of fibril and cell morphology, enabling medical practitioners to perform differential diagnosis of lung lesions in mere minutes. The demonstration of the strategy is also a necessary step toward in vivo point-of-care diagnosis of precancerous and cancerous lung lesions with a fiber-based CARS microendoscope.

Correlations between pathologic subtypes/immunohistochemical implication and CT characteristics of lung adenocarcinoma ≤ 1 cm with ground-glass opacity.

PubMed

Wu, Fang; Cai, Zu-long; Tian, Shu-ping; Jin, Xin; Jing, Rui; Yang, Yue-qing; Li, Ying-na; Zhao, Shao-hong

2015-04-01

To discuss the correlation of pathologic subtypes and immunohistochemical implication with CT features of lung adenocarcinoma 1 cm or less in diameter with focal ground-glass opacity (fGGO). CT appearances of 59 patients who underwent curative resection of lung adenocarcinoma ≤ 1 cm with fGGO were analyzed in terms of lesion location, size, density, shape (round, oval, polygonal, irregular), margin (smooth, lobular, spiculated, lobular and spiculated), bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface. Histopathologic subtypes were classified according to International Association for the Study of Lung Cancer/ American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma. Common molecular markers in immunohistochemical study included human epidermal growth factor receptor (HER)-1,HER-2,Ki-67, vascular endothelial growth factor (VEGF) and DNA topoisomerase 2Α.Patients' age and lesions' size and density were compared with pathologic subtypes using analysis of variance or nonparametric Wilcoxon tests. Patients' gender, lesion location, shape and margin, bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface were compared with histopathologic subtypes and immunohistochemical implication using ψ² test or Fisher's exact test. The patients' gender, age, lesion location, shape, air bronchogram, pleural tag, and tumor-lung interface were not significantly different among different histopathologic subtypes (P=0.194, 0.126, 0.609, 0.678, 0.091, 0.374, and 0.339, respectively), whereas the lesion size,density,bubble-like sign, and margin showed significant differences (P=0.028, 0.002, 0.003, 0.046, respectively). The expression of Ki-67 significantly differed among nodules with different shapes(P=0.015). Statistically significant difference also existed between tumor-lung interface and HER-1 expression (P=0.019) and between bubble sign and HER-2 expression (P=0.049). Of lung adenocarcinoma ≤ 1 cm

Trends in lung cancer incidence in Lebanon by gender and histological type over the period 2005-2008.

PubMed

Temraz, Sally; Charafeddine, Maya; Mukherji, Deborah; Shamseddine, Ali

2017-09-01

Lung cancer incidence rates, overall and by histologic subtypes, vary substantially by gender and smoking. This study's aim was to review data regarding trends in the number of cases of different lung-cancer histologies and relate these to smoking habits by gender in Lebanon. Lung cancer data using ICD-O, 3rd edition, from the Lebanese National Cancer Registry from 2005 to 2008 were stratified by gender for histology type for patients aged over 18years. Lung cancer cases among males were 2.5 times higher than those in females. The most common lung cancer histology type for males and females was adenocarcinoma for all observed years. The proportion of squamous cell carcinoma in incident cases was significantly higher in males than in females for the total period from 2005 to 2008, P=0.032, but not in individual years. The ratio of adenocarcinoma to squamous cell carcinoma in incident cases between 2005 and 2008 was 2:45 for males and 3:15 for females. Lung cancer histology in Lebanon is following a pattern similar to that found in most countries of North America and in Europe, where adenocarcinoma is the most prevalent subtype among both males and females. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeman, Jonathan E.; Rimner, Andreas; Montecalvo, Joseph

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. Methods and Materials: We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 Worldmore » Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non–high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score–weighted Cox regression models. Results: The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non–high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. Conclusions: The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy.

PubMed

Leeman, Jonathan E; Rimner, Andreas; Montecalvo, Joseph; Hsu, Meier; Zhang, Zhigang; von Reibnitz, Donata; Panchoo, Kelly; Yorke, Ellen; Adusumilli, Prasad S; Travis, William; Wu, Abraham J

2017-01-01

Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 World Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non-high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score-weighted Cox regression models. The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non-high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have

Lung cancer

MedlinePlus

Cancer - lung ... lung cancer than of breast, colon, and prostate cancers combined. Lung cancer is more common in older adults. It ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung: non-small cell lung cancer and small cell ...

Radiomics-based features for pattern recognition of lung cancer histopathology and metastases.

PubMed

Ferreira Junior, José Raniery; Koenigkam-Santos, Marcel; Cipriano, Federico Enrique Garcia; Fabro, Alexandre Todorovic; Azevedo-Marques, Paulo Mazzoncini de

2018-06-01

lung cancer is the leading cause of cancer-related deaths in the world, and its poor prognosis varies markedly according to tumor staging. Computed tomography (CT) is the imaging modality of choice for lung cancer evaluation, being used for diagnosis and clinical staging. Besides tumor stage, other features, like histopathological subtype, can also add prognostic information. In this work, radiomics-based CT features were used to predict lung cancer histopathology and metastases using machine learning models. local image datasets of confirmed primary malignant pulmonary tumors were retrospectively evaluated for testing and validation. CT images acquired with same protocol were semiautomatically segmented. Tumors were characterized by clinical features and computer attributes of intensity, histogram, texture, shape, and volume. Three machine learning classifiers used up to 100 selected features to perform the analysis. radiomics-based features yielded areas under the receiver operating characteristic curve of 0.89, 0.97, and 0.92 at testing and 0.75, 0.71, and 0.81 at validation for lymph nodal metastasis, distant metastasis, and histopathology pattern recognition, respectively. the radiomics characterization approach presented great potential to be used in a computational model to aid lung cancer histopathological subtype diagnosis as a "virtual biopsy" and metastatic prediction for therapy decision support without the necessity of a whole-body imaging scanning. Copyright © 2018 Elsevier B.V. All rights reserved.

Lung cancer stem cells and implications for future therapeutics.

PubMed

Wang, Jing; Li, Ze-hong; White, James; Zhang, Lin-bo

2014-07-01

Lung cancer is the most dreaded of all cancers because of the higher mortality rates associated with it worldwide. The various subtypes of lung cancer respond differently to a particular treatment regime, which makes the therapeutic interventions all the more complicated. The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased resistance to radiation and chemotherapy. They are considered as the factors responsible for the cases of tumor relapse. The CSCs may have significant role in the development of lung tumorigenesis based on the identification of the CSCs which respond during injury. The properties of multi-potency and self-renewal are shared in common by the lung CSCs with the normal pluripotent stem cells which can be isolated using the similar markers. This review deals with the origin and characteristics of the lung cancer stem cells. The role of different markers used to isolate lung CSCs like CD44, ALDH (aldehyde dehydrogenase), CD133 and ABCG2 (ATP binding cassette sub family G member 2) have been discussed in detail. Analysis of the developmental signaling pathways such as Wnt/β-catenin, Notch, hedgehog in the regulation and maintenance of the lung CSCs have been done. Finally, before targeting the lung CSC biomarkers for potential therapeutics, challenges faced in lung cancer stem cell research need to be taken into account. With the accepted notion that the CSCs are to blame for cancer relapse and drug resistance, targeting them can be an important aspect of lung cancer therapy in the future.

Classification of lung cancer histology by gold nanoparticle sensors

PubMed Central

Barash, Orna; Peled, Nir; Tisch, Ulrike; Bunn, Paul A.; Hirsch, Fred R.; Haick, Hossam

2016-01-01

We propose a nanomedical device for the classification of lung cancer (LC) histology. The device profiles volatile organic compounds (VOCs) in the headspace of (subtypes of) LC cells, using gold nanoparticle (GNP) sensors that are suitable for detecting LC-specific patterns of VOC profiles, as determined by gas chromatography–mass spectrometry analysis. Analyzing the GNP sensing signals by support vector machine allowed significant discrimination between (i) LC and healthy cells; (ii) small cell LC and non–small cell LC; and between (iii) two subtypes of non–small cell LC: adenocarcinoma and squamous cell carcinoma. The discriminative power of the GNP sensors was then linked with the chemical nature and composition of the headspace VOCs of each LC state. These proof-of-concept findings could totally revolutionize LC screening and diagnosis, and might eventually allow early and differential diagnosis of LC subtypes with detectable or unreachable lung nodules. PMID:22033081

[Self defense instead of offense - Immunotherapy in lung cancer].

PubMed

Moldvay, Judit; Ostoros, Gyula

2016-03-02

Lung cancer is the leading cause of cancer death worldwide and also in Hungary, therefore new therapeutic strategies are of great importance. Among immunotherapeutic approaches immune checkpoint inhibition appears to be the most promising. Recent studies have shown efficacy of immunotherapy, especially in squamous cell lung cancer, which is a big step forward in the treatment of this histological subtype. Unlike in the molecularly targeted therapies, the patient selection method has not yet been developed, although some studies indicate the predictive value of tumor cell PD-L1 immunopositivity, especially in lung adenocarcinoma. Introduction of immunotherapy carries challenge for clinicians regarding the radiological assessment of therapeutic efficiency as well as the management of side effects of new profile. The favorable results of recent studies, however, provide hope in this malignancy still presenting a major therapeutic challenge.

Lung cancer survival in England: trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit

PubMed Central

Khakwani, A; Rich, A L; Powell, H A; Tata, L J; Stanley, R A; Baldwin, D R; Duffy, J P; Hubbard, R B

2013-01-01

Background: In comparison with other European and North American countries, England has poor survival figures for lung cancer. Our aim was to evaluate the changes in survival since the introduction of the National Lung Cancer Audit (NLCA). Methods: We used data from the NLCA to identify people with non-small-cell lung cancer (NSCLC) and stratified people according to their performance status (PS) and clinical stage. Using Cox regression, we calculated hazard ratios (HRs) for death according to the year of diagnosis from 2004/2005 to 2010; adjusted for patient features including age, sex and co-morbidity. We also assessed whether any changes in survival were explained by the changes in surgical resection rates or histological subtype. Results: In this cohort of 120 745 patients, the overall median survival did not change; but there was a 1% annual improvement in survival over the study period (adjusted HR 0.99, 95% confidence interval (CI) 0.98–0.99). Survival improvement was only seen in patients with good PS and early stage (adjusted HR 0.97, 95% CI 0.95–0.99) and this was partly accounted for by changes in resection rates. Conclusion: Survival has only improved for a limited group of people with NSCLC and increasing surgical resection rates appeared to explain some of this improvement. PMID:24052044

[Changes of 2015 WHO Histological Classification of Lung Cancer 
and the Clinical Significance].

PubMed

Yang, Xin; Lin, Dongmei

2016-06-20

Due in part to remarkable advances over the past decade in our understanding of lung cancer, particularly in area of medical oncology, molecular biology, and radiology, there is a pressing need for a revised classification, based not on pathology alone, but rather on an integrated multidisciplinary approach to classification of lung cancer. The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The revised classification has been greatly improved in helping advance the field, increasing the impact of research, improving patient care and assisting in predicting outcome. The most significant changes will be summarized in this paper as follows: (1) main changes of lung adenocarcinoma as proposed by the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, (2) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (3) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (4) grouping of neuroendocrine tumors together in one category, (5) and the current viewpoint of histologic grading of lung cancer.

Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study

PubMed Central

2010-01-01

Background Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. Methods We conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis. Results Inverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking. Conclusions Our findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers. PMID:20423504

Smoking and Lung Cancer: A Geo-Regional Perspective.

PubMed

Rahal, Zahraa; El Nemr, Shaza; Sinjab, Ansam; Chami, Hassan; Tfayli, Arafat; Kadara, Humam

2017-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) represents the most frequently diagnosed subtype of this morbid malignancy. NSCLC is causally linked to tobacco consumption with more than 500 million smokers worldwide at high risk for this fatal malignancy. We are currently lagging in our knowledge of the early molecular (e.g., genomic) effects of smoking in NSCLC pathogenesis that would constitute ideal markers for early detection. This limitation is further amplified when considering the variable etiologic factors in NSCLC pathogenesis among different regions around the globe. In this review, we present our current knowledge of genomic alterations arising during early stages of smoking-induced lung cancer initiation and progression, including discussing the premalignant airway field of injury induced by smoking. The review also underscores the wider spectra and higher age-adjusted rates of tobacco (e.g., water-pipe smoke) consumption, along with elevated environmental carcinogenic exposures and relatively poorer socioeconomic status, in low-middle income countries (LMICs), with Lebanon as an exemplar. This "cocktail" of carcinogenic exposures warrants the pressing need to understand the complex etiology of lung malignancies developing in LMICs such as Lebanon.

Progress and prospects of early detection in lung cancer

PubMed Central

Blandin Knight, Sean; Crosbie, Phil A.; Balata, Haval; Chudziak, Jakub; Hussell, Tracy; Dive, Caroline

2017-01-01

Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I). However, most patients (approx. 75%) have advanced disease at the time of diagnosis (stage III/IV) and despite significant developments in the oncological management of late stage lung cancer over recent years, survival remains poor. In 2014, the UK Office for National Statistics reported that patients diagnosed with distant metastatic disease (stage IV) had a 1-year survival rate of just 15–19% compared with 81–85% for stage I. PMID:28878044

Clinico-pathology of lung cancer in a regional cancer center in Northeastern India.

PubMed

Mandal, Sanjeet Kumar; Singh, Thaudem Tomcha; Sharma, Takhenchangbam Dhaneshor; Amrithalingam, Venkatesan

2013-01-01

Globally, there have been important changes in trends amongst gender, histology and smoking patterns of lung cancer cases. This retrospective study was conducted on 466 patients with lung cancer who were registered in Regional Cancer Center, Regional Institute of Medical Sciences, Manipur from January 2008 to December 2012. Most were more than 60 years of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in 16.3% of patients. The most frequent symptom was coughing (36.6%) and most common radiological presentation was a mass lesion (70%). Most of the patients had primary lung cancer in the right lung (60.3%). The most common histological subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%). As many as 91.9% of squamous cell carcinoma patients had a history of smoking. About 32.5% of patients had distant metastasis at presentation with brain (23.8%) and positive malignant cells in pleural effusions (23.1%) as common sites. The majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II (30.2%). Our analysis suggests that the gender gap has been narrowed such that about half of the patients diagnosed with lung cancer are women in this part of India. This alarming rise in female incidence is mainly attributed to an increased smoking pattern. Squamous cell carcinoma still remains the commonest histological subtype. Most of the patients were elderly aged and presented at locally or distantly advanced stages.

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer

PubMed Central

Chang, Yu-Chun; Ding, Yan; Dong, Lingsheng; Zhu, Lang-Jing; Jensen, Roderick V.

2018-01-01

Background Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these “housekeeping genes” (HKGs) could separate one normal human tissue type from another. Current focus on identifying “specific disease markers” is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. Methods Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD), squamous cell carcinomas of the lung (SQCLC), and small cell carcinomas of the lung (SCLC) were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. Results This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS) and were involved in the most common biological processes (e.g., metabolism, stress response). In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of overall

Fatty acid metabolism in breast cancer subtypes

PubMed Central

Monaco, Marie E.

2017-01-01

Dysregulation of fatty acid metabolism is recognized as a component of malignant transformation in many different cancers, including breast; yet the potential for targeting this pathway for prevention and/or treatment of cancer remains unrealized. Evidence indicates that proteins involved in both synthesis and oxidation of fatty acids play a pivotal role in the proliferation, migration and invasion of breast cancer cells. The following essay summarizes data implicating specific fatty acid metabolic enzymes in the genesis and progression of breast cancer, and further categorizes the relevance of specific metabolic pathways to individual intrinsic molecular subtypes of breast cancer. Based on mRNA expression data, the less aggressive luminal subtypes appear to rely on a balance between de novo fatty acid synthesis and oxidation as sources for both biomass and energy requirements, while basal-like, receptor negative subtypes overexpress genes involved in the utilization of exogenous fatty acids. With these differences in mind, treatments may need to be tailored to individual subtypes. PMID:28412757

Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations.

PubMed

Nishimura, Toshihide; Nakamura, Haruhiko

2016-01-01

Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development. Both identification and quantification of gatekeeper mutations need to be performed using lung cancer tissue specimens obtained from patients to improve the treatment for lung cancer patients: (1) identification and quantitation data of targeted mutated proteins, including investigation of mutation heterogeneity within a tissue; (2) exploratory mass spectrometry (MS)-based clinical proteogenomic analysis of mutated proteins; and also importantly (3) analysis of dynamic protein-protein interaction (PPI) networks of proteins significantly related to a subgroup of patients with lung cancer not only with good efficacy but also with acquired resistance. MS-based proteogenomics is a promising approach to directly capture mutated and fusion proteins expressed in a clinical sample. Technological developments are further expected, which will provide a powerful solution for the stratification of patients and drug discovery (Precision Medicine).

MicroRNA-dependent regulation of transcription in non-small cell lung cancer.

PubMed

Molina-Pinelo, Sonia; Gutiérrez, Gabriel; Pastor, Maria Dolores; Hergueta, Marta; Moreno-Bueno, Gema; García-Carbonero, Rocío; Nogal, Ana; Suárez, Rocío; Salinas, Ana; Pozo-Rodríguez, Francisco; Lopez-Rios, Fernando; Agulló-Ortuño, Maria Teresa; Ferrer, Irene; Perpiñá, Asunción; Palacios, José; Carnero, Amancio; Paz-Ares, Luis

2014-01-01

Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies.

Angiotensin receptor blockers: are they related to lung cancer?

PubMed Central

Rao, Gowtham Adamane; Mann, Joshua R.; Shoaibi, Azza; Pai, Sachin G.; Bottai, Matteo; Sutton, Shawn Scott; Haddock, Kathlyn Sue; Bennett, Charles Lee; Hebert, James R.

2013-01-01

Introduction Angiotensin receptor blockers (ARBs) are commonly used antihypertensive medication with several other additional proven benefits. Recent controversy on association of lung cancer and other solid malignancy with the use of ARBs is concerning, although the follow-up studies have shown no such association. Methods We used data from the Department of Veterans Affairs electronic medical record system and registries to conduct a retrospective cohort study that compared first-time ARB users with nonusers in 1:15 ratio, after balancing for many baseline differences using inverse probability of treatment weights. We conducted time-to-event survival analyses on the weighted cohort. Results Of the 1 229 902 patients in the analytic cohort, 346 (0.44%) of the 78 075 treated individuals had a newly incident lung cancer and 6577 (0.57%) of 1 151 826 nontreated individuals were diagnosed with lung cancer. On double robust regression, the weighted hazard ratio was 0.74 (0.67–0.83, P<0.0001), suggesting a lung cancer reduction effect with ARB use. There was no difference in rates by ARB subtype. Conclusion In this large nationwide cohort of United States Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with nonusers. Our findings were consistent with a protective effect of ARBs. PMID:23822929

Influence of quartz exposure on lung cancer types in cases of lymph node-only silicosis and lung silicosis in German uranium miners.

PubMed

Mielke, Stefan; Taeger, Dirk; Weitmann, Kerstin; Brüning, Thomas; Hoffmann, Wolfgang

2018-05-04

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.

An integrated nanotechnology-enabled transbronchial image-guided intervention strategy for peripheral lung cancer

PubMed Central

Jin, Cheng S.; Wada, Hironobu; Anayama, Takashi; McVeigh, Patrick Z; Hu, Hsin Pei; Hirohashi, Kentaro; Nakajima, Takahiro; Kato, Tatsuya; Keshavjee, Shaf; Hwang, David; Wilson, Brian C.; Zheng, Gang; Yasufuku, Kazuhiro

2016-01-01

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current non-surgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically-administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460 and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon non-surgical treatment of early-stage peripheral lung cancer. PMID:27543602

Optimizing Tissue Sampling for the Diagnosis, Subtyping, and Molecular Analysis of Lung Cancer

PubMed Central

Ofiara, Linda Marie; Navasakulpong, Asma; Beaudoin, Stephane; Gonzalez, Anne Valerie

2014-01-01

Lung cancer has entered the era of personalized therapy with histologic subclassification and the presence of molecular biomarkers becoming increasingly important in therapeutic algorithms. At the same time, biopsy specimens are becoming increasingly smaller as diagnostic algorithms seek to establish diagnosis and stage with the least invasive techniques. Here, we review techniques used in the diagnosis of lung cancer including bronchoscopy, ultrasound-guided bronchoscopy, transthoracic needle biopsy, and thoracoscopy. In addition to discussing indications and complications, we focus our discussion on diagnostic yields and the feasibility of testing for molecular biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase, emphasizing the importance of a sufficient tumor biopsy. PMID:25295226

Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes

PubMed Central

Dhanasekaran, Saravana M.; Balbin, O. Alejandro; Chen, Guoan; Nadal, Ernest; Kalyana-Sundaram, Shanker; Pan, Jincheng; Veeneman, Brendan; Cao, Xuhong; Malik, Rohit; Vats, Pankaj; Wang, Rui; Huang, Stephanie; Zhong, Jinjie; Jing, Xiaojun; Iyer, Matthew; Wu, Yi-Mi; Harms, Paul W.; Lin, Jules; Reddy, Rishindra; Brennan, Christine; Palanisamy, Nallasivam; Chang, Andrew C.; Truini, Anna; Truini, Mauro; Robinson, Dan R.; Beer, David G.; Chinnaiyan, Arul M.

2014-01-01

Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here, we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyze 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations. In addition, we observe exon skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations. PMID:25531467

MicroRNA-Dependent Regulation of Transcription in Non-Small Cell Lung Cancer

PubMed Central

Molina-Pinelo, Sonia; Gutiérrez, Gabriel; Pastor, Maria Dolores; Hergueta, Marta; Moreno-Bueno, Gema; García-Carbonero, Rocío; Nogal, Ana; Suárez, Rocío; Salinas, Ana; Pozo-Rodríguez, Francisco; Lopez-Rios, Fernando; Agulló-Ortuño, Maria Teresa; Ferrer, Irene; Perpiñá, Asunción; Palacios, José; Carnero, Amancio; Paz-Ares, Luis

2014-01-01

Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies. PMID:24625834

Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses.

PubMed

Guyard, Alice; Danel, Claire; Théou-Anton, Nathalie; Debray, Marie-Pierre; Gibault, Laure; Mordant, Pierre; Castier, Yves; Crestani, Bruno; Zalcman, Gérard; Blons, Hélène; Cazes, Aurélie

2017-06-15

Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry. Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%. This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.

Clinical applications of textural analysis in non-small cell lung cancer.

PubMed

Phillips, Iain; Ajaz, Mazhar; Ezhil, Veni; Prakash, Vineet; Alobaidli, Sheaka; McQuaid, Sarah J; South, Christopher; Scuffham, James; Nisbet, Andrew; Evans, Philip

2018-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.

Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals

PubMed Central

Suneja, Gita; Shiels, Meredith S.; Melville, Sharon K.; Williams, Melanie A.; Rengan, Ramesh; Engels, Eric A.

2013-01-01

Objectives HIV-infected people have elevated risk for lung cancer and higher mortality following cancer diagnosis than HIV-uninfected individuals. It is unclear whether HIV-infected individuals with lung cancer receive similar cancer treatment as HIV-uninfected individuals. Design/methods We studied adults more than 18 years of age with lung cancer reported to the Texas Cancer Registry (N = 156 930) from 1995 to 2009. HIV status was determined by linkage with the Texas enhanced HIV/AIDS Reporting System. For nonsmall cell lung cancer (NSCLC) cases, we identified predictors of cancer treatment using logistic regression. We used Cox regression to evaluate effects of HIV and cancer treatment on mortality. Results Compared with HIV-uninfected lung cancer patients (N = 156 593), HIV-infected lung cancer patients (N = 337) were more frequently young, black, men, and with non-Hispanic distant stage disease. HIV-infected NSCLC patients less frequently received cancer treatment than HIV-uninfected patients [60.3 vs. 77.5%; odds ratio 0.39, 95% confidence interval (CI) 0.30–0.52, after adjustment for diagnosis year, age, sex, race, stage, and histologic subtype]. HIV infection was associated with higher lung cancer-specific mortality (hazard ratio 1.34, 95% CI 1.15–1.56, adjusted for demographics and tumor characteristics). Inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality (hazard ratio 1.25; 95% CI 1.06–1.47). Also, there was a suggestion that HIV was more strongly associated with mortality among untreated than among treated patients (adjusted hazard ratio 1.32 vs. 1.16, P-interaction = 0.34). Conclusion HIV-infected NSCLC patients were less frequently treated for lung cancer than HIV-uninfected patients, which may have affected survival. PMID:23079809

6 Common Cancers - Lung Cancer

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

Low-dose computed tomography volumetry for subtyping chronic lung allograft dysfunction.

PubMed

Saito, Tomohito; Horie, Miho; Sato, Masaaki; Nakajima, Daisuke; Shoushtarizadeh, Hassan; Binnie, Matthew; Azad, Sassan; Hwang, David M; Machuca, Tiago N; Waddell, Thomas K; Singer, Lianne G; Cypel, Marcelo; Liu, Mingyao; Paul, Narinder S; Keshavjee, Shaf

2016-01-01

The long-term success of lung transplantation is challenged by the development of chronic lung allograft dysfunction (CLAD) and its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). However, the current diagnostic criteria for CLAD subtypes rely on total lung capacity (TLC), which is not always measured during routine post-transplant assessment. Our aim was to investigate the utility of low-dose 3-dimensional computed tomography (CT) lung volumetry for differentiating RAS from BOS. This study was a retrospective evaluation of 63 patients who had developed CLAD after bilateral lung or heart‒lung transplantation between 2006 and 2011, including 44 BOS and 19 RAS cases. Median post-transplant follow-up was 65 months in BOS and 27 months in RAS. The median interval between baseline and the disease-onset time-point for CT volumetry was 11 months in both BOS and RAS. Chronologic changes and diagnostic accuracy of CT lung volume (measured as percent of baseline) were investigated. RAS showed a significant decrease in CT lung volume at disease onset compared with baseline (mean 3,916 ml vs 3,055 ml when excluding opacities, p < 0.0001), whereas BOS showed no significant post-transplant change (mean 4,318 ml vs 4,396 ml, p = 0.214). The area under the receiver operating characteristic curve of CT lung volume for differentiating RAS from BOS was 0.959 (95% confidence interval 0.912 to 1.01, p < 0.0001) and the calculated accuracy was 0.938 at a threshold of 85%. In bilateral lung or heart‒lung transplant patients with CLAD, low-dose CT volumetry is a useful tool to differentiate patients who develop RAS from those who develop BOS. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Lung Cancer Screening

MedlinePlus

... healthy people with a high risk of lung cancer. Lung cancer screening is recommended for older adults who ... last 15 years. What you can expect During lung cancer screening During an LDCT scan of the lungs, ...

Racial disparities in molecular subtypes of endometrial cancer.

PubMed

Dubil, Elizabeth A; Tian, Chunqiao; Wang, Guisong; Tarney, Christopher M; Bateman, Nicholas W; Levine, Douglas A; Conrads, Thomas P; Hamilton, Chad A; Maxwell, George Larry; Darcy, Kathleen M

2018-04-01

Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated. Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients. There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients. The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities. Copyright © 2017. Published by Elsevier Inc.

What Is Lung Cancer?

MedlinePlus

... Shareable Graphics Infographics “African-American Men and Lung Cancer” “Lung Cancer Is the Biggest Cancer Killer in Both ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ...

Expression and significance of Ki-67 in lung cancer.

PubMed

Folescu, Roxana; Levai, Codrina Mihaela; Grigoraş, Mirela Loredana; Arghirescu, Teodora Smaranda; Talpoş, Ioana Cristina; Gîndac, Ciprian Mihai; Zamfir, Carmen Lăcrămioara; Poroch, Vladimir; Anghel, Mirella Dorina

2018-01-01

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor's aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

PubMed Central

Oh, Juliana J.; Koegel, Ashley; Phan, Diana T.; Razfar, Ali; Slamon, Dennis J.

2007-01-01

Summary Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. PMID:17606309

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer.

PubMed

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-09-01

Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.

The prognostic value of node status in different breast cancer subtypes

PubMed Central

Hou, Xin-Wei; Chi, Jiang-Rui; Ge, Jie; Wang, Xin; Cao, Xu-Chen

2017-01-01

Nodal metastases and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. However, the association between nodal metastases and BCS, and the prognostic value of nodal metastases in different BCS are still remains unclear. Our aim was to investigate the association between nodal metastases and BCS, and the prognostic value of nodal metastases in the different BCS. We found that the breast cancer subtype was closely associated with the pN stage. pN stage and breast cancer subtype were significantly associated with disease-free survival. The subgroup analysis showed that the patients in higher pN stage had a poor outcome than patients in lower pN stage in each breast cancer subtype. Furthermore, when the analysis was stratified by breast cancer subtype, we found that even in the same pN stage (pN0-pN2), there was significant survival difference among patients in different BCS, and Luminal A breast cancer patients had the best survival outcome. However, there were no significant survival difference between Luminal A patients and other breast cancer subtype when patients in pN3 stage. Thus, our study suggested that both lymph node status and molecular subtype played important roles in the outcome of breast cancer patients and they cannot replace each other. PMID:27999188

Lung cancer risk among bakers, pastry cooks and confectionary makers: the SYNERGY study.

PubMed

Behrens, Thomas; Kendzia, Benjamin; Treppmann, Tabea; Olsson, Ann; Jöckel, Karl-Heinz; Gustavsson, Per; Pohlabeln, Hermann; Ahrens, Wolfgang; Brüske, Irene; Wichmann, Hans-Erich; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabianova, Eleonora; Tardón, Adonina; Field, John; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Siemiatycki, Jack; Parent, Marie-Elise; McLaughlin, John; Demers, Paul; Landi, Maria Teresa; Caporaso, Neil; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Benhamou, Simone; Stücker, Isabelle; Guida, Florence; Consonni, Dario; Bueno-de-Mesquita, Bas; 't Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Plato, Nils; Boffetta, Paolo; Straif, Kurt; Schüz, Joachim; Pesch, Beate; Brüning, Thomas

2013-11-01

Some studies have suggested increased lung cancer risks among bakers, however the results overall were inconsistent. The authors studied lung cancer risks among bakers and baking-related occupations in the SYNERGY pooled case-control database from 16 countries. Occupation in a baking-related job was identified from the subjects' job histories. ORs adjusted for log(age), study centre, smoking behaviour and ever employment in a job with known exposure to occupational lung carcinogens were calculated by unconditional logistic regression. Findings were stratified by sex, histological subtype of lung cancer and smoking status. 19 366 cases (15 606 men) and 23 670 control subjects (18 528 men) were included. 473 cases (415 men, 58 women) and 501 controls (437 men, 64 women) had ever worked in baking or a related job. We did not observe an increased risk for men in baking (OR 1.01; 95% CI 0.86 to 1.18). No linear trends were observed for duration of employment. Some results suggested increased lung cancer risks for women, for example, for working as a baker for >30 years and in never-smokers, but after exclusion of one study these increased risks disappeared. The findings from this study do not suggest increased lung cancer risks in baking-related professions.

CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy.

PubMed

Tuscano, Joseph M; Kato, Jason; Pearson, David; Xiong, Chengyi; Newell, Laura; Ma, Yunpeng; Gandara, David R; O'Donnell, Robert T

2012-11-01

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets. ©2012 AACR.

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

PubMed

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Lung Cancer

MedlinePlus

Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

A new biomarker panel in bronchoalveolar lavage for an improved lung cancer diagnosis.

PubMed

Uribarri, María; Hormaeche, Itsaso; Zalacain, Rafael; Lopez-Vivanco, Guillermo; Martinez, Antonio; Nagore, Daniel; Ruiz-Argüello, M Begoña

2014-10-01

The enormous biological complexity and high mortality rate of lung cancer highlights the need for new global approaches for the discovery of reliable early diagnostic biomarkers. The study of bronchoalveolar lavage samples by proteomic techniques could identify new lung cancer biomarkers and may provide promising noninvasive diagnostic tools able to enhance the sensitivity of current methods. First, an observational prospective study was designed to assess protein expression differences in bronchoalveolar lavages from patients with (n = 139) and without (n = 49) lung cancer, using two-dimensional gel electrophoresis and subsequent protein identification by mass spectrometry. Second, validation of candidate biomarkers was performed by bead-based immunoassays with a different patient cohort (204 patients, 48 controls). Thirty-two differentially expressed proteins were identified in bronchoalveolar lavages, 10 of which were confirmed by immunoassays. The expression levels of APOA1, CO4A, CRP, GSTP1, and SAMP led to a lung cancer diagnostic panel that reached 95% sensitivity and 81% specificity, and the quantification of STMN1 and GSTP1 proteins allowed the two main lung cancer subtypes to be discriminated with 90% sensitivity and 57% specificity. Bronchoalveolar lavage represents a promising noninvasive source of lung cancer specific protein biomarkers with high diagnostic accuracy. Measurement of APOA1, CO4A, CRP, GSTP1, SAMP, and STMN1 in this fluid may be a useful tool for lung cancer diagnosis, although a further validation in a larger clinical set is required for early stages.

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

PubMed Central

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J.; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R.; Dougall, William

2017-01-01

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. PMID:29118048

KRAS: Reasons for optimism in lung cancer.

PubMed

Lindsay, C R; Jamal-Hanjani, M; Forster, M; Blackhall, F

2018-06-09

Despite being the most frequent gain-of-function genetic alteration in human cancer, KRAS mutation has to date offered only limited potential as a prognostic and predictive biomarker. Results from the phase III SELECT-1 trial in non-small cell lung cancer (NSCLC) recently added to a number of historical and more contemporary disappointments in targeting KRAS mutant disease, including farnesyl transferase inhibition and synthetic lethality partners such as STK33. This narrative review uses the context of these previous failures to demonstrate how the knowledge gained from these experiences can be used as a platform for exciting advances in NSCLC on the horizon. It now seems clear that mutational subtype (most commonly G12C) of individual mutations is of greater relevance than the categorical evaluation of KRAS mutation presence or otherwise. A number of direct small molecules targeted to these subtypes are in development and have shown promising biological activity, with some in the late stages of preclinical validation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

PubMed Central

Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

2014-01-01

Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

Impact of Computer-Aided CT and PET Analysis on Non-invasive T Staging in Patients with Lung Cancer and Atelectasis.

PubMed

Flechsig, Paul; Rastgoo, Ramin; Kratochwil, Clemens; Martin, Ole; Holland-Letz, Tim; Harms, Alexander; Kauczor, Hans-Ulrich; Haberkorn, Uwe; Giesel, Frederik L

2018-04-20

Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [ 18 F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue. Seventy-two patients with histologically proven lung cancer and adjacent atelectasis were investigated. Non-contrast-enhanced [ 18 F]FDG-PET/CT was performed within 2 weeks before surgery/biopsy. Boundaries of the primary within the atelectasis were determined visually on the basis of [ 18 F]FDG uptake; CT density was quantified manually within each primary and each atelectasis. CT density of the primary (36.4 Hounsfield units (HU) ± 6.2) was significantly higher compared to that of atelectatic lung (24.3 HU ± 8.3; p < 0.01), irrespective of the histological subtype. The discrimination between different malignant tumors using density analysis failed. SUVmax was increased in squamous cell carcinomas compared to adenocarcinomas. Irrespective of the malignant subtype, a possible cutoff value of 24 HU may help to exclude the presence of a primary in lesions below 24 HU, whereas a density above a threshold of 40 HU can help to exclude atelectatic lung. Density measurements in patients with lung cancer and surrounding atelectasis may help to delineate the primary tumor, irrespective of the specific lung cancer subtype. This could improve T staging and radiation treatment planning (RTP) without additional application of a contrast

Lung Cancers Associated with Cystic Airspaces: Underrecognized Features of Early Disease.

PubMed

Sheard, Sarah; Moser, Joanna; Sayer, Charlie; Stefanidis, Konstantinos; Devaraj, Anand; Vlahos, Ioannis

2018-01-01

Early lung cancers associated with cystic airspaces are increasingly being recognized as a cause of delayed diagnoses-owing to data gathered from screening trials and encounters in routine clinical practice as more patients undergo serial imaging. Several morphologic subtypes of cancers associated with cystic airspaces exist and can exhibit variable patterns of progression as the solid elements of the tumor grow. Current understanding of the pathogenesis of these malignancies is limited, and the numbers of cases reported in the literature are small. However, several tumor cell types are represented in these lesions, with adenocarcinoma predominating. The features of cystic airspaces differ among cases and include emphysematous bullae, congenital or fibrotic cysts, subpleural blebs, bronchiectatic airways, and distended distal airspaces. Once identified, these cystic lesions pose management challenges to radiologists in terms of distinguishing them from benign mimics of cancer that are commonly seen in patients who also are at increased risk of lung cancer. Rendering a definitive tissue-based diagnosis can be difficult when the lesions are small, and affected patients tend to be in groups that are at higher risk of requiring biopsy or resection. In addition, the decision to monitor these cases can add to patient anxiety and cause the additional burden of strained departmental resources. The authors have drawn from their experience, emerging evidence from international lung cancer screening trials, and large databases of lung cancer cases from other groups to analyze the prevalence and evolution of lung cancers associated with cystic airspaces and provide guidance for managing these lesions. Although there are insufficient data to support specific management guidelines similar to those for managing small solid and ground-glass lung nodules, these data and guidelines should be the direction for ongoing research on early detection of lung cancer. © RSNA, 2018.

Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men.

PubMed

Villeneuve, Paul J; Parent, Marie-Élise; Sahni, Vanita; Johnson, Kenneth C

2011-07-01

The International Agency for Research on Cancer classifies diesel exhaust as a probable human carcinogen; this decision is based largely from lung cancer evidence. Gasoline exhaust is classified as a possible carcinogen. Epidemiological studies are needed that improve upon some of the limitations of previous research with respect to the characterization of exposure, and the control for the potential confounding influence of smoking and other occupational exposures. Our objective was to investigate associations between occupational exposure to diesel and gasoline engine emissions and lung cancer. We used a case-control study design that involved men 40 years of age and older at the time of interview. Analyses are based on 1681 incident cases of lung cancer and 2,053 population controls. A self-reported questionnaire elicited a lifetime occupational history, including general tasks, and information on other potential risk factors. Occupational exposures to diesel and gasoline emissions, crystalline silica, and asbestos were assigned to each job held by study subjects by industrial hygienists who were blind to case-control status. Exposure metrics for diesel and gasoline emissions that were modeled included: ever exposure, cumulative exposure, and concentration of exposure. We found a dose-response relationship between cumulative occupational exposure to diesel engine emissions and lung cancer. This association was more pronounced for the squamous and large cell subtypes with adjusted odds ratios across the three increasing tertiles of cumulative lifetime exposure relative to those with no exposure of 0.99, 1.25, and 1.32 (p=0.04) for squamous cell carcinoma, and 1.06, 1.19, 1.68 (p=0.02) for large cell carcinoma. While the association with cumulative exposure to gasoline was weakly positive, it was not statistically significant. Our findings suggest that exposure to diesel engine emissions increases the risk of lung cancer particularly for squamous and large cell

Patterns in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009.

PubMed

Houston, Keisha A; Henley, S Jane; Li, Jun; White, Mary C; Richards, Thomas B

2014-10-01

The examination of lung cancer by histology type is important for monitoring population trends that have implications for etiology and prevention, screening and clinical diagnosis, prognosis and treatment. We provide a comprehensive description of recent histologic lung cancer incidence rates and trends in the USA using combined population-based registry data for the entire nation. Histologic lung cancer incidence data was analyzed from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Standardized rates and trends were calculated for men and women by age, race/ethnicity, and U.S. Census region. Rate ratios were examined for differences in rates between men and women, and annual percent change was calculated to quantify changes in incidence rates over time. Trend analysis demonstrate that overall rates have decreased, but incidence has remained stable for women aged 50 or older. Adenocarcinoma and squamous cell carcinoma were the two most common histologic subtypes. Adenocarcinoma rates continued to increase in men and women, and squamous cell rates increased in women only. All histologic subtype rates for white women exceeded rates for black women. Histologic rates for black men exceeded those for white men, except for small cell carcinoma. The incidence rate for Hispanics was nearly half the rate for blacks and whites. The continuing rise in incidence of lung adenocarcinoma, the rise of squamous cell cancer in women, and differences by age, race, ethnicity and region points to the need to better understand factors acting in addition to, or in synergy with, cigarette smoking that may be contributing to observed differences in lung cancer histology. Published by Elsevier Ireland Ltd.

Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens*

PubMed Central

Kriegsmann, Mark; Casadonte, Rita; Kriegsmann, Jörg; Dienemann, Hendrik; Schirmacher, Peter; Hendrik Kobarg, Jan; Schwamborn, Kristina; Stenzinger, Albrecht; Warth, Arne; Weichert, Wilko

2016-01-01

Histopathological subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (ADC), and squamous cell carcinoma (SqCC) is of utmost relevance for treatment stratification. However, current immunohistochemistry (IHC) based typing approaches on biopsies are imperfect, therefore novel analytical methods for reliable subtyping are needed. We analyzed formalin-fixed paraffin-embedded tissue cores of NSCLC by Matrix-assisted laser desorption/ionization (MALDI) imaging on tissue microarrays to identify and validate discriminating MALDI imaging profiles for NSCLC subtyping. 110 ADC and 98 SqCC were used to train a Linear Discriminant Analysis (LDA) model. Results were validated on a separate set of 58 ADC and 60 SqCC. Selected differentially expressed proteins were identified by tandem mass spectrometry and validated by IHC. The LDA classification model incorporated 339 m/z values. In the validation cohort, in 117 cases (99.1%) MALDI classification on tissue cores was in accordance with the pathological diagnosis made on resection specimen. Overall, three cases in the combined cohorts were discordant, after reevaluation two were initially misclassified by pathology whereas one was classified incorrectly by MALDI. Identification of differentially expressed peptides detected well-known IHC discriminators (CK5, CK7), but also less well known differentially expressed proteins (CK15, HSP27). In conclusion, MALDI imaging on NSCLC tissue cores as small biopsy equivalents is capable to discriminate lung ADC and SqCC with a very high accuracy. In addition, replacing multislide IHC by an one-slide MALDI approach may also save tissue for subsequent predictive molecular testing. We therefore advocate to pursue routine diagnostic implementation strategies for MALDI imaging in solid tumor typing. PMID:27473201

Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens.

PubMed

Kriegsmann, Mark; Casadonte, Rita; Kriegsmann, Jörg; Dienemann, Hendrik; Schirmacher, Peter; Hendrik Kobarg, Jan; Schwamborn, Kristina; Stenzinger, Albrecht; Warth, Arne; Weichert, Wilko

2016-10-01

Histopathological subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (ADC), and squamous cell carcinoma (SqCC) is of utmost relevance for treatment stratification. However, current immunohistochemistry (IHC) based typing approaches on biopsies are imperfect, therefore novel analytical methods for reliable subtyping are needed. We analyzed formalin-fixed paraffin-embedded tissue cores of NSCLC by Matrix-assisted laser desorption/ionization (MALDI) imaging on tissue microarrays to identify and validate discriminating MALDI imaging profiles for NSCLC subtyping. 110 ADC and 98 SqCC were used to train a Linear Discriminant Analysis (LDA) model. Results were validated on a separate set of 58 ADC and 60 SqCC. Selected differentially expressed proteins were identified by tandem mass spectrometry and validated by IHC. The LDA classification model incorporated 339 m/z values. In the validation cohort, in 117 cases (99.1%) MALDI classification on tissue cores was in accordance with the pathological diagnosis made on resection specimen. Overall, three cases in the combined cohorts were discordant, after reevaluation two were initially misclassified by pathology whereas one was classified incorrectly by MALDI. Identification of differentially expressed peptides detected well-known IHC discriminators (CK5, CK7), but also less well known differentially expressed proteins (CK15, HSP27). In conclusion, MALDI imaging on NSCLC tissue cores as small biopsy equivalents is capable to discriminate lung ADC and SqCC with a very high accuracy. In addition, replacing multislide IHC by an one-slide MALDI approach may also save tissue for subsequent predictive molecular testing. We therefore advocate to pursue routine diagnostic implementation strategies for MALDI imaging in solid tumor typing. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

PubMed

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

2017-10-15

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

Correlation of clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification.

PubMed

Chen, Rongrong; Ding, Zhengping; Zhu, Lei; Lu, Shun; Yu, Yongfeng

2017-12-01

This study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma (LSCC) subtypes according to the 2015 WHO classification. We identified 824 operable LSCC patients undergoing a complete surgical resection at Shanghai Chest Hospital between April 2015 and January 2017. Immunohistochemistry was used to investigate the clinicopathologic features. Among them, the percentages of LSCC subtypes were 66.1% (545/824), 28.6% (236/824), and 5.2% (43/824) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more males, more smokers, and more pneumonectomy surgeries in KSCC patients (p = 0.008, p = 0.000, p = 0.043). There were more N2 lymph node involvement and pathological stage III in NKSCC patients (p = 0.01, p = 0.03). BSCC did not demonstrate specificity to anything, but expressed adenocarcinoma markers more frequently. No significant difference existed between pathological subtypes and other clinicopathologic features, such as age, location type, visceral pleural involvement and lymphovascular invasion. The frequencies of EGFR sensitive mutations and ALK rearrangements were not significantly different among three subtypes. Significant relationships exist between some clinicopathologic features and LSCC subtypes. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Epidemiology of Lung Cancer

PubMed Central

Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

Lung cancer - small cell

MedlinePlus

Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

Intersections of lung progenitor cells, lung disease and lung cancer.

PubMed

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Breast cancer subtypes: two decades of journey from cell culture to patients.

PubMed

Zhao, Xiangshan; Gurumurthy, Channabasavaiah Basavaraju; Malhotra, Gautam; Mirza, Sameer; Mohibi, Shakur; Bele, Aditya; Quinn, Meghan G; Band, Hamid; Band, Vimla

2011-01-01

Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer

PubMed Central

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-01-01

Background Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. Methods We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. Results In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Conclusions Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer. PMID:27722145

Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer.

PubMed

Lim, Byungho; Kim, Jong-Hwan; Kim, Mirang; Kim, Seon-Young

2016-01-21

Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr virus-positive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.

The consumption of coffee and black tea and the risk of lung cancer.

PubMed

Pasquet, Romain; Karp, Igor; Siemiatycki, Jack; Koushik, Anita

2016-11-01

Coffee and black tea are among the most consumed beverages worldwide. Although their potential role in lung cancer occurrence has been investigated in several studies, results have been inconclusive. We investigated the associations between intake of coffee and black tea with lung cancer in a population-based case-control study in Montreal, Canada. These analyses included 1130 cases and 1483 controls. Adjusted odds ratios (ORs) were estimated between four metrics of coffee and black tea consumption (frequency, average daily amount, duration, and cumulative amount) and lung cancer, using unconditional logistic regression. The adjusted ORs (95% confidence intervals) for lung cancer comparing daily to never consumers were 0.73 (0.49-1.10) for coffee and 1.05 (0.85-1.31) for black tea. Analyses of other metrics did not reveal any clear patterns of increasing or decreasing risk with increasing amounts or duration of consumption. There was no strong evidence of OR modification by sex or smoking level. The OR estimates did not materially differ by histological subtype for either of the beverages. Our results do not provide strong support for associations between consumption of coffee and black tea and lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of the cell of origin for small cell lung cancer

PubMed Central

Park, Kwon-Sik; Liang, Mei-Chih; Raiser, David M; Zamponi, Raffaella; Roach, Rebecca R; Curtis, Stephen J; Walton, Zandra; Schaffer, Bethany E; Roake, Caitlin M; Zmoos, Anne-Flore; Kriegel, Christina; Wong, Kwok-Kin

2011-01-01

Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer that affects more than 200,000 people worldwide every year with a very high mortality rate. Here, we used a mouse genetics approach to characterize the cell of origin for SCLC; in this mouse model, tumors are initiated by the deletion of the Rb and p53 tumor suppressor genes in the lung epithelium of adult mice. We found that mouse SCLCs often arise in the lung epithelium, where neuroendocrine cells are located, and that the majority of early lesions were composed of proliferating neuroendocrine cells. In addition, mice in which Rb and p53 are deleted in a variety of non-neuroendocrine lung epithelial cells did not develop SCLC. These data indicate that SCLC likely arises from neuroendocrine cells in the lung. PMID:21822053

Staging of Lung Cancer

MedlinePlus

... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

eMBI: Boosting Gene Expression-based Clustering for Cancer Subtypes.

PubMed

Chang, Zheng; Wang, Zhenjia; Ashby, Cody; Zhou, Chuan; Li, Guojun; Zhang, Shuzhong; Huang, Xiuzhen

2014-01-01

Identifying clinically relevant subtypes of a cancer using gene expression data is a challenging and important problem in medicine, and is a necessary premise to provide specific and efficient treatments for patients of different subtypes. Matrix factorization provides a solution by finding checker-board patterns in the matrices of gene expression data. In the context of gene expression profiles of cancer patients, these checkerboard patterns correspond to genes that are up- or down-regulated in patients with particular cancer subtypes. Recently, a new matrix factorization framework for biclustering called Maximum Block Improvement (MBI) is proposed; however, it still suffers several problems when applied to cancer gene expression data analysis. In this study, we developed many effective strategies to improve MBI and designed a new program called enhanced MBI (eMBI), which is more effective and efficient to identify cancer subtypes. Our tests on several gene expression profiling datasets of cancer patients consistently indicate that eMBI achieves significant improvements in comparison with MBI, in terms of cancer subtype prediction accuracy, robustness, and running time. In addition, the performance of eMBI is much better than another widely used matrix factorization method called nonnegative matrix factorization (NMF) and the method of hierarchical clustering, which is often the first choice of clinical analysts in practice.

eMBI: Boosting Gene Expression-based Clustering for Cancer Subtypes

PubMed Central

Chang, Zheng; Wang, Zhenjia; Ashby, Cody; Zhou, Chuan; Li, Guojun; Zhang, Shuzhong; Huang, Xiuzhen

2014-01-01

Identifying clinically relevant subtypes of a cancer using gene expression data is a challenging and important problem in medicine, and is a necessary premise to provide specific and efficient treatments for patients of different subtypes. Matrix factorization provides a solution by finding checker-board patterns in the matrices of gene expression data. In the context of gene expression profiles of cancer patients, these checkerboard patterns correspond to genes that are up- or down-regulated in patients with particular cancer subtypes. Recently, a new matrix factorization framework for biclustering called Maximum Block Improvement (MBI) is proposed; however, it still suffers several problems when applied to cancer gene expression data analysis. In this study, we developed many effective strategies to improve MBI and designed a new program called enhanced MBI (eMBI), which is more effective and efficient to identify cancer subtypes. Our tests on several gene expression profiling datasets of cancer patients consistently indicate that eMBI achieves significant improvements in comparison with MBI, in terms of cancer subtype prediction accuracy, robustness, and running time. In addition, the performance of eMBI is much better than another widely used matrix factorization method called nonnegative matrix factorization (NMF) and the method of hierarchical clustering, which is often the first choice of clinical analysts in practice. PMID:25374455

Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

PubMed Central

Parker, Joel S.; Mullins, Michael; Cheang, Maggie C.U.; Leung, Samuel; Voduc, David; Vickery, Tammi; Davies, Sherri; Fauron, Christiane; He, Xiaping; Hu, Zhiyuan; Quackenbush, John F.; Stijleman, Inge J.; Palazzo, Juan; Marron, J.S.; Nobel, Andrew B.; Mardis, Elaine; Nielsen, Torsten O.; Ellis, Matthew J.; Perou, Charles M.; Bernard, Philip S.

2009-01-01

Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. Conclusion Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy. PMID:19204204

Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

PubMed

Wu, Mingxiang; Ma, Jie

2017-04-01

Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P <0.05). The BLBC subtype was more commonly associated with "rim enhancement" and persistent inflow type enhancement in delayed phase (P <0.05). HER2 overexpressed cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P <0.05). Certain radiological features are strongly associated with the molecular subtype and hormone receptor status of breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vulcano, Francesca, E-mail: francesca.vulcano@iss.it; Milazzo, Luisa, E-mail: luisa.milazzo@iss.it; Ciccarelli, Carmela, E-mail: carmela.ciccarelli@univaq.it

Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC wasmore » observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes. - Highlights: • CM from WJMSC induces apoptosis of SCC-LCSC and reduction of ALDH+ and CD133+ cells. • Specificity of SCC-LCSC inhibition by WJ-CM is proved by the use of a CM from NHDF. • WJ-CM enhance AC-LCSC proliferation and increase CD133+ and ALDH+ cell fractions. • Coinjection of WJMSC with AC-LCSC increase tumor growth with SCC-LCSC has no effect.« less

Social determinants of lung cancer incidence in Canada: A 13-year prospective study.

PubMed

Mitra, Debjani; Shaw, Amanda; Tjepkema, Michael; Peters, Paul

2015-06-01

The risk of lung cancer has been shown to be inversely related to socioeconomic status (SES). Because the Canadian Cancer Registry does not contain socioeconomic data, the 1991 Canadian Census Cohort was used to study social determinants of lung cancer risk in the general Canadian population. This study examines incidence rates of lung cancer and histologic subtypes by educational attainment, income and occupation in a broadly representative sample of Canadians aged 25 or older. Data for the 1991 Canadian Census Cohort were analyzed. The cohort comprised 2,734,835 individuals, among whom 215,700 new cancer cases were diagnosed from 1991 through 2003. Age-standardized incidence rates were calculated by age, sex, and SES using the direct method. Rate ratios, rate differences, and excess incidence were also calculated. An inverse risk between lung cancer incidence and educational attainment, income and occupation emerged among men and women, and a stepped negative gradient in RRs was evident for all SES variables and age groups. If all cohort members had experienced the rate of those with a university degree, lung cancer incidence would have been 56% lower in men and 55% lower in women. If all cohort members had experienced the incidence rate of those in the highest income quintile, incidence would have been 33% lower in men and 25% lower in women. If all cohort members had experienced the rate of those in managerial occupations, incidence would have been 54% lower in men and 44% lower in women. A negative gradient in lung cancer risk was evident for all SES variables studied.

High prevalence of luminal B breast cancer intrinsic subtype in Colombian women

PubMed Central

Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2016-01-01

Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P < 0.001) and recurrence (P < 0.001) according to intrinsic subtype. Patients diagnosed with HER2-enriched, basal-like and NBTN breast cancer had the highest African ancestry. Future studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. PMID:27207651

Epidemiology of Lung Cancer.

PubMed

Schwartz, Ann G; Cote, Michele L

2016-01-01

Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines.

Cancer Genes in Lung Cancer

PubMed Central

El-Telbany, Ahmed

2012-01-01

Cancer is now known as a disease of genomic alterations. Mutational analysis and genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent “oncogenic drivers” in the processes of tumorigenesis and progression. In this review, we will highlight the key driver oncogenic gene mutations and fusions identified in lung cancer. The review will summarize and report the available demographic and clinicopathological data as well as molecular details behind various lung cancer gene alterations in the context of race. We hope to shed some light into the disparities in the incidence of various genetic mutations among lung cancer patients of different racial backgrounds. As molecularly targeted therapy continues to advance in lung cancer, racial differences in specific genetic/genomic alterations can have an important impact in the choices of therapeutics and in our understanding of the drug sensitivity/resistance profile. The most relevant genes in lung cancer described in this review include the following: EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1. Commonly identified genetic/genomic alterations such as missense or nonsense mutations, small insertions or deletions, alternative splicing, and chromosomal fusion rearrangements were discussed. Relevance in current targeted therapeutic drugs was mentioned when appropriate. We also highlighted various targeted therapeutics that are currently under clinical development, such as the MET inhibitors and antibodies. With the advent of next-generation sequencing, the landscape of genomic alterations in lung cancer is expected to be much transformed and detailed in upcoming years. These genomic landscape differences in the context of racial disparities should be emphasized both in tumorigenesis and in drug

Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry.

PubMed

Telli, Melinda L; Chang, Ellen T; Kurian, Allison W; Keegan, Theresa H M; McClure, Laura A; Lichtensztajn, Daphne; Ford, James M; Gomez, Scarlett L

2011-06-01

The distribution of breast cancer molecular subtypes has been shown to vary by race/ethnicity, highlighting the importance of host factors in breast tumor biology. We undertook the current analysis to determine population-based distributions of breast cancer subtypes among six ethnic Asian groups in California. We defined immunohistochemical (IHC) surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese, and South Asian patients diagnosed with incident, primary, invasive breast cancer between 2002 and 2007 in the California Cancer Registry as: hormone receptor-positive (HR+)/HER2- [estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-negative (HER2-)], triple-negative (ER-, PR-, and HER2-), and HER2-positive (ER±, PR±, and HER2+). We calculated frequencies of breast cancer subtypes among Asian ethnic groups and evaluated their associations with clinical and demographic factors. Complete IHC data were available for 8,140 Asian women. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5-2.2], Filipina (OR = 1.3, 95% CI = 1.2-1.5), Vietnamese (OR = 1.3, 95% CI = 1.1-1.6), and Chinese (OR = 1.1, 95% CI = 1.0-1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. We report a significant ethnic disparity in HER2-positive breast cancer in a large population-based cohort enriched for Asian-Americans. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care.

Interplay between the lung microbiome and lung cancer.

PubMed

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies in Lung Cancer by Suppressing BIM.

PubMed

Song, Kyung-A; Niederst, Matthew J; Lochmann, Timothy L; Hata, Aaron N; Kitai, Hidenori; Ham, Jungoh; Floros, Konstantinos V; Hicks, Mark A; Hu, Haichuan; Mulvey, Hillary E; Drier, Yotam; Heisey, Daniel A R; Hughes, Mark T; Patel, Neha U; Lockerman, Elizabeth L; Garcia, Angel; Gillepsie, Shawn; Archibald, Hannah L; Gomez-Caraballo, Maria; Nulton, Tara J; Windle, Brad E; Piotrowska, Zofia; Sahingur, Sinem E; Taylor, Shirley M; Dozmorov, Mikhail; Sequist, Lecia V; Bernstein, Bradley; Ebi, Hiromichi; Engelman, Jeffrey A; Faber, Anthony C

2018-01-01

Purpose: Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. Experimental Design: We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR -mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR -mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment. Mechanistically, we observed that the EMT transcription factor ZEB1 inhibits BIM expression by binding directly to the BIM promoter and repressing transcription. Derepression of BIM expression by depletion of ZEB1 or treatment with the BH3 mimetic ABT-263 to enhance "free" cellular BIM levels both led to resensitization of mesenchymal EGFR -mutant cancers to EGFRi. This relationship between EMT and loss of BIM is not restricted to EGFR -mutant lung cancers, as it was also observed in KRAS -mutant lung cancers and large datasets, including different cancer subtypes. Conclusions: Altogether, these data reveal a novel mechanistic link between EMT and resistance to lung cancer targeted therapies. Clin Cancer Res; 24(1); 197-208. ©2017 AACR . ©2017 American Association for Cancer Research.

American Cancer Society lung cancer screening guidelines.

PubMed

Wender, Richard; Fontham, Elizabeth T H; Barrera, Ermilo; Colditz, Graham A; Church, Timothy R; Ettinger, David S; Etzioni, Ruth; Flowers, Christopher R; Gazelle, G Scott; Kelsey, Douglas K; LaMonte, Samuel J; Michaelson, James S; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Sullivan, Daniel C; Travis, William; Walter, Louise; Wolf, Andrew M D; Brawley, Otis W; Smith, Robert A

2013-01-01

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. Copyright © 2013 American Cancer Society, Inc.

Occurrence of breast cancer subtypes in adolescent and young adult women

PubMed Central

2012-01-01

Introduction Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER-/PR-/HER2-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood. Methods Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+), and logistic regression was used to evaluate differences in subtype characteristics by age group. Results AYAs had higher proportions of HR+/HER2+, triple-negative and HR-/HER2+ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR+/HER2- and triple-negative subtypes in AYAs varied substantially by race/ethnicity. Conclusions The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs. PMID:22452927

High prevalence of luminal B breast cancer intrinsic subtype in Colombian women.

PubMed

Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2016-07-01

Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P < 0.001) and recurrence (P < 0.001) according to intrinsic subtype. Patients diagnosed with HER2-enriched, basal-like and NBTN breast cancer had the highest African ancestry. Future studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection.

PubMed

Lee, Su Hyun; Chang, Jung Min; Shin, Sung Ui; Chu, A Jung; Yi, Ann; Cho, Nariya; Moon, Woo Kyung

2017-12-01

To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review. DBT features and the cancer detectability score according to molecular subtype were compared using Fisher's exact test and analysis of variance. Of 288 invasive cancers, 194 were hormone receptor (HR)-positive, 48 were human epidermal growth factor receptor 2 (HER2) positive and 46 were triple negative breast cancers. The most common DBT findings were irregular spiculated masses for HR-positive cancer, fine pleomorphic or linear branching calcifications for HER2 positive cancer and irregular masses with circumscribed margins for triple negative breast cancers (p < 0.001). Cancer detectability on DBT was not significantly different according to molecular subtype (p = 0.213) but rather affected by tumour size, breast density and presence of mass or calcifications. Breast cancers showed different imaging features according to molecular subtype; however, it did not affect the cancer detectability on DBT. Advances in knowledge: DBT showed characteristic imaging features of breast cancers according to molecular subtype. However, cancer detectability on DBT was not affected by molecular subtype of breast cancers.

American Cancer Society Lung Cancer Screening Guidelines

PubMed Central

Wender, Richard; Fontham, Elizabeth T. H.; Barrera, Ermilo; Colditz, Graham A.; Church, Timothy R.; Ettinger, David S.; Etzioni, Ruth; Flowers, Christopher R.; Gazelle, G. Scott; Kelsey, Douglas K.; LaMonte, Samuel J.; Michaelson, James S.; Oeffinger, Kevin C.; Shih, Ya-Chen Tina; Sullivan, Daniel C.; Travis, William; Walter, Louise; Wolf, Andrew M. D.; Brawley, Otis W.; Smith, Robert A.

2013-01-01

Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. PMID:23315954

Lung cancer in patients with lung transplants.

PubMed

Espinosa, D; Baamonde, C; Illana, J; Arango, E; Carrasco, G; Moreno, P; Algar, F J; Alvarez, A; Cerezo, F; Santos, F; Vaquero, J M; Redel, J; Salvatierra, A

2012-09-01

The aim of our study was to describe the incidence of lung cancer in patients after lung transplantation (LT). We performed an observational, retrospective, descriptive study based on data from 340 patients undergoing lung transplantation between October 1993 and December 2010. We collected data about the donors, recipients, intra- and postoperative periods, and survivals. We identified 9 (2.6%) patients who developed lung cancer after LT. Their average age was 56 ± 9.3 years (range, 18-63). All cases were men with 8/9 (88.8%) having received a single lung transplant. All cancers developed in the native lung. The indications for transplantation were: emphysema type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers. All of the COPD patient were affected. The interval from transplantation to diagnosis was 53.3 ± 12 months (range 24-86). Survival after cancer diagnosis was 49.3 ± 6.3 (range = 0-180) months. LT was associated with a relatively high incidence of lung cancer, particularly in the native lung. In our series, lung cancer was related more to patients with emphysema-type COPD and a history of smoking. We believe that these patients should be closely followed to establish the diagnosis and apply early treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

TCGA researchers identify 4 subtypes of stomach cancer

Cancer.gov

Stomach cancers fall into four distinct molecular subtypes, researchers with The Cancer Genome Atlas (TCGA) Network have found. Scientists report that this discovery could change how researchers think about developing treatments for stomach cancer, also c

Epidemiological changes in the histological subtypes of 35,018 non-small-cell lung cancer cases in Brazil.

PubMed

Costa, Guilherme; Thuler, Luiz Claudio Santos; Ferreira, Carlos Gil

2016-07-01

Regarding the fatality rates stemming from various existing forms of cancers worldwide, lung cancer (LC) is ranked as the main cause of death amongst those who suffer from cancer. Although the epidemiological, clinical, and histological profile of patients with this type of cancer is largely unknown, Brazil has made tremendous efforts to generate data for supporting healthcare policies concerning lung cancer. Taking these factors into account, this study aims to analyse the epidemiological, clinical, and histological profiles of patients with non-small-cell lung cancer (NSCLC) in Brazil. For this study, a cross-sectional epidemiological study was conducted to nationally analyse patient's data within the cancer hospital registries found in the National Cancer Institute (INCA) and the São Paulo Cancer Foundation (FOSP) between 2000 and 2011. A total of 35,018 patients diagnosed with NSCLC in Brazil between 2000 and 2011 were analysed. The analysis demonstrated the occurrence of an epidemiological shift, related to the most prevalent histological type of NSCLC in the study population from 2003. The shift resulted in a higher percentage of adenocarcinoma (43.3%) over squamous cell carcinoma (36.5%). Additionally, there was a significant increase in both the number of cases of LC in women and in the rates of patients diagnosed with metastatic disease. The use of filtered cigarettes since the 60's and the increase in the number of LC cases in women, were one of the causes for the switch in the histological profile of NSCLC in Brazil. Consequently, adenocarcinoma is now the predominant type of cancer detected. Late diagnosis is a hallmark sign. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Frequent and Focal FGFR1 Amplification Associates With Therapeutically Tractable FGFR1 Dependency in Squamous-cell Lung Cancer

PubMed Central

Weiss, Jonathan; Sos, Martin L.; Seidel, Danila; Peifer, Martin; Zander, Thomas; Heuckmann, Johannes M.; Ullrich, Roland T.; Menon, Roopika; Maier, Sebastian; Soltermann, Alex; Moch, Holger; Wagener, Patrick; Fischer, Florian; Heynck, Stefanie; Koker, Mirjam; Schöttle, Jakob; Leenders, Frauke; Gabler, Franziska; Dabow, Ines; Querings, Silvia; Heukamp, Lukas C.; Balke-Want, Hyatt; Ansén, Sascha; Rauh, Daniel; Baessmann, Ingelore; Altmüller, Janine; Wainer, Zoe; Conron, Matthew; Wright, Gavin; Russell, Prudence; Solomon, Ben; Brambilla, Elisabeth; Brambilla, Christian; Lorimier, Philippe; Sollberg, Steinar; Brustugun, Odd Terje; Engel-Riedel, Walburga; Ludwig, Corinna; Petersen, Iver; Sänger, Jörg; Clement, Joachim; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Daniëlle; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Hallek, Michael; Beroukhim, Rameen; Pao, William; Klebl, Bert; Baumann, Matthias; Buettner, Reinhard; Ernestus, Karen; Stoelben, Erich; Wolf, Jürgen; Nürnberg, Peter; Perner, Sven; Thomas, Roman K.

2014-01-01

Lung cancer remains one of the leading causes for cancer-related death in developed countries. In lung adenocarcinomas, EGFR mutations and EML4-ALK fusions are associated with response to EGFR and ALK inhibition. By contrast, therapeutically exploitable genetic alterations have been lacking in squamous-cell lung cancer. We conducted a systematic search for alterations that are therapeutically amenable and performed high-resolution gene-copy number analyses in a set of 232 lung cancer specimens. We identified frequent and focal FGFR1 amplification in squamous-cell lung cancer (n=155), but not in other lung cancer subtypes, and confirmed its presence in an independent cohort of squamous-cell lung cancer samples employing FISH (22% of cases). Using cell-based screening with the FGFR inhibitor (PD173074) in a large (n=83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth (p=0.0002) and induced apoptosis (p=0.008) specifically in those lung cancer cells carrying amplified FGFR1. We validated the dependency on FGFR1 of FGFR1-amplified cell lines by knockdown of FGFR1 and by ectopic expression of a resistance allele of FGFR1 (FGFR1V561M), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Focal FGFR1 amplification is common in squamous-cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients. PMID:21160078

Lung cancer and socioeconomic status in a pooled analysis of case-control studies

PubMed Central

Hovanec, Jan; Siemiatycki, Jack; Conway, David I.; Olsson, Ann; Stücker, Isabelle; Guida, Florence; Jöckel, Karl-Heinz; Pohlabeln, Hermann; Ahrens, Wolfgang; Brüske, Irene; Wichmann, Heinz-Erich; Gustavsson, Per; Consonni, Dario; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Fortes, Cristina; Parent, Marie-Elise; McLaughlin, John; Demers, Paul; Landi, Maria Teresa; Caporaso, Neil; Tardón, Adonina; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabianova, Eleonora; Field, John; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kromhout, Hans; Vermeulen, Roel; Boffetta, Paolo; Straif, Kurt; Schüz, Joachim; Kendzia, Benjamin; Pesch, Beate; Brüning, Thomas; Behrens, Thomas

2018-01-01

Background An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. Methods Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. Results The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61–2.09); ESeC OR 1.53 (95% CI 1.44–1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20–1.98); ESeC OR 1.34 (95% CI 1.19–1.52)). Conclusion SES remained a risk factor for lung cancer after adjustment for smoking behavior. PMID:29462211

Age-Specific Incidence of Breast Cancer Subtypes: Understanding the Black–White Crossover

PubMed Central

2012-01-01

Background Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black–white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity. Methods We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)—together referred to as hormone receptor (HR)—and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR+/HER2−), ER or PR positive and HER2 positive (HR+/HER2+), ER and PR negative and HER2 positive (HR−/HER2+), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age-specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided. Results We did not observe an age-related black–white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR+/HER2− breast cancers after age 35 years (all P < .05). The age-specific incidence of HR+/HER2+ and HR−/HER2+ subtypes did not vary markedly between white and black women. Conclusions The black–white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR+/HER2− breast cancers in black vs white women. PMID:22773826

Epidemiological risk factors associated with inflammatory breast cancer subtypes.

PubMed

Atkinson, Rachel L; El-Zein, Randa; Valero, Vicente; Lucci, Anthony; Bevers, Therese B; Fouad, Tamer; Liao, Weiqin; Ueno, Naoto T; Woodward, Wendy A; Brewster, Abenaa M

2016-03-01

In this single-institution case-control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu-), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER-/PR-/HER2neu-). In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37-8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15-0.62) and luminal IBC (OR 0.35, 95% CI 0.18-0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24-4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m(2)) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies.

Lung cancer-A global perspective.

PubMed

McIntyre, Amanda; Ganti, Apar Kishor

2017-04-01

Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment. © 2017 Wiley Periodicals, Inc.

KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients.

PubMed

Gao, Weimin; Jin, Jide; Yin, Jinling; Land, Stephanie; Gaither-Davis, Autumn; Christie, Neil; Luketich, James D; Siegfried, Jill M; Keohavong, Phouthone

2017-02-01

Mutations in the KRAS and TP53 genes have been found frequently in lung tumors and specimens from individuals at high risk for lung cancer and have been suggested as predictive markers for lung cancer. In order to assess the prognostic value of these two genes' mutations in lung cancer recurrence, we analyzed mutations in codon 12 of the KRAS gene and in hotspot codons of the TP53 gene in 176 bronchial biopsies obtained from 77 former lung cancer patients. Forty-seven patients (61.0%) showed mutations, including 35/77 (45.5%) in the KRAS gene and 25/77 (32.5%) in the TP53 gene, among them 13/77 (16.9%) had mutations in both genes. When grouped according to past or current smoking status, a higher proportion of current smokers showed mutations, in particular those in the TP53 gene (P = 0.07), compared with ex-smokers. These mutations were found in both abnormal lesions (8/20 or 40%) and histologically normal tissues (70/156 or 44.9%) (P = 0.812). They consisted primarily of G to A transition and G to T transversion in both the KRAS (41/56 or 73.2%) and TP53 (24/34 or 70.6%) genes, consistent with mutations found in lung tumors of smoking lung cancer patients. Overall, recurrence-free survival (RFS) among all subjects could be explained by age at diagnosis, tumor stage, tumor subtype, and smoking (P < 0.05, Cox proportional hazard). Therefore, KRAS and TP53 mutations were frequently detected in bronchial tissues of former lung cancer patients. However, the presence of mutation of bronchial biopsies was not significantly associated with a shorter RFS time. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Family history and lung cancer risk: international multicentre case-control study in Eastern and Central Europe and meta-analyses.

PubMed

Lissowska, Jolanta; Foretova, Lenka; Dabek, Joanna; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Fabianova, Eleonora; Cassidy, Adrian; Mates, Dana; Bencko, Vladimir; Janout, Vladimir; Hung, Rayjean J; Brennan, Paul; Boffetta, Paolo

2010-07-01

Lung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer and other tobacco-related cancers might be a strong predictor of the lung cancer risk. We investigated family history of cancer among first-degree relatives of 2,861 patients with lung cancer and 3,118 controls from the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and United Kingdom within the IARC Multicenter Case-Control Study. Odds ratios (ORs) and 95% CI were calculated using logistic regression, adjusting for age, gender, study center, education, tobacco smoking, and number of first-degree relatives. In addition, we conducted a meta-analysis of 41 studies on FH of cancer and lung cancer risk. Positive FH of lung cancer increased risk of lung cancer with OR of 1.63 (95%CI: 1.31-2.01), and having two or more affected relatives with lung cancer further increased the risk of lung cancer with OR 3.60 (95%CI: 1.56-8.31). Among subjects aged less than 50, the OR for FH of lung cancer was 2.08 (95%CI: 1.18-3.63). The associations were generally stronger for squamous cell carcinoma and large cell carcinoma subtypes. Heterogeneity in results was not found with respect to smoking status and gender. A significant association was not observed for FH of other smoking-related tumors. The results of meta-analysis were consistent with that of our study with regard to young onset, non-smokers and histology. FH of lung cancer is a predictor of an increased risk of lung cancer, especially in subjects aged less than 50.

Wood dust exposure and lung cancer risk: a meta-analysis.

PubMed

Hancock, David G; Langley, Mary E; Chia, Kwan Leung; Woodman, Richard J; Shanahan, E Michael

2015-12-01

Occupational lung cancers represent a major health burden due to their increasing prevalence and poor long-term outcomes. While wood dust is a confirmed human carcinogen, its association with lung cancer remains unclear due to inconsistent findings in the literature. We aimed to clarify this association using meta-analysis. We performed a search of 10 databases to identify studies published until June 2014. We assessed the lung cancer risk associated with wood dust exposure as the primary outcome and with wood dust-related occupations as a secondary outcome. Random-effects models were used to pool summary risk estimates. 85 publications were included in the meta-analysis. A significantly increased risk for developing lung cancer was observed among studies that directly assessed wood dust exposure (RR 1.21, 95% CI 1.05 to 1.39, n=33) and that assessed wood dust-related occupations (RR 1.15, 95% CI 1.07 to 1.23, n=59). In contrast, a reduced risk for lung cancer was observed among wood dust (RR 0.63, 95% CI 0.39 to 0.99, n=5) and occupation (RR 0.96, 95% CI 0.95 to 0.98, n=1) studies originating in Nordic countries, where softwood dust is the primary exposure. These results were independent of the presence of adjustment for smoking and exposure classification methods. Only minor differences in risk between the histological subtypes were identified. This meta-analysis provides strong evidence for an association between wood dust and lung cancer, which is critically influenced by the geographic region of the study. The reasons for this region-specific effect estimates remain to be clarified, but may suggest a differential effect for hardwood and softwood dusts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Lung cancer mimicking lung abscess formation on CT images.

PubMed

Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer

PubMed Central

Savas, Peter; Hughes, Brett

2013-01-01

Advances in the treatment of non-small cell lung cancer (NSCLC) over the last decade have predominantly involved the development of therapies directed at molecular targets such as mutations in the epidermal growth factor receptor (EGFR) or rearrangements in the anaplastic lymphoma kinase (ALK) gene. Other targets have been discovered at low frequency, with multiple agents approved or in development for treatment of these rare molecular subtypes. The tumour microenvironment has also provided opportunities for therapies targeting angiogenesis and the host immune response. This review will provide an overview of current targeted therapies in NSCLC and promising treatment approaches on the horizon. PMID:24163750

Triple test with tumor markers CYFRA 21.1, HE4, and ProGRP might contribute to diagnosis and subtyping of lung cancer.

PubMed

Korkmaz, Elif Tugce; Koksal, Deniz; Aksu, Funda; Dikmen, Z Gunnur; Icen, Duygu; Maden, Emin; Onder, Sevgen; Akbiyik, Filiz; Emri, Salih

2018-05-02

Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC. Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated. Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC. A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

KRAS and the Reality of Personalized Medicine in Non-Small Cell Lung Cancer

PubMed Central

Kilgoz, Havva O; Bender, Guzide; Scandura, Joseph M; Viale, Agnes; Taneri, Bahar

2016-01-01

Lung cancer is the leading cause of mortality among all cancer types worldwide. The latest available global statistics of the World Health Organization report 1.59 million casualities in 2012. Worldwide, 1 in 5 cancer deaths are caused by lung cancer. In 2016, in the United States alone, there are an estimated 224,390 new cases of lung cancer, of which 158,080 are expected to result in death, as reported by the National Cancer Institute. Non-small cell lung cancer (NSCLC), a histological subtype, comprises about 85% of all cases, which is nearly 9 out of 10 lung cancer patients. Efforts are under way to develop and improve targeted therapy strategies. Certain mutations are being clinically targeted, such as those in EGFR and ALK genes. However, one of the most frequently mutated genes in NSCLC is the Kirsten rat sarcoma viral oncogene homolog (KRAS), which is currently not targetable. Approximately 25% of all types of NSCLC tumors contain KRAS mutations, which remain as an undruggable challenge. These mutations are indicative of poor prognosis and show negative response to standard chemotherapy. Furthermore, tumors harboring KRAS mutations are unlikely to respond to currently available targeted treatments such as tyrosine kinase inhibitors. Therefore, there is a definitive, urgent need to generate new targeted therapy approaches for KRAS mutations. Current strategies have major limitations and revolve around targeting molecules upstream and downstream of KRAS. Direct targeting is not available in the clinic. Combination therapies using multiple agents are being sought. Concentrated efforts are needed to accelerate basic research and consecutive clinical trials to achieve effective targeting of KRAS. PMID:27447490

Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

PubMed Central

Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2015-01-01

The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

Breast cancer molecular subtype classification using deep features: preliminary results

NASA Astrophysics Data System (ADS)

Zhu, Zhe; Albadawy, Ehab; Saha, Ashirbani; Zhang, Jun; Harowicz, Michael R.; Mazurowski, Maciej A.

2018-02-01

Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

Lung Cancer Screening.

PubMed

Hoffman, Richard M; Sanchez, Rolando

2017-07-01

Lung cancer is the leading cause of cancer death in the United States. More than 80% of these deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden. The National Lung Screening Trial showed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography. The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years. Published by Elsevier Inc.

Lung Cancer and Lung Transplantation.

PubMed

Brand, Timothy; Haithcock, Benjamin

2018-02-01

Lung transplantation remains a viable option for patients with endstage pulmonary disease. Despite removing the affected organ and replacing both lungs, the risk of lung malignancies still exists. Regardless of the mode of entry, lung cancer affects the prognosis in these patients and diligence is required. Copyright © 2017 Elsevier Inc. All rights reserved.

Lung Cancer: Glossary

MedlinePlus

... effects of radiation therapy Randomized Clinical Trial: Trial design in which participants are assigned by chance to ... effect caused by treatment. Small Cell Lung Cancer: One of the two main categories of lung cancer; ...

Stages of Small Cell Lung Cancer

MedlinePlus

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key ...

Impact of breast cancer subtypes and patterns of metastasis on outcome.

PubMed

Kast, Karin; Link, Theresa; Friedrich, Katrin; Petzold, Andrea; Niedostatek, Antje; Schoffer, Olaf; Werner, Carmen; Klug, Stefanie J; Werner, Andreas; Gatzweiler, Axel; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

2015-04-01

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive

Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

PubMed Central

Choi, Hye Joo; Lee, Jinseon; Jung, Kyungsoo; Irwin, Darry; Liu, Xiao; Lira, Maruja E.; Mao, Mao; Kim, Hong Kwan; Choi, Yong Soo; Shim, Young Mog; Park, Woong Yang; Choi, Yoon-La; Kim, Jhingook

2015-01-01

The aim of this study was to determine the distribution of known oncogenic driver mutations in female never-smoker Asian patients with lung adenocarcinoma. We analyzed 214 mutations across 26 lung cancer-associated genes and three fusion genes using the MassARRAY® LungCarta Panel and the ALK, ROS1, and RET fusion assays in 198 consecutively resected lung adenocarcinomas from never-smoker females at a single institution. EGFR mutation, which was the most frequent driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS, PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7%, 4%, 2.5%, 1.5%, 1%, 1%, and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never-smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas tended to have a lower frequency of known driver gene mutations than other histologic subtypes. EGFR mutation was associated with older age and a predominantly acinar pattern, while ALK rearrangement was associated with younger age and a predominantly solid pattern. Lung cancer in never-smoker Asian females is a distinct entity, with the majority of these cancers developing from oncogenic mutations. PMID:25760072

Systematical analysis of lncRNA-mRNA competing endogenous RNA network in breast cancer subtypes.

PubMed

Zhou, Shunheng; Wang, Lihong; Yang, Qian; Liu, Haizhou; Meng, Qianqian; Jiang, Leiming; Wang, Shuyuan; Jiang, Wei

2018-06-01

Breast cancer is one of the most common solid tumors in women involving multiple subtypes. However, the mechanism for subtypes of breast cancer is still complicated and unclear. Recently, several studies indicated that long non-coding RNAs (lncRNAs) could act as sponges to compete miRNAs with mRNAs, participating in various biological processes. We concentrated on the competing interactions between lncRNAs and mRNAs in four subtypes of breast cancer (basal-like, HER2+, luminal A and luminal B), and analyzed the impacts of competing endogenous RNAs (ceRNAs) on each subtype systematically. We constructed four breast cancer subtype-related lncRNA-mRNA ceRNA networks by integrating the miRNA target information and the expression data of lncRNAs, miRNAs and mRNAs. We constructed the ceRNA network for each breast cancer subtype. Functional analysis revealed that the subtype-related ceRNA networks were enriched in cancer-related pathways in KEGG, such as pathways in cancer, miRNAs in cancer, and PI3k-Akt signaling pathway. In addition, we found three common lncRNAs across the four subtype-related ceRNA networks, NEAT1, OPI5-AS1 and AC008124.1, which played specific roles in each subtype through competing with diverse mRNAs. Finally, the potential drugs for treatment of basal-like subtype could be predicted through reversing the differentially expressed lncRNA in the ceRNA network. This study provided a novel perspective of lncRNA-involved ceRNA network to dissect the molecular mechanism for breast cancer.

S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Na; Sato, Daisuke; Saiki, Yuriko

2014-05-09

Highlights: • We observed frequent overexpression of S100A4 in lung cancer cell lines. • Knockdown of S100A4 suppressed proliferation in lung cancer cells. • Forced expression of S100A4 accelerated cell motility in lung cancer cells. • PRDM2 was found to be one of the downstream suppressed genes of S100A4. - Abstract: S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells. However, its biological role in lung carcinogenesis is largely unknown. In thismore » study, we found that S100A4 was frequently overexpressed in lung cancer cells, irrespective of histological subtype. Then we performed knockdown and forced expression of S100A4 in lung cancer cell lines and found that specific knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer cells with S100A4-overexpression; forced expression of S100A4 accelerated cell motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1, identified as novel upregulated genes by microarray after specific knockdown of S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was significantly upregulated after S100A4-knockdown in one of two analyzed S100A4-overexpressing lung cancer cells. Our present results suggest that S100A4 plays an important role in lung carcinogenesis by means of cell proliferation and motility by a pathway similar to that in pancreatic cancer.« less

Molecular subtype shift in breast cancer upon trastuzumab treatment: a case report.

PubMed

Āboliņš, Arnis; Vanags, Andrejs; Trofimovičs, Genadijs; Miklaševičs, Edvīns; Gardovskis, Jānis; Štrumfa, Ilze

2011-01-01

Breast cancer is the most common cancer in women. The mortality remains significant despite advanced treatment possibilities. The management of breast cancer is guided by immunohistochemical data that are summarized into molecular subtypes, namely, luminal A, luminal B, HER2 positive and triple negative. HER2 positive and triple negative subtypes of breast cancer are considered to be biologically distinct. We present a case of clinically aggressive breast cancer in a 58-year-old female. Along the course of the disease, the molecular type switched from HER2 positive to triple negative. The patient deteriorated despite combined therapy. We recommend making a possible change of the molecular subtype and employing repeated immunohistochemical investigation in case of relapse.

An MRM-Based Cytokeratin Marker Assay as a Tool for Cancer Studies: Application to Lung Cancer Pleural Effusions.

PubMed

Perzanowska, Anna; Fatalska, Agnieszka; Wojtas, Grzegorz; Lewandowicz, Andrzej; Michalak, Agata; Krasowski, Grzegorz; Borchers, Christoph H; Dadlez, Michal; Domanski, Dominik

2018-03-01

The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis, and therapy monitoring. Second, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity. The potential clinical applicability was demonstrated by the analysis of 118 PE samples. The MRM assay was evaluated for endogenous detection, linearity, precision, upper and lower limits of quantification, selectivity, reproducibility and peptide stability, and is generally applicable to any epithelial cancer study. A set of 118 patients with known pathologies allowed us to define the range of CK levels in clinical PE samples. Specific CKs were able to differentiate cancer-related PEs from those caused by benign ailments. In addition, they allowed to differentiate between PEs from subjects with small cell lung cancer versus non-small cell lung carcinoma, and to further differentiate the latter into its two subtypes, adenocarcinoma and squamous cell carcinoma. An MRM-based CK assay for carcinoma studies can differentiate between the three lung cancer histological types using less-invasive PE sampling providing potential therapy-guiding information on patients that are inoperable. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile.

PubMed

Goto, Taichiro; Hirotsu, Yosuke; Mochizuki, Hitoshi; Nakagomi, Takahiro; Shikata, Daichi; Yokoyama, Yujiro; Oyama, Toshio; Amemiya, Kenji; Okimoto, Kenichiro; Omata, Masao

2017-05-09

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

PubMed

Li, Yafang; Xiao, Xiangjun; Han, Younghun; Gorlova, Olga; Qian, David; Leighl, Natasha; Johansen, Jakob S; Barnett, Matt; Chen, Chu; Goodman, Gary; Cox, Angela; Taylor, Fiona; Woll, Penella; Wichmann, H-Erich; Manz, Judith; Muley, Thomas; Risch, Angela; Rosenberger, Albert; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Houlston, Richard; Soler Artigas, María; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Liu, Geoffrey; Bojesen, Stig E; Wu, Xifeng; Marchand, Loic Le; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C; Bush, William S; Tardon, Adonina; Rennert, Gad; Teare, M Dawn; Field, John K; Kiemeney, Lambertus A; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B; Andrew, Angeline S; Bertazzi, Pier Alberto; Pesatori, Angela C; Christiani, David C; Caporaso, Neil; Johansson, Mattias; McKay, James D; Brennan, Paul; Hung, Rayjean J; Amos, Christopher I

2018-03-08

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Subtype and pathway specific responses to anticancer compounds in breast cancer.

PubMed

Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

2012-02-21

Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

LUNG CANCER AND PULMONARY THROMBOEMBOLISM

PubMed Central

Cukic, Vesna; Ustamujic, Aida

2015-01-01

Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

Breast cancer subtype distribution is different in normal weight, overweight, and obese women.

PubMed

Gershuni, Victoria; Li, Yun R; Williams, Austin D; So, Alycia; Steel, Laura; Carrigan, Elena; Tchou, Julia

2017-06-01

Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women. A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared. Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008). We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.

Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

PubMed

Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

2008-08-15

The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

Lung Cancer Indicators Recurrence

Cancer.gov

This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

PubMed

Lee, Michael S; Menter, David G; Kopetz, Scott

2017-03-01

Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

Brain microvascular endothelium induced-annexin A1 secretion contributes to small cell lung cancer brain metastasis.

PubMed

Liu, Yi; Liu, Yong-Shuo; Wu, Peng-Fei; Li, Qiang; Dai, Wu-Min; Yuan, Shuai; Xu, Zhi-Hua; Liu, Ting-Ting; Miao, Zi-Wei; Fang, Wen-Gang; Chen, Yu-Hua; Li, Bo

2015-09-01

Small cell lung cancer is the most aggressive histologic subtype of lung cancer, with a strong predilection for metastasizing to brain early. However, the cellular and molecular basis is poorly known. Here, we provided evidence to reveal the role of annexin A1 in small cell lung cancer metastasis to brain. Firstly, the elevated annexin A1 serum levels in small cell lung cancer patients were associated with brain metastasis. The levels of annexin A1 were also upregulated in NCI-H446 cells, a small cell lung cancer cell line, upon migration into the mice brain. More interestingly, annexin A1 was secreted by NCI-H446 cells in a time-dependent manner when co-culturing with human brain microvascular endothelial cells, which was identified with the detections of annexin A1 in the co-cultured cellular supernatants by ELISA and western blot. Further results showed that blockage of annexin A1 in the co-cultured cellular supernatants using a neutralized antibody significantly inhibited NCI-H446 cells adhesion to brain endothelium and its transendothelial migration. Conversely, the addition of Ac2-26, an annexin A1 mimic peptide, enhanced these effects. Furthermore, knockdown of annexin A1 in NCI-H446 cells prevented its transendothelial migration in vitro and metastasis to mice brain in vivo. Our data showed that small cell lung cancer cell in brain microvasculature microenvironment could express much more annexin A1 and release it outside, which facilitated small cell lung cancer cell to gain malignant properties of entry into brain. These findings provided a potential target for the management of SCLC brain metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.

PubMed

Gao, Hongjun; Liu, Wenjing; Yang, Shaoxing; Zhang, Wen; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Zhao, Changyun

2018-01-01

This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment. Sixty-six newly diagnosed patients were evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0-81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, respectively. There was no statistically significant difference in the CTC detection rates between these different pathological subtypes (P = 0.738). The CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung cancer, respectively, were not significantly different (P = 0.427). The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients with lung cancer, independent of pathological type and disease stage, and is ideal for large-scale clinical applications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis

PubMed Central

Schwede, Matthew; Spentzos, Dimitrios; Bentink, Stefan; Hofmann, Oliver; Haibe-Kains, Benjamin; Harrington, David; Quackenbush, John; Culhane, Aedín C.

2013-01-01

Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable

Lung cancer: biology and treatment options

PubMed Central

Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

2015-01-01

Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

Lung cancer risk from radon in Ontario, Canada: how many lung cancers can we prevent?

PubMed

Peterson, Emily; Aker, Amira; Kim, JinHee; Li, Ye; Brand, Kevin; Copes, Ray

2013-11-01

To calculate the burden of lung cancer illness due to radon for all thirty-six health units in Ontario and determine the number of radon-attributable lung cancer deaths that could be prevented. We calculated the population attributable risk percent, excess life-time risk ratio, life-years lost, the number of lung cancer deaths due to radon, and the number of deaths that could be prevented if all homes above various cut-points were effectively reduced to background levels. It is estimated that 13.6 % (95 % CI 11.0, 16.7) of lung cancer deaths in Ontario are attributable to radon, corresponding to 847 (95 % CI 686, 1,039) lung cancer deaths each year, approximately 84 % of these in ever-smokers. If all homes above 200 Bq/m(3), the current Canadian guideline, were remediated to background levels, it is estimated that 91 lung cancer deaths could be prevented each year, 233 if remediation was performed at 100 Bq/m(3). There was important variation across health units. Radon is an important contributor to lung cancer deaths in Ontario. A large portion of radon-attributable lung cancer deaths are from exposures below the current Canadian guideline, suggesting interventions that install effective radon-preventive measures into buildings at build may be a good alternative population prevention strategy to testing and remediation. For some health units, testing and remediation may also prevent a portion of radon-related lung cancer deaths. Regional attributable risk estimates can help with local public health resource allocation and decision making.

Histological, molecular and functional subtypes of breast cancers

PubMed Central

Malhotra, Gautam K; Zhao, Xiangshan; Band, Hamid

2010-01-01

Increased understanding of the molecular heterogeneity that is intrinsic to the various subtypes of breast cancer will likely shape the future of breast cancer diagnosis, prognosis and treatment. Advances in the field over the last several decades have been remarkable and have clearly translated into better patient care as evidenced by the earlier detection, better prognosis and new targeted therapies. There have been two recent advances in the breast cancer research field that have lead to paradigm shifts: first, the identification of intrinsic breast tumor subtypes, which has changed the way we think about breast cancer and second, the recent characterization of cancer stem cells (CSCs), which are suspected to be responsible for tumor initiation, recurrence and resistance to therapy. These findings have opened new exciting avenues to think about breast cancer therapeutic strategies. While these advances constitute major paradigm shifts within the research realm, the clinical arena has yet to adopt and apply our understanding of the molecular basis of the disease to early diagnosis, prognosis and therapy of breast cancers. Here, we will review the current clinical approach to classification of breast cancers, newer molecular-based classification schemes and potential future of biomarkers representing a functional classification of breast cancer. PMID:21057215

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

PubMed Central

Travis, William D.; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G.; Geisinger, Kim R.; Yatabe, Yasushi; Beer, David G.; Powell, Charles A.; Riely, Gregory J.; Van Schil, Paul E.; Garg, Kavita; Austin, John H. M.; Asamura, Hisao; Rusch, Valerie W.; Hirsch, Fred R.; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M.; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A.; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

2015-01-01

Introduction Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

PubMed

Travis, William D; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G; Geisinger, Kim R; Yatabe, Yasushi; Beer, David G; Powell, Charles A; Riely, Gregory J; Van Schil, Paul E; Garg, Kavita; Austin, John H M; Asamura, Hisao; Rusch, Valerie W; Hirsch, Fred R; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

2011-02-01

Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

PubMed

Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Statistical methods for studying disease subtype heterogeneity.

PubMed

Wang, Molin; Spiegelman, Donna; Kuchiba, Aya; Lochhead, Paul; Kim, Sehee; Chan, Andrew T; Poole, Elizabeth M; Tamimi, Rulla; Tworoger, Shelley S; Giovannucci, Edward; Rosner, Bernard; Ogino, Shuji

2016-02-28

A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, and non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism, and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available. Copyright © 2015 John Wiley & Sons, Ltd.

Lung cancer in younger patients.

PubMed

Abbasowa, Leda; Madsen, Poul Henning

2016-07-01

Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. To assess the age differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly diagnosed lung cancer patients were included. Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours, a significantly higher proportion of the younger patients presented with advanced stage disease (p = 0.0392). Combined modality therapy was more common in younger patients (p = 0.0009), while chemotherapy appeared less prevalent among the elderly (p = 0.0015). Lung cancer in younger patients comprises a distinct clinicopathological entity with more frequent advanced stage disease and a significantly greater proportion with a family history of cancer. Implementing genetic background assessments and considering lung cancer as a possible diagnosis in younger, symptomatic patients, is of paramount importance. none. The study was approved by the -Danish Data Protection Agency.

Lung cancer in persons with HIV.

PubMed

Sigel, Keith; Makinson, Alain; Thaler, Jonathan

2017-01-01

Lung cancer is emerging as a leading cause of death in HIV-infected persons. This review will discuss the latest scientific evidence regarding the mechanisms driving lung cancer risk in HIV infection, the clinical presentation of lung cancer in HIV-infected persons and recent data regarding the outcomes, treatment and prevention of lung cancer in this group. Increased risk of lung cancer in HIV-infected persons is primarily due to higher smoking rates, but emerging evidence also implicates immunosuppression and inflammatory processes. Lung cancer outcomes may be worse in HIV-infected persons in the antiretroviral era, but this may stem, in part, from treatment disparities. Early detection of lung cancer using chest computed tomography (CT) is being increasingly adopted for smokers in the general population, and recent studies suggest that it may be safe and efficacious in HIV-infected smokers. Lung cancer is an important complication associated with chronic HIV infection. It is associated with unique HIV-related causal mechanisms, and may be associated with worse outcomes in some HIV-infected persons. Smoking cessation and early cancer detection with chest CT are likely to benefit HIV-infected smokers.

Scientific Advances in Lung Cancer 2015.

PubMed

Tsao, Anne S; Scagliotti, Giorgio V; Bunn, Paul A; Carbone, David P; Warren, Graham W; Bai, Chunxue; de Koning, Harry J; Yousaf-Khan, A Uraujh; McWilliams, Annette; Tsao, Ming Sound; Adusumilli, Prasad S; Rami-Porta, Ramón; Asamura, Hisao; Van Schil, Paul E; Darling, Gail E; Ramalingam, Suresh S; Gomez, Daniel R; Rosenzweig, Kenneth E; Zimmermann, Stefan; Peters, Solange; Ignatius Ou, Sai-Hong; Reungwetwattana, Thanyanan; Jänne, Pasi A; Mok, Tony S; Wakelee, Heather A; Pirker, Robert; Mazières, Julien; Brahmer, Julie R; Zhou, Yang; Herbst, Roy S; Papadimitrakopoulou, Vassiliki A; Redman, Mary W; Wynes, Murry W; Gandara, David R; Kelly, Ronan J; Hirsch, Fred R; Pass, Harvey I

2016-05-01

Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective

PubMed Central

Cabanero, M.; Sangha, R.; Sheffield, B.S.; Sukhai, M.; Pakkal, M.; Kamel-Reid, S.; Karsan, A.; Ionescu, D.; Juergens, R.A.; Butts, C.; Tsao, M.S.

2017-01-01

Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed. PMID:28490925

Screening for Lung Cancer

PubMed Central

Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

2013-01-01

Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

Greater absolute risk for all subtypes of breast cancer in the US than Malaysia.

PubMed

Horne, Hisani N; Beena Devi, C R; Sung, Hyuna; Tang, Tieng Swee; Rosenberg, Philip S; Hewitt, Stephen M; Sherman, Mark E; Anderson, William F; Yang, Xiaohong R

2015-01-01

Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.

Breast Cancer Subtype is Associated With Axillary Lymph Node Metastasis

PubMed Central

He, Zhen-Yu; Wu, San-Gang; Yang, Qi; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin

2015-01-01

Abstract The purpose of this study was to assess whether breast cancer subtype (BCS) as determined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 can predict the axillary lymph node metastasis in breast cancer. Patients who received breast conserving surgery or mastectomy and axillary lymph node dissection were identified from 2 cancer centers. The associations between clinicopathological variables and axillary lymph node involvement were evaluated in univariate and multivariate regression analyses. A total of 3471 patients met the inclusion criteria, and 53.0% had axillary lymph node metastases at diagnosis. Patients with hormone receptor (HR)−/human epidermal growth factor receptor 2 (HER2)− subtype had a higher grade disease and the lowest rate of lymphovascular invasion. Univariate and multivariable logistic regression analyses showed that BCS was significantly associated with lymph node involvement. Patients with the HR−/HER2− subtype had the lowest odds of having nodal positivity than those with other BCSs. HR+/HER2− (odds ratio [OR] 1.651, 95% confidence interval [CI]: 1.349–2.021, P < 0.001), HR+/HER2+ (OR 1.958, 95%CI 1.542–2.486, P < 0.001), and HR−/HER2+ (OR 1.525, 95%CI 1.181–1.970, P < 0.001) tumors had higher risk of nodal positivity than the HR−/HER2− subtype. The other independent predictors of nodal metastases included tumor size, tumor grade, and lymphovascular invasion. Breast cancer subtype can predict the presence of axillary lymph node metastasis in breast cancer. HR−/HER2− is associated with a reduced risk of axillary lymph node metastasis compared to other BCSs. Our findings may play an important role in guiding axillary treatment considerations if further confirmed in larger sample size studies. PMID:26632910

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

PubMed Central

2014-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment. PMID:25560450

Occupational exposure to endotoxins and lung cancer risk: results of the ICARE Study

PubMed Central

Ben Khedher, Soumaya; Neri, Monica; Guida, Florence; Matrat, Mireille; Cenée, Sylvie; Sanchez, Marie; Menvielle, Gwenn; Molinié, Florence; Luce, Danièle; Stücker, Isabelle

2017-01-01

Objectives To investigate the role of occupational exposure to endotoxins in lung cancer in a French population-based case–control study (ICARE (Investigation of occupational and environmental causes of respiratory cancers)). Methods Detailed information was collected on the occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. We evaluated each subject’s endotoxin exposure after cross referencing International Standard Classification of Occupations (ISCO) codes (for job tasks) and Nomenclature d'Activités Françaises (NAF) codes (for activity sectors). Endotoxin exposure levels were attributed to each work environment based on literature reports. ORs and 95% CIs were estimated using unconditional logistic regression models and controlled for main confounding factors. Results An inverse association between exposure to endotoxins and lung cancer was found (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and cumulative exposure, and the risk was decreased decades after exposure cessation (all statistically significant). Lung cancer risk was particularly reduced among workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in those weakly exposed (eg, in waste treatment). Statistically significant interactions were shown with smoking, and never/light smokers were more sensitive to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest cumulative exposure, compared with those never exposed). Pronounced inverse associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI 0.25 to 0.55 in the highly exposed). Conclusions Our findings suggest that exposure to endotoxins, even at a low level, reduces the risk of lung cancer. PMID:28490662

Systematic Identification of Molecular Subtype-Selective Vulnerabilities in Non Small Cell Lung Cancer

PubMed Central

Kim, Hyun Seok; Mendiratta, Saurabh; Kim, Jiyeon; Pecot, Chad Victor; Larsen, Jill E.; Zubovych, Iryna; Seo, Bo Yeun; Kim, Jimi; Eskiocak, Banu; Chung, Hannah; McMillan, Elizabeth; Wu, Sherry; De Brabander, Jef; Komurov, Kakajan; Toombs, Jason E.; Wei, Shuguang; Peyton, Michael; Williams, Noelle; Gazdar, Adi F.; Posner, Bruce A.; Brekken, Rolf; Sood, Anil K.; Deberardinis, Ralph J.; Roth, Michael G.; Minna, John D.; White, Michael A.

2013-01-01

SUMMARY Context-specific molecular vulnerabilities that arise during tumor evolution represent an attractive intervention target class. However, the frequency and diversity of somatic lesions detected among lung tumors can confound efforts to identify these targets. To confront this challenge, we have applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. Anchoring this analysis on a matched tumor/normal cell model from a lung adenocarcinoma patient identified three distinct target/response-indicator pairings that are represented with significant frequencies (6–16%) in the patient population. These include NLRP3 mutation/inflammasome activation-dependent FLIP addiction, co-occuring KRAS and LKB1 mutation-driven COPI addiction, and selective sensitivity to a synthetic indolotriazine that is specified by a 7-gene expression signature. Target efficacies were validated in vivo, and mechanism of action studies uncovered new cancer cell biology. PMID:24243015

Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer.

PubMed

Kim, Hyun Seok; Mendiratta, Saurabh; Kim, Jiyeon; Pecot, Chad Victor; Larsen, Jill E; Zubovych, Iryna; Seo, Bo Yeun; Kim, Jimi; Eskiocak, Banu; Chung, Hannah; McMillan, Elizabeth; Wu, Sherry; De Brabander, Jef; Komurov, Kakajan; Toombs, Jason E; Wei, Shuguang; Peyton, Michael; Williams, Noelle; Gazdar, Adi F; Posner, Bruce A; Brekken, Rolf A; Sood, Anil K; Deberardinis, Ralph J; Roth, Michael G; Minna, John D; White, Michael A

2013-10-24

Context-specific molecular vulnerabilities that arise during tumor evolution represent an attractive intervention target class. However, the frequency and diversity of somatic lesions detected among lung tumors can confound efforts to identify these targets. To confront this challenge, we have applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. Anchoring this analysis on a matched tumor/normal cell model from a lung adenocarcinoma patient identified three distinct target/response-indicator pairings that are represented with significant frequencies (6%-16%) in the patient population. These include NLRP3 mutation/inflammasome activation-dependent FLIP addiction, co-occurring KRAS and LKB1 mutation-driven COPI addiction, and selective sensitivity to a synthetic indolotriazine that is specified by a seven-gene expression signature. Target efficacies were validated in vivo, and mechanism-of-action studies informed generalizable principles underpinning cancer cell biology. Copyright © 2013 Elsevier Inc. All rights reserved.

Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences.

PubMed

Valla, Marit; Vatten, Lars Johan; Engstrøm, Monica Jernberg; Haugen, Olav Anton; Akslen, Lars Andreas; Bjørngaard, Johan Håkon; Hagen, Anne Irene; Ytterhus, Borgny; Bofin, Anna Mary; Opdahl, Signe

2016-12-01

Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886-1977. A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886-1928 and 1929-1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs. Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2 - ) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50-54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8-6.9 and 2.5; 95% CI, 1.2-5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3-0.5), Luminal B (HER2 - ; HR 0.5; 95% CI, 0.3-0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2-0.9). We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2 - ) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype. This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625-34. ©2016 AACR. ©2016 American Association for Cancer Research.

Serum pleiotrophin could be an early indicator for diagnosis and prognosis of non-small cell lung cancer.

PubMed

Du, Zi-Yan; Shi, Min-Hua; Ji, Cheng-Hong; Yu, Yong

2015-01-01

Pleiotrophin (PTN), an angiogenic factor, is associated with various types of cancer, including lung cancer. Our aim was to investigate the possibility of using serum PTN as an early indicator regarding disease diagnosis, classification and prognosis, for patients with non-small cell lung cancer (NSCLC). Significant differences among PTN levels in patients with small cell lung cancer (SCLC, n=40), NSCLC (n=136), and control subjects with benign pulmonary lesions (n=21), as well as patients with different pathological subtypes of NSCLC were observed. A serum level of PTN of 300.1 ng/ml, was determined as the cutoff value differentiating lung cancer patients and controls, with a sensitivity and specificity of 78.4% and 66.7%, respectively. Negative correlations between serum PTN level and pathological differentiation level, stage, and survival time were observed in our cohort of patients with NSCLC. In addition, specific elevation of PTN levels in pulmonary tissue in and around NSCLC lesions in comparison to normal pulmonary tissue obtained from the same subjects was also observed (n=2). This study suggests that the serum PTN level of patients with NSCLC could be an early indicator for diagnosis and prognosis. This conclusion should be further assessed in randomized clinical trials.

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.

PubMed

Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart

2016-07-01

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.

Meta-markers for the differential diagnosis of lung cancer and lung disease.

PubMed

Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

2016-10-04

Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pain management in lung cancer.

PubMed

Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Lung Cancer Trends

MedlinePlus

... the Biggest Cancer Killer in Both Men and Women” Stay Informed Trends for Other Kinds of Cancer Breast Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend ...

Curbing the burden of lung cancer.

PubMed

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

ClinicalTrials.gov

2017-08-28

Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

PubMed

Rooney, Claire; Sethi, Tariq

2015-10-01

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

[Current treatment concepts of lung cancer].

PubMed

Kaiser, F; Engelhardt, M; Rawluk, J; Mertelsmann, R; Passlick, B; Wäsch, R

2011-09-01

Lung cancer occurs with a median age of 69 years. The main cause is cigarette smoking. For both genders lung cancer is the third-most frequent tumor in Germany. While in an operable tumor stage 30-80% of the patients can reach long-term survival, the prognosis in the metastasised stage is unfavourable with a 5-year overall survival rate of 6% for small cell lung cancer (SCLC) and 18% for non-small cell lung cancer (NSCLC). Lung cancer is subject of intense research to improve the outcome. This article gives an overview of current treatment options. © Georg Thieme Verlag KG Stuttgart · New York.

What You Need to Know about Lung Cancer

MedlinePlus

... Publications Reports What You Need To Know About™ Lung Cancer This booklet is about lung cancer. Learning about medical care for your cancer can ... The anatomy of the lungs and basics about lung cancer Treatment for lung cancer, including taking part in ...

Risk factors of Lung Cancer in nonsmoker.

PubMed

Akhtar, Nahid; Bansal, Jeena Gupta

Generally, the cause of lung cancer is attributed to tobacco smoking. But many of the new lung cancer cases have been reported in nonsmokers. Apart from smoking; air pollution, environmental exposure, mutations, and single-nucleotide polymorphisms are known to be associated with lung cancer. Improper diet, alcohol consumption, marijuana smoking, estrogen, infections with human papillomavirus (HPV), HIV, and Epstein-Barr virus are suggested to be linked with lung cancer but clear evidences to ascertain their relation is not available. This article provides a comprehensive review of various risk factors and the underlying molecular mechanisms responsible for increasing the incidence of lung cancer. The pathologic, histologic, and genetic differences exist with lung cancer among smokers and nonsmokers. A better understanding of the risk factors, differences in pathology and molecular features of lung cancer in smokers and nonsmokers and the mode of action of various carcinogens will facilitate the prevention and management of lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Stages of Non-Small Cell Lung Cancer

MedlinePlus

... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

PubMed

Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

2016-08-20

An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.

Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium

PubMed Central

Poole, Elizabeth M.; Trabert, Britton; White, Emily; Arslan, Alan A.; Patel, Alpa V.; Setiawan, V. Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A.; Buring, Julie; Butler, Lesley M.; Chamosa, Saioa; Clendenen, Tess V.; Dossus, Laure; Fortner, Renee; Gapstur, Susan M.; Gaudet, Mia M.; Gram, Inger T.; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V.; Lee, I-Min; Lundin, Eva; Merritt, Melissa A.; Onland-Moret, N. Charlotte; Peters, Ulrike; Poynter, Jenny N.; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schouten, Leo J.; Sjöholm, Louise K.; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A.; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P.; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S.

2016-01-01

Purpose An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Patients and Methods Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Results Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. Conclusion The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. PMID:27325851

Customizing Therapies for Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery,

Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011-2015.

PubMed

Wang, Pingli; Zou, Jixia; Wu, Jingni; Zhang, Chengyan; Ma, Chengxi; Yu, Juan; Zhou, You; Li, Baizhou; Wang, Kai

2017-07-01

More than one-third of lung cancer worldwide occurring in China. However, the clinical profiles of lung cancer patients in the mainland of China are rarely reported and largely unknown. The objective of this study is to analyze the characteristics and time trends of newly diagnosed lung cancer cases during the past 5 years in East China. The data came from an academic tertiary care hospital of East China. Patients who were newly diagnosed as lung cancer from 2011 to 2015 were enrolled. All new cases got pathological supports by lung biopsy or surgery. Tumor staging was performed according to the seventh edition of the tumor node metastasis (TNM) classification of malignant tumors. The patients' disease information was collected from the database of the hospital information system (HIS). From 2011 to 2015, aggregately 5,779 patients, including 3,719 males and 2,060 females, were diagnosed as lung cancer. The major histologic subtypes of lung cancer were adenocarcinoma (ADC, 60.0%), squamous cell carcinoma (SCC, 25.6%), small cell lung cancer (SCLC, 8.5%), large cell carcinoma (0.6%), adenosquamous carcinoma (1%), other non-small cell carcinoma (1.6%) and unclassified or rare carcinoma (2.8%). ADC proportion of female was much higher than that of male. A higher proportion of advanced stage (stage IIIB, IV) of lung cancer existed in patients who were admitted to hospital due to respiratory or cancer related symptoms (RCRS) than those without RCRS. Smoking rate in male patients reached 80.2%, while it was only 2.7% in females. EGFR mutation existed in 66% of female and 37% of male patients with ADC. This study demonstrates the clinicopathologic characteristics of lung cancer patients from East China, including histologic composition, staging proportion, smoking prevalence and gene mutation status. During the past 5 years, the proportion of ADC has increased gradually whereas SCC decreased.

The Impact of the Cancer Genome Atlas on Lung Cancer

PubMed Central

Chang, Jeremy Tzu-Huai; Lee, Yee-Ming; Huang, R. Stephanie

2015-01-01

The Cancer Genome Atlas (TCGA) has profiled over 10,000 samples derived from 33 types of cancer to date, with the goal of improving our understanding of the molecular basis of cancer and advancing our ability to diagnose, treat, and prevent cancer. This review focuses on lung cancer as it is the leading cause of cancer-related mortality worldwide in both men and women. Particularly, non-small cell lung cancers (including lung adenocarcinoma and lung squamous cell carcinoma) were evaluated. Our goal is to demonstrate the impact of TCGA on lung cancer research under four themes: namely, diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools. Examples were given related to DNA mutation, copy number variation, mRNA, and microRNA expression along with methylation profiling. PMID:26318634

Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women

PubMed Central

2013-01-01

Introduction Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women. Methods Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010. Results With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women

Profile of lung cancer in kuwait.

PubMed

El-Basmy, Amani

2013-01-01

Lung cancer is the most frequent cancer in males and the fourth most frequent site in females, worldwide. This study is the first to explore the profile of lung cancer in Kuwait. Cases of primary lung cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10 years each) from 1970-2009. Epidemiological measures; age standardized incidence rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and Cumulative risk and Forecasting to year 2020-2029 used for analysis. Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females. The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was 2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is the leading cause cancer death in males 168 (14.2%) and the fifth cause of death due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3) deaths/100,000 population in males and females respectively. The estimated Mortality to incidence Ratio was 0.6. The incidence of lung cancer between years 2000-2009 is not different from that reported in the seventies. KCR is expecting the number of lung cancer cases to increase.

Lung cancer and air pollution.

PubMed

Aoki, K; Shimizu, H

1977-12-01

The relationship between incidence of lung cancer and the volume of traffic as indicated by auto exhaust concentration was examined; the results, though suggestive, did not yield consistent evidence of the association between them. Traffic jams in Nagoya began 15 years ago, a period that may not be long enough to provide definitive data on the incidence of lung cancer. The high standardized mortality ratio (SMR) of lung cancer was observed in cities with a population of less than 1 million and guns (rural areas) along the coast, although those in the metropolitan areas with populations of more than 1 million were average. The SMR did not correlate with various socioeconomic conditions and industrial air pollution. Meteorologic or geologic conditions and ocean currents were not associated with SMR of lung cancer by city and gun. The population of a gun or of some cities was not large enough to be statistically significant, and the mortality rate of lung cancer was not always stable.

Bidi smoking and lung cancer.

PubMed

Prasad, Rajendra; Singhal, Sanjay; Garg, Rajiv

2009-04-01

This article discusses the role of bidi smoking as a risk factor for lung cancer. A review of the documented evidence is presented. The literature from Pubmed has been searched using the key words 'beedi smoking', 'bidi smoking' and 'lung cancer'. The bibliographies of all papers found were further searched for additional relevant articles. After this thorough search, eight studies were found. The evidence suggests that bidi smoking poses a higher risk for lung cancer than cigarette smoking and risk further increases with both the length of time and amount of bidi smoking. The focus of tobacco control programs should be expanded to all types of tobacco use, including bidis, to reduce the increasing problem of lung cancer.

[ALK gene fusion associated non-small cell lung cancer: automated immunostainer detection and clinicopathologic perspectives].

PubMed

Shen, Qin; Pan, Yi; Yu, Bo; Shi, Shanshan; Liu, Biao; Xu, Yan; Wang, Yanfen; Xia, Qiuyuan; Rao, Qiu; Lu, Zhenfeng; Shi, Qunli; Zhou, Xiaojun

2015-03-01

To explore the automated immunostainer screening anaplastic lymphoma kinase (ALK) gene fusion non-small cell lung cancer (NSCLC) and clinicopathological characteristics of the molecular subtype lung cancers. Methods Five hundred and sixty-six cases of NSCLC were collected over a 16 month period. The test for ALK was performed by Ventana automated immunostainer with anti-ALK D5F3. The histological features, treatment and outcome of patients were assessed. Results Thirty-eight cases (6.7%, 38/566) of NSCLC showed ALK gene fusion. The frequency of ALK gene fusion was higher in male (7.1%, 25/350) than that in female (6.0%, 13/216) patients, but not achieving statistical significance (chi2 = 0.270, P = 0.604). ALK + NSCLC was more significantly more frequent in patients < or = 60 years (9.9%, 28/282) than >60 years (3.5% , 10/284) of age. Histologically, the ALK + NSCLCs were mostly adenocarcinoma (81.6%, 31/38) , among which eighteen cases were solid predominant subtype with mucin production; nine cases were acinar predominant subtype; one case was papillary predominant subtype and three cases were invasive mucinous adenocarcinoma. The ALK + non-adenocarcinoma included three cases of squamous cell carcinoma, three cases of adenosquamous carcinoma and one case of pleomorphic carcinoma. Among the ALK + NSCLC patients, the number of non/light cigarette smokers (86. 8% , 33/38) was more than that of heavy smokers. Twenty-nine cases were stages III and IV; twenty-nine cases showed lymph node metastasis; twenty cases showed metastases mostly to brain and bone; and one case showed EGFR gene mutation coexisting with ALK gene fusion. Twelve of fifteen patients received crizotinib therapy and remained stable. Conclusions NSCLC with ALK gene rearrangement shows distinctive clinical and histological features. Ventana-IHC may he a feasible and valid technique for detection of ALK rearrangement in NSCLC.

ALK-rearranged squamous cell lung carcinoma responding to crizotinib: A missing link in the field of non-small cell lung cancer?

PubMed

Vergne, Florence; Quéré, Gilles; Andrieu-Key, Sophie; Descourt, Renaud; Quintin-Roué, Isabelle; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale; Uguen, Arnaud

2016-01-01

ALK-rearrangements are mainly encountered in lung adenocarcinomas and allow treating patients with anti-ALK targeted therapy. ALK-rearranged squamous cell lung carcinomas are rare tumors that can also respond to anti-ALK-targeted therapy. Nevertheless, ALK screening is not always performed in patients with squamous cell lung carcinomas making the identification and treatment of this molecular tumor subtype challenging. We intend to report a rare case of ALK-rearranged lung squamous cell carcinoma with response to crizotinib therapy. We report clinical, pathological, immunohistochemical and fluorescent in situ hybridization data concerning a patient having an ALK-rearranged squamous cell lung cancer diagnosed in our institution. The patient was a 58-year old woman with a metastatic-stage lung cancer. Histopathological and immunohistochemical analyses were performed on a bronchial biopsy sample and concluded in a non-keratinizing squamous cell lung carcinoma expressing strongly cytokeratin 5/6, p63 and p40, which are classic hallmarks of lung squamous cell carcinomas, but also cytokeratin 7 which is more commonly expressed in lung adenocarcinomas. The tumor did not express thyroid transcription factor-1. ALK rearrangement was searched because of the never-smoker status of the patient and resulted in strong positive fluorescent in situ hybridization test and ALK/p80 immunohistochemistry. The patient responded to crizotinib therapy during 213 days. Our observation points out the interest of considering ALK screening in patients with metastatic lung squamous cell carcinomas, especially in patients lacking a usual heavy-smoker clinical history. The histopathological and immunohistochemical features of this particular tumor highlighting the overlapping criteria between lung adenocarcinomas and rare ALK-rearranged squamous cell lung carcinomas could also be relevant to extend ALK screening to tumors with intermediate phenotypes between squamous cell carcinomas and

Treatment Options by Stage (Small Cell Lung Cancer)

MedlinePlus

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key ...

Revisiting the role of radiation treatment for non-serous subtypes of epithelial ovarian cancer.

PubMed

Thomas, G

2013-01-01

Except for its palliative use, radiation has been largely abandoned in the management of ovarian cancers because of the recognized efficacy of chemotherapy agents. Whole abdominal irradiation (WAR), however, has been shown to be of adjuvant and curative value in ovarian cancer with microscopic or minimal residual disease in the pelvis, the so-called "intermediate risk group." Recent hypothesis generating data from the use of adjuvant radiation following adjuvant chemotherapy in ovarian cancer has shown an incremental survival benefit for the rarer non-serous ovarian subtypes including clear cell, endometrioid, and mucinous. No incremental benefit was observed for the more common serous subtype. A retrospective examination of early trials using WAR as the sole postoperative treatment in ovarian cancer has determined that the majority of patients in these studies and cured by radiation actually had the non-serous subtypes. The recognition that the non-serous subtypes differ from the serous cancers in their stage of presentation, their molecular characteristics, their response to classic chemotherapy, and their outcomes suggest the non-serous subtypes should be treated as rare and different cancers. In addition to specific targeting therapies that may be developed, radiation should be reconsidered as part of the treatment armamentarium for these diseases.

Current questions in HIV-associated lung cancer.

PubMed

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease

PubMed Central

Karmouty-Quintana, Harry; Cicko, Sanja; Ayata, Korcan; Zissel, Gernot; Goldmann, Torsten; Lungarella, Giuseppe; Ferrari, Davide; Di Virgilio, Francesco; Robaye, Bernard; Boeynaems, Jean-Marie; Blackburn, Michael R.; Idzko, Marco

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases. The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis. In addition expression of P2Y2 receptors by different cell types was determined. To investigate the functional relevance of P2Y2 receptors for the pathogenesis of the disease the bleomycin model of pulmonary fibrosis was used. Finally, experiments were performed in pursuit of the involved mechanisms. Compared to healthy individuals or vehicle treated animals, extracellular nucleotide levels in the BAL fluid were increased in patients with IPF and in mice after bleomycin administration, paralleled by a functional up-regulation of P2Y2R expression. Both bleomycin-induced inflammation and fibrosis were reduced in P2Y2R-deficient compared to wild type animals. Mechanistic studies demonstrated that recruitment of neutrophils into the lungs, proliferation and migration of lung fibroblasts as well as IL6 production are key P2Y2R mediated processes. Our results clearly demonstrate the involvement of P2Y2R subtypes in the pathogenesis of fibrotic lung diseases in humans and mice and hence support the development of selective P2Y2R antagonists for the treatment of IPF. PMID:28415591

Customizing Therapies for Lung Cancer | Center for Cancer Research

Cancer.gov

Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery, chemotherapy, and radiation therapy. Increasing attention has been paid in recent years to customizing therapies based on the molecular characteristics of patients’ tumors. Some of these targeted regimens have already been integrated into the treatment arsenal for lung cancer and others are still being studied in clinical trials, including several being conducted by researchers at NCI’s Center for Cancer Research.

Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

ClinicalTrials.gov

2016-02-18

Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells

PubMed Central

Wu, Ching-Yuan; Cherng, Jong-Yuh; Yang, Yao-Hsu; Lin, Chun-Liang; Kuan, Feng-Che; Lin, Yin-Yin; Lin, Yu-Shih; Shu, Li-Hsin; Cheng, Yu-Ching; Liu, Hung Te; Lu, Ming-Chu; Lung, Jthau; Chen, Pau-Chung; Lin, Hui Kuan; Lee, Kuan-Der; Tsai, Ying-Huang

2017-01-01

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C–C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation. PMID:29207614

Expression of pleiotrophin in small cell lung cancer.

PubMed

Wang, H Q; Wang, J

2015-01-01

Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to tumor progression. This study aimed to discuss the significance of the expression of PTN in benign and malignant lung cancer tissues, especially small cell lung cancer. Lung cancer samples were collected for study and lung tissue samples with benign lesions were taken as controls. The expression of PTN was detected using tissue chip combined with the immunohistochemical method, and the differences of small cell lung cancer with non-small cell lung cancer and benign lesion tissue were compared. It was found that PTN expression was mainly located in the cytoplasm and membrane of cells; PTN expression in the lung cancer group was higher than that in the control group (p < 0.01), and PTN expression in the small cell cancer group was higher than that in the squamous carcinoma group and glandular cancer group (p < 0.05). In addition, PTN expression quantity in patients with lung cancer were in close correlation with TNM staging, pathological type and tumor differentiation degree (p < 0.05). PTN was found to express abnormally high in lung cancer, especially small cell lung cancer tissue. PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung cancer.

Treatment and prognosis of breast cancer patients with brain metastases according to intrinsic subtype.

PubMed

Kuba, Sayaka; Ishida, Mayumi; Nakamura, Yoshiaki; Yamanouchi, Kosho; Minami, Shigeki; Taguchi, Kenichi; Eguchi, Susumu; Ohno, Shinji

2014-11-01

How breast cancer subtypes should affect treatment decisions for breast cancer patients with brain metastases is unclear. We analyzed local brain metastases treatments and their outcomes according to subtype in patients with breast cancer and brain metastases. We reviewed records and database information for women treated at the National Kyushu Cancer Center between 2001 and 2010. Patients were divided into three breast cancer subtype groups: Luminal (estrogen receptor positive and/or progesterone receptor positive, but human epidermal growth factor receptor 2 negative); human epidermal growth factor receptor 2 positive and triple negative (estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor 2 negative). Of 524 advanced breast cancer patients, we reviewed 65 (12%) with brain metastases and records showing estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status, as well as outcome data; there were 26 (40%) Luminal, 26 (40%) had human epidermal growth factor receptor 2 and 13 (20%) had triple negative subtypes. There was no statistical difference in the number of brain metastases among subtypes; however, rates of stereotactic radiosurgery or surgery for brain metastases differed significantly by subtype (human epidermal growth factor receptor 2: 81%, Luminal: 42% and triple negative: 47%; P = 0.03). Patients having the human epidermal growth factor receptor 2 subtype, a performance status of ≤1 and ≤4 brain metastases, who underwent systemic therapy after brain metastases and underwent stereotactic radiosurgery or surgery, were predicted to have longer overall survival after brain metastases. Multivariate analysis demonstrated that not having systemic therapy and not having the human epidermal growth factor receptor 2 subtype were independent factors associated with an increased risk of death (hazard ratio 2.4, 95% confidence interval 1.01-5.6; P = 0.05 and hazard ratio 2.9, 95

Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study.

PubMed

Troester, Melissa A; Sun, Xuezheng; Allott, Emma H; Geradts, Joseph; Cohen, Stephanie M; Tse, Chiu-Kit; Kirk, Erin L; Thorne, Leigh B; Mathews, Michelle; Li, Yan; Hu, Zhiyuan; Robinson, Whitney R; Hoadley, Katherine A; Olopade, Olufunmilayo I; Reeder-Hayes, Katherine E; Earp, H Shelton; Olshan, Andrew F; Carey, Lisa A; Perou, Charles M

2018-02-01

African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs > 50 years) using chi-square tests and analysis of variance tests. Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR = 1.45, 95% CI = 1.02 to 2.06, for Luminal B; OR = 2.04, 95% CI = 1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women. Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Associations of Epstein-Barr Virus DNA in PBMCs and the Subtypes with Breast Cancer Risk

PubMed Central

Zhang, Wei; Wang, Min-Yi; Wei, Xue-Ling; Lin, Ying; Su, Feng-Xi; Xie, Xiao-Ming; Tang, Lu-Ying; Ren, Ze-Fang

2017-01-01

Objective: Epstein-Barr virus (EBV) has been found to be implicated in the development of breast cancer. The purpose of the present study was to identify the associations of EBV DNA and the subtypes in peripheral blood mononuclear cells (PBMCs) with the risk of breast cancer. Material and Methods: A case-control study with 671 breast cancer cases and 859 age-matched controls was conducted in Guangzhou, China. Face-to-face interviews were performed and blood samples were collected immediately after admission to the hospital for patients or after the interview for controls. EBV DNA in PBMCs and the subtypes were detected using Polymerase Chain Reaction (PCR) and restricted fragment length polymorphisms (RFLP). IgA antibodies against EBV VCA-p18 and EBNA-1 were examined using commercial enzyme-linked immunosorbent assay kits. Unconditional logistic regression analysis was applied to evaluate the associations of the DNA positivity and subtypes of EBV with the risk of breast cancer. Results: Among the 1530 subjects, 164 cases (24.4 %) and 206 controls (24.0 %) were positive for EBV DNA in PBMCs and no significant difference occurred between cases and controls. The presence of EBV DNA was related to the positivity of EBV IgA antibodies. Of the DNA positive samples, 71 cases and 109 controls for F/f subtype and 58 cases and 112 controls for C/D subtype were successfully obtained. The D subtype was associated with an increased breast cancer risk compared with the C subtype [OR (95% CI): 2.86 (1.25~6.53)]. We did not find an association of the F/f polymorphism with breast cancer risk. Conclusions: The present study suggested that the presence of EBV DNA in PBMCs may not be an appropriate biomarker for breast cancer risk. The subtype D of EBV was likely to be related to breast tumorigenesis. PMID:28928885

Overview of Genetically Engineered Mouse Models of Distinct Breast Cancer Subtypes.

PubMed

Usary, Jerry; Darr, David Brian; Pfefferle, Adam D; Perou, Charles M

2016-03-18

Advances in the screening of new therapeutic options have significantly reduced the breast cancer death rate over the last decade. Despite these advances, breast cancer remains the second leading cause of cancer death among women. This is due in part to the complexity of the disease, which is characterized by multiple subtypes that are driven by different genetic mechanisms and that likely arise from different cell types of origin. Because these differences often drive treatment options and outcomes, it is important to select relevant preclinical model systems to study new therapeutic interventions and tumor biology. Described in this unit are the characteristics and applications of validated genetically engineered mouse models (GEMMs) of basal-like, luminal, and claudin-low human subtypes of breast cancer. These different subtypes have different clinical outcomes and require different treatment strategies. These GEMMs can be considered faithful surrogates of their human disease counterparts. They represent alternative preclinical tumor models to cell line and patient-derived xenografts for preclinical drug discovery and tumor biology studies. Copyright © 2016 John Wiley & Sons, Inc.

TG4010 and Nivolumab in Patients With Lung Cancer

ClinicalTrials.gov

2018-03-01

Recurrent Non-Small Cell Lung Carcinoma; Stage I Non-Small Cell Lung Cancer; Stage II Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium

PubMed Central

Zhang, Li Rita; Morgenstern, Hal; Greenland, Sander; Chang, Shen-Chih; Lazarus, Philip; Teare, M. Dawn; Woll, Penella J.; Orlow, Irene; Cox, Brian; Brhane, Yonathan; Liu, Geoffrey; Hung, Rayjean J.

2014-01-01

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study-specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack-years; odds-ratio estimates were pooled using random effects models. Subgroup analyses were done for sex, histology and tobacco smoking status. The shapes of dose-response associations were examined using restricted cubic spline regression. The overall pooled OR for habitual versus nonhabitual or never users was 0.96 (95% CI: 0.66–1.38). Compared to nonhabitual or never users, the summary OR was 0.88 (95%CI: 0.63–1.24) for individuals who smoked 1 or more joint-equivalents of cannabis per day and 0.94 (95%CI: 0.67–1.32) for those consumed at least 10 joint-years. For adenocarcinoma cases the ORs were 1.73 (95%CI: 0.75–4.00) and 1.74 (95%CI: 0.85–3.55), respectively. However, no association was found for the squamous cell carcinoma based on small numbers. Weak associations between cannabis smoking and lung cancer were observed in never tobacco smokers. Spline modeling indicated a weak positive monotonic association between cumulative cannabis use and lung cancer, but precision was low at high exposure levels. Results from our pooled analyses provide little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers, although the possibility of potential adverse effect for heavy consumption cannot be excluded. PMID:24947688

Racing Against Lung Cancer: Imaging Tools Help Patient in Cancer Fight

MedlinePlus

... Against Lung Cancer Follow us Racing Against Lung Cancer Imaging tools help patient in cancer fight Photo: Courtesy of Ted Simon In early ... primary care doctor. The diagnosis? Stage 4 lung cancer—advanced cancer that had already spread to some ...

Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer.

PubMed

Jiang, Z F; Wang, M; Xu, J L

2018-02-01

Thymidine kinase 1 (TK1) is a tumor biomarker in human malignancies. The purpose of this study was to evaluate the diagnostic efficiency of this marker for lung cancer using the combined analysis of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), neuron specific enolase (NSE) and TK1. From 2013 to 2014, 147 patients with lung cancer and 228 patients with lung benign diseases who were admitted to our hospital were reviewed. Peripheral blood samples were collected for the detection of TK1, CEA, CYFRA21-1 and NSE. The diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic regression equations. The serum levels of TK1, CEA, CYFRA21-1 and NSE were significantly higher than those in patients with lung benign diseases (all P<0.05). The TK1 concentration was dependent on TNM stage (P=0.005). The ROC curve analyses showed that the diagnostic value of TK1 combined with CEA, CYFRA21-1 and NSE in lung cancer was significantly higher than that of each biomarker alone (all P<0.0001). In addition, TK1 combined with CEA, CYFRA21-1, or NSE could also improve the diagnosis of the squamous cell carcinoma, adenocarcinoma and small cell lung cancer subtypes, respectively. The combined detection of TK1 and the other three markers significantly improved the diagnosis of lung cancer. Furthermore, the detection of TK1 combined with that of CYFRA21-1, CEA or NSE increased the diagnostic value of TK1 for lung squamous cell carcinoma, adenocarcinoma and SCLC, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Saudi lung cancer management guidelines 2017.

PubMed

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

Lung Cancer Brain Metastases.

PubMed

Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

2015-01-01

Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

PubMed

Xu, C-h; Wang, W; Wei, Y; Hu, H-d; Zou, J; Yan, J; Yu, L-k; Yang, R-s; Wang, Y

2015-10-01

Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy. Copyright © 2015. Published by Elsevier Ltd.

Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

PubMed

Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

2017-10-01

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Occupational exposure to endotoxins and lung cancer risk: results of the ICARE Study.

PubMed

Ben Khedher, Soumaya; Neri, Monica; Guida, Florence; Matrat, Mireille; Cenée, Sylvie; Sanchez, Marie; Menvielle, Gwenn; Molinié, Florence; Luce, Danièle; Stücker, Isabelle

2017-09-01

To investigate the role of occupational exposure to endotoxins in lung cancer in a French population-based case-control study (ICARE (Investigation of occupational and environmental causes of respiratory cancers)). Detailed information was collected on the occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. We evaluated each subject's endotoxin exposure after cross referencing International Standard Classification of Occupations (ISCO) codes (for job tasks) and Nomenclature d'Activités Françaises (NAF) codes (for activity sectors). Endotoxin exposure levels were attributed to each work environment based on literature reports. ORs and 95% CIs were estimated using unconditional logistic regression models and controlled for main confounding factors. An inverse association between exposure to endotoxins and lung cancer was found (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and cumulative exposure, and the risk was decreased decades after exposure cessation (all statistically significant). Lung cancer risk was particularly reduced among workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in those weakly exposed (eg, in waste treatment). Statistically significant interactions were shown with smoking, and never/light smokers were more sensitive to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest cumulative exposure, compared with those never exposed). Pronounced inverse associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI 0.25 to 0.55 in the highly exposed). Our findings suggest that exposure to endotoxins, even at a low level, reduces the risk of lung cancer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is

Lung Cancer Precision Medicine Trials

Cancer.gov

Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

Saudi lung cancer management guidelines 2017

PubMed Central

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

BACKGROUND: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. METHODS: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. RESULTS: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. CONCLUSION: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country. PMID:29118855

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype.

PubMed

Bae, Soo Youn; Jung, Seung Pil; Jung, Eun Sung; Park, Sung Min; Lee, Se Kyung; Yu, Jong Han; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

2018-06-18

Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2-12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1-11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2-87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC. © 2018 S. Karger AG, Basel.

Role of natural killer cells in lung cancer.

PubMed

Aktaş, Ozge Nur; Öztürk, Ayşe Bilge; Erman, Baran; Erus, Suat; Tanju, Serhan; Dilege, Şükrü

2018-06-01

One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. The relevant literature from PubMed and Medline databases is reviewed in this article. The cytolytic potential of NK cells are reduced in lung cancer and increasing evidence suggests that improving NK cell functioning may induce tumor regression. Recent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival. The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.

Molecular understanding of lung cancers-A review

PubMed Central

Singh, Chinnappan Ravinder; Kathiresan, Kandasamy

2014-01-01

Lung cancer is considered to be the most common cancer in the world. The purpose of this paper is to review scientific evidence, particularly epidemiologic evidence of overall lung cancer burden in the world. And molecular understanding of lung cancer at various levels by dominant and suppressor oncogenes. PMID:25183110

Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

PubMed

Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

2013-07-01

Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

The evolution of lung cancer screening.

PubMed

Wilkinson, Neal W; Loewen, Gregory M; Klippenstein, Donald L; Litwin, Alan M; Anderson, Timothy M

2003-12-01

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes.

PubMed

Ebben, Johnathan D; You, Ming

2016-09-01

Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances. Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

PubMed

Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

2018-01-01

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

Lung Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

Incidence of lung cancer histologic cell-types according to neighborhood factors: A population based study in California

PubMed Central

McKinley, Meg; Gali, Kathleen; Patel, Manali; Clarke, Christina; Wakelee, Heather; Haile, Robert; Gomez, Scarlett Lin; Cheng, Iona

2018-01-01

Background The relationships between neighborhood factors (i.e., neighborhood socioeconomic status (nSES) and ethnic enclave) and histologic subtypes of lung cancer for racial/ethnic groups, particularly Hispanics and Asian American/Pacific Islanders (AAPIs), are poorly understood. Methods We conducted a population-based study of 75,631 Californians diagnosed with lung cancer from 2008 through2012. We report incidence rate ratios (IRRs) for lung cancer histologic cell-types by nSES among racial/ethnic groups (non-Hispanic (NH) Whites, NH Blacks, Hispanics and AAPIs) and according to Hispanic or Asian neighborhood ethnic enclave status among Hispanics and AAPIs, respectively. In addition, we examined incidence jointly by nSES and ethnic enclave. Results Patterns of lung cancer incidence by nSES and ethnic enclave differed across race/ethnicity, sex, and histologic cell-type. For adenocarcinoma, Hispanic males and females, residing in both low nSES and high nSES neighborhoods that were low enclave, had higher incidence rates compared to those residing in low nSES, high enclave neighborhoods; males (IRR, 1.17 [95% CI, 1.04–1.32] and IRR, 1.15 [95% CI, 1.02–1.29], respectively) and females (IRR, 1.29 [95% CI, 1.15–1.44] and IRR, 1.51 [95% CI, 1.36–1.67], respectively). However, AAPI males residing in both low and high SES neighborhoods that were also low enclave had lower adenocarcinoma incidence. Conclusions Neighborhood factors differentially influence the incidence of lung cancer histologic cell-types with heterogeneity in these associations by race/ethnicity and sex. For Hispanic males and females and AAPI males, neighborhood ethnic enclave status is strongly associated with lung adenocarcinoma incidence. PMID:29791458

An analysis of the relationship between metastases and cachexia in lung cancer patients.

PubMed

Shiono, Masatoshi; Huang, Kan; Downey, Robert J; Consul, Nikita; Villanueva, Nicolas; Beck, Kristen; Fenn, Kathleen; Dietz, Donald; Yamaguchi, Takuhiro; Kato, Shunsuke; Divgi, Chaitanya; Kalinsky, Kevin; Wei, Ying; Zhang, Yuan; Borczuk, Alain C; Inoue, Akira; Halmos, Balazs; Acharyya, Swarnali

2016-09-01

Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild-type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Lung Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Learn more about tests to detect lung cancer and their potential benefits and harms in this expert-reviewed summary.

Revealing cancer subtypes with higher-order correlations applied to imaging and omics data.

PubMed

Graim, Kiley; Liu, Tiffany Ting; Achrol, Achal S; Paull, Evan O; Newton, Yulia; Chang, Steven D; Harsh, Griffith R; Cordero, Sergio P; Rubin, Daniel L; Stuart, Joshua M

2017-03-31

Patient stratification to identify subtypes with different disease manifestations, severity, and expected survival time is a critical task in cancer diagnosis and treatment. While stratification approaches using various biomarkers (including high-throughput gene expression measurements) for patient-to-patient comparisons have been successful in elucidating previously unseen subtypes, there remains an untapped potential of incorporating various genotypic and phenotypic data to discover novel or improved groupings. Here, we present HOCUS, a unified analytical framework for patient stratification that uses a community detection technique to extract subtypes out of sparse patient measurements. HOCUS constructs a patient-to-patient network from similarities in the data and iteratively groups and reconstructs the network into higher order clusters. We investigate the merits of using higher-order correlations to cluster samples of cancer patients in terms of their associations with survival outcomes. In an initial test of the method, the approach identifies cancer subtypes in mutation data of glioblastoma, ovarian, breast, prostate, and bladder cancers. In several cases, HOCUS provides an improvement over using the molecular features directly to compare samples. Application of HOCUS to glioblastoma images reveals a size and location classification of tumors that improves over human expert-based stratification. Subtypes based on higher order features can reveal comparable or distinct groupings. The distinct solutions can provide biologically- and treatment-relevant solutions that are just as significant as solutions based on the original data.

Parity and risk of lung cancer in women.

PubMed

Paulus, Jessica K; Asomaning, Kofi; Kraft, Peter; Johnson, Bruce E; Lin, Xihong; Christiani, David C

2010-03-01

Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women.

Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.

PubMed

O'Brien, Katie M; Cole, Stephen R; Tse, Chiu-Kit; Perou, Charles M; Carey, Lisa A; Foulkes, William D; Dressler, Lynn G; Geradts, Joseph; Millikan, Robert C

2010-12-15

Previous research identified differences in breast cancer-specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2(+)/ER(-)). We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Cancer subtypes luminal A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer-specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0). Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. ©2010 AACR.

Contralateral pulmonary metastases in lung cancer

PubMed Central

Onuigbo, Wilson I. B.

1974-01-01

Onuigbo, W. I. B. (1974).Thorax, 29, 132-133. Contralateral pulmonary metastases in lung cancer. It has long been known that lung cancer may attack many organs and yet spare the opposite lung. In 100 cases of this tumour studied at necropsy, only 22 showed contralateral pulmonary spread. Contralateral deposits are generally small and may be related to damaged tissues. Although tissue unsuitability is supposed to underlie the limitation of metastases in recipient organs, this does not apply to the contralateral lung. Since lung tissue is readily accessible to bloodborne cancer cells, research should be directed towards explaining the paradoxical paucity of the metastases. PMID:4825544

[Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

PubMed

Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

2008-08-01

To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

Extraintestinal roles of bombesin-like peptides and their receptors: lung.

PubMed

Qin, Xiao-Qun; Qu, Xiangping

2013-02-01

Description of the recent findings of the biological roles of bombesin-like peptides and their receptors in lungs. Gastrin-releasing peptide (GRP) was involved in the airway inflammation in murine models of airway hyperreactivity. The circulating proGRP could serve as a valuable tumor marker for small-cell lung cancers, and the plasma level of proGRP is more stable compared with that of serum proGRP. Recent studies also shed light on the intracellular signaling pathways of bombesin receptor subtype-3 (BRS-3) activation in cultured human lung cancer cells. The relevant biology of BLPs and their receptors in lung cancers and other lung diseases still remains largely unknown. With the development of several highly specific BRS-3 agonists, recent studies provided some insights into the biological effects of BRS-3 in lungs.

Peptide hormones and lung cancer.

PubMed

Moody, T W

2006-03-01

Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer

PubMed Central

Weiskopf, Kipp; Jahchan, Nadine S.; Schnorr, Peter J.; Ring, Aaron M.; Maute, Roy L.; Volkmer, Anne K.; Volkmer, Jens-Peter; Liu, Jie; Lim, Jing Shan; Yang, Dian; Seitz, Garrett; Nguyen, Thuyen; Wu, Di; Guerston, Heather; Trapani, Francesca; George, Julie; Poirier, John T.; Gardner, Eric E.; Miles, Linde A.; de Stanchina, Elisa; Lofgren, Shane M.; Vogel, Hannes; Winslow, Monte M.; Dive, Caroline; Thomas, Roman K.; Rudin, Charles M.; van de Rijn, Matt; Majeti, Ravindra; Garcia, K. Christopher; Weissman, Irving L.

2016-01-01

Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPα using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture. In a murine model, administration of CD47-blocking antibodies or targeted inactivation of the Cd47 gene markedly inhibited SCLC tumor growth. Furthermore, using comprehensive antibody arrays, we identified several possible therapeutic targets on the surface of SCLC cells. Antibodies to these targets, including CD56/neural cell adhesion molecule (NCAM), promoted phagocytosis in human SCLC cell lines that was enhanced when combined with CD47-blocking therapies. In light of recent clinical trials for CD47-blocking therapies in cancer treatment, these findings identify disruption of the CD47/SIRPα axis as a potential immunotherapeutic strategy for SCLC. This approach could enable personalized immunotherapeutic regimens in patients with SCLC and other cancers. PMID:27294525

[Development of the lung cancer diagnostic system].

PubMed

Lv, You-Jiang; Yu, Shou-Yi

2009-07-01

To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

Lung and Upper Aerodigestive Cancer | Division of Cancer Prevention

Cancer.gov

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Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer.

PubMed

Domagala, Pawel; Wokolorczyk, Dominika; Cybulski, Cezary; Huzarski, Tomasz; Lubinski, Jan; Domagala, Wenancjusz

2012-04-01

Germline mutations in BRCA1 were already linked to basal-like subtype of immunophenotypic molecular classification of breast cancer (BC). However, it is not known whether mutations in other BC susceptibility genes are associated with molecular subtypes of this cancer. We tested the hypothesis that distinct mutations in another BC susceptibility gene involved in DNA repair, i.e., CHEK2 may be associated with particular immunophenotypic molecular subtypes of this cancer. Two groups of patients: 1255 with BCs and 5496 healthy controls were genotyped for four CHEK2 mutations (I157T and three truncating mutations: 1100delC, IVS2 + 1G > A, del5395). BCs were tested by immunohistochemistry on tissue microarrays for ER, PR, HER-2, EGFR, and CK5/6 and were assigned to appropriate subtypes of immunophenotypic molecular classification. There was a significant association between CHEK2 mutations and the immunophenotypic molecular classification (P = 0.004). CHEK2-associated cancers were predominantly luminal (108/117 = 92.3%). CHEK2-I157T variant was associated with the luminal A subtype (P = 0.01), whereas CHEK2-truncating mutations were associated with the luminal B subtype (P = 0.005). Comparing the prevalence of CHEK2 mutations in BC with controls revealed that carriers of an I157T variant had OR of 1.80 for luminal A subtype and carriers of truncating mutations had OR of 6.26 for luminal B subtype of BC. To our knowledge, this is the first study showing that specific mutations in the same susceptibility gene are associated with different immunophenotypic molecular subtypes of BC. This association represents independent evidence supporting the biological significance of immunophenotypic molecular classification of BC.

Methylation Markers for Early Detection and Differentiation of Follicular Thyroid Cancer Subtypes

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Merritt, Jason; Chitale, Dhananjay; Divine, George; Worsham, Maria J.

2016-01-01

Thyroid cancer has the fastest rising incidence rates and is the fifth most common cancer in women. There are four main types of which the papillary and follicular types together account for >90%, followed by medullary cancers (3%−5%) and anaplastic carcinomas (<3%). For individuals who present with early stage disease of papillary and follicular cancers, there are no accurate markers to predict whether they will develop metastatic or recurrent disease. Our immediate goal is to molecularly differentiate follicular cancer subtypes for enhanced classification. Promoter methylation status of genes with reported associations in thyroid cancer (CASP8, CDKN2A, DAPK1, ESR1, NIS, RASSF1 and TIMP3) were examined in a cohort of follicular thyroid cancers comprising of 26 Hurthle and 27 Classic subtypes utilizing quantitative methylation-specific PCR. RASSF1 was differentially methylated in Classic tumor tissue compared to Hurthle (p<0.001). Methylation of RASSF1 pointed to racial group differences between African Americans and Caucasian Americans (p=0.05). Extra thyroidal extension was found to be associated with DAPK1 (p=0.014) and ESR1 (p=0.036) methylation. Late stage disease was associated with older age (p<0.001) and methylation of DAPK1 (p=0.034) and ESR1 (p=0.035). The methylation status of RASSF1, DAPK1 and ESR1 suggests the utility of methylation markers to molecularly differentiate thyroid cancer subtypes for enhanced classification and early detection of thyroid cancer. PMID:27158284

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

PubMed

Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma.

PubMed

Nakasone, Shoko; Mimaki, Sachiyo; Ichikawa, Tomohiro; Aokage, Keiju; Miyoshi, Tomohiro; Sugano, Masato; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Tsuboi, Masahiro; Goto, Koichi; Tsuchihara, Katsuya; Ishii, Genichiro

2018-05-01

Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs. Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled. First, we analyzed the clinicopathological features of the cases, and then, evaluated the relationship between genetic features of cancer cells (major driver mutations and the number of single nucleotide variants, SNVs) and the presence of podoplanin-positive CAFs. The presence of podoplanin-positive CAFs was associated with smoking history, solid predominant subtype, and lymph node metastasis. We could not find any significant correlations between major genetic mutations (EGFR, KRAS, TP53, MET, ERBB2, BRAF, and PIC3CA) in cancer cells and the presence of podoplanin-positive CAFs. However, cases with podoplanin-positive CAFs had a significantly higher number of SNVs in cancer cells than the podoplanin-negative CAFs cases (median 84 vs 37, respectively; p = 0.001). This was also detected in a non-smoker subgroup (p = 0.037). Multivariate analyses revealed that the number of SNVs in cancer cells was the only statistically significant independent predictor for the presence of podoplanin-positive CAFs (p = 0.044). In lung adenocarcinoma, the presence of podoplanin-positive CAFs was associated with higher numbers of SNVs in cancer cells, suggesting a relationship between accumulations of SNVs in cancer cells and the generation of a tumor-promoting microenvironment.

High intra-tumoral stromal content defines Reactive breast cancer as a low-risk breast cancer subtype

PubMed Central

Dennison, Jennifer B.; Shahmoradgoli, Maria; Liu, Wenbin; Ju, Zhenlin; Meric-Bernstam, Funda; Perou, Charles M.; Sahin, Aysegul A.; Welm, Alana; Oesterreich, Steffi; Sikora, Matthew J.; Brown, Robert E.; Mills, Gordon B.

2016-01-01

Purpose The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior. Experimental design Formalin-fixed paraffin embedded tissue and matched protein lysates were evaluated from two independent breast cancer patient data sets (TCGA and MD Anderson). Reverse-phase protein arrays (RPPA) were utilized to create a proteomics signature to define breast tumor subtypes. Expression patterns of cell lines and normal breast tissues were utilized to determine markers that were differentially expressed in stroma and cancer cells. Protein localization and stromal contents were evaluated for matched cases by imaging. Results A subtype of breast cancers designated “Reactive,” previously identified by RPPA that was not predicted by mRNA profiling, was extensively characterized. These tumors were primarily estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER)2-negative, low-risk cancers as determined by enrichment of low-grade nuclei, lobular or tubular histopathology, and the luminal A subtype by PAM50. Reactive breast cancers contained high numbers of stromal cells and the highest extracellular matrix content typically without infiltration of immune cells. For ER-positive/HER2-negative cancers, the Reactive classification predicted favorable clinical outcomes in the TCGA cohort (HR = 0.36, P < 0.05). Conclusions A protein stromal signature in breast cancers is associated with a highly differentiated phenotype. The stromal compartment content and proteins are an extended phenotype not predicted by mRNA expression that could be utilized to sub-classify ER-positive/HER2-negative breast cancers. PMID:27172895

Proteomic biomarkers in lung cancer.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

2013-09-01

The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

Radiation-induced heart disease in lung cancer radiotherapy

PubMed Central

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-01-01

Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

Occupational lung cancer in US women, 1984-1998.

PubMed

Robinson, Cynthia F; Sullivan, Patricia A; Li, Jia; Walker, James T

2011-02-01

Lung cancer is the leading cause of cancer death in US women, accounting for 72,130 deaths in 2006. In addition to smoking cessation, further reduction of the burden of lung cancer mortality can be made by preventing exposure to occupational lung carcinogens. Data for occupational exposures and health outcomes of US working women are limited. Population-based mortality data for 4,570,711 women who died between 1984 and 1998 in 27 US States were used to evaluate lung cancer proportionate mortality over time by the usual occupation and industry reported on death certificates. Lung cancer proportionate mortality ratios were adjusted for smoking, using data from the National Health Interview Survey (NHIS) and the American Cancer Society's Cancer Prevention Study II. Analyses revealed that 194,382 white, 18,225 Black and 1,515 Hispanic women died 1984-1998 with lung cancer reported as the underlying cause of death. Following adjustment for smoking, significant excess proportionate lung cancer mortality was observed among US women working in the US manufacturing; transportation; retail trade; agriculture, forestry, and fishing; and nursing/personal care industries. Women employed in precision production, technical, managerial, professional specialty, and administrative occupations experienced some of the highest significantly excess proportionate lung cancer mortality during 1984-1998. The results of our study point to significantly elevated risks for lung cancer after adjustment for smoking among women in several occupations and industries. Because 6-17% of lung cancer in US males is attributable to known exposures to occupational carcinogens, and since synergistic interactions between cigarette smoke and other occupational lung carcinogens have been noted, it is important to continue research into the effects of occupational exposures on working men and women. Copyright © 2010 Wiley-Liss, Inc.

Concerns About Lung Cancer Among Prisoners.

PubMed

Renault, Luc; Perrot, Emmanuel; Pradat, Eric; Bartoli, Christophe; Greillier, Laurent; Remacle-Bonnet, Anne; Telmon, Norbert; Mazières, Julien; Molinier, Laurent; Couraud, Sébastien

2018-02-01

Few studies have looked at lung cancer in prisoners, despite this population is possibly at increased risk of malignancy. In a previous study, we found an early onset of lung cancer in prisoners. Thus, the present CARCAN study was aimed at assessing the epidemiological characteristics, management, prognosis, and incidence of lung cancer in prisoners compared to a sample of non-prisoner patients. We performed a multi-center observational case-control study. Cases were prisoners diagnosed with lung cancer from 2005 to 2013. Controls were non-prisoner lung cancer patients selected from hospital databases and randomly matched to cases (targeted case-control ratio: 1:3). Incidence rates in both groups were calculated using national statistics. Seventy-two cases and 170 controls met inclusion criteria. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (± 11.0) in cases and 64.3 (± 10.1) in controls (p < 0.0001). More case patients were current smokers compared to control patients (83% vs 53%; p < 0.0001). We found no significant differences between the two groups as concerns histologic types, TNM stages at diagnosis, initially-employed treatments, times to management or survival. Incidence rates (2008-2012) in male prisoners were higher than those in the general population in all concerned age groups. There is a shift of lung cancer toward young people in prisons. However, the presentation, management, and prognosis of lung cancer are similar between prisoners and non-prisoners. These finding could justify a specific screening policy for the incarcerated populations.

Drug delivery and nanodetection in lung cancer.

PubMed

Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad; Badrzadeh, Kazem; Valizadeh, Alireza; Zarghami, Nosratollah; Farkhani, Samad Mussa; Akbarzadeh, Abolfazl

2016-01-01

Lung carcinoma is the most widespread type of cancer worldwide, and is responsible for more deaths than other types of cancer. Lung cancer remains the chief cause of cancer-related deaths in both men and women worldwide, and is increasingly common in women. Each year, the number of deaths from lung cancer is greater than the number due to breast and colorectal cancer combined. Lung cancer accounted for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. In Iran, lung cancer is one of the five leading tumors. Among females, it was the fourth most commonly diagnosed cancer, and the second leading cause of cancer death. Nanotechnology can be defined as the science and engineering involved in the design, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale, i.e. one billionth of a meter. It is an exciting multidisciplinary field that involves the design and engineering of nano objects or nanotools with diameters less than 500 nanometers (nm), and it is one of the most interesting fields of the 21st century. Nanotechnology also offers the ability to detect diseases, such as tumors, much earlier than ever imaginable. This article presents nano devices for lung cancer detection and drug delivery systems.

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.

PubMed

Olsen, Catherine M; Nagle, Christina M; Whiteman, David C; Ness, Roberta; Pearce, Celeste Leigh; Pike, Malcolm C; Rossing, Mary Anne; Terry, Kathryn L; Wu, Anna H; Risch, Harvey A; Yu, Herbert; Doherty, Jennifer A; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Goodman, Marc T; Carney, Michael E; Matsuno, Rayna K; Lurie, Galina; Moysich, Kirsten; Kjaer, Susanne K; Jensen, Allan; Hogdall, Estrid; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Larson, Melissa C; Schildkraut, Joellen; Hoyo, Cathrine; Moorman, Patricia; Weber, Rachel P; Cramer, Daniel W; Vitonis, Allison F; Bandera, Elisa V; Olson, Sara H; Rodriguez-Rodriguez, Lorna; King, Melony; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Lissowska, Jolanta; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Webb, Penelope M

2013-04-01

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m(2); 95% CI 1.18-1.30), invasive endometrioid (1.17; 1.11-1.23) and invasive mucinous (1.19; 1.06-1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94-1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03-1.25) and in pre-menopausal women (1.11; 1.04-1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State.

PubMed

Kohler, Betsy A; Sherman, Recinda L; Howlader, Nadia; Jemal, Ahmedin; Ryerson, A Blythe; Henry, Kevin A; Boscoe, Francis P; Cronin, Kathleen A; Lake, Andrew; Noone, Anne-Michelle; Henley, S Jane; Eheman, Christie R; Anderson, Robert N; Penberthy, Lynne

2015-06-01

The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data. Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011 [corrected]. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100000 non-Hispanic white women, respectively). HR+/HER2- breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P < .001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100000 non-Hispanic black women), which is reflected in high rates in southeastern states. Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection

[Survey and analysis of awareness of lung cancer prevention and control in a LDCT lung cancer screening project in Tianjin Dagang Oilfield of China].

PubMed

Ren, Guanhua; Ye, Jianfei; Fan, Yaguang; Wang, Jing; Sun, Zhijuan; Jia, Hui; Du, Xinxin; Hou, Chaohua; Wang, Ying; Zhao, Yongcheng; Zhou, Qinghua

2014-02-01

It has been proven that increase of the awareness level of lung cancer prevention and control could enhance participation of lung cancer screening of lung cancer high risk group. The aim of this study is to investigate the awareness level of lung cancer prevention and control and the effect of individual characteristics on lung cancer awareness, and to provide evidence for comprehensive lung cancer prevention in high risk areas of lung cancer. Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer screening by cluster sampling or according to voluntary principle were surveyed, data of lung cancer awareness were collected by questionnaire. A total of 1,633 valid questionnaires were collected. The average age of respondents was 60.08±6.58. Most participants were males (82.2%) while female only accounted for 17.8%. The proportions of awareness about lung cancer in China, risk factors, screening methods and the knowledge of health examination were 64.5%, 77.1%, 43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed that education level, smoking (pack-year), age, prior tuberculosis were the influencing factors of lung cancer awareness with adjusted Ors for education and age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739) respectively. 80.3% of the participants can accept health examination once a year, while the ability to pay the medical expenses was not high. The influencing factors of health examination willingness were gender, age, income, the knowledge of lung cancer. Education level and smoking affect the awareness of lung cancer prevention and control, health education for lung cancer should be conducted especially in population with low education level. Comprehensive lung cancer control in high risk areas should combined lung cancer screening, tobacco control and health education.

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PubMed

Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

2014-01-01

Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Lung cancer among women in north-east China.

PubMed Central

Wu-Williams, A. H.; Dai, X. D.; Blot, W.; Xu, Z. Y.; Sun, X. W.; Xiao, H. P.; Stone, B. J.; Yu, S. F.; Feng, Y. P.; Ershow, A. G.

1990-01-01

A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung. PMID:2257230

Cell-surface marker discovery for lung cancer

PubMed Central

Cohen, Allison S.; Khalil, Farah K.; Welsh, Eric A.; Schabath, Matthew B.; Enkemann, Steven A.; Davis, Andrea; Zhou, Jun-Min; Boulware, David C.; Kim, Jongphil; Haura, Eric B.; Morse, David L.

2017-01-01

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients. PMID:29371917

Paraneoplastic syndromes associated with lung cancer

PubMed Central

Kanaji, Nobuhiro; Watanabe, Naoki; Kita, Nobuyuki; Bandoh, Shuji; Tadokoro, Akira; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

2014-01-01

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer. PMID:25114839

HIV Infection in the Etiology of Lung Cancer

PubMed Central

Kirk, Gregory D.; Merlo, Christian A.

2011-01-01

Persons infected with HIV have an elevated risk of lung cancer, but whether the increase simply reflects a higher smoking prevalence continues to be debated. This review summarizes existing data on the association of HIV infection and lung cancer, with particular attention to study design and adjustment for cigarette smoking. Potential mechanisms by which HIV infection may lead to lung cancer are discussed. Finally, irrespective of causality and mechanisms, lung cancer represents an important and growing problem confronting HIV-infected patients and their providers. Substantial efforts are needed to promote smoking cessation and to control lung cancer among HIV-infected populations. PMID:21653536

Lung Cancer and Lung Injury: The Dual Role of Ceramide

PubMed Central

Goldkorn, Tzipora; Chung, Samuel; Filosto, Simone

2015-01-01

Sphingolipids play key roles in cancer, yet our current understanding of sphingolipid function in lung cancer is limited to a few key players. The best characterized of these are sphingosine-1-phoshate and ceramide which are described for their opposing roles in cell fate. However, because sphingolipids as a whole are readily interconverted by a complex enzymatic machinery, no single sphingolipid appears to have exactly one role. Instead, the roles of specific sphingolipids appear to be context specific as demonstrated by findings that ceramide-1-phosphate has both proliferative and apoptotic effects depending on its concentration. Therefore, we present herein several years of research on ceramide, a sphingolipid linked to apoptotic signaling, that is emerging in cancer research for its potential roles in proliferation and cell-to-cell communication via exosomes. Ceramide is a well-studied sphingolipid in both normal and pathological conditions ranging from skin development to lung cancer. Interestingly, several groups have previously reported its increased levels in emphysema patients who are smokers, a patient subpopulation greatly susceptible to lung cancer. However, the molecular mechanisms through which cigarette smoke (CS) and ceramide accumulation lead to lung cancer, non-small cell lung cancer (NSCLC) specifically, are unknown. Interestingly, recent studies clearly establish that two signaling pathways are activated during CS exposure in the lung airway. One centers on the activation of neutral sphingomyelinase2 (nSMase2), an enzyme that hydrolyzes sphingomyelin to ceramide. The other pathway focuses on the oncogenic EGF receptor (EGFR), which becomes aberrantly activated but not degraded, leading to prolonged proliferative signaling. Recent studies show that these two signaling pathways may actually converge and integrate. Specifically, Goldkorn et al. demonstrated that during CS exposure, EGFR is favorably co-localized in ceramide-enriched regions of the

An updated review of case-control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer?

PubMed

Sheen, Seungsoo; Lee, Keu Sung; Chung, Wou Young; Nam, Saeil; Kang, Dae Ryong

2016-01-01

Lung cancer is a leading cause of cancer-related death in the world. Smoking is definitely the most important risk factor for lung cancer. Radon ((222)Rn) is a natural gas produced from radium ((226)Ra) in the decay series of uranium ((238)U). Radon exposure is the second most common cause of lung cancer and the first risk factor for lung cancer in never-smokers. Case-control studies have provided epidemiological evidence of the causative relationship between indoor radon exposure and lung cancer. Twenty-four case-control study papers were found by our search strategy from the PubMed database. Among them, seven studies showed that indoor radon has a statistically significant association with lung cancer. The studies performed in radon-prone areas showed a more positive association between radon and lung cancer. Reviewed papers had inconsistent results on the dose-response relationship between indoor radon and lung cancer risk. Further refined case-control studies will be required to evaluate the relationship between radon and lung cancer. Sufficient study sample size, proper interview methods, valid and precise indoor radon measurement, wide range of indoor radon, and appropriate control of confounders such as smoking status should be considered in further case-control studies.

Molecular pathways and therapeutic targets in lung cancer

PubMed Central

Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

2014-01-01

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

Dilemmas in Lung Cancer Staging.

PubMed

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Multilevel Opportunities to Address Lung Cancer Stigma across the Cancer Control Continuum.

PubMed

Hamann, Heidi A; Ver Hoeve, Elizabeth S; Carter-Harris, Lisa; Studts, Jamie L; Ostroff, Jamie S

2018-05-22

The public health imperative to reduce the burden of lung cancer has seen unprecedented progress in recent years. Realizing fully the advances in lung cancer treatment and control requires attention to potential barriers in their momentum and implementation. In this analysis, we present and evaluate the argument that stigma is a highly significant barrier to fulfilling the clinical promise of advanced care and reduced lung cancer burden. This evaluation of lung cancer stigma is based on a multilevel perspective that incorporates the individual, persons in their immediate environment, the healthcare system, and the larger societal structure which shapes perceptions and decisions. We also consider current interventions and interventional needs within and across aspects of the lung cancer continuum, including prevention, screening, diagnosis, treatment, and survivorship. Current evidence suggests that stigma detrimentally impacts psychosocial, communication, and behavioral outcomes over the entire lung cancer control continuum and across multiple levels. Interventional efforts to alleviate stigma in the context of lung cancer show promise, yet more work is needed to evaluate their impact. Understanding and addressing the multi-level role of stigma is a crucial area for future study in order to realize the full benefits offered by lung cancer prevention, control, and treatment. Coordinated, interdisciplinary, and well-conceptualized efforts have the potential to reduce the barrier of stigma in the context of lung cancer and facilitate demonstrable improvements in clinical care and quality of life. Copyright © 2018. Published by Elsevier Inc.

Ion Channel Gene Expression in Lung Adenocarcinoma: Potential Role in Prognosis and Diagnosis

PubMed Central

Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A.; Zhou, Tong

2014-01-01

Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts. PMID:24466154

Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA Biomarkers in Tumor and Urine.

PubMed

Koo, Kevin M; Wee, Eugene J H; Mainwaring, Paul N; Wang, Yuling; Trau, Matt

2016-12-01

Cancer is a heterogeneous disease which manifests as different molecular subtypes due to the complex nature of tumor initiation, progression, and metastasis. The concept of precision medicine aims to exploit this cancer heterogeneity by incorporating diagnostic technology to characterize each cancer patient's molecular subtype for tailored treatments. To characterize cancer molecular subtypes accurately, a suite of multiplexed bioassays have currently been developed to detect multiple oncogenic biomarkers. Despite the reliability of current multiplexed detection techniques, novel strategies are still needed to resolve limitations such as long assay time, complex protocols, and difficulty in interpreting broad overlapping spectral peaks of conventional fluorescence readouts. Herein a rapid (80 min) multiplexed platform strategy for subtyping prostate cancer tumor and urine samples based on their RNA biomarker profiles is presented. This is achieved by combining rapid multiplexed isothermal reverse transcription-recombinase polymerase amplification (RT-RPA) of target RNA biomarkers with surface-enhanced Raman spectroscopy (SERS) nanotags for "one-pot" readout. This is the first translational application of a RT-RPA/SERS-based platform for multiplexed cancer biomarker detection to address a clinical need. With excellent sensitivity of 200 zmol (100 copies) and specificity, we believed that this platform methodology could be a useful tool for rapid multiplexed subtyping of cancers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exhaled breath analysis for lung cancer

PubMed Central

Sutedja, Tom G.; Zimmerman, Paul V.

2013-01-01

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

PubMed Central

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-01-01

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

Radon exposure and cancers other than lung cancer in Swedish iron miners.

PubMed Central

Darby, S C; Radford, E P; Whitley, E

1995-01-01

Data are presented on the risks of cancers other than lung cancer in a cohort of iron miners from northern Sweden occupationally exposed to elevated levels of the radioactive gas radon. Compared with rates for the four northernmost counties of Sweden, mortality was increased for all cancers other than lung cancer (ratio of observed to expected deaths 1.21, 95% confidence interval 1.03-1.41), stomach cancer (ratio of observed to expected deaths 1.45, 95% confidence interval 1.04-1.98), and rectal cancer (ratio of observed to expected deaths 1.94, 95% confidence interval 1.03-3.31). Despite these overall increases, mortality was not significantly associated with cumulative exposure to radon, either for all cancers other than lung cancer or for any site of cancer other than lung cancer individually. However, the data from this cohort on its own have limited power; and for several sites of cancer the data in this study would be consistent with a radon-related increase. Further study of cancers other than lung cancer in populations exposed to radon is required. PMID:7614946

Early Lung Cancer Diagnosis by Biosensors

PubMed Central

Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

2013-01-01

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

Regular aspirin use and lung cancer risk.

PubMed

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-11-26

Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41-0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day x years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Regular aspirin use and lung cancer risk

PubMed Central

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-01-01

Background Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. Methods We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Conclusions Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer. PMID:12453317

Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK.

PubMed

Rothschild, Sacha I

2015-05-26

Systemic therapy for non-small cell lung cancer (NSCLC) has undergone a dramatic paradigm shift over the past decade. Advances in our understanding of the underlying biology of NSCLC have revealed distinct molecular subtypes. A substantial proportion of NSCLC depends on oncogenic molecular aberrations (so-called "driver mutations") for their malignant phenotype. Personalized therapy encompasses the strategy of matching these subtypes with effective targeted therapies. EGFR mutations and ALK translocation are the most effectively targeted oncogenes in NSCLC. EGFR mutations and ALK gene rearrangements are successfully being targeted with specific tyrosine kinase inhibitors. The number of molecular subgroups of NSCLC continues to grow. The scope of this review is to discuss recent data on novel molecular targets as ROS1, BRAF, KRAS, HER2, c-MET, RET, PIK3CA, FGFR1 and DDR2. Thereby the review will focus on therapeutic strategies targeting these aberrations. Moreover, the emerging challenge of acquired resistance to initially effective therapies will be discussed.

The liquid biopsy in lung cancer.

PubMed

Ansari, Junaid; Yun, Jungmi W; Kompelli, Anvesh R; Moufarrej, Youmna E; Alexander, Jonathan S; Herrera, Guillermo A; Shackelford, Rodney E

2016-11-01

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.

Lung cancer disparities and African-Americans.

PubMed

Sin, Mo-Kyung

2017-07-01

African-Americans, as historically disadvantaged minorities, have more advanced stages of cancer when diagnosed, lower survival rates, and lower rates of accessing timely care than do Caucasians. Lung cancer incidence and mortality, in particular, are high among African-Americans. The U.S. Preventive Services Task Force recently released an evidence-based lung cancer screening technology called low-dose computerized tomography. High-risk African-Americans might benefit greatly from such screening but not many are aware of this technology. Public health nurses can play a key role in increasing awareness of the technology among African-American communities and encouraging qualified African-Americans to obtain screening. This study discusses issues with lung cancer and smoking among African-Americans, a recently released evidence-based lung cancer screening technology, and implications for public health nurses to enhance uptake of the new screening technology among high-risk African-Americans. © 2017 Wiley Periodicals, Inc.

Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients.

PubMed

Rozman, Ales; Silar, Mira; Kosnik, Mitja

2012-12-01

BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.

Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients

PubMed Central

Rozman, Ales; Silar, Mira; Kosnik, Mitja

2012-01-01

Background. Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. Patients and methods. Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. Results. We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. Conclusion. Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF. PMID:23412843

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study

PubMed Central

Carreras-Torres, Robert; Johansson, Mattias; Haycock, Philip C.; Wade, Kaitlin H.; Relton, Caroline L.; Martin, Richard M.; Davey Smith, George; Albanes, Demetrius; Aldrich, Melinda C.; Andrew, Angeline; Bickeböller, Heike; Bojesen, Stig E.; Brunnström, Hans; Manjer, Jonas; Brüske, Irene; Caporaso, Neil E.; Chen, Chu; Christiani, David C.; Christian, W. Jay; Doherty, Jennifer A.; Duell, Eric J.; Goodman, Gary E.; Grankvist, Kjell; Haugen, Aage; Hong, Yun-Chul; Johansson, Mikael B.; Lam, Stephen; Landi, Maria Teresa; Lazarus, Philip; Le Marchand, Loïc; Liu, Geoffrey; Melander, Olle; Rennert, Gad; Risch, Angela; Haura, Eric B.; Scelo, Ghislaine; Zaridze, David; Mukeriya, Anush; Savić, Milan; Lissowska, Jolanta; Swiatkowska, Beata; Janout, Vladimir; Holcatova, Ivana; Mates, Dana; Shen, Hongbing; Tardon, Adonina; Woll, Penella; Tsao, Ming-Sound; Wu, Xifeng; Yuan, Jian-Min; Hung, Rayjean J.; Amos, Christopher I.; Brennan, Paul

2017-01-01

Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01–1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15–2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79–1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84–0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25–2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously

Treatment Options by Stage (Non-Small Cell Lung Cancer)

MedlinePlus

... Cancer Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key ...

TCGA divides gastric cancer into four molecular subtypes: implications for individualized therapeutics.

PubMed

Zhang, Wei

2014-10-01

Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is challenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especially the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY Study.

PubMed

Vlaanderen, Jelle; Portengen, Lützen; Schüz, Joachim; Olsson, Ann; Pesch, Beate; Kendzia, Benjamin; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Forastiere, Francesco; Bueno-de-Mesquita, Bas; Peters, Susan; Brüning, Thomas; Kromhout, Hans; Straif, Kurt; Vermeulen, Roel

2014-02-01

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.

Effect Modification of the Association of Cumulative Exposure and Cancer Risk by Intensity of Exposure and Time Since Exposure Cessation: A Flexible Method Applied to Cigarette Smoking and Lung Cancer in the SYNERGY Study

PubMed Central

Vlaanderen, Jelle; Portengen, Lützen; Schüz, Joachim; Olsson, Ann; Pesch, Beate; Kendzia, Benjamin; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Field, John K.; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Forastiere, Francesco; Bueno-de-Mesquita, Bas; Peters, Susan; Brüning, Thomas; Kromhout, Hans; Straif, Kurt; Vermeulen, Roel

2014-01-01

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985–2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20–30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive. PMID:24355332

Missed lung cancer: when, where, and why?