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Sample records for sensitizes lung cancer

  1. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

  2. Kinase Impaired BRAF Mutations Confer Lung Cancer Sensitivity to Dasatinib

    PubMed Central

    Sen, Banibrata; Peng, Shaohua; Tang, Ximing; Erickson, Heidi S.; Galindo, Hector; Mazumdar, Tuhina; Stewart, David J.; Wistuba, Ignacio; Johnson, Faye M.

    2013-01-01

    During a clinical trial of the tyrosine kinase inhibitor dasatinib for advanced non–small cell lung cancer (NSCLC) one patient responded dramatically and remains cancer-free 4 years later. A comprehensive analysis of his tumor revealed a previously undescribed, kinase inactivating BRAF mutation (Y472CBRAF); no inactivating BRAF mutations were found in the non-responding tumors taken from other patients. Cells transfected with Y472CBRAF exhibited CRAF, MEK, and ERK activation – characteristics identical to signaling changes that occur with previously known kinase inactivating BRAF mutants. Dasatinib selectively induced senescence in NSCLC cells with inactivating BRAF mutations. Transfection of other NSCLC cells with these BRAF mutations also increased these cells’ dasatinib sensitivity, whereas transfection with an activating BRAF mutation led to their increased dasatinib resistance. The sensitivity induced by Y472CBRAF was reversed by the introduction of a BRAF mutation that impairs RAF dimerization. Dasatinib inhibited CRAF modestly, but concurrently induced RAF dimerization resulting in ERK activation in NSCLC cells with kinase inactivating BRAF mutations. The sensitivity of NSCLC with kinase impaired BRAF to dasatinib suggested synthetic lethality of BRAF and a dasatinib target. Inhibiting BRAF in NSCLC cells expressing wild-type BRAF likewise enhanced these cells’ dasatinib sensitivity. Thus, the patient’s BRAF mutation was likely responsible for his tumor’s marked response to dasatinib, suggesting that tumors bearing kinase impaired BRAF mutations may be exquisitely sensitive to dasatinib. Moreover, the potential synthetic lethality of combination therapy including dasatinib and BRAF inhibitors may lead to additional therapeutic options against cancers with wild-type BRAF. PMID:22649091

  3. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  4. Lung Cancer

    MedlinePlus

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

  5. Lung cancer

    PubMed Central

    Dong, Jie; Kislinger, Thomas; Jurisica, Igor; Wigle, Dennis A.

    2010-01-01

    High-throughput genomic data for both lung development and lung cancer continue to accumulate. Significant molecular intersection between these two processes has been hypothesized due to overlap in phenotypes and genomic variation. Examining the network biology of both cancer and development of the lung may shed functional light on the individual signaling modules involved. Stem cell biology may explain a portion of this network intersection and consequently studying lung organogenesis may have relevance for understanding lung cancer. This review summarizes our understanding of the potential overlapping mechanisms involved in lung development and lung tumorigenesis. PMID:19202349

  6. 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 ...

  7. What Is Lung Cancer?

    MedlinePlus

    ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ... lung cancer. For more information, visit the National Cancer Institute’s Lung Cancer. Previous Basic Information Basic Information Basic Information ...

  8. Regression of Lung Cancer by Hypoxia Sensitizing Ruthenium Polypyridyl Complexes

    PubMed Central

    Yadav, Abhishek; Janaratne, Thamara; Krishnan, Arthi; Singhal, Sharad S.; Yadav, Sushma; Dayoub, Adam S.; Hawkins, Doyle L.; Awasthi, Sanjay; MacDonnell, Frederick M.

    2013-01-01

    The ruthenium (II) polypyridyl complexes (RPCs) Δ-[(phen)2Ru(tatpp)]Cl2 (Δ-[3]Cl2) and ΔΔ-[(phen)2Ru(tatpp)Ru(phen)2]Cl4 (ΔΔ-[4]Cl4) are a new generation of metal-based anti-tumor agents. These RPCs bind DNA via intercalation of the tatpp ligand which itself is redox-active and easily reduced at biologically relevant potentials. We have previously shown that RPC 44+ cleaves DNA when reduced by glutathione to a radical species, and that this DNA cleavage is potentiated under hypoxic conditions in vitro. Here we show that 32+ also exhibits free-radical mediated DNA cleavage in vitro, and that 32+ and 44+ both exhibit selective cytotoxicity towards cultured malignant cell lines, and marked inhibition of tumor growth in vivo. The murine acute toxicity of RPCs 32+ and 44+ (maximum tolerable doses (MTD’s) ~ 65 µmol/kg) is comparable with that for cisplatin (LD50 ~57 µmol/kg) but unlike cisplatin, RPC’s are generally cleared from the body unchanged via renal excretion without appreciable metabolism or nephrotoxic side effects. RPCs 32+ and 44+ are demonstrated to suppress growth of human non-small cell lung carcinoma (~83%), show potentiated cytotoxicity in vitro under hypoxic conditions, and induce apoptosis through both intrinsic and extrinsic pathways. The novel hypoxia-enhanced DNA cleavage activity and biological activity suggest a promising new anti-cancer pharmacophore based on metal complexes with aromatic ligands that are easily reduced at biologically accessible potentials. PMID:23443803

  9. Smad4 loss promotes lung cancer formation but increases sensitivity to DNA topoisomerase inhibitors.

    PubMed

    Haeger, S M; Thompson, J J; Kalra, S; Cleaver, T G; Merrick, D; Wang, X-J; Malkoski, S P

    2016-02-01

    Non-small-cell lung cancer (NSCLC) is a common malignancy with a poor prognosis. Despite progress targeting oncogenic drivers, there are no therapies targeting tumor-suppressor loss. Smad4 is an established tumor suppressor in pancreatic and colon cancer; however, the consequences of Smad4 loss in lung cancer are largely unknown. We evaluated Smad4 expression in human NSCLC samples and examined Smad4 alterations in large NSCLC data sets and found that reduced Smad4 expression is common in human NSCLC and occurs through a variety of mechanisms, including mutation, homozygous deletion and heterozygous loss. We modeled Smad4 loss in lung cancer by deleting Smad4 in airway epithelial cells and found that Smad4 deletion both initiates and promotes lung tumor development. Interestingly, both Smad4(-/-) mouse tumors and human NSCLC samples with reduced Smad4 expression demonstrated increased DNA damage, whereas Smad4 knockdown in lung cancer cells reduced DNA repair and increased apoptosis after DNA damage. In addition, Smad4-deficient NSCLC cells demonstrated increased sensitivity to both chemotherapeutics that inhibit DNA topoisomerase and drugs that block double-strand DNA break repair by non-homologous end joining. In sum, these studies establish Smad4 as a lung tumor suppressor and suggest that the defective DNA repair phenotype of Smad4-deficient tumors can be exploited by specific therapeutic strategies. PMID:25893305

  10. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    SciTech Connect

    Yang, Heekyoung; Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710; Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 ; Yoon, Su Jin; Jin, Juyoun; Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710; Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 ; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il; and others

    2011-03-04

    Research highlights: {yields} The most important therapeutic tool in brain metastasis is radiation therapy. {yields} Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. {yields} Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. {yields} Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  11. Dendrofalconerol A sensitizes anoikis and inhibits migration in lung cancer cells.

    PubMed

    Pengpaeng, Premkamol; Sritularak, Boonchoo; Chanvorachote, Pithi

    2015-04-01

    Resistance to anoikis, enhanced cell motility, and growth in anchorage-independent conditions are hallmarks of highly metastatic cancer cells. The present study demonstrates the anoikis-sensitizing and anti-migration activities of dendrofalconerol A (DF-A), a pure bis(bibenzyl) isolated from the stem of Dendrobium falconeri (Orchidaceae), and its underlying mechanisms in human lung cancer H460 cells. DF-A at non-toxic concentrations significantly increased the anoikis response of the cancer cells, but caused no toxic effect on normal keratinocytes. In addition, DF-A significantly inhibited the growth of lung cancer cells in anchorage-independent conditions. Western blot analysis revealed that the anoikis-sensitizing effect of such a compound involves its ability to suppress survival signals as well as anti-apoptotic proteins, namely, activated protein kinase B (Akt) and Bcl-2. Furthermore, DF-A decreased caveolin-1 (Cav-1), a protein responsible for aggressiveness, while having no effect on Bax, Mcl-1, and activated Erk (p42/44) proteins. In the case of cell motility, DF-A exhibited strong anti-migration activity with the mechanism involving suppression of pFAK and Rho-GTP, but had no effect on Rac-GTP in lung cancer cells. Taken together, DF-A possesses anoikis-sensitizing activity along with anti-migration effects, and may be developed as a novel active compound for cancer treatment. PMID:25391454

  12. Atypical Protein Kinase Cι Expression and Aurothiomalate Sensitivity in Human Lung Cancer Cells

    PubMed Central

    Regala, Roderick P.; Thompson, E. Aubrey; Fields, Alan P.

    2008-01-01

    The anti-rheumatoid agent aurothiomalate (ATM) is a potent inhibitor of oncogenic PKCι ATM inhibits non-small lung cancer (NSCLC) growth by binding PKCι and blocking activation of a PKCι-Par6-Rac1-Pak-Mek 1,2-Erk 1,2 signaling pathway. Here, we assessed the growth inhibitory activity of ATM in a panel of human cell lines representing major lung cancer subtypes. ATM inhibited anchorage-independent growth in all lines tested with IC50s ranging from ~300 nM – >100 µM. ATM sensitivity correlates positively with expression of PKCι and Par6, but not with the PKCι binding protein p62, or the proposed targets of ATM in rheumatoid arthritis (RA), thioredoxin reductase 1 or 2 (TrxR1 and TrxR2). PKCι expression profiling revealed that a significant subset of primary NSCLC tumors express PKCι at or above the level associated with ATM sensitivity. ATM sensitivity is not associated with general sensitivity to the cytotoxic agents cis-platin, placitaxel and gemcitabine. ATM inhibits tumorigenicity of both sensitive and insensitive lung cell tumors in vivo at plasma drug concentrations achieved in RA patients undergoing ATM therapy. ATM inhibits Mek/Erk signaling and decreases proliferative index without effecting tumor apoptosis or vascularization in vivo. We conclude that ATM exhibits potent anti-tumor activity against major lung cancer subtypes, particularly tumor cells that express high levels of the ATM target PKCι and Par6. Our results indicate that PKCι expression profiling will be useful in identifying lung cancer patients most likely to respond to ATM therapy in an ongoing clinical trial. PMID:18632643

  13. Pharmacogenomic Approach to Identify Drug Sensitivity in Small-Cell Lung Cancer

    PubMed Central

    Wildey, Gary; Chen, Yanwen; Lent, Ian; Stetson, Lindsay; Pink, John; Barnholtz-Sloan, Jill S.; Dowlati, Afshin

    2014-01-01

    There are currently no molecular targeted approaches to treat small-cell lung cancer (SCLC) similar to those used successfully against non-small-cell lung cancer. This failure is attributable to our inability to identify clinically-relevant subtypes of this disease. Thus, a more systematic approach to drug discovery for SCLC is needed. In this regard, two comprehensive studies recently published in Nature, the Cancer Cell Line Encyclopedia and the Cancer Genome Project, provide a wealth of data regarding the drug sensitivity and genomic profiles of many different types of cancer cells. In the present study we have mined these two studies for new therapeutic agents for SCLC and identified heat shock proteins, cyclin-dependent kinases and polo-like kinases (PLK) as attractive molecular targets with little current clinical trial activity in SCLC. Remarkably, our analyses demonstrated that most SCLC cell lines clustered into a single, predominant subgroup by either gene expression or CNV analyses, leading us to take a pharmacogenomic approach to identify subgroups of drug-sensitive SCLC cells. Using PLK inhibitors as an example, we identified and validated a gene signature for drug sensitivity in SCLC cell lines. This gene signature could distinguish subpopulations among human SCLC tumors, suggesting its potential clinical utility. Finally, circos plots were constructed to yield a comprehensive view of how transcriptional, copy number and mutational elements affect PLK sensitivity in SCLC cell lines. Taken together, this study outlines an approach to predict drug sensitivity in SCLC to novel targeted therapeutics. PMID:25198282

  14. In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer

    PubMed Central

    Miyazaki, Ryohei; Anayama, Takashi; Hirohashi, Kentaro; Okada, Hironobu; Kume, Motohiko; Orihashi, Kazumasa

    2016-01-01

    Background Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI) test and collagen gel droplet embedded culture drug sensitivity test (CD-DST) are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs. Methods The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status. Results HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003). The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026) in CD-DST. Conclusions In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically. PMID:27070423

  15. Lung cancer.

    PubMed

    Akhurst, Tim; MacManus, Michael; Hicks, Rodney J

    2015-04-01

    (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) plays a key role in the evaluation of undiagnosed lung nodules, when primary lung cancer is strongly suspected, or when it has already been diagnosed by other techniques. Although technical factors may compromise characterization of small or highly mobile lesions, lesions without apparent FDG uptake can generally be safely observed, whereas FDG-avid lung nodules almost always need further evaluation. FDG-PET/CT is now the primary staging imaging modality for patients with lung cancer who are being considered for curative therapy with either surgery or definitive radiation therapy. PMID:25829084

  16. REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.

    PubMed

    Wang, Wenjie; Sheng, Wenjiong; Yu, Chenxiao; Cao, Jianping; Zhou, Jundong; Wu, Jinchang; Zhang, Huojun; Zhang, Shuyu

    2015-09-01

    Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC. PMID:26165320

  17. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy.

    PubMed

    Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il; Nam, Do-Hyun; Yoo, Hae Yong

    2011-03-01

    The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity. PMID:21291864

  18. CHMP4C Disruption Sensitizes the Human Lung Cancer Cells to Irradiation

    PubMed Central

    Li, Kang; Liu, Jianxiang; Tian, Mei; Gao, Gang; Qi, Xuesong; Pan, Yan; Ruan, Jianlei; Liu, Chunxu; Su, Xu

    2015-01-01

    Human lung cancer is highly invasive and the most malignant among human tumors. Adenocarcinoma as a specific type of non-small cell lung cancer occurs with high frequency and is also highly resistant to radiation therapy. Thus, how to avoid radiation resistance and improve radiotherapy effectiveness is a crucial question. In the present study, human lung cancer A549 and H1299 cells were irradiated using γ-rays from a Co60 irradiator. Protein expression was detected by Western blotting. Cell cycle and apoptosis were measured by flow cytometry. Surviving fraction was determined by colony formation assay. γH2AX and 53BP1 foci formation were examined by fluorescence microscopy. In the results, we show that CHMP4C, a subunit of Endosomal sorting complex-III (ESCRT-III), is involved in radiation-induced cellular response. Radiation-induced Aurora B expression enhances CHMP4C phosphorylation in non-small cell lung cancer (NSCLC) cells, maintaining cell cycle check-point and cellular viability as well as resisting apoptosis. CHMP4C depletion enhances cellular sensitivity to radiation, delays S-phase of cell cycle and reduces ionizing radiation (IR)-induced γH2AX foci formation. We found that Aurora B targets CHMP4C and inhibition of Aurora B exhibits similar effects with silencing of CHMP4C in radioresistance. We also confirm that CHMP4C phosphorylation is elevated after IR both in p53-positive and-negative cells, indicating that the close correlation between CHMP4C and Aurora B signaling pathway in mediating radiation resistance is not p53 dependent. Together, our work establishes a new function of CHMP4C in radiation resistance, which will offer a potential strategy for non-small cell lung cancer by disrupting CHMP4C. PMID:26712741

  19. CHMP4C Disruption Sensitizes the Human Lung Cancer Cells to Irradiation.

    PubMed

    Li, Kang; Liu, Jianxiang; Tian, Mei; Gao, Gang; Qi, Xuesong; Pan, Yan; Ruan, Jianlei; Liu, Chunxu; Su, Xu

    2016-01-01

    Human lung cancer is highly invasive and the most malignant among human tumors. Adenocarcinoma as a specific type of non-small cell lung cancer occurs with high frequency and is also highly resistant to radiation therapy. Thus, how to avoid radiation resistance and improve radiotherapy effectiveness is a crucial question. In the present study, human lung cancer A549 and H1299 cells were irradiated using γ-rays from a Co60 irradiator. Protein expression was detected by Western blotting. Cell cycle and apoptosis were measured by flow cytometry. Surviving fraction was determined by colony formation assay. γH2AX and 53BP1 foci formation were examined by fluorescence microscopy. In the results, we show that CHMP4C, a subunit of Endosomal sorting complex-III (ESCRT-III), is involved in radiation-induced cellular response. Radiation-induced Aurora B expression enhances CHMP4C phosphorylation in non-small cell lung cancer (NSCLC) cells, maintaining cell cycle check-point and cellular viability as well as resisting apoptosis. CHMP4C depletion enhances cellular sensitivity to radiation, delays S-phase of cell cycle and reduces ionizing radiation (IR)-induced γH2AX foci formation. We found that Aurora B targets CHMP4C and inhibition of Aurora B exhibits similar effects with silencing of CHMP4C in radioresistance. We also confirm that CHMP4C phosphorylation is elevated after IR both in p53-positive and-negative cells, indicating that the close correlation between CHMP4C and Aurora B signaling pathway in mediating radiation resistance is not p53 dependent. Together, our work establishes a new function of CHMP4C in radiation resistance, which will offer a potential strategy for non-small cell lung cancer by disrupting CHMP4C. PMID:26712741

  20. 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 ...

  1. 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 ...

  2. Imperatorin sensitizes anoikis and inhibits anchorage-independent growth of lung cancer cells.

    PubMed

    Choochuay, Kanuengnit; Chunhacha, Preedakorn; Pongrakhananon, Varisa; Luechapudiporn, Rataya; Chanvorachote, Pithi

    2013-07-01

    The anoikis-sensitization activity of imperatorin, an active furanocoumarin component of Angelica dahurica root, is reported herein for the first time. The present study demonstrated that the imperatorin treatment at sub-toxic concentrations enhanced human lung cancer H23 cell apoptosis after detachment. A Western blot analysis showed that imperatorin significantly enhanced the p53 protein level, which subsequently down-regulated Mcl-1 protein and up-regulated Bax, while it had a minimal effect on Bcl-2 expression. In addition, an anchorage-independent growth assay was performed to support the anti-metastasis potential of imperatorin. Consistent with anoikis assay, imperatorin exhibited a strong inhibitory effect on the anchorage-independent growth of the cells. Further, this study demonstrated that imperatorin sensitizes anoikis in other lung cancer cells, namely, H292 and A549. Because anoikis was shown to be a critical hindrance in preventing cancer cell metastasis, the knowledge regarding such an activity and an underlying mechanism may lead to the development of this compound for a cancer therapy. PMID:23108812

  3. Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344.

    PubMed

    Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D; Townsend, Danyelle M; Tew, Kenneth D

    2016-08-01

    ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. PMID:27255112

  4. 6 Common Cancers - Lung Cancer

    MedlinePlus

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

  5. 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 ...

  6. EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment

    PubMed Central

    Zhang, Hongjuan; Zhan, Cheng; Ke, Ji; Xue, Zhiqiang; Zhang, Aiqun; Xu, Kaifeng; Shen, Zhirong; Yu, Lei; Chen, Liang

    2016-01-01

    Lung cancer is the global leading cause of cancer-related deaths. A significant portion of lung cancer patients harbor kinase domain mutations in the epidermal growth factor receptor (EGFR). While EGFR tyrosine kinase inhibitors (TKI) effectively shrink tumors harboring mutant EGFR, clinical efficacy is limited by the development of TKI resistance. Effective alternatives are desperately needed in clinic for treating EGFR kinase domain mutation positive lung cancer. In our clinic in treating M1a lung cancer patients through intrapleural perfusion with hyperthermic chemotherapy (IPHC) followed by cycles of systemic chemotherapy (we termed this procedure IPHC complete treatment, IPHC-CT), we found dramatic tumor shrinkage in mutant EGFR-positive patients. We further confirmed the sensitivity of EGFR mutation-positive lung cancer cell lines derived from patients to HC (hyperthermic chemotherapy) treatment. We found that hyperthermia promoted accumulation of cisplatin in lung cancer cells. Hyperthermia and cisplatin synergistically downregulated the EGFR protein level, leading to quenching of signal from EGFR and induction of apoptosis. Our work therefore showed IPHC-CT is an effective treatment for EGFR kinase domain mutation positive lung cancer patients. PMID:26654941

  7. Lung Cancer Screening

    MedlinePlus

    ... Cancer Treatment Small Cell Lung Cancer Treatment Lung cancer is the leading cause of cancer death in the United States. Lung cancer is ... non- skin cancer in the United States. Lung cancer is the leading cause of cancer death in men and in women. ...

  8. The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells

    PubMed Central

    Voortman, Jens; Chęcińska, Agnieszka; Giaccone, Giuseppe

    2007-01-01

    Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing potential of bortezomib in NSCLC cells was found to be dependent not only on the apoptotic phenotype but also on the proteasomal phenotype of individual cell lines. Upon effective proteasome inhibition, H460 cells were more susceptible to apoptosis induction by bortezomib than SW1573 cells, indicating a different apoptotic phenotype. However, exposure to a low dose of bortezomib did only result in SW1573 cells, and not in H460 cells, in inhibition of proteasome activity and subsequent apoptosis. This suggests a different proteasomal phenotype as well. Additionally, overexpression of anti-apoptotic protein Bcl-2 in H460 cells did not affect the proteasomal phenotype of H460 cells but did result in decreased bortezomib-induced apoptosis. In conclusion, successful proteasome-inhibitor based treatment strategies in NSCLC face the challenge of having to overcome apoptosis resistance as well as proteasomal resistance of individual lung cancer cells. Further studies in NSCLC are warranted to elucidate underlying mechanisms. PMID:18021420

  9. Metastatic signature in lung cancer is associated with sensitivity to anti-integrin α(V) monoclonal antibody intetumumab.

    PubMed

    Liu, Huiqing; Park, Jaehong; Manning, Carol; Goehlmann, Hinrich W H; Marshall, Deborah J

    2014-04-01

    Intetumumab is a fully human monoclonal antibody that inhibits αv integrins. It has been shown in in vitro assays to effectively inhibit cell viability, metastasis, and adhesion of human cancer cells and endothelial cells. However, the response to Intetumumab varies in different tumor cell lines. To understand the growth inhibition mechanism of Intetumumab and to identify a molecular signature that can predict sensitivity, we focused on lung cancer cell lines and performed a series of proliferation assays. We then assessed the global gene expression profiles, DNA copy number variations, and microRNA profiles from a total of 23 lung cancer lines. The results revealed that lung cancer sensitivity to Intetumumab is associated with several chromosomal alterations, particularly genetic loss at chromosome arm 19p, which resulted in gene expression changes. We identified a genetic signature that can be used to predict Intetumumab sensitivity for lung cancer cell lines. Independently, microRNA analysis revealed a panel of signature microRNAs that includes several markers of epithelial to mesenchymal transition and tumor metastasis such as miR-200 family and miR-205. Both the genetic and microRNA signatures provide insights into the potential mechanism of Intetumumab activity and serve as the first step to develop a patient stratification strategy for Intetumumab therapy in lung cancer. PMID:24488787

  10. PKC 412 sensitizes U1810 non-small cell lung cancer cells to DNA damage

    SciTech Connect

    Hemstroem, Therese H.; Joseph, Bertrand; Schulte, Gunnar; Lewensohn, Rolf; Zhivotovsky, Boris . E-mail: Boris.Zhivotovsky@imm.ki.se

    2005-04-15

    Non-small cell lung carcinoma (NSCLC) is characterized by resistance to drug-induced apoptosis, which might explain the survival of lung cancer cells following treatment. Recently we have shown that the broad-range kinase inhibitor staurosporine (STS) reactivates the apoptotic machinery in U1810 NSCLC cells [Joseph et al., Oncogene 21 (2002) 65]. Lately, several STS analogs that are more specific in kinase inhibition have been suggested for tumor treatment. In this study the apoptosis-inducing ability of the STS analogs PKC 412 and Ro 31-8220 used alone or in combination with DNA-damaging agents in U1810 cells was investigated. In these cells Ro 31-8220 neither induced apoptosis when used alone, nor sensitized cells to etoposide treatment. PKC 412 as a single agent induced death of a small number of U1810 cells, whereas it efficiently triggered a dose- and time-dependent apoptosis in U1285 small cell lung carcinoma cells. In both cell types PKC 412 triggered release of mitochondrial proteins followed by caspase activation. However, concomitant activation of a caspase-independent pathway was essential to kill NSCLC cells. Importantly, PKC 412 was able to sensitize etoposide- and radiation-induced death of U1810 cells. The best sensitization was achieved when PKC 412 was administered 24 h after treatments. In U1810 cells, Ro 31-8220 decreased PMA-induced ERK phosphorylation as efficiently as PKC 412, indicating that the failure of Ro 31-8220 to induce apoptosis was not due to weaker inhibition of conventional and novel PKC isoforms. However, Ro 31-8220 increased the basal level of ERK and Akt phosphorylation in both cell lines, whereas Akt phosphorylation was suppressed in the U1810 cells, which might influence apoptosis. These results suggest that PKC 412 could be a useful tool in increasing the efficiency of therapy of NSCLC.

  11. CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR

    DOE PAGESBeta

    Wang, Yunshan; Zhang, Pengju; Liu, Ziming; Wang, Qin; Wen, Mingxin; Wang, Yuli; Yuan, Hongtu; Mao, Jian-Hua; Wei, Guangwei

    2014-11-21

    CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively. We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpressionmore » of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities. In conclusion, our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients.« less

  12. CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR

    SciTech Connect

    Wang, Yunshan; Zhang, Pengju; Liu, Ziming; Wang, Qin; Wen, Mingxin; Wang, Yuli; Yuan, Hongtu; Mao, Jian-Hua; Wei, Guangwei

    2014-11-21

    CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively. We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpression of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities. In conclusion, our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients.

  13. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    SciTech Connect

    Nakadate, Yusuke; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  14. Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

    PubMed Central

    Dutt, Amit; Ramos, Alex H.; Hammerman, Peter S.; Mermel, Craig; Cho, Jeonghee; Sharifnia, Tanaz; Chande, Ajit; Tanaka, Kumiko Elisa; Stransky, Nicolas; Greulich, Heidi; Gray, Nathanael S.; Meyerson, Matthew

    2011-01-01

    Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer. PMID:21666749

  15. Assessment of sensitivity and specificity of immunohistochemical staining of p53 in lung and head and neck cancers.

    PubMed Central

    Melhem, M. F.; Law, J. C.; el-Ashmawy, L.; Johnson, J. T.; Landreneau, R. J.; Srivastava, S.; Whiteside, T. L.

    1995-01-01

    Thirty-two primary carcinomas of the lung and 17 carcinomas of the head and neck (HN) were systematically analyzed for p53 mutations in the highly conserved regions of the gene (exons 5-8). Frozen sections of the same tumors were stained immunohistochemically to assess the sensitivity and specificity of p53 expression as determined by the presence or absence of the protein. On the basis of histology, the lung tumors studied were divided into adenocarcinomas (AC; n = 15), squamous-cell carcinomas (SCC; n = 12), and large-cell carcinomas (LCC; n = 5). All the HN cancers were SCC. Mutations in the p53 gene were detected by direct sequencing of amplified polymerase chain reaction products in six AC of the lungs (40%), three SCC of the lungs (25%), and one LCC (20%), with an overall mutation frequency of 31%. Nine AC (60%) of the lungs, five SCC (42%), and four LCC (80%) were p53-positive by immunohistochemistry. Among HN cancers, p53 mutations were detected in seven tumors (41%). Nine HN tumors (53%) were positive for p53. Negative staining, despite the presence of p53 mutations, was confined to nonsense mutations with truncated p53 and to single-base mutations not causing any change in the amino acid. Although immunohistochemical staining for mutated p53 is sensitive and simple to perform as a screening method, it is not as specific for evaluation of p53 mutations in lung and HN cancers. Images Figure 1 PMID:7747811

  16. Lung cancer.

    PubMed

    Frödin, J E

    1996-01-01

    This synthesis of the literature on radiotherapy for lung cancer is based on 80 scientific articles, including 2 meta-analyses, 29 randomized studies, 19 prospective studies, and 21 retrospective studies. These studies involve 28172 patients. Basic treatment for limited-stage small cell lung cancer (SCLC), is chemotherapy. Addition of radiotherapy to the primary tumor and mediastinum reduces local recurrence, prolongs long-term survival, and is often indicated. Current, and future, studies can be expected to show successive improvements in results for SCLC by optimizing the combination of radiotherapy and chemotherapy. Should these treatments be given simultaneously or sequentially, and in which order? Which fractionation is best? Probably, no change in resource requirements for radiotherapy will be necessary, with the possible exception of changes in fractionation. Surgery constitutes primary treatment for nonsmall cell lung cancer (NSCLC) stages I and II. Radiotherapy may provide an alternative for patients who are inoperable for medical reasons. The value of radiotherapy following radical surgery for NSCLC remains to be shown. It is not indicated based on current knowledge. For NSCLC stage III, radiotherapy shrinks tumors and prolongs survival at 2 and 3 years. Whether it influences long-term survival after 5 years has not been shown. Considering the side effects of treatment, one must question whether limited improvements in survival motivate routine radiotherapy in these patients. Earlier attempts to add chemotherapy to radiotherapy to improve treatment results of NSCLC have not yielded convincing results. Several studies are currently on-going. Prophylactic cranial irradiation (PCI) greatly reduces the risk for brain metastases from SCLC. However, it has little influence on survival. Many treatment centers give PCI to SCLC patients who have achieved complete remission. This practice may be questioned since PCI is associated with serious complications. PCI is

  17. Differential Sensitivity of Glioma- versus Lung Cancer-specific EGFR mutations to EGFR Kinase Inhibitors

    PubMed Central

    Vivanco, Igor; Robins, H. Ian; Rohle, Daniel; Campos, Carl; Grommes, Christian; Nghiemphu, Phioanh Leia; Kubek, Sara; Oldrini, Barbara; Chheda, Milan G.; Yannuzzi, Nicolas; Tao, Hui; Zhu, Shaojun; Iwanami, Akio; Kuga, Daisuke; Dang, Julie; Pedraza, Alicia; Brennan, Cameron W.; Heguy, Adriana; Liau, Linda M.; Lieberman, Frank; Yung, W.K. Alfred; Gilbert, Mark R.; Reardon, David A.; Drappatz, Jan; Wen, Patrick Y.; Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.; Fine, Howard A.; Horvath, Steve; Wu, Nian; Lassman, Andrew B.; DeAngelis, Lisa M.; Yong, William H.; Kuhn, John G.; Mischel, Paul S.; Mehta, Minesh P.; Cloughesy, Timothy F.; Mellinghoff, Ingo K.

    2012-01-01

    Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions in the extracellular (EC) domain. Unlike lung cancers with EGFR kinase domain (KD) mutations, GBMs respond poorly to the EGFR inhibitor erlotinib. Using RNAi, we show that GBM cells carrying EGFR EC mutations display EGFR addiction. In contrast to KD mutants found in lung cancer, glioma-specific EGFR EC mutants are poorly inhibited by EGFR inhibitors that target the active kinase conformation (e.g., erlotinib). Inhibitors which bind to the inactive EGFR conformation, on the other hand, potently inhibit EGFR EC mutants and induce cell death in EGFR mutant GBM cells. Our results provide first evidence for single kinase addiction in GBM, and suggest that the disappointing clinical activity of first-generation EGFR inhibitors in GBM versus lung cancer may be attributed to the different conformational requirements of mutant EGFR in these two cancer types. PMID:22588883

  18. Small Cell Lung Cancer

    PubMed Central

    Kalemkerian, Gregory P.; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura QM; Downey, Robert J.; Gandhi, Leena; Ganti, Apar Kishor P.; Govindan, Ramaswamy; Grecula, John C.; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W.; Merritt, Robert E.; Moran, Cesar A.; Niell, Harvey B.; O’Malley, Janis; Patel, Jyoti D.; Ready, Neal; Rudin, Charles M.; Williams, Charles C.; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. PMID:23307984

  19. Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer.

    PubMed

    Ai, Yong; Zhu, Bin; Ren, Caiping; Kang, Fenghua; Li, Jinlong; Huang, Zhangjian; Lai, Yisheng; Peng, Sixun; Ding, Ke; Tian, Jide; Zhang, Yihua

    2016-03-10

    The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer. PMID:26891099

  20. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint.

    PubMed

    Nakadate, Yusuke; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy. PMID:24211580

  1. Marsdenia tenacissima extract restored gefitinib sensitivity in resistant non-small cell lung cancer cells.

    PubMed

    Han, Shu-Yan; Zhao, Ming-Bo; Zhuang, Gui-Bao; Li, Ping-Ping

    2012-01-01

    Most non-small cell lung cancer (NSCLC) patients responding to gefitinib harbor activating mutations in the epidermal growth factor receptor (EGFR). However, the responsive cases eventually develop the resistance to gefitinib. Besides, K-ras mutations were identified as the primary resistance to gefitinib. We investigated whether Marsdenia tenacissima extract (MTE, trade name: Xiao-Ai-Ping injection) combined with gefitinib could overcome the resistance of NSCLC cells to gefitinib. NSCLC cell lines with different sensitivities to gefitinib were studied. Cell growth and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The EGFR-related signaling molecule phosphorylation was assessed by Western blotting. We found that MTE inhibited cell growth in gefitinib-sensitive and -resistant cells. In gefitinib-resistant cells, the MTE→MTE+gefitinib (M→M+G) treatment was most potent over the concurrent administration of MTE and gefitinib (M+G) or gefitinib→gefitinib+MTE (G→G+M) treatment in cell growth inhibition and apoptosis induction. The M→M+G treatment significantly reduced the phosphorylation of EGFR downstream signaling molecules PI3K/Akt/mTOR and ERK, on which MTE and gefitinib alone had no obvious effects on the resistant cells. The M→M+G treatment attenuated c-Met phosphorylation in H460 and H1975 as well. Thus, we found that the M→M+G treatment improved the sensitivity of resistant NSCLC cells carrying T790M or K-ras mutations to gefitinib, suggesting that the M→M+G treatment may be a promising therapeutic strategy to overcome gefitinib resistance in NSCLC. PMID:21757251

  2. Epidemiology of Lung Cancer

    PubMed Central

    Ridge, Carole A.; McErlean, Aoife M.; Ginsberg, Michelle S.

    2013-01-01

    Incidence and mortality attributed to lung cancer has risen steadily since the 1930s. Efforts to improve outcomes have not only led to a greater understanding of the etiology of lung cancer, but also the histologic and molecular characteristics of individual lung tumors. This article describes this evolution by discussing the extent of the current lung cancer epidemic including contemporary incidence and mortality trends, the risk factors for development of lung cancer, and details of promising molecular targets for treatment. PMID:24436524

  3. Lung cancer prevention.

    PubMed

    Slatore, Christopher; Sockrider, Marianna

    2014-11-15

    Lung cancer is a common form of cancer.There are things you can do to lower your risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help in quitting, including use of medicines to help with nicotine dependence. discuss with your healthcare provider,what you are taking or doing to decrease your risk for lung cancer PMID:25398122

  4. Inhibition of microRNA-155 sensitizes lung cancer cells to irradiation via suppression of HK2-modulated glucose metabolism.

    PubMed

    Lv, Xin; Yao, Li; Zhang, Jianli; Han, Ping; Li, Cuiyun

    2016-08-01

    MicroRNAs (miRNAs) are small non-coding regulatory RNAs, which are involved in the post-transcriptional regulation of gene expression. miRNA (miR)-155, which has previously been reported to be overexpressed in lung cancer, is correlated with poor patient prognosis. The present study aimed to investigate the effects of miR‑155 on the radiosensitivity of human non‑small cell lung cancer (NSCLC) cells. To explore the roles of miRNAs in the regulation of irradiation sensitivity of human lung cancer cells, the expressions of miR‑155 in response to irradiation, have been studied by RT‑qPCR, and the putative direct target of miR‑155 was identified by western blot and luciferase assays. The results of the present study revealed that the expression of miR‑155 was induced by irradiation, thus suggesting a positive correlation between miR‑155 and radiosensitivity. Furthermore, overexpression of miR‑155 rendered lung cancer cells resistant to irradiation. In addition, hexokinase 2 (HK2) was identified as an indirect target of miR‑155; exogenous overexpression of miR‑155 upregulated the expression of HK2, whereas inhibition of miR‑155 by antisense miRNA suppressed HK2 expression. In addition, HK2‑modulated glucose metabolism was significantly upregulated by overexpression of miR‑155. Notably, inhibition of miR‑155 sensitized lung cancer cells to irradiation via suppression of glucose metabolism. In conclusion, the present study reported a novel function for miR‑155 in the regulation of NSCLC cell radiosensitivity, thus suggesting that miR‑155 may be considered a therapeutic target for the development of anticancer drugs. PMID:27315591

  5. Epidemiology of Lung Cancer.

    PubMed

    Mao, Yousheng; Yang, Ding; He, Jie; Krasna, Mark J

    2016-07-01

    Lung cancer has been transformed from a rare disease into a global problem and public health issue. The etiologic factors of lung cancer become more complex along with industrialization, urbanization, and environmental pollution around the world. Currently, the control of lung cancer has attracted worldwide attention. Studies on the epidemiologic characteristics of lung cancer and its relative risk factors have played an important role in the tertiary prevention of lung cancer and in exploring new ways of diagnosis and treatment. This article reviews the current evolution of the epidemiology of lung cancer. PMID:27261907

  6. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer

    PubMed Central

    Rizvi, Naiyer A.; Hellmann, Matthew D.; Snyder, Alexandra; Kvistborg, Pia; Makarov, Vladimir; Havel, Jonathan J.; Lee, William; Yuan, Jianda; Wong, Phillip; Ho, Teresa S.; Miller, Martin L.; Rekhtman, Natasha; Moreira, Andre L.; Ibrahim, Fawzia; Bruggeman, Cameron; Gasmi, Billel; Zappasodi, Roberta; Maeda, Yuka; Sander, Chris; Garon, Edward B.; Merghoub, Taha; Wolchok, Jedd D.; Schumacher, Ton N.; Chan, Timothy A.

    2016-01-01

    Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy. PMID:25765070

  7. 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

  8. Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3.

    PubMed

    Shou, Jiawei; You, Liangkun; Yao, Junlin; Xie, Jiansheng; Jing, Jing; Jing, Zhao; Jiang, Liming; Sui, Xinbing; Pan, Hongming; Han, Weidong

    2016-08-28

    The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically prolonged the overall survival of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, but the presence of primary or acquired resistance eventually leads to therapeutic failure. Thus, how to improve the efficacy and reverse the resistance to EGFR-TKIs remains a significant challenge. In this study, we found that CsA significantly augmented the anti-cancer effect of gefitinib in EGFR-TKI-sensitive and -resistant NSCLC cells. Mechanistically, CsA promoted gefitinib-induced apoptosis through inhibition of the STAT3 pathway. Similar with the function of CsA, siRNAs against STAT3 also enhanced gefitinib-induced apoptosis in multiple lung cancer cells. Xenograft studies further demonstrated that CsA promoted the anti-cancer activity of gefitinib on lung cancer cells through inhibition of STAT3. Moreover, NSCLC patients with high levels of phosphorylated STAT3 (Y705) showed a significantly poorer therapeutic response to EGFR-TKIs. This study provides preclinical evidence that the combination of CsA or a STAT3 inhibitor with EGFR-TKIs is a promising approach to improve the efficacy of EGFR-TKIs for the treatment of patients with advanced NSCLC. PMID:27264264

  9. Occupational lung cancer.

    PubMed

    Cone, J E

    1987-01-01

    The author addresses the attribution of lung cancer to cigarette smoking and the problems of confounding synergistic effects of occupational and other carcinogenic risk factors, as well as the divergent trends of declining smoking rates and increasing rates of lung cancer. He also reviews the existing literature to document associations between lung cancer and occupational exposures. Finally, interventions for prevention of occupational lung cancer are discussed. PMID:3303381

  10. Occupational lung cancer

    SciTech Connect

    Cone, J.E.

    1987-04-01

    The author addresses the attribution of lung cancer to cigarette smoking and the problems of confounding synergistic effects of occupational and other carcinogenic risk factors, as well as the divergent trends of declining smoking rates and increasing rates of lung cancer. He also reviews the existing literature to document associations between lung cancer and occupational exposures. Finally, interventions for prevention of occupational lung cancer are discussed.

  11. Lung cancer in women.

    PubMed

    Coscio, Angela M; Garst, Jennifer

    2006-07-01

    Lung cancer is the most common cancer in both men and women; however, there are some clear gender-based differences. As the incidence of lung cancer is declining in men, the incidence of lung cancer is increasing in women. Women are more likely than men to have adenocarcinoma, a histologic subtype that correlates with worsened prognosis, but women have improved survival compared with men. Genetic predisposition and the presence of estrogen receptors in lung cancer cells may predispose women to developing lung cancer. Further studies are needed to understand the mechanism and significance of these findings. PMID:17254523

  12. Pulmonary Codelivery of Doxorubicin and siRNA by pH-Sensitive Nanoparticles for Therapy of Metastatic Lung Cancer.

    PubMed

    Xu, Caina; Wang, Ping; Zhang, Jingpeng; Tian, Huayu; Park, Kinam; Chen, Xuesi

    2015-09-01

    A pulmonary codelivery system that can simultaneously deliver doxorubicin (DOX) and Bcl2 siRNA to the lungs provides a promising local treatment strategy for lung cancers. In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis-aconitic anhydride (CA, a pH-sensitive linker) to obtain PEI-CA-DOX conjugates. The PEI-CA-DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI-CA-DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI-CA-DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed into the lungs of B16F10 melanoma-bearing mice, the PEI-CA-DOX/Bcl2 siRNA complex nanoparticles exhibit enhanced antitumor efficacy compared with the single delivery of DOX or Bcl2 siRNA. Compared with systemic delivery, most drug and siRNA show a long-term retention in the lungs via pulmonary delivery, and a considerable number of the drug and siRNA accumulate in tumor tissues of lungs, but rarely in normal lung tissues. The PEI-CA-DOX/Bcl2 siRNA complex nanoparticles are promising for the treatment of metastatic lung cancer by pulmonary delivery with low side effects on the normal tissues. PMID:26136261

  13. Inhibition of ceramide glucosylation sensitizes lung cancer cells to ABC294640, a first-in-class small molecule SphK2 inhibitor.

    PubMed

    Guan, Shuhong; Liu, Yuan Y; Yan, Tingzan; Zhou, Jun

    2016-08-01

    Sphingosine kinase 2 (SphK2) is proposed as a novel oncotarget for lung cancer. Here, we studied the anti-lung cancer cell activity by ABC294640, a first-in-class SphK2 inhibitor. We showed that ABC294640 suppressed growth of primary and A549 human lung cancer cells, but sparing SphK2-low lung epithelial cells. Inhibition of SphK2 by ABC294640 increased ceramide accumulation, but decreased pro-survival sphingosine-1-phosphate (S1P) content, leading to lung cancer cell apoptosis activation. Significantly, we show that glucosylceramide synthase (GCS) might be a major resistance factor of ABC294640. The GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) or GCS shRNA/siRNA knockdown facilitated ABC294640-induced ceramide production and lung cancer cell apoptosis. Reversely, forced overexpression of GCS reduced ABC294640's sensitivity, resulting in decreased ceramide accumulation and apoptosis induction in A549 cells. These findings provide further evidences to support that targeting SphK2 by ABC294640 may be a rational treatment option for lung cancer. Ceramide glucosylation inhibition may further sensitize lung cancer cells to ABC294640. PMID:27221045

  14. FGFR1 mRNA and Protein Expression, not Gene Copy Number, Predict FGFR TKI Sensitivity Across All Lung Cancer Histologies

    PubMed Central

    Wynes, Murry W.; Hinz, Trista K.; Gao, Dexiang; Martini, Michael; Marek, Lindsay A.; Ware, Kathryn E.; Edwards, Michael G.; Böhm, Diana; Perner, Sven; Helfrich, Barbara A.; Dziadziuszko, Rafal; Jassem, Jacek; Wojtylak, Szymon; Sejda, Aleksandra; Gozgit, Joseph M.; Bunn, Paul A.; Camidge, D. Ross; Tan, Aik-Choon; Hirsch, Fred R.; Heasley, Lynn E.

    2014-01-01

    Purpose FGFR1 gene copy number (GCN) is being evaluated as a biomarker for FGFR tyrosine kinase inhibitor (TKI) response in squamous-cell lung cancers (SCC). The exclusive use of FGFR1 GCN for predicting FGFR TKI sensitivity assumes increased GCN is the only mechanism for biologically-relevant increases in FGFR1 signaling. Herein, we tested whether FGFR1 mRNA and protein expression may serve as better biomarkers of FGFR TKI sensitivity in lung cancer. Experimental Design Histologically diverse lung cancer cell lines were submitted to assays for ponatinib sensitivity, a potent FGFR TKI. A tissue microarray comprised of resected lung tumors was submitted to FGFR1 GCN and mRNA analyses and the results were validated with TCGA lung cancer data. Results 14/58 cell lines exhibited ponatinib sensitivity (IC50 values ≤ 50 nM) that correlated with FGFR1 mRNA and protein expression, but not with FGFR1 GCN or histology. Moreover, ponatinib sensitivity associated with mRNA expression of the ligands, FGF2 and FGF9. In resected tumors, 22% of adenocarcinomas and 28% of SCCs expressed high FGFR1 mRNA. Importantly, only 46% of SCCs with increased FGFR1 GCN expressed high mRNA. Lung cancer TCGA data validated these findings and unveiled overlap of FGFR1 mRNA positivity with KRAS and PIK3CA mutations. Conclusions FGFR1 dependency is frequent across various lung cancer histologies and FGFR1 mRNA may serve as a better biomarker of FGFR TKI response in lung cancer than FGFR1 GCN. The study provides important and timely insight into clinical testing of FGFR TKIs in lung cancer and other solid tumor types. PMID:24771645

  15. Metastatic cancer to the lung

    MedlinePlus

    ... Bladder cancer Breast cancer Colon cancer Kidney cancer Neuroblastoma Prostate cancer Sarcoma Wilms tumor Symptoms Symptoms may ... Breast cancer Cancer Chemotherapy Colon cancer Lung cancer Neuroblastoma Prostate cancer Radiation therapy Wilms tumor Update Date ...

  16. Risks of Lung Cancer Screening

    MedlinePlus

    ... Cancer Treatment Small Cell Lung Cancer Treatment Lung cancer is the leading cause of cancer death in the United States. Lung cancer is ... non- skin cancer in the United States. Lung cancer is the leading cause of cancer death in men and in women. ...

  17. Lung cancer

    MedlinePlus

    ... any symptoms. Symptoms depend on the type of cancer you have, but may include: Chest pain Cough that does not go away Coughing up blood Fatigue Losing weight without trying Loss of appetite Shortness of breath ...

  18. Drugs Approved for Lung Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Lung Cancer This page lists cancer ... in lung cancer that are not listed here. Drugs Approved for Non-Small Cell Lung Cancer Abitrexate ( ...

  19. Rare lung cancers.

    PubMed

    2015-12-01

    There are several different kinds of lung cancer, often referred to as lung cancer subtypes. Some of these occur more often than others. In this factsheet we will specifically look at the subtypes of cancers that do not happen very often and are considered 'rare'. PMID:27066129

  20. 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

  1. 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. PMID:26667337

  2. Sensitivity of Small Cell Lung Cancer to BET Inhibition Is Mediated by Regulation of ASCL1 Gene Expression.

    PubMed

    Lenhart, Ryan; Kirov, Stefan; Desilva, Heshani; Cao, Jian; Lei, Ming; Johnston, Kathy; Peterson, Russell; Schweizer, Liang; Purandare, Ashok; Ross-Macdonald, Petra; Fairchild, Craig; Wong, Tai; Wee, Susan

    2015-10-01

    The BET (bromodomain and extra-terminal) proteins bind acetylated histones and recruit protein complexes to promote transcription elongation. In hematologic cancers, BET proteins have been shown to regulate expression of MYC and other genes that are important to disease pathology. Pharmacologic inhibition of BET protein binding has been shown to inhibit tumor growth in MYC-dependent cancers, such as multiple myeloma. In this study, we demonstrate that small cell lung cancer (SCLC) cells are exquisitely sensitive to growth inhibition by the BET inhibitor JQ1. JQ1 treatment has no impact on MYC protein expression, but results in downregulation of the lineage-specific transcription factor ASCL1. SCLC cells that are sensitive to JQ1 are also sensitive to ASCL1 depletion by RNAi. Chromatin immunoprecipitation studies confirmed the binding of the BET protein BRD4 to the ASCL1 enhancer, and the ability of JQ1 to disrupt the interaction. The importance of ASCL1 as a potential driver oncogene in SCLC is further underscored by the observation that ASCL1 is overexpressed in >50% of SCLC specimens, an extent greater than that observed for other putative oncogenes (MYC, MYCN, and SOX2) previously implicated in SCLC. Our studies have provided a mechanistic basis for the sensitivity of SCLC to BET inhibition and a rationale for the clinical development of BET inhibitors in this disease with high unmet medical need. PMID:26253517

  3. Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity

    PubMed Central

    Yagyu, Shigeki; Tao, Wade; Ramos, Carlos A.; Dotti, Gianpietro; Brenner, Malcolm K.; Bouchier-Hayes, Lisa

    2014-01-01

    Delivery of suicide genes to solid tumors represents a promising tumor therapy strategy. However, slow or limited killing by suicide genes and ineffective targeting of the tumor has reduced effectiveness. We have adapted a suicide system based on an inducible caspase-9 (iC9) protein that is activated using a specific chemical inducer of dimerization (CID) for adenoviral based delivery to lung tumors via mesenchymal stromal cells (MSC). Four independent human non-small cell lung cancer (NSCLC) cell lines were transduced with adenovirus encoding iC9 and all underwent apoptosis when iC9 was activated by adding CID. However, there was a large variation in the percentage of cell killing induced by CID across the different lines. The least responsive cell lines were sensitized to apoptosis by combined inhibition of the proteasome using bortezomib. These results were extended to an in vivo model using human NSCLC xenografts. E1A-expressing MSC replicated Ad.iC9 and delivered the virus to lung tumors in SCID mice. Treatment with CID resulted in some reduction of tumor growth but addition of bortezomib led to greater reduction of tumor size. The enhanced apoptosis and anti-tumor effect of combining MSC-delivered Ad.iC9, CID and bortezomib appears to be due to increased stabilization of active caspase-3, since proteasomal inhibition increased the levels of cleaved caspase-9 and caspase-3. Knockdown of XIAP, a caspase inhibitor that targets active caspase-3 to the proteasome, also sensitized iC9-transduced cells to CID, suggesting that blocking the proteasome counteracts XIAP to permit apoptosis. Thus, MSC-based delivery of the iC9 suicide gene to human NSCLC effectively targets lung cancer cells for elimination. Combining this therapy with bortezomib, a drug that is otherwise inactive in this disease, further enhances the anti-tumor activity of this strategy. PMID:25323693

  4. Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity.

    PubMed

    Ando, M; Hoyos, V; Yagyu, S; Tao, W; Ramos, C A; Dotti, G; Brenner, M K; Bouchier-Hayes, L

    2014-11-01

    Delivery of suicide genes to solid tumors represents a promising tumor therapy strategy. However, slow or limited killing by suicide genes and ineffective targeting of the tumor has reduced effectiveness. We have adapted a suicide system based on an inducible caspase-9 (iC9) protein that is activated using a specific chemical inducer of dimerization (CID) for adenoviral-based delivery to lung tumors via mesenchymal stromal cells (MSCs). Four independent human non-small cell lung cancer (NSCLC) cell lines were transduced with adenovirus encoding iC9, and all underwent apoptosis when iC9 was activated by adding CID. However, there was a large variation in the percentage of cell killing induced by CID across the different lines. The least responsive cell lines were sensitized to apoptosis by combined inhibition of the proteasome using bortezomib. These results were extended to an in vivo model using human NSCLC xenografts. E1A-expressing MSCs replicated Ad.iC9 and delivered the virus to lung tumors in SCID mice. Treatment with CID resulted in some reduction of tumor growth, but addition of bortezomib led to greater reduction of tumor size. The enhanced apoptosis and anti-tumor effect of combining MSC-delivered Ad.iC9, CID and bortezomib appears to be due to increased stabilization of active caspase-3, as proteasomal inhibition increased the levels of cleaved caspase-9 and caspase-3. Knockdown of X-linked inhibitor of apoptosis protein (XIAP), a caspase inhibitor that targets active caspase-3 to the proteasome, also sensitized iC9-transduced cells to CID, suggesting that blocking the proteasome counteracts XIAP to permit apoptosis. Thus, MSC-based delivery of the iC9 suicide gene to human NSCLC effectively targets lung cancer cells for elimination. Combining this therapy with bortezomib, a drug that is otherwise inactive in this disease, further enhances the anti-tumor activity of this strategy. PMID:25323693

  5. Lung Cancer Screening.

    PubMed

    Wu, Geena X; Raz, Dan J

    2016-01-01

    Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Since lung cancer outcomes are dependent on stage at diagnosis with early disease resulting in longer survival, the goal of screening is to capture lung cancer in its early stages when it can be treated and cured. Multiple studies have evaluated the use of chest X-ray (CXR) with or without sputum cytologic examination for lung cancer screening, but none has demonstrated a mortality benefit. In contrast, the multicenter National Lung Screening Trial (NLST) from the United States found a 20 % reduction in lung cancer mortality following three consecutive screenings with low-dose computed tomography (LDCT) in high-risk current and former smokers. Data from European trials are not yet available. In addition to a mortality benefit, lung cancer screening with LDCT also offers a unique opportunity to promote smoking cessation and abstinence and may lead to the diagnoses of treatable chronic diseases, thus decreasing the overall disease burden. The risks of lung cancer screening include overdiagnosis, radiation exposure, and false-positive results leading to unnecessary testing and possible patient anxiety and distress. However, the reduction in lung cancer mortality is a benefit that outweighs the risks and major health organizations currently recommend lung cancer screening using age, smoking history, and quit time criteria derived from the NLST. Although more research is needed to clearly define and understand the application and utility of lung cancer screening in the general population, current data support that lung cancer screening is effective and should be offered to eligible beneficiaries. PMID:27535387

  6. Immunotherapy for lung cancer.

    PubMed

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy. PMID:27101251

  7. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  8. TUBERCULOSIS AND LUNG CANCER.

    PubMed

    Tamura, Atsuhisa

    2016-01-01

    The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept

  9. Staging of Lung Cancer

    MedlinePlus

    ... of N2 means cancer has spread to the middle part of the chest (called the mediastinum). A rating ... so that the surgeon can remove the cancerous part of the lung and/or lymph node ... biopsied are your lungs, bones, and brain. These types of biopsies can be done with ...

  10. Occupational lung cancer

    SciTech Connect

    Coultas, D.B.; Samet, J.M. )

    1992-06-01

    The overall importance of occupational agents as a cause of lung cancer has been a controversial subject since the 1970s. A federal report, released in the late 1970s, projected a surprisingly high burden of occupational lung cancer; for asbestos and four other agents, from 61,000 to 98,000 cases annually were attributed to these agents alone. Many estimates followed, some much more conservative. For example, Doll and Peto estimated that 15% of lung cancer in men and 5% in women could be attributed to occupational exposures. A number of population-based case-control studies also provide relevant estimates. In a recent literature review, Vineis and Simonato cited attributable risk estimates for occupation and lung cancer that ranged from 4% to 40%; for asbestos alone, the estimates ranged from 1% to 5%. These estimates would be expected to vary across locations and over time. Nevertheless, these recent estimates indicate that occupation remains an important cause of lung cancer. Approaches to Prevention. Prevention of lung cancer mortality among workers exposed to agents or industrial processes that cause lung cancer may involve several strategies, including eliminating or reducing exposures, smoking cessation, screening, and chemo-prevention. For example, changes in industrial processes that have eliminated or reduced exposures to chloromethyl ethers and nickel compounds have provided evidence of reduced risk of lung cancer following these changes. Although occupational exposures are important causes of lung cancer, cigarette smoking is the most important preventable cause of lung cancer. For adults, the work site offers an important location to target smoking cessation efforts. In fact, the work site may be the only place to reach many smokers.

  11. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation

    PubMed Central

    Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-01-01

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation. PMID:25714021

  12. Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy.

    PubMed

    Wang, Lei; Fu, Jia-Ning; Wang, Jing-Yu; Jin, Cun-Jing; Ren, Xiao-Yuan; Tan, Qiang; Li, Jing; Yin, Han-Wei; Xiong, Kun; Wang, Tian-Yu; Liu, Xin-Min; Zeng, Hui-Hui

    2011-09-01

    It has been proposed that thioredoxin reductase (TR) is a mediator that allows non-small cell lung cancer (NSCLC) to develop resistance to irradiation; however, little is known regarding the detailed mechanisms of action. Thus, ethaselen {1, 2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)] ethane, BBSKE}, a novel organoselenium TR inhibitor, is currently being investigated in a phase I clinical trial in China. However, its radiosensitizing effect remains unexplored. In this study, we found that the activity of TR increased dramatically in both A549 and H1299 cells after radiation, and moreover, could be inhibited by pretreatment with BBSKE (5 μmol/l). As a TR inhibitor, BBSKE enhanced the efficacy of radiation therapy both in vivo and in vitro without observable toxicity. BBSKE was found to suppress irradiation-induced NF-κB activation dramatically when using A549 cells stably transfected with NF-κB luciferase reporter. These results show the critical role of TR in the radioresistance of NSCLC and suggest that BBSKE is a potentially promising agent for the treatment of patients with NSCLC clinically. PMID:21562407

  13. LXR ligands sensitize EGFR-TKI-resistant human lung cancer cells in vitro by inhibiting Akt activation.

    PubMed

    Wu, Ying; Yu, Dan-dan; Hu, Yong; Cao, Hai-xia; Yu, Shao-rong; Liu, Si-wen; Feng, Ji-feng

    2015-11-27

    Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. Here we investigate the effects of two novel liver x receptor (LXR) ligands (T0901317 or GW3965) on the development of acquired resistance to an EGFR TKI gefitinib. We observed known mechanisms of acquired resistance to EGFR TKI, including the EGFR T790M mutation, MET gene amplification and loss of PTEN in the gefitinib-resistant HCC827-8-1 cells. However, we found expression of MET was lower in HCC827-8-1 cells than in HCC827 cells. T0901317 or GW3965 inhibited Akt activation and sensitized HCC827-8-1 cells to gefitinib-induced cytotoxicity. In contrast, LXR ligands alone had no significant effect on HCC827-8-1 cells. In conclusion, this combined treatment may be of interest for treatment of lung adenocarcinomas harboring EGFR mutations and acquired resistance to gefitinib. PMID:26471306

  14. Lung cancer in Australia.

    PubMed

    McLennan, G; Roder, D M

    1989-02-20

    Lung cancer is the leading cause of death of cancer in Australian men and the third leading cause in Australian women. Efforts are being made to reduce the incidence of this disease by smoking-cessation programmes and improved industrial hygiene, and these measures need to be encouraged strongly by all sectors of the community. On a population basis, insufficient evidence is available to justify screening procedures for the early detection of lung cancer in "at-risk" groups. Cure is possible by surgical resection in early cases. Improvements in therapeutic results with traditional cancer treatments largely have reached a plateau, but a number of newer therapies, and combinations of standard therapies, currently are being evaluated. Of particular interest is concurrent radiotherapy and chemotherapy in localized non-small-cell lung cancer; laser "debulking" in conjunction with radiotherapy in non-small-cell lung cancer, and biological response-modifying agents in non-small-cell and small-cell lung cancer. It is important that data be collected adequately to define epidemiological changes and to evaluate treatment results (including repeat bronchoscopy, to assess local control of tumour), and that the quality of life is recorded and reported in the evaluation process. Finally, phase-III studies in lung-cancer treatments require adequate numbers of subjects to enable meaningful conclusions to be achieve objectives within a reasonable study period. PMID:2469943

  15. Silence of fibronectin 1 increases cisplatin sensitivity of non-small cell lung cancer cell line.

    PubMed

    Gao, Weiwei; Liu, Ying; Qin, Ruiling; Liu, Daijian; Feng, Qingqing

    2016-07-15

    Fibronectin 1 (FN1) is a member of the glycoprotein family which is widely expressed by multiple cell types and involved in cellular adhesion and migration processes. Recent studies have reported that FN1 might have a role in regulating chemoresistance in tumors. However, the regulation of FN1 on cisplatin resistance in non-small cell lung cancer (NSCLC) has not been investigated. The present study aims to illustrate the effect of FN1 on cisplatin resistance in NSCLC and explore potential mechanisms. In the present study, the mRNA and protein expression levels of FN1 were investigated by RT-PCR and Western blot analysis, respectively, and the 50% inhibitory concentration (IC50) value of cisplatin was measured by MTT assay. Apoptotic ratio and migration were determined using an annexin V-FITC/PI detection kit and a Transwell assay, respectively. The interaction between FN1 and integrin-β1 was evaluated by co-immunoprecipitation assay. The protein expression of β-catenin, cyclin D1 and c-myc were tested using Western blot analysis. The results showed that FN1 was more highly expressed in A549/DDP than in A549 cells, and significantly upregulated by cisplatin treatment in H1299 cells. Knockdown of FN1 reduced the IC50 value of cisplatin, inhibited cell migration and promoted apoptosis. FN1 and integrin-β1 protein directly interacted with each other both in A549 and A549/DDP cells. FN1 silencing suppressed the Wnt/β-catenin signaling pathway, and this effect was dampened by integrin-β1-blocking antibody. Taken together, our findings first suggest that FN1 plays a role in the development of cisplatin resistance in NSCLC, possibly by modulation of β-catenin signaling through interaction with integrin-β1 in NSCLC. PMID:27207836

  16. Lung and Bronchus Cancer

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 224,390 % of All New Cancer Cases 13.3% Estimated Deaths in 2016 158,080 % of All Cancer ... of This Cancer : In 2013, there were an estimated 415,707 people living with lung and bronchus ...

  17. A recognition-before-labeling strategy for sensitive detection of lung cancer cells with a quantum dot-aptamer complex.

    PubMed

    Wu, Chunlei; Liu, Jianbo; Zhang, Pengfei; Li, Jing; Ji, Haining; Yang, Xiaohai; Wang, Kemin

    2015-09-01

    A highly specific recognition-before-labeling strategy has been developed for sensitive detection of non-small cell lung cancer A549 cells, by using fluorescent QDs as signal units and DNA aptamers as recognition elements. A QD-aptamer system used for cell imaging and bioanalysis mostly relies on the recognition-after-labeling strategy in which aptamers were firstly labeled with QDs and then the QD-aptamer conjugates as a whole were utilized for specific recognition. Here in our strategy, aptamers were used firstly to recognize target cells, and then fluorescent QDs were sequentially added to bind the aptamers and light the target cells. The proposed recognition-before-labeling strategy didn't require the complex process of QD functionalization, and avoided the possible impact on the aptamer configuration from steric hindrance. Meanwhile, QDs, with strong fluorescence and good photostability, also give this method a high signal-to-background ratio (S/B). The recognition-before-labeling strategy is simple and sensitive, suggesting a new method for in vitro diagnostic assays of cancer cells. PMID:26200911

  18. CD133-Positive Cells from Non-Small Cell Lung Cancer Show Distinct Sensitivity to Cisplatin and Afatinib.

    PubMed

    Alama, Angela; Gangemi, Rosaria; Ferrini, Silvano; Barisione, Gaia; Orengo, Anna Maria; Truini, Mauro; Bello, Maria Giovanna Dal; Grossi, Francesco

    2015-06-01

    The standard of care for advanced non-small cell lung cancer (NSCLC) consists in cisplatin-combination chemotherapy. In patients bearing tumors with activating mutations of the epidermal growth factor receptor (EGFR), the inhibition of the EGFR intracellular tyrosine kinase can induce up to 80 % response rates. However, both therapeutic strategies will eventually lead to recurrent disease due to the development of drug resistance. The identification of rare cancer stem-like cells able to repopulate the tumor, after failure to standard treatment modalities, has led to characterize these cells as potential therapeutic targets. This article will address the role of the CD133/EpCAM stem cell-related markers and explore cell sensitivity to cisplatin and to the EGFR-tyrosine kinase inhibitor, afatinib. Three human NSCLC cell lines, one wild-type (A549) and two harboring EGFR mutations (H1650 and H1975), as well as 20 NSCLC primary cultures, were grown in non-differentiating culture conditions for stem cell enrichment. Flow-cytometry analyses of CD133 and EpCAM and cell sensitivity to cisplatin and afatinib were performed. Moreover, the expression of activated EGFR was assessed by Western blot. The cell lines and primary cultures grown in non-differentiating culture conditions were enriched with CD133/EpCAM-positive cells and were significantly more resistant to cisplatin and more sensitive to afatinib as compared to the differentiated counterpart. In addition, increased EGFR-phosphorylation in non-differentiated cultures was observed. The present findings suggest that afatinib might be beneficial for patients bearing tumors with constitutively activated EGFR, to target chemo-resistant CD133/EpCAM-positive cancer stem cells. PMID:25678473

  19. Lung Cancer Screening Update.

    PubMed

    Ruchalski, Kathleen L; Brown, Kathleen

    2016-07-01

    Since the release of the US Preventive Services Task Force and Centers for Medicare and Medicaid Services recommendations for lung cancer screening, low-dose chest computed tomography screening has moved from the research arena to clinical practice. Lung cancer screening programs must reach beyond image acquisition and interpretation and engage in a multidisciplinary effort of clinical shared decision-making, standardization of imaging and nodule management, smoking cessation, and patient follow-up. Standardization of radiologic reports and nodule management will systematize patient care, provide quality assurance, further reduce harm, and contain health care costs. Although the National Lung Screening Trial results and eligibility criteria of a heavy smoking history are the foundation for the standard guidelines for low-dose chest computed tomography screening in the United States, currently only 27% of patients diagnosed with lung cancer would meet US lung cancer screening recommendations. Current and future efforts must be directed to better delineate those patients who would most benefit from screening and to ensure that the benefits of screening reach all socioeconomic strata and racial and ethnic minorities. Further optimization of lung cancer screening program design and patient eligibility will assure that lung cancer screening benefits will outweigh the potential risks to our patients. PMID:27306387

  20. Highly sensitive single domain antibody-quantum dot conjugates for detection of HER2 biomarker in lung and breast cancer cells.

    PubMed

    Rakovich, Tatsiana Y; Mahfoud, Omar K; Mohamed, Bashir M; Prina-Mello, Adriele; Crosbie-Staunton, Kieran; Van Den Broeck, Tina; De Kimpe, Line; Sukhanova, Alyona; Baty, Daniel; Rakovich, Aliaksandra; Maier, Stefan A; Alves, Frauke; Nauwelaers, Frans; Nabiev, Igor; Chames, Patrick; Volkov, Yuri

    2014-06-24

    Despite the widespread availability of immunohistochemical and other methodologies for screening and early detection of lung and breast cancer biomarkers, diagnosis of the early stage of cancers can be difficult and prone to error. The identification and validation of early biomarkers specific to lung and breast cancers, which would permit the development of more sensitive methods for detection of early disease onset, is urgently needed. In this paper, ultra-small and bright nanoprobes based on quantum dots (QDs) conjugated to single domain anti-HER2 (human epidermal growth factor receptor 2) antibodies (sdAbs) were applied for immunolabeling of breast and lung cancer cell lines, and their performance was compared to that of anti-HER2 monoclonal antibodies conjugated to conventional organic dyes Alexa Fluor 488 and Alexa Fluor 568. The sdAbs-QD conjugates achieved superior staining in a panel of lung cancer cell lines with differential HER2 expression. This shows their outstanding potential for the development of more sensitive assays for early detection of cancer biomarkers. PMID:24873349

  1. Lung Cancer Prevention

    MedlinePlus

    ... from the breakdown of uranium in rocks and soil. It seeps up through the ground, and leaks ... substances increases the risk of lung cancer: Asbestos . Arsenic . Chromium. Nickel. Beryllium. Cadmium . Tar and soot. These ...

  2. Women and Lung Cancer

    MedlinePlus

    ... Horrigan Conners Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, April, ... Lung Cancer in Women: The Differences in Epidemiology, Biology and Treatment Outcomes, Maria Patricia Rivera MD Expert ...

  3. Lycopene and Lung Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  4. Lung Cancer Rates by State

    MedlinePlus

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who ...

  5. Molecular oncology of lung cancer.

    PubMed

    Toyooka, Shinichi; Mitsudomi, Tetsuya; Soh, Junichi; Aokage, Keiju; Yamane, Masaomi; Oto, Takahiro; Kiura, Katsuyuki; Miyoshi, Shinichiro

    2011-08-01

    Progress in genetic engineering has made it possible to elucidate the molecular biological abnormalities in lung cancer. Mutations in KRAS and P53 genes, loss of specific alleles, and DNA methylation of the tumor suppressor genes were the major abnormalities investigated between 1980 and the 2000s. In 2004, mutations in the epidermal growth factor receptor (EGFR) gene that cause oncogene addiction were discovered in non-small-cell lung cancers (NSCLCs), especially in adenocarcinomas. Because they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), a great deal of knowledge has been acquired in regard to both EGFR and other genes in the EGFR family and their downstream genes. Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was discovered in NSCLC; and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers that have this translocation. These discoveries graphically illustrate that molecular biological findings are directly linked to the development of clinical oncology and to improving the survival rates of lung cancer patients. Here, we review the remarkable progress in molecular biological knowledge acquired thus far in regard to lung cancer, especially NSCLC, and the future possibilities. PMID:21850578

  6. Immunotherapy in lung cancer.

    PubMed Central

    Al-Moundhri, M.; O'Brien, M.; Souberbielle, B. E.

    1998-01-01

    More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer. PMID:9703271

  7. Chemoprevention of lung cancer.

    PubMed

    Keith, Robert L

    2009-04-15

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. While avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or inhibit the carcinogenic process and has been successfully applied to common malignancies other than lung. Despite previous studies in lung cancer chemoprevention failing to identify effective agents, our ability to determine higher risk populations and the understanding of lung tumor and pre-malignant biology continues to advance. Additional biomarkers of risk continue to be investigated and validated. The World Health Organization/International Association for the Study of Lung Cancer classification for lung cancer now recognizes distinct histologic lesions that can be reproducibly graded as precursors of non-small cell lung cancer. For example, carcinogenesis in the bronchial epithelium starts with normal epithelium and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ to invasive squamous cell cancer. Similar precursor lesions exist for adenocarcinoma, and these pre-malignant lesions are targeted by chemopreventive agents in current and future trials. At this time, chemopreventive agents can only be recommended as part of well-designed clinical trials, and multiple trials are currently in progress and additional trials are in the planning stages. This review will discuss the principles of chemoprevention, summarize the completed trials, and discuss ongoing and potential future trials with a focus on targeted pathways. PMID:19349487

  8. [Pathology of lung cancer].

    PubMed

    Theegarten, D; Hager, T

    2016-09-01

    Lung cancer is the leading cause of cancer death in men and the second most frequent cause in women. The pathology of lung tumors is of special relevance concerning therapy and prognosis and current classification systems have to be taken into consideration. The results of molecular tissue subtyping allow further classification and therapeutic options. The histological entities are mainly associated with typical X‑ray morphological features. PMID:27495784

  9. Tandem mass spectrometry-based newborn screening strategy could be used to facilitate rapid and sensitive lung cancer diagnosis

    PubMed Central

    Huang, Ting; Cao, Yunfeng; Zeng, Jia; Dong, Jun; Sun, Xiaoyu; Chen, Jianxing; Gao, Peng

    2016-01-01

    Objective Newborn screening (NBS) helps in the early detection of inborn errors of metabolism (IEM). The most effective NBS strategy prevailing in clinics is tandem mass spectrometry (MS/MS) analysis using dried blood spot (DBS) samples. Taking lung cancer (LC) as an example, this study tried to explore if this technique could be of any assistance for the discovery of tumor metabolite markers. Materials and methods Twenty-six acylcarnitines and 23 amino acids, which are commonly used in IEM screening, were quantified using DBS samples from 222 LC patients, 118 benign lung disease (LD) patients, and 96 healthy volunteers (CONT). Forty-four calculated ratios based on the abovementioned metabolites were also included using MS/MS quantification results. Results This pilot study led to the findings of 65 significantly changed amino acids, acylcarnitines, and some of their ratios for the LC, LD, and CONT groups. Among the differential parameters, 12 items showed reverse changing trends between the LC and LD groups compared to the CONT group. Regression analysis demonstrated that six of them – Arg, Pro, C10:1, Arg/Orn, Cit/Arg, and C5-OH/C0 – could be used to diagnose LC with a sensitivity of 91.3% and a specificity of 92.7%. Conclusion This study demonstrated the DBS-based MS/MS strategy was a promising tool for the discovery of tumor metabolite markers. Remarkably, this MS/MS analysis could be finished in several minutes, implying that it was a proper measure complementary to the traditional serum protein biomarker quantitation strategy for cancerous disease diagnosis and screening purposes. PMID:27217771

  10. [Chemoprevention of lung cancer].

    PubMed

    Tsuchida, Takaaki; Saito, Makoto; Honda, Hidetoshi; Hirata, Takeshi; Kato, Harubumi

    2003-02-01

    Since a high concentration of beta-carotene in blood reduces the risk of lung cancer, a large-scale intervention examination containing beta-carotene was conducted, mainly by the National Cancer Institute. The results showed that the risk of lung cancer increased with administration of beta-carotene. This result demonstrates that continuation of smoking is an important factor in the increased risk, and not smoking is confirmed to be the most important prevention method. The authors examined the treatment effect of raising the concentration of folic acid and vitamin B12 in blood on bronchial dysplasia as a pre-cancerous lesion. A significant medical treatment effect was see in the folic acid and vitamin B12 medication groups, which seems promising for the chemoprevention of lung cancer. PMID:12610863

  11. Radon and lung cancer.

    PubMed

    Sethi, Tarsheen K; El-Ghamry, Moataz N; Kloecker, Goetz H

    2012-03-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Radon exposure is the second leading cause of lung cancer, following tobacco smoke. Radon is not only an independent risk factor; it also increases the risk of lung cancer in smokers. Numerous cohort, case-control, and experimental studies have established the carcinogenic potential of radon. The possibility of radon having a causative effect on other cancers has been explored but not yet proven. One of the postulated mechanisms of carcinogenesis is DNA damage by alpha particles mediated by the production of reactive oxygen species. The latter are also thought to constitute one of the common mechanisms underlying the synergistic effect of radon and tobacco smoke. With an estimated 21,000 lung cancer deaths attributable to radon in the United States annually, the need for radon mitigation is well acknowledged. The Environmental Protection Agency (EPA) has established an indoor limit of 4 picocuries (pCi)/L, and various methods are available for indoor radon reduction when testing shows higher levels. Radon mitigation should accompany smoking cessation measures in lung cancer prevention efforts. PMID:22402423

  12. Tankyrase Inhibitor Sensitizes Lung Cancer Cells to Endothelial Growth Factor Receptor (EGFR) Inhibition via Stabilizing Angiomotins and Inhibiting YAP Signaling.

    PubMed

    Wang, Hui; Lu, Bo; Castillo, Johnny; Zhang, Yue; Yang, Zinger; McAllister, Gregory; Lindeman, Alicia; Reece-Hoyes, John; Tallarico, John; Russ, Carsten; Hoffman, Greg; Xu, Wenqing; Schirle, Markus; Cong, Feng

    2016-07-15

    YAP signaling pathway plays critical roles in tissue homeostasis, and aberrant activation of YAP signaling has been implicated in cancers. To identify tractable targets of YAP pathway, we have performed a pathway-based pooled CRISPR screen and identified tankyrase and its associated E3 ligase RNF146 as positive regulators of YAP signaling. Genetic ablation or pharmacological inhibition of tankyrase prominently suppresses YAP activity and YAP target gene expression. Using a proteomic approach, we have identified angiomotin family proteins, which are known negative regulators of YAP signaling, as novel tankyrase substrates. Inhibition of tankyrase or depletion of RNF146 stabilizes angiomotins. Angiomotins physically interact with tankyrase through a highly conserved motif at their N terminus, and mutation of this motif leads to their stabilization. Tankyrase inhibitor-induced stabilization of angiomotins reduces YAP nuclear translocation and decreases downstream YAP signaling. We have further shown that knock-out of YAP sensitizes non-small cell lung cancer to EGFR inhibitor Erlotinib. Tankyrase inhibitor, but not porcupine inhibitor, which blocks Wnt secretion, enhances growth inhibitory activity of Erlotinib. This activity is mediated by YAP inhibition and not Wnt/β-catenin inhibition. Our data suggest that tankyrase inhibition could serve as a novel strategy to suppress YAP signaling for combinatorial targeted therapy. PMID:27231341

  13. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  14. Lung cancer chemoprevention.

    PubMed

    Keith, Robert L

    2012-05-01

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfully applied to common malignancies other than lung (including recent reports on the prevention of breast cancer in high-risk individuals). Despite previous studies in lung cancer chemoprevention failing to identify effective agents, our ability to define the highest-risk populations and the understanding of lung tumor and premalignant biology continue to make advances. Squamous cell carcinogenesis in the bronchial epithelium starts with normal epithelium and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ to invasive cancer. Precursor lesions also have been identified for adenocarcinoma, and these premalignant lesions are targeted by chemopreventive agents in current and future trials. Chemopreventive agents can currently only be recommended as part of well-designed clinical trials, and multiple trials have recently been completed or are enrolling subjects. PMID:22550242

  15. LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

    PubMed Central

    Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

    2009-01-01

    LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies. PMID:19165201

  16. Lung cancer screening

    PubMed Central

    Pastorino, U

    2010-01-01

    Lung cancer is the primary cause of cancer mortality in developed countries. First diagnosis only when disease has already reached the metastatic phase is the main reason for failure in treatment. To this regard, although low-dose spiral computed tomography (CT) has proven to be effective in the early detection of lung cancer (providing both higher resectability and higher long-term survival rates), the capacity of annual CT screening to reduce lung cancer mortality in heavy smokers has yet to be demonstrated. Numerous ongoing large-scale randomised trials are under way in high-risk individuals with different study designs. The initial results should be available within the next 2 years. PMID:20424610

  17. Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy

    PubMed Central

    Ma, Wei; Ma, Chao-nan; Zhou, Nan-nan; Li, Xian-dong; Zhang, Yi-jie

    2016-01-01

    MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells’ sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC. PMID:27530148

  18. Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

    PubMed

    Ma, Wei; Ma, Chao-Nan; Zhou, Nan-Nan; Li, Xian-Dong; Zhang, Yi-Jie

    2016-01-01

    MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC. PMID:27530148

  19. MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

    PubMed

    Chattopadhyay, S; Machado-Pinilla, R; Manguan-García, C; Belda-Iniesta, C; Moratilla, C; Cejas, P; Fresno-Vara, J A; de Castro-Carpeño, J; Casado, E; Nistal, M; Gonzalez-Barón, M; Perona, R

    2006-06-01

    Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK and p38 than in the parental cells, and this correlated with a 10-fold increase in sensitivity to cisplatin. A similar response was also observed in H-460 and H-23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover, expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460 cell viability response to cisplatin. Tumors induced by H-460 cells expressing MKP1 siRNA grew slower in nu(-)/nu(-) mice and showed more susceptibility to cisplatin than parental cells, and resulted in an impaired growth of the tumor in mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell line resulted in further resistance to cisplatin. Overall, the results showed that inhibition of MKP1 expression contributes to a slow down in cell growth in mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can be an attractive target in sensitizing cells to cisplatin to increase the effectiveness of the drug in treating NSCLC. PMID:16462770

  20. miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells

    PubMed Central

    NISHIJIMA, NOBUHIKO; SEIKE, MASAHIRO; SOENO, CHIE; CHIBA, MIKA; MIYANAGA, AKIHIKO; NORO, RINTARO; SUGANO, TEPPEI; MATSUMOTO, MASARU; KUBOTA, KAORU; GEMMA, AKIHIKO

    2016-01-01

    Nintedanib (BIBF1120) is a multi-targeted angiokinase inhibitor and has been evaluated in idiopathic pulmonary fibrosis and advanced non-small cell lung cancer (NSCLC) patients in clinical studies. In the present study, we evaluated the antitumor effects of nintedanib in 16 NSCLC cell lines and tried to identify microRNA (miRNA) associated with sensitivity to nintedanib. No correlations between FGFR, PDGFR and VEGFR family activation and sensitivity to nintedanib were found. The difference in miRNA expression profiles between 5 nintedanib-sensitive and 5 nintedanib-resistant cell lines was evaluated by miRNA array and quantitative RT-PCR analysis (qRT-PCR). Expression of miR-200b, miR-200a and miR-141 belonging to the miR-200 family which contributes to epithelial-mesenchymal transition (EMT), was significantly lower in 5 nintedanib-resistant than in 5 nintedanib-sensitive cell lines. We examined the protein expression of EMT markers in these 10 NSCLC cell lines. E-cadherin expression was lower, and vimentin and ZEB1 expression were higher in 5 nintedanib-resistant cell lines. PC-1 was the most sensitive of the NSCLC cell lines to nintedanib. We established nintedanib-resistant PC-1 cells (PC-1R) by the stepwise method. PC-1R cells also showed decreased expression of miR-200b, miR-141 and miR-429 and increased expression of ZEB1 and ZEB2. We confirmed that induction of miR-200b or miR-141 enhanced sensitivity to nintedanib in nintedanib-resistant A549 and PC1-R cells. In addition, we evaluated the response to gefitinib in combination with nintedanib after TGF-β1 exposure of A549 cells. Nintedanib was able to reverse TGF-β1-induced EMT and resistance to gefitinib caused by miR-200b and miR-141 upregulation and ZEB1 downregulation. These results suggested that the miR-200/ZEB axis might be predictive biomarkers for sensitivity to nintedanib in NSCLC cells. Furthermore, nintedanib combined with gefitinib might be a novel therapeutic strategy for NSCLC cells with EMT

  1. The ALCHEMIST Lung Cancer Trial

    Cancer.gov

    A collection of material about the ALCHEMIST lung cancer trial that will examine tumor tissue from patients with early-stage, completely resected lung cancer for gene mutations in the EGFR and ALK genes, and a

  2. Screening for lung cancer.

    PubMed Central

    Carter, D.

    1981-01-01

    The survival from bronchogenic carcinoma is highly dependent upon stage at the time of treatment. This is particularly true for squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, but holds true for small cell carcinoma as well. The problem presented to the medical profession has been to find a practical means of detecting lung cancer while it is still at an early stage. Three studies in progress have indicated that a larger proportion of the patients may be found to have early stage lung cancer when screened with a combination of chest X-rays and sputum cytology. However, the detection of these early stage cases has not yet been translated into an improvement in the overall mortality rate from lung cancer. PMID:6278787

  3. [Smoking and lung cancer].

    PubMed

    Postmus, P E

    1999-11-01

    Since fifty years it is clear now that smoking of tobacco products is responsible for the lung cancer epidemic that is currently in progress worldwide. Although in the Western world a small decrease of lung cancer in males is found, the number of female patients is steadily increasing. Changes in tobacco production have resulted in exposition of smokers to other carcinogens. This is probably the cause of the change in the histological pattern with an increase of adenocarcinoma and stabilisation of squamous cell lung cancer. Despite the bad prognosis there is some hope that with improvement of early detection methods more patients can be cured. However, for a real change it is necessary to discourage smoking by all means. PMID:11930407

  4. Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFα- and NK cytotoxicity

    SciTech Connect

    Kulesza, Dorota W.; Carré, Thibault; Chouaib, Salem; Kaminska, Bozena

    2013-02-15

    Transcription factor STAT3 (Signal Transducers and Activators of Transcription 3) is persistently active in human tumors and may contribute to tumor progression. Inhibition of STAT3 expression/activity could be a good strategy to modulate tumor cell survival and responses to cancer chemotherapeutics or immune cytotoxicity. We silenced STAT3 expression in human A549 lung cancer cells to elucidate its role in cell survival and resistance to chemotherapeutics, TNFα and natural killer (NK)-mediated cytotoxicity. We demonstrate that STAT3 is not essential for basal survival and proliferation of A549 cancer cells. Stable silencing of STAT3 expression sensitized A549 cells to DNA damaging chemotherapeutics doxorubicin and cisplatin in a p53-independent manner. Sensitization to DNA damage-inducing chemotherapeutics could be due to down-regulation of the Bcl-xL expression in STAT3 depleted cells. In contrast, knockdown of STAT3 in cancer cells did not modulate responses to TNFα and NK-mediated cytotoxicity. We found that STAT3 depletion increased the NFκB activity likely providing the compensatory, pro-survival signal. The treatment with TNFα, but not doxorubicin, enhanced this effect. We conclude that STAT3 is not crucial for the control of basal cell proliferation and survival of lung carcinoma cells but modulates susceptibility to DNA damaging chemotherapeutics by regulation of intrinsic pro-survival pathways. - Highlights: ► STAT3 silencing is negligent for basal lung cancer cell viability and proliferation. ► STAT3 depletion sensitizes lung cancer cells to DNA damaging chemotherapeutics. ► STAT3 depletion has no effect on susceptibility to extrinsic apoptosis inducers. ► Increased pro-survival NFκB activity may compensate for STAT3 depletion.

  5. 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

  6. MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer

    PubMed Central

    Ge, Xin; Jiang, Cheng-Fei; Shi, Zhu-Mei; Li, Dong-Mei; Liu, Wei-Tao; Yu, Xiaobo; Shu, Yong-Qian

    2016-01-01

    Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. In this study, we explored miR-137's role in the chemosensitivity of lung cancer. We found that the expression level of miR-137 is down-regulated in the human lung cancer tissues and the resistant cells strains: A549/paclitaxel(A549/PTX) and A549/cisplatin (A549/CDDP) when compared with lung cancer A549 cells. Moreover, we found that overe-expression of miR-137 inhibited cell proliferation, migration, cell survival and arrest the cell cycle in G1 phase in A549/PTX and A549/CDDP. Furthermore, Repression of miR-137 significantly promoted cell growth, migration, cell survival and cell cycle G1/S transition in A549 cells. We further demonstrated that the tumor suppressive role of miR-137 was mediated by negatively regulating Nuclear casein kinase and cyclin-dependent kinase substrate1(NUCKS1) protein expression. Importantly, miR-137 inhibits A549/PTX, A549/CDDP growth and angiogenesis in vivo. Our study is the first to identify the tumor suppressive role of over-expressed miR-137 in chemosensitivity. Identification of a novel miRNA-mediated pathway that regulates chemosensitivity in lung cancer will facilitate the development of novel therapeutic strategies in the future. PMID:26989074

  7. siRNA delivered by EGFR-specific scFv sensitizes EGFR-TKI-resistant human lung cancer cells.

    PubMed

    Lu, Yuan; Liu, Li; Wang, Yuan; Li, Fakai; Zhang, Jian; Ye, Mingxiang; Zhao, Hu; Zhang, Xiang; Zhang, Mi; Zhao, Jing; Yan, Bo; Yang, Angang; Feng, Huasong; Zhang, Rui; Ren, Xinling

    2016-01-01

    The overexpression of epidermal growth factor receptor (EGFR) is closely associated with a poor outcome in non-small cell lung cancer (NSCLC), and EGFR is an ideal biomarker for the targeted therapy of NSCLC. Although patients with EGFR-activating mutations respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs), they eventually acquire resistance, which typically results from a secondary EGFR mutation or the activation of other signaling pathways. Novel approaches to overcome or prevent EGFR-TKI resistance are clinically important. In this study, we developed an EGFR-scFv-arginine nonamer peptide fusion protein, s-9R, as an siRNA carrier. Here, we show that s-9R effectively and specifically delivers EGFR-siRNAs, KRAS-siRNA and MET-siRNA into NSCLC cells and silences the expression of target genes. The sensitivity of NSCLC cells to gefitinib was restored after treatment with the s-9R/siRNA complex, and the apoptosis rates of the treated cells were significantly higher than those of the control groups. Furthermore, the co-administration of s-9R/siRNA and gefitinib successfully suppressed the progression of H1975 xenograft tumors and extended the life span of tumor-bearing nude mice. Collectively, the results of this study provide not only a new scFv derivative for delivering siRNA into EGFR-overexpressing, TKI-resistant NSCLC cells but also a novel method for overcoming TKI resistance. PMID:26524539

  8. Radiotherapy for lung cancer

    SciTech Connect

    Bleehen, N.M.; Cox, J.D.

    1985-05-01

    The role of radiation therapy in the management of lung cancer was reviewed at a workshop held in Cambridge, England, in June 1984. It was concluded that there was a continuing role for radiation therapy in the primary management of small cell lung cancer, including the loco-regional treatment for patients with limited disease. Radical radiotherapy for patients with non-small cell carcinoma could be curative for a proportion of patients with limited disease. Careful planning and quality control was essential. Palliative radiotherapy provided useful treatment for many other patients. Other related aspects of treatment are also presented.

  9. Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation

    PubMed Central

    Zhang, Weiqing; Liu, Jin; Hu, Enze; Zhang, Jinsan; Li, Mingying; Wang, Junhao; Kong, Fei; Li, Yunguang; Wang, Rui; Tan, Xiaohua; He, Dacheng; Xiao, Xueyuan

    2016-01-01

    Our previous study revealed that knockdown of CABYR-a/b increases the chemosensitivity of lung cancer cells through inactivation of Akt. Here, we demonstrated that depletion of CABYR-a/b significantly increased DR5 expression and sensitized lung cancer cells to TRAIL-induced apoptosis in vitro and/or in vivo. Importantly, treatment with AD5-10, a DR5-specific agonistic monoclonal antibody, was able to mimic TRAIL-induced apoptosis in CABYR-a/b-silenced cells. Strikingly, we identified that depletion of CABYR-a/b not only increased the expressions of p73 and DR5 but also decreased the phosphorylation of YAP S127. Loss- or gain-of-function studies of YAP and p73 revealed that double deletions of YAP and p73 effectively decreased the expression of DR5 and abolished TRAIL-induced apoptosis in CABYR-a/b knockdown cells. Conversely, the co-overexpression of YAP and p73 promoted the expression of DR5 and sensitized cells to TRAIL-induced apoptosis. Taken together, our results demonstrate that depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation. PMID:26843620

  10. Lung Cancer – Vaccines

    PubMed Central

    Kelly, Ronan J.; Giaccone, Giuseppe

    2011-01-01

    In lung cancer, early attempts to modulate the immune system via vaccine based therapeutics have to date, been unsuccessful. An improved understanding of tumor immunology has facilitated the production of more sophisticated lung cancer vaccines. It is anticipated, that it will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors employ. Other issues to overcome include optimal patient selection, which adjuvant agent to use and how to adequately monitor for an immunological response. This review discusses the most promising vaccination strategies for non small cell lung cancer including the allogeneic tumor cell vaccine belagenpumatucel-L, which is a mixture of 4 allogeneic non small cell lung cancer cell lines genetically modified to secrete an antisense oligonucleotide to TGF-β2 and three other target protein-specific vaccines designed to induce responses against melanoma-associated antigen A3 (MAGE-A3), mucin 1 (MUC1) and epidermal growth factor (EGF). PMID:21952280

  11. Nonsmall cell lung cancer.

    PubMed

    Sculier, Jean-Paul

    2013-03-01

    The objective of this review is to report the Clinical Year in Review proceedings in the field of nonsmall cell lung cancer that were presented at the 2012 European Respiratory Society Congress in Vienna, Austria. Various topics were reviewed, including epidemiology, screening, diagnosis, treatment, prognosis, and palliative and end of life care. PMID:23457162

  12. Update in Lung Cancer 2014.

    PubMed

    Spira, Avrum; Halmos, Balazs; Powell, Charles A

    2015-08-01

    In the past 2 years, lung cancer research and clinical care have advanced significantly. Advancements in the field have improved outcomes and promise to lead to further reductions in deaths from lung cancer, the leading cause of cancer death worldwide. These advances include identification of new molecular targets for personalized targeted therapy, validation of molecular signatures of lung cancer risk in smokers, progress in lung tumor immunotherapy, and implementation of population-based lung cancer screening with chest computed tomography in the United States. In this review, we highlight recent research in these areas and challenges for the future. PMID:26230235

  13. Silicon photonic crystal microarrays for high throughput label-free detection of lung cancer cell line lysates with sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Gemmill, Robert M.; Chen, Ray T.

    2013-03-01

    Detection of biomolecules on microarrays based on label-free on-chip optical biosensors is very attractive since this format avoids complex chemistries caused by steric hindrance of labels. Application areas include the detection of cancers and allergens, and food-borne pathogens to name a few. We have demonstrated photonic crystal microcavity biosensors with high sensitivity down to 1pM concentrations (67pg/ml). High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the photonic crystal microcavity resonance mode. Resonances with high quality factor Q~26,760 in liquid ambient, coupled with larger optical mode volumes allowed enhanced interaction with the analyte biomolecules which resulted in sensitivities down to 10 cells per micro-liter to lung cancer cell lysates. The specificity of detection was ensured by multiplexed detections from multiple photonic crystal microcavities arrayed on the arms of a multimode interference power splitter. Specific binding interactions and control experiments were performed simultaneously at the same instant of time with the same 60 microliter sample volume. Specificity is further ensured by sandwich assay methods in the multiplexed experiment. Sandwich assay based amplification increased the sensitivity further resulting in the detection of lung cancer cell lysates down to concentrations of 2 cells per micro-liter. The miniaturization enabled by photonic crystal biosensors coupled with waveguide interconnected layout thus offers the potential of high throughput proteomics with high sensitivity and specificity.

  14. World conference on lung cancer.

    PubMed

    Felip, Enriqueta; Rosell, Rafael

    2003-12-01

    Lung cancer is the most frequent cause of cancer death. Improving this dismal outcome requires cooperation among several specialists. The 10th World Conference on Lung Cancer was held in Vancouver, Canada last month. The meeting was organised on behalf of the International Association for the Study of Lung Cancer (IASLC) and the British Columbia Cancer Agency. This Conference was chaired by Nevin Murray and the scientific sessions took place 10 - 14 August, with > 3000 participating lung cancer experts. The Vancouver programme included > 140 invited speakers throughout the 'meet the professor', plenary and interactive sessions, as well as 300 oral and 500 poster presentations. PMID:14640956

  15. Treatment Option Overview (Small Cell Lung Cancer)

    MedlinePlus

    ... 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 Points ...

  16. Stages of Small Cell Lung Cancer

    MedlinePlus

    ... 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 Points ...

  17. SULF2 Methylation is Prognostic for Lung Cancer Survival and Increases Sensitivity to Topoisomerase-I inhibitors via Induction of ISG15

    PubMed Central

    Tessema, Mathewos; Yingling, Christin M.; Thomas, Cynthia L.; Klinge, Donna M.; Bernauer, Amanda M.; Liu, Yushi; Dacic, Sanja; Siegfried, Jill M.; Dahlberg, Suzanne E.; Schiller, Joan H.; Belinsky, Steven A.

    2011-01-01

    The heparan sulfate 6-O-endosulfatase (SULF2) promotes growth and metastasis of solid tumors. We recently identified that cytosine methylation of the SULF2 promoter is associated with better survival of resected lung adenocarcinoma patients and now also demonstrate a marginal improvement in survival of advanced non-small cell lung cancer (NSCLC) patients receiving standard chemotherapy (HR = 0.63, p = 0.07). Subsequent studies focused on investigating the effect of methylation on SULF2 expression and its genome-wide impact. The genes and pathways modulated by epigenetic inactivation of SULF2 and the effects on sensitivity to chemotherapy were characterized in vitro and in vivo. Silencing SULF2 through siRNA or methylation primarily increased expression of interferon-inducible genes including ISG15, a marker for increased sensitivity to topoisomerase-1 inhibitors such as camptothecin. NSCLC cell lines with methylated SULF2 (SULF2M) express 60-fold higher ISG15 compared to SULF2 unmethylated (SULF2U) NSCLC cell lines and normal human bronchial epithelial cells. In vitro, SULF2M and high ISG15 (ISG15H) expressing NSCLC cell lines were 134-fold more sensitive to camptothecin than SULF2U and low ISG15 (ISG15L) expressing cell lines. Topotecan, a soluble analogue of camptothecin and FDA approved anti-cancer drug, dramatically arrested the growth of SULF2M-ISG15H, but not SULF2U-ISG15L lung tumors in nude mice (p < 0.002). Similarly, high ISG15 expression that is comparable to the topotecan sensitive NSCLC cell lines was found in tumors from 25% of NSCLC patients compared to normal lung indicating a potential to identify and target the most sensitive NSCLC subpopulation for personalized topotecan therapy. PMID:22158045

  18. Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection.

    PubMed

    Hassan, Mohamed K; Watari, Hidemichi; Salah-Eldin, Alaa-Eldin; Sultan, Ahmed S; Mohamed, Zainab; Fujioka, Yoichiro; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer. PMID:24728004

  19. SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP dependent but TNFα independent manner

    PubMed Central

    Greer, Rachel M.; Peyton, Michael; Larsen, Jill E.; Girard, Luc; Xie, Yang; Gazdar, Adi; Harran, Patrick; Wang, Lai; Brekken, Rolf A.; Wang, Xiaodong; Minna, John D.

    2012-01-01

    Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are inhibited by the second mitocondrial activator of caspases (SMAC). Previously, a small subset of TNFα-expressing non-small cell lung cancers (NSCLCs) was found to be sensitive to SMAC mimetics alone. In this study we determined if a SMAC mimetic (JP1201) could sensitize non-responsive NSCLC cell lines to standard chemotherapy. We found that JP1201 sensitized NSCLCs to doxorubicin, erlotinib, gemcitabine, paclitaxel, vinorelbine, and the combination of carboplatin with paclitaxel in a synergistic manner at clinically achievable drug concentrations. Sensitization did not occur with platinum alone. Furthermore, sensitization was specific for tumor compared to normal lung epithelial cells, increased in NSCLCs harvested after chemotherapy treatment, and did not induce TNFα secretion. Sensitization also was enhanced in vivo with increased tumor inhibition and increased survival of mice carrying xenografts. These effects were accompanied by caspase 3, 4, and 9 activation, indicating that both mitochondrial and ER stress-induced apoptotic pathways are activated by the combination of vinorelbine and JP1201. Chemotherapies that induce cell death through the mitochondrial pathway required only inhibition of XIAP for sensitization, while chemotherapies that induce cell death through multiple apoptotic pathways required inhibition of cIAP1, cIAP2, and XIAP. Therefore, the data suggest that IAP-targeted therapy using a SMAC mimetic provides a new therapeutic strategy for synergistic sensitization of NSCLCs to standard chemotherapy agents, which appears to occur independently of TNFα secretion. PMID:22049529

  20. Lung Cancer in Never Smokers.

    PubMed

    Rivera, Gabriel Alberto; Wakelee, Heather

    2016-01-01

    Lung cancer is predominantly associated with cigarette smoking; however, a substantial minority of patients with the disease have never smoked. In the US it is estimated there are 17,000-26,000 annual deaths from lung cancer in never smokers, which as a separate entity would be the seventh leading cause of cancer mortality. Controversy surrounds the question of whether or not the incidence of lung cancer in never-smokers is increasing, with more data to support this observation in Asia. There are several factors associated with an increased risk of developing lung cancer in never smokers including second hand smoke, indoor air pollution, occupational exposures, and genetic susceptibility among others. Adenocarcinoma is the most common histology of lung cancer in never smokers and in comparison to lung cancer in smokers appears less complex with a higher likelihood to have targetable driver mutations. PMID:26667338

  1. Screening for lung cancer.

    PubMed

    Miettinen, O S

    2000-05-01

    Screening for lung cancer serves to prevent deaths from this disease insofar as earlier resections are associated with higher rates of cure. There is good reason to believe that this is the case: in stage I, the 5-year survival rate with resection is 70%, whereas without resection the corresponding rate is only 10%. Before this evidence emerged, various authoritative organizations and agencies in North America advised against screening for lung cancer on the grounds of the results of several RCTs. As for CXR, I argue that the study results are consistent with up to 40% reduction in the fatality rate. Moreover, modern helical CT screening provides for detecting much smaller tumors than were detected in those studies. It is time to revoke the conclusion that screening for lung cancer does not serve to prevent deaths from this disease, and to quantify the usefulness of CT screening in particular. As for the requisite research, the prevailing orthodoxy has it that RCTs are to be used, but I argue that more meaningful results are obtainable, more rapidly and much less expensively, by the use of noncomparative (and hence unrandomized) studies. PMID:10855255

  2. Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.

    PubMed

    Granja, Sara; Marchiq, Ibtissam; Le Floch, Renaud; Moura, Conceição Souto; Baltazar, Fátima; Pouysségur, Jacques

    2015-03-30

    Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via 'Zinc-Finger Nucleases'. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for MCT1 and MCT4, respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor metformin/phenformin in normoxia. However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice. Our results demonstrate that inhibiting glycolysis by targeting lactic acid export sensitizes NSCLC to phenformin. PMID:25894929

  3. Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer.

    PubMed

    Feng, Jianguo; Zhang, Shirong; Wu, Kan; Wang, Bing; Wong, Jeffrey Y C; Jiang, Hong; Xu, Rujun; Ying, Lisha; Huang, Haixiu; Zheng, Xiaoliang; Chen, Xufeng; Ma, Shenglin

    2016-05-01

    Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on cancer cell invasion. Our results showed that SAHA and cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in cisplatin-treated primary NSCLC tumor tissues in response to IR. SAHA combined with cisplatin also significantly increased inhibitory effect of radiotherapy on tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell-like cancer cell population, reduce tumorigenicity, and decrease invasiveness of human lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a chemoradiotherapy regimen for NSCLC. Mol Cancer Ther; 15(5); 842-53. ©2016 AACR. PMID:26839308

  4. Controversies in Lung Cancer Screening.

    PubMed

    Gill, Ritu R; Jaklitsch, Michael T; Jacobson, Francine L

    2016-02-01

    There remains an extensive debate over lung cancer screening, with lobbying for and against screening for very compelling reasons. The National Lung Screening Trial, International Early Lung Cancer Program, and other major screening studies favor screening with low-dose CT scans and have shown a reduction in lung cancer-specific mortality. The increasing incidence of lung cancer and the dismal survival rate for advanced disease despite improved multimodality therapy have sparked an interest in the implementation of national lung cancer screening. Concerns over imaging workflow, radiation dose, management of small nodules, overdiagnosis bias, lead-time and length-time bias, emerging new technologies, and cost-effectiveness continue to be debated. The authors address each of these issues as they relate to radiologic practice. PMID:26846531

  5. Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine

    PubMed Central

    Yue, Haiying; Huang, Dongning; Qin, Li; Zheng, Zhiyong; Hua, Li; Wang, Guodong; Huang, Jian

    2016-01-01

    Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells. PMID:27556038

  6. Drugs Approved for Lung Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog, EB 1089

    PubMed Central

    Sharma, Khushboo; Goehe, Rachel W; Di, Xu; Hicks, Mark Anthony; Torti, Suzy V; Torti, Frank M; Harada, Hisashi; Gewirtz, David A.

    2015-01-01

    The standard of care for unresectable lung cancer is chemoradiation. However, therapeutic options are limited and patients are rarely cured. We have previously shown that vitamin D and vitamin D analogs such as EB 1089 can enhance the response to radiation in breast cancer through the promotion of a cytotoxic form of autophagy. In A549 and H460 non-small cell lung cancer (NSCLC) cells, 1,25-D3 (the hormonally active form of vitamin D) and EB 1089 prolonged the growth arrest induced by radiation alone and suppressed proliferative recovery, which translated to a significant reduction in clonogenic survival. In H838 or H358 NSCLC cells, which lack VDR/vitamin D receptor or functional TP53, respectively, 1,25-D3 failed to modify the extent of radiation-induced growth arrest or suppress proliferative recovery post-irradiation. Sensitization to radiation in H1299 NSCLC cells was evident only when TP53 was induced in otherwise tp53-null H1299 NSCLC cells. Sensitization was not associated with increased DNA damage, decreased DNA repair or an increase in apoptosis, necrosis, or senescence. Instead sensitization appeared to be a consequence of the conversion of the cytoprotective autophagy induced by radiation alone to a novel cytostatic form of autophagy by the combination of 1,25-D3 or EB 1089 with radiation. While both pharmacological and genetic suppression of autophagy or inhibition of AMPK phosphorylation sensitized the NSCLC cells to radiation alone, inhibition of the cytostatic autophagy induced by the combination treatment reversed sensitization. Evidence for selectivity was provided by lack of radiosensitization in normal human bronchial cells and cardiomyocytes. Taken together, these studies have identified a unique cytostatic function of autophagy that appears to be mediated by VDR, TP53, and possibly AMPK in the promotion of an enhanced response to radiation by 1,25-D3 and EB 1089 in NSCLC. PMID:25629933

  8. 3'-Phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes non-small cell lung cancer cells to DNA damaging agents.

    PubMed

    Leung, Ada W Y; Dragowska, Wieslawa H; Ricaurte, Daniel; Kwok, Brian; Mathew, Veena; Roosendaal, Jeroen; Ahluwalia, Amith; Warburton, Corinna; Laskin, Janessa J; Stirling, Peter C; Qadir, Mohammed A; Bally, Marcel B

    2015-07-10

    Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known driver mutation is platinum-based chemotherapy, which has a response rate of only 30-33%. Through an siRNA screen, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces clonogenicity of NSCLC cells by 98.7% (p < 0.001), increases DNA damage, and induces G1/S phase cell cycle arrest and apoptosis. PAPSS1 silencing also sensitized NSCLC cells to other DNA crosslinking agents, radiation, and topoisomerase I inhibitors, but not topoisomerase II inhibitors. Chemo-sensitization was not observed in normal epithelial cells. Knocking out the PAPSS1 homolog did not sensitize yeast to cisplatin, suggesting that sulfate bioavailability for amino acid synthesis is not the cause of sensitization to DNA damaging agents. Rather, sensitization may be due to sulfation reactions involved in blocking the action of DNA damaging agents, facilitating DNA repair, promoting cancer cell survival under therapeutic stress or reducing the bioavailability of DNA damaging agents. Our study demonstrates for the first time that PAPSS1 could be targeted to improve the activity of multiple anticancer agents used to treat NSCLC. PMID:26220590

  9. 3′-Phosphoadenosine 5′-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes non-small cell lung cancer cells to DNA damaging agents

    PubMed Central

    Leung, Ada W. Y.; Dragowska, Wieslawa H.; Ricaurte, Daniel; Kwok, Brian; Mathew, Veena; Roosendaal, Jeroen; Ahluwalia, Amith; Warburton, Corinna; Laskin, Janessa J.; Stirling, Peter C.; Qadir, Mohammed A.; Bally, Marcel B.

    2015-01-01

    Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known driver mutation is platinum-based chemotherapy, which has a response rate of only 30–33%. Through an siRNA screen, 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces clonogenicity of NSCLC cells by 98.7% (p < 0.001), increases DNA damage, and induces G1/S phase cell cycle arrest and apoptosis. PAPSS1 silencing also sensitized NSCLC cells to other DNA crosslinking agents, radiation, and topoisomerase I inhibitors, but not topoisomerase II inhibitors. Chemo-sensitization was not observed in normal epithelial cells. Knocking out the PAPSS1 homolog did not sensitize yeast to cisplatin, suggesting that sulfate bioavailability for amino acid synthesis is not the cause of sensitization to DNA damaging agents. Rather, sensitization may be due to sulfation reactions involved in blocking the action of DNA damaging agents, facilitating DNA repair, promoting cancer cell survival under therapeutic stress or reducing the bioavailability of DNA damaging agents. Our study demonstrates for the first time that PAPSS1 could be targeted to improve the activity of multiple anticancer agents used to treat NSCLC. PMID:26220590

  10. Screening for Lung Cancer.

    PubMed

    Stiles, Brendon M; Pua, Bradley; Altorki, Nasser K

    2016-07-01

    Lung cancer is a global health burden and is among the most common and deadliest of all malignancies worldwide. The goal of screening programs is to detect tumors in earlier, curable stages, consequently reducing disease-specific mortality. The issue of screening has great relevance to thoracic surgeons, who should play a leading role in the debate over screening and its consequences. The burden is on thoracic surgeons to work in a multidisciplinary setting to guide and treat these patients safely and responsibly, ensuring low morbidity and mortality of potential diagnostic or therapeutic interventions. PMID:27261909

  11. miR-223/FBW7 axis regulates doxorubicin sensitivity through epithelial mesenchymal transition in non-small cell lung cancer

    PubMed Central

    Li, Renyuan; Wu, Shengjun; Chen, Xin; Xu, Hongfei; Teng, Peng; Li, Weidong

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths in the world. F-box/WD repeat-containing protein 7 (FBW7) plays important roles in human cancers, such as gastric cancer, breast cancer, and hepatocellular carcinoma. In this study, we found that high levels of FBW7 expression were associated with increased doxorubicin sensitivity in NSCLC cells. Down-regulation of FBW7 reduced the chemosensitivity in tumor cells. Twist is a critical transcription factor in epithelial-mesenchymal transition (EMT), and NSCLC cells with silenced Twist showed increased doxorubicin sensitivity. Treatment of cells with doxorubicin or hypoxia was shown to trigger EMT as evidenced by decreased E-cadherin and increased Vimentin. In contrast, ectopic expression of FBW7 prevented doxorubicin-or hypoxia-induced EMT. In addition, FBW7 was identified as a functional target of miR-223 in NSCLC cells. These findings define a critical role of miR-223/FBW7 pathway in regulating EMT and chemosensitivity in NSCLC cells. PMID:27398136

  12. UK partnership targets lung cancer.

    PubMed

    2014-07-01

    Cancer Research UK has joined with two major pharmaceutical companies to launch a large multiarm clinical trial, dubbed the National Lung Matrix trial, to test the effectiveness of promising experimental therapies in treating rare forms of advanced lung cancer. PMID:25002593

  13. 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

  14. [Grading of lung cancer].

    PubMed

    Bohle, R M; Schnabel, P A

    2016-07-01

    In comparison with other tumor entities there is no common generally accepted grading system for lung cancer with clearly defined criteria and clinical relevance. In the recent fourth edition of the World Health Organization (WHO) classification from 2015 of tumors of the lungs, pleura, thymus and heart, there is no generally applicable grading for pulmonary adenocarcinomas, squamous cell carcinomas or rarer forms of carcinoma. Since the new IASLC/ATS/ERS classification of adenocarcinomas published in 2011, 5 different subtypes with significantly different prognosis are proposed. This results in an architectural (histologic) grading, which is usually applied to resection specimens. For squamous cell carcinoma the number of different histological subtypes in the new WHO classification was reduced compared to earlier versions but without a common grading system. In recent publications nesting and budding were proposed as the main (histologic) criteria for a grading of squamous cell carcinomas. The grading of neuroendocrine tumors (NET) of the lungs in comparison with NET in other organs is presented in a separate article in this issue. Certain rare tumor types are high grade per definition: small cell, large cell and pleomorphic carcinomas, carcinosarcomas and pulmonary blastomas. In the future it is to be expected that these developments will be further refined, e. g. by adding further subtypes for adenocarcinomas and cytologic and/or nuclear criteria for adenocarcinoma and/or squamous cell carcinomas. PMID:27356985

  15. miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway

    SciTech Connect

    Lan, Fengming; Yue, Xiao; Ren, Gang; Li, Hongqi; Ping, Li; Wang, Yingjie; Xia, Tingyi

    2015-01-01

    Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealed in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate that miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.

  16. [The epidemiology of lung cancer].

    PubMed

    Kosacka, Monika; Jankowska, Renata

    2007-01-01

    Lung cancer is currently most frequently diagnosed neoplasm in males and the fifth most frequent cancer in females. In developed countries only breast cancer is diagnosed more often in women. Worldwide, lung cancer is the most common cause of cancer mortality in males and females. In the Europe lung cancer accounts for 21% of all cancer cases in males and 29% of all cancer deaths. The rapid increase in lung cancer incidence was observed the since beginning of the XX century till 1990-1994. The incidence in males decreased recently, but still increases in females, especially in young women. The changes in frequency of various histological subtypes of lung cancer are observed too. Despite many clinical trials, modern diagnostic techniques and improved supportive care, the prognosis remains unfavourable and long-term survival almost did not change. In Poland the incidence of lung cancer in 2002 was 81.9/100 000 in males and 22.2/100 000 in females. In both genders 1-year and 5-year survivals time are one of the shortest in Europe. PMID:17541915

  17. Bronchoscopy of Lung Cancer

    PubMed Central

    Emslander, H. P.

    1994-01-01

    Lung cancer is a leading cancer site in men and women with a high incidence and mortality rate. Most patients are diagnosed when the disease has already spread. An early, detection and immediate and accurate histological or cytological diagnosis are essential for a hopeful outcome. In most patients, bronchoscopy is the method of choice in establishing a suspected lung neoplasm. With the rigid and flexible method, two complementary techniques are available. The methods bear a very low mortality rate if sufficient monitoring and resuscitative instrumentation is available. Rigid bronchoscopy offers the possibility of obtaining large biopsy specimens from the tumorous tissue and provides an effective tool in the control of major haemorrhage. However, it cannot be used for the inspection of further peripherally located parts of the bronchial system and needs general anaesthesia. In contrast, the flexible method can be quickly and readily performed at practically any location using portable equipment. Bronchi can be inspected up to the 8th order and with bronchial washing, forceps biopsy, brush biopsy and fluorescence bronchoscopy techniques with a high diagnostic yield are available. This holds true, especially if these sampling techniques are used as complementary methods. PMID:18493335

  18. Polonium and Lung Cancer

    PubMed Central

    Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

    2011-01-01

    The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties. PMID:21772848

  19. Inhibition of NF-κB and DNA double-strand break repair by DMAPT sensitizes non-small-cell lung cancers to X-rays.

    PubMed

    Estabrook, Neil C; Chin-Sinex, Helen; Borgmann, Anthony J; Dhaemers, Ryan M; Shapiro, Ronald H; Gilley, David; Huda, Nazmul; Crooks, Peter; Sweeney, Christopher; Mendonca, Marc S

    2011-12-15

    We investigated the efficacy and mechanism of dimethylaminoparthenolide (DMAPT), an NF-κB inhibitor, to sensitize human lung cancer cells to X-ray killing in vitro and in vivo. We tested whether DMAPT increased the effectiveness of single and fractionated X-ray treatment through inhibition of NF-κB and/or DNA double-strand break (DSB) repair. Treatment with DMAPT decreased plating efficiency, inhibited constitutive and radiation-induced NF-κB binding activity, and enhanced radiation-induced cell killing by dose modification factors of 1.8 and 1.4 in vitro. X-ray fractionation demonstrated that DMAPT inhibited split-dose recovery/repair, and neutral DNA comet assays confirmed that DMAPT altered the fast and slow components of X-ray-induced DNA DSB repair. Knockdown of the NF-κB family member p65 by siRNA increased radiation sensitivity and completely inhibited split-dose recovery in a manner very similar to DMAPT treatment. The data suggest a link between inhibition of NF-κB and inhibition of DSB repair by DMAPT that leads to enhancement of X-ray-induced cell killing in vitro in non-small-cell lung cancer cells. Studies of A549 tumor xenografts in nude mice demonstrated that DMAPT enhanced X-ray-induced tumor growth delay in vivo. PMID:22019440

  20. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines

    PubMed Central

    Bai, Xiao-Yan; Zhang, Xu-Chao; Yang, Su-Qing; An, She-Juan; Chen, Zhi-Hong; Su, Jian; Xie, Zhi; Gou, Lan-Ying; Wu, Yi-Long

    2016-01-01

    Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. PMID:26943330

  1. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines.

    PubMed

    Bai, Xiao-Yan; Zhang, Xu-Chao; Yang, Su-Qing; An, She-Juan; Chen, Zhi-Hong; Su, Jian; Xie, Zhi; Gou, Lan-Ying; Wu, Yi-Long

    2016-01-01

    Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. PMID:26943330

  2. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  3. Lung Cancer Surgery Worthwhile for Older Patients

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158689.html Lung Cancer Surgery Worthwhile for Older Patients Study found those ... 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Older lung cancer patients are surviving longer when they have lung ...

  4. Lung Cancer Surgery Worthwhile for Older Patients

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_158689.html Lung Cancer Surgery Worthwhile for Older Patients Study found those ... 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Older lung cancer patients are surviving longer when they have lung ...

  5. Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

    PubMed

    Wang, Lei; Li, Xiankui; Song, Yi-Min; Wang, Bin; Zhang, Fu-Rui; Yang, Rui; Wang, Hua-Qi; Zhang, Guo-Jun

    2015-07-01

    At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression. PMID:25738799

  6. Occupational exposure and lung cancer

    PubMed Central

    Spyratos, Dionysios; Porpodis, Konstantinos; Tsakiridis, Kosmas; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kallianos, Anastasios; Rapti, Aggeliki; Li, Chen; Zarogoulidis, Konstantinos

    2013-01-01

    Lung cancer is the leading cause of cancer death for male and the second most usual cancer for women after breast cancer. Currently there are available several non-specific cytotoxic agents and several targeted agents for lung cancer therapy. However; early stage diagnosis is still unavailable and several efforts are being made towards this direction. Novel biomarkers are being investigated along with new biopsy techniques. The occupational and environmental exposure to carcinogenic agents is an everyday phenomenon. Therefore until efficient early diagnosis is available, avoidance of exposure to carcinogenic agents is necessary. In the current mini-review occupational and environmental carcinogenic agents will be presented. PMID:24102018

  7. Target Therapy in Lung Cancer.

    PubMed

    Cafarotti, Stefano; Lococo, Filippo; Froesh, Patrizia; Zappa, Francesco; Andrè, Dutly

    2016-01-01

    Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way. PMID:26667341

  8. miR-223 enhances the sensitivity of non-small cell lung cancer cells to erlotinib by targeting the insulin-like growth factor-1 receptor

    PubMed Central

    ZHAO, FENG-YI; HAN, JING; CHEN, XIE-WAN; WANG, JIANG; WANG, XU-DONG; SUN, JIAN-GUO; CHEN, ZHENG-TANG

    2016-01-01

    Lung cancer is the leading cause of cancer-related fatalities worldwide, and non-small cell lung cancer (NSCLC) is the main pathological type. MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs, which are involved in tumor initiation and progression. miR-223 is a tumor suppressor miRNA that has been reported in various types of cancer, including lung cancer. In the present study, to characterize the biological behavior of miR-223 in NSCLC, we established an miR-223 overexpression model in erlotinib-resistant PC-9 (PC-9/ER) cells by infection with lentivirus to induce the overexpression of miR-223. As a result, miR-223 enhanced the sensitivity of the PC-9/ER cells to erlotinib by inducing apoptosis in vitro. Additionally, in vivo experiments were performed using nude mice which were injected with the cancer cells [either the PC-9 (not resistant), PC-9/ER, or the PC-9/ER cells infected with miR-223)]. We found that the tumor volumes were reduced in the rats injected with the cells infected with miR-223. To further explore the underlying mechanisms, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to identify the target molecules of miR-223. miR-223 was demonstrated to act as a local regulator of insulin-like growth factor-1 receptor (IGF-1R) in the acquired resistance to tyrosine kinase inhibitors (TKIs). Notably, the οverexpression of IGF-1R in NSCLC was downregulated by miR-223, and the activation of Akt/S6, the downstream pathway, was also inhibited. The inhibition of IGF-1R by miR-223 was attenuated by exogenous IGF-1 expression. Therefore, miR-223 may regulate the acquired resistance of PC-9/ER cells to erlotinib by targeting the IGF-1R/Akt/S6 signaling pathway. The overexpression of miR-223 may partially reverse the acquired resistance to epidermal growth factor receptor-TKIs, thus, providing a potential therapeutic strategy for TKI-resistant NSCLC. PMID:27177336

  9. miR-223 enhances the sensitivity of non-small cell lung cancer cells to erlotinib by targeting the insulin-like growth factor-1 receptor.

    PubMed

    Zhao, Feng-Yi; Han, Jing; Chen, Xie-Wan; Wang, Jiang; Wang, Xu-Dong; Sun, Jian-Guo; Chen, Zheng-Tang

    2016-07-01

    Lung cancer is the leading cause of cancer-related fatalities worldwide, and non-small cell lung cancer (NSCLC) is the main pathological type. MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs, which are involved in tumor initiation and progression. miR‑223 is a tumor suppressor miRNA that has been reported in various types of cancer, including lung cancer. In the present study, to characterize the biological behavior of miR‑223 in NSCLC, we established an miR‑223 overexpression model in erlotinib-resistant PC‑9 (PC‑9/ER) cells by infection with lentivirus to induce the overexpression of miR‑223. As a result, miR‑223 enhanced the sensitivity of the PC‑9/ER cells to erlotinib by inducing apoptosis in vitro. Additionally, in vivo experiments were performed using nude mice which were injected with the cancer cells [either the PC‑9 (not resistant), PC‑9/ER, or the PC‑9/ER cells infected with miR‑223)]. We found that the tumor volumes were reduced in the rats injected with the cells infected with miR‑223. To further explore the underlying mechanisms, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to identify the target molecules of miR‑223. miR‑223 was demonstrated to act as a local regulator of insulin-like growth factor-1 receptor (IGF-1R) in the acquired resistance to tyrosine kinase inhibitors (TKIs). Notably, the οverexpression of IGF-1R in NSCLC was downregulated by miR‑223, and the activation of Akt/S6, the downstream pathway, was also inhibited. The inhibition of IGF-1R by miR‑223 was attenuated by exogenous IGF-1 expression. Therefore, miR‑223 may regulate the acquired resistance of PC‑9/ER cells to erlotinib by targeting the IGF-1R/Akt/S6 signaling pathway. The overexpression of miR‑223 may partially reverse the acquired resistance to epidermal growth factor receptor-TKIs, thus, providing a potential therapeutic strategy for TKI

  10. A systematic analysis of the resistance and sensitivity of HER2YVMA receptor tyrosine kinase mutant to tyrosine kinase inhibitors in HER2-positive lung cancer.

    PubMed

    Shen, Xiaokun; Chen, Beibei; Ma, Zhaosheng; Xie, Bojian; Cao, Xinguang; Yang, Tiejun; Zhao, Yuzhou; Qin, Jianjun; Li, Jicheng; Cao, Feilin; Chen, Xiaobing

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2) has become a well-established target for the treatment of HER2-positive lung cancer. However, a frequently observed in-frame mutation that inserts amino acid quadruplex Tyr776-Val777-Met778-Ala779 at G776 (G776(YVMA)) in HER2 kinase domain can cause drug resistance and sensitivity, largely limiting the application of reversible tyrosine kinase inhibitors in lung cancer therapy. A systematic investigation of the intermolecular interactions between the HER2(YVMA) mutant and clinical small-molecule inhibitors would help to establish a complete picture of drug response to HER2 G776(YVMA) insertion in lung cancer, and to design new tyrosine kinase inhibitors with high potency and selectivity to target the lung cancer-related HER2(YVMA) mutant. Here, we combined homology modeling, ligand grafting, structure minimization, molecular simulation and binding affinity analysis to profile a number of tyrosine kinase inhibitors against the G776(YVMA) insertion in HER2. It is found that the insertion is far away from HER2 active pocket and thus cannot contact inhibitor ligand directly. However, the insertion is expected to induce marked allosteric effect on some regions around the pocket, including A-loop and hinges connecting between the N- and C-lobes of HER2 kinase domain, which may exert indirect influence to inhibitor binding. Most investigated inhibitors exhibit weak binding strength to both wild-type and mutant HER2, which can be attributed to steric hindrance that impairs ligand compatibility with HER2 active pocket. However, the cognate inhibitor lapatinib and the non-cognate inhibitor bosutinib were predicted to have low affinity for wild-type HER2 but high affinity for HER2(YVMA) mutant, which was confirmed by subsequent kinase assay experiments; the inhibitory potencies of bosutinib against wild-type and mutant HER2 were determined to be IC(50) > 1000 and =27 nM, respectively, suggesting that the bosutinib might be

  11. Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel.

    PubMed

    Lee, Jong Hyun; Kim, Chulwon; Sethi, Gautam; Ahn, Kwang Seok

    2015-03-20

    Persistent phosphorylation of signal transducers and activators of transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive and IL-6-inducible STAT3 activation in lung cancer cells. Moreover, BSN induced PIAS-3 protein and mRNA, whereas the expression of SOCS-3 was reduced. Knockdown of PIAS-3 by small interfering RNA prevented inhibition of STAT3 and cytotoxicity by BSN. Overexpression of SOCS-3 in BSN-treated cells increased STAT3 phosphorylation and cell viability. BSN down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced apoptosis. Most importantly, when administered intraperitoneally, combination of BSN and paclitaxel significantly decreased the tumor development in a xenograft lung cancer mouse model associated with down-modulation of phospho-STAT3, Ki-67 and CD31. We suggest that BSN inhibits STAT3 signaling through modulation of PIAS-3 and SOCS-3, thereby attenuating tumor growth and increasing sensitivity to paclitaxel. PMID:25788267

  12. Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel

    PubMed Central

    Lee, Jong Hyun; Kim, Chulwon; Sethi, Gautam; Ahn, Kwang Seok

    2015-01-01

    Persistent phosphorylation of signal transducers and activators of transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive and IL-6-inducible STAT3 activation in lung cancer cells. Moreover, BSN induced PIAS-3 protein and mRNA, whereas the expression of SOCS-3 was reduced. Knockdown of PIAS-3 by small interfering RNA prevented inhibition of STAT3 and cytotoxicity by BSN. Overexpression of SOCS-3 in BSN-treated cells increased STAT3 phosphorylation and cell viability. BSN down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced apoptosis. Most importantly, when administered intraperitoneally, combination of BSN and paclitaxel significantly decreased the tumor development in a xenograft lung cancer mouse model associated with down-modulation of phospho-STAT3, Ki-67 and CD31. We suggest that BSN inhibits STAT3 signaling through modulation of PIAS-3 and SOCS-3, thereby attenuating tumor growth and increasing sensitivity to paclitaxel. PMID:25788267

  13. 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. PMID:23606351

  14. Screening for occult lung cancer.

    PubMed Central

    Barclay, T. H.; MacIntosh, J. H.

    1983-01-01

    A pilot screening program for the early detection of lung cancer was carried out in Saskatchewan in 1968 using chest roentgenography and cytologic examination of sputum samples. The yield from 23 000 men aged 40 years and over was only 10 cases. Nine of the men had advanced disease. One had occult lung cancer. A period of 31 months elapsed between the discovery of malignant cells in this patient's sputum and roentgenographic localization of the tumour. Following pneumonectomy he has survived with no discernible residual or metastatic tumour for 12 years. The morphologic changes in the resected lung provided a basis for discussing the preclinical phase of squamous cancer of the lung, the treatment of occult cancer and multicentric primary pulmonary tumours. The survey would have been more successful with a narrower target group and more frequent examination. Images FIG. 1 FIG. 2 FIG. 3 PMID:6299495

  15. [Photodynamic Therapy for Lung Cancer].

    PubMed

    Ohtani, Keishi; Ikeda, Norihiko

    2016-07-01

    In Japan, Photodynamic therapy (PDT) is recommended as a treatment option for centrally located early-stage lung cancers (CLELCs). It is a minimally invasive treatment with excellent anti-tumor effects. The 2nd generation photosensitizer, talaporfin sodium has strong anti-tumor effects with much less photosensitivity than porfimer sodium. Moreover, the laser equipment is compact and portable, and talaporfin sodium is now the current mainstay of PDT for lung cancer. For successful PDT, accurate evaluation of tumor extent and bronchial invasion is crucial. Detailed examination of the tumor using autofluorescence bronchoscopy and endobronchial ultrasonography or optical coherence tomography is extremely useful before PDT. At present, PDT has become the 1st choice of treatment for CLELC in institutions with the necessary equipment. It can also be effective for advanced lung cancer causing tracheobronchial obstruction. With such advances in PDT for CLELC, we are expanding the indications of PDT for not only CLELC, but also peripheral type lung cancer. PMID:27440036

  16. Lung Cancer Screening Recommendation Questioned.

    PubMed

    2016-06-01

    According to a retrospective analysis of data from the National Lung Screening Trial, participants with a history of heavy smoking who test negative for abnormalities suggestive of lung cancer on an initial low-dose CT screen may not need yearly CT scans. Instead, they could work with their doctors to devise an appropriate screening schedule based on individual risk factors. PMID:27076372

  17. Lung Cancer and Hispanics: Know the Facts

    MedlinePlus

    ... other segments of the American population. However, lung cancer is still the leading cause of cancer death among Hispanic men and the second-leading cause among Hispanic women. November is Lung Cancer Awareness ...

  18. Study of the radiotherapy sensitization effects and mechanism of capecitabine (Xeloda) against non-small-cell lung cancer cell line A549.

    PubMed

    Zhu, J J; Shan, J J; Sun, L B; Qiu, W S

    2015-01-01

    The purpose of this study was to explore the radiotherapy sensitization effects and the mechanism of capecitabine (Xeloda) against the non-small-cell lung cancer cell line, A549. γ-[(60)Co] radiation was used as the intervention method. Proliferative inhibition of capecitabine on A549 cells was determined by the CCK-8 method. The effects of capecitabine on the apoptosis rate and cell cycle distribution of A549 were detected with the flow cytometric method. We found that capecitabine inhibited the proliferation of A549 in a dose-dependent manner, notably increased the cell apoptosis rate and blocked the cellular G0/G1 phase after radiotherapy by γ-[(60)Co]. Therefore, capecitabine can significantly increase the radiosensitivity of A549; its mechanism may be related to cell cycle arrest and induction of apoptosis. PMID:26662434

  19. Targeted Therapies in Lung Cancer

    PubMed Central

    Chirieac, Lucian R.; Dacic, Sanja

    2010-01-01

    An ongoing research and multiple clinical trials involve new targeted therapies and less aggressive treatment regimens that improve survival in patients with lung cancer. Targeted therapeutic agents are based on the concept of discovering genetic alterations and the signaling pathways altered in cancer and have added significantly to our armamentarium in order to prolong patient survival and minimizing drug toxicity. Among 34 molecularly targeted drugs approved by U.S. Food and Drug Administration (FDA) for treatment of various cancers since 1998 three targeted therapies have been approved for treatment of lung cancer (gefitinib in 2002, erlotinib in 2003, and bevacizumab in 2006). This review focuses on the targeted therapies in lung cancer, the molecular biomarkers that help identify patients that will benefit for these targeted therapies, describes the basic molecular biology principles and selected molecular diagnostic techniques and the pathological features correlated with molecular abnormalities in lung cancer. Lastly, new molecular abnormalities described in lung cancer that are predictive to novel promising targeted agents in various phases of clinical trials are discussed. PMID:20680095

  20. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    SciTech Connect

    Kim, In Gyu; Kim, Seo Yoen; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  1. Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells.

    PubMed

    Gupta, Seema; Koru-Sengul, Tulay; Arnold, Susanne M; Devi, Gayathri R; Mohiuddin, Mohammed; Ahmed, Mansoor M

    2011-02-01

    In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non-small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 × 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D(0), the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF(2))] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin + 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non-small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition. PMID:21216938

  2. Predictive efficacy of (11)C-PD153035 PET imaging for EGFR-tyrosine kinase inhibitor sensitivity in non-small cell lung cancer patients.

    PubMed

    Dai, Dong; Li, Xiao-Feng; Wang, Jian; Liu, Jian-Jing; Zhu, Yan-Jia; Zhang, Ying; Wang, Qi; Xu, Wen-Gui

    2016-02-15

    To determine the correlation of (11)C-PD153035 uptake with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity and phosphorylated EGFR (pEGFR) expression in non-small cell lung cancer (NSCLC) cell lines with different EGFR-TKI sensitivities and in their corresponding xenografts. Four human NSCLC cell lines (HCC827, PC9, A549, and H1975) in the logarithmic phase were co-incubated with (11)C-PD153035 to analyze the correlation of (11)C-PD153035 uptake with EGFR-TKI sensitivity, and EGFR/pEGFR expression. Nude mice xenograft models bearing the four NSCLCs were prepared. (11)C-PD153035 positron-emission tomography (PET)-computed tomography (CT) was used to image the xenografts and observe radioactive uptakes. Correlation of the in vivo uptakes with EGFR-TKI sensitivity, and EGFR/pEGFR expression was analyzed. HCC827 and PC9 cells, which were highly sensitive to EGFR-TKIs, exhibited higher (11)C-PD153035 uptakes than the other cells. A549 cells, which were moderately sensitive to EGFR-TKIs, showed higher uptake than the EGFR-TKI-resistant H1975 cells, which showed little or no uptake. Radioactive uptakes were positively correlated with pEGFR expression in all cells. PET-CT showed that radioactivity was highest in HCC827 xenografts. The radioactivity in PC9 xenografts was higher than that in A549 and H1975 xenografts. Tumor vs. non-tumor tissue ratio values were positively correlated with pEGFR expression in HCC827 and PC9 xenografts, but not in A549 and H1975 xenografts. In conclusion, (11)C-PD153035 can serve as an EGFR imaging agent in vitro and in vivo, and predicts sensitivity to EGFR-TKIs. This will provide an experimental basis for clinical applications of (11)C-PD153035 and individualized NSCLC therapy. PMID:26334931

  3. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines

    PubMed Central

    Engelman, Jeffrey A.; Jänne, Pasi A.; Mermel, Craig; Pearlberg, Joseph; Mukohara, Toru; Fleet, Christina; Cichowski, Karen; Johnson, Bruce E.; Cantley, Lewis C.

    2005-01-01

    Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). The differences in intracellular signaling networks between gefitinib-sensitive and -resistant NSCLCs remain poorly understood. In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. To elucidate the mechanism underlying this observation, we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to activate the PI3K/Akt pathway. In fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs. PMID:15731348

  4. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  5. Early detection of lung cancer

    PubMed Central

    Midthun, David E.

    2016-01-01

    Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer. PMID:27158468

  6. Early detection of lung cancer.

    PubMed

    Midthun, David E

    2016-01-01

    Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer. PMID:27158468

  7. Carotenoids and lung cancer prevention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the molecular actions of carotenoids is critical for human studies involving carotenoids for prevention of lung cancer and cancers at other tissue sites. While the original hypothesis prompting the beta-carotene intervention trials was that beta-carotene exerts beneficial effects thro...

  8. CIGARETTE SMOKE AND LUNG CANCER

    EPA Science Inventory

    Cigarette smoke has been implicated in a causal relationship with carcinoma of the lung. An intriguing feature of the disease is the site-selectivity with which bronchogenic cancer manifests itself; most cancers are detected in the main, lobar and segmental bronchi, perhaps speci...

  9. Palliative Care in Lung Cancer.

    PubMed

    Shinde, Arvind M; Dashti, Azadeh

    2016-01-01

    Lung cancer is the most common cancer worldwide and is the leading cause of cancer death for both men and women in the USA. Symptom burden in patients with advanced lung cancer is very high and has a negative impact on their quality of life (QOL). Palliative care with its focus on the management of symptoms and addressing physical, psychosocial, spiritual, and existential suffering, as well as medically appropriate goal setting and open communication with patients and families, significantly adds to the quality of care received by advanced lung cancer patients. The Provisional Clinical Opinion (PCO) of American Society of Clinical Oncology (ASCO) as well as the National Cancer Care Network's (NCCN) clinical practice guidelines recommends early integration of palliative care into routine cancer care. In this chapter, we will provide an overview of palliative care in lung cancer and will examine the evidence and recommendations with regard to a comprehensive and interdisciplinary approach to symptom management, as well as discussions of goals of care, advance care planning, and care preferences. PMID:27535397

  10. Lung Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  12. 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

  13. Small interfering RNA targeting S100A4 sensitizes non-small-cell lung cancer cells (A549) to radiation treatment

    PubMed Central

    Qi, Ruixue; Qiao, Tiankui; Zhuang, Xibing

    2016-01-01

    RNA-directed S100A4 knockdown may represent a viable clinical therapy for lung cancer. Conclusion S100A4 downregulation potentially enhances the sensitivity of human A549 cells to radiotherapy. PMID:27382312

  14. Lung cancer and air pollution.

    PubMed Central

    Cohen, A J; Pope, C A

    1995-01-01

    Epidemiologic studies over the last 40 years suggest rather consistently that general ambient air pollution, chiefly due to the incomplete combustion of fossil fuels, may be responsible for increased rates of lung cancer. This evidence derives from studies of lung cancer trends, studies of occupational groups, comparisons of urban and rural populations, and case-control and cohort studies using diverse exposure metrics. Recent prospective cohort studies observed 30 to 50% increases in lung cancer rates associated with exposure to respirable particles. While these data reflect the effects of exposures in past decades, and despite some progress in reducing air pollution, large numbers of people in the United States continue to be exposed to pollutant mixtures containing known or suspected carcinogens. It is not known how many people in the United States are exposed to levels of fine respirable particles that have been associated with lung cancer in recent epidemiologic studies. These observations suggest that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the United States based largely on the results of animal studies, may be too low. It is important that better epidemiologic research be conducted to allow improved estimates of lung cancer risk from air pollution among the general population. The development and application of new epidemiologic methods, particularly the improved characterization of population-wide exposure to mixtures of air pollutants and the improved design of ecologic studies, could improve our ability to measure accurately the magnitude of excess cancer associated with air pollution. PMID:8741787

  15. Epidemiology of lung cancer in China

    PubMed Central

    Chen, Wanqing; Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei

    2015-01-01

    Background Lung cancer is the most common cancer and the leading cause of cancer death in China. Along with socioeconomic development, environmental problems have intensified and the burden of lung cancer continues to increase. Methods In this study, national cancer registry data was used for evaluating incidence, mortality, time trend, and prediction. Results In China in 2010, 605 900 patients were diagnosed and 486 600 patients died of lung cancer. Throughout the last three decades, the mortality of lung cancer has dramatically increased, as shown in national death surveys. From 2000 to 2010, age specific incidence of lung cancer increased in most age groups. It is estimated that in 2015, the total number of new cases of lung cancer will reach 733 300. Conclusions Lung cancer is a serious disease affecting public health and an effective control strategy is needed in China. PMID:26273360

  16. General Information about Small Cell Lung Cancer

    MedlinePlus

    ... Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  17. Risk Profiling May Improve Lung Cancer Screening

    Cancer.gov

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  18. Magnetic resonance imaging for lung cancer screen.

    PubMed

    Wang, Yi-Xiang J; Lo, Gladys G; Yuan, Jing; Larson, Peder E Z; Zhang, Xiaoliang

    2014-09-01

    Lung cancer is the leading cause of cancer related death throughout the world. Lung cancer is an example of a disease for which a large percentage of the high-risk population can be easily identified via a smoking history. This has led to the investigation of lung cancer screening with low-dose helical/multi-detector CT. Evidences suggest that early detection of lung cancer allow more timely therapeutic intervention and thus a more favorable prognosis for the patient. The positive relationship of lesion size to likelihood of malignancy has been demonstrated previously, at least 99% of all nodules 4 mm or smaller are benign, while noncalcified nodules larger than 8 mm diameter bear a substantial risk of malignancy. In the recent years, the availability of high-performance gradient systems, in conjunction with phased-array receiver coils and optimized imaging sequences, has made MR imaging of the lung feasible. It can now be assumed a threshold size of 3-4 mm for detection of lung nodules with MRI under the optimal conditions of successful breath-holds with reliable gating or triggering. In these conditions, 90% of all 3-mm nodules can be correctly diagnosed and that nodules 5 mm and larger are detected with 100% sensitivity. Parallel imaging can significantly shorten the imaging acquisition time by utilizing the diversity of sensitivity profile of individual coil elements in multi-channel radiofrequency receive coil arrays or transmit/receive coil arrays to reduce the number of phase encoding steps required in imaging procedure. Compressed sensing technique accelerates imaging acquisition from dramatically undersampled data set by exploiting the sparsity of the images in an appropriate transform domain. With the combined imaging algorithm of parallel imaging and compressed sensing and advanced 32-channel or 64-channel RF hardware, overall imaging acceleration of 20 folds or higher can then be expected, ultimately achieve free-breathing and no ECG gating acquisitions

  19. Magnetic resonance imaging for lung cancer screen

    PubMed Central

    Lo, Gladys G.; Yuan, Jing; Larson, Peder E. Z.

    2014-01-01

    Lung cancer is the leading cause of cancer related death throughout the world. Lung cancer is an example of a disease for which a large percentage of the high-risk population can be easily identified via a smoking history. This has led to the investigation of lung cancer screening with low-dose helical/multi-detector CT. Evidences suggest that early detection of lung cancer allow more timely therapeutic intervention and thus a more favorable prognosis for the patient. The positive relationship of lesion size to likelihood of malignancy has been demonstrated previously, at least 99% of all nodules 4 mm or smaller are benign, while noncalcified nodules larger than 8 mm diameter bear a substantial risk of malignancy. In the recent years, the availability of high-performance gradient systems, in conjunction with phased-array receiver coils and optimized imaging sequences, has made MR imaging of the lung feasible. It can now be assumed a threshold size of 3-4 mm for detection of lung nodules with MRI under the optimal conditions of successful breath-holds with reliable gating or triggering. In these conditions, 90% of all 3-mm nodules can be correctly diagnosed and that nodules 5 mm and larger are detected with 100% sensitivity. Parallel imaging can significantly shorten the imaging acquisition time by utilizing the diversity of sensitivity profile of individual coil elements in multi-channel radiofrequency receive coil arrays or transmit/receive coil arrays to reduce the number of phase encoding steps required in imaging procedure. Compressed sensing technique accelerates imaging acquisition from dramatically undersampled data set by exploiting the sparsity of the images in an appropriate transform domain. With the combined imaging algorithm of parallel imaging and compressed sensing and advanced 32-channel or 64-channel RF hardware, overall imaging acceleration of 20 folds or higher can then be expected, ultimately achieve free-breathing and no ECG gating acquisitions

  20. Lunasin sensitivity in non-small cell lung cancer cells is linked to suppression of integrin signaling and changes in histone acetylation.

    PubMed

    Inaba, Junichi; McConnell, Elizabeth J; Davis, Keith R

    2014-01-01

    Lunasin is a plant derived bioactive peptide with both cancer chemopreventive and therapeutic activity. We recently showed lunasin inhibits non-small cell lung cancer (NSCLC) cell proliferation in a cell-line-specific manner. We now compared the effects of lunasin treatment of lunasin-sensitive (H661) and lunasin-insensitive (H1299) NSCLC cells with respect to lunasin uptake, histone acetylation and integrin signaling. Both cell lines exhibited changes in histone acetylation, with H661 cells showing a unique increase in H4K16 acetylation. Proximity ligation assays demonstrated lunasin interacted with integrins containing αv, α5, β1 and β3 subunits to a larger extent in the H661 compared to H1299 cells. Moreover, lunasin specifically disrupted the interaction of β1 and β3 subunits with the downstream signaling components phosphorylated Focal Adhesion Kinase (pFAK), Kindlin and Intergrin Linked Kinase in H661 cells. Immunoblot analyses demonstrated lunasin treatment of H661 resulted in reduced levels of pFAK, phosphorylated Akt and phosphorylated ERK1/2 whereas no changes were observed in H1299 cells. Silencing of αv expression in H661 cells confirmed signaling through integrins containing αv is essential for proliferation. Moreover, lunasin was unable to further inhibit proliferation in αv-silenced H661 cells. This indicates antagonism of integrin signaling via αv-containing integrins is an important component of lunasin's mechanism of action. PMID:25530619

  1. Tobacco Smoking and Lung Cancer

    PubMed Central

    Furrukh, Muhammad

    2013-01-01

    Tobacco smoking remains the most established cause of lung carcinogenesis and other disease processes. Over the last 50 years, tobacco refinement and the introduction of filters have brought a change in histology, and now adenocarcinoma has become the most prevalent subtype. Over the last decade, smoking also has emerged as a strong prognostic and predictive patient characteristic along with other variables. This article briefly reviews scientific facts about tobacco, and the process and molecular pathways involved in lung carcinogenesis in smokers and never-smokers. The evidence from randomised trials about tobacco smoking’s impact on lung cancer outcomes is also reviewed. PMID:23984018

  2. Mouse models for lung cancer.

    PubMed

    Kwon, Min-chul; Berns, Anton

    2013-04-01

    Lung cancer is a devastating disease and a major therapeutic burden with poor survival rates. It is responsible for 30% of all cancer deaths. Lung cancer is strongly associated with smoking, although some subtypes are also seen in non-smokers. Tumors in the latter group are mostly adenocarcinomas with many carrying mutations in the epidermal growth factor receptor (EGFR). Survival statistics of lung cancer are grim because of its late detection and frequent local and distal metastases. Although DNA sequence information from tumors has revealed a number of frequently occurring mutations, affecting well-known tumor suppressor genes and proto-oncogenes, many of the driver mutations remain ill defined. This is likely due to the involvement of numerous rather infrequently occurring driver mutations that are difficult to distinguish from the very large number of passenger mutations detected in smoking-related lung cancers. Therefore, experimental model systems are indispensable to validate putative driver lesions and to gain insight into their mechanisms of action. Whereas a large fraction of these analyzes can be performed in cell cultures in vitro, in many cases the consequences of the mutations have to be assessed in the context of an intact organism, as this is the context in which the Mendelian selection process of the tumorigenic process took place and the advantages of particular mutations become apparent. Current mouse models for cancer are very suitable for this as they permit mimicking many of the salient features of human tumors. The capacity to swiftly re-engineer complex sets of lesions found in human tumors in mice enables us to assess the contribution of defined combinations of lesions to distinct tumor characteristics such as metastatic behavior and response to therapy. In this review we will describe mouse models of lung cancer and how they are used to better understand the disease and how they are exploited to develop better intervention strategies

  3. Lung Cancer in the Era of Precision Medicine

    PubMed Central

    Politi, Katerina; Herbst, Roy S.

    2015-01-01

    The past decade has been transformative for lung cancer patients, physicians and scientists. The discovery of EGFR mutations that confer sensitivity to tyrosine kinase inhibitors in lung adenocarcinomas in 2004 heralded the beginning of the era of precision medicine for lung cancer. It also precipitated concerted efforts by many investigators to define molecular subgroups of lung cancer, characterize the genomic landscape of lung cancer subtypes, identify novel therapeutic targets and define mechanisms of sensitivity and resistance to targeted therapies. The fruits of these efforts are visible every day now in lung cancer clinics: patients receive molecular testing to determine whether their tumor harbors an actionable mutation, new and improved targeted therapies that can overcome resistance to first-generation drugs are in clinical trials and drugs targeting the immune system are showing activity in patients. This extraordinary promise is tempered by the sobering fact that even the newest treatments for metastatic disease are rarely curative and are effective only in a small fraction of patients. Ongoing and future efforts to find new vulnerabilities of lung cancers, unravel the complexity of drug resistance, increase the efficacy of immunotherapies and perform biomarker-driven clinical trials are necessary to improve outcomes for lung cancer patients. PMID:25979927

  4. Urinary volatile compounds as biomarkers for lung cancer.

    PubMed

    Hanai, Yosuke; Shimono, Ken; Matsumura, Koichi; Vachani, Anil; Albelda, Steven; Yamazaki, Kunio; Beauchamp, Gary K; Oka, Hiroaki

    2012-01-01

    Lung cancer is a leading cause of deaths in cancer. Hence, developing early-stage diagnostic tests that are non-invasive, highly sensitive, and specific is crucial. In this study, we investigated to determine whether biomarkers derived from urinary volatile organic compounds (VOCs) can be used to discriminate between lung cancer patients and normal control patients. The VOCs were extracted from the headspace by solid-phase microextraction and were analyzed by gas chromatography time-of-flight mass spectrometry. Nine putative volatile biomarkers were identified as elevated in the lung cancer group. Receiver operating characteristic curve analysis was also performed, and the markers were found to be highly sensitive and specific. Next we used principal component analysis (PCA) modeling to make comparisons compare within the lung cancer group, and found that 2-pentanone may have utility in differentiating between adenocarcinoma and squamous cell carcinomas. PMID:22484930

  5. Atmospheric pollution and lung cancer.

    PubMed Central

    Doll, R

    1978-01-01

    Lung cancer is consistently more common in urban areas than in rural. The excess cannot be accounted for by specific occupational hazards but some of it might be due to the presence of carcinogens in urban air. The excess cannot be wholly due to such agents, because the excess in nonsmokers is small and variable. Cigarette consumption has also been greater in urban areas, but it is difficult to estimate how much of the excess it can account for. Occupational studies confirm that pollutants present in town air are capable of causing lung cancer in man and suggest that the pollutants and cigarette smoke act synergistically. The trends in the mortality from lung cancer in young and middle-aged men in England and Wales provide uncertain evidence but support the belief that atmospheric pollution has contributed to the production of the disease. In the absence of cigarette smoking, the combined effect of all atmospheric carcinogens is not responsible for more than about 5 cases of lung cancer per 100,000 persons per year in European populations. PMID:648488

  6. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    2016-01-01

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms. PMID:27535389

  7. Radiotherapy of inoperable lung cancer

    SciTech Connect

    Namer, M.; Lalanne, C.M.; Boublil, J.L.; Hery, M.; Chauvel, P.; Verschoore, J.; Aubanel, J.M.; Bruneton, J.N.

    1980-08-01

    Evaluation of loco-regional results obtained by radiotherapy for 31 patients with inoperable epidermoid lung cancer revealed objective remission (over 50%) in only 25% of patients. These results emphasize the limited effectiveness of radiotherapy in such cases and point out the need for increased research in radiotherapy techniques if survival rates are to be improved.

  8. Lung cancer screening: from imaging to biomarker.

    PubMed

    Xiang, Dong; Zhang, Bicheng; Doll, Donald; Shen, Kui; Kloecker, Goetz; Freter, Carl

    2013-01-01

    Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein. PMID:24252206

  9. Lung cancer screening: from imaging to biomarker

    PubMed Central

    2013-01-01

    Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein. PMID:24252206

  10. [Geographic spreading of lung cancer in Azerbaijan].

    PubMed

    Soltanov, A A

    2009-01-01

    Lung cancer is the second most common cancer and the leading cause of cancer death for both men and women. The impact of geographic as well as of exogenous factor and factors of risk, life style and environment play an important role in etiology of lung cancer. Geographic spread of lung cancer data in literature is fragmentary. The limited existing literature does not report a consistent story of geographic variation in Azerbaijan for the incidence associated with lung cancer. The aim of this study was to evaluate the impact of geographic variation on spread of lung cancer in Azerbaijan. Frequency of lung cancer in various regions of Azerbaijan; different histological types, sex, age and particular risk factors were investigated. It was revealed that epidermoid cancer was the most common histological type in all regions. The highest rate of epidermoid cancer 230 (55.56%) was revealed in industrial regions and industrial cities (Baku and Sumgait). The lowest rate of lung cancer was found in mountain region 12 (3.76%). Smoking and drinking alcohol increases risk of epidermoid cancer (41.2% of patients smoke and drink alcohol). The highest morbidity (13.55 per 100,000 population) and mortality (0.11) rates from lung cancer were observed in industrial regions. Analyses revealed that different endogenous and exogenous factors are associated with lung cancer. PMID:19202230

  11. Guidance molecules in lung cancer

    PubMed Central

    Nasarre, Patrick; Potiron, Vincent; Drabkin, Harry

    2010-01-01

    Guidance molecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidance molecule families and their corresponding receptors are described, including the semaphorins/neuropilins/plexins, ephrins and Eph receptors, netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to target these molecules as a therapeutic approach in cancer is discussed. PMID:20139699

  12. Uranium miner lung cancer study. Final report

    SciTech Connect

    Saccomanno, G.

    1986-06-01

    This study on uranium miners was started in 1957 and extended through June 30, 1986. It consisted of the routine screening of sputum from uranium miners of the Colorado Plateau, and collection of surgical and autopsy material from uranium miners who developed lung cancer. The projects resulted in: (1) Proof, for the first time, that cancer takes from 10 to 15 years to develop from the maximum accumulated carcinogenic insult and can be demonstrated through progressive cellular changes of the bronchial tree; (2) Development of a method for preserving, concentrating, and processing sputum samples. This is known as the Saccomanno Technique, and is used worldwide in diagnosing lung cancer; (3) Publication of the 1st and 2nd editions of a full-color textbook entitled ''Diagnostic Pulmonary Cytology;'' (4) Presentation of conclusive data on the effects of cigarette smoking and alpha progeny radiation on uranium miners, and information on safe radiation exposure levels; (5) Development of a brush-wash tube for collecting, concentrating, and preparing bronchial brushings and washings; (6) Development of cytological criteria which has improved sensitivity from 30% to about 60%; (7) Development of criteria for cytologic identification of carcinoma in situ, making it possible to diagnose lung cancer before it can be detected on chest x-ray.

  13. Lung cancer treatment outcomes in recipients of lung transplant

    PubMed Central

    Du, Lingling; Pennell, Nathan A.; Elson, Paul

    2015-01-01

    Background Lung transplant recipients develop lung cancer more commonly than the general population. The best treatment approach for these patients is unclear. The goal of this study is to evaluate treatment outcomes in this population. Methods We used the Cleveland Clinic lung transplant database to identify patients diagnosed with lung cancer at the time of or after lung transplant. Transplant and lung cancer-related data were retrospectively reviewed. Results Among 847 patients underwent lung transplant between 2005 and 2013, 17 (2%) were diagnosed with lung cancer and included. Median age was 61 (range, 48–70) years. Majority were stage I/II (n=11), one had stage IIIA, five had stage IV. Non-small cell lung cancer (NSCLC) were more common than small cell lung cancer (SCLC) (n=15 vs. 2). Curative treatment was performed as lobectomy in native lung (n=1), and radiation in transplanted lung (n=2). Chemotherapy was given in 10 patients, primarily carboplatin-based doublets with docetaxel, pemetrexed, or etoposide. Six of these received palliative chemotherapy for either metastases at diagnosis (n=3) or recurrence after early stage disease (n=3). Except for one patient with complete response, all others had progressive disease following palliative chemotherapy. Overall, patients who received chemotherapy had a median survival of 7.5 months from the initiation of chemotherapy, but 30% developed grade 5 sepsis. Median survival for stage I–IIIA and stage IV were 23.2 and 2.5 months respectively. Conclusions Lung cancer in lung transplant recipients carries various clinical courses. Patients with metastatic disease have substantial toxicities from chemotherapy and poor survival. Early stage patients should be offered treatment with modified dosages to decrease the risk of severe toxicities. PMID:26798588

  14. Treatment Options by Stage (Small Cell Lung Cancer)

    MedlinePlus

    ... 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 Points ...

  15. Enhancement of Radiation Sensitivity in Lung Cancer Cells by a Novel Small Molecule Inhibitor That Targets the β-Catenin/Tcf4 Interaction.

    PubMed

    Zhang, Qinghao; Gao, Mei; Luo, Guifen; Han, Xiaofeng; Bao, Wenjing; Cheng, Yanyan; Tian, Wang; Yan, Maocai; Yang, Guanlin; An, Jing

    2016-01-01

    Radiation therapy is an important treatment choice for unresectable advanced human lung cancers, and a critical adjuvant treatment for surgery. However, radiation as a lung cancer treatment remains far from satisfactory due to problems associated with radiation resistance in cancer cells and severe cytotoxicity to non-cancer cells, which arise at doses typically administered to patients. We have recently identified a promising novel inhibitor of β-catenin/Tcf4 interaction, named BC-23 (C21H14ClN3O4S), which acts as a potent cell death enhancer when used in combination with radiation. Sequential exposure of human p53-null non-small cell lung cancer (NSCLC) H1299 cells to low doses of x-ray radiation, followed 1 hour later by administration of minimally cytotoxic concentrations of BC-23, resulted in a highly synergistic induction of clonogenic cell death (combination index <1.0). Co-treatment with BC-23 at low concentrations effectively inhibits Wnt/β-catenin signaling and down-regulates c-Myc and cyclin D1 expression. S phase arrest and ROS generation are also involved in the enhancement of radiation effectiveness mediated by BC-23. BC-23 therefore represents a promising new class of radiation enhancer. PMID:27014877

  16. Enhancement of Radiation Sensitivity in Lung Cancer Cells by a Novel Small Molecule Inhibitor That Targets the β-Catenin/Tcf4 Interaction

    PubMed Central

    Luo, Guifen; Han, Xiaofeng; Bao, Wenjing; Cheng, Yanyan; Tian, Wang; Yan, Maocai; Yang, Guanlin; An, Jing

    2016-01-01

    Radiation therapy is an important treatment choice for unresectable advanced human lung cancers, and a critical adjuvant treatment for surgery. However, radiation as a lung cancer treatment remains far from satisfactory due to problems associated with radiation resistance in cancer cells and severe cytotoxicity to non-cancer cells, which arise at doses typically administered to patients. We have recently identified a promising novel inhibitor of β-catenin/Tcf4 interaction, named BC-23 (C21H14ClN3O4S), which acts as a potent cell death enhancer when used in combination with radiation. Sequential exposure of human p53-null non-small cell lung cancer (NSCLC) H1299 cells to low doses of x-ray radiation, followed 1 hour later by administration of minimally cytotoxic concentrations of BC-23, resulted in a highly synergistic induction of clonogenic cell death (combination index <1.0). Co-treatment with BC-23 at low concentrations effectively inhibits Wnt/β-catenin signaling and down-regulates c-Myc and cyclin D1 expression. S phase arrest and ROS generation are also involved in the enhancement of radiation effectiveness mediated by BC-23. BC-23 therefore represents a promising new class of radiation enhancer. PMID:27014877

  17. Lung cancer screening and management.

    PubMed

    Jones, G S; Baldwin, D R

    2015-12-01

    Deaths from lung cancer are greater than for any other type of malignancy. Many people present with advanced stage cancer at diagnosis and survival is limited. Low radiation dose CT (LDCT) screening appears to offer part of the solution to this. The US National Lung Screening Trial (NLST) showed a 20% reduction in cancer related mortality and a 6.7% reduction in all cause mortality in patients who had LDCT compared to chest X-ray. Lung Cancer screening is now being implemented in the US using the NLST screening criteria but many questions remain about the details of the methodology of screening and its cost effectiveness. Many of these questions are being answered by ongoing European trials that are reporting their findings. In this review we objectively analyse current research evidence and explore the issues that need to be resolved before implementation, including technical considerations, selection criteria and effective nodule management protocols. We discuss the potential barriers that will be faced when beginning a national screening programme and possible solutions to them. PMID:26605556

  18. Phosphoproteomics and Lung Cancer Research

    PubMed Central

    López, Elena; Cho, William C. S.

    2012-01-01

    Massive evidence suggests that genetic abnormalities contribute to the development of lung cancer. These molecular abnormalities may serve as diagnostic, prognostic and predictive biomarkers for this deadly disease. It is imperative to search these biomarkers in different tumorigenesis pathways so as to provide the most appropriate therapy for each individual patient with lung malignancy. Phosphoproteomics is a promising technology for the identification of biomarkers and novel therapeutic targets for cancer. Thousands of proteins interact via physical and chemical association. Moreover, some proteins can covalently modify other proteins post-translationally. These post-translational modifications ultimately give rise to the emergent functions of cells in sequence, space and time. Phosphoproteomics clinical researches imply the comprehensive analysis of the proteins that are expressed in cells or tissues and can be employed at different stages. In addition, understanding the functions of phosphorylated proteins requires the study of proteomes as linked systems rather than collections of individual protein molecules. In fact, proteomics approaches coupled with affinity chromatography strategies followed by mass spectrometry have been used to elucidate relevant biological questions. This article will discuss the relevant clues of post-translational modifications, phosphorylated proteins, and useful proteomics approaches to identify molecular cancer signatures. The recent progress in phosphoproteomics research in lung cancer will be also discussed. PMID:23202899

  19. Biological considerations in lung cancer.

    PubMed

    Almand, B; Carbone, D P

    2001-01-01

    Our understanding of lung cancer biology has rapidly expanded in recent years. Lung cancer, unlike most human cancers, can be traced to an environmental risk factor in the majority of cases, and this fact is reflected in the vast number of genetic alterations discovered in lung tumors whose pathogenesis is believed to be mediated by carcinogen exposure. The discovery of these alterations has led to a greater understanding of tumor development. The dramatic progress in the understanding of the genetic and molecular basis of oncogenesis and the induction of immunity has led to a rejuvenation of efforts to apply this new knowledge to this common and refractory disease. Further, the resurgent interest in cancer immunology and tumor-host interactions holds promise for the development of new approaches to treatment based on harvesting the immune systems ability to recognize these alterations. Hopefully, this understanding will lead to novel approaches with real and convincing clinical efficacy once some of these strategies are tested in carefully performed randomized clinical trials with appropriate power to detect meaningful differences. PMID:11224984

  20. Analysis of Lung Flute-collected Sputum for Lung Cancer Diagnosis.

    PubMed

    Su, Jian; Anjuman, Nigar; Guarnera, Maria A; Zhang, Howard; Stass, Sanford A; Jiang, Feng

    2015-01-01

    Molecular analysis of sputum can help diagnose lung cancer. We have demonstrated that Lung Flute can be used to collect sputum from individuals who cannot spontaneously expectorate sputum. The objective of this study is to further evaluate the performance of the Lung Flute by comparing the characteristics of parallel samples collected with and without the Lung Flute and the usefulness for diagnosis of lung cancer. Fifty-six early-stage lung cancer patients (40 current smokers and 16 former smokers) and 73 cancer-free individuals (52 current smokers and 21 former smokers) were instructed to spontaneously cough and use Lung Flute for sputum sampling. Sputum cytology and polymerase chain reaction analysis of three miRNAs (miRs-21, 31, and 210) were performed in the specimens. All 92 current smokers and 11 (28.7%) of 37 former smokers spontaneously expectorated sputum and also produced sputum when using the Lung Flute. Twenty-seven former smokers (70.3%) who could not spontaneously expectorate sputum, however, were able to produce sputum when using the Lung Flute. The specimens were of low respiratory origin without contamination from other sources, eg, saliva. There was no difference of sputum volume and cell populations, diagnostic efficiency of cytology, and analysis of the miRNAs in the specimens collected by the two approaches. Analysis of the sputum miRNAs produced 83.93% sensitivity and 87.67% specificity for identifying lung cancer. Therefore, sputum collected by the Lung Flute has comparable features as spontaneously expectorated sputum. Using the Lung Flute enables former smokers who cannot spontaneously expectorate to provide adequate sputum to improve sputum collection for lung cancer diagnosis. PMID:26309391

  1. Analysis of Lung Flute–collected Sputum for Lung Cancer Diagnosis

    PubMed Central

    Su, Jian; Anjuman, Nigar; Guarnera, Maria A; Zhang, Howard; Stass, Sanford A; Jiang, Feng

    2015-01-01

    Molecular analysis of sputum can help diagnose lung cancer. We have demonstrated that Lung Flute can be used to collect sputum from individuals who cannot spontaneously expectorate sputum. The objective of this study is to further evaluate the performance of the Lung Flute by comparing the characteristics of parallel samples collected with and without the Lung Flute and the usefulness for diagnosis of lung cancer. Fifty-six early-stage lung cancer patients (40 current smokers and 16 former smokers) and 73 cancer-free individuals (52 current smokers and 21 former smokers) were instructed to spontaneously cough and use Lung Flute for sputum sampling. Sputum cytology and polymerase chain reaction analysis of three miRNAs (miRs-21, 31, and 210) were performed in the specimens. All 92 current smokers and 11 (28.7%) of 37 former smokers spontaneously expectorated sputum and also produced sputum when using the Lung Flute. Twenty-seven former smokers (70.3%) who could not spontaneously expectorate sputum, however, were able to produce sputum when using the Lung Flute. The specimens were of low respiratory origin without contamination from other sources, eg, saliva. There was no difference of sputum volume and cell populations, diagnostic efficiency of cytology, and analysis of the miRNAs in the specimens collected by the two approaches. Analysis of the sputum miRNAs produced 83.93% sensitivity and 87.67% specificity for identifying lung cancer. Therefore, sputum collected by the Lung Flute has comparable features as spontaneously expectorated sputum. Using the Lung Flute enables former smokers who cannot spontaneously expectorate to provide adequate sputum to improve sputum collection for lung cancer diagnosis. PMID:26309391

  2. Lung cancer in pregnancy.

    PubMed

    Holzmann, Kornelia; Kropfmüller, Roland; Schinko, Herwig; Bogner, Stephan; Fellner, Franz; Arzt, Wolfgang; Lamprecht, Bernd

    2015-08-01

    In the 26th week of gestation, a 29-year-old pregnant office employee was referred to the pulmonary department of Linz General Hospital (AKH) under the suspicion of tuberculosis. She complained of a cough with intermittent hemoptysis and pain in the thoracic spine from which she had been suffering the past 9 weeks. A plain chest X-ray showed a dense infiltrate on the right side and multiple smaller shadows in both lungs. Laboratory testing revealed anemia, leukocytosis, and an increase of C-reactive protein. All tests for tuberculosis were negative.A bronchoscopy was performed and biopsies were taken from the right upper and middle lobe. The histopathological examination found cells of an adenocarcinoma. A magnetic resonance imaging (MRI) revealed a large tumor and surrounding atelectasis were seen in the right upper and middle lobe, as well as multiple intrapulmonary metastases in both lungs. In addition, not only metastases in the thoracic spine (level Th2/3) but also at other osseous locations and multiple cerebral metastases were detected. The patient received one cycle of chemotherapy consisting of docetaxel and carboplatin (AUC5) in the 27th week of gestation. Additional radiotherapy was applied to the involved thoracic spine. Due to positive epidermal growth factor receptor mutation, therapy with gefitinib 250 mg/day was started 2 days after a Caesarean section (preceded by treatment for fetal lung maturation). A healthy girl was delivered in the 30th week of pregnancy. Staging with computed tomography (CT) after delivery revealed an unstable fracture of Th2 with compression of the spinal cord. Neurosurgery was performed, consisting of a ventral corporectomy of Th1-2 followed by an anterior and posterior osteosynthesis for stabilization. The patient was discharged without neurological deficits within 1 week. Subsequent treatment with gefitinib improved the performance status of the patient, and CT scans of the chest and an MRI of the brain showed the size of

  3. Vaccine Therapy and Sargramostim With or Without Docetaxel in Treating Patients With Metastatic Lung Cancer or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2014-03-28

    Extensive Stage Small Cell Lung Cancer; Recurrent Colon Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Rectal Cancer; Recurrent Small Cell Lung Cancer; Stage IV Colon Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Rectal Cancer

  4. Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

    ClinicalTrials.gov

    2014-08-04

    Adenocarcinoma of the Lung; Bronchoalveolar Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  5. Lung cancer: Biology and treatment options.

    PubMed

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    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 (SCLCs) and non-small cell lung carcinomas (NSCLCs). 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

  6. Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen.

    PubMed

    Li, Ping; Wang, Ya-Di; Cheng, Jian; Chen, Jun-Chen; Ha, Min-Wen

    2015-12-01

    BCL-2 Associated athanogene 1 (BAG-1) and Xeroderma pigmentosum group D (XPD) are involved in the nucleotide excision repair pathway and DNA repair. We aimed to investigate whether polymorphisms in BAG-1 and XPD have effects on chemotherapy sensitivity and survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine combined cisplatin (NP) regimen. A total of 142 patients with diagnosed advanced NSCLC were recruited in the current study. NP regimen was applied for all eligible patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for BAG-1 (codon 324) and XPD (codons 312 and 751) genotyping. The treatment response was evaluated according to the RECIST guidelines. Progression-free survival (PFS) and overall survival (OS) were record as median and end point, respectively. As for BAG-1 codon 324, the chemotherapy sensitivity in NSCLC patients with CT genotype was 0.383 times of those with CC genotype (P < 0.05). With respect to XPD codon 751, the chemotherapy sensitivity in NSCLC patients with Lys/Gln genotype was 0.400 times of those with Lys/Lys genotype (P < 0.05). In addition, NSCLC patients carrying combined C/C genotype at codon 324 in BAG-1, Asp/Asp of XPD codon 312, and Lys/Lys of XPD codon 751 produced a higher efficacy of NP chemotherapy compared to those carrying mutation genotypes (all P < 0.05). Further, there were significant differences in PFS between patients with combined C/C genotype of BAG-1 codon 324, Lys/Lys genotype of XPD codon 751, and Asp/Asp genotype of XPD codon 312 and patients carrying BAG-1 codon 324 C/T genotype, XPD codon751 Lys/Gln genotype, and XPD codon312 Asp/Asn genotype (P < 0.05). Multivariate Cox regression analysis indicated that the combined wild-type of codon 324 XPD, codon 751 XPD, and codon 312 BAG-1 is the protective factor for OS and PFS, and clinical stages is the risk factor for OS and PFS. In conclusion, our research

  7. Lung cancer stem cells—characteristics, phenotype

    PubMed Central

    George, Rachel; Sethi, Tariq

    2016-01-01

    Lung cancer remains a major cause of cancer-related deaths worldwide with unfavourable prognosis mainly due to the late stage of disease at presentation. High incidence and disease recurrence rates are a fact despite advances in treatment. Ongoing experimental and clinical observations suggest that the malignant phenotype in lung cancer is sustained by lung cancer stem cells (CSCs) which are putative stem cells situated throughout the airways that have the potential of initiating lung cancer formation. These cells share the common characteristic of increased proliferation and differentiation, long life span and resistance to chemotherapy and radiation therapy. This review summarises the current knowledge on their characteristics and phenotype. PMID:27413709

  8. Lung Cancer Awareness Week

    ERIC Educational Resources Information Center

    Glennon, Catherine; Laczko, Lori

    2003-01-01

    Smoking is the most preventable cause of death in our society. Tobacco use is responsible for nearly one in five deaths in the United States and the cause of premature death of approximately 2 million individuals in developed countries. Smoking accounts for at least 30% of all cancer deaths and is a major cause of heart disease, cerebrovascular…

  9. Cryotherapy in Treating Patients With Lung Cancer That Has Spread to the Other Lung or Parts of the Body

    ClinicalTrials.gov

    2012-03-16

    Advanced Malignant Mesothelioma; Extensive Stage Small Cell Lung Cancer; Lung Metastases; Recurrent Malignant Mesothelioma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  10. [Cannabis smoking and lung cancer].

    PubMed

    Underner, M; Urban, T; Perriot, J; de Chazeron, I; Meurice, J-C

    2014-06-01

    Cannabis is the most commonly smoked illicit substance in the world. It can be smoked alone in plant form (marijuana) but it is mainly smoked mixed with tobacco. The combined smoking of cannabis and tobacco is a common-place phenomenon in our society. However, its use is responsible for severe pulmonary consequences. The specific impact of smoking cannabis is difficult to assess precisely and to distinguish from the effect of tobacco. Marijuana smoke contains polycyclic aromatic hydrocarbons and carcinogens at higher concentration than tobacco smoke. Cellular, tissue, animal and human studies, and also epidemiological studies, show that marijuana smoke is a risk factor for lung cancer. Cannabis exposure doubles the risk of developing lung cancer. This should encourage clinicians to identify cannabis use and to offer patients support in quitting. PMID:25012035

  11. Bronchoplastic procedures for lung cancer.

    PubMed

    Naruke, T; Yoneyama, T; Ogata, T; Suemasu, K

    1977-06-01

    Twenty patients with lung cancer have undergone bronchoplastic procedures September, 1965, to June, 1976 in our hospital. Bronchoplastic procedures are considered to be indicated for early cases of hilar lung cancer rather than for somewhat advanced cases. Endoscopic examination and roentgenograms of the bronchial arteries are needed to delineate resectional lines of bronchus, the former for deciding the mucosal extent and the latter the intrabronchial extent of the tumor. The bronchoplastic procedures we adopted were free from the risks and dangers generally accompanying the operation, and there were no postoperative deaths. For the prevention of postoperative complications, careful attention to suture technique is needed, and postoperative bronchoscopic suction of intrabronchial secretions is absolutely necessary. These procedures assure good quality of life postoperatively and improvement in the survival rate by preserving pulmonary function, enhancing curability, and increasing the operative indications. These advantages warrant high evaluation of the operation. PMID:870767

  12. Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality

    PubMed Central

    Jiang, Yanyan; Verbiest, Tom; Devery, Aoife M.; Bokobza, Sivan M.; Weber, Anika M.; Leszczynska, Katarzyna B.; Hammond, Ester M.; Ryan, Anderson J.

    2016-01-01

    Purpose Poly(ADP-ribose) polymerase (PARP) inhibitors potentiate radiation therapy in preclinical models of human non-small cell lung cancer (NSCLC) and other types of cancer. However, the mechanisms underlying radiosensitization in vivo are incompletely understood. Herein, we investigated the impact of hypoxia on radiosensitization by the PARP inhibitor olaparib in human NSCLC xenograft models. Methods and Materials NSCLC Calu-6 and Calu-3 cells were irradiated in the presence of olaparib or vehicle under normoxic (21% O2) or hypoxic (1% O2) conditions. In vitro radiosensitivity was assessed by clonogenic survival assay and γH2AX foci assay. Established Calu-6 and Calu-3 subcutaneous xenografts were treated with olaparib (50 mg/kg, daily for 3 days), radiation (10 Gy), or both. Tumors (n=3/group) were collected 24 or 72 hours after the first treatment. Immunohistochemistry was performed to assess hypoxia (carbonic anhydrase IX [CA9]), vessels (CD31), DNA double strand breaks (DSB) (γH2AX), and apoptosis (cleaved caspase 3 [CC3]). The remaining xenografts (n=6/group) were monitored for tumor growth. Results In vitro, olaparib showed a greater radiation-sensitizing effect in Calu-3 and Calu-6 cells in hypoxic conditions (1% O2). In vivo, Calu-3 tumors were well-oxygenated, whereas Calu-6 tumors had extensive regions of hypoxia associated with down-regulation of the homologous recombination protein RAD51. Olaparib treatment increased unrepaired DNA DSB (P<.001) and apoptosis (P<.001) in hypoxic cells of Calu-6 tumors following radiation, whereas it had no significant effect on radiation-induced DNA damage response in nonhypoxic cells of Calu-6 tumors or in the tumor cells of well-oxygenated Calu-3 tumors. Consequently, olaparib significantly increased radiation-induced growth inhibition in Calu-6 tumors (P<.001) but not in Calu-3 tumors. Conclusions Our data suggest that hypoxia potentiates the radiation-sensitizing effects of olaparib by contextual

  13. Unmasking the lung cancer epigenome.

    PubMed

    Belinsky, Steven A

    2015-01-01

    The reprogramming of the epigenome through silencing of genes and microRNAs by cytosine DNA methylation and chromatin remodeling is critical for the initiation and progression of lung cancer through affecting all major cell regulatory pathways. Importantly, the fact that epigenetic reprogramming is reversible by pharmacological agents has opened new avenues for clinical intervention. This review focuses on the tremendous progress made in elucidating genes and microRNAs that are epigenetically silenced in lung cancer and highlights how loss of function impacts cell phenotype and major signaling pathways. The article describes the utility of (a) an in vitro model using hTERT/Cdk4 immortalized human bronchial epithelial cell lines to identify genes and microRNAs silenced during premalignancy and (b) an in vivo orthotopic nude rat lung cancer model to evaluate response to epigenetic therapy. New insights regarding the advantage of aerosol delivery of demethylating agents and the concept of priming tumors for subsequent therapy are presented and discussed. PMID:25668024

  14. Attitudes and Stereotypes in Lung Cancer versus Breast Cancer

    PubMed Central

    Sriram, N.

    2015-01-01

    Societal perceptions may factor into the high rates of nontreatment in patients with lung cancer. To determine whether bias exists toward lung cancer, a study using the Implicit Association Test method of inferring subconscious attitudes and stereotypes from participant reaction times to visual cues was initiated. Participants were primarily recruited from an online survey panel based on US census data. Explicit attitudes regarding lung and breast cancer were derived from participants’ ratings (n = 1778) regarding what they thought patients experienced in terms of guilt, shame, and hope (descriptive statements) and from participants’ opinions regarding whether patients ought to experience such feelings (normative statements). Participants’ responses to descriptive and normative statements about lung cancer were compared with responses to statements about breast cancer. Analyses of responses revealed that the participants were more likely to agree with negative descriptive and normative statements about lung cancer than breast cancer (P<0.001). Furthermore, participants had significantly stronger implicit negative associations with lung cancer compared with breast cancer; mean response times in the lung cancer/negative conditions were significantly shorter than in the lung cancer/positive conditions (P<0.001). Patients, caregivers, healthcare providers, and members of the general public had comparable levels of negative implicit attitudes toward lung cancer. These results show that lung cancer was stigmatized by patients, caregivers, healthcare professionals, and the general public. Further research is needed to investigate whether implicit and explicit attitudes and stereotypes affect patient care. PMID:26698307

  15. Attitudes and Stereotypes in Lung Cancer versus Breast Cancer.

    PubMed

    Sriram, N; Mills, Jennifer; Lang, Edward; Dickson, Holli K; Hamann, Heidi A; Nosek, Brian A; Schiller, Joan H

    2015-01-01

    Societal perceptions may factor into the high rates of nontreatment in patients with lung cancer. To determine whether bias exists toward lung cancer, a study using the Implicit Association Test method of inferring subconscious attitudes and stereotypes from participant reaction times to visual cues was initiated. Participants were primarily recruited from an online survey panel based on US census data. Explicit attitudes regarding lung and breast cancer were derived from participants' ratings (n = 1778) regarding what they thought patients experienced in terms of guilt, shame, and hope (descriptive statements) and from participants' opinions regarding whether patients ought to experience such feelings (normative statements). Participants' responses to descriptive and normative statements about lung cancer were compared with responses to statements about breast cancer. Analyses of responses revealed that the participants were more likely to agree with negative descriptive and normative statements about lung cancer than breast cancer (P<0.001). Furthermore, participants had significantly stronger implicit negative associations with lung cancer compared with breast cancer; mean response times in the lung cancer/negative conditions were significantly shorter than in the lung cancer/positive conditions (P<0.001). Patients, caregivers, healthcare providers, and members of the general public had comparable levels of negative implicit attitudes toward lung cancer. These results show that lung cancer was stigmatized by patients, caregivers, healthcare professionals, and the general public. Further research is needed to investigate whether implicit and explicit attitudes and stereotypes affect patient care. PMID:26698307

  16. [Innovation in Surgery for Advanced Lung Cancer].

    PubMed

    Nakano, Tomoyuki; Yasunori, Sohara; Endo, Shunsuke

    2016-07-01

    Thoracoscopic surgery can be one of less invasive surgical interventions for early stage lung cancer. Locally advanced lung cancer, however, cannot avoid aggressive procedures including pneumonectomy and/or extended combined resection of chest wall, aorta, esophagus, etc. for complete resection. Surgical approach even for advanced lung cancer can be less invasive by benefit from new anti-cancer treatment, innovated manipulations of bronchoplasty and angioplasty, and bench surgery( lung autotransplantation technique). We herein reviewed the strategy to minimize invasive interventions for locally advanced lung cancer, introducing 2 successful cases with advanced lung cancer. The 1st patient is a 62-year old man with centrally advanced lung cancer invading to mediastinum. Right upper sleeve lobectomy with one-stoma carinoplasty following induction chemoradiation therapy was successful. The operation time was 241 minutes. The performance status is good with no recurrence for 60 months after surgery. The 2nd is a 79-year old man with advanced lung cancer invading to the distal aortic arch. Left upper segmentectomy following thoracic endovascular aortic repair with stentgraft was successful with no extracorporeal circulation. The operation time was 170 minutes. The performance status is good with no recurrence for 30 months after surgery. The invasiveness of surgical interventions for local advanced lung cancer can be minimized by innovated device and new anti-cancer drugs. PMID:27440037

  17. GM3 synthase gene is a novel biomarker for histological classification and drug sensitivity against epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.

    PubMed

    Noguchi, Mariko; Suzuki, Tomoko; Kabayama, Kazuya; Takahashi, Hiroki; Chiba, Hirofumi; Shiratori, Masanori; Abe, Shosaku; Watanabe, Atsushi; Satoh, Masaaki; Hasegawa, Tadashi; Tagami, Seiichi; Ishii, Atsushi; Saitoh, Masaki; Kaneko, Masanori; Iseki, Ken; Igarashi, Yasuyuki; Inokuchi, Jin-ichi

    2007-10-01

    Expression of gangliosides and alterations in their composition have been observed during cell proliferation and differentiation and in certain cell cycle phases, brain development and cancer malignancy. To investigate the characteristics of GM3 synthase, SAT-I mRNA and ganglioside GM3 expression levels in lung cancer, we examined the expression levels of SAT-I mRNA as well as GM3 in 40 tumor tissues surgically removed from non-small cell lung cancer patients. Adenocarcinoma tissues expressed SAT-I mRNA levels that were significantly higher than those of squamous and other carcinomas (P < 0.0001). Moreover, the SAT-I mRNA levels were high in the bronchioalveolar carcinoma subtype and low in the solid and mucin subtypes of adenocarcinomas (P = 0.049, 0.049 and 0.013, respectively). To clarify the relationship between SAT-I mRNA and epidermal growth factor receptor (EGFR)-tyrosine kinase (TK) inhibitor sensitivity, we carried out drug sensitivity tests for the EGFR-TK inhibitors gefitinib and AG1478 using eight adenocarcinoma cell lines expressing no EGFR mutations. The IC(50) values for gefitinib and AG1478 decreased dramatically with increasing SAT-I mRNA levels (R(2) = 0.81 and 0.59, respectively), representing a wide range of drug sensitivities among adenocarcinoma cell lines. To explore a possible mechanism of how GM3 could enhance the sensitivity to EGFR-TK inhibitors, the SAT-I gene was introduced stably into a GM3-negative clone of murine 3LL lung cancer cells to produce GM3-reconstituted clones. We found an increase in EGFR protein levels and gefitinib sensitivity in GM3-reconstituted cells, suggesting the involvement of GM3 in the turnover of EGFR protein. Therefore, it is highly expected that, by measuring the expression levels of SAT-I mRNA in lung biopsy samples from non-small cell lung cancer patients, enhanced pathological identification and individualized chemotherapeutic strategies can be established for the appropriate use of EGFR-TK inhibitors

  18. Lung Cancer and Interstitial Lung Diseases: A Systematic Review

    PubMed Central

    Archontogeorgis, Kostas; Steiropoulos, Paschalis; Tzouvelekis, Argyris; Nena, Evangelia; Bouros, Demosthenes

    2012-01-01

    Interstitial lung diseases (ILDs) represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis. PMID:22900168

  19. Small non-coding RNA biomarkers in sputum for lung cancer diagnosis.

    PubMed

    Su, Yun; Guarnera, Maria A; Fang, HongBin; Jiang, Feng

    2016-01-01

    The early detection of lung cancer can reduce the mortality. However, there is no effective means in clinical settings for noninvasively detecting lung cancer. We previously developed 3 sputum miRNA biomarkers and 2 sputum small nucleolar RNA (snoRNA) biomarkers that can potentially be used for noninvasively diagnosing lung cancer. Here we evaluate the individual and combined applications of the two types of biomarkers in different sets of lung cancer patients and controls. Combined analysis of the miRNAs and snoRNAs has a synergistic effect with 89 % sensitivity and 89 % specificity, and may provide a useful tool for lung cancer early detection. PMID:27176474

  20. Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica, Reduces LRRC8A Expression and Volume-Sensitive Release of Organic Osmolytes in Human Lung Epithelial Cancer Cells.

    PubMed

    Thorsteinsdottir, Unnur Arna; Thorsteinsdottir, Margret; Lambert, Ian Henry

    2016-01-01

    We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 µg/mL, 24 h), a γ-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 µg/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4 ) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells. PMID:26549524

  1. Year-in-Review of Lung Cancer

    PubMed Central

    2012-01-01

    In the last several years, we have made slow but steady progress in understanding molecular biology of lung cancer. This review is focused on advances in understanding the biology of lung cancer that have led to proof of concept studies on new therapeutic approaches. The three selected topics include genetics, epigenetics and non-coding RNA. This new information represents progress in the integration of molecular mechanisms that to identify more effective ways to target lung cancer. PMID:23166546

  2. 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. PMID:27178304

  3. Chemotherapy for lung cancers: here to stay.

    PubMed

    Kris, Mark G; Hellmann, Matthew D; Chaft, Jamie E

    2014-01-01

    Four decades of clinical research document the effectiveness of chemotherapy in patients with lung cancers. Chemotherapeutic agents can improve lung cancer symptoms, lengthen life in most patients with lung cancers, and enhance curability in individuals with locoregional disease when combined with surgery or irradiation. Chemotherapy's effectiveness is enhanced in patients with EGFR-mutant and ALK-positive lung cancers and can "rescue" individuals whose oncogene-driven cancers have become resistant to targeted agents. As immunotherapies become part of the therapeutic armamentarium for lung cancers, chemotherapeutic drugs have the potential to modulate the immune system to enhance the effectiveness of immune check point inhibitors. Even in this era of personalized medicine and targeted therapies, chemotherapeutic agents remain essential components in cancer care. PMID:24857127

  4. Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-06-04

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  5. TNM classification for lung cancer.

    PubMed

    Watanabe, Yoh

    2003-12-01

    The international tumor-node-metastasis (TNM) staging system is the "international language" in cancer diagnosis and treatment. Six revisions of the TNM staging system for lung cancer have been repeated over the past 35 years after the beginning of UICC-TNM classification in 1968. The 1997 revision for lung cancer has undergone an extensive correction for many deficiencies of the old staging system. As a result, the new staging system appears to be a great improvement over previous editions. There are, however, still some controversies and proposals for revising, even when the new staging system is applied in daily diagnoses and treatment for lung cancer. In the present paper, these problems are presented and discussed. Main subjects for discussions are as follows: (1). Since the 2nd revision, T1 and T2 lesions were divided at the border of a 3 cm tumor size. Is 3 cm diameter an appropriate cut-off point for dividing T1 and T2 lesions? (2). Is it valid to subdivide T1 and T2 lesions into each A and B? (3). Is it appropriate to down-stage all of T3N0M0 to stage IIB, because there exists heterogeneity of T3? (4). Definitions of T4 lesion. (5). Controversies in three kinds of lymph node maps. Especially, where there is a boundary between N1 and N2 station in each map? (6) How to classify separate tumor nodules (STN) in the same lobe, and in the non-primary lobe. (7) Controversy exists concerning the validity of present stage grouping, because there are no significant difference of survivals between IB and IIA, IIA and IIB in most reports and also between T3N0M0 and T3N1M0 in some reports. PMID:15003094

  6. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients. PMID:26483336

  7. Relevance of particle-induced rat lung tumors for assessing lung carcinogenic hazard and human lung cancer risk.

    PubMed Central

    Mauderly, J L

    1997-01-01

    Rats and other rodents are exposed by inhalation to identify agents that might present hazards for lung cancer in humans exposed by inhalation. In some cases, the results are used in attempts to develop quantitative estimates of human lung cancer risk. This report reviews evidence for the usefulness of the rat for evaluation of lung cancer hazards from inhaled particles. With the exception of nickel sulfate, particulate agents thought to be human lung carcinogens cause lung tumors in rats exposed by inhalation. The rat is more sensitive to carcinogenesis from nonfibrous particles than mice or Syrian hamsters, which have both produced false negatives. However, rats differ from mice and nonhuman primates in both the pattern of particle retention in the lung and alveolar epithelial hyperplastic responses to chronic particle exposure. Present evidence warrants caution in extrapolation from the lung tumor response of rats to inhaled particles to human lung cancer hazard, and there is considerable uncertainty in estimating unit risks for humans from rat data. It seems appropriate to continue using rats in inhalation carcinogenesis assays of inhaled particles, but the upper limit of exposure concentrations must be set carefully to avoid false-positive results. A positive finding in both rats and mice would give greater confidence that an agent presents a carcinogenic hazard to man, and both rats and mice should be used if the agent is a gas or vapor. There is little justification for including Syrian hamsters in assays of the intrapulmonary carcinogenicity of inhaled agents. PMID:9400748

  8. Lung Cancer in Never Smokers

    PubMed Central

    Yang, Ping

    2012-01-01

    Lung cancer in never smokers (LCINS) has lately been recognized as a unique disease based on rapidly gained knowledge from genomic changes to treatment responses. The focus of this article is on current knowledge and challenges with regard to LCINS expanded from recent reviews highlighting five areas: (1) distribution of LCINS by temporal trends, geographic regions, and populations; (2) three well-recognized environmental risk factors; (3) other plausible environmental risk factors; (4) prior chronic lung diseases and infectious diseases as risk factors; and (5) lifestyles as risk or protective factors. This article will also bring attention to recently published literature in two pioneering areas: (1) histological characteristics, clinical features with emerging new effective therapies, and social and psychological stigma; and (2) searching for susceptibility genes using integrated genomic approaches. PMID:21500120

  9. Enhanced Quitline Intervention in Smoking Cessation for Patients With Non-Metastatic Lung Cancer

    ClinicalTrials.gov

    2015-09-28

    Limited Stage 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; Tobacco Use Disorder

  10. 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 ... ePub This booklet covers: The anatomy of the lungs and basics about lung cancer Treatment for lung ...

  11. MET inhibition in lung cancer

    PubMed Central

    Giaj Levra, Matteo; Novello, Silvia

    2013-01-01

    Targeted agents have completely changed cancer treatment strategy, leading it from a “one size fits all” approach to a customized therapy. In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming “druggable” only in this last period of time. Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell-cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization. Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis. Met amplification is also described to be linked to EGFR acquired resistance. Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment. This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation. PMID:25806202

  12. Lung cancer among Navajo uranium miners

    SciTech Connect

    Gottlieb, L.S.; Husen, L.A.

    1982-04-01

    Lung cancer has been a rare disease among the Indians of the southwestern United States. However, the advent of uranium mining in the area has been associated with an increased incidence of lung cancer among Navajo uranium miners. This study centers on Navajo men with lung cancer who were admitted to the hospital from February 1965 to May 1979. Of a total of 17 patients with lung cancer, 16 were uranium miners, and one was a nonminer. The mean value of cumulative radon exposure for this group was 1139.5 working level months (WLMs). The predominant cancer type was the small cell undifferentiated category (62.5 percent). The low frequency of cigarette smoking in this group supports the view that radiation is the primary cause of lung cancer among uranium miners and that cigarette smoking acts as a promoting agent.

  13. Taste thresholds in patients with small-cell lung cancer.

    PubMed

    Ovesen, L; Hannibal, J; Sørensen, M

    1991-01-01

    Recognition thresholds for the four basic tastes (salt, sour, sweet and bitter) were tested by the forced-choice technique in 27 patients with small-cell lung cancer, and 22 weight-matched control patients with non-malignant diseases. No significant differences in threshold concentrations could be demonstrated. When patients who were losing weight were compared with weight-stable patients, significantly lower taste thresholds for bitter substances were found in weight losing groups in both cancer and control patients. Small-cell lung cancer patients who responded to therapy had obtained an increased threshold for bitter taste at the time of reevaluation than at the time of diagnosis, an effect that may be explained by the chemotherapeutic regimen. The results suggest that in patients with small-cell lung cancer it is not the cancer disease per se but the weight loss that often accompanies it that causes an increased taste sensitivity for bitter substances. PMID:1847701

  14. Chemoprevention studies within lung cancer screening programmes.

    PubMed

    Veronesi, G; Guerrieri-Gonzaga, A; Infante, M; Bonanni, B

    2015-01-01

    While aggressive tobacco control and help to stop smoking are essential weapons in the fight against lung cancer, screening with low-dose computed tomography (LDCT) in high-risk populations and chemoprevention may also contribute to reducing lung cancer deaths. Persons undergoing LDCT screening are an ideal population to be tested for agents potentially able to prevent the development of lung cancer by the regression of precancerous lesions, which are routinely monitored as part of the screening process. Peripheral subsolid nodules appear as particularly suitable targets, since many are adenocarcinoma precursors. A study on inhaled budesonide (a potential chemopreventive drug) for 1 year found that the mean size of non-solid lung nodules was significantly reduced over 5 years of follow-up, compared to inhaled placebo, in a population of high-risk individuals with indeterminate lung nodules not requiring immediate specific investigation for lung cancer and detected as part of a lung cancer screening program with LDCT. A new randomised placebo-controlled phase-II trial to test the ability of aspirin to induce the regression of non-solid and partially solid nodules detected by LDCT screening has been started. The effect of aspirin on a miRNA signature able to predict the presence of both cancer and precancerous lesions in high-risk asymptomatic individuals is also being monitored in the trial. This signature was previously shown to predict the presence of both lung cancer and non-solid lung nodules in asymptomatic individuals. PMID:26635901

  15. [Developing surgical options for lung cancer].

    PubMed

    Sihvo, Eero

    2016-01-01

    The selection of correct treatment for lung cancer is multidisciplinary collaboration and requires careful assessment of the extent of the tumor and the condition of the patient. In localized non-small cell lung cancer, mere surgery or surgery in combination with adjuvant therapies are the best options for curing the disease. The trend in modern surgery is mini-invasiveness and preservation of lung tissue. Accordingly, any unit conducting lung cancer operations should have access to all modern techniques in order to provide each patient with optimal, patient-tailored surgical therapy. PMID:27132298

  16. Classification and Pathology of Lung Cancer.

    PubMed

    Zheng, Min

    2016-07-01

    Advancement in the understanding of lung tumor biology enables continued refinement of lung cancer classification, reflected in the recently introduced 2015 World Health Organization classification of lung cancer. In small biopsy or cytology specimens, special emphasis is placed on separating adenocarcinomas from the other lung cancers to effectively select tumors for targeted molecular testing. In resection specimens, adenocarcinomas are further classified based on architectural pattern to delineate tissue types of prognostic significance. Neuroendocrine tumors are divided into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma based on a combination of features, especially tumor cell proliferation rate. PMID:27261908

  17. The impact of the Cancer Genome Atlas on lung cancer.

    PubMed

    Chang, Jeremy T-H; Lee, Yee Ming; Huang, R Stephanie

    2015-12-01

    The Cancer Genome Atlas (TCGA) has profiled more than 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 was to demonstrate the impact of TCGA on lung cancer research under 4 themes: diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools. Examples are given related to DNA mutation, copy number variation, messenger RNA, and microRNA expression along with methylation profiling. PMID:26318634

  18. Lung Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Arabic) سرطان الرئة - العربية Bilingual PDF Health Information Translations Bosnian (Bosanski) Lung Cancer Karcinom pluća - Bosanski (Bosnian) Bilingual PDF Health Information Translations Chinese - Simplified (简体中文) Lung Cancer 肺癌 - 简体中文 (Chinese - ...

  19. Lung Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Lung Cancer URL of this page: https://medlineplus.gov/languages/lungcancer.html Other topics ... V W XYZ List of All Topics All Lung Cancer - Multiple Languages ... To use the sharing features on this page, please enable JavaScript. Arabic (العربية) Bosnian (Bosanski) Chinese - ...

  20. Recent advances in lung cancer biology

    SciTech Connect

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  1. Gene Therapy for Lung Cancer.

    PubMed

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein. PMID:27481008

  2. Endoscopic mediastinal staging of lung cancer.

    PubMed

    Khoo, Kay-Leong; Ho, Khek-Yu

    2011-04-01

    The advent of endoscopic ultrasound-guided sampling procedures such as endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has lead to significant advances in the mediastinal diagnosis and staging of lung cancer. These endoscopic techniques can be performed in the outpatient setting under conscious sedation and local anesthesia, in contrast to the surgical standard, mediastinoscopy (MS), which requires operating theatre time and general anesthesia. Proponents of mediastinoscopy have always emphasized the advantages of mediastinoscopy, namely its sensitivity even with a low prevalence of mediastinal metastases and its low false negative rate. Newer endoscopic techniques such as EBUS-TBNA are showing sensitivities exceeding that of mediastinoscopy, even in the setting of an equally low prevalence of mediastinal metastases. However, endoscopic techniques have double the false negative rate of mediastinoscopy. As the tracheobronchial route and esophageal route provide almost complete access to mediastinal lymph nodes, these endoscopic techniques are complementary rather than competing. When used in combination, it is possible mediastinoscopy may be superseded. The challenge however, is how best to select the appropriate endoscopic procedures to accurately stage lung cancer in the most cost-effective manner. PMID:21130638

  3. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    PubMed Central

    Chen, Yingrong; Ma, Zhihong; Min, Lishan; Li, Hongwei; Wang, Bin; Zhong, Jing; Dai, Licheng

    2015-01-01

    Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC) curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA) and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer. PMID:25961003

  4. [Idiopathic pulmonary fibrosis and lung cancer].

    PubMed

    Yoshimura, Akinobu; Kudoh, Syoji

    2003-02-01

    It is widely known that patients with idiopathic pulmonary fibrosis (IPF) are frequently associated with lung cancer. Although a complication with lung cancer is an important prognostic factor for IPF, standard treatments for lung cancer cannot be given because of IPF. Especially, the administration of many anticancer agents is limited by a complication with IPF, which is recognized as a risk factor for the development of fatal lung injury in cancer chemotherapy. Epidemiological studies reveal that cigarette smoking and occupational and environmental exposure to toxic substances are common risk factors for both IPF and lung cancer. It has been assumed that metaplasia in fibrous lesions is pathologically a precancerous lesion, but it is necessary to prove several genetic abnormalities in the process of carcinogenesis in order to clarify that. Currently, several genetic abnormalities in IPF, including in p53, K-ras, FHIT and transforming growth factor (TGF)-beta 1 type II receptor, have been reported. PMID:12610869

  5. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent 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

  6. Early diagnosis of lung cancer

    NASA Astrophysics Data System (ADS)

    Saccomanno, Geno; Bechtel, Joel J.

    1991-06-01

    Lung cancer remains the leading cause of death in the United States. Although the incidence of cigarette smoking is decreasing in the United States it appears to be increasing worldwide. The five-year survival rate has not improved in cases with advanced disease, but several articles have indicated that survival can be improved in cases diagnosed early by sputum cytology and chest x-ray. In cases diagnosed while the lesion is in the in-situ stage or measures less than 1 cm in diameter, surgical excision and/or radiation therapy improves survival; therefore, the early diagnosis of high-risk patients should be vigorously pursued. A recent study at a community hospital in Grand Junction, Colorado, presented 45 lung cancer cases diagnosed with positive sputum cytology and negative chest x-ray, and indicates that early diagnosis does improve survival. This study has been conducted during the past six years; 16 cases have survived three years and six cases show five-year survival.

  7. Asbestos, Lung Cancers, and Mesotheliomas

    PubMed Central

    Heintz, Nicholas H.; Janssen-Heininger, Yvonne M. W.; Mossman, Brooke T.

    2010-01-01

    Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun proto-oncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-oncogene expression and several of the signaling pathways activated by asbestos were redox dependent, explaining why antioxidants and antioxidant enzymes were elevated in lung and pleura after exposure to asbestos and how they alleviated many of the phenotypic and functional effects of asbestos in vitro or after inhalation. Since these original studies, our efforts have expanded to understand the interface between asbestos-induced redox-dependent signal transduction cascades, the relationship between these pathways and cell fate, and the role of asbestos and cell interactions in development of asbestos-associated diseases. Of considerable significance is the fact that the signal transduction pathways activated by asbestos are also important in survival and chemoresistance of MMs and lung cancers. An understanding of the pathogenic features of asbestos fibers and dysregulation of signaling pathways allows strategies for the prevention and therapy of asbestos-related diseases. PMID:20068227

  8. Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

    ClinicalTrials.gov

    2016-06-07

    Adenocarcinoma of the Lung; Extensive Stage Small Cell Lung Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent 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

  9. Frizzled-8 as a putative therapeutic target in human lung cancer

    SciTech Connect

    Wang, Hua-qing; Xu, Mei-lin; Ma, Jie; Zhang, Yi; Xie, Cong-hua

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fzd-8 is over-expressed in human lung cancer. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 inhibits proliferation and Wnt pathway in lung cancer cells. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 suppresses tumor growth in vivo. Black-Right-Pointing-Pointer shRNA knock-down Fzd-8 sensitizes lung cancer cells to chemotherapy Taxotere. -- Abstract: Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p < 0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.

  10. A clinically relevant canine lung cancer model

    SciTech Connect

    Benfield, J.R.; Shors, E.C.; Hammond, W.G.; Paladugu, R.R.; Cohen, A.H.; Jensen, T.; Fu, P.C.; Pak, H.Y.; Teplitz, R.L.

    1981-12-01

    Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo(a)pyrene, nitrosomethylurea, dimethylbenzanthracene, and methylcholanthrene, singly or in combinations. Sustained-release discs were placed into lung parenchyma or sutured into major bronchi. Tracheal segments were isolated as cervical pedicle grafts. Gross and histological evolution was reproducible. Columnar and basal hyperplasia and squamous metaplasia were early changes. Atypia occurred within 6 weeks and was found in all dogs within 16 to 18 weeks. Invasive cancers occurred within 8 to 65 months. No tracheal graft developed cancer. Of 15 dogs with parenchymal sustained-release implants, 1 to date has developed cancer in 8 months. Four endobronchial regimens have produced 16 cancers in 56 lungs at risk for 18 to 65 months. No cancers developed in 23 lungs at risk from eight other regimens. Of 10 dogs at risk for unilateral endobronchial cancer, 5 have had cancer. Of 23 dogs with both lungs at risk, 9 developed cancer. We have shown focal carcinogenesis with well-defined pathogenesis and an extended preneoplastic period at predictable sites in a lung cancer model.

  11. [Development of molecular targeted therapies in lung cancers].

    PubMed

    Suda, Kenichi; Mitsudomi, Tetsuya

    2014-05-01

    Human cancers usually possess cumulative genetic aberrations. However, recent studies have revealed that the proliferation and survival of specific subsets of lung cancer depend on a few somatic mutation(s), so-called driver mutations. Representative driver mutations include the EGFR mutation and ALK translocation identified in about 40% and 3% of lung adenocarcinomas in Japan, respectively. These tumors are extremely sensitive to the respective tyrosine kinase inhibitors. This sensitivity has encouraged researchers and clinicians to explore novel driver mutations in lung cancers as future molecular targets. Driver mutations reported so far include the HER2 mutation, BRAF mutation, ROS1 translocation, RET translocation, and NTRK translocation in lung adenocarcinomas, and FGFR1 amplification, DDR2 mutation, and FGFR3 translocation in lung squamous cell carcinomas. However, despite initial dramatic responses, the acquisition of resistance to molecular targeted drugs is almost inevitable. Overcoming resistance to molecular targeted drugs, the key drugs at this time, is an urgent issue to improve the outcomes of lung cancer patients. PMID:24946519

  12. Mass Spectrometry–based Proteomic Profiling of Lung Cancer

    PubMed Central

    Ocak, Sebahat; Chaurand, Pierre; Massion, Pierre P.

    2009-01-01

    In an effort to further our understanding of lung cancer biology and to identify new candidate biomarkers to be used in the management of lung cancer, we need to probe these tissues and biological fluids with tools that address the biology of lung cancer directly at the protein level. Proteins are responsible of the function and phenotype of cells. Cancer cells express proteins that distinguish them from normal cells. Proteomics is defined as the study of the proteome, the complete set of proteins produced by a species, using the technologies of large-scale protein separation and identification. As a result, new technologies are being developed to allow the rapid and systematic analysis of thousands of proteins. The analytical advantages of mass spectrometry (MS), including sensitivity and high-throughput, promise to make it a mainstay of novel biomarker discovery to differentiate cancer from normal cells and to predict individuals likely to develop or recur with lung cancer. In this review, we summarize the progress made in clinical proteomics as it applies to the management of lung cancer. We will focus our discussion on how MS approaches may advance the areas of early detection, response to therapy, and prognostic evaluation. PMID:19349484

  13. 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. PMID:27013409

  14. A reevaluation of CD22 expression in human lung cancer.

    PubMed

    Pop, Laurentiu M; Barman, Stephen; Shao, Chunli; Poe, Jonathan C; Venturi, Guglielmo M; Shelton, John M; Pop, Iliodora V; Gerber, David E; Girard, Luc; Liu, Xiao-yun; Behrens, Carmen; Rodriguez-Canales, Jaime; Liu, Hui; Wistuba, Ignacio I; Richardson, James A; Minna, John D; Tedder, Thomas F; Vitetta, Ellen S

    2014-01-01

    CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22(+) Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22(+) Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins. PMID:24395821

  15. Early diagnosis of lung cancer.

    PubMed

    Yasufuku, Kazuhiro

    2010-03-01

    Early detection and surgical resection is essential for the treatment of lung cancer. Although the introduction of low-dose spiral computed tomography (CT) is considered to be one of the most promising clinical research developments, CT screening is used for detecting small peripheral lesions. Tumors arising in the central airways require other techniques for early detection. Centrally arising squamous cell carcinoma of the airway, especially in heavy smokers, is thought to develop through multiple stages from squamous metaplasia to dysplasia, followed by carcinoma in situ (CIS), progressing to invasive cancer. It would be ideal to be able to detect and treat preinvasive bronchial lesions defined as dysplasia and CIS before progressing to invasive cancer. Great efforts have been made to develop new mucosal imaging techniques. Bronchoscopic imaging techniques capable of detecting preinvasive lesions and currently available in clinical practice include autofluorescence bronchoscopy (AFB), high magnification ronchovideoscope, and narrow band imaging (NBI). For a more precise evaluation of newly detected preinvasive lesions, endobronchial ultrasound (EBUS) and optical coherence tomography (OCT) can be used. PMID:20172431

  16. Sequencing study on familial lung squamous cancer

    PubMed Central

    LI, SHAOMIN; WANG, LINA; MA, ZHENCHUAN; MA, YUEFENG; ZHAO, JIANGMAN; PENG, BO; QIAO, ZHE

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer-related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer. PMID:26622902

  17. Metallothioneins in the lung cancer.

    PubMed

    Werynska, Bozena; Pula, Bartosz; Kobierzycki, Christopher; Dziegiel, Piotr; Podhorska-Okolow, Marzenna

    2015-01-01

    Metallothioneins (MTs) are low weight proteins involved in several key cellular processes such as metal ions homeostasis, detoxification and scavenging of free radicals. Four groups of MTs are distinguished: MT-1, MT-2, MT-3 and MT-4. Regardless of the type, MTs are characterized by high content of cysteine, responsible for their biological properties such as binding of relevant zinc and copper ions, as well as toxic ions such as lead and cadmium. MTs were additionally shown to protect cells against oxidative stress damage and participate in differentiation, proliferation and/or apoptosis of normal and cancer cells. Many studies of different neoplasms showed association of elevated MTs levels with occurrence of chemo- and radiotherapy resistance and poor patients' outcome. In this review, we summarize and discuss the potential mechanism of action of metallotioneins in lung physiology and pathology. PMID:25815626

  18. Lung cancer during pregnancy: A narrative review.

    PubMed

    Mitrou, Sotirios; Petrakis, Dimitrios; Fotopoulos, George; Zarkavelis, George; Pavlidis, Nicholas

    2016-07-01

    Lung cancer, the leading cause of cancer deaths in males for decades, has recently become one of commonest causes for women too. As women delay the start of their family, the co-existence of cancer and pregnancy is increasingly observed. Nevertheless, lung cancer during pregnancy remains a rather uncommon condition with less than 70 cases published in recent years. Non-small cell lung carcinoma is the commonest type accounting for about 85% of all cases. Overall survival rates are low. Chemotherapy and/or targeted treatment have been used with poor outcomes. The disease has been also found to affect the products of conception with no short- or long-term consequences for the neonate. This article is referring to a narrative review of lung cancers diagnosed in pregnant women around the world. PMID:27408759

  19. Lung Cancer:Symptoms, Diagnosis, Treatments & Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Lung Cancer Lung Cancer: Symptoms, Diagnosis, Treatments & Research Past Issues / Winter 2013 ... lung cancer are given intravenously or by mouth. Lung Cancer Research The large-scale National Lung Screening Trial, ...

  20. Cryptogenic fibrosing alveolitis and lung cancer.

    PubMed

    Turner-Warwick, M; Lebowitz, M; Burrows, B; Johnson, A

    1980-07-01

    Lung cancer was found in 20 (9.8%) of 205 patients with cryptogenic fibrosing alveolitis (CFA) or 12.9% of the 155 patients in this series followed to death. An excess relative risk of lung cancer of 14.1 was found in patients with CFA compared to the general population of comparable age and sex, allowing for the lengths of follow-up of the CFA patients. The relative risk for male smokers was (observed/expected) 15+1.06 = 14.2, and for female smokers (O/E) 2/0.3 = 6.7. Only one male and one female non-smoker had lung cancer. These data suggest that there is an excess risk of lung cancer not wholly accounted for by age, sex, or smoking habit. The distribution of histological types was not obviously different from that found in lung cancer without pulmonary fibrosis. Large opacities suggestive of lung cancer were present at the time of first hospital attendance for symptoms relating to CFA in four of the 20 patients. Finger clubbing was present in 19 (95%) compared with 116/185 (63%) of those so far not developing cancer. There were no other clinical differences at presentation. In particular, cancer was not found especially in those with longer survival from the onset of symptoms of CFA or with a greater initial radiographic change. PMID:7434310

  1. Immune checkpoint blockade in lung cancer.

    PubMed

    Somasundaram, Aswin; Socinski, Mark A; Villaruz, Liza C

    2016-08-01

    Immunotherapy has revolutionized the therapeutic landscape of advanced lung cancer. The adaptive immune system has developed a sophisticated method of tumor growth control, but T-cell activation is regulated by various checkpoints. Blockade of the immune checkpoints with therapies targeting the PD-1 pathway, such as nivolumab and pembrolizumab, has been validated as a therapeutic approach in non-small cell lung cancer. Newer therapies and novel combinations are also being evaluated, and the use of biomarkers in conjunction with these drugs is an area of active investigation. This review summarizes the current evidence for the efficacy and safety of the above approaches in the treatment of lung cancer. PMID:27585231

  2. The Canadian Lung Cancer Conference 2016

    PubMed Central

    Melosky, B.; Ho, C.

    2016-01-01

    Each February, the Canadian Lung Cancer Conference brings together lung cancer researchers, clinicians, and care professionals who are united in their commitment to improve the care of patients with lung cancer. This year’s meeting, held 11–12 February, featured a resident education session, a welcome dinner, networking sessions, lectures, breakout sessions, debates, and a satellite symposium. Key themes from this year’s meeting included innovations across the care spectrum and results of recent clinical trials with targeted agents, immuno-oncology agents, and novel drug combinations.

  3. 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

    PubMed

    Onion, David; Argent, Richard H; Reece-Smith, Alexander M; Craze, Madeleine L; Pineda, Robert G; Clarke, Philip A; Ratan, Hari L; Parsons, Simon L; Lobo, Dileep N; Duffy, John P; Atherton, John C; McKenzie, Andrew J; Kumari, Rajendra; King, Peter; Hall, Brett M; Grabowska, Anna M

    2016-04-01

    There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753-63. ©2016 AACR. PMID:26873730

  4. Lung and Upper Aerodigestive Cancer | Division of Cancer Prevention

    Cancer.gov

    This group conducts and supports research on the prevention and early detection of lung and head and neck cancers, as well as new approac | Conducts and supports research on the prevention and early detection of lung and head and neck cancers.

  5. Analysis of small nucleolar RNAs in sputum for lung cancer diagnosis

    PubMed Central

    Guarnera, Maria A.; Zhan, Min; Fang, HongBin; Stass, Sanford A.; Jiang, Feng

    2016-01-01

    Molecular analysis of sputum presents a noninvasive approach for diagnosis of lung cancer. We have shown that dysregulation of small nucleolar RNAs (snoRNAs) plays a vital role in lung tumorigenesis. We have also identified six snoRNAs whose changes are associated with lung cancer. Here we investigated if analysis of the snoRNAs in sputum could provide a potential tool for diagnosis of lung cancer. Using qRT-PCR, we determined expressions of the six snoRNAs in sputum of a training set of 59 lung cancer patients and 61 cancer-free smokers to develop a biomarker panel, which was validated in a testing set of 67 lung cancer patients and 69 cancer-free smokers for the diagnostic performance. The snoRNAs were robustly measurable in sputum. In the training set, a panel of two snoRNA biomarkers (snoRD66 and snoRD78) was developed, producing 74.58% sensitivity and 83.61% specificity for identifying lung cancer. The snoRNA biomarkers had a significantly higher sensitivity (74.58%) compared with sputum cytology (45.76%) (P < 0.05). The changes of the snoRNAs were not associated with stage and histology of lung cancer (All P >0.05). The performance of the biomarker panel was confirmed in the testing cohort. We report for the first time that sputum snoRNA biomarkers might be useful to improve diagnosis of lung cancer. PMID:26246471

  6. Lung cancer screening guidelines: common ground and differences

    PubMed Central

    Gulati, Swati

    2014-01-01

    Lung cancer accounts for almost one-third of all cancer related deaths. Lung cancer risk persists even after smoking cessation and so many lung cancers now are diagnosed in former smokers. Five-year survival of lung cancer has marginally improved over decades and significantly lags behind that of colon, breast and prostate cancer. Over the past one decade, lung cancer screening trials have shown promising results. Results from National Lung Cancer Screening Trial (NLST), have shown a significant 20% reduction in mortality with annual low dose computed tomography (LDCT) screening. Based on these results, annual LDCT testing has been recommended for lung cancer screening in high risk population. However, development and acceptance of lung cancer screening as a public health policy is still in the nascent stages. Major concerns relate to risk of radiation, overdiagnosis bias, proportion of false positives and cost benefit analysis. This article reviews the literature pertaining to lung cancer screening guidelines and above mentioned concerns. PMID:25806292

  7. Lung cancer screening guidelines: common ground and differences.

    PubMed

    Gulati, Swati; Mulshine, James L

    2014-06-01

    Lung cancer accounts for almost one-third of all cancer related deaths. Lung cancer risk persists even after smoking cessation and so many lung cancers now are diagnosed in former smokers. Five-year survival of lung cancer has marginally improved over decades and significantly lags behind that of colon, breast and prostate cancer. Over the past one decade, lung cancer screening trials have shown promising results. Results from National Lung Cancer Screening Trial (NLST), have shown a significant 20% reduction in mortality with annual low dose computed tomography (LDCT) screening. Based on these results, annual LDCT testing has been recommended for lung cancer screening in high risk population. However, development and acceptance of lung cancer screening as a public health policy is still in the nascent stages. Major concerns relate to risk of radiation, overdiagnosis bias, proportion of false positives and cost benefit analysis. This article reviews the literature pertaining to lung cancer screening guidelines and above mentioned concerns. PMID:25806292

  8. Management of Lung Cancer in the Elderly.

    PubMed

    Rao, Archana; Sharma, Namita; Gajra, Ajeet

    2016-01-01

    Lung cancer is the leading cause of cancer-associated mortality in the USA. The median age at diagnosis of lung cancer is 70 years, and thus, about one-half of patients with lung cancer fall into the elderly subgroup. There is dearth of high level of evidence regarding the management of lung cancer in the elderly in the three broad stages of the disease including early-stage, locally advanced, and metastatic disease. A major reason for the lack of evidence is the underrepresentation of elderly in prospective randomized clinical trials. Due to the typical decline in physical and physiologic function associated with aging, most elderly do not meet the stringent eligibility criteria set forth in age-unselected clinical trials. In addition to performance status, ideally, comorbidity, cognitive, and psychological function, polypharmacy, social support, and patient preferences should be taken into account before applying prevailing treatment paradigms often derived in younger, healthier patients to the care of the elderly patient with lung cancer. The purpose of this chapter was to review the existing evidence of management of early-stage, locally advanced disease, and metastatic lung cancer in the elderly. PMID:27535398

  9. Highly Sensitive Droplet Digital PCR Method for Detection of EGFR-Activating Mutations in Plasma Cell-Free DNA from Patients with Advanced Non-Small Cell Lung Cancer.

    PubMed

    Zhu, Guanshan; Ye, Xin; Dong, Zhengwei; Lu, Ya Chao; Sun, Yun; Liu, Yi; McCormack, Rose; Gu, Yi; Liu, Xiaoqing

    2015-05-01

    Epidermal growth factor receptor (EGFR) mutation testing in plasma cell-free DNA from lung cancer patients is an emerging clinical tool. However, compared with tissue testing, the sensitivity of plasma testing is not yet satisfactory because of the highly fragmented nature of plasma cell-free DNA, low fraction of tumor DNA, and limitations of available detection technologies. We therefore developed a highly sensitive and specific droplet digital PCR method for plasma EGFR mutation (exon19 deletions and L858R) testing. Plasma from 86 EGFR-tyrosine kinase inhibitor-naive lung cancer patients was tested and compared with EGFR mutation status of matched tumor tissues tested by amplification refractory mutation system. By using EGFR mutation-positive cell DNA, we optimized the droplet digital PCR assays to reach 0.04% sensitivity. The plasma testing sensitivity and specificity, compared with the matched tumor tissues tested by amplification refractory mutation system, were 81.82% (95% CI, 59.72%-94.81%) and 98.44% (95% CI, 91.60%-99.96%), respectively, for exon19 deletions, with 94.19% concordance rate (κ = 0.840; 95% CI, 0.704-0.976; P < 0.0001), whereas they were 80.00% (95% CI, 51.91%-95.67%) and 95.77% (95% CI, 88.14%-99.12%), respectively, for L858R, with 93.02% concordance rate (κ = 0.758; 95% CI, 0.571-0.945; P < 0.0001). The reported highly sensitive and specific droplet digital PCR assays for EGFR mutation detection have potential in clinical blood testing. PMID:25769900

  10. Lung cancer in the Indian subcontinent.

    PubMed

    Noronha, Vanita; Pinninti, Rakesh; Patil, Vijay M; Joshi, Amit; Prabhash, Kumar

    2016-01-01

    Smoking tobacco, both cigarettes and beedis, is the principal risk factor for causation of lung cancer in Indian men; however, among Indian women, the association with smoking is not strong, suggesting that there could be other risk factors besides smoking. Despite numerous advances in recent years in terms of diagnostic methods, molecular changes, and therapeutic interventions, the outcomes of the lung cancer patients remain poor; hence, a better understanding of the risk factors may impact the preventive measures to be implemented at the community level. There is a lack of comprehensive data on lung cancer in India. In this review, we attempt to collate the available data on lung cancer from India. PMID:27606290

  11. Lung cancer in the Indian subcontinent

    PubMed Central

    Noronha, Vanita; Pinninti, Rakesh; Patil, Vijay M.; Joshi, Amit; Prabhash, Kumar

    2016-01-01

    Smoking tobacco, both cigarettes and beedis, is the principal risk factor for causation of lung cancer in Indian men; however, among Indian women, the association with smoking is not strong, suggesting that there could be other risk factors besides smoking. Despite numerous advances in recent years in terms of diagnostic methods, molecular changes, and therapeutic interventions, the outcomes of the lung cancer patients remain poor; hence, a better understanding of the risk factors may impact the preventive measures to be implemented at the community level. There is a lack of comprehensive data on lung cancer in India. In this review, we attempt to collate the available data on lung cancer from India. PMID:27606290

  12. Surgery for small cell lung cancer.

    PubMed

    de Hoyos, Alberto; DeCamp, Malcolm M

    2014-11-01

    Small-cell lung cancer (SCLC) comprises approximately 14% of all lung cancer cases. Most patients present with locally advanced or metastatic disease and are therefore treated nonoperatively with chemotherapy, radiotherapy, or both. A small subset of patients with SCLC present with early-stage disease and will benefit from surgical resection plus chemotherapy. The rationale for radiotherapy in these patients remains controversial. PMID:25441133

  13. Advances in bronchoscopy for lung cancer

    PubMed Central

    Dhillon, Samjot Singh; Dexter, Elisabeth U.

    2012-01-01

    Bronchoscopic techniques have seen significant advances in the last decade. The development and refinement of different types of endobronchial ultrasound and navigation systems have led to improved diagnostic yield and lung cancer staging capabilities. The complication rate of these minimally invasive procedures is extremely low as compared to traditional transthoracic needle biopsy and surgical sampling. These advances augment the safe array of methods utilized in the work up and management algorithms of lung cancer. PMID:23346012

  14. [Lung cancer: psychological and psychiatric aspects].

    PubMed

    Domingues, Vera; Albuquerque, Emília

    2008-01-01

    According to the literature, lung cancer patients experience greater emotional distress than other cancer patients, with scores as high as 61,6%. Poor prognosis, guilt and stigma associated with a history of smoking, may be related with this morbidity. Several studies mention the prevalence of depression to be between 16 and 22%. As distress affects the family as well, mostly those members involved in the patient care, they should not be forgotten and must be involved in the treatment plan. The authors conclude that lung cancer patients' distress is highly prevalent and interferes with quality of live and, possibly, prognosis. Therefore, psychosocial care should be integrated early in cancer treatment. PMID:18363022

  15. Immunotherapy for lung cancer: advances and prospects.

    PubMed

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  16. Immunotherapy for lung cancer: advances and prospects

    PubMed Central

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  17. Optimizing the Detection of Circulating Markers to Aid in Early Lung Cancer Detection

    PubMed Central

    Murlidhar, Vasudha; Ramnath, Nithya; Nagrath, Sunitha; Reddy, Rishindra M.

    2016-01-01

    Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify non-cancer lung nodules that lead to unnecessary interventions for some. There is a critical need to develop alternative, less invasive methods to identify patients who have early-stage lung cancer. The detection of circulating tumor cells (CTCs) are a promising area of research, but current technology is limited by a low yield of CTCs. Alternate studies are investigating circulating nucleic acids and proteins as possible tumor markers. It is critical to develop innovative methods for early lung cancer detection that may include CTCs or other markers that are low-risk and low-cost, yet specific and sensitive, to facilitate improved survival by diagnosing the disease when it is surgically curable. PMID:27367729

  18. Optimizing the Detection of Circulating Markers to Aid in Early Lung Cancer Detection.

    PubMed

    Murlidhar, Vasudha; Ramnath, Nithya; Nagrath, Sunitha; Reddy, Rishindra M

    2016-01-01

    Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify non-cancer lung nodules that lead to unnecessary interventions for some. There is a critical need to develop alternative, less invasive methods to identify patients who have early-stage lung cancer. The detection of circulating tumor cells (CTCs) are a promising area of research, but current technology is limited by a low yield of CTCs. Alternate studies are investigating circulating nucleic acids and proteins as possible tumor markers. It is critical to develop innovative methods for early lung cancer detection that may include CTCs or other markers that are low-risk and low-cost, yet specific and sensitive, to facilitate improved survival by diagnosing the disease when it is surgically curable. PMID:27367729

  19. Genome Wide Methylome Alterations in Lung Cancer.

    PubMed

    Mullapudi, Nandita; Ye, Bin; Suzuki, Masako; Fazzari, Melissa; Han, Weiguo; Shi, Miao K; Marquardt, Gaby; Lin, Juan; Wang, Tao; Keller, Steven; Zhu, Changcheng; Locker, Joseph D; Spivack, Simon D

    2015-01-01

    Aberrant cytosine 5-methylation underlies many deregulated elements of cancer. Among paired non-small cell lung cancers (NSCLC), we sought to profile DNA 5-methyl-cytosine features which may underlie genome-wide deregulation. In one of the more dense interrogations of the methylome, we sampled 1.2 million CpG sites from twenty-four NSCLC tumor (T)-non-tumor (NT) pairs using a methylation-sensitive restriction enzyme- based HELP-microarray assay. We found 225,350 differentially methylated (DM) sites in adenocarcinomas versus adjacent non-tumor tissue that vary in frequency across genomic compartment, particularly notable in gene bodies (GB; p<2.2E-16). Further, when DM was coupled to differential transcriptome (DE) in the same samples, 37,056 differential loci in adenocarcinoma emerged. Approximately 90% of the DM-DE relationships were non-canonical; for example, promoter DM associated with DE in the same direction. Of the canonical changes noted, promoter (PR) DM loci with reciprocal changes in expression in adenocarcinomas included HBEGF, AGER, PTPRM, DPT, CST1, MELK; DM GB loci with concordant changes in expression included FOXM1, FERMT1, SLC7A5, and FAP genes. IPA analyses showed adenocarcinoma-specific promoter DMxDE overlay identified familiar lung cancer nodes [tP53, Akt] as well as less familiar nodes [HBEGF, NQO1, GRK5, VWF, HPGD, CDH5, CTNNAL1, PTPN13, DACH1, SMAD6, LAMA3, AR]. The unique findings from this study include the discovery of numerous candidate The unique findings from this study include the discovery of numerous candidate methylation sites in both PR and GB regions not previously identified in NSCLC, and many non-canonical relationships to gene expression. These DNA methylation features could potentially be developed as risk or diagnostic biomarkers, or as candidate targets for newer methylation locus-targeted preventive or therapeutic agents. PMID:26683690

  20. Genome Wide Methylome Alterations in Lung Cancer

    PubMed Central

    Suzuki, Masako; Fazzari, Melissa; Han, Weiguo; Shi, Miao K.; Marquardt, Gaby; Lin, Juan; Wang, Tao; Keller, Steven; Zhu, Changcheng; Locker, Joseph D.; Spivack, Simon D.

    2015-01-01

    Aberrant cytosine 5-methylation underlies many deregulated elements of cancer. Among paired non-small cell lung cancers (NSCLC), we sought to profile DNA 5-methyl-cytosine features which may underlie genome-wide deregulation. In one of the more dense interrogations of the methylome, we sampled 1.2 million CpG sites from twenty-four NSCLC tumor (T)–non-tumor (NT) pairs using a methylation-sensitive restriction enzyme- based HELP-microarray assay. We found 225,350 differentially methylated (DM) sites in adenocarcinomas versus adjacent non-tumor tissue that vary in frequency across genomic compartment, particularly notable in gene bodies (GB; p<2.2E-16). Further, when DM was coupled to differential transcriptome (DE) in the same samples, 37,056 differential loci in adenocarcinoma emerged. Approximately 90% of the DM-DE relationships were non-canonical; for example, promoter DM associated with DE in the same direction. Of the canonical changes noted, promoter (PR) DM loci with reciprocal changes in expression in adenocarcinomas included HBEGF, AGER, PTPRM, DPT, CST1, MELK; DM GB loci with concordant changes in expression included FOXM1, FERMT1, SLC7A5, and FAP genes. IPA analyses showed adenocarcinoma-specific promoter DMxDE overlay identified familiar lung cancer nodes [tP53, Akt] as well as less familiar nodes [HBEGF, NQO1, GRK5, VWF, HPGD, CDH5, CTNNAL1, PTPN13, DACH1, SMAD6, LAMA3, AR]. The unique findings from this study include the discovery of numerous candidate The unique findings from this study include the discovery of numerous candidate methylation sites in both PR and GB regions not previously identified in NSCLC, and many non-canonical relationships to gene expression. These DNA methylation features could potentially be developed as risk or diagnostic biomarkers, or as candidate targets for newer methylation locus-targeted preventive or therapeutic agents. PMID:26683690

  1. Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells.

    PubMed

    Allen, Kah Tan; Chin-Sinex, Helen; DeLuca, Thomas; Pomerening, Joseph R; Sherer, Jeremy; Watkins, John B; Foley, John; Jesseph, Jerry M; Mendonca, Marc S

    2015-12-01

    We investigated whether altering Warburg metabolism (aerobic glycolysis) by treatment with the metabolic agent dichloroacetate (DCA) could increase the X-ray-induced cell killing of the radiation-resistant human non-small-cell lung cancer (NSCLC) cell lines A549 and H1299. Treatment with 50mM DCA decreased lactate production and glucose consumption in both A549 and H1299, clear indications of attenuated aerobic glycolysis. In addition, we found that DCA treatment also slowed cell growth, increased population-doubling time, and altered cell cycle distribution. Furthermore, we report that treatment with 50mM DCA significantly increased single and fractionated X-ray-induced cell killing of A549 and H1299 cells. Assay of DNA double-strand break repair by neutral comet assays demonstrated that DCA inhibited both the fast and the slow kinetics of X-ray-induced DSB repair in both A549 and H1299 NSCL cancer cells. Taken together the data suggest a correlation between an attenuated aerobic glycolysis and enhanced cytotoxicity and radiation-induced cell killing in radiation-resistant NSCLC cells. PMID:26393423

  2. Lung Cancer Screening with Low Dose CT

    PubMed Central

    Caroline, Chiles

    2014-01-01

    SUMMARY The announcement of the results of the NLST, showing a 20% reduction in lung-cancer specific mortality with LDCT screening in a high risk population, marked a turning point in lung cancer screening. This was the first time that a randomized controlled trial had shown a mortality reduction with an imaging modality aimed at early detection of lung cancer. Current guidelines endorse LDCT screening for smokers and former smokers ages 55 to 74, with at least a 30 pack year smoking history. Adherence to published algorithms for nodule follow-up is strongly encouraged. Future directions for screening research include risk stratification for selection of the screening population, and improvements in the diagnostic follow-up for indeterminate pulmonary nodules. As with screening for other malignancies, screening for lung cancer with LDCT has revealed that there are indolent lung cancers which may not be fatal. More research is necessary if we are to maximize the risk-benefit ratio in lung cancer screening. PMID:24267709

  3. Current Controversies in Lung Cancer Staging.

    PubMed

    Carter, Brett W; Godoy, Myrna C B; Wu, Carol C; Erasmus, Jeremy J; Truong, Mylene T

    2016-07-01

    Lung cancer remains the leading cause of cancer-related mortality in the United States, and accurate staging of disease plays an important role in the formulation of treatment strategies and optimization of patient outcomes. The International Association for the Study of Lung Cancer has recently proposed changes to the upcoming eighth edition of the tumor, node, and metastasis (TNM-8) staging system used for lung cancer. This revised classification is based on significant differences in patient survival identified on analysis of a new large international database of lung cancer cases. Key changes include: further modifications to the T descriptors based on 1 cm increments in tumor size; grouping of tumors resulting in partial or complete lung atelectasis/pneumonitis; grouping of tumors involving a main bronchus with respect to distance from the carina; reassignment of diaphragmatic invasion; elimination of mediastinal pleural invasion as a descriptor; and further subdivision of metastatic disease into distinct descriptors based on the number of extrathoracic metastases and involved organs. Because of these changes, several new stage groups have been developed, and others have shifted. Although TNM-8 represents continued improvement upon modifications previously made to the staging system, reflecting an evolving understanding of tumor behavior and patient management, several limitations and unaddressed issues persist. Understanding the proposed revisions to TNM-8 and awareness of key limitations and potential controversial issues still unaddressed will allow radiologists to accurately stage patients with lung cancer and optimize treatment decisions. PMID:27306388

  4. Lung cancer screening overdiagnosis: reports of overdiagnosis in screening for lung cancer are grossly exaggerated.

    PubMed

    Mortani Barbosa, Eduardo J

    2015-08-01

    The National Lung Cancer Screening Trial (NLST) demonstrated a mortality reduction benefit associated with low-dose computed tomography (LDCT) screening for lung cancer. There has been considerable debate regarding the benefits and harms of LDCT lung cancer screening, including the challenges related to its practical implementation. One of the controversies regards overdiagnosis, which conceptually denotes diagnosing a cancer that, either because of its indolent, low-aggressiveness biologic behavior or because of limited life expectancy, is unlikely to result in significant morbidity during the patient's remainder lifetime. In theory, diagnosing and treating these cancers offer no measurable benefit while incurring costs and risks. Therefore, if a screening test detects a substantial number of overdiagnosed cancers, it is less likely to be effective. It has been argued that LDCT screening for lung cancer results in an unacceptably high rate of overdiagnosis. This article aims to defend the opposite stance. Overdiagnosis does exist and to a certain extent is inherent to any cancer-screening test. Nonetheless, the concept is less dualistic and more nuanced than it has been suggested. Furthermore, the average estimates of overdiagnosis in LDCT lung cancer screening based on the totality of published data are likely much lower than the highest published estimates, if a careful definition of a positive screening test reflecting our current understanding of lung cancer biology is utilized. This article presents evidence on why reports of overdiagnosis in lung cancer screening have been exaggerated. PMID:25772581

  5. Role of STAT3 in lung cancer

    PubMed Central

    Dutta, Pranabananda; Sabri, Nafiseh; Li, Jinghong; Li, Willis X

    2014-01-01

    Lung cancer remains a challenging disease. It is responsible for the high cancer mortality rates in the US and worldwide. Elucidation of the molecular mechanisms operative in lung cancer is an important first step in developing effective therapies. Accumulating evidence over the last 2 decades suggests a critical role for Signal Transducer and Activator of Transcription 3 (STAT3) as a point of convergence for various signaling pathways that are dysregulated in the disease. In this review, we discuss possible molecular mechanisms involving STAT3 in lung tumorigenesis based on recent literature. We consider possible roles of STAT3 in cancer cell proliferation and survival, in the tumor immune environment, and in epigenetic regulation and interaction of STAT3 with other transcription factors. We also discuss the potential role of STAT3 in tumor suppression, which complicates strategies of targeting STAT3 in cancer therapy. PMID:26413424

  6. Mineral particles, mineral fibers, and lung cancer

    SciTech Connect

    Churg, A.; Wiggs, B.

    1985-08-01

    The total fibrous and nonfibrous mineral content of the lung has been analyzed in a series of 14 men with lung cancer but no history of occupational dust exposure, and in a series of 14 control men matched for age, smoking history, and general occupational class. The lung cancer patients had an average of 525 +/- 369 X 10(6) exogenous mineral particles and 17.4 +/- 19.6 X 10(6) exogenous mineral fibers/g dry lung, while the controls had averages of 261 +/- 175 mineral particles and 4.7 +/- 3.2 X 10(6) mineral fibers/g dry lung. These differences are statistically significant for both particles and fibers. Kaolinite, talc, mica, feldspars, and crystalline silica comprised the majority of particles of both groups. Approximately 90% of the particles were smaller than 2 micron in diameter and approximately 60% smaller than 1 micron. In both groups, patients who had smoked more than 35 pack years had greater numbers of particles than patients who had smoked less than 35 pack years. It is concluded that, in this study, lungs from patients with lung cancer had statistically greater numbers of mineral particles and fibers than lungs from controls, and that smoking influences total long-term retention of particles from all sources.

  7. CAXII Is a Sero-Diagnostic Marker for Lung Cancer

    PubMed Central

    Kobayashi, Makoto; Matsumoto, Toshihide; Ryuge, Shinichiro; Yanagita, Kengo; Nagashio, Ryo; Kawakami, Yoshitaka; Goshima, Naoki; Jiang, Shi-Xu; Saegusa, Makoto; Iyoda, Akira; Satoh, Yukitoshi; Masuda, Noriyuki; Sato, Yuichi

    2012-01-01

    To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for

  8. 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

  9. Transbronchial Dissemination of Squamous Cell Lung Cancer

    PubMed Central

    Tadokoro, Akira; Kanaji, Nobuhiro; Ishii, Tomoya; Watanabe, Naoki; Inoue, Takuya; Kadowaki, Norimitsu; Bandoh, Shuji

    2015-01-01

    We report a case of squamous cell lung cancer with transbronchial dissemination in a 73-year-old man. Bronchoscopic examination revealed multiple bronchial mucosal nodules that existed independently of one another. We reviewed 16 previous cases of endobronchial metastasis in lung cancer. All patients were men. Among the reports that described the smoking history, most patients were smokers (6/7), and the most frequent histological type of cancer was squamous cell carcinoma (11/17). Although hematogenous and lymphogenous routes have been reported as metastatic mechanisms, no previous cases involving transbronchial dissemination have been described. Transbronchial dissemination may be an alternative pathway of endobronchial metastasis. PMID:26672760

  10. 28 CFR 79.54 - Proof of primary lung cancer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  11. 28 CFR 79.54 - Proof of primary lung cancer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  12. 28 CFR 79.54 - Proof of primary lung cancer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  13. 28 CFR 79.64 - Proof of primary lung cancer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by...

  14. 28 CFR 79.64 - Proof of primary lung cancer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by...

  15. 28 CFR 79.45 - Proof of primary lung cancer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  16. 28 CFR 79.45 - Proof of primary lung cancer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  17. 28 CFR 79.54 - Proof of primary lung cancer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  18. 28 CFR 79.64 - Proof of primary lung cancer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by...

  19. 28 CFR 79.45 - Proof of primary lung cancer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  20. 28 CFR 79.64 - Proof of primary lung cancer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by...

  1. 28 CFR 79.45 - Proof of primary lung cancer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  2. 28 CFR 79.64 - Proof of primary lung cancer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by...

  3. 28 CFR 79.54 - Proof of primary lung cancer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  4. 28 CFR 79.45 - Proof of primary lung cancer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To...

  5. 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

  6. Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-05-26

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  7. Biomarkers along the continuum of care in lung cancer.

    PubMed

    Holdenrieder, Stefan

    2016-01-01

    Blood-based biomarkers are valuable diagnostic tools for the management of lung cancer patients. They support not only differential diagnosis and histological subtyping, but are also applied for estimation of prognosis, stratification for specific therapies, monitoring of therapy response, surveillance monitoring and early detection of residual or progressive disease. Early diagnosis of lung cancer in high risk populations (screening) is a promising future indication but poses high medical and economic challenges to marker performance. The five mostly used classical 'tumor markers' show characteristic profiles of sensitivity and specificity for non-small cell lung cancer (NSCLC) like cytokeratin 19-fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and squamous cancer cell antigen (SCCA) as well as for small cell lung cancer (SCLC) like progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE). Combined use and pattern recognition approaches enable highly accurate diagnosis, subtyping and therapy monitoring. For the interpretation of serial measurements on an individual level, marker-specific algorithms have to be developed. So-called companion diagnostics identify druggable molecular changes in signaling pathways of tumor tissue that can be addressed by targeted therapies. New highly sensitive technologies enable the convenient and serial molecular characterization on circulating tumor DNA (ctDNA) in the blood, too. This approach is helpful when biopsies are not available and to overcome tumor molecular heterogeneity and plasticity. As only a portion of patients have such druggable molecular changes, future strategies will imply the combined use of classical and new ctDNA-based biomarkers to optimize the management of lung cancer patients during the course of disease. PMID:27542002

  8. Clinical significance of joint detection of serum CEA, SCCA, and bFGF in the diagnosis of lung cancer

    PubMed Central

    Zhao, Wei; Yu, Haixiang; Han, Zhifeng; Gao, Nan; Xue, Jinru; Wang, Yan

    2015-01-01

    Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction. PMID:26464712

  9. Targeted therapy for squamous cell lung cancer

    PubMed Central

    Liao, Rachel G.; Watanabe, Hideo; Meyerson, Matthew; Hammerman, Peter S.

    2013-01-01

    SUMMARY Lung squamous cell carcinoma (SqCC) is the second most common subtype of non-small-cell lung cancer and leads to 40,000–50,000 deaths per year in the USA. Management of non-small-cell lung cancer has dramatically changed over the past decade with the introduction of targeted therapeutic agents for genotypically selected individuals with lung adenocarcinoma. These agents lead to improved outcomes, and it has now become the standard of care to perform routine molecular genotyping of lung adenocarcinomas. By contrast, progress in lung SqCC has been modest, and there has yet to be a successful demonstration of targeted therapy in this disease. Here, we review exciting work from ongoing genomic characterization and biomarker validation efforts that have nominated several likely therapeutic targets in lung SqCCs. These studies suggest that targeted therapies are likely to be successful in the treatment of lung SqCCs and should be further explored in both preclinical models and in clinical trials. PMID:23956794

  10. Intermediate endpoint biomarkers for lung cancer chemoprevention

    NASA Astrophysics Data System (ADS)

    MacAulay, Calum E.; Lam, Stephen; Klein-Parker, Helga; Gazdar, Adi; Guillaud, Martial; Payne, Peter W.; Le Riche, Jean C.; Dawe, Chris; Band, Pierre; Palcic, Branko

    1998-04-01

    Given the demographics of current and ex-smoking populations in North America, lung cancer will be a major problem in the foreseeable future. Early detection and treatment of lung cancer holds great promise for the management of this disease. Unlike cervical cancer, the physical, complete removal/destruction of all dysplastic lesions in the bronchial tree is not possible; however, treatment of the lesions using a chemopreventive agent is. Intermediate biomarkers have been used to screen promising chemopreventive agents for larger population studies. We have examined the natural history of lung cancer development by following a group of subjects at high risk of developing lung cancer using fluorescence endoscopy to identify the areas of abnormality for biopsy. Approximately 900 biopsies have been collected in this fashion and graded by at least two experienced, expert pathologists. Using an interactive version of the Cyto-Savant (Oncometrics Imaging Corp.), cytometric and tissue architectural data were collected from these biopsies. Using only the data from the normal and invasive cancer biopsies, quantitative morphometric and architectural indices were generated and calculated for all the collected biopsies. These indices were compared with Loss of Heterozygosity (LOH) of ten sites commonly associated with cancer. These results and the application of these quantitative measures to two small chemoprevention studies will be reported.

  11. Detection and minimally invasive treatment of early squamous lung cancer

    PubMed Central

    Sutedja, Thomas G.

    2013-01-01

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer deaths worldwide. The majority of patents presenting with NSCLC have advanced disease, which precludes curative treatment. Early detection and treatment might result in the identification of more patients with early central lung cancer and improve survival. In addition, the study of early lung cancer improves understanding of lung carcinogenesis and might also reveal new treatment targets for advanced lung cancer. Bronchoscopic investigation of the central airways can reveal both early central lung cancer in situ (stage 0) and other preinvasive lesions such as dysplasia. In the current review we discuss the detection of early squamous lung cancer, the natural history of preinvasive lesions and whether biomarkers can be used to predict progression to cancer. Finally we will review the staging and management of preinvasive lung cancer lesions and the different therapeutic modalities that are available. PMID:23858332

  12. Isolating and Testing Circulating Tumor DNA and Soluble Immune Markers During the Course of Treatment for Lung Cancer

    ClinicalTrials.gov

    2016-07-11

    Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

  13. Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer.

    PubMed

    Singhal, Sharad S; Singhal, Jyotsana; Nair, Maya P; Lacko, A G; Awasthi, Yogesh C; Awasthi, Sanjay

    2007-03-01

    RALBP1 (RLIP76) is the major transporter of doxorubicin (DOX) in lung cancer cells, and that the difference in sensitivity of small cell lung cancer (SCLC) cells to DOX is due to differential phosphorylation by PKCalpha. Our recent studies have suggested that RALBP1 present in MCF-7 breast cancer cells has significantly lower specific activity for transport of DOX than wild-type recombinant protein, and its level of expression is significantly lower than that in lung cancer cells. In the present study, we have explored whether or not this is a generalized phenomenon for breast cancer, and have compared the relative contributions of RALBP1 and the ABC-family transporter, ABCG2 to total DOX transport activities in two SCLC (H1417 and H1618), two non-small cell lung cancer (NSCLC) (H358 and H520), and three breast cancer (T-47D, MDA-MB231, and MCF-7) cell lines. Results of these studies show lower protein expression and specific activity of RALBP1 in all three breast cancer cell lines as compared with lung cancer cell lines. Furthermore, we demonstrate that RALBP1 contributes only a minor fraction of DOX transport activity in breast cancer cell lines, suggesting that greater DOX sensitivity of breast cancer may be related to lower RALBP1 transporter activity and that the transport mechanisms involved in multidrug resistance of lung and breast cancer are distinct. PMID:17273774

  14. Targeted Therapies for Lung Cancer.

    PubMed

    Stinchcombe, Thomas E

    2016-01-01

    Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival. PMID:27535394

  15. Photoradiation Therapy Of Obstructing Endobronchial Lung Cancer

    NASA Astrophysics Data System (ADS)

    Balchum, Oscar J.; Doiron, Daniel R.

    1982-12-01

    Clinical trials of photoradiation therapy (PRT) have been carried out in 32 patients with lung cancer, 10 of which are reported here. The aim is the palliative treatment and control of cancer lesions obstructing an airway, whether in the trachea or in a large bronchus leading to a lung or to a lobe of a lung. The objective or patient benefit is the opening up of the lumen of the airway to improve ventilation to relieve shortness of breath, and to prevent the retention of secretions containing bacteria, that cause lung infections. Immediate results (one to several weeks) were uniformly good. Air passageways were opened up as revealed by subsequent bronchoscopy, after clearing away tumor debris. Short-term (several months) observations were limited in number but indicate potentially good results. Future research is directed toward better criteria for patient selection improved patient evaluation that will reveal potential cardiac and pulmonary complications, and the devising of more suitable laser light delivery techniques.

  16. Successes and limitations of targeted cancer therapy in lung cancer.

    PubMed

    Suda, Kenichi; Mitsudomi, Tetsuya

    2014-01-01

    Human cancers usually evolve through multistep processes. These processes are driven by the accumulation of abundant genetic and epigenetic abnormalities. However, some lung cancers depend on a single activated oncogene by somatic mutation, termed 'driver oncogenic mutations', for their proliferation and survival. EGFR(epidermal growth factor receptor) mutations and ALK(anaplastic lymphoma kinase) rearrangement are typical examples of such driver oncogenic mutations found in lung adenocarcinomas. EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs significantly improved treatment outcomes compared with conventional cytotoxic chemotherapy in patients with lung cancers harboring EGFR mutations or ALK rearrangement, respectively. Therefore, treatment strategies for lung cancers have dramatically changed from a 'general and empiric' to a 'personalized and evidence-based' approach according to the driver oncogenic mutation. Several novel driver oncogenic mutations, which are candidates as novel targets, such as ERBB2, BRAF, ROS1, and RET, have been discovered. Despite these successes, several limitations have arisen. One example is that some lung cancers do not respond to treatments targeting driver oncogenic mutations, as exemplified in KRAS-mutated lung cancers. Another is resistance to molecular-targeted drugs. Such resistance includes de novo resistance and acquired resistance. A number of molecular mechanisms underlying such resistance have been reported. These mechanisms can be roughly divided into three categories: alteration of the targeted oncogenes themselves by secondary mutations or amplification, activation of an alternative oncogenic signaling track, and conversion of cellular characteristics. Overcoming resistance is a current area of urgent clinical research. PMID:24727987

  17. Lung cancer: chemoprevention and intermediate effect markers.

    PubMed

    Tockman, M S

    2001-01-01

    Even after smoking cessation, genetic damage in the airways epithelium may lead to focal progression of lung carcinogenesis. Some centres now report as many new lung cancer cases among former smokers as among current smokers. Chemoprevention is a potential approach to diminish the progression of pre-clinical genetic damage. The most intensively studied lung cancer chemoprevention agents are the retinoids, including vitamin A and its synthetic analogues and precursors. While effective in suppressing lung carcinogenesis in animal models, retinoids have failed to inhibit carcinogenesis in human chemoprevention trials with premalignant end-points (sputum atypia, bronchial metaplasia). In trials with lung cancer end-points, administration of retinoids either was ineffective or, in the case of beta-carotene, led to greater lung cancer incidence and mortality. In view of these findings, markers of specific retinoid effect (i.e., levels of RAR-beta) become less relevant. Other markers of genetic instability and proliferation may be useful for both early detection and potentially as intermediate-effect markers for new chemoprevention trials. Cytological atypia, bronchial metaplasia, protein (hnRNP A2/B1) overexpression, ras oncogene activation and tumour-suppressor gene deletion, genomic instability (loss of heterozygosity, microsatellite alterations), abnormal methylation, helical CT detection of atypical adenomatous hyperplasia and fluorescent bronchoscopic detection of angiogenic squamous dysplasia offer great promise for molecular diagnosis of lung cancer far in advance of clinical presentation. These end-points can now be evaluated as monitors of response to chemoprevention as potential intermediate-effect markers. PMID:11220665

  18. Better Lung Cancer Survival? There's an App for That

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_159289.html Better Lung Cancer Survival? There's an App for That Study found ... HealthDay News) -- A new smartphone app may help lung cancer patients live longer and better by monitoring their ...

  19. Do Too Many Lung Cancer Patients Miss Out on Surgery?

    MedlinePlus

    ... medlineplus/news/fullstory_159488.html Do Too Many Lung Cancer Patients Miss Out on Surgery? Study evaluates treatment ... 21, 2016 (HealthDay News) -- Many patients with advanced lung cancer might live longer if treated surgically, but few ...

  20. General Information about Non-Small Cell Lung Cancer

    MedlinePlus

    ... most patients with non-small cell lung cancer, current treatments do not cure the cancer. If lung ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  1. Treatment Option Overview (Non-Small Cell Lung Cancer)

    MedlinePlus

    ... lung cancer include a cough that doesn't go away and shortness of breath. Sometimes lung cancer ... discomfort or pain. A cough that doesn’t go away or gets worse over time. Trouble breathing. ...

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

    MedlinePlus

    ... lung cancer include a cough that doesn't go away and shortness of breath. Sometimes lung cancer ... discomfort or pain. A cough that doesn’t go away or gets worse over time. Trouble breathing. ...

  3. Stages of Non-Small Cell Lung Cancer

    MedlinePlus

    ... lung cancer include a cough that doesn't go away and shortness of breath. Sometimes lung cancer ... discomfort or pain. A cough that doesn’t go away or gets worse over time. Trouble breathing. ...

  4. Better Lung Cancer Survival? There's an App for That

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159289.html Better Lung Cancer Survival? There's an App for That Study ... HealthDay News) -- A new smartphone app may help lung cancer patients live longer and better by monitoring ...

  5. New genes linked to lung cancer susceptibility in Asian women

    Cancer.gov

    An international group of scientists has identified three genes that predispose Asian women who have never smoked to lung cancer. The discovery of specific genetic variations, which have not previously been associated with lung cancer risk in other popul

  6. Xalkori Approved for Rare Genetic Form of Lung Cancer

    MedlinePlus

    ... html Xalkori Approved For Rare Genetic Form of Lung Cancer ROS-1 positive NSCLC To use the sharing ... Drug Administration to treat advanced non-small cell lung cancer (NSCLC) with tumors that have a rare ROS- ...

  7. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    PubMed Central

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.; Aftab, Blake T.; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John; Rudin, Charles M.; Tran, Phuoc T.; Hales, Russell K.

    2012-01-01

    Purpose Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of KrasG12D-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radio-sensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. PMID:23182391

  8. Smoking cessation and lung cancer screening

    PubMed Central

    Pedersen, Jesper Holst; Tønnesen, Philip

    2016-01-01

    Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect has to do with participation in screening alone and not dependent on the CT scan. Participants in both CT and control arm in randomized screening trials had higher smoking abstinence rate compared to that of the general population. A positive screening test seems to further promote smoking cessation and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated part of future lung cancer screening trials. PMID:27195275

  9. Contemplating Genetic Feedback Regarding Lung Cancer Susceptibility

    PubMed Central

    Shepperd, James A.; Novell, Corinne A.; O'Neill, Suzanne C.; Docherty, Sharron L.; Sanderson, Saskia C.; McBride, Colleen M.; Lipkus, Isaac M.

    2013-01-01

    Background and Purpose We examined three theoretical models (self-enhancement theory, consistency theory, and combined model) for understanding how expectations and test result favorability influence smokers' desire for a retest following hypothetical genetic test results. Method College smokers (N = 128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk). Participants then reported whether they would get retested if they received favorable GSTM1 results versus unfavorable GSTM1 results. Results Participants were most likely to want a retest, suggesting rejection of the results, if they expected favorable news yet received unfavorable news. Conclusion The findings supported the combined model such that smokers expressed greatest interest in a retest when they imagined genetic risk feedback that challenges both enhancement and consistency motives. PMID:24222509

  10. Narcissus, the Beam, and lung cancer.

    PubMed

    Rocco, Gaetano

    2016-08-01

    In the management of lung cancer, the rules of engagement of stereotactic ablative radiotherapy (SABR) are not clearly defined. The potential for SABR to affect to an unprecedented level current protocols and in all disease stages emerges vehemently from the literature. However, in a time when the role of surgery is being reassessed, surgeons need to take a closer look at the evidence for the use of SABR in lung cancer patients and clearly define their indisputable role within the context of multidisciplinary teams. The myth of Narcissus exemplified in the absolute masterpiece by Caravaggio seems to represent an ideal metaphor to explain the ever-evolving interaction between surgery and SABR in lung cancer management. PMID:27209014

  11. Fluorescence imaging of early lung cancer

    NASA Astrophysics Data System (ADS)

    Lam, Stephen; MacAulay, Calum E.; Le Riche, Jean C.; Ikeda, Norihiko; Palcic, Branko

    1995-01-01

    The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected State I nonsmall cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least one pack of cigarettes per day for twenty-five years or more. Using differences in tissue autofluorescence between premalignant, malignant and normal tissues, fluorescence bronchoscopy was found to detect more than twice as many moderate-severe dysplasia and carcinoma in situ sites than conventional white-light bronchoscopy. The use of fluorescence imaging to detect small peripheral lung nodules was investigated in a micro metastatic lung model of mice implanted with Lewis lung tumor cells. Fluorescence imaging was found to be able to detect small malignant lung lesions. The use of (delta) -aminolevulinic acid (ALA) to enhance fluorescence detection of CIS was investigated in a patient after oral administration of 60 mg/kg of ALA four hours prior to bronchoscopy, although ALA enhanced the tumor's visibility, multiple sites of false positive fluorescence were observed in areas of inflammation or metaplasia.

  12. Glucocorticoid Receptor Status is a Principal Determinant of Variability in the Sensitivity of Non-Small Cell Lung Cancer Cells to Pemetrexed

    PubMed Central

    Patki, Mugdha; Gadgeel, Shirish; Huang, Yanfang; McFall, Thomas; Shields, Anthony F.; Matherly, Larry H.; Bepler, Gerold; Ratnam, Manohar

    2014-01-01

    Introduction Pemetrexed is an S-phase targeted drug in front-line or maintenance therapy of advanced non-squamous non-small cell lung cancer (NSCLC) but methods are needed for predicting the drug response. Dexamethasone is typically administered the day before, the day of and the day after pemetrexed. As dexamethasone strongly regulates many genes including p53 through the glucocorticoid receptor (GR), we hypothesized that dexamethasone influences tumor response to pemetrexed. Methods Eight non-squamous NSCLC cell line models with varied p53 and GRα/GRβ status were used for gene expression and cell cycle analyses and for loss/gain-of-function experiments. Results In three cell lines dexamethasone profoundly, but reversibly, suppressed the fraction of S-phase cells. Dexamethasone also reversibly repressed expression of thymidylate synthase and dihydrofolate reductase which are primary targets of pemetrexed but are also quintessential S-phase enzymes as well as the S-phase dependent expression of thymidine kinase 1. Dexamethasone also decreased expression of the major pemetrexed transporters, the reduced folate carrier and the proton coupled folate transporter. Only cells expressing relatively high GRα showed these dexamethasone effects, regardless of p53 status. In cells expressing low GRα, the dexamethasone response was rescued by ectopic GRα. Further, depletion of p53 did not attenuate the dexamethasone effects. The presence of dexamethasone during pemetrexed treatment protected against pemetrexed cytotoxicity, in only the dexamethasone responsive cells. Conclusions The results predict that in non-squamous NSCLC tumors, reversible S-phase suppression by dexamethasone, possibly combined with a reduction in the drug transporters, attenuates responsiveness to pemetrexed and that GR status is a principal determinant of tumor variability of this response. PMID:24736075

  13. Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-12-16

    Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  14. Mitochondrial DNA Content and Lung Cancer Risk

    PubMed Central

    Bonner, Matthew R.; Shen, Min; Liu, Chin-San; DiVita, Margaret; He, Xingzhou; Lan, Qing

    2010-01-01

    Smoky coal contains polycyclic aromatic hydrocarbons (PAHs) and has been strongly implicated in etiology of lung cancer in Xuan Wei, China. While PAHs have been demonstrated to form bulky adducts in nuclear DNA, they have a 90-fold greater affinity for mitochondrial DNA (mtDNA). To compensate for mitochondrial dysfunction or damage, mtDNA content is thought to increase. We conducted a population-based case-control study of lung cancer in Xuan Wei, China hypothesizing that mtDNA content is associated with lung cancer risk. Cases (n = 122) and controls (n = 121) were individually matched on age (±2yrs), sex, village of residence, and type of heating/cooking fuel currently used. Lifetime smoky coal use and potential confounders were determined with questionnaires. mtDNA was extracted from sputum and content was determined with quantitative RT-PCR. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with unconditional logistic regression. mtDNA content was dichotomized at the median based on the distribution among the controls. mtDNA content > 157 was associated with a 2-fold increase in lung cancer risk (OR = 1.8; 95% CI = 1.0–3.2) compared with those with ≤157 copies. Risk was higher among those >57 years of age compared with those ≤ 57 years (p interaction = 0.01). In summary, mtDNA content was positively associated with lung cancer risk. Furthermore, there was some evidence that mtDNA content was more strongly associated with lung cancer risk among older individuals. However, due to the small sample size, additional studies are needed to evaluate these associations. PMID:18691788

  15. Targeted therapies in small cell lung cancer: a review

    PubMed Central

    Abidin, Aidalena Z.; Garassino, Marina C.; Califano, Raffaele; Harle, Amelie; Blackhall, Fiona

    2010-01-01

    Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease. PMID:21789124

  16. The lung cancer nurse role in the management of paraneoplastic syndromes in lung cancer

    PubMed Central

    2016-01-01

    Paraneoplastic syndromes (PNS) associated with lung cancer are well recognised, are often complex to diagnose, and have minimal evidence to promote nursing and medical management. This paper aims to help guide lung cancer nurses to identify the most common and rarer PNS together with basic clinical management advice to help develop nursing assessments and interventions. The issues regarding the pathway of care at diagnosis together with palliative and supportive care requirements will be addressed and will aim to promote best practice in patients diagnosed with PNS and lung cancer. PMID:27413699

  17. Knockdown of Merm1/Wbscr22 attenuates sensitivity of H460 non-small cell lung cancer cells to SN-38 and 5-FU without alteration to p53 expression levels.

    PubMed

    Yan, Dongmei; Zheng, Xiaoliang; Tu, Linglan; Jia, Jing; Li, Qin; Cheng, Liyan; Wang, Xiaoju

    2015-01-01

    Merm1/Wbscr22 is a novel metastasis promoter that has been shown to be involved in tumor metastasis, viability and apoptosis. To the best of our knowledge, there are currently no studies suggesting the possible correlation between the expression of Merm1/Wbscr22 in tumor cells and chemosensitivity to antitumor agents. In the present study, two human non-small cell lung cancer cell lines, H1299 and H460, were used to investigate whether Merm1/Wbscr22 affects chemosensitivity to antitumor agents, including cisplatin (CDDP), doxorubicin (ADM), paclitaxel (PTX), mitomycin (MMC), 7-Ethyl-10-hydroxycamptothecin (SN-38; the active metabolite of camptothecin) and 5-fluorouracil (5-FU). Merm1/Wbscr22 knockdown cell lines (H1299-shRNA and H460-shRNA) and negative control cell lines (H1299-NC and H460-NC) were established by stable transfection, and the efficiency of Merm1/Wbscr22 knockdown was confirmed by western blotting, immunofluorescence microscopy and quantitative polymerase chain reaction. The results demonstrated that shRNA-mediated knockdown of Merm1/Wbscr22 did not affect cell proliferation in vitro and in vivo. The H460 cells harboring wild type p53 were markedly more sensitive to all six antitumor agents as compared with the p53-null H1299 cells. Downregulation of Merm1/Wbscr22 did not affect H1299 sensitivity to any of the six antitumor agents, whereas attenuated H460 sensitivity to SN-38 and 5-FU, without significant alteration in p53 at both mRNA and protein levels, was identified. The reduced H460 sensitivity to SN-38 was further confirmed in vivo. SN-38 demonstrated significant tumor growth inhibitory activity in both H460 and H460‑NC tumor xenograft models, but only marginally suppressed the H460-shRNA xenograft tumor growth. Furthermore, CDDP (4, 10, 15 µg/ml)-resistant human non-small lung cancer cells A549 (A549-CDDPr-4, 10, 15) expressed significant amounts of Merm1/Wbscr22 protein, as compared with the parental A549 cells. In conclusion, sh

  18. Aryl Hydrocarbon Receptor and Lung Cancer

    PubMed Central

    Tsay, Junchieh J.; Tchou-Wong, Kam-Meng; Greenberg, Alissa K.; Pass, Harvey; Rom, William N.

    2013-01-01

    The leading cause of lung cancer is exposure to cigarette smoke and other environmental pollutants, which include formaldehyde, acrolein, benzene, dioxin, and polycyclic aromatic hydrocarbons (PAHs). PAHs and dioxins are exogenous ligands that directly bind to the aryl hydrocarbon receptor (AhR), a transcription factor that activates xenobiotic metabolism, histone modification (an important step in DNA methylation), and, ultimately, tumorigenesis. Here we summarize the current understanding of AhR and its role in the development of lung cancer, including its influence on cell proliferation, angiogenesis, inflammation, and apoptosis. PMID:23564762

  19. VOC breath biomarkers in lung cancer.

    PubMed

    Saalberg, Yannick; Wolff, Marcus

    2016-08-01

    This review provides an overview of volatile organic compounds (VOCs) which are considered lung cancer biomarkers for diagnostic breath analysis. It includes results of scientific publications from 1985 to 2015. The identified VOCs are listed and ranked according to their occurrence of nomination. The applied detection and sampling methods are specified but not evaluated. Possible reasons for the different results of the studies are stated. Among the most frequently emerging biomarkers are 2-butanone and 1-propanol as well as isoprene, ethylbenzene, styrene and hexanal. The outcome of this review may be helpful for the development of a lung cancer screening device. PMID:27221203

  20. Smoking Cessation: An Integral Part of Lung Cancer Treatment

    PubMed Central

    Cataldo, Janine K.; Dubey, Sarita; Prochaska, Jodi J.

    2010-01-01

    Lung cancer is the leading cause of cancer death in the US. About 50% of lung cancer patients are current smokers at the time of diagnosis and up to 83% continue to smoke after diagnosis. A recent study suggests that people who continue to smoke after a diagnosis of early-stage lung cancer almost double their risk of dying. Despite a growing body of evidence that continued smoking by patients after a lung cancer diagnosis is linked with less effective treatment and a poorer prognosis, the belief prevails that treating tobacco dependence is useless. With improved cancer treatments and survival rates, smoking cessation among lung cancer patients has become increasingly important. There is a pressing need to clarify the role of smoking cessation in the care of lung cancer patients. Objective This paper will report on the benefits of smoking cessation for lung cancer patients and the elements of smoking cessation treatment, with consideration of tailoring to the needs of lung cancer patients. Results Given the significant benefits of smoking cessation and that tobacco dependence remains a challenge for many lung cancer patients, cancer care providers need to offer full support and intensive treatment with a smoking cessation program that is tailored to lung cancer patients’ specific needs. Conclusion A tobacco dependence treatment plan for lung cancer patients is provided. PMID:20699622

  1. Bromodomain and hedgehog pathway targets in small cell lung cancer.

    PubMed

    Kaur, Gurmeet; Reinhart, Russell A; Monks, Anne; Evans, David; Morris, Joel; Polley, Eric; Teicher, Beverly A

    2016-02-28

    Small cell lung cancer (SCLC) is an extremely aggressive cancer that frequently recurs. Twenty-three human SCLC lines were selected representing varied Myc status. Gene expression of lung cancer, stem-like, hedgehog pathway, and notch pathway genes were determined by RT(2)-PCR array and Exon 1.0 ST array. Etoposide and topotecan concentration response was examined. The IC50's for etoposide and topotecan ranged over nearly 3 logs upon 96 hrs exposure to the drugs. Myc status, TOP2A, TOP2B and TOP1 mRNA expression or topoisomerase 1 and topoisomerase 2 protein did not account for the range in the sensitivity to the drugs. γ-secretase inhibitors, RO429097 and PF-03084014, had little activity in the SCLC lines over ranges covering the clinical Cmax concentrations. MYC amplified lines tended to be more sensitive to the bromodomain inhibitor JQ1. The Smo antagonists, erismodegib and vismodegib and the Gli antagonists, HPI1 and SEN-450 had a trend toward greater sensitivity of the MYC amplified line. Recurrent SCLC is among the most recalcitrant cancers and drug development efforts in this cancer are a high priority. PMID:26683772

  2. Photodynamic therapy in lung and gastrointestinal cancers.

    PubMed

    Karanov, S; Kostadinov, D; Shopova, M; Kurtev, P

    1990-06-01

    Twelve central bronchial carcinoma patients and two gastrointestinal (GI) tract (oesophageal and colonic) early-stage cancer patients were treated with photodynamic therapy (PDT). Haematoporphyrin (HP/5, Jacopo Monico, Italy) at a dose of 5 mg kg-1 body weight was used as photosensitizer. Laser light at 628.2-630 nm generated by two different laser systems (gold vapour laser (I.P. Optics, Sofia, Bulgaria) in lung cancer cases and an argon dye laser system (Spectra Physics, Mountain View, U.S.A.) in GI tract cancers) was used. Lung cancers were irradiated 48 h after drug administration and GI tract cancers were irradiated 72 h after infusion of the photosensitizer. Both tumour sites were treated with a total energy dose in the range 350-600 J cm-2. Efficiency of PDT in lung cancer was evaluated by X-rays and endoscopic and functional respiratory tests for bronchial de-obstruction. Complete remission after PDT of GI tract cancers was considered to be tumour eradication (histologically and cytologically proved) and a tumour-free interval of at least 12 months. PMID:2121932

  3. Circulating tumor cells in lung cancer.

    PubMed

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. PMID:23207444

  4. The relationship between COPD and lung cancer

    PubMed Central

    Durham, A.L.; Adcock, I.M.

    2015-01-01

    Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments. PMID:26363803

  5. Lung Cancer Gene Signatures and Clinical Perspectives

    PubMed Central

    Kuner, Ruprecht

    2013-01-01

    Microarrays have been used for more than two decades in preclinical research. The tumor transcriptional profiles were analyzed to select cancer-associated genes for in-deep functional characterization, to stratify tumor subgroups according to the histopathology or diverse clinical courses, and to assess biological and cellular functions behind these gene sets. In lung cancer—the main type of cancer causing mortality worldwide—biomarker research focuses on different objectives: the early diagnosis of curable tumor diseases, the stratification of patients with prognostic unfavorable operable tumors to assess the need for further therapy regimens, or the selection of patients for the most efficient therapies at early and late stages. In non-small cell lung cancer, gene and miRNA signatures are valuable to differentiate between the two main subtypes’ squamous and non-squamous tumors, a discrimination which has further implications for therapeutic schemes. Further subclassification within adenocarcinoma and squamous cell carcinoma has been done to correlate histopathological phenotype with disease outcome. Those tumor subgroups were assigned by diverse transcriptional patterns including potential biomarkers and therapy targets for future diagnostic and clinical applications. In lung cancer, none of these signatures have entered clinical routine for testing so far. In this review, the status quo of lung cancer gene signatures in preclinical and clinical research will be presented in the context of future clinical perspectives.

  6. [Metastatic hormone-sensitive prostate cancer].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  7. Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

    PubMed Central

    DING, HONGMEI; LIU, JIANHUA; XUE, RONG; ZHAO, PENG; QIN, YI; ZHENG, FANG; SUN, XUGUO

    2014-01-01

    Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. PMID:25054025

  8. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  9. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-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

  10. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    SciTech Connect

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.

  11. Receptor Tyrosine Kinase EphA5 Is a Functional Molecular Target in Human Lung Cancer*

    PubMed Central

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

    2015-01-01

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. PMID:25623065

  12. [Therapeutic strategy for secondary lung cancer].

    PubMed

    Miura, Hiroyuki; Nakajima, Norio; Takahashi, Hidenobu; Kinoshita, Masao; Ikeda, Norihiko

    2010-10-01

    Among 659 resected lung cancer cases from 1994 to 2009, 57 secondary lung cancers (8.6%) were evaluated. The secondary tumors were synchronous, located in the same lobe in 10, the ipsilateral different lobe in 17, and the contralateral lobe in 13, or metachronous, located in the contralateral lobe in 15, and the ipsilateral different lobe in 5. Both the tumors were removed in 49 cases. Chemotherapy, stereotactic radiotherapy (SRT), photo dynamic therapy (PDT), or best supportive care (BSC) was selected after a lobectomy or segmentectomy of the 1st tumor in 8 cases considering the patient's condition. Lobectomy or segmentectomy should be indicated for the 1st tumor considering curability. Bilobectomy is adopted for multiple cancers involving middle lobe. According to the operability or pulmonary function, the same strategy is adopted for secondary cancer. Considering the patient's condition, possibility of metastases and the tumor location and histologic type, partial resection, SRT, PDT, or BSC could be selected. PMID:20954350

  13. Genomics of Squamous Cell Lung Cancer

    PubMed Central

    Rooney, Melissa; Devarakonda, Siddhartha

    2013-01-01

    Approximately 30% of patients with non-small cell lung cancer have the squamous cell carcinoma (SQCC) histological subtype. Although targeted therapies have improved outcomes in patients with adenocarcinoma, no agents are currently approved specifically for use in SQCC. The Cancer Genome Atlas (TCGA) recently published the results of comprehensive genomic analyses of tumor samples from 178 patients with SQCC of the lung. In this review, we briefly discuss key molecular aberrations reported by TCGA and other investigators and their potential therapeutic implications. Carefully designed preclinical and clinical studies based on these large-scale genomic analyses are critical to improve the outcomes of patients with SQCC of lung in the near future. PMID:23728941

  14. Expanding a Comprehensive Lung Cancer Screening Program.

    PubMed

    Jansak, Buffy

    2015-01-01

    The OhioHealth Lung Cancer Screening Program is a high quality multi-disciplinary program that was launched in July 2013 at OhioHealth Riverside Methodist Hospital, OhioHealth Doctors Hospital, and OhioHealth Grant Medical Center in Columbus, Ohio. With the assistance of the AHRA & Toshiba Putting Patients First grant, we were able to expand community access for people at high risk of developing lung cancer by opening several more programs at OhioHealth Marion General and OhioHealth Grady Memorial Hospitals. A subsequent patient educational video was developed to highlight the comprehensive program, nurse navigational involvement, potential risks, benefits, and tobacco cessation. The tobacco cessation educational skills of the OhioHealth Lung Nurse Navigators were enhanced with the completion of the Tobacco Treatment Specialist certification. PMID:26710574

  15. Occupation, Gender, Race, and Lung Cancer

    PubMed Central

    Amr, Sania; Wolpert, Beverly; Loffredo, Christopher A.; Zheng, Yun-Ling; Shields, Peter G.; Jones, Raymond; Harris, Curtis C.

    2008-01-01

    Objective To examine associations between occupation and lung cancer by gender and race. Methods We used data from the Maryland Lung Cancer Study of nonsmall cell lung carcinoma (NSCLC), a multicenter case control study, to estimate odds ratios (ORs) of NSCLC in different occupations. Results After adjusting for smoking, environmental tobacco smoke, and other covariates, NSCLC ORs among women but not men were elevated in clerical-sales, service, and transportation-material handling occupations; ORs were significantly increased in all three categories (OR [95% confidence interval]: 4.07 [1.44 to 11.48]; 5.15 [1.62 to 16.34]; 7.82 [1.08 to 56.25], respectively), among black women, but only in transportation-material handling occupations (OR [95% confidence interval[: 3.43 [1.02 to 11.50]) among white women. Conclusions Women, especially black women, in certain occupations had increased NSCLC ORs. PMID:18849762

  16. Treatment of Brain Metastasis from Lung Cancer

    PubMed Central

    Chi, Alexander; Komaki, Ritsuko

    2010-01-01

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well. PMID:24281220

  17. Parathyroid adenoma upstaging the lung cancer.

    PubMed

    Okuyucu, Kursat; Kavakli, Kuthan; Ozaydın, Sukru; Karahatay, Serdar; Karatas, Okan; Doğan, Deniz

    2015-05-01

    Mediastinal staging of NSCLC with noninvasive methods such as PET/CT can be misleading when a mediastinal disease accompany. Histopathologic confirmation should be made before any treatment plan. Herein, we presented a case of parathyroid adenoma upstaging the lung cancer. PMID:25618011

  18. [Immunotherapy in lung cancer: checkpoint inhibitors].

    PubMed

    Wehler, Thomas; Wehler, Beatrice; Stehle, Ingo

    2015-12-01

    Monoclonal antibodies against the PD-1 receptor or its ligands result in a recovery of T cell responses against tumor antigens. Nivolumab is the first antibody that has been approved in lung cancer. This mode of action is very intersting, especially because of long term responses and the moderate toxicity. PMID:26625234

  19. Outdoor air pollution and lung cancer.

    PubMed Central

    Cohen, A J

    2000-01-01

    In the 1950s evidence of an ongoing epidemic of lung cancer in the United States and Western Europe led researchers to examine the role of outdoor air pollution, which was considered by some to be a likely cause. Although epidemiologic research quickly identified the central role of cigarette smoking in this epidemic, and despite progress in reducing outdoor air pollution in Western industrialized countries, concerns that ambient air pollution is causing lung cancer have persisted to the present day. This concern is based on the fact that known carcinogens continue to be released into outdoor air from industrial sources, power plants, and motor vehicles, and on a body of epidemiologic research that provides some evidence for an association between outdoor air pollution and lung cancer. This article reviews the epidemiologic evidence for this association and discusses the limitations of current studies for estimating the lung cancer risk in the general population. It also identifies research needs and suggests possible approaches to addressing outstanding questions. PMID:10931793

  20. Screening and early detection of lung cancer.

    PubMed

    Vansteenkiste, J; Dooms, C; Mascaux, C; Nackaerts, K

    2012-09-01

    The greatest news of the past year in this field was the first large-scale early detection trial that could prove a 20% reduction in lung cancer-related mortality by screening high-risk individuals with low-dose computed tomography (LDCT). Several expert groups and medical societies have assessed the data and concluded that LDCT screening for lung cancer is, however, not ready for large-scale population-based implementation. Too many open questions remain, such as definition of the at-risk population, timing and intervals of screening, optimal method of acquisition and interpretation of the images, how to handle (false) positive findings, and especially cost-effectiveness in relation to other lung cancer prevention strategies, mainly smoking cessation. Further analyses and several ongoing European trials are eagerly awaited. Much hope also resides in the use of biomarkers, as their use in, e.g., blood or exhaled air may provide more easy-to-use tests to better stratify high-risk populations for screening studies. While exciting research is ongoing in this domain--e.g. with microRNAs--none of the tests has yet reached sufficient validation for clinical use. Early central lung cancers are more difficult to visualise by CT. For these patients, standard bronchoscopy, complemented by autofluoresence endoscopy, has been studied in different screening and follow-up settings. PMID:22987984

  1. The wind god promotes lung cancer.

    PubMed

    Frisch, Steven M; Schaller, Michael D

    2014-05-12

    In this issue of Cancer Cell, Li and colleagues demonstrate that the hematopoietic transcription factor Aiolos (named after the Wind God of Greek mythology) confers anoikis resistance in lung tumor cells through repression of cell adhesion-related genes including the mechanosensor p66Shc. PMID:24823631

  2. Aiolos and Lymphocyte Mimicry in Lung Cancer

    PubMed Central

    Terada, Lance S; Liu, Zhe

    2014-01-01

    Aggressive carcinomas tend to adopt behaviors normally restricted to lymphocytes, including anchorage-independent mobilization, response to chemokines, and modulation of local inflammatory conditions. In a recent study we identified the lymphocyte-restricted chromatin regulator Aiolos as an epigenetic driver of lymphocyte mimicry in lung cancer that links immune cell development to metastatic behavior. PMID:27308319

  3. Gene variant linked to lung cancer risk

    Cancer.gov

    A variation of the gene NFKB1, called rs4648127, is associated with an estimated 44 percent reduction in lung cancer risk. When this information, derived from samples obtained as part of a large NCI-sponsored prevention clinical trial, was compared with d

  4. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    ClinicalTrials.gov

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  5. Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

    2016-03-01

    Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

  6. Ouabain enhances lung cancer cell detachment.

    PubMed

    Ruanghirun, Thidarat; Pongrakhananon, Varisa; Chanvorachote, Pithi

    2014-05-01

    A human steroid hormone, ouabain, has been shown to play a role in several types of cancer cell behavior; however, its effects on cancer metastasis are largely unknown. Herein, we demonstrate that sub-toxic concentrations of ouabain facilitate cancer cell detachment from the extracellular matrix in human lung cancer cells. Ouabain at concentrations of 0-10 pM significantly enhanced cell detachment in dose- and time- dependent manners, while having minimal effect on cell viability. The detachment-inducing effect of ouabain was found to be mediated through focal-adhesion kinase and ATP-dependent tyrosine kinase pathways. Alpha-5 and beta-1 integrins were found to be down-regulated in response to ouabain treatment. Since detachment of cancer cells is a prerequisite process for metastasis to begin, these insights benefit our understanding over the molecular basis of cancer biology. PMID:24778025

  7. Digital tomosynthesis in lung cancer: state of the art

    PubMed Central

    Viti, Andrea; Terzi, Alberto

    2015-01-01

    Chest digital tomosynthesis (CDT) is a limited angle image tomography, which improves the visibility of anatomy compared with radiographic imaging. Due to the limited acquisition angle of CDT, it has the potential to significantly increase the temporal resolution of patient surveillance at the cost of reduced resolution in one direction. CDT is 3 times more effective in identifying pulmonary nodules compared to conventional radiography and at lower doses and cost compared with routine chest computed tomography (CT) examinations. There is only one report in which CDT was used in a single-arm observational study for lung cancer detection in at-risk population while a few studies suggested that CDT sensitivity is superior to radiography but inferior to CT in detecting lung nodules, other studies on the accuracy of CDT suggest that the specificity is much closer to CT than radiography. Therefore, large-scale randomized controlled trial would be needed to confirm benefits of CDT and identify where it is best used in the clinical setting. CDT seems to be a cost-effectiveness first-line lung cancer screening tool to detect potential lung cancer nodule. PMID:26207232

  8. Role of acetylcholinesterase in lung cancer

    PubMed Central

    Xi, Hui-Jun; Wu, Ren-Pei; Liu, Jing-Jing; Zhang, Ling-Juan; Li, Zhao-Shen

    2015-01-01

    Acetylcholinesterase (AChE) plays a key role in catalytic hydrolysis of cholinergic neurotransmitters. Intensive research has proven the involvement of this protein in novel functions, such as cell adhesion, differentiation, and proliferation. In addition, several recent studies have indicated that acetylcholinesterase is potentially a marker and regulator of apoptosis. Importantly, AChE is also a promising tumor suppressor. In this review, we briefly summarize the involvement of AChE in apoptosis and cancer, focusing on the role of AChE in lung cancer, as well as the therapeutic consideration of AChE for cancer therapy. PMID:26273392

  9. Deaths in Canada from lung cancer due to involuntary smoking.

    PubMed Central

    Wigle, D T; Collishaw, N E; Kirkbride, J; Mao, Y

    1987-01-01

    Recently published evidence indicates that involuntary smoking causes an increased risk of lung cancer among nonsmokers. Information was compiled on the proportion of people who had never smoked among victims of lung cancer, the risk of lung cancer for nonsmokers married to smokers and the prevalence of such exposure. On the basis of these data we estimate that 50 to 60 of the deaths from lung cancer in Canada in 1985 among people who had never smoked were caused by spousal smoking; about 90% occurred in women. The total number of deaths from lung cancer attributable to exposure to tobacco smoke from spouses and other sources (mainly the workplace) was derived by applying estimated age- and sex-specific rates of death from lung cancer attributable to such exposure to the population of Canadians who have never smoked; about 330 deaths from lung cancer annually are attributable to such exposure. PMID:3567810

  10. Breath sensors for lung cancer diagnosis.

    PubMed

    Adiguzel, Yekbun; Kulah, Haluk

    2015-03-15

    The scope of the applications of breath sensors is abundant in disease diagnosis. Lung cancer diagnosis is a well-fitting health-related application of this technology, which is of utmost importance in the health sector, because lung cancer has the highest death rate among all cancer types, and it brings a high yearly global burden. The aim of this review is first to provide a rational basis for the development of breath sensors for lung cancer diagnostics from a historical perspective, which will facilitate the transfer of the idea into the rapidly evolving sensors field. Following examples with diagnostic applications include colorimetric, composite, carbon nanotube, gold nanoparticle-based, and surface acoustic wave sensor arrays. These select sensor applications are widened by the state-of-the-art developments in the sensors field. Coping with sampling sourced artifacts and cancer staging are among the debated topics, along with the other concerns like proteomics approaches and biomimetic media utilization, feature selection for data classification, and commercialization. PMID:25461148

  11. LUNG CANCER IN NEVER SMOKERS: MOLECULAR PROFILES AND THERAPEUTIC IMPLICATIONS

    PubMed Central

    Rudin, Charles M.; Avila-Tang, Erika; Harris, Curtis C.; Herman, James G.; Hirsch, Fred R.; Pao, William; Schwartz, Ann G.; Vahakangas, Kirsi H.; Samet, Jonathan M.

    2010-01-01

    The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. While a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years demonstrates that lung cancers in never smokers are much more likely to carry activating mutations of the Epidermal Growth Factor Receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anti-cancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers. PMID:19755392

  12. Nonsmall-cell lung cancer: chemoprevention studies.

    PubMed

    Karp, Daniel D; Tsao, Anne S; Kim, Edward S

    2003-10-01

    Lung cancer is the leading cause of cancer-related death in the world. Tobacco is an addictive agent producing carcinogenic effects that have been extremely difficult to prevent or detect in a curable stage. Important randomized controlled studies have been published in "healthy" smokers (primary prevention); patients with early lesions, such as mucosal dysplasia/metaplasia (secondary prevention); and those who have already had definitive treatment for their first tobacco-related malignancy (tertiary prevention). To date, the results have been generally disappointing. It is critical to remember that lung cancer is usually diagnosed decades after the patient has begun or even stopped smoking. We must intervene with more effective agents or combinations of agents and do it earlier in the process of carcinogenesis. Approximately 10% of patients with lung cancer either never smoked or only were "passive" smokers due to their environment, workplace. These "never-smokers" may actually benefit from retinoids, while current smokers have not benefited from alpha-tocopherol, retinal, N-acetylcysteine, or isotretinoin. Smokers are actually harmed by the concurrent use of beta-carotene. We now have unprecedented knowledge regarding the control of cellular growth and senescence. New diagnostic tools also allow detection of smaller lesions. We must use all our knowledge of the cancer biology, new risk models, more refined intermediate markers, and modern detection tools to focus more clearly on the pathology of lung cancer and design research to ask more probing and relevant questions so we can begin to put an end to the worldwide scourge of this terrible killer. PMID:14710383

  13. Cutaneous manifestations of lung cancer.

    PubMed

    Owen, Cindy England

    2016-06-01

    Skin findings can serve as a clue to internal disease. In this article, cutaneous manifestations of underlying lung malignancy are reviewed. Paraneoplastic dermatoses are rare, but when recognized early, can lead to early diagnosis of an underlying neoplasm. Malignancy-associated dermatoses comprise a broad group of hyperproliferative and inflammatory disorders, disorders caused by tumor production of hormonal or metabolic factors, autoimmune connective tissue diseases, among others. In this review, paraneoplastic syndromes associated with lung malignancy are discussed, including ectopic ACTH syndrome, bronchial carcinoid variant syndrome, secondary hypertrophic osteoarthropathy/digital clubbing, erythema gyratum repens, malignant acanthosis nigricans, sign of Leser-Trélat, tripe palms, hypertrichosis lanuginosa, acrokeratosis paraneoplastica, and dermatomyositis. PMID:27178690

  14. [Minimally Invasive Open Surgery for Lung Cancer].

    PubMed

    Nakagawa, Kazuo; Watanabe, Shunichi

    2016-07-01

    Significant efforts have been made to reduce the invasiveness of surgical procedures by surgeons for a long time. Surgeons always keep it in mind that the basic principle performing less invasive surgical procedures for malignant tumors is to decrease the invasiveness for patients without compromising oncological curability and surgical safety. Video-assisted thoracic surgery (VATS) has been used increasingly as a minimally invasive approach to lung cancer surgery. Whereas, whether VATS lobectomy is a less invasive procedure and has equivalent or better clinical effect compared with open lobectomy for patients with lung cancer remains controversial because of the absence of randomized prospective studies. The degree of difficulty for anatomical lung resection depends on the degree of the fissure development, mobility of hilar lymph nodes, and the degree of pleural adhesions. During pulmonary surgery, thoracic surgeons always have to deal with not only these difficulties but other unexpected events such as intraoperative bleeding. Recently, we perform pulmonary resection for lung cancer with minimally invasive open surgery (MIOS) approach. In this article, we introduce the surgical procedure of MIOS and demonstrate short-term results. Off course, the efficacy of MIOS needs to be further evaluated with long-term results. PMID:27440030

  15. The Utility of Exercise Testing in Patients with Lung Cancer.

    PubMed

    Ha, Duc; Mazzone, Peter J; Ries, Andrew L; Malhotra, Atul; Fuster, Mark

    2016-09-01

    The harm associated with lung cancer treatment include perioperative morbidity and mortality and therapy-induced toxicities in various organs, including the heart and lungs. Optimal treatment therefore entails a need for risk assessment to weigh the probabilities of benefits versus harm. Exercise testing offers an opportunity to evaluate a patient's physical fitness/exercise capacity objectively. In lung cancer, it is most often used to risk-stratify patients undergoing evaluation for lung cancer resection. In recent years, its use outside this context has been described, including in nonsurgical candidates and lung cancer survivors. In this article we review the physiology of exercise testing and lung cancer. Then, we assess the utility of exercise testing in patients with lung cancer in four contexts (preoperative evaluation for lung cancer resection, after lung cancer resection, lung cancer prognosis, and assessment of efficiency of exercise training programs) after systematically identifying original studies involving the most common forms of exercise tests in this patient population: laboratory cardiopulmonary exercise testing and simple field testing with the 6-minute walk test, shuttle walk test, and/or stair-climbing test. Lastly, we propose a conceptual framework for risk assessment of patients with lung cancer who are being considered for therapy and identify areas for further studies in this patient population. PMID:27156441

  16. Mucins in lung cancer: diagnostic, prognostic, and therapeutic implications.

    PubMed

    Lakshmanan, Imayavaramban; Ponnusamy, Moorthy P; Macha, Muzafar A; Haridas, Dhanya; Majhi, Prabin Dhangada; Kaur, Sukhwinder; Jain, Maneesh; Batra, Surinder K; Ganti, Apar Kishor

    2015-01-01

    Aberrant expression of mucins is associated with cancer development and metastasis. An overexpression of few mucins contributes to oncogenesis by enhancing cancer cell growth and providing constitutive survival signals. This review focuses on the importance of mucins both in the normal bronchial epithelial cells and the malignant tumors of the lung and their contribution in the diagnosis and prognosis of lung cancer patients. During lung cancer progression, mucins either alone or through their interaction with many receptor tyrosine kinases mediate cell signals for growth and survival of cancer cells. Also, stage-specific expression of certain mucins, like MUC1, is associated with poor prognosis from lung cancer. Thus, mucins are emerging as attractive targets for developing novel therapeutic approaches for lung cancer. Several strategies targeting mucin expression and function are currently being investigated to control lung cancer progression. PMID:25319180

  17. Cancer stem cells: progress and challenges in lung cancer

    PubMed Central

    Templeton, Amanda K.; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called “cancer stem cells” (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs.

  18. A combinatorial strategy for treating KRAS-mutant lung cancer.

    PubMed

    Manchado, Eusebio; Weissmueller, Susann; Morris, John P; Chen, Chi-Chao; Wullenkord, Ramona; Lujambio, Amaia; de Stanchina, Elisa; Poirier, John T; Gainor, Justin F; Corcoran, Ryan B; Engelman, Jeffrey A; Rudin, Charles M; Rosen, Neal; Lowe, Scott W

    2016-06-30

    Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by the US Food and Drug Administration, which acts downstream of KRAS to suppress signalling through the mitogen-activated protein kinase (MAPK) cascade. Informed by a short-hairpin RNA screen, we show that trametinib provokes a compensatory response involving the fibroblast growth factor receptor 1 (FGFR1) that leads to signalling rebound and adaptive drug resistance. As a consequence, genetic or pharmacological inhibition of FGFR1 in combination with trametinib enhances tumour cell death in vitro and in vivo. This compensatory response shows distinct specificities: it is dominated by FGFR1 in KRAS-mutant lung and pancreatic cancer cells, but is not activated or involves other mechanisms in KRAS wild-type lung and KRAS-mutant colon cancer cells. Importantly, KRAS-mutant lung cancer cells and patients’ tumours treated with trametinib show an increase in FRS2 phosphorylation, a biomarker of FGFR activation; this increase is abolished by FGFR1 inhibition and correlates with sensitivity to trametinib and FGFR inhibitor combinations. These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer. PMID:27338794

  19. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... whether surgery will be helpful for you EXTERNAL BEAM RADIATION THER APY External beam radiation therapy is the safe delivery of high- ... your cancer. A linear accelerator focuses the radiation beam to a precise location in your body for ...

  20. Smog May Shorten Lives of Lung Cancer Patients

    MedlinePlus

    ... 5, 2016 FRIDAY, Aug. 5, 2016 (HealthDay News) -- Air pollution may shorten the lives of lung cancer patients, ... the International Agency for Research on Cancer classifies air pollution as a cancer-causing agent. "This study, along ...

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

    PubMed

    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

    2015-02-15

    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

  2. Palliative care in patients with lung cancer

    PubMed Central

    Farbicka, Paulina

    2013-01-01

    Lung cancer accounts for 12% of all cancers and has the highest annual rate of mortality in men and women. The overall aim is cure or prolongation of life without evidence of disease. Almost 60% of patients at the moment of diagnosis are not eligible for radical treatment. Therefore soothing and supportive treatment is the only treatment of choice. Patients with lung cancer who have symptoms of dyspnea, chronic cough, severe pain, exhaustion and cachexia syndrome, fear and depression and significantly reduced physical and intellectual activities are qualified for inpatient or home palliative care. Knowledge about various methods used in palliative treatment allows one to alleviate symptoms that occur in an advanced stage of disease with an expected short survival period. Methods of oncological treatment that are often used in patients with advanced lung cancer include radiotherapy and chemotherapy. Drawing attention to the earlier implementation of palliative care is an objective of research carried out during recent years. Advances in surgical and conservative treatment of these patients have contributed to better outcomes and longer survival time. PMID:24596508

  3. Lung cancer: Current status and prospects for the future

    SciTech Connect

    Mountain, C.F.; Carr, D.T.

    1986-01-01

    This book contains 32 papers. Some of the titles are: Activation of cellular ras genes in human neoplasms; The valve of definitive radiation therapy of unresectable squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung; Current concepts of chemotherapy and radiotherapy for small cell lung cancer, and Current status of immunotherapy for lung cancer.

  4. Testing lung cancer drugs and therapies in mice

    Cancer.gov

    National Cancer Institute (NCI) investigators have designed a genetically engineered mouse for use in the study of human lung squamous cell carcinoma (SCC). SCC is a type of non-small cell lung carcinoma, one of the most common types of lung cancer, with

  5. MicroRNA In Lung Cancer: Novel Biomarkers and Potential Tools for Treatment

    PubMed Central

    Inamura, Kentaro; Ishikawa, Yuichi

    2016-01-01

    Lung cancer is the leading cause of cancer death in men and women worldwide. The lack of specific and sensitive tools for early diagnosis as well as still-inadequate targeted therapies contribute to poor outcomes. MicroRNAs are small non-coding RNAs, which regulate gene expression post-transcriptionally by translational repression or degradation of target mRNAs. A growing body of evidence suggests various roles of microRNAs including development and progression of lung cancer. In lung cancer, several studies have showed that certain microRNA profiles classified lung cancer subtypes, and that specific microRNA expression signatures distinguished between better-prognosis and worse-prognosis lung cancers. Furthermore, microRNAs circulate in body fluids, and therefore may serve as promising biomarkers for early diagnosis of lung cancer as well as for predicting prognosis of patients. In the present review, we briefly summarize microRNAs in the development and progression of lung cancer, focusing on possible applications of microRNAs as novel biomarkers and tools for treatment. PMID:27005669

  6. The role of new PET tracers for lung cancer.

    PubMed

    Szyszko, Teresa A; Yip, Connie; Szlosarek, Peter; Goh, Vicky; Cook, Gary J R

    2016-04-01

    18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer

  7. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    DOE PAGESBeta

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; et al

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lungmore » cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.« less

  8. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  9. DIETARY AGENTS FOR PREVENTION AND TREATMENT OF LUNG CANCER

    PubMed Central

    Khan, Naghma; Mukhtar, Hasan

    2015-01-01

    Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy. Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets. In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer. PMID:25644088

  10. Attenuation of the DNA Damage Response by Transforming Growth Factor-Beta Inhibitors Enhances Radiation Sensitivity of Non–Small-Cell Lung Cancer Cells In Vitro and In Vivo

    SciTech Connect

    Du, Shisuo; Bouquet, Sophie; Lo, Chen-Hao; Pellicciotta, Ilenia; Bolourchi, Shiva; Parry, Renate; Barcellos-Hoff, Mary Helen

    2015-01-01

    Purpose: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non–small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. Methods and Materials: TGF-β–mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure. The DNA damage response was assessed by ataxia telangiectasia mutated (ATM) or Trp53 protein phosphorylation, γH2AX foci formation, or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing syngeneic subcutaneous LLC tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody. Results: The NCI-H1299, A549, and LLC NSCLC cell lines pretreated with LY364947 before radiation exposure exhibited compromised DNA damage response, indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. The NCI-H292 cells were unresponsive. Transforming growth factor-β signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGF-β neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation. Conclusions: Inhibition of TGF-β before radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC cells in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGF-β inhibition and RT to provide therapeutic benefit in NSCLC.

  11. Recent developments in the epidemiology of lung cancer

    SciTech Connect

    Kabat, G.C. )

    1993-03-01

    Lung cancer is currently the leading cause of cancer death in the United States and also the most common tumor worldwide. Changes in the distribution of histologic types over the past two decades in the United States, as well as high rates of lung cancer in certain subpopulations, require explanation. While cigarette smoking and specific occupational exposures are firmly established as important risk factors for lung cancer, recent work provides evidence that other factors may play a role either as independent risk factors or as modifiers of the effect of smoking. This paper reviews the epidemiology of lung cancer, with an emphasis on developments in the past decade. 79 refs.

  12. An update on sputum MicroRNAs in lung cancer diagnosis.

    PubMed

    Sheervalilou, Roghayeh; Ansarin, Khalil; Fekri Aval, Sedigheh; Shirvaliloo, Sakine; Pilehvar-Soltanahmadi, Yones; Mohammadian, Mozhdeh; Zarghami, Nosratollah

    2016-05-01

    Lung cancer is one of the leading cause of cancer mortality in the world. It is well known that genetic damages could result in lung tumor genesis. Despite years of research, the survival rate of the patients has not been markedly improved. According to lack of high sensitivity and specificity in diagnostic tests, just about 15-20% of lung cancer cases are discovered prior to progression of the disease. In last decade, sputum biomarkers have been developed for early detection/diagnosis of lung cancer. MicroRNAs are a class of small endogenous noncoding RNAs, which act as post-transcriptional regulators. Some specific miRNAs can have multifunctions in lung development and their aberrant expression could induce lung tumor genesis. The differences in miRNAs between the normal and cancerous lung lead to emerging of a novel type of biomarkers, which can be helpful in screening of high risk individuals, diagnosis of lung cancer as well as its therapy. Diagn. Cytopathol. 2016;44:442-449. © 2016 Wiley Periodicals, Inc. PMID:26865409

  13. Lung Cancer Ablation: Technologies and Techniques

    PubMed Central

    Alexander, Erica S.; Dupuy, Damian E.

    2013-01-01

    The incidence of lung cancers in 2012 is estimated to reach 226,160 new cases, with only a third of patients suitable surgical candidates. Tumor ablation has emerged as an important and efficacious treatment option for nonsurgical lung cancer patients. This localized minimally invasive therapy is best suited for small oligonodular lesions or favorably located metastatic tumors. Radiofrequency ablation has been in use for over a decade, and newer modalities including microwave ablation, cryoablation, and irreversible electroporation have emerged as additional treatment options for patients. Ablation therapies can offer patients and clinicians a repeatable and effective therapy for palliation and, in some cases, cure of thoracic malignancies. This article discusses the available technologies and techniques available for tumor ablation of thoracic malignancies including patient selection, basic aspects of procedure technique, imaging follow-up, treatment outcomes, and comparisons between various therapies. PMID:24436530

  14. Spectral characteristic analysis of lung cancer serum

    NASA Astrophysics Data System (ADS)

    Li, Xiao Zhou; Jin, Huiqiang; Liu, Huasheng; Ding, Jianhua; Lin, Junxiu

    2001-10-01

    Spectral changes of lung cancer serum in the process of tumor evolution were investigated in this study. We kept close watch on the tumor progression of a group of patients, and measured their serum spectra using 488.0nm and 514.5nm excitation of an Ar-ion laser once a week. There was no apparent change observed in fluorescence spectrum in different period. However, the relative intensity of three Raman peaks (mode A, B and C) decreased every week later. For quantitative analysis of such changes, a parameter Ir (relative intensity of C Raman peak) was introduced and Ir-value was calculated. Calculation showed that Ir-value was degressive with tumor evolution, but (beta) (Ir5145 /Ir4880) varied irregularly. To the end, no Raman peak was observed. We assumed that three Raman peaks were derived from beta carotene. It indicated that the content of beta carotene decreased with the aggravation of lung cancer.

  15. Lung cancer-a fractal viewpoint.

    PubMed

    Lennon, Frances E; Cianci, Gianguido C; Cipriani, Nicole A; Hensing, Thomas A; Zhang, Hannah J; Chen, Chin-Tu; Murgu, Septimiu D; Vokes, Everett E; Vannier, Michael W; Salgia, Ravi

    2015-11-01

    Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has shown considerable promise for measuring processes as varied as heart and respiratory rates, neuronal cell characterization, and vascular development. Despite the advantages of fractal mathematics and numerous studies demonstrating its applicability to lung cancer research, many researchers and clinicians remain unaware of its potential. Therefore, this Review aims to introduce the fundamental basis of fractals and to illustrate how analysis of fractal dimension (FD) and associated measurements, such as lacunarity (texture) can be performed. We describe the fractal nature of the lung and explain why this organ is particularly suited to fractal analysis. Studies that have used fractal analyses to quantify changes in nuclear and chromatin FD in primary and metastatic tumour cells, and clinical imaging studies that correlated changes in the FD of tumours on CT and/or PET images with tumour growth and treatment responses are reviewed. Moreover, the potential use of these techniques in the diagnosis and therapeutic management of lung cancer are discussed. PMID:26169924

  16. Analysis of MicroRNAs in Sputum to Improve Computed Tomography for Lung Cancer Diagnosis

    PubMed Central

    Shen, Jun; Liao, Jipei; Guarnera, Maria A.; Fang, HongBin; Cai, Ling; Stass, Sanford A.; Jiang, Feng

    2016-01-01

    Introduction Computed tomography (CT) plays a central role in lung cancer diagnosis. However, CT has relatively low specificity, presenting a challenge in clinical settings. We previously identified 12 microRNAs (miRNAs) whose expressions in tumor tissues were associated with lung cancer. Methods Using quantitative reverse transcriptase polymerase chain reaction, we aimed to identify miRNA biomarkers in sputum that could complement CT for diagnosis of lung cancer. Results In a training set consisting of 66 lung cancer patients and 68 cancer-free smokers, 10 of the 12 miRNAs were differentially expressed between the cases and controls (p ≤ 0.01). From the miRNAs, a logistic regression model was built on the basis of miR-31 and miR-210, both of which had the best prediction for lung cancer, producing an area under receiver operating characteristic curve of 0.83. Combined use of the two miRNAs yielded 65.2% sensitivity and 89.7% specificity, CT had 93.9% sensitivity and 83.8% specificity for lung cancer diagnosis. Notably, combined analysis of the miRNA biomarkers and CT produced a higher specificity than does CT used alone (91.2% versus 83.8%; p < 0.05). The diagnostic performance of the biomarkers was confirmed in a testing set comprising 64 lung cancer patients and 73 cancer-free smokers. Conclusion The sputum miRNA biomarkers might be useful in improving CT for diagnosis of lung cancer, but further independent validation on an external and prospective cohort of patients is required. PMID:24305007

  17. Discovery of Lung Cancer Biomarkers by Profiling the Plasma Proteome with Monoclonal Antibody Libraries*

    PubMed Central

    Guergova-Kuras, Mariana; Kurucz, István; Hempel, William; Tardieu, Nadège; Kádas, János; Malderez-Bloes, Carole; Jullien, Anne; Kieffer, Yann; Hincapie, Marina; Guttman, András; Csánky, Eszter; Dezső, Balázs; Karger, Barry L.; Takács, László

    2011-01-01

    A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC. PMID:21947365

  18. Discovery of lung cancer biomarkers by profiling the plasma proteome with monoclonal antibody libraries.

    PubMed

    Guergova-Kuras, Mariana; Kurucz, István; Hempel, William; Tardieu, Nadège; Kádas, János; Malderez-Bloes, Carole; Jullien, Anne; Kieffer, Yann; Hincapie, Marina; Guttman, András; Csánky, Eszter; Dezso, Balázs; Karger, Barry L; Takács, László

    2011-12-01

    A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC. PMID:21947365

  19. Black Smokers Less Likely to Get Lung Cancer Screening

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_157850.html Black Smokers Less Likely to Get Lung Cancer Screening ... 2016 (HealthDay News) -- Differences in smoking habits between black and white Americans may lead to lower lung ...

  20. Discovery – Lung Cancer Screening Saves Lives: The NLST

    Cancer.gov

    NCI funded the National Lung Screening Trial, an eight-year study that used new technology to detect small, aggressive tumors early enough to surgically remove them. This approach reduced lung cancer deaths among participants by 20 percent.

  1. [Lung Cancer as an Occupational Disease].

    PubMed

    Baur, X; Woitowitz, H-J

    2016-08-01

    Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated. PMID:27512930

  2. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    PubMed Central

    Huang, Shang-Lang; Chao, Chuck C.-K.

    2015-01-01

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug. PMID:26086592

  3. The National Lung Screening Trial (NLST) | Division of Cancer Prevention

    Cancer.gov

    The National Lung Screening Trial (NLST) compared two ways of detecting lung cancer: low-dose helical computed tomography (CT) and standard chest X-ray. Both chest X-rays and low-dose helical CT scans have been used to find lung cancer early, but the effects of these screening techniques on lung cancer mortality rates had not been determined. NLST enrolled 53,454 current or former heavy smokers from 33 sites and coordinating centers across the United States. | The National Lung Screening Trial (NLST) compared two ways of detecting lung cancer: participants who received low-dose helical CT scans had a 20% lower risk of dying from lung cancer than participants who received standard chest X-rays.

  4. Pemetrexed (Alimta) in small cell lung cancer.

    PubMed

    Socinski, Mark A

    2005-04-01

    Small cell lung cancer (SCLC) comprises approximately 13% of all lung cancers. In limited stage (LS)-SCLC, combined-modality therapy represents the standard of care. Therapy should be approached curatively in fit patients with a good performance status because 5-year survival rates approach 26% in aggressively treated patients. In contrast, cure is not possible in extensive stage (ES)-SCLC with median 2-year survival rates with current therapy remaining at less than 10%. Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a novel, multi-targeted antifolate that inhibits several folate-dependent enzymes involved in purine and pyrimidine synthesis, and is active as a single-agent or in combination with a platinum in both non-small cell lung cancer and malignant pleural mesothelioma. Pemetrexed/platinum combinations appear active in ES-SCLC based on objective response rates observed in a randomized phase II trial. However, no survival data is yet available from this trial. The toxicity profile of both cisplatin and carboplatin in combination with pemetrexed was extremely favorable, as was the ability to deliver full doses of each of the component drugs. Given the limited options available for patients in the relapsed setting, the activity of single-agent pemetrexed is interesting. Also, preliminary data indicates that full doses of carboplatin/pemetrexed can be administered with thoracic radiation therapy, supporting a future clinical trial initiative in LS-SCLC. PMID:15818532

  5. Dietary factors in lung cancer prognosis.

    PubMed

    Goodman, M T; Kolonel, L N; Wilkens, L R; Yoshizawa, C N; Le Marchand, L; Hankin, J H

    1992-01-01

    A hypothesis-generating analysis of the role of diet on survival was conducted among a sample of 463 men and 212 women with histologically-confirmed lung cancer. Interview information was obtained from two population-based case-control studies of lung cancer conducted on the Island of Oahu, Hawaii, between 1979 and 1985. The interview consisted of a quantitative dietary history to assess the usual intake of foods 1 year prior to diagnosis, a complete tobacco history, and other demographic and lifestyle information. Records from the Hawaii Tumor Registry were reviewed for data on stage, histology, and follow-up status of these patients. A food group analysis showed a significant reduction in the risk of death with increasing consumption of all vegetables combined among women (P for trend = 0.03), but not among men. The covariate-adjusted median survival times for women from the highest to the lowest quartiles of vegetable intake were 33, 21, 15, and 18 months, respectively. The results also suggested an association of fruit intake and survival among women (P for trend = 0.02), although a similar effect was not found among men. Increased consumption of certain foods, such as tomatoes and oranges among men, and broccoli and, perhaps, tomatoes among women, appeared to improve survival. This exploratory analysis provides mixed indications that certain components of vegetables and fruits may prolong survival in lung cancer patients. PMID:1591072

  6. Reprocessed uranium exposure and lung cancer risk.

    PubMed

    Canu, Irina Guseva; Jacob, Sophie; Cardis, Elisabeth; Wild, Pascal; Caër-Lorho, Sylvaine; Auriol, Bernard; Laurier, Dominique; Tirmarche, Margot

    2010-09-01

    This study investigated the risk of lung cancer in regards to protracted occupational exposure to reprocessed uranium compounds. Two thousand seven hundred and nine male workers employed at the AREVA NC uranium processing plant between 1960 and 2005 in France were included in the cohort. Historical exposure to reprocessed uranium compounds classified by their solubility type was assessed on the basis of the plant's specific job-exposure matrix. Cox proportional hazard models adjusted for attained age, calendar period, and socioeconomic status were used to estimate relative risks in regards of each type of uranium compound. The relative risk of lung cancer tended to increase with decreasing solubility of reprocessed uranium compounds. The highest-though not statistically significant-relative risk was observed among workers exposed to slowly soluble reprocessed uranium dioxide. This study is the first suggesting an increasing risk of lung cancer associated with exposure to reprocessed uranium. Our results are consistent with data from experimental studies of biokinetics and the action mechanism of slowly soluble uranium compounds, but need to be confirmed in larger studies with more detailed dose-response analyses. PMID:20699691

  7. Lung Cancer Ablation: What Is the Evidence?

    PubMed Central

    de Baere, Thierry; Farouil, Geoffroy; Deschamps, Frederic

    2013-01-01

    Percutaneous ablation of small non-small cell lung cancer (NSCLC) has been demonstrated to be both feasible and safe in nonsurgical candidates. Radiofrequency ablation (RFA), the most commonly used technique for ablation, has a reported rate of complete ablation of ~90%, with best results obtained in tumors <2 to 3 cm in diameter. The best reported 1-, 3-, and 5-year overall survival rates after RFA of NSCLC are 97.7%, 72.9%, and 55.7%, respectively. It is noteworthy that in most studies, cancer-specific survival is greater than overall survival due to severe comorbidities in patients treated with RFA for NSCLC. Aside from tumor size and tumor stage, these comorbidities are predictive of survival. Other ablation techniques such as microwave and irreversible electroporation may in the future prove to overcome some of the limitations of RFA, namely for large tumors or tumors close to large vessels. Stereotactic body radiation therapy has also been demonstrated to be highly efficacious in treating small lung tumors and will need to be compared with percutaneous ablation. This article reviews the current evidence regarding RFA for lung cancer. PMID:24436531

  8. Hyperspectral imaging of skin and lung cancers

    NASA Astrophysics Data System (ADS)

    Zherdeva, Larisa A.; Bratchenko, Ivan A.; Alonova, Marina V.; Myakinin, Oleg O.; Artemyev, Dmitry N.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

    2016-04-01

    The problem of cancer control requires design of new approaches for instrumental diagnostics, as the accuracy of cancer detection on the first step of diagnostics in clinics is slightly more than 50%. In this study, we present a method of visualization and diagnostics of skin and lung tumours based on registration and processing of tissues hyperspectral images. In a series of experiments registration of hyperspectral images of skin and lung tissue samples is carried out. Melanoma, basal cell carcinoma, nevi and benign tumours are studied in skin ex vivo and in vivo experiments; adenocarcinomas and squamous cell carcinomas are studied in ex vivo lung experiments. In a series of experiments the typical features of diffuse reflection spectra for pathological and normal tissues were found. Changes in tissues morphology during the tumour growth lead to the changes of blood and pigments concentration, such as melanin in skin. That is why tumours and normal tissues maybe differentiated with information about spectral response in 500-600 nm and 600 - 670 nm areas. Thus, hyperspectral imaging in the visible region may be a useful tool for cancer detection as it helps to estimate spectral properties of tissues and determine malignant regions for precise resection of tumours.

  9. 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

  10. Staging of lung cancer. A cost-effectiveness analysis

    SciTech Connect

    Houston, G.A.; Sanders, J.A.; Little, D.D.; Griffith, J.E.; Clericuzio, C.; Balducci, L.

    1985-06-01

    Previous reports found the WXGa scan highly accurate in staging lung cancer. In the present study the cost-effectiveness of the WXGa scan was measured and compared with that of routine tests (radionuclide liver and bone scans, brain CT scan) used to stage lung cancer. In 160 patients, the WXGa scan had a lower sensitivity, specificity, and negative predictive value than the combination of routine tests in detecting metastatic disease. The WXGa scan was less accurate than the appropriate routine test in establishing the presence of liver, bone, and brain metastases. In the mediastinum the WXGa scan was not more accurate than the chest radiograph. The average cost to accurately stage a patient by WXGa scan was $812.12 and by routine tests was $737.60. The cost for metastatic disease was $1,417.70 by WXGa scan and $1,287.70 by routine tests. It is concluded that at our institution the use of WXGa scan to stage lung cancer is not cost-effective.

  11. Death Concerns among Individuals Newly Diagnosed with Lung Cancer

    ERIC Educational Resources Information Center

    Lehto, Rebecca; Therrien, Barbara

    2010-01-01

    Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

  12. Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

    PubMed

    Sigurdson, Alice J; Jones, Irene M; Wei, Qingyi; Wu, Xifeng; Spitz, Margaret R; Stram, Douglas A; Gross, Myron D; Huang, Wen-Yi; Wang, Li-E; Gu, Jian; Thomas, Cynthia B; Reding, Douglas J; Hayes, Richard B; Caporaso, Neil E

    2011-01-01

    Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk. PMID:20929901

  13. An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.

    PubMed

    Fang, K

    1996-12-01

    Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-alpha is lower in the conditioned medium of H226Br than in that of NCI-H226. demonstrating down-regulation of TGF-alpha transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-alpha and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line. PMID:8956792

  14. Epidemiology of Lung Cancer in Korea: Recent Trends

    PubMed Central

    Park, Ji Young

    2016-01-01

    Lung cancer causes the most cancer deaths in Korea. Although the smoking rate has begun to decrease, the prevalence of lung cancer is still increasing. We reviewed the national lung cancer registry data and the data published about lung cancer in Korea. In 2012, the crude incidence rate of lung cancer was 43.9 per 100,000. The age-standardized mortality rate of lung cancer was 19.8 per 100,000. The 5-year relative survival rate for lung cancer was 11.3% from 1993 to 1995 and increased to 21.9% in the period from 2008 to 2012. Lung cancer occurring in never-smokers was estimated to increase in Korea. Adenocarcinoma is steadily increasing in both women and men and has replaced squamous cell carcinoma as the most common type of lung cancer in Korea. In patients with adenocarcinoma, the frequency of EGFR mutations was 43% (range, 20%–56%), while that of the EMK4-ALK gene was less than 5%. PMID:27064578

  15. Perspectives of African Americans on Lung Cancer: A Qualitative Analysis

    PubMed Central

    Waldman, Laura Tesler; Browning, Emily; Gagne, Joshua; Emmons, Karen

    2015-01-01

    Background. Disparities in incidence and mortality for lung cancer in African Americans are well documented; however, the extent to which disparities reflect differences in patient perceptions of tobacco and lung cancer treatment is unclear. The objective of this study was to explore African Americans’ knowledge of lung cancer, perceived risk, interest in smoking cessation, attitudes toward lung cancer treatment, and lung cancer diagnosis and treatment experiences. Patients and Methods. The cohort comprised 32 African-American current and former smokers without a cancer diagnosis who participated in focus groups and 10 African Americans with lung cancer who participated in in-depth interviews. Transcripts were analyzed using a modified grounded theory approach. Results. Participants without a cancer diagnosis were aware of the link between smoking and lung cancer, the common symptoms of the disease, and its poor prognosis. They desired specific, personalized smoking-cessation information. If diagnosed, the majority reported, they would seek medical care. Most believed that insurance and socioeconomic factors were more likely to affect treatment access than racial discrimination. Participants with a cancer diagnosis were also aware of the relationship between smoking and lung cancer. They felt their treatment plans were appropriate and trusted their physicians. Most did not believe that race affected their care. Conclusion. This qualitative study suggests that African-American smokers are aware of the relationship between smoking and lung cancer and are interested in smoking-cessation treatment. These data also indicate that lung cancer disparities are unlikely to be associated with differential willingness to receive care but that African Americans may perceive financial and insurance barriers to lung cancer treatment. PMID:25795634

  16. Identification of serum biomarkers for lung cancer using magnetic bead-based SELDI-TOF-MS

    PubMed Central

    Song, Qi-bin; Hu, Wei-guo; Wang, Peng; Yao, Yi; Zeng, Hua-zong

    2011-01-01

    Aim: To identify novel serum biomarkers for lung cancer diagnosis using magnetic bead-based surface-enhanced laser desorption/ionization time-of-flight mass spectrum (SELDI-TOF-MS). Methods: The protein fractions of 121 serum specimens from 30 lung cancer patients, 30 pulmonary tuberculosis patients and 33 healthy controls were enriched using WCX magnetic beads and subjected to SELDI-TOF-MS. The spectra were analyzed using Bio-marker Wizard version 3.1.0 and Biomarker Patterns Software version 5.0. A diagnostic model was constructed with the marker proteins using a linear discrimination analysis method. The validity of this model was tested in a blind test set consisted of 8 randomly selected lung cancer patients, 10 pulmonary tuberculosis patients and 10 healthy volunteers. Results: Seventeen m/z peaks were identified, which were significantly different between the lung cancer group and the control (tuberculosis and healthy control) groups. Among these peaks, the 6445, 9725, 11705, and 15126 m/z peaks were selected by the Biomarker Pattern Software to construct a diagnostic model for lung cancer. This four-peak model established in the training set could discriminate lung cancer patients from non-cancer patients with a sensitivity of 93.3% (28/30) and a specificity of 90.5% (57/63). The diagnostic model showed a high sensitivity (75.0%) and a high specificity (95%) in the blind test validation. Database searching and literature mining indicated that the featured 4 peaks represented chaperonin (M9725), hemoglobin subunit beta (M15335), serum amyloid A (M11548), and an unknown protein. Conclusion: A lung cancer diagnostic model based on bead-based SELDI-TOF-MS has been established for the early diagnosis or differential diagnosis of lung cancers. PMID:22019958

  17. Lung cancer screening in patients with chronic obstructive pulmonary disease.

    PubMed

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo; Zulueta, Javier J

    2016-04-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  18. Lung cancer screening in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  19. Mediastinal Staging in Non-Small Cell Lung Cancer.

    PubMed

    Gamliel, Ziv

    2016-07-01

    In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer. PMID:27261911

  20. New therapeutic perspectives in CCDC6 deficient lung cancer cells.

    PubMed

    Morra, Francesco; Luise, Chiara; Visconti, Roberta; Staibano, Stefania; Merolla, Francesco; Ilardi, Gennaro; Guggino, Gianluca; Paladino, Simona; Sarnataro, Daniela; Franco, Renato; Monaco, Roberto; Zitomarino, Federica; Pacelli, Roberto; Monaco, Guglielmo; Rocco, Gaetano; Cerrato, Aniello; Linardopoulos, Spiros; Muller, Mark T; Celetti, Angela

    2015-05-01

    Non-small cell lung cancer (NSCLC) is the main cause of cancer-related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled-coil-domain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index <1. Finally, CCDC6 is expressed at low levels in about 30% of the NSCL tumors we analyzed by TMA immunostaining. The weak CCDC6 protein staining is significatively correlated with the presence of lymph node metastasis (p ≤ 0.02) and negatively correlated to the disease free survival (p ≤ 0.01) and the overall survival (p ≤ 0.05). Collectively, the data indicate that CCDC6 levels provide valuable insight for OS. CCDC6 could represent a predictive biomarker of resistance to conventional single mode therapy and yield insight on tumor sensitivity to PARP inhibitors in NSCLC. PMID:25302833

  1. Antitumor effect of traditional Chinese herbal medicines against lung cancer.

    PubMed

    Chen, Yuezhou; Zhu, Jianping; Zhang, Wenpeng

    2014-10-01

    Traditional Chinese herbal medicine (TCHM) is used widely alone or in combination with chemotherapy to treat lung cancer in China. Meta-analysis of clinical trials of TCHM against lung cancer suggested the potential, but not confirmed therapeutic effect. To gain detailed insight into the antilung cancer effects of TCHM, we searched for preclinical studies of TCHM against lung cancer published from 1995 to 2012 and systematically analyzed published articles focusing on the antitumor effect of individual TCHM in lung cancer cell lines or animal models. Among 93 herbal components isolated from 73 Chinese herbs, we found 10 herbal compounds that showed the strongest cytotoxicity in lung cancer cell lines through apoptosis or cell cycle arrest, and agents isolated from seven Chinese herbs that inhibited the primary tumor growth more than 35% in A549 xenografted mice models. In addition, three herbal components suppressed lung cancer cell migration in vitro at the concentration without cytotoxicity. Polyphyllin I, tanshinone IIA, isochaihulactone, 25-OCH3-PPD, and andrographolide were the five TCHM compounds that showed strong antilung cancer effects both in cells and in animal models, and studies of their analogs showed their structure-activity relationships. This review summarizes and analyzes contemporary studies on the antitumor effect of individual TCHM against lung cancer and animal models, providing perspectives to better understand the TCHM effect in lung cancer treatment and develop new antilung cancer drugs from TCHM. PMID:24892722

  2. Lung cancer molecular epidemiology in China: recent trends

    PubMed Central

    2014-01-01

    Lung cancer is both the most common diagnosed cancer and the leading cause of cancer related deaths in China. During the past three decades, the incidence and mortality of lung cancer in China are increasing rapidly. According to data from National Central Cancer Registry (NCCR) in 2010, the crude incidence of lung cancer in China was 46.08 per 100,000 population (61.86 per 100,000 men and 29.54 per 100,000 women), with an estimated over 600,000 new diagnosed lung cancer patients (416,333 males and 189,613 females). Meanwhile, the crude mortality of lung cancer in China was 37.00 per 100,000 population (50.04 per 100,000 men and 23.33 per 100,000 women). Consistent with the change in developed countries, adenocarcinoma has become the most predominant histological subtype of lung cancer in China. For the majority advanced non-small-cell lung cancer (NSCLC) patients, especially patients with adenocarcinoma, targeted therapy became increasing important in the treatment. Chinese researcher have done a lot work in terms of lung cancer molecular epidemiology, therefore, in this review, we further summarized the epidemiology of driver genes in NSCLC, hoping to help clinicians to better screen certain driver genes in China for treatment decisions. PMID:25806311

  3. Quantitative imaging features to predict cancer status in lung nodules

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Balagurunathan, Yoganand; Atwater, Thomas; Antic, Sanja; Li, Qian; Walker, Ronald; Smith, Gary T.; Massion, Pierre P.; Schabath, Matthew B.; Gillies, Robert J.

    2016-03-01

    Background: We propose a systematic methodology to quantify incidentally identified lung nodules based on observed radiological traits on a point scale. These quantitative traits classification model was used to predict cancer status. Materials and Methods: We used 102 patients' low dose computed tomography (LDCT) images for this study, 24 semantic traits were systematically scored from each image. We built a machine learning classifier in cross validation setting to find best predictive imaging features to differentiate malignant from benign lung nodules. Results: The best feature triplet to discriminate malignancy was based on long axis, concavity and lymphadenopathy with average AUC of 0.897 (Accuracy of 76.8%, Sensitivity of 64.3%, Specificity of 90%). A similar semantic triplet optimized on Sensitivity/Specificity (Youden's J index) included long axis, vascular convergence and lymphadenopathy which had an average AUC of 0.875 (Accuracy of 81.7%, Sensitivity of 76.2%, Specificity of 95%). Conclusions: Quantitative radiological image traits can differentiate malignant from benign lung nodules. These semantic features along with size measurement enhance the prediction accuracy.

  4. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors.

    PubMed

    Ji, Hongbin; Zhao, Xiaojun; Yuza, Yuki; Shimamura, Takeshi; Li, Danan; Protopopov, Alexei; Jung, Boonim L; McNamara, Kate; Xia, Huili; Glatt, Karen A; Thomas, Roman K; Sasaki, Hidefumi; Horner, James W; Eck, Michael; Mitchell, Albert; Sun, Yangping; Al-Hashem, Ruqayyah; Bronson, Roderick T; Rabindran, Sridhar K; Discafani, Carolyn M; Maher, Elizabeth; Shapiro, Geoffrey I; Meyerson, Matthew; Wong, Kwok-Kin

    2006-05-16

    The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation. PMID:16672372

  5. 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

  6. Invasive thymoma associated with lung cancer: report of a case.

    PubMed

    Shimada, T; Terashima, H; Shimizu, T; Hirayama, K

    2001-01-01

    We report herein a case of invasive thymoma simultaneously associated with lung cancer. A 64-year-old man presented with a cough and anterior chest pain, and preoperative examinations revealed an anterior mediastinal tumor as well as lung cancer. The patient underwent a total thymectomy, partial resection of the right lung, left lower lobectomy, and mediastinal lymph node dissection, followed by radiotherapy. Although it is well known that thymomas may be accompanied by nonthymic cancers, invasive thymomas occurring coincidentally with lung cancer are rarely reported in Japan. This case is very interesting in its relation to the oncogenesis of thymomas. PMID:11428602

  7. A case of three synchronous primary lung cancers within the same lung lobe

    PubMed Central

    Misiak, Piotr; Brocki, Marian

    2016-01-01

    We present the case of a 74-year-old patient with three synchronous primary lung cancers within the same lung lobe. Computed tomography and positron emission tomography investigations revealed two suspicious nodular lesions in the upper lobe of the left lung. Fine-needle aspiration biopsy confirmed that one of the lesions was non-small cell lung cancer. The patient was qualified for surgical treatment, and left upper lobectomy plus lymphadenectomy was performed. Histopathological examination confirmed the presence of three primary cancers in the left lung: keratinizing squamous cell carcinoma, neuroendocrine carcinoma, and acinar adenocarcinoma, localized within the same lung lobe. The patient was classified as having stage T3N1M0 lung cancer (stage IIIA) according to the latest, 7th edition of the TNM classification. PMID:27516792

  8. Tumor specific lung cancer diagnostics with multiplexed FRET immunoassays

    NASA Astrophysics Data System (ADS)

    Geißler, D.; Hill, D.; Löhmannsröben, H.-G.; Thomas, E.; Lavigne, A.; Darbouret, B.; Bois, E.; Charbonnière, L. J.; Ziessel, R. F.; Hildebrandt, N.

    2010-02-01

    An optical multiplexed homogeneous (liquid phase) immunoassay based on FRET from a terbium complex to eight different fluorescent dyes is presented. We achieved highly sensitive parallel detection of four different lung cancer specific tumor markers (CEA, NSE, SCC and CYFRA21-1) within a single assay and show a proof-of-principle for 5- fold multiplexing. The method is well suited for fast and low-cost miniaturized point-of-care testing as well as for highthroughput screening in a broad range of in-vitro diagnostic applications.

  9. Understanding and Preventing Lung Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of cancer death in both men and women. Lung cancer is the second most common cancer in the United States, after skin cancer. The number of new cases and deaths from lung cancer is highest in black men. Risk Factors ...

  10. Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

    PubMed Central

    Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

    2015-01-01

    Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a

  11. In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin.

    PubMed Central

    Jensen, P. B.; Holm, B.; Sorensen, M.; Christensen, I. J.; Sehested, M.

    1997-01-01

    The acquisition of drug-resistant tumour cells is the main problem in the medical treatment of a range of malignant diseases. In recent years, three new classes of anti-cancer agents, each with a novel mechanism of action, have been brought forward to clinical trials. These are the topoisomerase I (topo I) poisons topotecan and irinotecan, which are both camptothecin derivatives, the taxane tubulin stabilizers taxol and taxotere and, finally, the antimetabolite gemcitabin, which is active in solid tumours. The process of optimizing their use in a combination with established agents is very complex, with numerous possible drug and schedule regimens. We describe here how a broad panel of drug-resistant small-cell lung cancer (SCLC) cell lines can be used as a model of tumour heterogeneity to aid in the selection of non-cross-resistant regimens. We have selected low-fold (3-10x) drug-resistant sublines from a classic (NCI-H69) and a variant (OC-NYH) SCLC cell line. The resistant cell lines include two sublines with different phenotypes towards alkylating agents (H69/BCNU and NYH/CIS), two sublines with different phenotypes against topo I poisons (NYH/CAM and NYH/TPT) and three multidrug resistant (MDR) sublines (H69/DAU, NYH/VM, and H69/VP) with combinations of mdr1 and MRP overexpression as well as topoisomerase II (topo II) down-regulation or mutation. Sensitivity to 20 established and new agents was measured in a standardized clonogenic assay. Resistance was highly drug specific. Thus, none of the cell lines was resistant to all drugs. In fact, all resistant cell lines exhibited patterns of collateral sensitivity to various different classes of drugs. The most intriguing pattern was collateral sensitivity to gemcitabin in two cell lines and to ara-C in five drug-resistant cell lines, i.e. in all lines except the lines resistant to topo I poisons. Next, all sensitivity patterns in the nine cell lines were compared by correlation analysis. A high correlation

  12. Primary lung cancer associated with Werner syndrome.

    PubMed

    Ohnishi, Shunichiro; Fujimoto, Masaki; Oide, Takashi; Nakatani, Yukio; Tsurutani, Yuya; Koshizaka, Masaya; Mezawa, Morito; Ishikawa, Takahiro; Takemoto, Minoru; Yokote, Koutaro

    2010-10-01

    A 52-year-old man with Werner Syndrome (WS) was admitted to our hospital for the treatment of skin ulcers on his thighs. Routine chest radiography revealed an abnormal shadow in the left upper lung field. Computed tomography (CT) revealed a poorly demarcated homogeneous mass (diameter, 4 cm) in the S1 + 2 lung area; no pleural effusion was observed. CT-guided percutaneous needle biopsy revealed the presence of an adenocarcinoma. Other imaging studies did not reveal any lymph-node involvement or presence of metastatic lesions. The patient was diagnosed with stage IB adenocarcinoma (T2N0M0), and a left upper lobectomy was successfully carried out; postoperative wound healing was steady and uneventful, with no obvious ulcer formation. Primary lung cancers very rarely develop in patients with WS; non-epithelial tumors are usually observed in such patients. Patients with WS usually develop severe skin problems, such as refractory skin ulcers in the extremities; however, our patient did not develop any skin-related complications after surgery. As the expected lifespan of patients with WS is increasing, we need to pay attention not only to the rare non-epithelial malignancy, but also cancer. Further, the expected short lifespan of patients with WS, as well as the possibility of skin-related problems after surgery, should not be considered while deciding whether to take the option of surgery in the case of malignancy. PMID:20887625

  13. Effects of Respiratory Motion on Passively Scattered Proton Therapy Versus Intensity Modulated Photon Therapy for Stage III Lung Cancer: Are Proton Plans More Sensitive to Breathing Motion?

    SciTech Connect

    Matney, Jason; Park, Peter C.; Bluett, Jaques; Chen, Yi Pei; Liu, Wei; Court, Laurence E.; Liao, Zhongxing; Li, Heng; Mohan, Radhe

    2013-11-01

    Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dose–volume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dose–volume histogram indices (mean ± SD) except the lung V5 (PSPT: +1.1% ± 0.9%; IMRT: +0.4% ± 1.2%) and maximum cord dose (PSPT: +1.5 ± 2.9 Gy; IMRT: 0.0 ± 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential

  14. The Effects of Respiratory Motion on Passively Scattered Proton Therapy vs. IMRT for Stage III Lung Cancer - Are Proton Plans More Sensitive to Breathing Motion?

    PubMed Central

    Matney, Jason; Park, Peter C.; Bluett, Jaques; Chen, Yi-Pei; Liu, Wei; Court, Laurence E.; Liao, Zhongxing; Li, Heng; Mohan, Radhe

    2013-01-01

    Purpose (1) To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans. (2) To establish the relationship between the magnitude of tumor motion and the respiratory induced dose difference for both modalities. Methods and Materials In a randomized clinical trial comparing PSPT and IMRT, radiotherapy plans have been designed following common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging 3-17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dose-volume histogram (DVH) differences (4D-3D) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19/20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the two modalities were not statistically significant (p <0.05) for all DVH indices (mean ± SD) except the lung V5 (PSPT: +1.1±0.9%, IMRT: +0.4±1.2%) and maximum cord dose (PSPT: +1.5±2.9 Gy, IMRT: 0.0±0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only two indices: Dose to 95% PTV, and heterogeneity index. Conclusions With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2/11 of 4D-3D indices (Lung V5 and spinal cord max) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Due to the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion. PMID:24074932

  15. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

  16. The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

    PubMed Central

    Othman, Norahayu; Nagoor, Noor Hasima

    2014-01-01

    Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment. PMID:24999473

  17. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    NASA Astrophysics Data System (ADS)

    Krivonogov, Nikolay G.; Efimova, Nataliya Y.; Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-01

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  18. Smoking and Lung Cancer: It's Never Too Late To Quit | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Lung Cancer Smoking and Lung Cancer: It's Never Too Late to Quit Past Issues / ... Table of Contents Because most people who get lung cancer were smokers, you may feel that doctors and ...

  19. Smoking and Lung Cancer: It's Never Too Late To Quit | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Lung Cancer Smoking and Lung Cancer: It's Never Too Late to Quit Past ... Table of Contents Because most people who get lung cancer were smokers, you may feel that doctors ...

  20. CDK2 Inhibition Causes Anaphase Catastrophe in Lung Cancer through the Centrosomal Protein CP110

    PubMed Central

    Hu, Shanhu; Danilov, Alexey V.; Godek, Kristina; Orr, Bernardo; Tafe, Laura J.; Rodriguez-Canales, Jaime; Behrens, Carmen; Mino, Barbara; Moran, Cesar A.; Memoli, Vincent A.; Mustachio, Lisa Maria; Galimberti, Fabrizio; Ravi, Saranya; DeCastro, Andrew; Lu, Yun; Sekula, David; Andrew, Angeline S; Wistuba, Ignacio I.; Freemantle, Sarah; Compton, Duane A.; Dmitrovsky, Ethan

    2015-01-01

    Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacological targeting of aneuploidy is an attractive therapeutic strategy as this would preferentially eliminate malignant over normal cells. We previously discovered that CDK2 inhibition causes lung cancer cells with more than two centrosomes to undergo multipolar cell division leading to apoptosis, defined as anaphase catastrophe. Cells with activating KRAS mutations were especially sensitive to CDK2 inhibition. Mechanisms of CDK2-mediated anaphase catastrophe and how activated KRAS enhances this effect were investigated. Live-cell imaging provided direct evidence that following CDK2 inhibition, lung cancer cells develop multipolar anaphase and undergo multipolar cell division with the resulting progeny apoptotic. Small interfering RNA (siRNA)-mediated repression of the CDK2 target and centrosome protein CP110 induced anaphase catastrophe of lung cancer cells. In contrast, CP110 overexpression antagonized CDK2 inhibitor-mediated anaphase catastrophe. Furthermore, activated KRAS mutations sensitized lung cancer cells to CDK2 inhibition by deregulating CP110 expression. Thus, CP110 is a critical mediator of CDK2-inhibition-driven anaphase catastrophe. Independent examination of murine and human paired normal-malignant lung tissues revealed marked upregulation of CP110 in malignant versus normal lung. Human lung cancers with KRAS mutations had significantly lower CP110 expression as compared to KRAS wild-type cancers. Thus, a direct link was found between CP110 and CDK2 inhibitor antineoplastic response. CP110 plays a mechanistic role in response of lung cancer cells to CDK2 inhibition, especially in the presence of activated KRAS mutations. PMID:25808870

  1. Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer.

    PubMed

    Okamura, Kyoko; Takayama, Koichi; Izumi, Miiru; Harada, Taishi; Furuyama, Kazuto; Nakanishi, Yoichi

    2013-04-01

    Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2 ng/mL CEA and 3.5 ng/mL CYFRA 21-1 and twice these respective levels (6.4 ng/mL and 7.0 ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes' theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%], and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1, or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should

  2. A Novel Use of Gentamicin in the ROS-Mediated Sensitization of NCI-H460 Lung Cancer Cells to Various Anticancer Agents

    PubMed Central

    Cuccarese, Michael F.; Singh, Amit; Amiji, Mansoor; O’Doherty, George A.

    2013-01-01

    Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of severe Gram-negative and Gram-positive bacterial infections. While bactericidal effects of aminoglycosides are due to binding to the 30S subunit of the bacterial ribosome, aminoglycosides can affect protein synthesis, intracellular calcium levels and levels of reactive oxygen species (ROS) in eukaryotic cells. While aminoglycosides can be cytotoxic at high concentrations, our results show that at much lower doses, gentamicin can be implemented as a sensitizing agent for the NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin and vinblastine in vitro. We have also established that this sensitization is reliant on the ROS response generated by gentamicin. PMID:24093441

  3. International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants

    PubMed Central

    Truong, Therese; Sauter, Wiebke; McKay, James D.; Hosgood, H.Dean; Gallagher, Carla; Amos, Christopher I.; Spitz, Margaret; Muscat, Joshua; Lazarus, Philip; Illig, Thomas; Wichmann, H.Erich; Bickeböller, Heike; Risch, Angela; Dienemann, Hendrik; Zhang, Zuo-Feng; Naeim, Behnaz Pezeshki; Yang, Ping; Zienolddiny, Shanbeh; Haugen, Aage; Le Marchand, Loïc; Hong, Yun-Chul; Kim, Jin Hee; Duell, Eric J.; Andrew, Angeline S.; Kiyohara, Chikako; Shen, Hongbing; Matsuo, Keitaro; Suzuki, Takeshi; Seow, Adeline; Ng, Daniel P.K.; Lan, Qing; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Constantinescu, Vali; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Caporaso, Neil E.; Albanes, Demetrius; Thun, Michael; Landi, Maria Teresa; Trubicka, Joanna; Lener, Marcin; Lubiński, Jan; Wang, Ying; Chabrier, Amélie; Boffetta, Paolo; Brennan, Paul; Hung, Rayjean J.

    2010-01-01

    Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 × 10−4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 × 10−4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations. PMID:20106900

  4. A Novel Bioluminescence Orthotopic Mouse Model for Advanced Lung Cancer

    PubMed Central

    Li, Bo; Torossian, Artour; Li, Wenyan; Schleicher, Stephen; Niu, Kathy; Giacalone, Nicholas J.; Kim, Sung June; Chen, Heidi; Gonzalez, Adriana; Moretti, Luigi; Lu, Bo

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in the United States despite recent advances in our understanding of this challenging disease. An animal model for high-throughput screening of therapeutic agents for advanced lung cancer could help promote the development of more successful treatment interventions. To develop our orthotopic lung cancer model, luciferase-expressing A549 cancer cells were injected into the mediastinum of athymic nude mice. To determine whether the model would allow easy monitoring of response to therapeutic interventions, tumors were treated with 30 mg/kg Paclitaxel or were irradiated with 5 fractions of 2 Gy, and tumor burden was monitored using bioluminescence imaging. Evidence of radiation-induced lung injury was assessed using immunohistochemical staining for phospho-Smad2/3 and cleaved caspase-3. We found that tumor implantation recapitulated advanced human lung cancer as evidenced by tumor establishment and proliferation within the mediastinum. The tumor responded to Paclitaxel or radiation as shown by decreased tumor bioluminescence and improved overall survival. Immunohistochemistry revealed increased phospho-Smad2/3 and cleaved caspase-3 in irradiated lungs, consistent with radiation-induced lung injury. This orthotopic lung cancer model may help provide a method to assess therapeutic interventions in a preclinical setting that recapitulates locally advanced lung cancer. PMID:21663394

  5. Implementation and organization of lung cancer screening

    PubMed Central

    Ashraf, Haseem

    2016-01-01

    CT screening for lung cancer is now being implemented in the US and China on a widespread national scale but not in Europe so far. The review gives a status for the implementation process and the hurdles to overcome in the future. It also describes the guidelines and requirements for the structure and components of high quality CT screening programs. These are essential in order to achieve a successful program with the fewest possible harms and a possible mortality benefit like that documented in the American National Lung Screening Trial (NLST). In addition the importance of continued research in CT screening methods is described and discussed with focus on the great potential to further improve this method in the future for the benefit of patients and society. PMID:27195270

  6. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  7. Interpretation of lung cancer study outcomes

    PubMed Central

    Abbate, Marida; Bidoli, Paolo; Pelizzoni, Davide; Canova, Stefania

    2015-01-01

    Lung cancer is the leading cause of cancer death in developed countries. However, in the last few years we observed an important acceleration in drug development due to oncogenic driver tumors discovery. Sharing and putting together preclinical data from benchmark and data from clinical research is the scientific paradigm that allows real breakthrough in clinical practice in this field, but only a few targeted agents are worthy and practice changing. The clinical research and proper use of statistical methodology are the pillars to continue to achieve important goals like improvement of overall survival. A good medical oncologist should be able to critically read a scientific paper and move from the observed outcomes into clinical perspective. Despite clinical improvements, sometimes the union of promising targeted agents and optimistic expectations misrepresent the reality and the value of clinical research. In this article, we try to analyze the meaning of statistical assumptions from clinical trials, especially in lung cancer, through a critical review of the concept of value-based medicine. We also attempt to give the reader some practical tools to weigh scientific value of literature reports. PMID:26716052

  8. Interpretation of lung cancer study outcomes.

    PubMed

    Cortinovis, Diego; Abbate, Marida; Bidoli, Paolo; Pelizzoni, Davide; Canova, Stefania

    2015-11-01

    Lung cancer is the leading cause of cancer death in developed countries. However, in the last few years we observed an important acceleration in drug development due to oncogenic driver tumors discovery. Sharing and putting together preclinical data from benchmark and data from clinical research is the scientific paradigm that allows real breakthrough in clinical practice in this field, but only a few targeted agents are worthy and practice changing. The clinical research and proper use of statistical methodology are the pillars to continue to achieve important goals like improvement of overall survival. A good medical oncologist should be able to critically read a scientific paper and move from the observed outcomes into clinical perspective. Despite clinical improvements, sometimes the union of promising targeted agents and optimistic expectations misrepresent the reality and the value of clinical research. In this article, we try to analyze the meaning of statistical assumptions from clinical trials, especially in lung cancer, through a critical review of the concept of value-based medicine. We also attempt to give the reader some practical tools to weigh scientific value of literature reports. PMID:26716052

  9. Protein Signature of Lung Cancer Tissues

    PubMed Central

    Mehan, Michael R.; Ayers, Deborah; Thirstrup, Derek; Xiong, Wei; Ostroff, Rachel M.; Brody, Edward N.; Walker, Jeffrey J.; Gold, Larry; Jarvis, Thale C.; Janjic, Nebojsa; Baird, Geoffrey S.; Wilcox, Sheri K.

    2012-01-01

    Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment. PMID:22509397

  10. [New biological treatments for lung cancer].

    PubMed

    Zalcman, G; Richard, N; Bergot, E

    2007-02-01

    Therapies targeted on cell signal pathways that control cell division and tumor angiogenesis have been developed over the last five years for non small cell lung cancer (NSCLC) with some amazing results, in subgroups of selected patients, predicting more significant success in the upcoming years. Compounds targeted on EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3 trials including thousands of patients. Their efficacy has been proved, in second and third line trials, after first line cisplatin-based chemotherapy for non-mucinous adenocarcinoma in non-smokers, women and Asian patients. Response rates vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian patients with long survivals. Therapeutic targeting improves success rates, either relying on EGFR gene amplification detection by FISH, or search for EGFR tyrosine kinase domain mutations. Commercial kits are available for routine molecular diagnosis of domain mutations potentially enabling molecular targeting in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal antibody to VEGF, bevacizumab, have also been developed in the last few years. Bevacizumab associated with classical cytotoxic chemotherapy led, in selected patients (with non squamous cell lung cancer and no past history of cardiovascular disease) to an increase of median survival to more than 12 months with tolerable toxicity. Other drugs that have both anti-EGFR activity and anti-angiogenic properties will be soon developed, since future bioactive anti-cancer drugs will probably be multi-targeted drugs. PMID:17457280

  11. Lung cancer biology: a genetic and genomic perspective.

    PubMed

    Sánchez-Céspedes, M

    2009-05-01

    Lung cancer is the leading cause of death due to cancer in most western countries and, as tobacco consumption is not significantly decreasing worldwide, will remain so in the coming decades. Thus, in addition to preventing uptake and encouraging cessation of the smoking habit, it is important to invest in understanding the biology of this type of cancer. Of particular interest are the recent efforts directed towards characterising the entire set of gene alterations in lung cancer. The present review describes the catalogue of known genetic alterations in lung cancer, their biological role and their use in clinical management. PMID:19451058

  12. Targeting lung cancer through inhibition of checkpoint kinases

    PubMed Central

    Syljuåsen, Randi G.; Hasvold, Grete; Hauge, Sissel; Helland, Åslaug

    2015-01-01

    Inhibitors of checkpoint kinases ATR, Chk1, and Wee1 are currently being tested in preclinical and clinical trials. Here, we review the basic principles behind the use of such inhibitors as anticancer agents, and particularly discuss their potential for treatment of lung cancer. As lung cancer is one of the most deadly cancers, new treatment strategies are highly needed. We discuss how checkpoint kinase inhibition in principle can lead to selective killing of lung cancer cells while sparing the surrounding normal tissues. Several features of lung cancer may potentially be exploited for targeting through inhibition of checkpoint kinases, including mutated p53, low ERCC1 levels, amplified Myc, tumor hypoxia and presence of lung cancer stem cells. Synergistic effects have also been reported between inhibitors of ATR/Chk1/Wee1 and conventional lung cancer treatments, such as gemcitabine, cisplatin, or radiation. Altogether, inhibitors of ATR, Chk1, and Wee1 are emerging as new cancer treatment agents, likely to be useful in lung cancer treatment. However, as lung tumors are very diverse, the inhibitors are unlikely to be effective in all patients, and more work is needed to determine how such inhibitors can be utilized in the most optimal ways. PMID:25774168

  13. Environmental tobacco smoke and lung cancer: a reappraisal.

    PubMed

    Nilsson, R

    1996-06-01

    It is biologically plausible that environmental tobacco smoke (ETS) has a contributory role in the induction of lung cancer in nonsmoking individuals. However, recent findings have strengthened previous assumptions that a major part of the observed increase in lung cancer risk reported from epidemiological studies on ETS-exposed nonsmokers can be related to misclassification of smoking status and inappropriate selection of controls as well as to certain confounding factors related to life-style, and possibly also to hereditary disposition. Dose-response extrapolation-supported by a more solid database for active smokers-reflects a possible increase in lung cancer that appears to be more than one order of magnitude lower than indicated by the epidemiological studies that have been used to support regulatory action in the United States. The epidemiological studies on ETS conducted so far lack the required sensitivity to confirm increases in risk of such low magnitudes. Self-reported information on exposure to tobacco smoke has been found to be unreliable, and data from interviews with proxy respondents even more so. In addition, determination of cotinine to establish smoking status is inadequate for use in this context, i.e., to assure that misclassification in the range 5-10% does not occur; due to genetically based differences in the rate of nicotine metabolism, some active smokers will not be detected. Further, due the short half-life of cotinine in the organism, a self-reported nonsmoker may, in principle, have been a lifelong heavy smoker until just before the sampling takes place. For some of the major studies, preferential inclusion of disease-prone individuals of very low socioeconomic status among cases seems to have been present to a varying extent. Due to inclusion of this group, life-style and hereditary disposition may result in a disproportionally large impact on the recorded overall lung cancer rate. Further, a possible major confounder causing

  14. Trends of lung cancer mortality in Mexico.

    PubMed

    Lazcano Ponce, E C; Tovar Guzman, V; Meneses Gonzalez, F; Rascon Pacheco, R A; Hernandez Avila, M

    1997-01-01

    Lung cancer (LC) is one of the most important public health problems in the world; 1,035,000 annual deaths are estimated each year and more than 80% of these are attributed to tobacco. The trend of lung cancer mortality in Mexico City from 1979 - 1993 was determined, as was the rate ratio of lung cancer mortality in 31 states in Mexico, taking Mexico City as a reference by means of a Poisson model. A strong linear regression model was used to evaluate the rate, where the dependent variable was LC mortality rate and the independent variable the year observed. In 15 years, 73,807 deaths from LC were reported, with an increase in mortality from 5.01 - 7.25 per 100,000 inhabitants. Mortality increases significantly after 60 years of age (B not equal to 0), p<.05) in men and in women. Mortality from LC was 70% in men, and more than 60% of deaths were reported after 65 years of age. Mortality risk is higher in the northern states of the country (e.g., Sonora, RR=2.40) than in the southern region (e.g., Oaxaca RR=0.40). In Mexico, almost 10,000 deaths by LC are estimated for the year 2010. Therefore, changes in lifestyle should be encouraged in order to decrease the smoking habit. The governmental tax on cigarettes should be increased, smoking restricted in squares and public spaces, and the risks should be announced on cigarette packages, among other measures. With respect to other emergent risk factors, the sources of industrial pollution and toxic emissions should be regulated. PMID:9428585

  15. Targeted Therapy and Immunotherapy for Lung Cancer.

    PubMed

    Naylor, Evan C; Desani, Jatin K; Chung, Paul K

    2016-07-01

    Targeted therapy and immunotherapy have changed the treatment paradigm of non-small cell lung cancer (NSCLC). Distinct molecular subtypes of NSCLC have been described over the past 20 years, enabling the emergence of treatments specific to that subtype. Agents targeting the driver mutations in NSCLC have revolutionized the approach to patients with metastatic disease, because oncologists now select a treatment based on the profile of that particular tumor. More recently, an understanding of immune checkpoints has led to the development of checkpoint inhibitors that enable the host immune system to better recognize tumor cells as foreign and to destroy them. PMID:27261918

  16. Right upper lobe lung cancer: Resection through left anterior mediastinotomy.

    PubMed

    Sirois, Marco; Abu Arab, Walid; Turcotte, Eric; Poulin, Yannick

    2016-01-01

    There is sparse information concerning approaches to metachronous lung cancer in patients who had a previous pneumonectomy for lung carcinoma. We describe the case of a 55-year-old woman who underwent a left pneumonectomy for lung carcinoma. Four years later, a radiological examination revealed a hypermetabolic nodule in the right upper lobe, which was located in the left hemithorax because of right lung hyperinflation and a mediastinal shift to the left. Wedge resection was carried out through a left anterior mediastinotomy. We believe that an anterior mediastinotomy represents a valuable option for the management of recurrent lung cancer after previous surgery. PMID:26124429

  17. Selective expression of transthyretin in subtypes of lung cancer.

    PubMed

    Hao, Shuai; Sun, Suozhu; Xiao, Xueyuan; He, Dacheng; Liu, Liyun

    2016-06-01

    Transthyretin (TTR) is expressed primarily in liver, choroid plexus of brain and pancreatic islet A and B cells. It is also synthesized in some endocrine tumors. In the present study, the protein expression of TTR in lung cancer tissues and cell lines was investigated by western blot. The mRNA expression of TTR in 24 pairs of frozen lung cancer tissues was examined by RT-PCR. The specific expression and cellular distribution of TTR were also evaluated in 104 paraffin-embedded lung cancer samples and 3 normal lung tissues by immunohistochemistry. Similarly, the subcellular localization and expression of TTR were further analyzed in lung cancer cell lines. With the exception of mucinous adenocarcinoma, the expression of TTR protein was observed in all tested subtypes of lung carcinoma. Adenocarcinoma displayed the highest positive expression rate of TTR, accounting for 84.4 %, and the positive expression rate of TTR was up to 85.7 % at stages III and IV. The secretory bubbles with strong TTR staining were observed in luminal cells of lung cancer. Furthermore, the localization of TTR in the cytoplasm of lung cancer cells and the secretion of TTR into extracellular milieu were also confirmed. Taken together, TTR is selectively synthesized in lung cancer cells and can be secreted extracellularly. PMID:26943652

  18. Early Events in the Molecular Pathogenesis of Lung Cancer.

    PubMed

    Kadara, Humam; Scheet, Paul; Wistuba, Ignacio I; Spira, Avrum E

    2016-07-01

    The majority of cancer-related deaths in the United States and worldwide are attributed to lung cancer. There are more than 90 million smokers in the United States who represent a significant population at elevated risk for lung malignancy. In other epithelial tumors, it has been shown that if neoplastic lesions can be detected and treated at their intraepithelial stage, patient prognosis is significantly improved. Thus, new strategies to detect and treat lung preinvasive lesions are urgently needed in order to decrease the overwhelming public health burden of lung cancer. Limiting these advances is a poor knowledge of the earliest events that underlie lung cancer development and that would constitute markers and targets for early detection and prevention. This review summarizes the state of knowledge of human lung cancer pathogenesis and the molecular pathology of premalignant lung lesions, with a focus on the molecular premalignant field that associates with lung cancer development. Lastly, we highlight new approaches and models to study genome-wide alterations in human lung premalignancy in order to facilitate the discovery of new markers for early detection and prevention of this fatal disease. Cancer Prev Res; 9(7); 518-27. ©2016 AACR. PMID:27006378

  19. Elevation of serum l-lactate dehydrogenase B correlated with the clinical stage of lung cancer.

    PubMed

    Chen, Yue; Zhang, Hao; Xu, Anjian; Li, Na; Liu, Jifu; Liu, Chuanjun; Lv, Dongxia; Wu, Shanshan; Huang, Lingyun; Yang, Shuanying; He, Dacheng; Xiao, Xueyuan

    2006-10-01

    To identify potential biomarkers related with lung cancer metastasis, conditional media (CM) proteins collected from a primary non-small cell lung cancer (NSCLC) cell line NCI-H226 and its brain metastatic subline H226Br were analyzed by one-dimensional electrophoresis (1-D PAGE) and matrix-assisted laser desorption/time of flight mass spectrometry (MALDI-TOF-MS). Twelve biomarkers were identified, of which l-lactate dehydrogenase B (LDHB) chain was significantly up-regulated in the CM of H226Br cell and was further validated in 105 lung cancer, 93 non-lung cancer, 41 benign lung disease, as well as 65 healthy individuals sera using enzyme-linked immunosorbent assay (ELISA). It was found that the levels of LDHB were specifically elevated in NSCLC sera compared with other groups and were progressively increased with the clinical stage. At the cutoff point 0.260 (OD value) on the receiver operating characteristic (ROC) curve, LDHB could comparatively discriminate lung cancer from benign lung disease and healthy control groups with sensitivity 81%, specificity 70% and total accuracy 76%. These findings demonstrated that secretome could open up a possibility to find, identify, and characterize novel biomarkers related with invasion and metastasis. PMID:16890323

  20. Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care

    PubMed Central

    Sesen, M. Berkan; Peake, Michael D.; Banares-Alcantara, Rene; Tse, Donald; Kadir, Timor; Stanley, Roz; Gleeson, Fergus; Brady, Michael

    2014-01-01

    Multidisciplinary team (MDT) meetings are becoming the model of care for cancer patients worldwide. While MDTs have improved the quality of cancer care, the meetings impose substantial time pressure on the members, who generally attend several such MDTs. We describe Lung Cancer Assistant (LCA), a clinical decision support (CDS) prototype designed to assist the experts in the treatment selection decisions in the lung cancer MDTs. A novel feature of LCA is its ability to provide rule-based and probabilistic decision support within a single platform. The guideline-based CDS is based on clinical guideline rules, while the probabilistic CDS is based on a Bayesian network trained on the English Lung Cancer Audit Database (LUCADA). We assess rule-based and probabilistic recommendations based on their concordances with the treatments recorded in LUCADA. Our results reveal that the guideline rule-based recommendations perform well in simulating the recorded treatments with exact and partial concordance rates of 0.57 and 0.79, respectively. On the other hand, the exact and partial concordance rates achieved with probabilistic results are relatively poorer with 0.27 and 0.76. However, probabilistic decision support fulfils a complementary role in providing accurate survival estimations. Compared to recorded treatments, both CDS approaches promote higher resection rates and multimodality treatments. PMID:24990290

  1. PESTICIDES AND LUNG CANCER RISK IN THE AGRICULTURAL HEALTH STUDY

    EPA Science Inventory

    We examined the relationship between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators, and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self...

  2. Association Between NAT2 Polymorphisms and Lung Cancer Susceptibility.

    PubMed

    Liu, Chang; Cui, Wei; Cong, Lin; Wang, Li; Ruan, Xinjian; Jia, Jia; Liu, Yanfang; Jia, Xiaoyan; Zhang, Xia

    2015-12-01

    To further investigate the association between NAT2 polymorphisms and lung cancer susceptibility.In terms of phenotypes, we investigated the acetylator status of NAT2 polymorphisms associated with lung cancer risk. Additionally, in view of genotypes, we mainly analyzed 5 single nucleotide polymorphisms (SNPs) in NAT2 gene, namely C282T, A803G, C481T, G590A, and G857A. Twenty-six eligible studies were included in our meta-analysis by searching PubMed, Embase, and CNKI databases. We used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to evaluate the susceptibility to lung cancer associated with NAT2 polymorphisms.Overall, based on phenotypes, the pooled ORs showed no significant association between NAT2 polymorphisms and lung cancer susceptibility. In the subgroup analyses by ethnicity and source of control, there was still no significant association. In terms of genotypes, overall, no obvious relationship was observed between NAT2 polymorphisms and lung cancer risk. But increased risk of lung cancer was found in association with NAT2 C282T polymorphism (TT vs. CC + TC: OR = 1.58, 95% CI = 1.11-2.25).Our meta-analysis demonstrates that TT genotype in NAT2 C282T polymorphism may be a risk factor for lung cancer susceptibility. Additionally, the acetylator status of 5 SNPs in NAT2 gene may not be associated with lung cancer risk. PMID:26656326

  3. Analysis of intratumor heterogeneity unravels lung cancer evolution.

    PubMed

    de Bruin, Elza C; McGranahan, Nicholas; Swanton, Charles

    2015-01-01

    Lung cancer is a disease with dismal outcome. We recently reported a detailed intratumor heterogeneity analysis in 7 non-small cell lung cancer samples, revealing spatially separated driver events as well as the temporal dynamics of mutational processes and demonstrating an important role for APOBEC-mediated heterogeneity later in disease evolution. PMID:27308463

  4. Analysis of intratumor heterogeneity unravels lung cancer evolution

    PubMed Central

    de Bruin, Elza C; McGranahan, Nicholas; Swanton, Charles

    2015-01-01

    Lung cancer is a disease with dismal outcome. We recently reported a detailed intratumor heterogeneity analysis in 7 non-small cell lung cancer samples, revealing spatially separated driver events as well as the temporal dynamics of mutational processes and demonstrating an important role for APOBEC-mediated heterogeneity later in disease evolution. PMID:27308463

  5. The Changing Landscape of Lung Cancer Research and Treatment

    Cancer.gov

    Along with the Lung Cancer Social Media (#LCSM) community, the National Cancer Institute will be co-hosting a lively and interactive Google Hangout on Air about the changing landscape of lung cancer research and treatment. During the chat, viewers will have the opportunity to pose questions to a panel of lung cancer experts including NCI's Dr. Shakun Malik, the head of thoracic oncology therapeutics, Roy S. Herbst, MD, PhD, Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven and David Tom Cooke MD FACS, Head, Section of General Thoracic Surgery University of California, Davis. You can also learn more and follow along on the #LCSM Chat page. The chat will be moderated by lung cancer advocate and #LCSM co-founder, Janet Freeman-Daily. To ask questions of our experts, simply use the #LCSM hashtag during the chat.

  6. Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer.

    PubMed

    Abbas, Ghulam; Danish, Adnan; Krasna, Mark J

    2016-07-01

    The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation. PMID:27261915

  7. Peptides from the variable region of specific antibodies are shared among lung cancer patients.

    PubMed

    de Costa, Dominique; Broodman, Ingrid; Calame, Wim; Stingl, Christoph; Dekker, Lennard J M; Vernhout, René M; de Koning, Harry J; Hoogsteden, Henk C; Sillevis Smitt, Peter A E; van Klaveren, Rob J; Luider, Theo M; Vanduijn, Martijn M

    2014-01-01

    Late diagnosis of lung cancer is still the main reason for high mortality rates in lung cancer. Lung cancer is a heterogeneous disease which induces an immune response to different tumor antigens. Several methods for searching autoantibodies have been described that are based on known purified antigen panels. The aim of our study is to find evidence that parts of the antigen-binding-domain of antibodies are shared among lung cancer patients. This was investigated by a novel approach based on sequencing antigen-binding-fragments (Fab) of immunoglobulins using proteomic techniques without the need of previously known antigen panels. From serum of 93 participants of the NELSON trial IgG was isolated and subsequently digested into Fab and Fc. Fab was purified from the digested mixture by SDS-PAGE. The Fab containing gel-bands were excised, tryptic digested and measured on a nano-LC-Orbitrap-Mass-spectrometry system. Multivariate analysis of the mass spectrometry data by linear canonical discriminant analysis combined with stepwise logistic regression resulted in a 12-antibody-peptide model which was able to distinguish lung cancer patients from controls in a high risk population with a sensitivity of 84% and specificity of 90%. With our Fab-purification combined Orbitrap-mass-spectrometry approach, we found peptides from the variable-parts of antibodies which are shared among lung cancer patients. PMID:24787687

  8. SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer

    PubMed Central

    Lv, Xiao-bin; Liu, Lijuan; Cheng, Chun; Yu, Bentong; Xiong, Longxin; Hu, Kaishun; Tang, Jianjun; Zeng, Lei; Sang, Yi

    2015-01-01

    SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell proliferation and migration. Additionally, SUN2 increases the sensitivity of lung cancer to cisplatin by inducing cell apoptosis. Mechanistically, we showed that SUN2 exerts its tumor suppressor functions by decreasing the expression of GLUT1 and LDHA to inhibit the Warburg effect. Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2.Taken together, our findings indicate that SUN2 is a key component in lung cancer progression by inhibiting the Warburg effect and that the novel SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer. PMID:26658802

  9. A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary Diagnosis of Small Cell Lung Cancer

    PubMed Central

    Si, Hongzong; Liu, Shihai; Li, Xianchao; Gao, Caihong; Cui, Lianhua; Li, Chuan; Yang, Xue; Yao, Xiaojun

    2015-01-01

    Background Lung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity. Methods We used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na+, Cl-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC. Results After appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients. Conclusion We have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use

  10. Lung Cancer: Are we up to the Challenge?

    PubMed Central

    Esposito, Luca; Conti, Daniele; Ailavajhala, Ramyasri; Khalil, Nansie; Giordano, Antonio

    2010-01-01

    Lung cancer is the leading cause of cancer deaths worldwide among both men and women, with more than 1 million deaths annually. Non–small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Although recent advances have been made in diagnosis and treatment strategies, the prognosis of NSCLC patients is poor and it is basically due to a lack of early diagnostic tools. However, in the last years genetic and biochemical studies have provided more information about the protein and gene’s mutations involved in lung tumors. Additionally, recent proteomic and microRNA’s approaches have been introduced to help biomarker discovery. Here we would like to discuss the most recent discoveries in lung cancer pathways, focusing on the genetic and epigenetic factors that play a crucial role in malignant cell proliferation, and how they could be helpful in diagnosis and targeted therapy. PMID:21532835

  11. Mortality study of beryllium industry workers' occupational lung cancer

    SciTech Connect

    Mancuso, T.F.

    1980-02-01

    A cohort of 3685 white males employed during 1937 to 1948 in two major industries manufacturing beryllium was followed to the end of 1976 to evaluate lung cancer mortality experience. Lung cancer mortality among beryllium-exposed workers was contrasted with that of workers employed in the viscose rayon industry. Study results demonstrated that lung cancer mortality among berylliumm-exposed workers was significantly greater than that expected on the basis of lung cancer mortality experience of workers in the viscose rayon industry having similar employment patterns. The results of the present study are consistent with earlier animal bioassay studies and recent epidemiologic studies indicating that beryllium is carcinogenic. The results of the present study are not consistent with speculation attributing the excessive lung cancer mortality among beryllium-exposed workers to personal characteristics of individuals having unstable employment patterns.

  12. [Graphic Evolution Witness the Development of Lung Cancer Translational Research].

    PubMed

    Zhang, Chao; Zhong, Wenzhao

    2016-06-20

    Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn't quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment. PMID:27335306

  13. Study of occupational lung cancer in asbestos factories in China.

    PubMed

    Zhu, H; Wang, Z

    1993-11-01

    A retrospective cohort study (1972-81) of occupational cancers in asbestos (chrysotile) factories has been previously published. In this paper the results of continued tracing and interviewing of members of this cohort from 1982 to 1986 is reported. The cohort included 5893 persons (45,974 person-years for men and 39,445 person-years for women). Malignant tumours played a large part in causes of death (36.9%). There were 183 cancers and 67 lung cancers among 496 deaths. The mortality due to lung cancer had a tendency to increase. By comparison with a control group, the RR of lung cancer was 5.32 (p < 0.01), and the SRR of lung cancer was 4.2 (p < 0.01), significantly higher than those of a control group. Among 148 cases of death from asbestosis there were 33 cases complicated with lung cancer (22.3%). The dose-response relations between exposure to asbestos and incidence of asbestosis and lung cancer were also studied in one asbestos factory. There was a positive correlation. A synergistic effect was found between cigarette smoking and lung cancer. Preventive and control measures and exposure limits for asbestos dust in the air of workplaces were recommended. PMID:8280629

  14. Antioxidants accelerate lung cancer progression in mice.

    PubMed

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. PMID:24477002

  15. The value of proteomics in lung cancer

    PubMed Central

    Hiltermann, Thijo J. N.; Groen, Harry J. M.

    2015-01-01

    Many studies have identified the prognostic and predictive value of proteins or peptides in lung cancer but most failed to provide strong evidence for their clinical applicability. The strongest predictive proteins seem to be fatty acid-binding protein heart (H-FABP), and the 8-peak mass spectrography signature of VeriStrat. When focusing on VeriStrat, a ‘VeriStrat good’ profile did not discriminate between chemotherapy and erlotinib. The ‘VeriStrat poor’ profile showed a better outcome to chemotherapy than to erlotinib. VeriStrat is a prognostic test and only the “poor profile” discriminates for the type of therapy that should be chosen. Whether it adds useful information in patients with advanced non-small cell lung cancer (NSCLC) and wild type EGFR mutations is still doubtful. The position of the VeriStrat test in clinical practice is still not clear and we are waiting for prospective studies where biomarker test are involved in clinical decision. PMID:25815290

  16. Occupational exposure and lung cancer risk.

    PubMed

    Kvåle, G; Bjelke, E; Heuch, I

    1986-02-15

    The importance of occupation held longest as a risk factor for lung cancer was examined in a prospective study in Norway of 11,995 men, among whom 125 cases occurred in a follow-up from 1966 through 1978. Based on information about occupation held longest, the respondents were classified into 3 groups according to suspected exposure to respiratory carcinogens at the workplace. After stratification for age, place of residence and cigarette smoking, we found a highly significant relative risk of 2.6 for those judged to have experienced definite exposure versus the group with no workplace exposure. The apparent risk-enhancing effect of occupational exposure was observed for all histologic subtypes. Stratification including a socioeconomic factor score led to a moderate reduction in the relative risk estimate. High risk estimates still obtained, however, for a limited number of occupations, the highest for workers in the mining and quarrying industries. Although the interpretation of the observed effect associated with a crude index of occupational exposure may be difficult, our results suggest that between 13 and 27% of the lung cancer cases observed among Norwegian men in the relevant time period can be attributed to harmful work-place exposure. PMID:3943919

  17. Treatment of small cell lung cancer patients.

    PubMed

    Zöchbauer-Müller, S; Pirker, R; Huber, H

    1999-01-01

    Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure. PMID:10676558

  18. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma

    PubMed Central

    Banat, G-Andre; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Wilhelm, Jochen; Weigert, Andreas; Olesch, Catherine; Ebel, Katharina; Stiewe, Thorsten; Grimminger, Friedrich; Seeger, Werner; Fink, Ludger; Savai, Rajkumar

    2015-01-01

    Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition. PMID:26413839

  19. Immunoproteasomes and immunotherapy—a smoking gun for lung cancer?

    PubMed Central

    Spits, Menno

    2016-01-01

    Lung cancer is the second most prevalent cancer in both women and men with some 221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis. Recently a new treatment option for NSCLC appeared that strongly improved treatment responses—immunotherapy. Here we review the various forms of immunotherapy and how immune modification of proteasomes in lung cancer may support the immune system in controlling NSCLC. These immunoproteasomes then support recognition of NSCLC and may act as a biomarker for selecting responding patients to immunotherapy. PMID:27501321

  20. Immunoproteasomes and immunotherapy-a smoking gun for lung cancer?

    PubMed

    Spits, Menno; Neefjes, Jacques

    2016-07-01

    Lung cancer is the second most prevalent cancer in both women and men with some 221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis. Recently a new treatment option for NSCLC appeared that strongly improved treatment responses-immunotherapy. Here we review the various forms of immunotherapy and how immune modification of proteasomes in lung cancer may support the immune system in controlling NSCLC. These immunoproteasomes then support recognition of NSCLC and may act as a biomarker for selecting responding patients to immunotherapy. PMID:27501321

  1. Lung cancers unrelated to smoking: characterized by single oncogene addiction?

    PubMed

    Suda, Kenichi; Tomizawa, Kenji; Yatabe, Yasushi; Mitsudomi, Tetsuya

    2011-08-01

    Lung cancer is a major cause of cancer-related mortality worldwide. Currently, adenocarcinoma is its most common histological subtype in many countries. In contrast with small cell lung cancer or squamous cell carcinoma, lung adenocarcinoma often arises in never-smokers, especially in East Asian countries, as well as in smokers. Adenocarcinoma in never-smokers is associated with a lower incidence of genetic alterations (i.e., somatic mutations, loss of heterozygosity, and methylation) than in smokers. In addition, most adenocarcinomas in never-smokers harbor one of the proto-oncogene aberrations that occur in a mutually exclusive manner (EGFR mutation, KRAS mutation, HER2 mutations, or ALK translocation). It is of note that the proliferation and survival of lung cancer cells that harbor one of these oncogenic aberrations depend on the signaling from each aberrantly activated oncoprotein (oncogene addiction). Therefore, most adenocarcinomas in never-smokers can be effectively treated by molecularly targeted drugs that inhibit each oncoprotein. Moreover, from a pathological aspect, lung adenocarcinoma in never-smokers is characterized by terminal respiratory unit-type adenocarcinoma and a particular gene expression profile. Finally, epidemiological analyses have identified many candidate causes of lung cancer in never-smokers (genetic, environmental, and hormonal factors). The elucidation of the particular features of lung cancer unrelated to smoking and the development of new therapeutic modalities may reduce the mortality from lung cancers in the future. PMID:21655907

  2. TP53 Mutations in Nonsmall Cell Lung Cancer

    PubMed Central

    Mogi, Akira; Kuwano, Hiroyuki

    2011-01-01

    The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC. PMID:21331359

  3. A Pessimistic Explanatory Style is Prognostic for Poor Lung Cancer Survival

    PubMed Central

    Novotny, Paul; Colligan, Robert C.; Szydlo, Daniel W.; Clark, Matthew M.; Rausch, Sarah; Wampfler, Jason; Sloan, Jeff A.; Yang, Ping

    2010-01-01

    Background Several studies have demonstrated the importance of personality constructs on health behaviors and health status. Having a pessimistic outlook has been related to negative health behaviors and higher mortality. However, the construct has not been well explored in cancer populations. Methods Survival time of 534 adults, who were diagnosed with lung cancer and had a pessimistic explanatory style, was examined. The patients had completed the Minnesota Multiphasic Personality Inventory (MMPI) approximately 18.2 years prior to receiving their lung cancer diagnosis. MMPI Optimism-Pessimism (PSM) scores were divided into high (60 or more) and low scores (less than 60), and log-rank tests and Kaplan-Meier curves were used to determine survival differences. Multivariate Cox models were used for assessing prognostic values of pessimism along with other known predictors for lung cancer survival outcome. Booting strapping of the survival models was used as a sensitivity analysis. Results At the time of lung cancer diagnosis, patients were on average 67 years old; 48% were female; 85% had non-small cell lung cancer (NSCLC); 15% had small cell lung cancer (SCLC); 30% were stage I; 4% were stage II; 31% were stage III/limited; and 35% were stage IV/extensive. Patients who exhibited a non-pessimistic explanatory style survived approximately six months longer than patients classified as having a pessimistic explanatory style. Conclusion Among lung cancer patients, those having a pessimistic explanatory style experienced less favorable survival outcome, which may be related to cancer treatment decisions. Further research in this area is warranted. PMID:20139778

  4. About the Lung and Upper Aerodigestive Cancer Research Group | Division of Cancer Prevention

    Cancer.gov

    The Lung and Upper Aerodigestive Cancer Research Group conducts and supports research on the prevention and early detection of lung and head and neck cancers, as well as new approaches to clinical prevention studies including cancer immunoprevention.Phase 0/I/II Cancer Prevention Clinical Trials ProgramThe group jointly administers the Phase 0/I/II Cancer Prevention Clinical Trials Program evaluating new agents, surrogate biomarkers, and technologies to identify premalignant lesions, and related cancers.  |

  5. Outcomes of lung cancers manifesting as nonsolid nodules.

    PubMed

    Yip, Rowena; Wolf, Andrea; Tam, Kathleen; Taioli, Emanuela; Olkin, Ingram; Flores, Raja M; Yankelevitz, David F; Henschke, Claudia I

    2016-07-01

    This is a comprehensive review and re-analysis of available literature to assess the outcome of lung cancer presenting as nonsolid nodules (NSNs), a more indolent form of cancer. PubMed and EMBASE were searched for articles reporting on CT-detected lung cancers manifesting as NSNs published in English on or before July 17, 2015. Only studies including clinicopathologic data, lung cancer-specific survival, or overall survival were included. Data extraction was performed by three independent reviewers using prespecified criteria. Twenty-four articles from 5 countries met criteria and they included 704 subjects with 712 lung cancers manifesting as NSNs. Each article reported from 2 to 100 lung cancer cases with a median follow up of 18-51 months. All NSNs were Stage I adenocarcinoma without pathologic nodal involvement upon resection, except for one case in which the NSN progressed to become part-solid nodule after 6 years of follow-up. The five-year lung cancer-specific survival rate was 100%. These findings suggest an indolent course for lung cancers manifesting as NSNs. PMID:27237025

  6. NK Cell Phenotypic Modulation in Lung Cancer Environment

    PubMed Central

    Hao, Jun-Wei; Li, Yang; Liu, Bin; Yu, Yan; Shi, Fu-Dong; Zhou, Qing-Hua

    2014-01-01

    Background Nature killer (NK) cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment. Materials and methods Our study analyzed the change about NK cells surface markers (NK cells receptors) through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse. Results We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently. Conclusions The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy. PMID:25299645

  7. [Current perspectives on supportive care for lung cancer patients].

    PubMed

    Serena, A; Zurkinden, C; Castellani, P; Eicher, M

    2015-05-20

    The fight against cancer comprises not only survival of the disease but also survival with the highest possible quality of life. Thus, supportive care in cancer aims at reducing physical and psycho-emotional symptom burden. Furthermore, supportive care in cancer includes self-management-support for patients and their families/caregivers. Due to high symptom prevalence and poor prognosis, lung cancer patients express more unmet supportive care needs than other patient populations with cancer. Interventions to meet these needs have been developed in the last decade. They involve new models of care that incorporate the role of a lung cancer nurse in comprehensive cancer centers and eHealth-systems to support lung cancer patients and their families/caregivers. PMID:26152086

  8. Effect of Resection of Lung Tumours on the Steroid Abnormalities in Patients with Lung Cancer

    PubMed Central

    Rao, L. G. S.

    1971-01-01

    The urinary excretion of androsterone, aetiocholanolone, total 17-oxosteroids, and 17-hydroxycorticosteroids (17-OHCS) was measured in 40 patients with lung cancer three days before resection and again 10-15 days after resection of their lung tumours. There was a significant postoperative increase in the excretion of 17-OHCS but a significant decrease in the excretion of androsterone and aetiocholanolone, resulting in an increase of the preoperative abnormalities in steroid excretion in these patients. Since there was no change in steroid excretion towards normal after resection of the lung tumours, it seems that the steroid abnormalities found in lung cancer are not the effect of the presence of the lung tumours. As the excretions of 17-OHCS and 11-deoxy-17-oxosteroids change in opposite directions after resection, it is suggested that a dissociation of factors that control the excretion of these two groups of steroids takes place as a response to surgical stress in patients with lung cancer. PMID:5130212

  9. Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics

    PubMed Central

    Gandara, David R.; Hammerman, Peter S.; Sos, Martin L.; Lara, Primo N.; Hirsch, Fred R.

    2016-01-01

    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the last several years, therapeutic progress in SCC has lagged behind the now more common NSCLC histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC. PMID:25979930

  10. Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens

    PubMed Central

    Cramer, Daniel W.; Bast, Robert C.; Berg, Christine D.; Diamandis, Eleftherios P.; Godwin, Andrew K.; Hartge, Patricia; Lokshin, Anna E.; Lu, Karen H.; McIntosh, Martin W.; Mor, Gil; Patriotis, Christos; Pinsky, Paul F.; Thornquist, Mark D.; Scholler, Nathalie; Skates, Steven J.; Sluss, Patrick M.; Srivastava, Sudhir; Ward, David C.; Zhang, Zhen; Zhu, Claire S.; Urban, Nicole

    2011-01-01

    Establishing a cancer screening biomarker’s intended performance requires “phase III” specimens obtained in asymptomatic individuals before clinical diagnosis rather than “phase II” specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network (EDRN) or Ovarian Cancer Specialized Program of Research Excellence (SPORE) sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within six months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study. PMID:21372036

  11. Protein Kinase Cα Mediates Erlotinib Resistance in Lung Cancer Cells

    PubMed Central

    Abera, Mahlet B.

    2015-01-01

    Overexpression and mutational activation of the epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of non–small cell lung cancer (NSCLC). EGFR tyrosine-kinase inhibitors (TKIs) are given as a primary therapy for advanced patients with EGFR-activating mutations; however, the majority of these tumors relapse and patients eventually develop resistance to TKIs. To address a potential role of protein kinase C (PKC) isozymes in the resistance to TKIs, we used the isogenic NSCLC H1650 cell line and its erlotinib-resistant derivative H1650-M3, a cell line that displays a mesenchymal-like morphology driven by transforming growth factor-β signaling. We found that H1650-M3 cells display remarkable PKCα upregulation and PKCδ downregulation. Notably, silencing PKCα from H1650-M3 cells using RNA interference caused a significant reduction in the expression of epithelial-to-mesenchymal transition (EMT) markers vimentin, Zeb2, Snail, and Twist. Moreover, pharmacological inhibition or PKCα RNA interference depletion and PKCδ restoring sensitized H1650-M3 cells to erlotinib. Whereas ectopic overexpression of PKCα in parental H1650 cells was not sufficient to alter the expression of EMT genes or to confer resistance to erlotinib, it caused downregulation of PKCδ expression, suggesting a unidirectional crosstalk. Finally, mechanistic studies revealed that PKCα upregulation in H1650-M3 cells is driven by transforming growth factor-β. Our results identified important roles for specific PKC isozymes in erlotinib resistance and EMT in lung cancer cells, and highlight PKCα as a potential target for lung cancer treatment. PMID:25724832

  12. Protein kinase Cα mediates erlotinib resistance in lung cancer cells.

    PubMed

    Abera, Mahlet B; Kazanietz, Marcelo G

    2015-05-01

    Overexpression and mutational activation of the epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of non-small cell lung cancer (NSCLC). EGFR tyrosine-kinase inhibitors (TKIs) are given as a primary therapy for advanced patients with EGFR-activating mutations; however, the majority of these tumors relapse and patients eventually develop resistance to TKIs. To address a potential role of protein kinase C (PKC) isozymes in the resistance to TKIs, we used the isogenic NSCLC H1650 cell line and its erlotinib-resistant derivative H1650-M3, a cell line that displays a mesenchymal-like morphology driven by transforming growth factor-β signaling. We found that H1650-M3 cells display remarkable PKCα upregulation and PKCδ downregulation. Notably, silencing PKCα from H1650-M3 cells using RNA interference caused a significant reduction in the expression of epithelial-to-mesenchymal transition (EMT) markers vimentin, Zeb2, Snail, and Twist. Moreover, pharmacological inhibition or PKCα RNA interference depletion and PKCδ restoring sensitized H1650-M3 cells to erlotinib. Whereas ectopic overexpression of PKCα in parental H1650 cells was not sufficient to alter the expression of EMT genes or to confer resistance to erlotinib, it caused downregulation of PKCδ expression, suggesting a unidirectional crosstalk. Finally, mechanistic studies revealed that PKCα upregulation in H1650-M3 cells is driven by transforming growth factor-β. Our results identified important roles for specific PKC isozymes in erlotinib resistance and EMT in lung cancer cells, and highlight PKCα as a potential target for lung cancer treatment. PMID:25724832

  13. COPD in primary lung cancer patients: prevalence and mortality

    PubMed Central

    Ytterstad, Elinor; Moe, Per C; Hjalmarsen, Audhild

    2016-01-01

    Background Previous studies have relied on international spirometry criteria to diagnose COPD in patients with lung cancer without considering the effect lung cancer might have on spirometric results. The aim of this study was to examine the prevalence of COPD and emphysema at the time of primary lung cancer diagnosis and to examine factors associated with survival. Materials and methods Medical records, pulmonary function tests, and computed tomography scans were used to determine the presence of COPD and emphysema in patients diagnosed with primary lung cancer at the University Hospital of North Norway in 2008–2010. Results Among the 174 lung cancer patients, 69% had COPD or emphysema (39% with COPD, 59% with emphysema; male:female ratio 101:73). Neither COPD nor emphysema were significantly associated with lung cancer mortality, whereas patients with non-small-cell lung cancer other than adenocarcinoma and squamous cell carcinoma had a risk of lung cancer mortality that was more than four times higher than that of patients with small-cell lung cancer (hazard ratio [HR] 4.19, 95% confidence interval [CI] 1.56–11.25). Females had a lower risk of lung cancer mortality than males (HR 0.63, 95% CI 0.42–0.94), and patients aged ≥75 years had a risk that was twice that of patients aged <75 years (HR 2.48, 95% CI 1.59–3.87). Low partial arterial oxygen pressure (4.0–8.4 kPa) increased the risk of lung cancer mortality (HR 2.26, 95% CI 1.29–3.96). So did low partial arterial carbon dioxide pressure (3.0–4.9 kPa) among stage IV lung cancer patients (HR 2.23, 95% CI 1.29–3.85). Several patients with respiratory failure had previously been diagnosed with COPD. Conclusion The observed prevalence of COPD was lower than that in previous studies. Neither COPD nor emphysema were significantly associated with lung cancer mortality. PMID:27042050

  14. Lung cancer and angiogenesis imaging using synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoxia; Zhao, Jun; Sun, Jianqi; Gu, Xiang; Xiao, Tiqiao; Liu, Ping; Xu, Lisa X.

    2010-04-01

    Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.

  15. Identification of five candidate lung cancer biomarkers by proteomics analysis of conditioned media of four lung cancer cell lines.

    PubMed

    Planque, Chris; Kulasingam, Vathany; Smith, Chris R; Reckamp, Karen; Goodglick, Lee; Diamandis, Eleftherios P

    2009-12-01

    Detection of lung cancer at an early stage is necessary for successful therapy and improved survival rates. We performed a bottom-up proteomics analysis using a two-dimensional LC-MS/MS strategy on the conditioned media of four lung cancer cell lines of different histological backgrounds (non-small cell lung cancer: H23 (adenocarcinoma), H520 (squamous cell carcinoma), and H460 (large cell carcinoma); small cell lung cancer: H1688) to identify secreted or membrane-bound proteins that could be useful as novel lung cancer biomarkers. Proteomics analysis of the four conditioned media allowed identification of 1,830 different proteins (965, 871, 726, and 847 from H1688, H23, H460, and H520, respectively). All proteins were assigned a subcellular localization, and 38% were classified as extracellular or membrane-bound. We successfully identified the internal control proteins (also detected by ELISA), kallikrein-related peptidases 14 and 11, and IGFBP2. We also identified known or putative lung cancer tumor markers such as squamous cell carcinoma antigen, carcinoembryonic antigen, chromogranin A, creatine kinase BB, progastrin-releasing peptide, neural cell adhesion molecule, and tumor M2-PK. To select the most promising candidates for validation, we performed tissue specificity assays, functional classifications, literature searches for association to cancer, and a comparison of our proteome with the proteome of lung-related diseases and serum. Five novel lung cancer candidates, ADAM-17, osteoprotegerin, pentraxin 3, follistatin, and tumor necrosis factor receptor superfamily member 1A were preliminarily validated in the serum of patients with lung cancer and healthy controls. Our results demonstrate the utility of this cell culture proteomics approach to identify secreted and shed proteins that are potentially useful as serological markers for lung cancer. PMID:19776420

  16. Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines*

    PubMed Central

    Planque, Chris; Kulasingam, Vathany; Smith, Chris R.; Reckamp, Karen; Goodglick, Lee; Diamandis, Eleftherios P.

    2009-01-01

    Detection of lung cancer at an early stage is necessary for successful therapy and improved survival rates. We performed a bottom-up proteomics analysis using a two-dimensional LC-MS/MS strategy on the conditioned media of four lung cancer cell lines of different histological backgrounds (non-small cell lung cancer: H23 (adenocarcinoma), H520 (squamous cell carcinoma), and H460 (large cell carcinoma); small cell lung cancer: H1688) to identify secreted or membrane-bound proteins that could be useful as novel lung cancer biomarkers. Proteomics analysis of the four conditioned media allowed identification of 1,830 different proteins (965, 871, 726, and 847 from H1688, H23, H460, and H520, respectively). All proteins were assigned a subcellular localization, and 38% were classified as extracellular or membrane-bound. We successfully identified the internal control proteins (also detected by ELISA), kallikrein-related peptidases 14 and 11, and IGFBP2. We also identified known or putative lung cancer tumor markers such as squamous cell carcinoma antigen, carcinoembryonic antigen, chromogranin A, creatine kinase BB, progastrin-releasing peptide, neural cell adhesion molecule, and tumor M2-PK. To select the most promising candidates for validation, we performed tissue specificity assays, functional classifications, literature searches for association to cancer, and a comparison of our proteome with the proteome of lung-related diseases and serum. Five novel lung cancer candidates, ADAM-17, osteoprotegerin, pentraxin 3, follistatin, and tumor necrosis factor receptor superfamily member 1A were preliminarily validated in the serum of patients with lung cancer and healthy controls. Our results demonstrate the utility of this cell culture proteomics approach to identify secreted and shed proteins that are potentially useful as serological markers for lung cancer. PMID:19776420

  17. Preferentially Expressed Antigen of Melanoma Prevents Lung Cancer Metastasis

    PubMed Central

    Sun, Zhengwang; Li, Lei; Lin, Zaijun; Xu, Wei; Han, Shuai; Cao, Wenjiao; Xu, Yunfei; Song, Dianwen; Yang, Xinghai; Xiao, Jianru

    2016-01-01

    Lung cancer is the most common cause of cancer death worldwide. The poor survival rate is largely due to the extensive local invasion and metastasis. However, the mechanisms underlying the invasion and metastasis of lung cancer cells remain largely elusive. In this study, we examined the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer metastasis. Our results show that PRAME is downregulated in lung adenocarcinoma and lung bone metastasis compared with normal human lung. Knockdown of PRAME decreases the expression of E-Cadherin and promotes the proliferation, invasion, and metastasis of lung cancer cells by regulating multiple critical genes, most of which are related to cell migration, including MMP1, CCL2, CTGF, and PLAU. Clinical data analysis reveals that the expression of MMP1 correlates with the clinical features and outcome of lung adenocarcinoma. Taken together, our data demonstrate that PRAME plays a role in preventing the invasion and metastasis of lung adenocarcinoma and novel diagnostic or therapeutic strategies can be developed by targeting PRAME. PMID:27391090

  18. Clinical test on circulating tumor cells in peripheral blood of lung cancer patients, based on novel immunomagnetic beads.

    PubMed

    Wang, Bo; Wang, Bin; Zhang, Daoyun; Guo, Hongyin; Zhang, Lianbin; Zhou, Wenpeng

    2016-05-01

    This paper aims to establish a novel and highly sensitive method to detect circulating tumor cells (CTCs) in the peripheral blood of patients with lung cancer. This therefore enables the discovery of invisible micrometastasis in the early stage of lung cancer, leading to better prognostic assessments of lung cancer and detection of the post-operative tumor recurrence and metastasis, treatment options, and evaluation of curative effects. In this research study, various lung cancer cells were mixed with adult blood samples to simulate blood samples of tumor patients. With novel test methods, CTCs in peripheral blood of lung cancer patients were calculated, after the reaction between the cells obtained from the mix and EpCAM (epithelial cell adhesion molecule) antibodies which were marked by immunomagnetic beads. The results showed that 18 out of 42 (42.9%) lung cancer patients had a positive CTCs, which increased with tumor enlargement or metastasis. CTCs were not detected in a total of 20 blood samples from healthy volunteers. This indicated that the technology of novel immunomagnetic bead-enrichment could effectively separate and identify CTCs in peripheral blood of lung cancer patients, which is of great clinical value for prognostic assessments and treatment guidance of lung cancer. PMID:25682839

  19. Epidemiologic characteristics of compensated occupational lung cancers among Korean workers.

    PubMed

    Ahn, Yeon-Soon; Jeong, Kyoung Sook

    2014-11-01

    An understanding of the characteristics of occupational lung cancer is important to establish policies that prevent carcinogen exposure and to compensate workers exposed to lung carcinogens. This study analyzed the characteristics of occupational lung cancers in workers who were compensated under the Industrial Accident Compensation Insurance Law between 1994 and 2011. A total of 179 occupational lung cancers were compensated. The main carcinogenic exposure was asbestos, followed by crystalline silica and hexavalent chromium. The mean exposure duration and latency were 19.8 and 23.2 yr. The most common industry was manufacturing, followed by construction and transportation. The most common occupation was maintenance and repair, followed by foundry work, welding, painting, and spinning or weaving. Although asbestos was predominant carcinogen, the proportion of these cases was relatively low compared to other developed countries. Proper surveillance system is needed to monitor occupational lung cancer and improve prevention measures. PMID:25408577

  20. Lung cancer in never smokers Epidemiology and risk prediction models

    PubMed Central

    McCarthy, William J.; Meza, Rafael; Jeon, Jihyoun; Moolgavkar, Suresh

    2012-01-01

    In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/ nonsmokers and describe the never smoker lung cancer risk models used by CISNET modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model. PMID:22882894