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Sample records for increase 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. 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 ...

  3. Free Lung Cancer Screening Trends Toward a Twofold Increase in Lung Cancer Prevalence in the Underserved Southeastern United States.

    PubMed

    Simmerman, Erika L; Thomson, Norman B; Dillard, Thomas A; Hao, Zhonglin; Sadek, Ramses F; Khleif, Samir N; Schroeder, Carsten

    2017-03-01

    The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.

  4. Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

    PubMed

    Hung, Ming-Szu; Chen, I-Chuan; You, Liang; Jablons, David M; Li, Ya-Chin; Mao, Jian-Hua; Xu, Zhidong; Lung, Jr-Hau; Yang, Cheng-Ta; Liu, Shih-Tung

    2016-07-01

    Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.

  5. Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

    SciTech Connect

    Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

    2009-10-15

    The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

  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. Lung cancer burden has increased during the last 40 years in Hebei Province, China

    PubMed Central

    He, Yutong; Li, Daojuan; Song, Guohui; Li, Yongwei; Liang, Di; Jin, Jing; Wen, Denggui

    2016-01-01

    Abstract Background In 2011, Hebei Province, located in North China with a population of 71 794 239, accounted for approximately 6% of the national population. It is well known as a heavily air polluted area. This study reports the lung cancer burden and mortality trend in Hebei Province from 1973 to 2011. Methods Eight cancer registries in Hebei Province submitted data to the Hebei Provincial Cancer Registry Center. Pooled data were stratified by area (urban/rural), gender, and age group. The proportions, cumulative incidence/mortality rates, and median age at death of lung cancer were calculated. Lung cancer mortality data of 1973–1975, 1990–1992, and 2004–2005 were extracted from national death surveys. Data of lung cancer from Cixian and Shexian were obtained from population‐based cancer registries in each county. Results The estimated numbers of newly diagnosed lung cancer cases and deaths in 2011 in Hebei Province were 32 623 and 27 612, respectively. The crude incidence rate of lung cancer was 45.44/100 000. The age‐standardized incidence rate by world standard population was 39.01/100 000, ranking second among all cancers. The lung cancer mortality rate was 38.46/100 000, ranking first among all cancer deaths, with a significantly increasing trend in Hebei Province from 1973–1975 to 2010–2011, with an increased rate of 189.15%. Conclusion Hebei Province suffers a heavy disease burden of lung cancer and an obvious increasing trend has been observed over the past 40 years. Preventive and control strategies should be encouraged. PMID:27148418

  8. Lung cancer in the elderly--increasing epidemiological problem of 21st century.

    PubMed

    Batura-Gabryel, H; Foremska-Iciek, J

    2005-01-01

    Lung cancer is the second most common malignant neoplasm after prostate and breast cancers. It is the most frequent cause of death related to neoplasms. The elderly people over 65, are the most numerous population suffering from lung cancer. Risk of incidence and death increases with aging process. In majority of patients, diagnose is established in highly advanced neoplastic process. More than 80% of all types of lung cancers make non-small cell lung cancer (NSCLC) and less than 20%--small cell lung cancer (SCLC). The choice of the managment must be individually considered and should be based on the stage of cancer clinical advance, clinical and functional status, concomitant diseases, nutritional status, cognitive functions. The patients age is not a contradiction for the introducement of the treatment. Surgical treatment is a method by choice at the early stages of NSCLC. Radical radiotherapy should be introduced in the elderly disqualified from the operation. Single-agent chemotherapy seems to be benficial for the elderly with advanced NSCLC in good general condition, mainly due to less toxicity and satisfactory the survival rate. In the cases of SCLC polychemotherapy with prophylactic brain radiation is the first-line managment. Unfortunately, the effectivity of the therapy is occupied by its toxicity. Still frequent occurrence and late diagnosis of lung cancer, high mortality, low efficiency of chemo- and radiotherapy causes the necessity of newer research for more effective screening methods, more effective and safer lung cancer treatment schemes for the elderly.

  9. Lung Cancer Prevention

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease ...

  10. Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

    PubMed

    Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

    2015-06-01

    Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients.

  11. 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

  12. Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients.

    PubMed

    Chiou, Yu-Hu; Wong, Ruey-Hong; Chao, Mu-Rong; Chen, Chih-Yi; Liou, Saou-Hsing; Lee, Huei

    2014-10-01

    Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.

  13. What Is Lung Cancer?

    MedlinePlus

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  14. Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  15. Intakes of red meat, processed meat, and meat mutagens increase lung cancer risk.

    PubMed

    Lam, Tram Kim; Cross, Amanda J; Consonni, Dario; Randi, Giorgia; Bagnardi, Vincenzo; Bertazzi, Pier Alberto; Caporaso, Neil E; Sinha, Rashmi; Subar, Amy F; Landi, Maria Teresa

    2009-02-01

    Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology, a population-based case-control study. Primary lung cancer cases (n = 2,101) were recruited from 13 hospitals within the Lombardy region of Italy examining approximately 80% of the cases from the area. Noncancer population controls (n = 2,120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1,903 cases and 2,073 controls and used in conjunction with a meat mutagen database to estimate intake of heterocyclic amines (HCA) and benzo(a)pyrene (BaP). Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR, 1.8; 95% CI, 1.5-2.2; P trend < 0.001 and OR, 1.7; 95% CI, 1.4-2.1; P trend < 0.001, respectively); the risks were strongest among never smokers (OR, 2.4; 95% CI, 1.4-4.0; P trend = 0.001 and OR, 2.5; 95% CI, 1.5-4.2; P trend = 0.001, respectively). HCAs and BaP were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat mutagens were independently associated with increased risk of lung cancer.

  16. Reduced fatalism and increased prevention behavior after two high-profile lung cancer events.

    PubMed

    Portnoy, David B; Leach, Corinne R; Kaufman, Annette R; Moser, Richard P; Alfano, Catherine M

    2014-01-01

    The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR = 0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services.

  17. Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium

    PubMed Central

    Coté, Michele L.; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G.; Christiani, David C.; Spitz, Margaret R.; Muscat, Joshua E.; Rennert, Gad; Aben, Katja K.; Andrew, Angeline S.; Bencko, Vladimir; Bickeböller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J.; Fabianova, Eleonora; Field, John K.; Foretova, Lenka; Friis, Søren; Harris, Curtis C.; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A.; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Marchand, Loic Le; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I.; McLaughlin, John R.; Morgenstern, Hal; Müeller, Heiko; Orlow, Irene; Park, Bernard J.; Pinchev, Mila; Raji, Olaide Y.; Rennert, Hedy S.; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Teare, M. Dawn; Tjønnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F.M.; Wichmann, Erich; Wiencke, John K.; Woll, Penella J.; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J.; Hung, Rayjean J.

    2012-01-01

    Background and Methods Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analyzed. Unconditional logistic regression models and generalized estimating equations were used to estimate odds ratios and 95% confidence intervals. Results Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in risk of lung cancer, after adjustment for smoking and other potential confounders(95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (OR=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions The increased risk among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those associated with cigarette smoking. While the role of genetic variation in the etiology of lung cancer remains to be fully characterized, family history assessment is immediately available and those with a positive history represent a higher risk group. PMID:22436981

  18. Lung cancer

    MedlinePlus

    ... Sputum test to look for cancer cells Thoracentesis (sampling of fluid buildup around the lung) In most ... quitting, talk with your provider. There are many methods to help you quit, from support groups to ...

  19. Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD.

    PubMed

    Wu, Ming-Fang; Jian, Zhi-Hong; Huang, Jing-Yang; Jan, Cheng-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Liaw, Yung-Po

    2016-10-10

    Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.

  20. Increased risk of lung cancer mortality among residents near an asbestos product manufacturing plant.

    PubMed

    Kumagai, Shinji; Kurumatani, Norio; Tsuda, Toshihide; Yorifuji, Takashi; Suzuki, Etsuji

    2010-01-01

    We investigated whether individuals exposed to asbestos by living near an asbestos-manufacturing facility experienced increased lung cancer mortality. We studied a neighborhood around such a plant in the central Japanese city of Hashima. From 1943 to 1991 this plant produced insulation and packing material using amosite- and chrysotile-type asbestos fibers. The study group was comprised of 577 households. We obtained demographic information by a questionnaire and determined the underlying cause of death for deceased household members from death certificates. Using hourly meteorological data from local observatories, we estimated relative asbestos concentrations in the plant's vicinity, determined the quartile boundaries, and designated each study subject's quartile of ambient exposure. Finally, we calculated standardized mortality ratios to evaluate the association of residential asbestos with lung cancer risk. Our findings strongly suggest that neighborhood asbestos exposure can increase the risk of lung cancer mortality in men and probably in women.

  1. Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease

    SciTech Connect

    van Leeuwen, F.E.; Somers, R.; Taal, B.G.; van Heerde, P.; Coster, B.; Dozeman, T.; Huisman, S.J.; Hart, A.A.

    1989-08-01

    The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. Sixty-nine SCs were observed one month or more after start of first treatment. These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma (NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome (MDS). The median interval between the diagnosis of HD and that of second lung cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The overall relative risks (RR) (observed/expected (O/E) ratios) of developing lung cancer, NHL, and leukemia were 4.9 (95% confidence limit (CL), 2.7 to 8.2), 31.0 (95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD has not frequently been clearly demonstrated before; that we were able to demonstrate such risk may be due to the completeness of follow-up over long periods that could be achieved in this study. Excess lung cancer risk was only noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose in irradiation fields. Excess risk of leukemia was only found in treatment regimens involving chemotherapy (CT). For NHL, combined modality treatment was shown to be the most important risk factor. Risk of lung cancer and NHL increased with time since diagnosis. A time-dependent covariate analysis (Cox model) performed on leukemia and MDS showed an increasing risk with intensity of CT, age (greater than 40 years), and a splenectomy.

  2. Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes

    SciTech Connect

    Marmorstein, J.

    1986-02-01

    This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Critical support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.

  3. Increased risk of lung cancer among different types of professional drivers in Denmark

    PubMed Central

    Hansen, J.; Raaschou-Nielsen, O.; Olsen, J. H.

    1998-01-01

    OBJECTIVES: To study risk of lung cancer among groups of professional drivers probably exposed to different levels of traffic exhaust fumes. METHODS: A nationwide case-control study (1970-89) based on employees comprising 28,744 men with primary lung cancer and incidence density sampled matched controls (1:1). Employment histories were reconstructed back to 1964 for each study subject from the records of a nationwide pension scheme with compulsory membership. Socioeconomic status was derived from the individual job title taken from the national population registry. Information on tobacco smoking habits was available from historical surveys. Relative risks were estimated by odds ratios (ORs) based on conditional logistic regression analyses. RESULTS: In total 2251 of the male lung cancer cases had been employed as bus, lorry, taxi, or unspecified drivers. No significant difference in tobacco smoking habits was found among professional male Danish drivers and the total employed population. The OR for lung cancer adjusted for socioeconomic status was 1.6 (95% confidence interval (95% CI) 1.2 to 2.2) among taxi drivers, who were considered to be exposed to the highest concentrations of vehicle exhaust fumes, and 1.3 (1.2 to 1.5) for bus and lorry drivers. The OR was 1.4 (1.3 to 1.5) for unspecified drivers. The adjusted risk of lung cancer increased significantly with increasing duration of employment as a driver, and the risk was highest for long term taxi drivers with 10 years of lag time (OR 3.0; 1.2 to 6.8). CONCLUSION: Occupational factors, probably exposure to vehicle exhaust, seems to play an important part in the development of lung cancer among drivers.   PMID:9614396

  4. Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: mechanism for immune evasion?

    PubMed

    Soriano, Cyd; Mukaro, Violet; Hodge, Greg; Ahern, Jessica; Holmes, Mark; Jersmann, Hubertus; Moffat, David; Meredith, David; Jurisevic, Craig; Reynolds, Paul N; Hodge, Sandra

    2012-07-01

    Cytotoxic CD8(+) T-cells mount immune responses to cancer via cytotoxic pathways including granzyme B. Cancer cells are also known to develop immune evasion mechanisms. We hypothesised that lung cancer cells would over-express the granzyme B-inhibitor, proteinase inhibitor-9 (PI-9) and down-regulate granzyme B expression by neighbouring CD8(+) T-cells. We investigated PI-9 expression in lung cancer cell lines, and primary lung cancer cells obtained at curative lung resection from cancer patients with/without chronic obstructive pulmonary disease (COPD). Granzyme B and PI-9 expression was also determined in CD8(+) T-cells from the cancer and non-cancer areas of resected lung tissue and from bronchoalveolar lavage (BAL). We then evaluated the effects of conditioned media from lung cancer cell lines on granzyme B expression and the cytotoxic activity of CD8(+) T-cells. PI-9 was highly expressed in lung cancer cell lines. Increased PI-9 expression was also observed in primary cancer cells vs. epithelial cells from non-cancer tissue or bronchial brushing-derived normal primary large airway epithelial cells. Expression significantly correlated with cancer stage. Significantly reduced granzyme B was noted in CD8(+) T-cells from cancer vs. non-cancer tissue. Granzyme B production by CD8(+) T-cells was reduced in the presence of conditioned media from lung cancer cell lines. Our data suggest that lung cancer cells utilise their increased PI-9 expression to protect from granzyme B-mediated cytotoxicity as an immune evasion mechanism, a function that increases with lung cancer stage.

  5. Lung Cancer Screening

    MedlinePlus

    Lung cancer screening Overview By Mayo Clinic Staff Lung cancer screening is a process that's used to detect the presence ... with a high risk of lung cancer. Lung cancer screening is recommended for older adults who are longtime ...

  6. 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 ...

  7. Familial risk for lung cancer

    PubMed Central

    Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi

    2017-01-01

    Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer. PMID:28356926

  8. Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer.

    PubMed

    Biaoxue, Rong; Xiguang, Cai; Hua, Liu; Tian, Fu; Wenlong, Gao

    2017-03-02

    Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.

  9. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... 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 ...

  10. Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

    PubMed Central

    Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

  11. Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

    PubMed

    Jian, Zhi-Hong; Huang, Jing-Yang; Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively. Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

  12. Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability

    PubMed Central

    Nishioka, T; Luo, L-Y; Shen, L; He, H; Mariyannis, A; Dai, W; Chen, C

    2014-01-01

    Background: Nicotine is able to activate mitogenic signalling pathways, which promote cell growth or survival as well as increase chemoresistance of cancer cells. However, the underlying mechanisms are not fully understood. Methods: In this study, we used immunoblotting and immunoprecipitation methods to test the ubiquitination and degradation of Bcl-2 affected by nicotine in lung cancer cells. Apoptotic assay was also used to measure the antagonising effect of nicotine on cisplatin-mediated cytotoxicity. Results: We demonstrated that the addition of nicotine greatly attenuated Bcl-2 ubiquitination and degradation, which further desensitised lung cancer cells to cisplatin-induced cytotoxicity. In this process, Bcl-2 was persistently phosphorylated in the cells cotreated with nicotine and cisplatin. Furthermore, Akt was proven to be responsible for sustained activation of Bcl-2 by nicotine, which further antagonised cisplatin-mediated apoptotic signalling. Conclusions: Our study suggested that nicotine activates its downstream signalling to interfere with the ubiquitination process and prevent Bcl-2 from being degraded in lung cancer cells, resulting in the increase of chemoresistance. PMID:24548862

  13. Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells

    PubMed Central

    Zhao, Li; Jia, Wenzhi; Yang, Hao; Liu, Liu; Zhou, Xiang; Miao, Ping; Sun, Xiaoguang; Song, Shaoli; Zhao, Xiaoping; Liu, Jianjun; Huang, Gang

    2016-01-01

    The clinical success of EGFR inhibitors in patients with lung cancer is limited by the inevitable development of treatment resistance. Here, we show that inhibition of SREBP increase gefitinib sensitivity in vitro and in vivo. Interference of SREBP1 binding partner MARVELD1 potentiate the therapeutic effect of gefitinib as well. Mechanistically, SREBP inhibition decreases the cell membrane fluidity, results in a decreased tyrosine phosphorylation of EGFR. Therefore, targeting lipid metabolism combined with EGFR-TKIs is potentially a novel therapeutic strategies for cancer treatment. PMID:27447558

  14. Obesity does not increase complications after anatomic resection for non-small cell lung cancer.

    PubMed

    Smith, Philip W; Wang, Hongkun; Gazoni, Leo M; Shen, K Robert; Daniel, Thomas M; Jones, David R

    2007-10-01

    The effect of obesity on complications after resection for lung cancer is unknown. We hypothesized that obesity is associated with increased complications after anatomic resections for non-small cell lung cancer. A review of our prospective general thoracic database identified 499 consecutive anatomic resections for non-small cell lung cancer from November 2002 to May 2006. Body mass index (BMI) was used to group patients as nonobese (BMI > 18.5 to < 30) and obese (BMI > or = 30). Patient characteristics and oncologic and operative variables were compared between groups. Multivariable logistic regression models were fit with BMI included at every level. Outcomes examined included in-hospital morbidity, mortality, length of stay, and readmission. Seventy-five percent (372 of 499) were nonobese, and 25% (127 of 499) were obese. Preoperative variables were similar, except for a greater incidence of diabetes mellitus (p < 0.0001) in the obese group. Overall mortality was 1.4% (7 of 499) and was not different between groups (p = 0.85). Thirty-day readmission rates (p = 0.76) and length of stay (p = 0.30) were similar. Obese patients had a higher incidence of acute renal failure (p = 0.001). A complication occurred in 33% (124 of 372) of nonobese and 31% (39 of 127) of obese patients (p = 0.59). Respiratory complications occurred in 22% (81 of 372) of nonobese and 14% (18 of 127) of obese patients (p = 0.06). Significant predictors of any complication include performance status, diffusing capacity, and tumor stage. Significant predictors of respiratory complications include performance status, diffusing capacity, chronic renal insufficiency, prior thoracic surgery, and chest wall resection. In contrast to our hypothesis, obesity does not increase the incidence of perioperative complications, mortality, or length of stay after anatomic resection for non-small cell lung cancer.

  15. Nutrition for Lung Cancer

    MedlinePlus

    ... by zip code or Select your state State Lung Cancer www.lung.org > Lung Health and Diseases > ... I Stay Healthy Share this page: Nutrition for Lung Cancer Key Points There is no prescribed diet ...

  16. Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer.

    PubMed

    Pine, Sharon R; Mechanic, Leah E; Enewold, Lindsey; Chaturvedi, Anil K; Katki, Hormuzd A; Zheng, Yun-Ling; Bowman, Elise D; Engels, Eric A; Caporaso, Neil E; Harris, Curtis C

    2011-07-20

    Previous studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking. Associations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case-control study. Results were validated in 532 case patients and 595 control subjects in a nested case-control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model. Serum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%). Although increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8 levels are associated with lung cancer risk

  17. Increased Levels of Circulating Interleukin 6, Interleukin 8, C-Reactive Protein, and Risk of Lung Cancer

    PubMed Central

    Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Chaturvedi, Anil K.; Katki, Hormuzd A.; Zheng, Yun-Ling; Bowman, Elise D.; Engels, Eric A.; Caporaso, Neil E.

    2011-01-01

    Background Previous studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking. Methods Associations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case–control study. Results were validated in 532 case patients and 595 control subjects in a nested case–control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model. Results Serum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%). Conclusions Although increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8

  18. Risks of Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  19. Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer

    PubMed Central

    Zeng, Chao; Wu, Da; Mu, Zhimin; Chen, Baokun; Xie, Yuancai; Ye, Yiwang; Liu, Jixian

    2016-01-01

    Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21. PMID:27894084

  20. Nutrition aspects of lung cancer.

    PubMed

    Cranganu, Andreea; Camporeale, Jayne

    2009-12-01

    Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

  1. Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk

    PubMed Central

    Olivo-Marston, Susan E.; Yang, Ping; Mechanic, Leah E.; Bowman, Elise D.; Pine, Sharon R.; Loffredo, Christopher A.; Alberg, Anthony J.; Caporaso, Neil; Shields, Peter G.; Chanock, Stephen; Wu, Yanhong; Jiang, Ruoxiang; Cunningham, Julie; Jen, Jin; Harris, Curtis C.

    2010-01-01

    Background Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. Methods Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. Results In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). Conclusions Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system. PMID:19959685

  2. Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

    PubMed

    Olivo-Marston, Susan E; Yang, Ping; Mechanic, Leah E; Bowman, Elise D; Pine, Sharon R; Loffredo, Christopher A; Alberg, Anthony J; Caporaso, Neil; Shields, Peter G; Chanock, Stephen; Wu, Yanhong; Jiang, Ruoxiang; Cunningham, Julie; Jen, Jin; Harris, Curtis C

    2009-12-01

    Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system.

  3. Increased APOBEC3B Predicts Worse Outcomes in Lung Cancer: A Comprehensive Retrospective Study

    PubMed Central

    Yan, Shumei; He, Fan; Gao, Bei; Wu, Huini; Li, Mei; Huang, Liyun; Liang, Jianzhong; Wu, Qiuliang; Li, Yong

    2016-01-01

    Lung cancer ranks as the most common and lethal malignancy in America and worldwide. APOBEC3B is a newly identified DNA cytosine deaminase, which is supposed to function as a major source of DNA mutation in many different tumors. In this study, we combine the data of online databases and two hundred and twenty-one primary non-small-cell lung carcinoma (NSCLC) specimens from Sun Yat-sen University Cancer Center to investigate, for the first time, the clinical role of APOBEC3B in lung cancer. We found that the APOBEC3 expression was commonly elevated in NSCLC tissues and overexpression of APOBEC3B was correlated with unfavorable prognosis of the patients with NSCLC. Furthermore, APOBEC3B expression was associated with nodal status, TNM staging and adjuvant chemotherapy of the patients with NSCLC. Further research is warranted. PMID:27076842

  4. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  5. Lung cancer screening update

    PubMed Central

    Dhillon, Samjot Singh; Loewen, Gregory; Jayaprakash, Vijayvel; Reid, Mary E.

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer. PMID:23599684

  6. 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

  7. Pulmonary Rehabilitation in Lung Cancer.

    PubMed

    Wang, Hongmei; Liu, Xin; Rice, Shawn J; Belani, Chandra P

    2016-10-01

    Lung cancer remains a challenging disease with high morbidity and mortality despite targeted therapy. Symptom burden related to cancer impairs quality of life and functional status in patients with lung cancer and in survivors. Pulmonary rehabilitation has been recognized as an effective, noninvasive intervention for patients with chronic respiratory disease. It is well established that pulmonary rehabilitation benefits patients with chronic obstruction pulmonary disease through improved exercise capacity and symptoms. Evidence is increasing that the benefit of pulmonary rehabilitation can be applied to patients with lung cancer. Comprehensive pulmonary rehabilitation has made its way as a cornerstone of integrated care for patients with lung cancer.

  8. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

    PubMed Central

    Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-01-01

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib. PMID:26513172

  9. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

    PubMed

    Schellhorn, Melina; Haustein, Maria; Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-11-17

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib.

  10. The expression of p73 is increased in lung cancer, independent of p53 gene alteration

    PubMed Central

    Tokuchi, Y; Hashimoto, T; Kobayashi, Y; Hayashi, M; Nishida, K; Hayashi, S; Imai, K; Nakachi, K; Ishikawa, Y; Nakagawa, K; Kawakami, Y; Tsuchiya, E

    1999-01-01

    p73 gene, a new p53 homologue, has been identified: it supposedly acts as tumour suppressor gene in neuroblastoma. To clarify whether p73 might be involved in lung carcinogenesis, we examined p73 expression in resected lung cancer and paired normal lung in 60 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We also examined p73 gene status in three representative cases using Southern blot, and p53 gene alteration in 49 cases using PCR-single-strand conformation polymorphism (PCR-SSCP) and direct sequence. In 87% of the cases (52/60) p73 expression in tumour was more than twice as high as that in paired normal lung tissues, and the difference between p73 expression in tumour and normal lung tissue was significant (P < 0.0001). However, Southern blot analysis revealed that none of the cases showed p73 gene amplification. Compared with clinicopathological characteristics, p73 expression correlates significantly with histological differences and age of patient, independently (P < 0.05). Concerning p53 gene status, 43% (21/49) showed p53 gene alteration, but there was no correlation between p73 overexpression and p53 gene alteration. Our results suggest that need for further functional analysis of the role of p73 in lung carcinogenesis. © 1999 Cancer Research Campaign PMID:10408409

  11. Enzymatic MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk

    PubMed Central

    Leitner-Dagan, Yael; Sevilya, Ziv; Pinchev, Mila; Kremer, Ran; Elinger, Dalia; Rennert, Hedy S.; Schechtman, Edna; Freedman, Laurence; Rennert, Gad; Paz-Elizur, Tamar

    2014-01-01

    DNA repair is a major mechanism for minimizing mutations and reducing cancer risk. Here, we present the development of reproducible and specific enzymatic assays for methylpurine DNA glycosylase (MPG) repairing the oxidative lesions 1,N6-ethenoadenine (εA) and hypoxanthine (Hx) in peripheral blood mononuclear cells protein extracts. Association of these DNA repair activities with lung cancer was determined using conditional logistic regression with specimens from a population-based case–control study with 96 lung cancer cases and 96 matched control subjects. The mean MPG-εA in case patients was 15.8 units/μg protein (95% CI 15.3–16.3), significantly higher than in control subjects—15.1 (14.6–15.5), *P = 0.011. The adjusted odds ratio for lung cancer associated with a one SD increase in MPG-εA activity (2.48 units) was significantly bigger than 1 (OR = 1.6, 95% CI = 1.1–2.4; *P = 0.013). When activity of OGG1, a different DNA repair enzyme for oxidative damage, was included in the model, the estimated odds ratio/SD for a combined MPG-εA-OGG1 score was 2.6 (95% CI 1.6–4.2) *P = 0.0001, higher than the odds ratio for each single assay. The MPG enzyme activity assays described provide robust functional risk biomarkers, with increased MPG-εA activity being associated with increased lung cancer risk, similar to the behavior of MPG-Hx. This underscores the notion that imbalances in DNA repair, including high DNA repair, usually perceived as beneficial, can cause cancer risk. Such DNA repair risk biomarkers may be useful for risk assessment of lung cancer and perhaps other cancer types, and for early detection techniques such as low-dose CT. PMID:25355292

  12. Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

    PubMed

    Haustein, Maria; Ramer, Robert; Linnebacher, Michael; Manda, Katrin; Hinz, Burkhard

    2014-11-15

    Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine-activated killer (LAK) cells and LAK cell-mediated cytotoxicity. Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently be lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody. Increased cancer cell lysis by CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to transient receptor potential vanilloid 1. In addition, enhanced killing of CBD-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC) and R(+)-methanandamide (MA), a hydrolysis-stable endocannabinoid analogue. Finally, each cannabinoid elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less pronounced (CBD, THC) or absent (MA) ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of cannabinoids. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Downregulation of miR-21 increases cisplatin sensitivity of non-small-cell lung cancer.

    PubMed

    Xu, Liyun; Huang, Yanyan; Chen, Dongdong; He, Jianying; Zhu, Wangyu; Zhang, Yongkui; Liu, Xiaoguang

    2014-05-01

    Recent studies have shown that plasma miR-21 is a biomarker of chemotherapeutic response in lung cancer, but the influence of miR-21 on the sensitivity of non-small-cell lung cancer (NSCLC) to cisplatin (DDP) has not been confirmed. The aim of this study was to evaluate the role of miR-21 in NSCLC sensitivity to DDP in vitro and in vivo. Real-time quantitative PCR was used to detect miR-21 expression in lung cancer cell lines. Synthesized locked nucleic acid (LNA) anti-miR-21 was transiently transfected into A549 cells and pre-miR-21 was transfected into SK-MES-1 cells. We also investigated the effects of miR-21 downregulation and upregulation on growth and colony formation in DDP-treated cells. Finally, the effect of miR-21 downregulation on in vivo sensitivity of A549 cells to DDP was determined in BALB/c nude mice. miR-21 expression was significantly higher in A549 than in other lung cancer cell lines. LNA-based knockdown of miR-21 significantly inhibited growth and induced death in A549 cells, possibly via apoptotic signaling. Pre-miR-21 significantly promoted growth and inhibited death in SK-MES-1 cells. Moreover, ectopic suppression of miR-21 sensitized A549 cells to DDP in vivo. Our findings demonstrate that miR-21 suppression enhances the sensitivity of lung cancer cells to DDP in vitro and in vivo.

  14. The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer

    PubMed Central

    Moreno, Paula; Lara-Chica, Maribel; Soler-Torronteras, Rafael; Caro, Teresa; Medina, Manuel; Álvarez, Antonio; Salvatierra, Ángel; Muñoz, Eduardo; Calzado, Marco A.

    2015-01-01

    Objectives Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH) proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry) in human non-small cell lung cancer (NSCLC) samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features. Materials and Methods One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables. Results The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry) in non-small cell lung cancer (NSCLC). We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC) and squamous cell lung cancer (SCC). Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(18F)fluoro-D-glucose) uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates

  15. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

    PubMed Central

    Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

    2009-01-01

    We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 µM) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was: control 100%; 1 µM vorinostat 83% ± 10%; 5 µM carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat 46% ± 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (a DNA damage marker) and increased α-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in α-tubulin acetylation, which reversed upon drug wash-out. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel. PMID:19621389

  16. Less Efficient G2-M Checkpoint Is Associated with an Increased Risk of Lung Cancer in African Americans

    PubMed Central

    Zheng, Yun-Ling; Loffredo, Christopher A.; Alberg, Anthony J.; Yu, Zhipeng; Jones, Raymond T.; Perlmutter, Donna; Enewold, Lindsey; Krasna, Mark J.; Yung, Rex; Shields, Peter G.; Harris, Curtis C.

    2006-01-01

    Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non–small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of γ-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy γ-radiation, and harvested at 3 hours after γ-radiation treatment. γ-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in γ-radiation-treated cultures from the same subject. The mean percentage of γ-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of γ-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97–5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (Ptrend = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98–14.3). This trend was most apparent among African American females (Ptrend < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47–94.04). The results suggest that a less-efficient DNA damage–induced G2-M checkpoint is associated with an increased risk of lung cancer among African

  17. Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

    PubMed

    Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

    2014-08-01

    From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. ©2014 American Association for Cancer Research.

  18. [Asbestos-related lung cancer].

    PubMed

    Lotti, M

    2010-01-01

    Lung cancer is the leading cause of tumour death and a large percentage of it is associated with tobacco smoking. Epidemiology has shown that asbestos cumulative exposures increase the risk of lung cancer to a variable extent, depending on the manufacturing process and the specific job. The risk appears relatively small (< or = 2) and is detectable after massive exposures only. Clinical diagnosis of asbestos-related lung cancer is based upon medical history (exposures > 25 ff.ml years double the risk), possible lung fibrosis and counts of asbestos bodies and fibers in bronchoalveolar lavage and lung tissues. Pleural plaques do not correlate with the cumulative exposures that are associated with lung cancer. The multiplicative interaction between smoke and asbestos is only detectable when the risk associated with asbestos exposure is increased, i.e. after high exposures.

  19. Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer

    PubMed Central

    Al Omar, Suliman Y; Marshall, Ernie; Middleton, Derek; Christmas, Stephen E

    2011-01-01

    Frequencies of natural killer (NK) cells from patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) did not differ from healthy controls. A higher proportion of NK cells from NSCLC patients expressed the killer immunoglobulin-like receptor (KIR) CD158b than in controls (P = 0·0004), in the presence or absence of its ligand, HLA-C1. A similar result was obtained for CD158e in the presence of its ligand HLA-Bw4 in NSCLC patients (P = 0·003); this was entirely attributable to the Bw4I group of alleles in the presence of which a fivefold higher percentage of CD158e+ NK cells was found in NSCLC patients than controls. Proportions of CD158b+ NK cells declined with advancing disease in NSCLC patients. Expression of NKp46, CD25 and perforin A, and production of interferon-γ following stimulation with interleukin-12 and interleukin-18, were all significantly lower in NK cells from NSCLC patients than in controls. Both NK cell cytotoxicity and granzyme B expression were also reduced in lung cancer patients. Increased inhibitory KIR expression would decrease NK cell cytotoxic function against tumour cells retaining class I HLA expression. Furthermore, the reduced ability to produce interferon-γ would restrict the ability of NK cells to stimulate T-cell responses in patients with lung cancer. PMID:21342183

  20. Chemoprevention of Lung Cancer

    PubMed Central

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  1. [Lung cancer screening].

    PubMed

    Sánchez González, M

    2014-01-01

    Lung cancer is a very important disease, curable in early stages. There have been trials trying to show the utility of chest x-ray or computed tomography in Lung Cancer Screening for decades. In 2011, National Lung Screening Trial results were published, showing a 20% reduction in lung cancer mortality in patients with low dose computed tomography screened for three years. These results are very promising and several scientific societies have included lung cancer screening in their guidelines. Nevertheless we have to be aware of lung cancer screening risks, such as: overdiagnosis, radiation and false positive results. Moreover, there are many issues to be solved, including choosing the appropriate group to be screened, the duration of the screening program, intervals between screening and its cost-effectiveness. Ongoing trials will probably answer some of these questions. This article reviews the current evidence on lung cancer screening.

  2. Increased Risk of Lung Cancer Associated with a Functionally Impaired Polymorphic Variant of the Human DNA Glycosylase NEIL2

    PubMed Central

    Dey, Sanjib; Maiti, Amit K; Hegde, Muralidhar L; Hegde, Pavana M; Boldogh, Istvan; Sarkar, Partha S; Abdel-Rahman, Sherif Z; Sarker, Altaf H.; Hang, Bo; Xie, Jingwu; Tomkinson, Alan E; Zhou, Mian; Shen, Binghui; Wang, Guanghai; Wu, Chen; Yu, Dianke; Lin, Dongxin; Cardenas, Victor; Hazra, Tapas K

    2012-01-01

    Human NEIL2, one of five oxidized base-specific DNA glycosylases, is unique in preferentially repairing oxidative damage in transcribed genes. Here we show that depletion of NEIL2 causes a 6- to 7-fold increase in spontaneous mutation frequency in the HPRT gene of the V79 Chinese hamster lung cell line. This prompted us to screen for NEIL2 variants in lung cancer patients’ genomic DNA. We identified several polymorphic variants, among which R103Q and R257L were frequently observed in lung cancer patients. We then characterized these variants biochemically, and observed a modest decrease in DNA glycosylase activity relative to the wild type (WT) only with the R257L mutant protein. However, in reconstituted repair assays containing WT NEIL2 or its R257L and R103Q variants together with other DNA base excision repair (BER) proteins (PNKP, Polβ, Lig IIIα and XRCC1) or using NEIL2-FLAG immunocomplexes, an ~ 5-fold decrease in repair was observed with the R257L variant compared to WT or R103Q NEIL2, apparently due to the R257L mutant’s lower affinity for other repair proteins, particularly Polβ. Notably, increased endogenous DNA damage was observed in NEIL2 variant (R257L)-expressing cells relative to WT cells. Taken together, our results suggest that the decreased DNA repair capacity of the R257L variant can induce mutations that lead to lung cancer development. PMID:22497777

  3. Acquired tumor cell resistance to sunitinib by increased invasion and epithelial-mesenchymal transition in LL/2 murine lung cancer.

    PubMed

    Du, Yang; Liu, Jia-Qi; Tang, Jie; Ge, Jun; Chen, Ye; Cheng, Ke; Ding, Jing; Li, Zhi-Ke; Liu, Ji-Yan

    2017-09-15

    This study aims to investigate biological behavior changes in a murine lung cancer cell characterized by acquired resistance to sunitinib, a potent inhibitor of multiple-targeted receptor tyrosine kinase. A lung cancer cell line resistant to sunitinib (LL/2-R) was developed from its parental cell line (LL/2-P). Differences in biological characteristics and associated molecular profiles between these two cells were compared in vitro and in vivo. LL/2-R cells showed an approximately 5-fold higher IC50 of sunitinib than LL/2-P cells and exhibited a reduced growth inhibition following sunitinib treatment compared with LL/2-P. In LL/2-R cells and tumors, increased migration, invasion and metastasis were observed, along with upregulation of MMP-2 and MMP-9. We also analyzed the molecular profiles involved in EMT, and found that E-cadherin was downregulated in LL/2-R tumors, and vimentin was upregulated in LL/2-R cells and tumors, along with β-catenin translocating to the nuclei in LL/2-R cells. Furthermore, transcriptional factors mediated EMT, snail and twist, and the secretion of TGFβ1 also increased in LL/2-R cells and tumors. We established a sunitinib-resistant lung cancer cell line and confirmed its drug-resistance to sunitinib in vivo. Our results implied that increased invasion and EMT may associate with the acquisition of resistant phenotype to sunitinib in cancer cells.

  4. Lung cancer in Brazil.

    PubMed

    Algranti, E; Menezes, A M; Achutti, A C

    2001-04-01

    Lung cancer is the second leading cause of death in Brazil, after exclusion of external causes. Registries in the country are not reliable because of under-registration and limited coverage. Incidence rates for Brazil are less then half those for selected areas with good registries. Crude and adjusted incidence and mortality rates for lung cancer are rising, particularly among women. The main reason is the acceleration in tobacco consumption and the spread of smoking among women. At present, approximately 40% of men and 25% of women, 15 years of age or older, are current smokers. In the state of Rio Grande do Sul, where registries are reliable, incidence and mortality for males are similar to US data and the figures for women are rapidly approaching those for men. Occupations associated with risks of exposure to respiratory carcinogens show a rise in the incidence of lung cancer in the industrialized area of São Paulo. The main occupational risk in Brazil is exposure to mineral dusts, silica, or asbestos. Although about 15 million Brazilians are exposed to pesticides, agricultural workers were not a risk group for lung cancer in a case-control study. Pesticides containing arsenic and dichlorodiphenyltrichloroethane (DDT) are banned. In recent years, a trend towards a decrease in male smoking has been noted, but there is still a high tobacco exposure burden in both males and females, with a forecast of a further increase in rates of lung cancer incidence and deaths. Control of respiratory carcinogens at work continues to be a problem, particularly in the present scenario of economic and political pressures on Brazil and other developing nations. Semin Oncol 28:143-152. Copyright 2001 by W.B. Saunders Company.

  5. Second lung cancers in patients successfully treated for lung cancer.

    PubMed

    Johnson, B E; Cortazar, P; Chute, J P

    1997-08-01

    The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.

  6. 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

  7. Enzymatic MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk.

    PubMed

    Leitner-Dagan, Yael; Sevilya, Ziv; Pinchev, Mila; Kremer, Ran; Elinger, Dalia; Rennert, Hedy S; Schechtman, Edna; Freedman, Laurence; Rennert, Gad; Livneh, Zvi; Paz-Elizur, Tamar

    2014-12-01

    DNA repair is a major mechanism for minimizing mutations and reducing cancer risk. Here, we present the development of reproducible and specific enzymatic assays for methylpurine DNA glycosylase (MPG) repairing the oxidative lesions 1,N6-ethenoadenine (εA) and hypoxanthine (Hx) in peripheral blood mononuclear cells protein extracts. Association of these DNA repair activities with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean MPG-εA in case patients was 15.8 units/μg protein (95% CI 15.3-16.3), significantly higher than in control subjects-15.1 (14.6-15.5), *P = 0.011. The adjusted odds ratio for lung cancer associated with a one SD increase in MPG-εA activity (2.48 units) was significantly bigger than 1 (OR = 1.6, 95% CI = 1.1-2.4; *P = 0.013). When activity of OGG1, a different DNA repair enzyme for oxidative damage, was included in the model, the estimated odds ratio/SD for a combined MPG-εA-OGG1 score was 2.6 (95% CI 1.6-4.2) *P = 0.0001, higher than the odds ratio for each single assay. The MPG enzyme activity assays described provide robust functional risk biomarkers, with increased MPG-εA activity being associated with increased lung cancer risk, similar to the behavior of MPG-Hx. This underscores the notion that imbalances in DNA repair, including high DNA repair, usually perceived as beneficial, can cause cancer risk. Such DNA repair risk biomarkers may be useful for risk assessment of lung cancer and perhaps other cancer types, and for early detection techniques such as low-dose CT. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Antiangiogenic therapy using endostatin increases the number of ALDH+ lung cancer stem cells by generating intratumor hypoxia

    PubMed Central

    Yu, Yang; Wang, Yu-yi; Wang, Yi-qin; Wang, Xia; Liu, Yan-Yang; Wang, Jian-Tao; Du, Chi; Wang, Li; Li, Mei; Luo, Feng; Jiang, Ming

    2016-01-01

    Antiangiogenic therapy is becoming a promising option for cancer treatment. However, many investigations have recently indicated that these therapies may have limited efficacy, and the cancers in most patients eventually develop resistance to these therapies. There is considerable recently acquired evidence for an association of such resistance with cancer stem-like cells (CSLCs). Here, we used xenograft tumor murine models to further suggest that antiangiogenic agents actually increase the invasive and metastatic properties of lung cancer cells. In our experiments with murine lung cancer xenografts, we found that the antiangiogenic agent endostatin increased the population of ALDH+ cells, and did so by generating intratumoral hypoxia in the xenografts. We further showed endostatin to cause an increase in the CSLC population by accelerating the generation of tumor hypoxia and by recruiting TAMs, MDSCs and Treg cells, which are inflammatory and immunosuppressive cells and which can secrete cytokines and growth factors such as IL-6, EGF, and TGF-β into the tumor microenvironment. All these factors are related with increased CSLC population in tumors. These results imply that improving the clinical efficacy of antiangiogenic treatments will require the concurrent use of CSLC-targeting agents. PMID:27703219

  9. PARP inhibition selectively increases sensitivity to cisplatin in ERCC1-low non-small cell lung cancer cells

    PubMed Central

    Halmos, Balazs

    2013-01-01

    Platinum compounds are the foundation of chemotherapy regimens for non-small cell lung cancer (NSCLC) despite poor response rates and limited response duration. It has been reported that tumor expression of excision repair cross-complementation group 1 (ERCC1), a key component in nucleotide excision repair, may correlate with clinical response to platinum agents. We found that most primary lung tumor specimens demonstrated a stronger protein expression of poly (adenosine diphosphate ribose) polymerases 1 (PARP1) than their normal counterparts. Therefore, we hypothesized that combining PARP inhibition with platinum compounds may be an approach to improve platinum-based therapy for NSCLC. Drug combination experiments revealed that two distinct PARP inhibitors, olaparib and veliparib, not only potentiated the cell killing by cisplatin but also conferred cytotoxicity as a single agent specifically in ERCC1-low HCC827 and PC9 but not in ERCC1-high A549 and H157 lung cancer cells. Moreover, small interfering RNA knockdown of ERCC1 in A549 and H157 cells increased their sensitivities to both cisplatin and olaparib in a synergistic manner in our model. Furthermore, mechanistic studies indicated that combined PARP inhibitor and cisplatin could lead to sustained DNA double-strand breaks, prolonged G2/M cell cycle arrest with distinct activation of checkpoint kinase 1 signaling and more pronounced apoptosis preferentially in lung cancer cells with low ERCC1 expression. Collectively, these data suggest that there is a synergistic relationship between PARP inhibition and low ERCC1 expression in NSCLC that could be exploited for novel therapeutic approaches in lung cancer therapy based on tumor ERCC1 expression. PMID:23275151

  10. Increased cytosine DNA-methyltransferase activity is target-cell-specific and an early event in lung cancer.

    PubMed Central

    Belinsky, S A; Nikula, K J; Baylin, S B; Issa, J P

    1996-01-01

    The association between increased DNA-methyltransferase (DNA-MTase) activity and tumor development suggest a fundamental role for this enzyme in the initiation and progression of cancer. A true functional role for DNA-MTase in the neoplastic process would be further substantiated if the target cells affected by the initiating carcinogen exhibit changes in enzyme activity. This hypothesis was addressed by examining DNA-MTase activity in alveolar type II (target) and Clara (nontarget) cells from A/J and C3H mice that exhibit high and low susceptibility, respectively, for lung tumor formation. Increased DNA-MTase activity was found only in the target alveolar type II cells of the susceptible A/J mouse and caused a marked increase in overall DNA methylation in these cells. Both DNA-MTase and DNA methylation changes were detected 7 days after carcinogen exposure and, thus, were early events in neoplastic evolution. Increased gene expression was also detected by RNA in situ hybridization in hypertrophic alveolar type II cells of carcinogen-treated A/J mice, indicating that elevated levels of expression may be a biomarker for premalignancy. Enzyme activity increased incrementally during lung cancer progression and coincided with increased expression of the DNA-MTase activity are strongly associated with neoplastic development and constitute a key step in carcinogenesis. The detection of premalignant lung disease through increased DNA-MTase expression and the possibility of blocking the deleterious effects of this change with specific inhibitors will offer new intervention strategies for lung cancer. Images Fig. 2 PMID:8633014

  11. Increased FLI-1 Expression is Associated With Poor Prognosis in Non-Small Cell Lung Cancers.

    PubMed

    Lin, Shiou-Fu; Wu, Chun-Chieh; Chai, Chee-Yin

    2016-09-01

    Friend leukemia integration-1 (FLI-1) antibody, a commercially available antibody directed against the C-terminus of FLI-1 protein-binding domain, has been used as a useful tool in the differential diagnosis of small blue round cell tumors and vascular neoplasms, but shows inconsistent expression in lung cancers. The aims of this study were to evaluate FLI-1 immunohistochemical expression in non-small cell lung cancer (NSCLC), and its relationships between the clinicopathologic parameters and prognosis. We investigated the FLI-1 expression in 108 cases of NSCLC by using multiple tumor microarrays. Correlations between the FLI-1 expression and clinicopathologic parameters and prognostic significance were analyzed. The effect of FLI-1 expression on survival is estimated by Kaplan-Meier survival analysis and Cox proportional hazards models. Our results revealed that patients with high FLI-1 expression had shorter overall survival (P=0.014) than those with low FLI-1 expression. In multivariate analysis, FLI-1 was confirmed as an independent poor prognostic factor in NSCLC (overall survival: hazard ratio, 7.292; 95% confidence interval, 0.294-0.823; P=0.007). In conclusion, this study shows that FLI-1 is expressed variably in different subtypes of NSCLC, and its expression is related to clinicopathologic parameters and poorer prognosis. However, further studies are required to elucidate its function in tumorigenesis of NSCLC.

  12. 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.

  13. 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 ...

  14. Lung cancer in women

    PubMed Central

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

  15. Immunotherapy in Lung Cancer.

    PubMed

    Du, Lingling; Herbst, Roy S; Morgensztern, Daniel

    2017-02-01

    The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab. Because only a minority of patients benefit from this class of drugs, there has been an intense search for biomarkers.

  16. Lung cancer among Chinese women.

    PubMed

    Gao, Y T; Blot, W J; Zheng, W; Ershow, A G; Hsu, C W; Levin, L I; Zhang, R; Fraumeni, J F

    1987-11-15

    A case-control study involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smoking was a strong risk factor, but accounted for only about one-fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also reported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

  17. Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults after Exposure to Arsenic in Utero and in Early Childhood

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Liaw, Jane; von Ehrenstein, Ondine; Steinmaus, Craig; Bates, Michael N.; Selvin, Steve

    2006-01-01

    Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989–2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30–49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950–1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4–8.9; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3–31.7; p < 0.001). For those born during the high-exposure period (1958–1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5–9.9; p < 0.001) for lung cancer and 46.2 (95% CI, 21.1–87.7; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease. PMID:16882542

  18. Justice and lung cancer.

    PubMed

    Wilson, Aaron

    2013-04-01

    Lung cancer is the leading cause of cancer deaths, yet research funding is by far the lowest for lung cancer than for any other cancer compared with respective death rates. Although this discrepancy should appear alarming, one could argue that lung cancer deserves less attention because it is more attributable to poor life choices than other common cancers. Accordingly, the general question that I ask in this article is whether victims of more avoidable diseases, such as lung cancer, deserve to have their needs taken into less consideration than those of less avoidable diseases, on the grounds of either retributive or distributive justice. Such unequal treatment may be the "penalty" one incurs for negligent or reckless behavior. However, I hope to show that such unequal treatment cannot be supported by any coherent accounts of retributive or distributive justice.

  19. Immunotherapy in Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-01-01

    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  20. Increased Lung and Bladder Cancer Incidence In Adults After In Utero and Early-Life Arsenic Exposure

    PubMed Central

    Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

    2014-01-01

    Background From 1958–70, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes including lung and bladder cancer. Methods We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007–2010, and 508 age and gender-matched controls. Results Odds ratios (ORs) adjusted for age, sex, and smoking in those only exposed in early-life to arsenic water concentrations of ≤110, 110–800, and >800 μg/L were 1.00, 1.88 (95% confidence interval (CI), 0.96–3.71), and 5.24 (3.05–9.00) (p-trend<0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25) (p-trend<0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures which started 49–52 years before, and ended 37–40 years before the cancer cases were diagnosed. Conclusion Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early-life, even up to 40 years after high exposures ceased. Findings like these have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Impact Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. PMID:24859871

  1. 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.

  2. Lung Cancer Screening.

    PubMed

    Hoffman, Richard M; Sanchez, Rolando

    2017-07-01

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

  3. Lung cancer and tobacco smoking.

    PubMed

    Boyle, P; Maisonneuve, P

    1995-06-01

    The dominant role of tobacco smoking in the causation of lung cancer has been repeatedly demonstrated over the past 50 years. Current lung cancer rates reflect cigarette smoking habits of men and women in the past decades, but not necessarily current smoking patterns, since there is an interval of several decades between the change in smoking habits in a population and its consequences on lung cancer rates. Over 90% of lung cancer may be avoidable simply through avoidance of cigarette smoking. There is at present a huge premature loss of life world-wide caused by smoking. Rates of lung cancer present in central and eastern Europe at the present time are higher than those ever before recorded elsewhere; lung cancer has increased 10-fold in men and eightfold in women in Japan since 1950. There is a world-wide epidemic of smoking among young women which will be translated into increasing rates of tobacco-related disease, including cancer, in the coming decades. There is another epidemic of lung cancer and tobacco-related deaths building up in China as the cohorts of men in whom tobacco smoking became popular reach ages where cancer is an important hazard. Many solutions have been attempted to reduce cigarette smoking and increasingly many countries are enacting legislation to curb this habit. Cigarette smoking remains the number one target for Public Health action aimed at reducing cancer risk in the general population. General practitioners, hospital physicians and everyone working in oncology have a particularly important exemplary role to play in this process.

  4. Lung cancer screening.

    PubMed

    Tanoue, Lynn T; Tanner, Nichole T; Gould, Michael K; Silvestri, Gerard A

    2015-01-01

    The United States Preventive Services Task Force recommends lung cancer screening with low-dose computed tomography (LDCT) in adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit within the past 15 years. This recommendation is largely based on the findings of the National Lung Screening Trial. Both policy-level and clinical decision-making about LDCT screening must consider the potential benefits of screening (reduced mortality from lung cancer) and possible harms. Effective screening requires an appreciation that screening should be limited to individuals at high risk of death from lung cancer, and that the risk of harm related to false positive findings, overdiagnosis, and unnecessary invasive testing is real. A comprehensive understanding of these aspects of screening will inform appropriate implementation, with the objective that an evidence-based and systematic approach to screening will help to reduce the enormous mortality burden of lung cancer.

  5. Increased expression of differentiation markers can accompany laminin-induced attachment of small cell lung cancer cells.

    PubMed Central

    Giaccone, G.; Broers, J.; Jensen, S.; Fridman, R. I.; Linnoila, R.; Gazdar, A. F.

    1992-01-01

    We investigated the interaction between human lung cancer cells, laminin, and several differentiating agents. When grown on laminin coated substrate eight out of 11 small cell lung cancer (SCLC) cell lines exhibited attachment to laminin and three had extensive outgrowth of long neurite-like processes. Of seven non-small cell lung cancer cell lines, selected for their in vitro anchorage-independent growth, attachment was observed in only three cell lines, and process formation was far less extensive than in SCLC cell lines. Among several differentiating agents, only dcAMP, which alone induced attachment and some process formation, increased laminin-mediated attachment and process formation of two SCLC cell lines, NCI-N417 a variant cell line, and NCI-H345, a classic cell line. The expression of several neuroendocrine and neuronal markers was investigated in these two SCLC cell lines. The expression of the light subunit of neurofilaments increased in NCI-N417 within 3 to 4 days of seeding, while NCI-H345 exhibited approximately 5 fold increase in expression of the GRP gene and a 3 fold increase expression of the beta-actin gene. The expression of a number of other neuroendocrine and neuronal markers did not change following growth on laminin. The doubling times remained unchanged independent of the presence of and attachment to laminin while topoisomerase II gene expression levels in NCI-N417 cells decreased approximately 5 fold when cells were growing on laminin. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1325826

  6. Increased Lung Cancer Mortality in Taconite Mining: The Potential for Disease from Elongate Mineral Particle Exposure.

    PubMed

    Mandel, Jeffrey H; Ramachandran, Gurumurthy; Alexander, Bruce H

    2016-02-15

    Taconite mining involves potential exposure to non-asbestiform amphibole mineral fiber. More recent studies have demonstrated increased mortality from respiratory cancers and heart disease among workers in the taconite industry. This finding is not consistent with recent exposure assessment findings, nor is the toxicology of this mineral suggestive of neoplastic disease. The understanding of respiratory disease in taconite mining is hampered by the lack of exposure data to asbestiform mineral fibers that occurred in the 1950s and 1960s. Other industries with similar mineral exposure have not demonstrated definitive associations with respiratory cancer, although non-malignant respiratory disease is a consistent finding in epidemiological studies.

  7. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.

    PubMed

    Machiela, Mitchell J; Hsiung, Chao Agnes; Shu, Xiao-Ou; Seow, Wei Jie; Wang, Zhaoming; Matsuo, Keitaro; Hong, Yun-Chul; Seow, Adeline; Wu, Chen; Hosgood, H Dean; Chen, Kexin; Wang, Jiu-Cun; Wen, Wanqing; Cawthon, Richard; Chatterjee, Nilanjan; Hu, Wei; Caporaso, Neil E; Park, Jae Yong; Chen, Chien-Jen; Kim, Yeul Hong; Kim, Young Tae; Landi, Maria Teresa; Shen, Hongbing; Lawrence, Charles; Burdett, Laurie; Yeager, Meredith; Chang, I-Shou; Mitsudomi, Tetsuya; Kim, Hee Nam; Chang, Gee-Chen; Bassig, Bryan A; Tucker, Margaret; Wei, Fusheng; Yin, Zhihua; An, She-Juan; Qian, Biyun; Lee, Victor Ho Fun; Lu, Daru; Liu, Jianjun; Jeon, Hyo-Sung; Hsiao, Chin-Fu; Sung, Jae Sook; Kim, Jin Hee; Gao, Yu-Tang; Tsai, Ying-Huang; Jung, Yoo Jin; Guo, Huan; Hu, Zhibin; Hutchinson, Amy; Wang, Wen-Chang; Klein, Robert J; Chung, Charles C; Oh, In-Jae; Chen, Kuan-Yu; Berndt, Sonja I; Wu, Wei; Chang, Jiang; Zhang, Xu-Chao; Huang, Ming-Shyan; Zheng, Hong; Wang, Junwen; Zhao, Xueying; Li, Yuqing; Choi, Jin Eun; Su, Wu-Chou; Park, Kyong Hwa; Sung, Sook Whan; Chen, Yuh-Min; Liu, Li; Kang, Chang Hyun; Hu, Lingmin; Chen, Chung-Hsing; Pao, William; Kim, Young-Chul; Yang, Tsung-Ying; Xu, Jun; Guan, Peng; Tan, Wen; Su, Jian; Wang, Chih-Liang; Li, Haixin; Sihoe, Alan Dart Loon; Zhao, Zhenhong; Chen, Ying; Choi, Yi Young; Hung, Jen-Yu; Kim, Jun Suk; Yoon, Ho-Il; Cai, Qiuyin; Lin, Chien-Chung; Park, In Kyu; Xu, Ping; Dong, Jing; Kim, Christopher; He, Qincheng; Perng, Reury-Perng; Kohno, Takashi; Kweon, Sun-Seog; Chen, Chih-Yi; Vermeulen, Roel C H; Wu, Junjie; Lim, Wei-Yen; Chen, Kun-Chieh; Chow, Wong-Ho; Ji, Bu-Tian; Chan, John K C; Chu, Minjie; Li, Yao-Jen; Yokota, Jun; Li, Jihua; Chen, Hongyan; Xiang, Yong-Bing; Yu, Chong-Jen; Kunitoh, Hideo; Wu, Guoping; Jin, Li; Lo, Yen-Li; Shiraishi, Kouya; Chen, Ying-Hsiang; Lin, Hsien-Chih; Wu, Tangchun; Wong, Maria Pik; Wu, Yi-Long; Yang, Pan-Chyr; Zhou, Baosen; Shin, Min-Ho; Fraumeni, Joseph F; Zheng, Wei; Lin, Dongxin; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

    2015-07-15

    Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

  8. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the Female Lung Cancer Consortium in Asia

    PubMed Central

    Machiela, Mitchell J; Hsiung, Chao Agnes; Shu, Xiao-Ou; Seow, Wei Jie; Wang, Zhaoming; Matsuo, Keitaro; Hong, Yun-Chul; Seow, Adeline; Wu, Chen; Hosgood, H Dean; Chen, Kexin; Wang, Jiu-Cun; Wen, Wanqing; Cawthon, Richard; Chatterjee, Nilanjan; Hu, Wei; Caporaso, Neil E; Park, Jae Yong; Chen, Chien-Jen; Kim, Yeul Hong; Kim, Young Tae; Landi, Maria Teresa; Shen, Hongbing; Lawrence, Charles; Burdett, Laurie; Yeager, Meredith; Chang, I-Shou; Mitsudomi, Tetsuya; Kim, Hee Nam; Chang, Gee-Chen; Bassig, Bryan A; Tucker, Margaret; Wei, Fusheng; Yin, Zhihua; An, She-Juan; Qian, Biyun; Lee, Victor Ho Fun; Lu, Daru; Liu, Jianjun; Jeon, Hyo-Sung; Hsiao, Chin-Fu; Sung, Jae Sook; Kim, Jin Hee; Gao, Yu-Tang; Tsai, Ying-Huang; Jung, Yoo Jin; Guo, Huan; Hu, Zhibin; Hutchinson, Amy; Wang, Wen-Chang; Klein, Robert J; Chung, Charles C; Oh, In-Jae; Chen, Kuan-Yu; Berndt, Sonja I; Wu, Wei; Chang, Jiang; Zhang, Xu-Chao; Huang, Ming-Shyan; Zheng, Hong; Wang, Junwen; Zhao, Xueying; Li, Yuqing; Choi, Jin Eun; Su, Wu-Chou; Park, Kyong Hwa; Sung, Sook Whan; Chen, Yuh-Min; Liu, Li; Kang, Chang Hyun; Hu, Lingmin; Chen, Chung-Hsing; Pao, William; Kim, Young-Chul; Yang, Tsung-Ying; Xu, Jun; Guan, Peng; Tan, Wen; Su, Jian; Wang, Chih-Liang; Li, Haixin; Sihoe, Alan Dart Loon; Zhao, Zhenhong; Chen, Ying; Choi, Yi Young; Hung, Jen-Yu; Kim, Jun Suk; Yoon, Ho-Il; Cai, Qiuyin; Lin, Chien-Chung; Park, In Kyu; Xu, Ping; Dong, Jing; Kim, Christopher; He, Qincheng; Perng, Reury-Perng; Kohno, Takashi; Kweon, Sun-Seog; Chen, Chih-Yi; Vermeulen, Roel C H; Wu, Junjie; Lim, Wei-Yen; Chen, Kun-Chieh; Chow, Wong-Ho; Ji, Bu-Tian; Chan, John K C; Chu, Minjie; Li, Yao-Jen; Yokota, Jun; Li, Jihua; Chen, Hongyan; Xiang, Yong-Bing; Yu, Chong-Jen; Kunitoh, Hideo; Wu, Guoping; Jin, Li; Lo, Yen-Li; Shiraishi, Kouya; Chen, Ying-Hsiang; Lin, Hsien-Chih; Wu, Tangchun; Wong, Maria Pik; Wu, Yi-Long; Yang, Pan-Chyr; Zhou, Baosen; Shin, Min-Ho; Fraumeni, Joseph F; Zheng, Wei; Lin, Dongxin; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

    2016-01-01

    Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women’s Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI=1.34–1.69) for upper vs. lower quartile of the weighted GRS, P-value=4.54×10−14) even after removing rs2736100 (P-value=4.81×10−3), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk. PMID:25516442

  9. Lung Cancer Biomarkers.

    PubMed

    I, Hoseok; Cho, Je-Yoel

    2015-01-01

    Lung cancer is the most frequently occurring cancer in the world and continually leads in mortality among cancers. The overall 5-year survival rate for lung cancer has risen only 4% (from 12% to 16%) over the past 4 decades, and late diagnosis is a major obstacle in improving lung cancer prognosis. Survival of patients undergoing lung resection is greater than 80%, suggesting that early detection and diagnosis of cancers before they become inoperable and lethal will greatly improve mortality. Lung cancer biomarkers can be used for screening, detection, diagnosis, prognosis, prediction, stratification, therapy response monitoring, and so on. This review focuses on noninvasive diagnostic and prognostic biomarkers. For that purpose, our discussion in this review will focus on biological fluid-based biomarkers. The body fluids include blood (serum or plasma), sputum, saliva, BAL, pleural effusion, and VOC. Since it is rich in different cellular and molecular elements and is one of the most convenient and routine clinical procedures, serum or plasma is the main source for the development and validation of many noninvasive biomarkers. In terms of molecular aspects, the most widely validated ones are proteins, some of which are used in the clinical sector, though in limited accessory purposes. We will also discuss the lung cancer (protein) biomarkers in clinical trials and currently in the validation phase with hundreds of samples. After proteins, we will discuss microRNAs, methylated DNA, and circulating tumor cells, which are being vigorously developed and validated as potential lung cancer biomarkers. The main aim of this review is to provide researchers and clinicians with an understanding of the potential noninvasive lung cancer biomarkers in biological fluids that have recently been discovered.

  10. Increased ZO-1 expression predicts valuable prognosis in non-small cell lung cancer

    PubMed Central

    Ni, Songshi; Xu, Liqin; Huang, Jianfei; Feng, Jian; Zhu, Huijun; Wang, Gui; Wang, Xudong

    2013-01-01

    Objective: The aim of this study was to investigate the expression of Zonula Occludens-1 (ZO-1) and its potential value as prognostic indicator of survival in patients with primary non-small cell lung cancer (NSCLC). Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry with tissue microarrays were used to characterize the expression of the ZO-1 mRNA and protein in NSCLC. The correlation of ZO-1 expression with clinical characteristics and prognosis was determined by statistical analysis. Results: The ZO-1 mRNA and protein levels were significantly lower in NSCLC tissue compared with corresponding peritumoral tissue (P<0.05). ZO-1 protein expression in NSCLC was related to age (P=0.042) and 5-year survival (P<0.001). Kaplan-Meier survival and Cox regression analyses revealed that low ZO-1 expression (P<0.001) and later stage grouping by TNM (P=0.031) were independent factors predicting poor prognosis for patients with NSCLC. Conclusions: Our findings provide the first evidence that high expression of ZO-1 is associated with good prognosis in NSCLC. PMID:24294375

  11. 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.

  12. Association of increased postoperative opioid administration with non-small-cell lung cancer recurrence: a retrospective analysis.

    PubMed

    Maher, D P; Wong, W; White, P F; McKenna, R; Rosner, H; Shamloo, B; Louy, C; Wender, R; Yumul, R; Zhang, V

    2014-07-01

    Evidence suggests that opioid-sparing anaesthetic techniques might be associated with increased cancer-free postoperative survival. This could be related to suppression of natural killer cells by opioid analgesics in the perioperative period. This retrospective analysis tested the hypothesis that greater opioid use in the postoperative period is associated with a higher incidence of recurrences after surgery for lung cancer. The medical records of 99 consecutive patients who underwent video-assisted thoracoscopic surgery with lobectomy for Stage I or IIa biopsy-proven non-small-cell lung cancer (NSCLC) were reviewed. Perioperative information including patient characteristics, laboratory data, and surgical, anaesthetic, nursing, and pharmacy reports were collected. Doses of opioids administered intra-operatively and for the first 96 h after operation were converted into equianalgesic doses of oral morphine using a standard conversion table. Data were then compared with the National Cancer Registry's incidence of disease-free survival for 5 yr. A total of 99 patients with similar characteristics were included in the final analysis, 73 of whom were NSCLC recurrence-free at 5 yr and 26 had NSCLC recurrence within 5 yr. Total opioid dose during the 96 h postoperative period was 124 (101) mg of morphine equivalents in the cancer-free group and 232 mg (355) mg in the recurrence group (P=0.02). This retrospective analysis suggests an association between increased doses of opioids during the initial 96 h postoperative period with a higher recurrence rate of NSCLC within 5 yr. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. [Possible cause of the increased incidence of lung cancer in 1987 in the 10th District of Budapest (1975-1989)].

    PubMed

    Abrahám, E; Karácsonyi, L; Dinya, E

    1990-12-30

    In 1975 in one of the major industrial districts of Budapest some longitudinal epidemiological examinations were carried out with the aim of, among others, determination of connection between environmental injuries and lung cancer incidence in connection with determination of lung cancer risk groups. Between 1975-1989 out of the environmental injuries the most important was the radioactive contamination observed due to the atomic power station catastrophe in Chernobil (1986). In 1987 the incidence of lung cancer increased. The increase was significant among the 50-69-year-old women, and expressly among the heavy smokers. In 1987, especially among women, but also in both sexes, the ratio among the major cell types of lung cancer shifted towards micro-cellular ones. In 1988 and 1989 lung cancer incidence has decreased. In view of the above a hypothesis was raised: patients who have previously suffered immunobiological hurt, could not prevent the increased radioactive burden and got ill with lung cancer earlier, than it should have been happened without this increased burden. For clarification this question further examinations are considered to be necessary.

  14. 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

  15. Molecular Epidemiology of Female Lung Cancer

    PubMed Central

    Yim, Seon-Hee; Chung, Yeun-Jun

    2011-01-01

    Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer. PMID:24212786

  16. Inactivation of TGF-beta signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF.

    PubMed

    Baek, Hye Jung; Kim, Sang Soo; da Silva, Fabio May; Volpe, Eugene A; Evans, Stephen; Mishra, Bibhuti; Mishra, Lopa; Marshall, M Blair

    2006-08-11

    Escape from TGF-beta inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-beta adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf-/- mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-beta signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-beta adaptor protein in suppressing early lung cancer.

  17. Inactivation of TGF-{beta} signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF

    SciTech Connect

    Baek, Hye Jung; Kim, Sang Soo; Silva, Fabio May da; Volpe, Eugene A.; Evans, Stephen; Mishra, Bibhuti; Mishra, Lopa . E-mail: lopamishra@yahoo.com; Blair Marshall, M. . E-mail: mbm5@gunet.georgetown.edu

    2006-08-11

    Escape from TGF-{beta} inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-{beta} adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf {sup -/-} mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-{beta} signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-{beta} adaptor protein in suppressing early lung cancer.

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

    PubMed

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    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.

  19. Lycopene and Lung Cancer

    USDA-ARS?s Scientific Manuscript database

    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 ...

  20. 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 ...

  1. Terminate lung cancer (TLC) study-A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky.

    PubMed

    Cardarelli, Roberto; Reese, David; Roper, Karen L; Cardarelli, Kathryn; Feltner, Frances J; Studts, Jamie L; Knight, Jennifer R; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

    2017-02-01

    For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region.

  2. 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 ...

  3. Screening for Lung Cancer

    PubMed Central

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

    2013-01-01

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

  4. 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 ...

  5. Development of APE1 enzymatic DNA repair assays: low APE1 activity is associated with increase lung cancer risk.

    PubMed

    Sevilya, Ziv; Leitner-Dagan, Yael; Pinchev, Mila; Kremer, Ran; Elinger, Dalia; Lejbkowicz, Flavio; Rennert, Hedy S; Freedman, Laurence S; Rennert, Gad; Paz-Elizur, Tamar; Livneh, Zvi

    2015-09-01

    The key role of DNA repair in removing DNA damage and minimizing mutations makes it an attractive target for cancer risk assessment and prevention. Here we describe the development of a robust assay for apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), an essential enzyme involved in the repair of oxidative DNA damage. APE1 DNA repair enzymatic activity was measured in peripheral blood mononuclear cell protein extracts using a radioactivity-based assay, and its association with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean APE1 enzyme activity in case patients was 691 [95% confidence interval (CI) = 655-727] units/ng protein, significantly lower than in control subjects (mean = 793, 95% CI = 751-834 units/ng protein, P = 0.0006). The adjusted odds ratio for lung cancer associated with 1 SD (211 units) decrease in APE1 activity was 2.0 (95% CI = 1.3-3.1; P = 0.002). Comparison of radioactivity- and fluorescence-based assays showed that the two are equivalent, indicating no interference by the fluorescent tag. The APE1Asp148Glu SNP was associated neither with APE1 enzyme activity nor with lung cancer risk. Taken together, our results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that 'bad DNA repair', rather than 'bad luck', is involved in cancer etiology. Such assays may be useful, along with additional DNA repair biomarkers, for risk assessment of lung cancer and perhaps other cancers, and for selecting individuals to undergo early detection techniques such as low-dose CT.

  6. Does increased cigarette consumption nullify any reduction in lung cancer risk associated with low-tar filter cigarettes?

    PubMed

    Lee, Peter N; Sanders, Edward

    2004-12-01

    Epidemiological data suggest that smoking filter and lower tar cigarettes is associated with less lung cancer risk than is smoking plain and higher tar cigarettes. A recent National Cancer Institute monograph claimed these apparent benefits of lower delivery products may be illusory if relative risks are adjusted for daily consumption, and switching leads to "compensation" for reduced nicotine intake by increasing numbers of cigarettes smoked. To investigate this, we compared relative risks unadjusted and adjusted for daily cigarette consumption. Overall estimates of the filter/plain relative risk, using random-effects meta-analysis, were 0.61 (95%confidence interval 0.54 to 0.70) for unadjusted data and 0.66 (0.58 to 0.76) for adjusted data. The lower tar/higher tar relative risk was estimated as 0.60 (0.45 to 0.81) for unadjusted data and 0.73 (0.64 to 0.83) for adjusted data. The risk reductions were clearly seen regardless of gender, study location, period, or design, and when only studies providing both unadjusted and adjusted estimates were considered. Whether or not relative risk estimates are adjusted for cigarette consumption is not crucial to the conclusion of a clear advantage to filter cigarettes and tar reduction. Data on "compensation" for amount smoked were reviewed and any increase following switching to reduced-tar-yield cigarettes was shown to be quite small. Other biases in the epidemiology are also discussed, and we conclude that the apparent advantage to reduced-tar-delivery products is real and likely to be a marked underestimate of the reduction in lung cancer risk from lifetime smoking of low-tar cigarettes.

  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. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    SciTech Connect

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F.

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  9. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    SciTech Connect

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  10. A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.

    PubMed

    Shen, Hongbing; Wang, Luo; Spitz, Margaret R; Hong, Waun K; Mao, Li; Wei, Qingyi

    2002-09-01

    DNA repair is central to genomic integrity. Reduced expression of several nucleotide excision repair genes has been demonstrated to be associated with increased risk of lung cancer. Because methylation of gene promoters is one of the major regulatory mechanisms of gene expression and most nucleotide excision repair gene promoters have not been fully characterized, we hypothesized that genetic variants of the genes that are responsible for regulating genomic methylation are associated with increased risk of lung cancer. Recently, we identified a C-->T transition at a novel promoter region of cytosine DNA-methyltransferase-3B (DNMT3B) and found that this polymorphic transition significantly increases the promoter activity. In this hospital-based case-control study of 319 patients with incident lung cancer and 340 healthy controls frequency matched on age (+/-5 years), sex, ethnicity, and smoking status, we genotyped subjects for this DNMT3B promoter polymorphism to determine the association between this genetic variant and risk of lung cancer. Compared with CC homozygotes, CT heterozygotes had a >2-fold increased risk of lung cancer [adjusted odds ratio (OR), 2.13; 95% confidence interval (CI), 1.47-3.08] and TT homozygotes an OR of 1.42 (95% CI, 0.91-2.21). The combined variant genotype (CT + TT) was associated with a nearly 2-fold increased risk (adjusted OR, 1.88; 95% CI, 1.32-2.66). These results suggest that this novel variant of DNMT3B is associated with increased risk of lung cancer and may contribute to identifying individuals genetically susceptible to tobacco-induced cancers. Additional studies on the underlying molecular mechanism of this polymorphism are warranted.

  11. Lung Cancer Epidemiology in Korea.

    PubMed

    Shin, Aesun; Oh, Chang-Mo; Kim, Byung-Woo; Woo, Hyeongtaek; Won, Young-Joo; Lee, Jin-Soo

    2017-07-01

    The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea. Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated. Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups. The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.

  12. Ascorbic acid increases drug accumulation and reverses vincristine resistance of human non-small-cell lung-cancer cells.

    PubMed Central

    Chiang, C D; Song, E J; Yang, V C; Chao, C C

    1994-01-01

    A human lung-cancer PC-9 subline with acquired resistance to vincristine (VCR), a chemotherapeutic agent, was established with incremental increases of the drug. The resistant PC-9 subline (PC-9/VCR) shows a 12-fold increase in resistance to VCR and a unique cross-resistance pattern: high cross-resistance to the potent VCR analogue colchicine (6.9-fold) and vinblastine (2.5-fold); lower cross-resistance to actinomycin D (1.8-fold), cisplatin (1.2-fold) and adriamycin (1.3-fold) and a sensitivity to melphalan and VP-16 which is similar to that of the parental cell line. A reduced accumulation of VCR in the resistant cells was demonstrated. Interestingly, the VCR resistance of the PC-9/VCR cell line was partially reversed by ascorbic acid, and the drug uptake was enhanced. In contrast, ascorbic acid had no effect on drug tolerance and drug accumulation was not observed in either PC-9 parental cells or known multidrug-resistant (MDR) cells, suggesting that VCR resistance in PC-9/VCR cells results essentially from reduced drug accumulation. It is worth noting that, whereas reduced drug accumulation in the PC-9/VCR cells was susceptible to modulation by ascorbic acid, the increased efflux rate characteristic of the resistant cells was not. Further, there was a higher efflux rate in resistant cells than in parental cells. DNA Southern- and RNA Northern-blot hybridization analyses indicate that PC-9/VCR cells do not contain amplified mdr genes or overexpress P-glycoprotein. In addition, the calcium-channel blocker verapamil, which acts as a competitive inhibitor of drug binding and efflux, did not affect the resistant phenotype of PC-9/VCR cells. These findings suggest an ascorbic acid-sensitive drug uptake mechanism which is important in mediating VCR resistance per se in human lung-cancer cells; this differs from the P-glycoprotein-mediated MDR mechanism. Images Figure 5 PMID:7914401

  13. 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

  14. 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

  15. Small cell lung cancer.

    PubMed

    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.

  16. 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.

  17. Lung Cancer Brain Metastases.

    PubMed

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

    2015-01-01

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

  18. Molecular biology of lung cancer.

    PubMed

    Cooper, Wendy A; Lam, David C L; O'Toole, Sandra A; Minna, John D

    2013-10-01

    Lung cancers are characterised by abundant genetic diversity with relatively few recurrent mutations occurring at high frequency. However, the genetic alterations often affect a common group of oncogenic signalling pathways. There have been vast improvements in our understanding of the molecular biology that underpins lung cancer in recent years and this has led to a revolution in the diagnosis and treatment of lung adenocarcinomas (ADC) based on the genotype of an individual's tumour. New technologies are identifying key and potentially targetable genetic aberrations not only in adenocarcinoma but also in squamous cell carcinoma (SCC) of the lung. Lung cancer mutations have been identified in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), BRAF and the parallel phosphatidylinositol 3-kinase (PI3K) pathway oncogenes and more recently in MEK and HER2 while structural rearrangements in ALK, ROS1 and possibly rearranged during transfection (RET) provide new therapeutic targets. Amplification is another mechanism of activation of oncogenes such as MET in adenocarcinoma, fibroblastgrowth factor receptor 1 (FGFR1) and discoidin domain receptor 2 (DDR2) in SCC. Intriguingly, many of these genetic alternations are associated with smoking status and with particular racial and gender differences, which may provide insight into the mechanisms of carcinogenesis and role of host factors in lung cancer development and progression. The role of tumour suppressor genes is increasingly recognised with aberrations reported in TP53, PTEN, RB1, LKB11 and p16/CDKN2A. Identification of biologically significant genetic alterations in lung cancer that lead to activation of oncogenes and inactivation of tumour suppressor genes has the potential to provide further therapeutic opportunities. It is hoped that these discoveries may make a major contribution to improving outcome for patients with this poor prognosis disease.

  19. [Epidemiology of lung cancer].

    PubMed

    Becker, N

    2010-08-01

    Lung cancer is by far the most common form of cancer worldwide and in Germany is now "only" still the commonest cause of death from cancer. The most important single risk factor is smoking but in selected population groups, for example in the professional area, other factors can also play a role which cannot be ignored and open up a corresponding potential for prevention. Effective early detection procedures are at present unknown. The most promising, however, is multislice computed tomography (MSCT) which for this reason is presently being tested for effectiveness in several large research projects. The results are not expected for some years. Until then the early detection of lung cancer with MSCT cannot be considered suitable for routine use but can only be justified within the framework of research studies.

  20. Other cancers in lung cancer families are overwhelmingly smoking-related cancers.

    PubMed

    Yu, Hongyao; Frank, Christoph; Hemminki, Akseli; Sundquist, Kristina; Hemminki, Kari

    2017-04-01

    Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

  1. [Secondary lung cancers].

    PubMed

    Etienne-Mastroïanni, Bénédicte; Freyer, Gilles; Cordier, Jean-François

    2003-04-01

    Lung is the most common site of metastatic involvement for many malignant tumors. The most frequent abnormalities are solitary or multiple pulmonary nodules (large "cannonball" nodules or diffuse miliary pattern), and lymphangitic carcinomatosis. Pulmonary metastases usually occur in a context of a previously known tumour, but sometimes may reveal a latent tumour. Most patients receive palliative treatment with chemotherapy, or hormone therapy (for metastases of breast cancer, thyroid, endometrial carcinoma or prostatic cancer). Patients may rarely benefit from resection of pulmonary metastases.

  2. Increased NDRG1 expression is associated with advanced T stages and poor vascularization in non-small cell lung cancer.

    PubMed

    Fan, Chuifeng; Yu, Juanhan; Liu, Yang; Xu, Hongtao; Wang, Enhua

    2012-07-01

    N-myc downstream regulated gene 1 (NDRG1) is a member of the N-myc downstream regulated gene family which belongs to the alpha/beta hydrolase superfamily. Earlier studies have shown its association with inhibition of tumor metastasis. However, its function in malignant tumors is not fully enunciated. Recently there was increasing evidence that NDRG1 is involved in stress responses. In the current study, we examined the expression of NDRG1 and its correlation with clinicopathological factors and microvessel density (MVD) in non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC). NDRG1 expression in NSCLC (71/115, 61.7%) was higher than that in normal lung tissues (32/115, 27.8%) (p < 0.05). NDRG1 expression in NSCLC cells was found in cytoplasm (63/115, 54.8%), nuclear (24/115, 20.9%) and cell membrane (13/115, 11.3%). NDRG1 expression in NSCLC with advanced T stages (T2-4) (63/84, 75.0%) was significantly higher than that with T1 stage (8/31, 25.8%) (P < 0.05). No other clinicopathological factors including lymph node metastasis were found to be associated with NDRG1 expression (p > 0.05). Moreover increased NDRG1 expression was associated with lower MVD in NSCLC (P < 0.05). MVD in adenocarcinoma (33.4 ± 8.4/HP) was significantly higher than that in squamous cell carcinoma (SCC) (19.3 ± 8.1/HP) (P < 0.05). No other clinicopathological factors were associated with MVD in NSCLC (p > 0.05). The present findings indicate an increase of NDRG1 expression with the progress of tumour extent which may be due to unbalanced tumor oxygenation on account of poor vascularization in NSCLC.

  3. [Lung cancer screening and management of small pulmonary nodules].

    PubMed

    Schulz, Christian

    2015-03-01

    Worldwide lung cancer is the leading cause of death from cancer. Most lung cancers are diagnosed at an advanced stage, so survival after lung cancer is generally poor. Diagnosis of lung cancer at earlier stages may be associated with an increased survival rate. This indicates that the implementation of lung cancer screening programs at the population level by means of low dose computed tomography might helpful to improve the outcome and mortality of lung cancer patients. By means of rapid advances in imaging technologies over the last decades it became possible to detect small lung nodules as small as a couple of millimeters. This recent developments require management algorithms to guide the clinical management of suspicious and indeterminate lung nodules found in computer tomography during lung cancer screening or by incidental finding.This review will focus on both, the recent advances in lung cancer screening and the guidelines for the management of small pulmonary nodules.

  4. Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors.

    PubMed

    Thommen, Daniela S; Schreiner, Jens; Müller, Philipp; Herzig, Petra; Roller, Andreas; Belousov, Anton; Umana, Pablo; Pisa, Pavel; Klein, Christian; Bacac, Marina; Fischer, Ozana S; Moersig, Wolfgang; Savic Prince, Spasenija; Levitsky, Victor; Karanikas, Vaios; Lardinois, Didier; Zippelius, Alfred

    2015-12-01

    Dysfunctional T cells present in malignant lesions are characterized by a sustained and highly diverse expression of inhibitory receptors, also referred to as immune checkpoints. Yet, their relative functional significance in different cancer types remains incompletely understood. In this study, we provide a comprehensive characterization of the diversity and expression patterns of inhibitory receptors on tumor-infiltrating T cells from patients with non-small cell lung cancer. In spite of the large heterogeneity observed in the amount of PD-1, Tim-3, CTLA-4, LAG-3, and BTLA expressed on intratumoral CD8(+) T cells from 32 patients, a clear correlation was established between increased expression of these inhibitory coreceptors and progression of the disease. Notably, the latter was accompanied by a progressively impaired capacity of T cells to respond to polyclonal activation. Coexpression of several inhibitory receptors was gradually acquired, with early PD-1 and late LAG-3/BTLA expression. PD-1 blockade was able to restore T-cell function only in a subset of patients. A high percentage of PD-1(hi) T cells was correlated with poor restoration of T-cell function upon PD-1 blockade. Of note, PD-1(hi) expression marked a particularly dysfunctional T-cell subset characterized by coexpression of multiple inhibitory receptors and thus may assist in identifying patients likely to respond to inhibitory receptor-specific antibodies. Overall, these data may provide a framework for future personalized T-cell-based therapies aiming at restoration of tumor-infiltrating lymphocyte effector functions.

  5. Lung Cancer Biomarkers.

    PubMed

    Villalobos, Pamela; Wistuba, Ignacio I

    2017-02-01

    The molecular characterization of lung cancer has changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it is possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has led to accelerated development of new drugs for lung cancer treatment. This article focuses on clinically relevant cancer biomarkers as targets for therapy and potential new targets for drug development. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Expression of GARP Is Increased in Tumor-Infiltrating Regulatory T Cells and Is Correlated to Clinicopathology of Lung Cancer Patients

    PubMed Central

    Jin, Hao; Sun, Liping; Tang, Lu; Yu, Wenwen; Li, Hui

    2017-01-01

    Regulatory T cells (Tregs) are immunosuppressive T cells that play an important role in immune homeostasis. Multiple markers have been associated with the characterization, as well as function of Tregs. Recently, glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine-rich repeats, has been found to be highly expressed on the surface of activated Tregs. GARP maintains Tregs’ regulatory function and homeostasis through the activation and secretion of transforming growth factor β. In this study, we investigated the expression of GARP in Tregs from the peripheral blood (PB) and tumor tissues of lung cancer patients. The association between the proportion and expression level of GARP on Tregs and the clinicopathological factors of lung cancer patients was also analyzed. Results showed that in the tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and was associated with lymph node metastasis, distant metastasis, and clinical stage. Furthermore, the infiltrating Tregs from early stage patients exhibited higher GARP expression than that from advanced cancer patients, which indicated that GARP might be an early prognostic biomarker. In vitro coculture studies demonstrated that human lung cancer cell lines might induce the expression of GARP in Tregs by certain mechanisms. Overall, this research demonstrated the potential value of GARP in Tregs definition and cancer immunotherapy. PMID:28261204

  7. Lung cancer in elderly patients

    PubMed Central

    Diso, Daniele; Onorati, Ilaria; Anile, Marco; Mantovani, Sara; Rendina, Erino A.

    2016-01-01

    There is a worldwide-accepted evidence of a population shift toward older ages. This shift favors an increased risk of developing lung cancer that is primarily a disease of older populations. Decision making is extremely difficult in elderly patients, since this group is under-represented in clinical trials with only 25% of them historically opening to patients older than 65 years. For all these reasons, a “customized” preoperative assessment to identify physiological or pathological frailty should be encouraged since standard tools may be less reliable. The work already done to improve patient selection for lung surgery in the elderly population clearly shows that surgical resection seems the treatment of choice for early stage lung cancer. Further studies are required to improve outcome by reducing postoperative morbidity and mortality. PMID:27942414

  8. Is obesity a preventive factor for lung cancer?

    PubMed

    Kollarova, H; Machova, L; Horakova, D; Cizek, L; Janoutova, G; Janout, V

    2008-01-01

    Lung cancer is a disease with multifactorial etiology, smoking playing the most important role among its risk factors. Some studies, however, indicate an inverse association between increased body-mass index (BMI) and the risk of lung cancer. In this paper, the association between BMI and lung cancer risk is analysed in two independent studies. In the first study, 751 lung cancer patients were compared to 30 058 controls. In the second study, 91 lung cancer patients were matched to 91 healthy controls. An inversed association was found between increased BMI and lung cancer risk. The inverse association remained significant after adjustment for age, sex, and smoking.

  9. 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 ...

  10. 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 ...

  11. General Information about 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 ...

  12. Wnt pathway activation predicts increased risk of tumor recurrence in patients with stage I nonsmall cell lung cancer.

    PubMed

    Shapiro, Mark; Akiri, Gal; Chin, Cynthia; Wisnivesky, Juan P; Beasley, Mary B; Weiser, Todd S; Swanson, Scott J; Aaronson, Stuart A

    2013-03-01

    To determine the incidence of Wnt pathway activation in patients with stage I NSCLC and its influence on lung cancer recurrence. Despite resection, the 5-year recurrence with localized stage I nonsmall cell lung cancer (NSCLC) is 18.4%-24%. Aberrant Wnt signaling activation plays an important role in a wide variety of tumor types. However, there is not much known about the role the Wnt pathway plays in patients with stage I lung cancer. Tumor and normal lung tissues from 55 patients following resection for stage I NSCLC were subjected to glutathione S-transferase (GST) E-cadherin pulldown and immunoblot analysis to assess levels of uncomplexed β-catenin, a reliable measure of Wnt signaling activation. The β-catenin gene was also screened for oncogenic mutations in tumors with activated Wnt signaling. Cancer recurrence rates were correlated in a blinded manner in patients with Wnt pathway-positive and -negative tumors. Tumors in 20 patients (36.4%) scored as Wnt positive, with only 1 exhibiting a β-catenin oncogenic mutation. Patients with Wnt-positive tumors experienced a significantly higher rate of overall cancer recurrence than those with Wnt-negative tumors (30.0% vs. 5.7%, P = 0.02), with 25.0% exhibiting distal tumor recurrence compared with 2.9% in the Wnt-negative group (P = 0.02). Wnt pathway activation occurred in a substantial fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt pathway activation was associated with a significantly higher rate of tumor recurrence. These findings suggest that Wnt pathway activation reflects a more aggressive tumor phenotype and identifies patients who may benefit from more aggressive therapy in addition to resection.

  13. Indoor radon and lung cancer in China

    SciTech Connect

    Blot, W.J.; Xu, Z.Y.; Boice, J.D. Jr.; Zhao, D.Z.; Stone, B.J.; Sun, J.; Jing, L.B.; Fraumeni, J.F. Jr. )

    1990-06-20

    Radon has long been known to contribute to risk of lung cancer, especially in undergound miners who are exposed to large amounts of the carcinogen. Recently, however, lower amounts of radon present in living areas have been suggested as an important cause of lung cancer. In an effort to clarify the relationship of low amounts of radon with lung cancer risk, we placed alpha-track radon detectors in the homes of 308 women with newly diagnosed lung cancer and 356 randomly selected female control subjects of similar age. Measurements were taken after 1 year. All study participants were part of the general population of Shenyang, People's Republic of China, an industrial city in the northeast part of the country that has one of the world's highest rates of lung cancer in women. The median time of residence in the homes was 24 years. The median household radon level was 2.3 pCi/L of air; 20% of the levels were greater than 4 pCi/L. Radon levels tended to be higher in single-story houses or on the first floor of multiple-story dwellings, and they were also higher in houses with increased levels of indoor air pollution from coal-burning stoves. However, the levels were not higher in homes of women who developed lung cancer than in homes of controls, nor did lung cancer risk increase with increasing radon level. No association between radon and lung cancer was observed regardless of cigarette-smoking status, except for a nonsignificant trend among heavy smokers. No positive associations of lung cancer cell type with radon were observed, except for a nonsignificant excess risk of small cell cancers among the more heavily exposed residents. Our data suggest that projections from surveys of miners exposed to high radon levels may have overestimated the overall risks of lung cancer associated with levels typically seen in homes in this Chinese city.

  14. Fulvestrant increases gefitinib sensitivity in non-small cell lung cancer cells by upregulating let-7c expression.

    PubMed

    Shen, Hua; Liu, Jinyuan; Wang, Rong; Qian, Xu; Xu, Ruitong; Xu, Tongpeng; Li, Qi; Wang, Lin; Shi, Zhumei; Zheng, Jitai; Chen, Qiudan; Shu, Yongqian

    2014-04-01

    Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), namely, gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. About 50% of this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as the one corresponding to T790M. In our previous study, we found that combined treatment with fulvestrant and gefitinib decreases the proliferation of H1975 NSCLC cells, compared to treatment with either fulvestrant or gefitinib alone; however, the molecular mechanism for the improved effects of the combination treatment are still unknown. In this study, we confirmed that fulvestrant increases the gefitinib sensitivity of H1975 cells and found that let-7c was most upregulated in the fulvestrant-treated cells. Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our findings suggest that let-7c plays an important role in fulvestrant-induced upregulation of gefitinib sensitivity in H1975 cells.

  15. Increased Sensitivity to Cisplatin in Non-Small Cell Lung Cancer Cell Lines after FHIT Gene Transfer1

    PubMed Central

    Andriani, F; Perego, P; Carenini, N; Sozzi, G; Roz, L

    2006-01-01

    Abstract To evaluate the relevance of fragile histidine triad (FHIT) status in relation to drug treatment, we analyzed the sensitivity of the Fhit-negative non-small cell lung cancer (NSCLC) cell line NCI-H460 to different drugs, after treatment with an adenoviral vector expressing the FHIT transgene. Expression of Fhit resulted in reduced sensitivity to etoposide, doxorubicin, and topotecan. This feature was associated with Fhit-induced downregulation of DNA topoisomerases I and II. In contrast, expression of Fhit did not modulate sensitivity to Taxol, but produced a slight increase in sensitivity to cisplatin, as shown by colony-forming assays. Analysis of apoptosis revealed that, after cisplatin exposure, the number of apoptotic cells was two-fold higher in Fhit-expressing H460 cells. Moreover, it appeared that wild-type p53 was required for sensitization to cisplatin because the effect was marginal in A549 and Calu-1 cells, where the p53 pathway is altered and simultaneous restoration of p53 and Fhit in Calu-1 cells increased cisplatin sensitivity. Fhit could also partially restore sensitivity to cisplatin in Bcl-2- and Bcl-xL-overexpressing H460 cells that are normally resistant to this drug. Our results support the possible relevance of FHIT in cisplatin-based chemotherapy as well as in the reversal of drug resistance in NSCLC. PMID:16533421

  16. Increased mortality of respiratory diseases, including lung cancer, in the area with large amount of ashfall from Mount Sakurajima volcano.

    PubMed

    Higuchi, Kenta; Koriyama, Chihaya; Akiba, Suminori

    2012-01-01

    Mount Sakurajima in Japan is one of the most active volcanoes in the world. This work was conducted to examine the effect of volcanic ash on the chronic respiratory disease mortality in the vicinity of Mt. Sakurajima. The present work examined the standardized mortality ratios (SMRs) of respiratory diseases during the period 1968-2002 in Sakurajima town and Tarumizu city, where ashfall from the volcano recorded more than 10.000 g/m2/yr on average in the 1980s. The SMR of lung cancer in the Sakurajima-Tarumizu area was 1.61 (95% CI=1.44-1.78) for men and 1.67 (95% CI=1.39-1.95) for women while it was nearly equal to one in Kanoya city, which neighbors Tarumizu city but located at the further position from Mt. Sakurajima, and therefore has much smaller amounts of ashfall. Sakurajima-Tarumizu area had elevated SMRs for COPDs and acute respiratory diseases while Kanoya did not. Cristobalite is the most likely cause of the increased deaths from those chronic respiratory diseases since smoking is unlikely to explain the increased mortality of respiratory diseases among women since the proportion of smokers in Japanese women is less than 20%, and SPM levels in the Sakurajima-Tarumizu area were not high. Further studies seem warranted.

  17. Multi-target interphase fluorescence in situ hybridization assay increases sensitivity of sputum cytology as a predictor of lung cancer.

    PubMed

    Varella-Garcia, Marileila; Kittelson, John; Schulte, Aline P; Vu, Kieu O; Wolf, Holly J; Zeng, Chan; Hirsch, Fred R; Byers, Tim; Kennedy, Tim; Miller, York E; Keith, Robert L; Franklin, Wilbur A

    2004-01-01

    Survival rates for lung cancer are low because patients have disseminated disease at diagnosis; therefore tests for early diagnosis are highly desirable. This pilot study investigated occurrence of chromosomal aneusomy in sputum from a 33 case-control cohort matched on age, gender, and date of sample collection. Subjects had chronic obstructive pulmonary disease and > or = 30 pack-years of tobacco use, and aneusomy was tested using a multi-target DNA FISH assay (LAVysion, Abbott/Vysis). In specimens collected within 12 months of lung cancer diagnosis, abnormality was more frequent among the 18 cases (41%) than the 17 controls (6%; P = 0.04). Aneusomy had no significant association with cytologic atypia, which might indicate that molecular and morphological changes could be independent markers of tumorigenesis. Combining both tests, abnormality was found in 83% of the cases and 20% of the controls (P = 0.0004) suggesting that FISH may improve the sensitivity of cytologic atypia as a predictor of lung cancer.

  18. Too Few Current, Former Smokers Screened for Lung Cancer

    MedlinePlus

    ... html Too Few Current, Former Smokers Screened for Lung Cancer Such testing could cut death rate by ... the United States don't get screened for lung cancer even though they're at increased risk ...

  19. Antisense bcl-2 treatment increases programmed cell death in non-small cell lung cancer cell lines.

    PubMed

    Koty, P P; Zhang, H; Levitt, M L

    1999-02-01

    Programmed cell death (PCD) is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the ratio of PCD inducers (Bax) or inhibitors (Bcl-2). An abnormally high ratio of Bcl-2 to Bax prevents PCD, thus contributing to resistance to chemotherapeutic agents, many of which are capable of inducing PCD. Non-small cell lung cancer (NSCLC) cells demonstrate resistance to these PCD-inducing agents. If Bcl-2 prevents NSCLC cells from entering the PCD pathway, then reducing the amount of endogenous Bcl-2 product may allow these cells to spontaneously enter the PCD pathway. Our purpose was to determine the effects of bcl-2 antisense treatment on the levels of programmed cell death in NSCLC cells. First, we determined whether bcl-2 and bax mRNA were expressed in three morphologically distinct NSCLC cell lines: NCI-H226 (squamous), NCI-H358 (adenocarcinoma), and NCI-H596 (adenosquamous). Cells were then exposed to synthetic antisense bcl-2 oligonucleotide treatment, after which programmed cell death was determined, as evidenced by DNA fragmentation. Bcl-2 protein expression was detected immunohistochemically. All three NSCLC cell lines expressed both bcl-2 and bax mRNA and had functional PCD pathways. Synthetic antisense bcl-2 oligonucleotide treatment resulted in decreased Bcl-2 levels, reduced cell proliferation, decreased cell viability, and increased levels of spontaneous PCD. This represents the first evidence that decreasing Bcl-2 in three morphologically distinct NSCLC cell lines allows the cells to spontaneously enter a PCD pathway. It also indicates the potential therapeutic use of antisense bcl-2 in the treatment of NSCLC.

  20. Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells.

    PubMed

    Kim, D R; Park, M-Y; Lee, C-S; Shim, S-H; Yoon, H-I; Lee, J H; Sung, M-W; Kim, Y-S; Lee, C-T

    2011-07-01

    Soluble TRAIL and adenovirus (ad)-TRAIL exhibit a strong antitumor effect by inducing apoptosis. Vorinostat is the histone deacetylase (HDAC) inhibitor that induces cell death in cancer cell lines and regulates the expression of epigenetically silenced genes, such as Coxackie adenoviral receptor (CAR), the receptor for adenoviral entry. We propose a new strategy in which vorinostat will induce high expression of ad-TRAIL and a strong antitumor response, and investigated the mechanism involved. The effect of vorinostat on transcription and expression of TRAIL from ad-TRAIL-transduced lung cancer cells were confirmed by reverse transciption-PCR (RT-PCR), quantitative real time-PCR and western blot assay. Anti-tumor effects were measured after cotreatment of vorinostat and ad-TRAIL, and the drug interactions were analyzed. After combined treatment of vorinostat and ad-TRAIL, apoptosis and western blot assays for Akt, Bcl-2 and caspase were performed. Vorinostat increased the expression of CAR in lung cancer cell lines and increased the expression of luciferase (luc) from ad-luc-transduced cells and TRAIL from ad-TRAIL-transduced cells. RT-PCR and quantitative real time-PCR, after sequential vorinostat treatment, revealed that vorinostat may enhance TRAIL expression from ad-TRAIL by increasing transduction through enhanced CAR expression and increasing adenoviral transgene transcription. Combined vorinostat and ad-TRAIL treatment showed the synergistic anti-tumor effect in lung cancer cell lines. Combined vorinostat and ad-TRAIL induced stronger apoptosis induction, suppression of NF-κB activation and breakdown of the anti-apoptotic molecule Bcl-2. In conclusion, the vorinostat synergistically enhanced the anti-tumor effect of ad-TRAIL by (1) increasing adenoviral transduction through the increased expression of CAR and (2) increasing adenoviral transgene (TRAIL) transcription in lung cancer cell lines.

  1. Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.

    PubMed

    Na, Sang-su; Aldonza, Mark Borris; Sung, Hye-Jin; Kim, Yong-In; Son, Yeon Sung; Cho, Sukki; Cho, Je-Yoel

    2015-06-01

    The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2015. Published by Elsevier B.V.

  2. Cholinergic Targets in Lung Cancer.

    PubMed

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.

  3. Tim-3 expression by peripheral natural killer cells and natural killer T cells increases in patients with lung cancer--reduction after surgical resection.

    PubMed

    Xu, Li-Yun; Chen, Dong-Dong; He, Jian-Ying; Lu, Chang-Chang; Liu, Xiao-Guang; Le, Han-Bo; Wang, Chao-Ye; Zhang, Yong-Kui

    2014-01-01

    The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients. We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-CD56dim cells, Tim-3+CD3-CD56bright cells, and Tim- 3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort. It was showed that expression of Tim-3 was significantly increased on CD3-CD56+ cells, CD3- CD56dim cells and CD3+CD56+ cells in lung cancer patients as compared to healthy controls (p=0.03, p=0.03 and p=0.04, respectively). When analyzing Tim-3 expression with cancer progression, results revealed more elevated Tim-3 expression in CD3-CD56+ cells, CD3-CD56dim cells and CD3+CD56+ cells in cases with advanced stages (III/IV) than those with stage I and II (p=0.02, p=0.04 and p=0.01, respectively). In addition, Tim-3 expression was significantly reduced on after surgical resection of the primary tumor (p<0.01). Tim-3 expression in natural killer cells from fresh peripheral blood may provide a useful indicator of disease progression of lung cancer. Furthermore, it was indicated that Tim-3 might be as a therapeutic target.

  4. Drug delivery and nanodetection in lung cancer.

    PubMed

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

    2016-01-01

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

  5. Pain management in lung cancer.

    PubMed

    Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

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

  6. The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells.

    PubMed

    Fernández Massó, Julio R; Oliva Argüelles, Brizaida; Tejeda, Yelaine; Astrada, Soledad; Garay, Hilda; Reyes, Osvaldo; Delgado-Roche, Livan; Bollati-Fogolín, Mariela; Vallespí, Maribel G

    2013-01-01

    We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.

  7. The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells

    PubMed Central

    Fernández Massó, Julio R.; Oliva Argüelles, Brizaida; Tejeda, Yelaine; Astrada, Soledad; Garay, Hilda; Reyes, Osvaldo; Delgado-Roche, Livan; Bollati-Fogolín, Mariela; Vallespí, Maribel G.

    2013-01-01

    We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies. PMID:23401744

  8. American Cancer Society lung cancer screening guidelines.

    PubMed

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

    2013-01-01

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

  9. Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway

    PubMed Central

    Yang, Jiali; Zhang, Kangjian; Wu, Jing; Shi, Juan; Xue, Jing; Li, Jing; Zhu, Yongzhao; Wei, Jun

    2016-01-01

    The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies. PMID:27895670

  10. Nutritional aspects regarding lung cancer chemoprevention.

    PubMed

    Thanopoulou, E; Baltayiannis, N; Lykogianni, V

    2006-01-01

    Lung cancer is still one of the major causes of cancer-related deaths and its mortality figures argue powerfully for new approaches to control this leading cancer threat. Chemoprevention can be defined as the use of specific agents to reverse, or prevent premalignancy from progressing to invasive cancer. The use of foods and dietary supplements present a safe chemopreventive strategy. Data for this review were identified by searches of PubMed and references from relevant articles. Articles were identified by use of the search terms "lung cancer", "chemoprevention", "carcinogenesis", and "retinoids". Only papers published in English were included. Trials in lung cancer chemoprevention have so far produced either neutral or harmful primary endpoint results, whether in the primary, secondary, or tertiary settings. Lung cancer was not prevented by beta-carotene, alpha-tocopherol, retinol, retinyl palmitate, N-acetylcysteine, or isotretinoin in smokers. Ongoing trials may help define new avenues for chemoprevention. The concept of chemoprevention in lung cancer is still in its infancy, but in the future it may have a significant impact on the incidence and mortality of lung cancer. In addition to epidemiologic studies, basic science research to detect mechanisms and evaluate the chemopreventive potential of food components is necessary. The overwhelming evidence of a major role of nutrition in carcinogenesis, the many leads that nutritional intervention may reduce cancer incidence, and the growth and increasing sophistication of clinical trials networks point to a very promising future for nutritional intervention trials leading to substantial public benefit.

  11. Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case-control studies in Montreal.

    PubMed

    Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

    2012-08-01

    We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

  12. The TP53 codon 72 Pro/Pro genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis

    PubMed Central

    Wang, Xin; Hao, Li-Ran; Yue, Kai

    2015-01-01

    Background: The polymorphism of TP53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Chinese have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of TP53 codon 72 Arg/Pro polymorphism on the development of lung cancer in the Chinese population. Material/Methods: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 10 October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. Results: A total of 12 case-control studies including 3681 lung cancer cases and 4358 controls were involved in this meta-analysis. Overall, no significant association was found between TP53 codon 72 variation and lung cancer risk when all studies in the Chinese population pooled into this meta-analysis. However, in the subgroup analysis by geographical locations, significantly increased risk was found in the population from North China under all genetic models (Allele model, OR=1.22, 95% CI: 1.04-1.43; Dominant model, OR=1.13, 95% CI: 1.01-1.25; Recessive model, OR=1.41, 95% CI: 1.07-1.87; Homozygous model, OR=1.47, 95% CI: 1.09-1.99; Heterozygous model, OR=1.40, 95% CI: 1.04-1.89). Conclusions: This meta-analysis provides the evidence that TP53 codon 72 polymorphism may contribute to the lung cancer development in North China and studies with large sample size and gene-gene (gene-environment) interactions are warranted to verify this finding. PMID:26064201

  13. Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case–control studies in Montreal

    PubMed Central

    Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

    2012-01-01

    We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case–control studies were conducted in Montreal. Study I (1979–1986) included 857 cases and 1066 controls, and Study II (1996–2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist–hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9–1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8–1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7–4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3–3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes. PMID:23342253

  14. Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non-Small-Cell Lung Cancer: A Competing Risks Analysis.

    PubMed

    Eguchi, Takashi; Bains, Sarina; Lee, Ming-Ching; Tan, Kay See; Hristov, Boris; Buitrago, Daniel H; Bains, Manjit S; Downey, Robert J; Huang, James; Isbell, James M; Park, Bernard J; Rusch, Valerie W; Jones, David R; Adusumilli, Prasad S

    2017-01-20

    Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

  15. American Cancer Society Lung Cancer Screening Guidelines

    PubMed Central

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

    2013-01-01

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

  16. 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.

  17. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... of the lung cancer and your overall health. Radiation Therapy Radiation is a high-energy X-ray that can ... surgery, chemotherapy or both depending upon the circumstances. Radiation therapy works within cancer cells by damaging their ...

  18. Low-Intensity Laser Irradiation at 636 nm Induces Increased Viability and Proliferation in Isolated Lung Cancer Stem Cells.

    PubMed

    Crous, Anine; Abrahamse, Heidi

    2016-11-01

    The purpose of this in vitro study was to evaluate the effects of low-intensity laser irradiation (LILI) on isolated lung cancer stem cells (CSCs) after several time intervals, using a wavelength of 636 nm and fluences between 5 and 20 J/cm(2). LILI has been proven to have a biomodulatory effect on various diseased conditions. A number of studies have been conducted on CSCs. Lung CSCs were isolated from lung cancer cells (A549), using cell surface marker CD 133. Isolated lung CSCs were divided into four groups: group 1 consisted of control cells receiving no irradiation; groups 2, 3, and 4 were exposed to laser irradiation at fluences of 5, 10, and 20 J/cm(2), respectively. LILI was performed using a 636 nm diode laser with a power output of ±85 mW. Cellular responses were evaluated after 24, 48, or 72 h, and included cell morphology, viability, and proliferation. Cellular morphology indicated an increase in cell density caused by cell proliferation over time. Biostimulatory effects were achieved in lung CSCs when examining viability and proliferation. It should, therefore, be noted that a low wavelength of 636 nm at various fluences induces biostimulation, which may have detrimental effects when using LILI as a form of regeneration.

  19. Methylenetetrahydrofolate Reductase 677TT Genotype may be Associated with an Increased Lung Cancer Risk in North China: An Updated Meta

    PubMed Central

    Liu, Nan-Bo; Li, Jun; Qi, Jia-Feng; Zhang, Zhen-Zhong; Wu, Xu; Zhang, Jun-Hua

    2014-01-01

    Background Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. Material/Methods Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14–1.44; TT vs. CC: OR=1.67, 95% CI: 1.33–2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15–1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03–2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14–1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07–1.45). Conclusions This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding. PMID:25544260

  20. Lung cancer disparities and African-Americans.

    PubMed

    Sin, Mo-Kyung

    2017-07-01

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

  1. The liquid biopsy in lung cancer.

    PubMed

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

    2016-11-01

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

  2. The liquid biopsy in lung cancer

    PubMed Central

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

    2016-01-01

    The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment. PMID:28191282

  3. 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

  4. Lung Cancer in HIV-Infected Patients.

    PubMed

    Mena, Álvaro; Meijide, Héctor; Marcos, Pedro J

    2016-01-01

    The widespread use of HAART for persons living with HIV since 1996 has resulted in a dramatic decline in AIDS-related mortality. However, other comorbidities are increasing, such as metabolic disturbances or cancers, including solid organ malignancies. Among the latest, lung cancer, especially the adenocarcinoma subtype, is on the rise. HIV infection, even controlling for smoking, is an independent risk factor for developing lung cancer. HIV could promote lung cancers through immunosuppression, chronic inflammation, and a direct oncogenic effect. Smoking, lung infections, and chronic pulmonary diseases are risk factors for lung cancer. All may contribute to the cumulative incidence of lung cancer in persons living with HIV. It is double that in the general population. The role of HAART in lung cancer development in persons living with HIV is not well established. Although data supporting it could be too preliminary, persons living with HIV should be considered within high-risk groups that could benefit from screening strategies with low-dose computed tomography, especially those with airway obstruction and emphysema. Current evidence suggests that quitting smoking strategies in persons living with HIV achieve abstinence rates comparable to those in healthy HIV-negative smokers.

  5. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    PubMed Central

    Kafka, Anja; Tomas, Davor; Beroš, Vili; Pećina, Hrvoje Ivan; Zeljko, Martina; Pećina-Šlaus, Nives

    2014-01-01

    The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p = 0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain. PMID:24933634

  6. Brain metastases from lung cancer show increased expression of DVL1, DVL3 and beta-catenin and down-regulation of E-cadherin.

    PubMed

    Kafka, Anja; Tomas, Davor; Beroš, Vili; Pećina, Hrvoje Ivan; Zeljko, Martina; Pećina-Šlaus, Nives

    2014-06-13

    The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p=0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p=0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  7. Lung Cancer and Hispanics: Know the Facts

    MedlinePlus

    Lung Cancer and Hispanics: Know the Facts By the National Cancer Institute First, the good news: the number of lung cancer cases diagnosed in ... myth from fact when it comes to lung cancer. So what are the facts?  Smoking is the primary cause of lung cancer. ...

  8. Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer.

    PubMed

    Morris, Patrick G; Zhou, Xi Kathy; Milne, Ginger L; Goldstein, Daniel; Hawks, Laura C; Dang, Chau T; Modi, Shanu; Fornier, Monica N; Hudis, Clifford A; Dannenberg, Andrew J

    2013-05-01

    Elevated levels of COX-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n = 200), lung metastases (n = 100), and metastases to other sites (n = 100). Patients completed a questionnaire, provided urine, and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to nonsteroidal anti-inflammatory drugs (NSAIDs) had the highest PGE-M levels. PGE-M levels were increased in association with elevated body mass index (BMI; P < 0.001), aging (P < 0.001), pack-year smoking history (P = 0.02), lung metastases (P = 0.02), and recent cytotoxic chemotherapy (P = 0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (P < 0.001). On the basis of the current findings, PGE-M is likely to be a useful biomarker for the selection of high-risk subgroups to determine the use of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women.

  9. Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging and lung metastases in patients with breast cancer

    PubMed Central

    Morris, Patrick G.; Zhou, Xi Kathy; Milne, Ginger L.; Goldstein, Daniel; Hawks, Laura C.; Dang, Chau T.; Modi, Shanu; Fornier, Monica N.; Hudis, Clifford A.; Dannenberg, Andrew J.

    2013-01-01

    Elevated levels of cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E-metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n=200), lung metastases (n=100) and metastases to other sites (n=100). Patients completed a questionnaire, provided urine and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to NSAIDs had the highest PGE-M levels. PGE-M levels were increased in association with elevated BMI (p<0.001), aging (p<0.001), pack-year smoking history (p=0.02), lung metastases (p=0.02) and recent cytotoxic chemotherapy (p=0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (p<0.001). Based on the current findings, PGE-M is likely to be a useful biomarker for the selection of high risk subgroups to determine the utility of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women. PMID:23531446

  10. 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

  11. cAMP signaling increases histone deacetylase 8 expression via the Epac2–Rap1A–Akt pathway in H1299 lung cancer cells

    PubMed Central

    Park, Ji-Yeon; Juhnn, Yong-Sung

    2017-01-01

    This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression. ISO and the Epac activator activated Rap1, and Rap1A activation increased HDAC8 expression; moreover, inhibition of Rap1A with a dominant negative Rap1A or by shRNA-mediated knockdown abolished the ISO-induced increase in HDAC8 expression. Activation of cAMP signaling and Rap1A decreased the activating phosphorylation of Akt. Akt inhibition with a pharmacological inhibitor or expression of a dominant negative Akt inhibited the MKK4/JNK pathway and increased HDAC8 expression. The Akt inhibitor-induced increase in HDAC8 expression was abolished by pretreatment with proteasomal or lysosomal inhibitors. The ISO treatment increased cisplatin-induced apoptosis, which was abolished by HDAC8 knockdown. Exogenous HDAC8 expression increased cisplatin-induced apoptosis and decreased TIPRL expression, and the knockdown of TIPRL increased the apoptosis of cisplatin-treated cells. The ISO treatment decreased cisplatin-induced transcription of the TIPRL gene in a HDAC8-dependent manner. In conclusion, the Epac–Rap1–Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells. PMID:28232663

  12. cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells.

    PubMed

    Park, Ji-Yeon; Juhnn, Yong-Sung

    2017-02-24

    This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression. ISO and the Epac activator activated Rap1, and Rap1A activation increased HDAC8 expression; moreover, inhibition of Rap1A with a dominant negative Rap1A or by shRNA-mediated knockdown abolished the ISO-induced increase in HDAC8 expression. Activation of cAMP signaling and Rap1A decreased the activating phosphorylation of Akt. Akt inhibition with a pharmacological inhibitor or expression of a dominant negative Akt inhibited the MKK4/JNK pathway and increased HDAC8 expression. The Akt inhibitor-induced increase in HDAC8 expression was abolished by pretreatment with proteasomal or lysosomal inhibitors. The ISO treatment increased cisplatin-induced apoptosis, which was abolished by HDAC8 knockdown. Exogenous HDAC8 expression increased cisplatin-induced apoptosis and decreased TIPRL expression, and the knockdown of TIPRL increased the apoptosis of cisplatin-treated cells. The ISO treatment decreased cisplatin-induced transcription of the TIPRL gene in a HDAC8-dependent manner. In conclusion, the Epac-Rap1-Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells.

  13. Reducing Length of Hospital Stay Does Not Increase Readmission Rates in Early-Stage Gastric, Colon, and Lung Cancer Surgical Cases in Japanese Acute Care Hospitals.

    PubMed

    Kunisawa, Susumu; Fushimi, Kiyohide; Imanaka, Yuichi

    2016-01-01

    The Japanese government has worked to reduce the length of hospital stay by introducing a per-diem hospital payment system that financially incentivizes the timely discharge of patients. However, there are concerns that excessively reducing length of stay may reduce healthcare quality, such as increasing readmission rates. The objective of this study was to investigate the temporal changes in length of stay and readmission rates as quality indicators in Japanese acute care hospitals. We used an administrative claims database under the Diagnosis Procedure Combination Per-Diem Payment System for Japanese hospitals. Using this database, we selected hospitals that provided data continuously from July 2010 to March 2014 to enable analyses of temporal changes in length of stay and readmission rates. We selected stage I (T1N0M0) gastric, colon, and lung cancer surgical patients who had been discharged alive from the index hospitalization. The outcome measures were length of stay during the index hospitalization and unplanned emergency readmissions within 30 days after discharge. From among 804 hospitals, we analyzed 42,585, 15,467, and 40,156 surgical patients for gastric, colon, and lung cancer, respectively. Length of stay was reduced by approximately 0.5 days per year. In contrast, readmission rates were generally stable at approximately 2% or had decreased slightly over the 4-year period. In early-stage gastric, colon, and lung cancer surgical patients in Japan, reductions in length of stay did not result in increased readmission rates.

  14. Reducing Length of Hospital Stay Does Not Increase Readmission Rates in Early-Stage Gastric, Colon, and Lung Cancer Surgical Cases in Japanese Acute Care Hospitals

    PubMed Central

    Kunisawa, Susumu; Fushimi, Kiyohide; Imanaka, Yuichi

    2016-01-01

    Background The Japanese government has worked to reduce the length of hospital stay by introducing a per-diem hospital payment system that financially incentivizes the timely discharge of patients. However, there are concerns that excessively reducing length of stay may reduce healthcare quality, such as increasing readmission rates. The objective of this study was to investigate the temporal changes in length of stay and readmission rates as quality indicators in Japanese acute care hospitals. Methods We used an administrative claims database under the Diagnosis Procedure Combination Per-Diem Payment System for Japanese hospitals. Using this database, we selected hospitals that provided data continuously from July 2010 to March 2014 to enable analyses of temporal changes in length of stay and readmission rates. We selected stage I (T1N0M0) gastric, colon, and lung cancer surgical patients who had been discharged alive from the index hospitalization. The outcome measures were length of stay during the index hospitalization and unplanned emergency readmissions within 30 days after discharge. Results From among 804 hospitals, we analyzed 42,585, 15,467, and 40,156 surgical patients for gastric, colon, and lung cancer, respectively. Length of stay was reduced by approximately 0.5 days per year. In contrast, readmission rates were generally stable at approximately 2% or had decreased slightly over the 4-year period. Conclusions In early-stage gastric, colon, and lung cancer surgical patients in Japan, reductions in length of stay did not result in increased readmission rates. PMID:27832182

  15. Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.

    PubMed

    Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Guo, Zhenzhen; Cao, Ning; Ma, Xiaofang; Du, Zhenhua; Li, Jiahuan; Duan, Yongjian; Du, Gangjun

    Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

  16. Customizing Therapies for Lung Cancer | Center for Cancer Research

    Cancer.gov

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

  17. Exercise therapy across the lung cancer continuum.

    PubMed

    Jones, Lee W; Eves, Neil D; Waner, Emily; Joy, Anil A

    2009-07-01

    A lung cancer diagnosis and associated therapeutic management are associated with unique and varying degrees of adverse physical/functional impairments that dramatically reduce patients' ability to tolerate exercise. Poor exercise capacity predisposes to increased susceptibility to other common age-related diseases, poor quality of life, and likely premature death. This article reviews the literature investigating the role of exercise as an adjunct therapy across the lung cancer continuum (ie, prevention to palliation). The current evidence suggests that exercise training is a safe and feasible adjunct therapy for patients with operable lung cancer both before and after pulmonary resection. Among patients with inoperable disease, feasibility and safety studies of carefully prescribed exercise training are warranted. Preliminary evidence in this area suggests that exercise therapy may be an important consideration in multidisciplinary management of patients diagnosed with lung cancer.

  18. Physical activity and lung cancer survivorship.

    PubMed

    Jones, Lee W

    2011-01-01

    A lung cancer diagnosis and associated therapeutic management is associated with unique and varying degrees of adverse physical/functional impairments that dramatically reduce a patient's ability to tolerate exercise. Poor exercise tolerance predisposes to increased susceptibility to other common age-related diseases, poor quality of life (QOL), and likely premature death. Here we review the putative literature investigating the role of exercise as an adjunct therapy across the lung cancer continuum (i.e., diagnosis to palliation). The current evidence suggests that exercise training is a safe and feasible adjunct therapy for operable lung cancer patients both before and after pulmonary resection. Among patients with inoperable disease, feasibility and safety studies of carefully prescribed exercise training are warranted. Preliminary evidence in this area supports that exercise therapy may be an important consideration in multidisciplinary management of patients diagnosed with lung cancer.

  19. SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers.

    PubMed

    Tagal, Vural; Wei, Shuguang; Zhang, Wei; Brekken, Rolf A; Posner, Bruce A; Peyton, Michael; Girard, Luc; Hwang, TaeHyun; Wheeler, David A; Minna, John D; White, Michael A; Gazdar, Adi F; Roth, Michael G

    2017-01-19

    Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells. AURKA inhibitors may provide a therapeutic strategy for biomarker-driven clinical studies to treat the NSCLCs harbouring SMARCA4/BRG1-inactivating mutations.

  20. SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers

    PubMed Central

    Tagal, Vural; Wei, Shuguang; Zhang, Wei; Brekken, Rolf A.; Posner, Bruce A.; Peyton, Michael; Girard, Luc; Hwang, TaeHyun; Wheeler, David A.; Minna, John D.; White, Michael A.; Gazdar, Adi F.; Roth, Michael G.

    2017-01-01

    Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells. AURKA inhibitors may provide a therapeutic strategy for biomarker-driven clinical studies to treat the NSCLCs harbouring SMARCA4/BRG1-inactivating mutations. PMID:28102363

  1. Cullin7 is required for lung cancer cell proliferation and is overexpressed in lung cancer.

    PubMed

    Men, Xuelin; Wang, Lingcheng; Yu, Wenfei; Ju, Yuanrong

    2015-01-01

    Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in lung cancer carcinogenesis remains unclear. In this study, we explored the functional role of Cullin7 in lung cancer cell proliferation and tumorigenesis and determined its expression profile in lung cancer. Knocking down Cullin7 expression by small interfering RNA (siRNA) in lung cancer cells inhibited cell proliferation and elevated the expression of p53, p27, and p21 proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. Cullin7 knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, Cullin7 expression was increased in primary lung cancer tissues of humans. Thus, Cullin7 is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in lung cancer and may be a potential therapeutic target for lung cancer management.

  2. Lung Cancer Risk Models for Screening (R package: lcrisks)

    Cancer.gov

    In both the absence and presence of screening, the R package lcrisks, calculates individual risks of lung cancer and lung cancer death based on covariates: age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. In the presence of CT screening akin to the NLST (3 yearly screens, 5 years of follow-up), it uses the covariates to estimate risk of false-positive CT screen as well as the reduction in risk of lung cancer death and increase in risk of lung cancer screening.

  3. 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

  4. [Lung cancer and epigenetic modifications].

    PubMed

    Darılmaz Yüce, Gülbahar; Ortaç Ersoy, Ebru

    2016-06-01

    Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA expression, have been reported to play a major role in the genesis of lung cancer. DNA methylation, histone modifications, and RNA expression are epigenetic markers in assesment of early detection, prognosis and evaluation of treatment of lung cancer. In this rewiev we summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and to provide an overview of the potential translational applications of these changes, including applications for early detection, diagnosis, prognostication, and therapeutics.

  5. An Online Learning Module to Increase Self-Efficacy and Involvement in Care for Patients With Advanced Lung Cancer: Research Protocol

    PubMed Central

    Nagrial, Adnan; Pene, Christopher; Rabbets, Melanie; Carlino, Matteo; Zachulski, Clare; Phillips, Jane; Birnbaum, Robert; Gandhi, Tejal; Harnett, Paul

    2016-01-01

    Background Improving patient care for individuals with lung cancer is a priority due to the increasing burden of the disease globally. One way this can be done is by improving patient self-management capabilities through increasing their self-efficacy. This can improve positive outcomes for patients with chronic conditions and increase their ability to manage the challenges of such illnesses. Unfortunately, patients with chronic conditions often struggle to travel far from home to engage with patient education events, a common means of improving self-efficacy. The development of more accessible tools for improving patient self-efficacy is required to increase quality of life for patients with chronic conditions. Objective To evaluate the feasibility of delivering symptom identification and management information to patients with advanced lung cancer using an online program. Methods This article describes a pre-post test study to evaluate a Qstream online learning platform to improve patient self-efficacy for managing advanced lung cancer symptoms. Undertaking this program should increase participant knowledge about the side-effects they may experience as a result of their treatment and in turn increase help-seeking behavior and self-efficacy for the participant cohort. Quantitative data collected by the Qstream platform on the completion rates of participants will be used as a tool to evaluate the intervention. Additionally, validated scales will be used to collect data on patient self-efficacy. Qualitative data will also be collected via an exit survey and thematic content analysis of semi-structured interviews. Results The research is in the preliminary stages but thus far a protocol has been approved in support of the project. Additionally, advisory committee members have been identified and initial meetings have been undertaken. Conclusions Development of new approaches for increasing patient understanding of their care is important to ensure high quality care

  6. An Online Learning Module to Increase Self-Efficacy and Involvement in Care for Patients With Advanced Lung Cancer: Research Protocol.

    PubMed

    Janssen, Anna; Shaw, Tim; Nagrial, Adnan; Pene, Christopher; Rabbets, Melanie; Carlino, Matteo; Zachulski, Clare; Phillips, Jane; Birnbaum, Robert; Gandhi, Tejal; Harnett, Paul

    2016-08-08

    Improving patient care for individuals with lung cancer is a priority due to the increasing burden of the disease globally. One way this can be done is by improving patient self-management capabilities through increasing their self-efficacy. This can improve positive outcomes for patients with chronic conditions and increase their ability to manage the challenges of such illnesses. Unfortunately, patients with chronic conditions often struggle to travel far from home to engage with patient education events, a common means of improving self-efficacy. The development of more accessible tools for improving patient self-efficacy is required to increase quality of life for patients with chronic conditions. To evaluate the feasibility of delivering symptom identification and management information to patients with advanced lung cancer using an online program. This article describes a pre-post test study to evaluate a Qstream online learning platform to improve patient self-efficacy for managing advanced lung cancer symptoms. Undertaking this program should increase participant knowledge about the side-effects they may experience as a result of their treatment and in turn increase help-seeking behavior and self-efficacy for the participant cohort. Quantitative data collected by the Qstream platform on the completion rates of participants will be used as a tool to evaluate the intervention. Additionally, validated scales will be used to collect data on patient self-efficacy. Qualitative data will also be collected via an exit survey and thematic content analysis of semi-structured interviews. The research is in the preliminary stages but thus far a protocol has been approved in support of the project. Additionally, advisory committee members have been identified and initial meetings have been undertaken. Development of new approaches for increasing patient understanding of their care is important to ensure high quality care continues to be delivered in the clinical setting.

  7. The early diagnosis of lung cancer

    PubMed Central

    Deeley, T. J.

    1972-01-01

    Earlier diagnosis of malignant disease in the lung may bring about improvements in the treatment. This article discusses the effects of early diagnosis on the prognosis. Cancer of the lung may be associated with other lung pathology, thus increasing the problems of diagnosis. Diagnosis depends on radiological examination, cytology of the sputum, radio-isotope lung scanning and mediastinoscopy: an account is given of how these may be used to diagnose the condition whilst it is still at an early stage and suitable for radical treatment. PMID:4552427

  8. Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway.

    PubMed

    Friedman, Jamie R; Perry, Haley E; Brown, Kathleen C; Gao, Ying; Lin, Ju; Stevenson, Cathyrn D; Hurley, John D; Nolan, Nicholas A; Akers, Austin T; Chen, Yi Charlie; Denning, Krista L; Brown, Linda G; Dasgupta, Piyali

    2017-04-01

    Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data foster hope for novel nutrition based combination therapies in SCLC.

  9. Indoor radon and lung cancer in China.

    PubMed

    Blot, W J; Xu, Z Y; Boice, J D; Zhao, D Z; Stone, B J; Sun, J; Jing, L B; Fraumeni, J F

    1990-06-20

    Radon has long been known to contribute to risk of lung cancer, especially in undergound miners who are exposed to large amounts of the carcinogen. Recently, however, lower amounts of radon present in living areas have been suggested as an important cause of lung cancer. In an effort to clarify the relationship of low amounts of radon with lung cancer risk, we placed alpha-track radon detectors in the homes of 308 women with newly diagnosed lung cancer and 356 randomly selected female control subjects of similar age. Measurements were taken after 1 year. All study participants were part of the general population of Shenyang, People's Republic of China, an industrial city in the northeast part of the country that has one of the world's highest rates of lung cancer in women. The median time of residence in the homes was 24 years. The median household radon level was 2.3 pCi/L of air; 20% of the levels were greater than 4 pCi/L. Radon levels tended to be higher in single-story houses or on the first floor of multiple-story dwellings, and they were also higher in houses with increased levels of indoor air pollution from coal-burning stoves. However, the levels were not higher in homes of women who developed lung cancer than in homes of controls, nor did lung cancer risk increase with increasing radon level. No association between radon and lung cancer was observed regardless of cigarette-smoking status, except for a nonsignificant trend among heavy smokers. No positive associations of lung cancer cell type with radon were observed, except for a nonsignificant excess risk of small cell cancers among the more heavily exposed residents. Our data suggest that projections from surveys of miners exposed to high radon levels may have overestimated the overall risks of lung cancer associated with levels typically seen in homes in this Chinese city. However, further studies in other population groups are needed to clarify the carcinogenic potential of indoor radon.

  10. Elemene Increases Autophagic Apoptosis and Drug Sensitivity in Human Cisplatin (DDP)-Resistant Lung Cancer Cell Line SPC-A-1/DDP By Inducing Beclin-1 Expression.

    PubMed

    Zhou, Kun; Wang, Liping; Cheng, Ruirui; Liu, Xia; Mao, Shengya; Yan, Yan

    2017-05-23

    Drug resistance is the major obstacle for the successful therapy of lung adenocarcinoma. It was suggested that ß-elemene, a major isoform of elemene, could reverse the drug resistance in lung cancer cells. However, the underlying mechanisms remains poorly known. Here, we aimed to investigate whether elemene is involved in the cisplatin (DDP)-resistance of lung adenocarcinoma cells and further explore the underlying mechanism. The results showed that human lung adenocarcinoma cell line SPC-A-1 and its DDP-resistant strain SPC-A-1/DDP had a similar sensitivity to elemene treatment. Low dose elemene increased the sensitivity of SPC-A-1/DDP cells to DDP, accompanied by a dramatically decrease in expression of multidrug-resistance proteins and cell proliferation, and an increase in cell autophagy and autophagic apoptosis. We found that the expression of Beclin-1, the key regulator of autophagy, was induced by elemene treatment in a dose-dependent manner. Furthermore, we found that Beclin-1 overexpression had a similar effect with elemene treatment on autophagy and autophagic apoptosis in SPC-A-1/DDP cells. In contrast, Beclin-1 knockdown could significantly rescue elemene-induced autophagic apoptosis and counteract elemene-induced sensitivity in SPC-A-1/DDP cells. Our findings demonstrate that elemene can reverses the drug resistance of SPC-A-1/DDP cells via promotion of Beclin-1-induced autophagy.

  11. Dark tobacco and lung cancer in Cuba.

    PubMed

    Joly, O G; Lubin, J H; Caraballoso, M

    1984-01-01

    A retrospective case control study of lung cancer was conducted in Havana, Cuba to investigate whether Cuban high lung cancer mortality rates could be explained by cigarette and cigar consumption habits, including the smoking of dark tobacco cigarettes. The cases were drawn from patients admitted from 1978 to 1980 to the city's 12 main general hospitals with a tentative diagnosis of lung cancer. Only patients whose final diagnosis was confirmed by cytology and/ or histology according to the World Health Organization's Classification of Lung Cancer were included. A hospital control selected from patients with a current admission for a nonsmoking-related disease was matched to each case by sex, age, hospital of admission, and admission date. Data on 826 confirmed lung cancer cases (219 females and 607 males), 979 hospital controls, and 539 neighborhood controls were analyzed with procedures for matched and unmatched studies. Lung cancer patients ranged in age from 23 to 89 years; approximately 1/2 were females and 2/3 of the males were 60 years or older at diagnosis. Education level was similar in all groups. 167 of the 219 female cases (76.3%) and 595 of the 607 male cases (98%) ever smoked regularly, compared with 31% and 80.3%, respectively, of female and male controls. The corresponding proportions for female hospital and neighborhood controls were 30.5 and 31.8%, whereas for males they were 80.5% and 80.1%. The overall relative risk (RR) of lung cancer in cigarette smokers was 7.3 for females and 14.1 for males. Most smokers consumed the local dark tobacco ciagrettes exclusively. There were increased risks of lung cancer in both sexes associated with smoking both tobaccos, but the excess was greater for dark tobacco. The differences were reduced after adjustment for amount smoked. With either dark or light tobacco, the longer the duration of smoking or the greater the total number of cigarettes consumed, the higher the risk, all trends being highly significant

  12. SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers. | Office of Cancer Genomics

    Cancer.gov

    Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models.

  13. Inflammation in the development of lung cancer: epidemiological evidence.

    PubMed

    Engels, Eric A

    2008-04-01

    The lung is a site for repeated or chronic inflammatory insults. Epidemiologic research has provided evidence to support the hypothesis that tissue damage caused by inflammation can initiate or promote the development of lung cancer, possibly in conjunction with tobacco use. For example, some studies suggest an increased risk of lung cancer among persons with lung infections, such as tuberculosis, bacterial pneumonia, or inflammatory lung diseases. Elevated serum levels of C-reactive protein, an inflammation marker, are associated with heightened lung cancer risk. Recent studies also demonstrate increased lung cancer risk among immunosuppressed individuals infected with HIV. Other research indicates an association between genetic polymorphisms in the inflammation pathway, which might modulate the inflammatory response and lung cancer risk.

  14. Metastatic cancer to the lung

    MedlinePlus

    ... lungs may include: Fluid between the lung and chest wall (pleural effusion), which can cause shortness of breath or pain when taking a deep breath Further spread of the cancer Side effects of chemotherapy or radiation therapy When to Contact a Medical Professional Call ...

  15. 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

  16. A high-fat diet increases angiogenesis, solid tumor growth, and lung metastasis of CT26 colon cancer cells in obesity-resistant BALB/c mice.

    PubMed

    Park, Heesook; Kim, Minhee; Kwon, Gyoo Taik; Lim, Do Young; Yu, Rina; Sung, Mi-Kyung; Lee, Ki Won; Daily, James W; Park, Jung Han Yoon

    2012-11-01

    We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right flank. Solid tumor growth and the number and volume of tumor nodules in the lung were increased markedly in the HFD group with only a slight increase in body weight (5.9%). HFD feeding increased tumor tissue levels of Ki67, cyclin A, cyclin D1, CDK2, Bcl-xL, and Bcl-2; reduced p53 levels and TUNEL-positive apoptotic cells; increased the levels of CD45, CD68, CD31, VEGF, P-VEGF receptor-2, iNOS, and COX-2 as well as hemoglobin content; and increased the levels of HIF-1α, P-STAT3-Y705, P-STAT3-S727, P-IκB-α, P-p65, p65, P-c-Jun, P-Akt, P-ERK1/2, P-p38, and P-SAPK/JNK. HFD feeding increased the serum levels of EGF, insulin, IGF-I, IFN-γ, leptin, RANTES, MCP-1, IL-1ra, and SDF-1α and media conditioned by epididymal fat tissue explants from HFD-fed mice caused an increase in microvessel outgrowth from the mouse aorta and tube formation of human umbilical vein endothelial cells. These results indicate that the chronic consumption of an HFD increases colon cancer cell proliferation, tumor angiogenesis, and lung metastasis in mice in the absence of discernible weight gain. HFD feeding increases the levels of growth factors which activate transcription factors, thereby inducing the expression of many genes involved in the stimulation of inflammation, angiogenesis, and cellular proliferation. Copyright © 2011 Wiley Periodicals, Inc.

  17. H460 non-small cell lung cancer stem-like holoclones yield tumors with increased vascularity

    PubMed Central

    Manley, Eugene; Waxman, David J.

    2014-01-01

    Cancer stem-like cells were isolated from several human tumor cell lines by limiting dilution assays and holoclone morphology, followed by assessment of self-renewal capacity, tumor growth, vascularity, and blood perfusion. H460 holoclone-derived tumors grew slower than parental H460 tumors, but displayed significantly increased microvessel density and tumor blood perfusion. Microarray analysis identified 177 differentially regulated genes in the holoclone-derived tumors, of which 47 were associated with angiogenesis. The dysregulated genes include several small leucine-rich proteoglycans that may modulate angiogenesis and serve as novel therapeutic targets for inhibiting cancer stem cell-driven angiogenesis. PMID:24334139

  18. H460 non-small cell lung cancer stem-like holoclones yield tumors with increased vascularity.

    PubMed

    Manley, Eugene; Waxman, David J

    2014-04-28

    Cancer stem-like cells were isolated from several human tumor cell lines by limiting dilution assays and holoclone morphology, followed by assessment of self-renewal capacity, tumor growth, vascularity, and blood perfusion. H460 holoclone-derived tumors grew slower than parental H460 tumors, but displayed significantly increased microvessel density and tumor blood perfusion. Microarray analysis identified 177 differentially regulated genes in the holoclone-derived tumors, of which 47 were associated with angiogenesis. The dysregulated genes include several small leucine-rich proteoglycans that may modulate angiogenesis and serve as novel therapeutic targets for inhibiting cancer stem cell-driven angiogenesis.

  19. 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

  20. Infectious complications in patients with lung cancer.

    PubMed

    Akinosoglou, K S; Karkoulias, K; Marangos, M

    2013-01-01

    Infections remain a part of the natural course of cancer. During the course of their disease, patients with lung cancer frequently present with an infection that can ultimately be fatal. Pathogenesis of infectious syndromes is usually determined by the underlying disease, as well as, the iatrogenic manipulations that occur during its management. Hence, lung cancer infections include lower respiratory tract infections in the context of COPD, aspiration, obstruction and opportunistic infections due to immunosuppression. Moreover, treatment-related infectious syndromes including post operative pneumonia, febrile neutropenia and superimposed infection following radiation/chemotherapy toxicity is common. Importantly, diagnosis of infection in the febrile lung cancer patient is challenging and requires a high index of suspicion in order to distinguish from other causes of fever, including malignant disease and pulmonary embolism. Prompt initiation of treatment is pivotal to avoid increased mortality. Careful consideration of infection pathogenesis can predict most likely pathogens and guide antibiotic management, thus, ensuring most favourable outcome.

  1. Lung cancer nanomedicine: potentials and pitfalls.

    PubMed

    Bölükbas, Deniz Ali; Meiners, Silke

    2015-01-01

    Lung cancer is by far the most common cause of cancer-related deaths in the world. Nanoparticle-based therapies enable targeted drug delivery for lung cancer treatment with increased therapeutic efficiency and reduced systemic toxicity. At the same time, nanomedicine has the potential for multimodal treatment of lung cancer that may involve 'all-in-one' targeting of several tumor-associated cell types in a timely and spatially controlled manner. Therapeutic approaches, however, are hampered by a translational gap between basic scientists, clinicians and pharma industry due to suboptimal animal models and difficulties in scale-up production of nanoagents. This calls for a disease-centered approach with interdisciplinary basic and clinical research teams with the support of pharma industries.

  2. MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines

    PubMed Central

    Grosso, S; Doyen, J; Parks, S K; Bertero, T; Paye, A; Cardinaud, B; Gounon, P; Lacas-Gervais, S; Noël, A; Pouysségur, J; Barbry, P; Mazure, N M; Mari, B

    2013-01-01

    The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional mode of hypoxia-inducible factor (HIF)-dependent transcriptional regulation, involving modulation of a specific set of micro RNAs (miRNAs), including miR-210, has emerged. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. Therefore, we hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed a non-small cell lung carcinoma (NSCLC)-derived cell line (A549) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). The miR-210-expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. Cells were subjected to radiation levels ranging from 0 to 10 Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of radioresistance as control cells in hypoxia. Under hypoxia, pmiR-210 cells showed a low mortality rate owing to a decrease in apoptosis, with an ability to grow even at 10 Gy. This miR-210 phenotype was reproduced in another NSCLC cell line (H1975) and in HeLa cells. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we have shown that genomic double-strand breaks (DSBs) foci disappear faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells removed the radioresistant phenotype, showing that this mechanism is dependent on HIF-1. In conclusion, miR-210 appears to be a component of the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could be used by tumor cells in conditions where reoxygenation has occurred and suggests that strategies targeting miR-210 could enhance tumor radiosensitization. PMID:23492775

  3. 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.

  4. Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer.

    PubMed

    Zhang, Fuquan; Duan, Shanzhou; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2016-06-01

    Cisplatin-resistant A549 and H157 (A549CisR and H157CisR) non-small cell lung cancer cells show increased stemness of cancer stem cells (CSCs) compared to their parental cells. We investigated whether interleukin-6 (IL-6) signaling contributes to this increased stemness in cisplatin-resistant cells. When A549CisR and H157CisR cells were treated with neutralizing IL-6 antibody, decreased cisplatin resistance was observed, whereas IL-6 treatment of parental cells resulted in increased cisplatin resistance. Expression of the CSC markers was significantly upregulated in IL-6-expressing scramble cells (in vitro) and scramble cell-derived tumor tissues (in vivo) after cisplatin treatment, but not in IL-6 knocked down (IL-6si) (in vitro) cells and in IL-6si cell-derived tumor tissues (in vivo), suggesting the importance of IL-6 signaling in triggering increased stemness during cisplatin resistance development. Hypoxia inducible factors (HIFs) were upregulated by IL-6 and responsible for the increased CSC stemness on cisplatin treatment. Mechanism dissection studies found that upregulation of HIFs by IL-6 was through transcriptional control and inhibition of HIF degradation. Treatment of HIF inhibitor (FM19G11) abolished the upregulation of CSC markers and increased sphere formations in IL-6 expressing cells on cisplatin treatment. In all, IL-6-mediated HIF upregulation is important in increasing stemness during cisplatin resistance development, and we suggest that the strategies of inhibiting IL-6 signaling or its downstream HIF molecules can be used as future therapeutic approaches to target CSCs after cisplatin treatment for lung cancer.

  5. 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.

  6. Carotenoids and lung cancer prevention

    USDA-ARS?s Scientific Manuscript database

    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...

  7. Cigarette smoke and lung cancer

    SciTech Connect

    Martonen, T.B.; Hofmann, W.; Lowe, J.E.

    1987-01-01

    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 specifically at airway bifurcations. The elevated risk of lung cancer to smokers may result from a complex interplay between smoking and exposure to ambient Rn progeny, including the promotional-effect role (as opposed to being the initiating event) of cigarette smoke in tumor development. It has been determined that smokers exposed to average indoor Rn progency levels receive surprisingly high doses at hot spots within bronchial bifurcations.

  8. 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

  9. Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells.

    PubMed

    An, Hyun-Kyu; Kim, Kyoung-Sook; Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon

    2014-01-01

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA), pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ) suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α) and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy.

  10. Mimulone-Induced Autophagy through p53-Mediated AMPK/mTOR Pathway Increases Caspase-Mediated Apoptotic Cell Death in A549 Human Lung Cancer Cells

    PubMed Central

    Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon

    2014-01-01

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA), pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ) suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α) and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy. PMID:25490748

  11. Does diesel exhaust cause human lung cancer?

    PubMed

    Cox, L A

    1997-12-01

    Recent reviews of epidemiological evidence on the relation between exposure to diesel exhaust (DE) and lung cancer risk have reached conflicting conclusions, ranging from belief that there is sufficient evidence to conclude that DE is a human lung carcinogen (California EPA, 1994) to conclusions that there is inadequate evidence to support a causal association between DE and human lung cancer (Muscat and Wynder, 1995). Individual studies also conflict, with both increases and decreases in relative risks of lung cancer mortality being cited with 95% statistical confidence. On balance, reports of elevated risk outnumber reports of reduced risk. This paper reexamines the evidence linking DE exposures to lung cancer risk. After briefly reviewing animal data and biological mechanisms, it surveys the relevant epidemiological literature and examines possible explanations for the discrepancies. These explanations emphasize the distinction between statistical associations, which have been found in many studies, and causal associations, which appear not to have been established. Methodological threats to valid causal inference are identified and new approaches for controlling them are proposed using recent techniques from artificial intelligence (AI) and computational statistics. These threats have not been adequately controlled for in previous epidemiological studies. They provide plausible noncausal explanations for the reported increases in relative risks, making it impossible to infer causality between DE exposure and lung cancer risk from these studies. A key contribution is to show how recent techniques developed in the AI-and-statistics literature can help clarify the causal interpretation of complex multivariate data sets used in epidemiological risk assessments. Applied to the key study of Garshick et al. (1988), these methods show that DE concentration has no positive causal association with occupational lung cancer mortality risk.

  12. Prevention and management of lung cancer in China.

    PubMed

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

    2015-09-01

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

  13. Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation.

    PubMed

    Ke, Xing; Zhang, Shuping; Xu, Jian; Liu, Genyan; Zhang, Lixia; Xie, Erfu; Gao, Li; Li, Daqian; Sun, Ruihong; Wang, Fang; Pan, Shiyang

    2016-05-01

    Patients with non-small-cell lung cancer (NSCLC) have immune defects that are poorly understood. Forkhead box protein P3 (Foxp3) is crucial for immunosuppression by CD4(+) regulatory T cells (Tregs). It is not well known how NSCLC induces Foxp3 expression and causes immunosuppression in tumor-bearing patients. Our study found a higher percentage of CD4(+) Tregs in the peripheral blood of NSCLC compared with healthy donors. NSCLC patients showed demethylation of eight CpG sites within the Foxp3 promoter with methylation ratios negatively correlated with CD4(+)CD25(+)Foxp3(+) T levels. Foxp3 expression in CD4(+) Tregs was directly regulated by Foxp3 promoter demethylation and was involved in immunosuppression by NSCLC. To verify the effect of tumor cells on the phenotype and function of CD4(+) Tregs, we established a coculture system using NSCLC cell line and healthy CD4(+) T cells and showed that SPC-A1 induced IL-10 and TGF-β1 secretion by affecting the function of CD4(+) Tregs. The activity of DNA methyltransferases from CD4(+) T was decreased during this process. Furthermore, eight CpG sites within the Foxp3 promoter also appeared to have undergone demethylation. Foxp3 is highly expressed in CD4(+) T cells, and this may be caused by gene promoter demethylation. These induced Tregs are highly immunosuppressive and dramatically inhibit the proliferative activity of naïve CD4(+) T cells. Our study provides one possible mechanism describing Foxp3 promoter demethylation changes by which NSCLC down-regulates immune responses and contributes to tumor progression. Foxp3 represents an important target for NSCLC anti-tumor immunotherapy.

  14. Lung cancer: a rare indication for, but frequent complication after lung transplantation

    PubMed Central

    Vos, Robin; Yserbyt, Jonas; Decaluwe, Herbert; De Leyn, Paul; Verleden, Geert M.

    2016-01-01

    Lung transplantation is an effective and safe therapy for carefully selected patients suffering from a variety of end-stage pulmonary diseases. Lung cancer negatively affects prognosis, particularly in patients who are no longer candidates for complete resection. Lung transplantation can be considered for carefully selected and well staged lung cancer patients with proven, lung-limited, multifocal, (minimally invasive) adenocarcinoma in situ (AIS) (previously called bronchioloalveolar cell carcinoma) causing respiratory failure. Despite a substantial risk of tumour recurrence (33–75%), lung transplantation may offer a survival benefit (50% at 5 years) with best palliation of their disease. Reports on lung transplantation for other low-grade malignancies are rare. Lung transplant candidates at higher risk for developing lung cancer [mainly previous smokers with chronic obstructive lung disease (COPD) and idiopathic pulmonary fibrosis (IPF) or older patients] should be thoroughly and repeatedly screened for lung cancer prior to listing, and preferably also during waiting list time if longer than 1 year, including the use of PET-CT scan and EBUS-assisted bronchoscopy in case of undefined, but suspicious pulmonary abnormalities. Double-lung transplantation should now replace single-lung transplantation in these high-risk patients because of a 6–9% prevalence of lung cancer developing in the remaining native lung. Patients with unexpected, early stage bronchial carcinoma in the explanted lung may have favourable survival without recurrence. Early PET-CT (at 3–6 months) following lung transplantation is advisable to detect early, subclinical disease progression. Donor lungs from (former) smokers should be well examined at retrieval. Suspicious nodules should be biopsied to avoid grafting cancer in the recipient. Close follow-up with regular visits and screening test in all recipients is needed because of the increased risk of developing a primary or secondary

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

    ClinicalTrials.gov

    2017-05-23

    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

  16. cAMP signaling increases histone deacetylase 8 expression by inhibiting JNK-dependent degradation via autophagy and the proteasome system in H1299 lung cancer cells.

    PubMed

    Park, Ji-Yeon; Juhnn, Yong-Sung

    2016-02-05

    This study aimed to investigate the roles of autophagy and the ubiquitin-proteasome system in the degradation of histone deacetylase 8 (HDAC8) and to clarify the mechanism by which cAMP signaling regulates this degradation. cAMP signaling was activated by treating H1299 non-small cell lung cancer cells with isoproterenol or forskolin/3-isobutyl-1-methylxanthine, and HDAC8 expression was assessed by western blot analysis. The inhibition of autophagy and ubiquitin-proteasome-dependent degradation increased HDAC8 expression. cAMP signaling inhibited JNK activation, which decreased the phosphorylation of Bcl-2, thereby reducing autophagy, and the phosphorylation of Itch, thereby reducing ubiquitination. These results suggest that the HDAC8 protein is degraded via autophagy and the ubiquitin-proteasome system and that cAMP signaling increases HDAC8 protein levels by reducing JNK-mediated autophagy and ubiquitin-proteasome-dependent degradation of the HDAC8 protein in H1299 lung cancer cells.

  17. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    SciTech Connect

    Krivonogov, Nikolay G.; Efimova, Nataliya Y. Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-02

    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. 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.

  19. Targeted Therapies for Lung Cancer

    PubMed Central

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V.; Minna, John D.

    2012-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic targets. Perhaps the most significant advance in the treatment of this challenging disease is the introduction of molecularly targeted therapies, a term that currently includes monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The development of effective targeted therapeutics requires knowledge of the genes and pathways involved and how they relate to the biologic behavior of lung cancer. Drugs targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and vascular endothelial growth factor are now U.S. Food and Drug Administration approved for the treatment of advanced non-small cell lung cancer. These agents are generally better tolerated than conventional chemotherapy and show dramatic efficacy when their use is coupled with a clear understanding of clinical data, mechanism, patient selection, drug interactions, and toxicities. Integrating genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes will provide a wealth of new possibilities for lung cancer–targeted therapeutics. Ongoing research efforts in these areas as well as a discussion of emerging targeted agents being evaluated in clinical trials are the subjects of this review. PMID:22157296

  20. 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

  1. COPD in primary lung cancer patients: prevalence and mortality.

    PubMed

    Ytterstad, Elinor; Moe, Per C; Hjalmarsen, Audhild

    2016-01-01

    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. 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. 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. The observed prevalence of COPD was lower than that in previous studies. Neither COPD nor emphysema were significantly associated with lung cancer mortality.

  2. 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

  3. 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

  4. Suicide Risk Quadruples After Lung Cancer Diagnosis

    MedlinePlus

    ... news/fullstory_165864.html Suicide Risk Quadruples After Lung Cancer Diagnosis Doctors, loved ones need to be on ... TUESDAY, May 23, 2017 (HealthDay News) -- People with lung cancer have a strikingly higher-than-normal risk of ...

  5. Lung cancer among women in north-east China.

    PubMed

    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

    1990-12-01

    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.

  6. Lung Cancer and Eye Metastases

    PubMed Central

    Lampaki, Sofia; Kioumis, Ioannis; Pitsiou, Georgia; Lazaridis, George; Syrigos, Konstantinos; Trakada, Georgia; Kakolyris, Stylianos; Zarogoulidis, Konstantinos; Mpoukovinas, Ioannis; Rapti, Aggeliki; Zarogoulidis, Paul

    2014-01-01

    It has been observed that lung cancer either non-small cell or small cell is responsible for eye metastases. This form of metastases in several cases was the first manifestation of the disease and further investigation led to the diagnosis of the underlying malignancy. Both types of lung cancer are equally responsible for this demonstration. Furthermore; both chemotherapy and tyrosine kinase inhibitors have shown equal positive results in treating the exophalmos manifestation. Up to date information will be presented in our current work. PMID:25738158

  7. Lung cancer in the meat industry.

    PubMed Central

    Coggon, D; Pannett, B; Pippard, E C; Winter, P D

    1989-01-01

    Routine statistics of occupational mortality and incidence of cancer have consistently shown high rates of lung cancer in butchers. Possible explanations include infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic hydrocarbons and nitrites in the preservation of meat, or a confounding effect of tobacco. To explore these possibilities, we have examined the mortality of 1610 men employed at three British companies processing pork, beef, lamb, bacon, and other meat products. The overall death rate was less than in the national population (271 deaths observed, 310 expected) but there was an excess of deaths from cancer (87 observed, 80 expected), and in particular from lung cancer (42 observed, 32 expected). The risk of lung cancer was concentrated in subjects exposed to recently slaughtered meat, especially after an interval of 10 or more years. These findings increase suspicions of a risk of lung cancer in butchers, although further information is needed about smoking habits in the meat industry. If there is a hazard infection by a papilloma virus would seem the most likely cause. PMID:2930728

  8. Science, medicine, and the future. Lung cancer.

    PubMed Central

    Sethi, T.

    1997-01-01

    Lung cancer, the most prevalent cancer in the Western world, is mainly caused by smoking. Nevertheless, only 20% of smokers develop lung cancer and while prevention is important, environmental factors are expected to contribute to the predicted rise in the incidence of lung cancer in the next 25 years. Survival of lung cancer is still poor, and new treatments are urgently needed. This review examines potential new therapeutic developments which have arisen from a greater understanding of the molecular and cellular biology of lung cancers. PMID:9066480

  9. Inhibitory effect of trans-ferulic acid on proliferation and migration of human lung cancer cells accompanied with increased endogenous reactive oxygen species and β-catenin instability.

    PubMed

    Fong, Yao; Tang, Chia-Chun; Hu, Huei-Ting; Fang, Hsin-Yu; Chen, Bing-Hung; Wu, Chang-Yi; Yuan, Shyng-Shiou; Wang, Hui-Min David; Chen, Yen-Chun; Teng, Yen-Ni; Chiu, Chien-Chih

    2016-01-01

    Trans-ferulic (FA) acid exhibits antioxidant effects in vitro. However, the underlying mechanism of trans-FA activity in cellular physiology, especially cancer physiology, remains largely unknown. This study investigated the cellular physiological effects of trans-FA on the H1299 human lung cancer cell line. The 2,2-diphenyl-1-picrylhydrazyl assay was used to determine free radical scavenging capability. Assessment of intracellular reactive oxygen species (ROS) was evaluated using oxidized 2',7'-dichlorofluorescin diacetate and dihydroethidium staining. Trypan blue exclusion, colony formation, and anchorage-independent growth assays were used to determine cellular proliferation. Annexin V staining assay was used to assess cellular apoptosis by flow cytometry. Wound healing and Boyden's well assays were used to detect the migration and invasion of cells. Gelatin zymography was used to detect matrix metalloproteinase (MMP-2 and MMP-9) activity. Western blotting was used to detect expression levels of various signaling pathway proteins. DPPH assay results indicated that trans-FA exerted potent antioxidant effects. However, trans-FA increased intracellular ROS levels, including hydrogen peroxide and superoxide anion, in H1299 cells. Trans-FA treatment inhibited cellular proliferation and induced moderate apoptotic cell death at the highest concentration used (0.6 mM). Furthermore, trans-FA moderately inhibited the migration of H1299 cells at the concentrations of 0.3 and 0.6 mM and attenuated MMP-2 and MMP-9 activity. Trans-FA caused the phosphorylation of β-catenin, resulting in proteasomal degradation of β-catenin. Conversely, trans-FA treatment increased the expression of pro-apoptotic factor Bax and decreased the expression of pro-survival factor survivin. Various concentrations (0.06-0.6 mM) of trans-FA exert both anti-proliferation and anti-migration effects in the human lung cancer cell line H1299.

  10. 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

  11. Electrochemical treatment of lung cancer

    SciTech Connect

    Xin, Y.L.; Xue, F.Z.; Ge, B.S.; Zhao, F.R.; Shi, B.; Zhang, W.

    1997-03-01

    A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter. The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.

  12. Prior lung disease and risk of lung cancer in a large prospective study.

    PubMed

    Littman, Alyson J; Thornquist, Mark D; White, Emily; Jackson, Lisa A; Goodman, Gary E; Vaughan, Thomas L

    2004-10-01

    While 75-90% of people who develop lung cancer are smokers, only a small proportion of smokers develop lung cancer. Identifying factors that increase a smoker's risk of developing lung cancer may help scientists to better understand the etiology of lung cancer and more effectively target high-risk groups for screening. Information on physician-diagnosed non-malignant lung diseases [asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia, and tuberculosis] was obtained at baseline from 17,698 men and women involved in CARET, a randomized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers. Hazard ratios for lung cancer were estimated through Cox regression models, after controlling for potential confounding factors, included smoking. Analyses were restricted to former and current smokers. During a median follow up of 9.1 years, 1028 cases of lung cancer occurred. Those who developed lung cancer were more likely to report a history of CB/E than controls (adjusted HR = 1.29, 95% CI: 1.09-1.53). In subgroup analyses, the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference, men in the heavy smoker cohort, former smokers, and those with squamous cell carcinomas. There was little association between a history of other lung diseases and lung cancer. Smokers with a history of CB/E may be at higher risk of developing lung cancer, independent of their smoking history.

  13. 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.

  14. Parity and risk of lung cancer in women.

    PubMed

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

    2010-03-01

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

  15. Parity and Risk of Lung Cancer in Women

    PubMed Central

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

    2010-01-01

    Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women. PMID:20123687

  16. Small RNA combination therapy for lung cancer.

    PubMed

    Xue, Wen; Dahlman, James E; Tammela, Tuomas; Khan, Omar F; Sood, Sabina; Dave, Apeksha; Cai, Wenxin; Chirino, Leilani M; Yang, Gillian R; Bronson, Roderick; Crowley, Denise G; Sahay, Gaurav; Schroeder, Avi; Langer, Robert; Anderson, Daniel G; Jacks, Tyler

    2014-08-26

    MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer.

  17. Cytogenetic and molecular aspects of lung cancer.

    PubMed

    Panani, Anna D; Roussos, Charis

    2006-07-28

    Lung cancer is one of the most common cancers worldwide and its pathogenesis is closely associated with tobacco smoking. Continuous exposure of smoking carcinogens results in the accumulation of several alterations of tumorigenesis related genes leading to neoplastic bronchial lesions. Lung cancer is divided in two main histological groups, non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep process in which a number of genetic events including alterations of oncogenes and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung cancer are very complex. However, a number of recurrent cytogenetic abnormalities have been identified. Many of these changes are common in both major histological groups of lung cancer while certain chromosomal abnormalities have been correlated with the stage or the grade of the tumors. In addition, several molecular alterations have been constantly found. Some of them are common in different histological subtypes of lung cancer and they appear to play an important role in the pathogenesis of lung cancer. A good understanding of the underlying genetic changes of lung tumorigenesis will provide new perspectives for early diagnosis and screening of high-risk individuals. In addition, a number of genetical prognostic factors have been identified as possibly helpful parameters in the evaluation of lung cancer patients. Further research is required in order to systematically investigate genetical alterations in lung cancer contributing to improvement of lung cancer classification and staging and to development of new molecular targeted therapies.

  18. Dark tobacco and lung cancer in Cuba.

    PubMed

    Joly, O G; Lubin, J H; Caraballoso, M

    1983-06-01

    A retrospective epidemiologic study of 826 cytologically and/or histologically confirmed lung cancer cases (219 females and 607 males), 979 hospital controls, and 539 neighborhood controls was undertaken in Havana, Cuba, to investigate whether the high lung cancer mortality rates in this country could be explained by the cigarette and cigar consumption habits, including the smoking of dark-tobacco cigarettes. Relative risk(s)(RR) of lung cancer among cigarette smokers were 7.3 in women and 14.1 in men and increased consistently with various measures of exposure to smoke. The findings suggested that duration of smoking, daily number of cigarettes consumed, and inhalation practices have independent effects. Most Cubans smoked dark tobacco. RR were higher for dark-tobacco users than for light-tobacco users (RR = 8.6 vs. 4.6 for women and 14.3 vs. 11.3 for men), but the differences were reduced after adjustment for amount smoked. Cigarette smoking was associated with all histologic types of lung cancer, although the risk for adenocarcinoma was lower than that for the other types. Men who smoked exclusively cigars had a fourfold risk of lung cancer. Mixed smokers (i.e., cigar and cigarette smoker) had a greater RR than cigarette-only smokers (15.0 vs. 14.1), which was perhaps related to the unusually deep and frequent inhalation of cigar smoke. The data support the hypothesis that smoking patterns account for the higher lung cancer mortality in Cuba than in other Latin American countries.

  19. 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

  20. Lung cancer from passive smoking at work.

    PubMed Central

    Wells, A J

    1998-01-01

    OBJECTIVES: This study was undertaken to determine whether exposure at work to environmental tobacco smoke is associated with an increased risk of lung cancer. METHODS: Data from 14 studies providing information on lung cancer and exposure to environmental tobacco smoke at work were examined. Six quality criteria were developed for determining usable data. A meta-analysis was performed to obtain a combined risk for those data that met the quality restrictions. RESULTS: Five studies met the quality standards. Their combined relative risk was 1.39 (95% confidence interval [CI] = 1.15, 1.68) based on 835 lung cancer cases. In various meta-analyses prepared by tobacco industry employees or consultants, no increase in risk was found. The main reason for this difference is that the earlier analysts failed to find errors in 2 underlying studies that resulted in overweighting of the odds ratios from those studies, both of which were less than unity. CONCLUSIONS: When appropriate cognizance is taken of the quality of data inputs, the increase in lung cancer risk from workplace exposure to environmental tobacco smoke is about the same as that from household exposure. PMID:9663148

  1. Lung Cancer Staging and Prognosis.

    PubMed

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

    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.

  2. Improving Therapeutic Outcomes in Non-small Cell Lung Cancer not Suitable for Curative Intent Therapy - A Review of the Role of Radiation Therapy in an Era of Increasing Systemic Therapy Options.

    PubMed

    Lehman, M

    2016-05-01

    Lung cancer is the highest cause of mortality from cancer worldwide. Most patients present with disease not suitable for curative therapeutic options. In these patients, radiation therapy provides durable palliation of symptoms due to intrathoracic disease, whereas systemic chemotherapy improves survival compared with best supportive care. Over recent years the systemic therapeutic options available for the non-curative management of advanced lung cancer, particularly non-small cell lung cancer, have expanded to include molecularly targeted agents and immune modulating agents. The aim of this overview is to review the role and future of radiation therapy in this era of increasing systemic therapy options with particular emphasis on how radiation therapy can be used to improve therapeutic outcomes. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  3. 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

  4. Women and lung cancer: waiting to exhale.

    PubMed

    Baldini, E H; Strauss, G M

    1997-10-01

    Lung cancer is now the leading cause of cancer deaths among women. In the United States, 64,300 women are expected to die of lung cancer in 1996. Smoking is responsible for about 80% of lung cancer cases. Unfortunately, the prevalence of smoking among women remains unacceptably high at about 22% and is expected to surpass the rate in men by the year 2000. Smoking rates are highest among young girls and the less educated. Whether lung cancer represents a different disease in women than in men is unclear. Data are conflicting regarding the magnitude of the relative risk of developing lung cancer due to smoking between the genders. There appears to be a difference in the relative distribution of lung cancer histologic features between men and women that is not explained entirely by differences in smoking patterns. Women who smoke appear to be at higher risk of developing small cell lung cancer than squamous cell lung cancer, whereas men who smoke have a similar risk for the two histologic conditions. Furthermore, women smokers are more likely to develop adenocarcinoma of the lung, and estrogens may play a causative role in this phenomenon. Data are unclear regarding whether the outcome of lung cancer treatment differs between genders. Solutions to the lung cancer epidemic among US women include (1) prevention of the disease by reducing smoking rates, (2) improving early detection methods, and (3) exploring new therapeutic strategies.

  5. Inactivation of LLC1 gene in nonsmall cell lung cancer

    PubMed Central

    Hong, Kyeong-Man; Yang, Sei-Hoon; Chowdhuri, Sinchita R.; Player, Audrey; Hames, Megan; Fukuoka, Junya; Meerzaman, Daoud; Dracheva, Tatiana; Sun, Zhifu; Yang, Ping; Jen, Jin

    2007-01-01

    Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium, but absent or downregulated in most primary non-small cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells, but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis. PMID:17304513

  6. Increased Sox2 copy number in lung squamous cell carcinomas

    PubMed Central

    SASAKI, HIDEFUMI; YOKOTA, KEISUKE; HIKOSAKA, YU; MORIYAMA, SATORU; YANO, MOTOKI; FUJII, YOSHITAKA

    2012-01-01

    The transcription factor Sox2 is necessary for foregut morphogenesis. Sox2 is also required for the normal development of the trachea and lung. Recently, Sox2 amplifications were investigated using large-scale single nucleotide polymorphism arrays in esophageal and lung cancer. We hypothesized that Sox2 overexpression might be correlated with clinicopathological features of lung cancers. The increased copy number of the Sox2 gene was analyzed by real-time polymerase chain reaction amplifications in 127 surgically treated non-small cell lung cancer cases from Nagoya City University Hospital, Japan. A total of 87 squamous cell carcinoma (SCC) cases were involved. An increased Sox2 gene copy number was found in 42 (33.1%) lung cancer patients. Increased Sox2 copy number status was significantly correlated with gender (females, 9.5% vs. males, 34.1%; p=0.0026), smoking status (never smoker, 4.8% vs. smoker, 32.9%; p=0.0003) and pathological subtypes (squamous cell carcinoma, 44.8% vs. non-squamous cell carcinoma, 7.5%; p<0.0001). However, among the SCCs, the Sox2 copy number status was not significantly correlated with gender, smoking status, pathological stage or differentiation status. An increased Sox2 copy number is common within SCC. PMID:22969842

  7. Thromboprophylaxis in ambulatory lung cancer treatment.

    PubMed

    Cavaliere, Loretta

    2013-02-01

    Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, are common problems experienced by patients with lung cancer that can impact treatment plans, prognoses, and survival. Patients with lung cancer are at greatest risk for development of VTE in the ambulatory care treatment setting. Literature does exist on VTE management for medical and surgical oncology inpatients, as well as clinical guidelines for inpatient prophylaxis; however, published evidence is lacking on outpatient risk and thromboprophylaxis in medical oncology outpatients, particularly patients with lung cancer. Because patients with lung cancer treated in the ambulatory setting have established risks for VTE, they may benefit from thromboprophylaxis. Clinical guidelines for outpatient thromboprophylaxis direct the clinical practice for thromboprophylaxis in lung cancer treatment. The purpose of the current article is to explore the VTE risks associated with ambulatory lung cancer treatment and to review the recommended guidelines for thromboprophylaxis to guide clinical decision making for patients with lung cancer.

  8. 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.

  9. 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

  10. The APE1 Asp/Asp genotype and the combination of APE1 Asp/Asp and hOGG1-Cys variants are associated with increased p53 mutation in non-small cell lung cancer.

    PubMed

    Lin, Chun-Hsuan; Chen, Po-Ming; Cheng, Ya-Wen; Chen, Chih-Yi; Yuan, Chiun-Jye; Lee, Huei

    2012-01-01

    The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer. Biological evidence shows that the hOGG1-Cys allele results in less DNA repair activity; however, this is not associated with p53 mutation in lung cancer. Therefore, we investigated whether an interaction between hOGG1 and APE1 is associated with the frequency of p53 mutation in lung cancer. We studied 217 Taiwanese adults with primary lung cancer. DNA polymorphisms of hOGG1 and APE1 were determined by polymerase chain reaction (PCR)-based restriction fragment length polymorphism. Mutations in p53 exons 5-8 were detected by direct sequencing. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE1 in lung cancer. As expected, no association between hOGG1 polymorphism and p53 mutation was observed in this population. However, a higher risk of p53 mutation was found in participants with the APE1 Asp/Asp genotype than in those with the APE1-Glu allele (OR, 2.15; 95% CI, 1.19-3.87; P = 0.011). The risk of p53 mutation was also higher in participants with APE1 Asp/Asp plus hOGG1-Cys than in those with APE1-Glu plus hOGG1 Ser/Ser (OR, 3.72; 95% CI, 1.33-10.40; P = 0.012). These results suggest that the APE1 Asp/Asp genotype and the combination of the APE1 Asp/Asp and hOGG1-Cys variants are associated with increased risk of p53 mutation in non-small cell lung cancer.

  11. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

    PubMed

    Alberg, Anthony J; Brock, Malcolm V; Ford, Jean G; Samet, Jonathan M; Spivack, Simon D

    2013-05-01

    Ever since a lung cancer epidemic emerged in the mid-1900 s, 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. 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. 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. 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.

  12. [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

    PubMed

    Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

    2016-01-01

    Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

  13. Lung Cancer: Glossary

    MedlinePlus

    ... used to fight cancer Chromosome: A strand of DNA and related proteins that carries the genes and ... structure, function and pathology ^ back to top D DNA (deoxyribonucleic acid): The part of the cell that ...

  14. Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.

    PubMed

    Tsilioni, Irene; Filippidis, Aristotelis S; Kerenidi, Theodora; Budanov, Andrei V; Zarogiannis, Sotirios G; Gourgoulianis, Konstantinos I

    2016-06-01

    Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean±SEM) of Sesn2 in patients with MPEs was 0.54±0.22ng/mL while in BPEs it was 0.12±0.04ng/mL (p=0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p=0.89 and p=0.64 respectively). Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  15. 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 ...

  16. Clinical and experimental pathology of lung cancer

    SciTech Connect

    McVie, J.G.; Bakker, W.; Wagenaar, S.C.; Carney, D.

    1986-01-01

    This book contains 17 selections. Some of the titles are: Flow cytometric DNA analysis in the study of small cell carcinoma of the lung; Mechanisms of oncogenesis; Adhesion mechanisms in liver metastasis; Current concepts in the therapy of small cell lung cancer; Application of monoclonal antibodies in imaging and therapy; and Clinical applications of the biologic properties of small cell lung cancer.

  17. Improving Spiritual Well-Being in Patients with Lung Cancers

    PubMed Central

    Piderman, Katherine M.; Euerle, Terin T.; Frost, Marlene H.; Novotny, Paul J.; Rausch Osian, Sarah M.; Nes, Lise Solberg; Patten, Christi A.; Sloan, Jeff A.; Rummans, Teresa A.; Bronars, Carrie A.; Yang, Ping; Clark, Matthew M.

    2016-01-01

    Patients with lung cancer report more disease burden and lower spiritual well-being (SWB) compared with other cancer patients. Understanding variables that lessen disease burden and improve SWB is essential. The aim of this study was to explore the relationship between motivational level for physical activity and SWB in patients with lung cancer. Linear regression showed increased SWB as stage of change for physical activity increased (p<0.0001), even after adjusting for multiple demographic variables. PMID:26463853

  18. 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.

  19. Pleural involvement in lung cancer.

    PubMed

    Agalioti, Theodora; Giannou, Anastasios D; Stathopoulos, Georgios T

    2015-06-01

    The pleural space, a sterile secluded environment in the thoracic cavity, represents an attractive metastatic site for various cancers of lung, breast and gastrointestinal origins. Whereas lung and breast adenocarcinomas could invade the pleural space because of their anatomic proximity, "distant" cancers like ovarian or gastrointestinal tract adenocarcinomas may employ more active mechanisms to the same end. A pleural metastasis is often accompanied by a malignant pleural effusion (MPE), an unfavorable complication that severely restricts the quality of life and expectancy of the cancer patient. MPE is the net "product" of three different processes, namely inflammation, enhanced angiogenesis and vascular leakage. Current efforts are focusing on the identification of cancer cell autocrine (specific mutation spectra and biochemical pathways) and paracrine (cytokine and chemokine signals) characteristics as well as host features (immunological or other) that underlie the MPE phenotype. Herein we examine the pleural histology, cytology and molecular characteristics that make the pleural cavity an attractive metastasis destination for lung adenocarcinoma. Mesothelial and tumor features that may account for the tumor's ability to invade the pleural space are highlighted. Finally, possible therapeutic interventions specifically targeting MPE are discussed.

  20. Pleural involvement in lung cancer

    PubMed Central

    Giannou, Anastasios D.; Stathopoulos, Georgios T.

    2015-01-01

    The pleural space, a sterile secluded environment in the thoracic cavity, represents an attractive metastatic site for various cancers of lung, breast and gastrointestinal origins. Whereas lung and breast adenocarcinomas could invade the pleural space because of their anatomic proximity, “distant” cancers like ovarian or gastrointestinal tract adenocarcinomas may employ more active mechanisms to the same end. A pleural metastasis is often accompanied by a malignant pleural effusion (MPE), an unfavorable complication that severely restricts the quality of life and expectancy of the cancer patient. MPE is the net “product” of three different processes, namely inflammation, enhanced angiogenesis and vascular leakage. Current efforts are focusing on the identification of cancer cell autocrine (specific mutation spectra and biochemical pathways) and paracrine (cytokine and chemokine signals) characteristics as well as host features (immunological or other) that underlie the MPE phenotype. Herein we examine the pleural histology, cytology and molecular characteristics that make the pleural cavity an attractive metastasis destination for lung adenocarcinoma. Mesothelial and tumor features that may account for the tumor’s ability to invade the pleural space are highlighted. Finally, possible therapeutic interventions specifically targeting MPE are discussed. PMID:26150915

  1. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    PubMed

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  2. 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. © 2014 UICC.

  3. Occupational Lung Cancer Surveillance in South Korea, 2006-2009

    PubMed Central

    Kim, Hwan-Cheol; Ryu, Jeong-Seon; Won, Jong Uk; Moon, Jai Dong; Kim, Young-Chul; Koh, Sang Baek; Yong, Suk Joong; Kim, Soo Geun; Park, Jae Yong; Kim, Inah; Kim, Jung Il; Kim, Jung Won; Lee, Eui-cheol; Kim, Hyoung-Ryoul; Kim, Dae-Hwan; Kang, Dong Mug; Hong, Yun-Chul

    2010-01-01

    Objectives The lung cancer mortality in Korea has increased remarkably during the last 20 years, and has been the first leading cause of cancer-related deaths since 2000. The aim of the current study was to examine the time trends of occupational lung cancer and carcinogens exposure during the period 2006-2009 in South Korea, by assessing the proportion of occupational burden. Methods We defined occupational lung cancer for surveillance, and developed a reporting protocol and reporting website for the surveillance of occupational lung cancer. The study patients were chosen from 9 participating university hospitals in the following 7 areas: Seoul, Incheon, Wonju, Daejeon, Daegu, Busan, and Gwangju. Results The combined proportion of definite and probable occupational lung cancer among all lung cancers investigated in this study was 10.0%, 8.6%, 10.7%, and 15.8% in the years 2006 to 2009, respectively, with an average of 11.7% over the four-year study period. The main carcinogens were asbestos, crystalline silica, radon, polyaromatic hydrocarbons (PAHs), diesel exhaust particles, chromium, and nickel. Conclusion We estimated that about 11.7% of the incident lung cancer was preventable. This reveals the potential to considerably reduce lung cancer by intervention in occupational fields. PMID:22953173

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

    ClinicalTrials.gov

    2017-01-17

    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

  5. 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

  6. Lung cancer: biology and treatment options

    PubMed Central

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

    2015-01-01

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

  7. 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.

  8. A 30-year perspective on psychosocial issues in lung cancer: how lung cancer "Came out of the Closet".

    PubMed

    Weiss, Talia; Weinberger, Mark; Schwerd, Arielle M; Holland, Jimmie

    2012-11-01

    Psychological responses to lung cancer have changed over the past 30 years as perceptions of the disease have changed. Previously seen as a fatal diagnosis, it is now regarded as a cancer whose treatment is increasingly effective as the science of the disease advances. The stigma of smoking is diminishing as more is learned about genetic factors and as more nonsmokers are diagnosed. Support groups are now widely available. The increasing social support and greater knowledge of lung cancer provide a more supportive environment in which patients cope with lung cancer today compared with 30 years ago. Published by Elsevier Inc.

  9. Percutaneous microwave ablation (MWA) increased the serum levels of VEGF and MMP-9 in Stage I non-small cell lung cancer (NSCLC).

    PubMed

    Ni, Yang; Ye, Xin; Wan, Chao; Ni, Qing; Yang, Xia; Huang, Guanghui; Li, Wenhong; Wang, Jiao; Han, Xiaoying; Wei, Zhigang; Meng, Min

    2017-02-02

    Lung cancer is the leading cause of cancer death around the world. Percutaneous microwave ablation (MWA) is an emerging treatment strategy for medically inoperable early-stage non-small cell lung cancer (NSCLC). In this study, we investigated the association of MWA and serum angiogensis promoters VEGF and MMP-9 in these patients subgroup. We enrolled 52 patients with Stage I NSCLC patients in this study. For each patient, blood samples were drawn by venous puncture, one immediately prior to MWA and the others on Post-Procedure Days (PPD) 1, 3, 5, 7, 10 and 14. Serum samples were analysed for VEGF and MMP-9 levels with use of commercially available enzyme-linked immunosorbent assay. Also, blood samples of 28 healthy volunteers were set as the healthy controls. We did not observe a significant difference of serum VEGF and MMP-9 between NSCLC patients and healthy controls. The VEGF levels increased on the first day (256.0 ± 6.16 pg/ml, p < 0.05) after MWA and peaked on the PPD3 (418.0 ± 14.54 pg/ml, p < 0.05). Although it gradually reduced afterwards, its levels on PPD14 (141.2 ± 4.41 pg/ml, p < 0.05) was still higher than pre-procedure level. The serum MMP-9 level was significantly elevated from PPD1 (231.3 ± 7.93 ng/ml, p < 0.05) until PPD10 (155.3 ± 5.62 ng/ml, p < 0.05), while it normalised to pre-procedure level on PPD14 (90.78 ± 3.36 ng/ml, p > 0.05). The highest MMP-9 level was observed on PPD5 (399.7 ± 17.70 ng/ml, p < 0.05). Our preliminary results indicated that percutaneous MWA resulted in increased serum levels of VEGF and MMP-9 in Stage I NSCLC patients. Antiangiogenesis approaches may be helpful for patients defending against metastases during the immediate post-ablation time window.

  10. Silver nanoparticles from Dendropanax morbifera Léveille inhibit cell migration, induce apoptosis, and increase generation of reactive oxygen species in A549 lung cancer cells.

    PubMed

    Castro Aceituno, Verónica; Ahn, Sungeun; Simu, Shakina Yesmin; Wang, Chao; Mathiyalagan, Ramya; Yang, Deok Chun

    2016-12-01

    Green synthesized silver nanoparticles have significant potential in the pharmaceutical field because of their biological functions such as antioxidant and anticancer activities. Novel silver nanoparticles synthesized from Dendropanax morbifera Léveille leaves (D-AgNPs) exhibit antimicrobial activity and reduce the viability of cancer cells without affecting the viability of RAW 264.7 macrophage-like cells. In this study, we evaluated the anticancer effect of D-AgNPs by measuring the levels of reactive oxygen species (ROS) production and toxicity against A549 and HepG2 cell lines. The effect of D-AgNPs on cell migration, induction of apoptosis, and modification of gene and/or protein expression of cancer-related markers was determined using A549 cells. D-AgNPs exhibited cytotoxicity in A549 and HepG2 cell at different concentrations and enhanced the production of ROS in both cell lines. An increase in cell apoptosis and a reduction in cell migration in A549 cells were also observed after D-AgNP treatment. Furthermore, the effect of D-AgNPs in A549 cells was shown to be related to modification of the EGFR/p38 MAPK pathway. Our data provide the first evidence supporting the potential of D-AgNPs as a possible anticancer agent, particularly for the treatment of non-small cell lung carcinoma.

  11. Adaptive Radiation for Lung Cancer

    PubMed Central

    Gomez, Daniel R.; Chang, Joe Y.

    2011-01-01

    The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed. PMID:20814539

  12. [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.

  13. 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…

  14. 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…

  15. 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

  16. Air pollution affects lung cancer survival.

    PubMed

    Eckel, Sandrah P; Cockburn, Myles; Shu, Yu-Hsiang; Deng, Huiyu; Lurmann, Frederick W; Liu, Lihua; Gilliland, Frank D

    2016-10-01

    Exposure to ambient air pollutants has been associated with increased lung cancer incidence and mortality, but due to the high case fatality rate, little is known about the impacts of air pollution exposures on survival after diagnosis. This study aimed to determine whether ambient air pollutant exposures are associated with the survival of patients with lung cancer. Participants were 352 053 patients with newly diagnosed lung cancer during 1988-2009 in California, ascertained by the California Cancer Registry. Average residential ambient air pollutant concentrations were estimated for each participant's follow-up period. Cox proportional hazards models were used to estimate HRs relating air pollutant exposures to all-cause mortality overall and stratified by stage (localised only, regional and distant site) and histology (squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell carcinoma and others) at diagnosis, adjusting for potential individual and area-level confounders. Adjusting for histology and other potential confounders, the HRs associated with 1 SD increases in NO2, O3, PM10, PM2.5 for patients with localised stage at diagnosis were 1.30 (95% CI 1.28 to 1.32), 1.04 (95% CI 1.02 to 1.05), 1.26 (95% CI 1.25 to 1.28) and 1.38 (95% CI 1.35 to 1.41), respectively. Adjusted HRs were smaller in later stages and varied by histological type within stage (p<0.01, except O3). The largest associations were for patients with early-stage non-small cell cancers, particularly adenocarcinomas. These epidemiological findings support the hypothesis that air pollution exposures after lung cancer diagnosis shorten survival. Future studies should evaluate the impacts of exposure reduction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells.

    PubMed

    Peters, Haley L; Tripathi, Satyendra C; Kerros, Celine; Katayama, Hiroyuki; Garber, Haven R; St John, Lisa S; Federico, Lorenzo; Meraz, Ismail M; Roth, Jack A; Sepesi, Boris; Majidi, Mourad; Ruisaard, Kathryn; Clise-Dwyer, Karen; Roszik, Jason; Gibbons, Don L; Heymach, John V; Swisher, Stephen G; Bernatchez, Chantale; Alatrash, Gheath; Hanash, Samir; Molldrem, Jeffrey J

    2017-03-02

    Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these reinvigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3. Additionally, NE and P3 enhanced the expression of human leukocyte antigen (HLA) class I molecules on lung cancer cells and induced unique, endogenous peptides in the immunopeptidome, as detected with mass spectrometry sequencing. Lung cancer patient tissues with high intratumoral TAMs were enriched for MHC class I genes and T-cell markers, and patients with high TAM and cytotoxic T lymphocyte (CTL) infiltration had improved overall survival. We confirmed the immunogenicity of unique, endogenous peptides with cytotoxicity assays against lung cancer cell lines, using CTLs from healthy donors that had been expanded against select peptides. Finally, CTLs specific for serine proteases-induced endogenous peptides were detected in lung cancer patients using peptide/HLA-A2 tetramers and were elevated in tumor-infiltrating lymphocytes. Thus, serine proteases in the tumor microenvironment of lung cancers promote the presentation of HLA class I immunogenic peptides that are expressed by lung cancer cells, thereby increasing the antigen repertoire that can be targeted in lung cancer. Cancer Immunol Res; 5(4); 1-11. ©2017 AACR.

  18. Individualized Risk Prediction Model for Lung Cancer in Korean Men

    PubMed Central

    Park, Sohee; Nam, Byung-Ho; Yang, Hye-Ryung; Lee, Ji An; Lim, Hyunsun; Han, Jun Tae; Park, Il Su; Shin, Hai-Rim; Lee, Jin Soo

    2013-01-01

    Purpose Lung cancer is the leading cause of cancer deaths in Korea. The objective of the present study was to develop an individualized risk prediction model for lung cancer in Korean men using population-based cohort data. Methods From a population-based cohort study of 1,324,804 Korean men free of cancer at baseline, the individualized absolute risk of developing lung cancer was estimated using the Cox proportional hazards model. We checked the validity of the model using C statistics and the Hosmer–Lemeshow chi-square test on an external validation dataset. Results The risk prediction model for lung cancer in Korean men included smoking exposure, age at smoking initiation, body mass index, physical activity, and fasting glucose levels. The model showed excellent performance (C statistic = 0.871, 95% CI = 0.867–0.876). Smoking was significantly associated with the risk of lung cancer in Korean men, with a four-fold increased risk in current smokers consuming more than one pack a day relative to non-smokers. Age at smoking initiation was also a significant predictor for developing lung cancer; a younger age at initiation was associated with a higher risk of developing lung cancer. Conclusion This is the first study to provide an individualized risk prediction model for lung cancer in an Asian population with very good model performance. In addition to current smoking status, earlier exposure to smoking was a very important factor for developing lung cancer. Since most of the risk factors are modifiable, this model can be used to identify those who are at a higher risk and who can subsequently modify their lifestyle choices to lower their risk of lung cancer. PMID:23408946

  19. Enhancement of radiation effect and increase of apoptosis in lung cancer cells by thio-glucose-bound gold nanoparticles at megavoltage radiation energies

    NASA Astrophysics Data System (ADS)

    Wang, Cuihong; Li, Xiaohong; Wang, Yang; Liu, Zhen; Fu, Lei; Hu, Likuan

    2013-05-01

    Gold nanoparticles (GNPs) (1-1,000 nm) modified by glucose have been considered to increase the toxicity of radiotherapy in human malignant cells. We report on the effect on lung-cancer cells, A549, of thio-glucose-bound gold nanoparticles (Glu-GNPs) with a size of 13 nm, combined with megavoltage (MV) X-ray. Viewed by transmission electron microscopy, Glu-GNPs were mainly distributed in the membrane-coated vesicles of A549 cells. The combination of Glu-GNPs with radiation resulted in a significant growth inhibition, compared with radiation alone ( P < 0.05). Glu-GNPs enhanced radiation effect by increasing the ratio of A549 cells in the G2/M phase, and inducing more apoptosis. Furthermore, when combined with radiation, Glu-GNPs resulted in deregulation of Bcl-2 and upregulation of Bax and active caspase 3. Our results suggest that Glu-GNPs, as a new radiosensitizer, combined with radiation, can increase cytotoxicity on A549 cells not only by arresting the G2/M phase, but also by increasing apoptosis—probably via regulating the expression of Bcl-2 family of proteins and mitochondrial apoptotic pathway.

  20. LUCIS: lung cancer imaging studies.

    PubMed

    Harders, Stefan Walbom

    2012-11-01

    Pulmonary nodules are of high clinical importance, as they may prove to be an early manifestation of lung cancer. Pulmonary nodules are small, focal opacities that may be solitary or multiple. A solitary pulmonary nodule (SPN) is a single, small (= 30 mm in diameter) radiographic opacity. Larger opacities are called masses and are often malignant. As imaging techniques improve and more nodules are detected, the optimal management of SPNs remains unclear. Current strategies include tissue sampling or CT follow-up. The aim of this PhD was to examine current non-invasive methods used to characterise pulmonary nodules and masses in patients with suspected lung cancer and to stage NSCLC. In doing so, this PhD helps to validate the existing methods used to diagnose and stage lung cancer correctly and, hopefully, aids in the development of new methods. In the first study, 213 participants with pulmonary nodules on CT were examined with an additional HRCT. In this study, it was concluded that HRCT of a solitary pulmonary nodule, assessed using attenuation and morphological criteria is a fast, widely available and effective method for diagnosing lung cancer correctly, and especially for ruling out cancer. In the second study, 168 patients with pulmonary lesions on CT were examined with an additional F-18-FDG PET/CT. It was concluded that when used early in the work-up of the lesions, CT raised the prevalence of lung cancer in the population to the point at which further diagnostic imaging examination could be considered redundant. Standard contrast-enhanced CT seems better suited to identify patients with lung cancer than to rule out cancer. Finally, the overall diagnostic accuracy as well as the classification probabilities and predictive values of the two modalities were not significantly different. The reproducibility of the above results was substantial. In the third study, 59 patients with pulmonary nodules or masses on chest radiography were examined with an

  1. 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

  2. Age and the treatment of lung cancer.

    PubMed Central

    Brown, J S; Eraut, D; Trask, C; Davison, A G

    1996-01-01

    BACKGROUND: The average age of patients with lung cancer is increasing and there are large numbers of elderly symptomatic patients with this common disease. However, there are few data on how the treatment of this group differs from that of younger patients. METHODS: From 1 January 1990 information was collected for the Southend Lung Cancer Registry on all patients with a diagnosis of lung cancer in a geographically well defined health district of the UK with a population of 325,000. Every effort was made to find new cases from all departments of the hospital, including all clinical diagnoses, histopathological and cytological reports, and necropsies. All death certificates in the district were examined, irrespective of age, for any diagnosis of lung cancer. This therefore included any patient not seen by the hospital services. The differences in initial treatment have been analysed for three age groups: under 65, 65-74 years, and over 75. RESULTS: The 563 cases of lung cancer diagnosed during a 30 month period were included in the study, of whom 240 (43%) were aged over 75 years. The overall mean age was 71 years (range 31-95). The incidence of lung cancer in the general population was 69 per 100,000, but in men over 75 years of age it rose to 751 per 100,000. For all patients the active treatment rate (chemotherapy, surgery, or radiotherapy) was 49%, but for patients not reviewed by a chest physician (n = 86) it was only 21%. There were large differences in initial treatment between age groups. For patients with non-small cell lung cancer (NSCLC) reviewed by a chest physician, surgery was undertaken in 18% of those under 65, 12% of the 65-74 age group, and 2.1% of those over 75. For patients with small cell lung cancer (SCLC) reviewed by a chest physician, 79% of those aged under 65, 64% of the 65-74 age group, and 41% of patients aged over 75 received chemotherapy. In patients with NSCLC reviewed by a chest physician, chemotherapy was given to 21% under 65, 6

  3. [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.

  4. Advances and Implications in Nanotechnology for Lung Cancer Management.

    PubMed

    Sarkar, Sana; Osama, Khwaja; Jamal, Qazi Mohammad Sajid; Kamal, Mohammad Amjad; Sayeed, Usman; Khan, M Kalim A; Siddiqui, Mohd Haris; Akhtar, Salman

    2016-11-14

    Lung cancer is one of the most important chronic diseases in the field of respiratory medicine. Conventional treatment strategies for lung cancer include chemotherapy, surgery and radiation therapy. These current therapies lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence.Nanotechnological intervention has greatly revolutionized the therapy of lung cancer by surmounting the current limitations in conventional therapies. Nanoparticles (NPs) achieve preferential accumulation in the tumor cells by employing two mechanisms: passive and active targeting. Several nanoscale drug delivery systems for lung cancer treatment are currently in clinical trials and few of them are already commercially available. Recently, the interest to develop pulmonary delivery system of nano-based drug formulations suitable for lung cancer has been also increased which have resulted in more effective and advanced treatment of Lung cancer. However, although nanotechnology based drug carriers for lung cancer treatment have established outstanding therapeutic potential at both preclinical and clinical Phases, but there are still many limitations to be solved. This review details the till date drug nanocarriers researches performed for lung cancer therapy.

  5. 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

  6. Lung Cancer in Railroad Workers Exposed to Diesel Exhaust

    PubMed Central

    Garshick, Eric; Laden, Francine; Hart, Jaime E.; Rosner, Bernard; Smith, Thomas J.; Dockery, Douglas W.; Speizer, Frank E.

    2004-01-01

    Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort. PMID:15531439

  7. Gremlin is Overexpressed in Lung Adenocarcinoma and Increases Cell Growth and Proliferation in Normal Lung Cells

    PubMed Central

    Lee, Sharon; Fang, Li Tai; Choi, Helen; Ray, Roshni; Kang, Hio Chung; Mao, Jian-Hua; Jablons, David; Kim, Il-Jin

    2012-01-01

    Background Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation. Methodology/Principal Findings Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro. Results Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation. Conclusions/Significance Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies. PMID:22870311

  8. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    DTIC Science & Technology

    2013-08-01

    with an evaluation of emphysema score in patients with lung cancer and non-cancer patients receiving CT evaluation. 15. SUBJECT TERMS 16...distribution, and pattern of low attenuation areas (“ emphysema ”), may be crucial to increasing our insights and effectiveness of determining lung... emphysema in these subjects. Of the group, 130 of the subjects had cancer, and 25 did not. Also, 115 of the subject were current of former smokers with an

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

    Cancer.gov

    [[{"fid":"180","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Lung and Upper Aerodigestive Cancer Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Lung and Upper Aerodigestive Cancer Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Lung and Upper Aerodigestive Cancer Research Group Homepage Logo","title":"Lung and Upper Aerodigestive Cancer Research Group Homepage Logo","heigh | Conducts and supports research on the prevention and early detection of lung and head and neck cancers.

  10. 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.

  11. Prognosis of Lung Cancer: Heredity or Environment

    DTIC Science & Technology

    2015-06-01

    AWARD NUMBER: W81XWH-12-1-0547 TITLE: Prognosis of Lung Cancer: Heredity or Environment? PRINCIPAL INVESTIGATOR: Melinda Aldrich...0547 Prognosis of Lung Cancer: Heredity or Environment? 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Aldrich...DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Lung cancer is the

  12. 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

  13. 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.

  14. Bronchoalveolar Lavage Proteomics in Patients with Suspected Lung Cancer

    PubMed Central

    Carvalho, Ana Sofia; Cuco, Célia Marina; Lavareda, Carla; Miguel, Francisco; Ventura, Mafalda; Almeida, Sónia; Pinto, Paula; de Abreu, Tiago Tavares; Rodrigues, Luís Vaz; Seixas, Susana; Bárbara, Cristina; Azkargorta, Mikel; Elortza, Felix; Semedo, Júlio; Field, John K.; Mota, Leonor; Matthiesen, Rune

    2017-01-01

    Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples. PMID:28169345

  15. Study of occupational lung cancer in asbestos factories in China.

    PubMed Central

    Zhu, H; Wang, Z

    1993-01-01

    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

  16. 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.

  17. Lung cancer: epidemiology, etiology, and prevention.

    PubMed

    Dela Cruz, Charles S; Tanoue, Lynn T; Matthay, Richard A

    2011-12-01

    Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. 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

  19. Lung cancer in patients with idiopathic pulmonary fibrosis.

    PubMed

    Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

    2017-08-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

  20. [Lung cancer and lymph drainage].

    PubMed

    Riquet, M

    2007-01-01

    Lung cancer is lymphophile and may involve lymph nodes (LN) belonging to lung lymph drainage. LN metastases are figured within stations numbered 1 to 14. These stations are located along lymph vessels. The lymph vessels and the LN are forming together anatomical chains. Lymph vessels are valved and pulsatile and travel to the cervical venous confluence where they pour the lung lymph into the blood circulation. They may be totally or partly nodeless along their travel, anastomose with each other around the trachea, and connect with the thoracic duct within the mediastinum. Within the anatomical LN chains, LN are variable in number and in size from one individual to another. They may be absent from one or several stations of the international mapping. Stations are located along the anatomical chains: pulmonary ligament (9), tracheal bifurcation(8 and 7), right paratracheal (4R, 2R and 1), preaortic (5 and 6), left paratracheal (4L, 2L and 1). Station 3 is located on 2 differents chains (phrenic and right esophagotracheal). Station 10 are located at the beginning of the mediastinal lymph nodes chains. Each chain connects with the blood circulation, anastomoses with he neighbouring chains and behave as an own entity whatever the number of its LN. International station mapping misknowns this anatomy and occults the true pronostic value of lung lymph drainage.

  1. Is Previous Respiratory Disease a Risk Factor for Lung Cancer?

    PubMed Central

    Denholm, Rachel; Schüz, Joachim; Straif, Kurt; Stücker, Isabelle; Jöckel, Karl-Heinz; Brenner, Darren R.; De Matteis, Sara; Boffetta, Paolo; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Ahrens, Wolfgang; Pohlabeln, Hermann; Zaridze, David; Field, John K.; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kendzia, Benjamin; Peters, Susan; Behrens, Thomas; Vermeulen, Roel; Brüning, Thomas; Kromhout, Hans

    2014-01-01

    Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case–control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20–1.48 and OR, 1.50; 95% CI, 1.21–1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33–4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis “only.” Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Conclusions: Findings from this large international case–control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer. PMID:25054566

  2. [Development of the lung cancer diagnostic system].

    PubMed

    Lv, You-Jiang; Yu, Shou-Yi

    2009-07-01

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

  3. 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

  4. Translating cancer epigenomics into the clinic: focus on lung cancer.

    PubMed

    Mari-Alexandre, Josep; Diaz-Lagares, Angel; Villalba, Maria; Juan, Oscar; Crujeiras, Ana B; Calvo, Alfonso; Sandoval, Juan

    2017-06-02

    Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients. Of particular relevance is the identification of epigenetic biomarkers in lung cancer, one of the most prevalent and deadly types of cancer. DNA methylation of SHOX2 and RASSF1A could be used as diagnostic markers to differentiate between normal and tumor samples. MicroRNA and long noncoding RNA signatures associated with lung cancer development or tobacco smoke have also been identified. In addition to the field of biomarkers, therapeutic approaches using DNA methylation and histone deacetylation inhibitors are being tested in clinical trials for several cancer types. Moreover, new DNA editing techniques based on zinc finger and CRISPR/Cas9 technologies allow specific modification of aberrant methylation found in oncogenes or tumor suppressor genes. We envision that epigenomics will translate into the clinical field and will have an impact on lung cancer diagnosis/prognosis and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. NK cell phenotypic modulation in lung cancer environment.

    PubMed

    Jin, Shi; Deng, Yi; Hao, Jun-Wei; Li, Yang; Liu, Bin; Yu, Yan; Shi, Fu-Dong; Zhou, Qing-Hua

    2014-01-01

    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. 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. 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. 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.

  6. Risk factors for lung cancer among nonsmoking Illinois residents.

    PubMed

    Keller, J E; Howe, H L

    1993-01-01

    The purpose of this study was to examine possible risk factors for lung cancer among nonsmokers. The Illinois State Cancer Registry was used to identify all nonsmoking lung cancer cases diagnosed between 1985 and 1987. Subjects were classified as nonsmokers only if their medical record specifically stated that they had never smoked during their lifetime. These cases were compared with nonsmoking colon cancer cases. White male nonsmoking lung cancer cases were more likely to have worked in the construction industry than controls [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.3] and to have worked in the bus service and urban transit industry (OR = 2.6, 95% CI = 1.0-6.9), in the trucking service industry (OR = 2.1, 95% CI = 1.3-3.6), and in blast furnaces, steelworks, and rolling and finishing mills (OR = 1.9, 95% CI = 1.0-3.6). White female cases were more likely to have worked as registered nurses than were the controls (OR = 1.9, 95% CI = 1.0-3.5). Negative associations between lung cancer and farming were found in both white males (OR = 0.6, 95% CI = 0.5-0.7) and white females (OR = 0.1, 95% CI = 0.01-0.6). Several other less plausible associations between employment and lung cancer were also found. To determine whether urban residence and associated air pollution increased the risk of lung cancer for nonsmokers, rates among nonsmokers in Cook County were compared with those in the remainder of Illinois. Cook County rates of nonsmoking lung cancer were elevated among white females and nonwhite females, but not among males. Residences of the white female and nonwhite female lung cancer cases were mapped to determine whether clustering within Chicago had occurred. The absence of observable clustering suggests that the excess of female lung cancer cases in Cook County is not attributable to pollution.

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

    ClinicalTrials.gov

    2017-02-20

    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

  8. Lung cancer in HIV infected patients: facts, questions and challenges.

    PubMed

    Cadranel, J; Garfield, D; Lavolé, A; Wislez, M; Milleron, B; Mayaud, C

    2006-11-01

    AIDS related mortality has fallen sharply in industrialised countries since 1996 following the introduction of highly active antiretroviral therapy. This has been accompanied by an increase in the proportion of deaths attributable to non-AIDS defining solid tumours, especially lung cancer. The risk of developing lung cancer seems to be higher in HIV infected subjects than in the general population of the same age, partly because the former tend more frequently to be smokers and, especially, intravenous drug users. The carcinogenic role of the antiretroviral nucleoside drugs and their interaction with smoking needs to be examined. Interestingly, there is no clear relationship between the degree of immunosuppression and the risk of lung cancer, so the reason for the increased risk is unknown. The mean age of HIV infected patients at the time of lung cancer diagnosis is 45 years and most are symptomatic. Lung cancer is diagnosed when locally advanced or metastatic (stage III-IV) in 75-90% of cases, similar to patients with unknown HIV status. Adenocarcinoma is the most frequent histological type. The prognosis is worse in HIV infected patients than in the general lung cancer population. Efficacy and toxicity data for chemotherapy and radiation therapy are few and imprecise. Surgery remains the treatment of choice for localised disease in patients with adequate pulmonary function and general good health, regardless of immune status. Prospective clinical trials are needed to define the optimal detection and treatment strategies for lung cancer in HIV infected patients.

  9. Screening and early detection of lung cancer.

    PubMed

    Van't Westeinde, Susan C; van Klaveren, Rob J

    2011-01-01

    Lung cancer with an estimated 342,000 deaths in 2008 (20% of total) is the most common cause of death from cancer, followed by colorectal cancer (12%), breast cancer (8%), and stomach cancer (7%) in Europe. In former smokers, the absolute lung cancer risk remains higher than in never-smokers; these data therefore call for effective secondary preventive measures for lung cancer in addition to smoking cessation programs. This review presents and discusses the most recent advances in the early detection and screening of lung cancer.An overview of randomized controlled computerized tomography-screening trials is given, and the role of bronchoscopy and new techniques is discussed. Finally, the approach of (noninvasive) biomarker testing in the blood, exhaled breath, sputum, and bronchoscopic specimen is reviewed.

  10. Silica, compensated silicosis, and lung cancer in Western Australian goldminers

    PubMed Central

    de Klerk, N. H.; Musk, A. W.

    1998-01-01

    OBJECTIVES: Silica has recently been reclassified as carcinogenic to humans based largely on the observed increase in rates of lung cancer in subjects with silicosis. Other recent reviews have arrived at different conclusions as to whether silicosis or silica itself is carcinogenic. This study aims to examine exposure-response relations between exposure to silica and subsequent silicosis and lung cancer in a cohort of goldminers. METHODS: 2,297 goldminers from Kalgoorlie in Western Australia were examined in 1961, 1974, and 1975. Data were collected on respiratory symptoms, smoking habits, and employment history. Subjects were followed up to the end of 1993. Survival analyses for lung cancer mortality and incidence of compensated silicosis were performed with age and year matched conditional logistic regression analyses. RESULTS: 89% of the cohort were traced to the end of 1993. 84% of the men had smoked at some time and 66% were current smokers. 1386 deaths occurred during the follow up period, 138 from lung cancer, and 631 subjects were compensated for silicosis. A strong effect of smoking on mortality from lung cancer, and a smaller effect on the incidence of compensated silicosis was found. There was a strong effect of duration and intensity of exposure on the incidence of silicosis. The risk of mortality from lung cancer increased after compensation for silicosis. Of all direct measures of exposure to silica, only log cumulative exposure was significantly related to incidence of lung cancer, but this effect disappeared once the onset of silicosis was taken into account. CONCLUSIONS: The incidence of silicosis was clearly related to exposure to silica and the onset of silicosis conferred a significant increase in risk for subsequent lung cancer, but there was no evidence that exposure to silica caused lung cancer in the absence of silicosis.   PMID:9624278

  11. Lung cancer stem cells: An epigenetic perspective.

    PubMed

    Shukla, Samriddhi; Khan, Sajid; Sinha, Sonam; Meeran, Syed Musthapa

    2017-02-05

    Lung cancer remains the major cause of human mortality among all the cancer types despite the colossal amount of efforts to prevent the cancer onset and to provide the appropriate cure. Recent reports have identified that important contributors of lung cancer-related mortality are the drug resistance and aggressive tumor relapse, the characteristics contributed by the presence of lung cancer stem cells (CSCs). The identification of lung CSCs is inherently complex due to the quiescent nature of lung epithelium, which makes the distinction between the normal lung epithelium and lung CSCs difficult. Recently, multiple researches have helped in the identification of lung CSCs based on the presence or absence of certain specific types of stem cell markers. Maintenance of lung CSCs is chiefly mediated through the epigenetic modifications of their genome. In this review, we will discuss about the origin of lung CSCs and the role of epigenetic modifications in their maintenance. We will also discuss in brief the major lung CSC markers and the therapeutic approaches to selectively target this population of cells.

  12. Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure

    PubMed Central

    Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

    2015-01-01

    Objectives Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. Methods A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940–2002), a revised cadmium (Cd) exposure matrix and improved work history information. Results Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure–response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m3 Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20–25 years. Conclusions These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m3 Cd. PMID:22271639

  13. Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

    PubMed Central

    Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

    2015-01-01

    Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

  14. Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients.

    PubMed

    Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

    2015-10-01

    Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

  15. Adaptive Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Does Not Underdose the Microscopic Disease and has the Potential to Increase Tumor Control

    SciTech Connect

    Guckenberger, Matthias; Richter, Anne; Wilbert, Juergen; Flentje, Michael; Partridge, Mike

    2011-11-15

    Purpose: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). Methods and Materials: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. Results: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% {+-} 10% to 73% {+-} 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. Conclusions: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40

  16. 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

  17. Chronic obstructive lung diseases and risk of non-small cell lung cancer in women

    PubMed Central

    Schwartz, Ann G.; Cote, Michele L.; Wenzlaff, Angela S.; Van Dyke, Alison; Chen, Wei; Ruckdeschel, John C.; Gadgeel, Shirish; Soubani, Ayman O.

    2009-01-01

    Introduction The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women. Methods We evaluated the relationship between COPD and non-small cell lung cancer (NSCLC) in a population-based case-control study of women and constructed a time course of chronic lung diseases in relation to onset of lung cancer. Five hundred sixty-two women aged 18–74, diagnosed with NSCLC and 564 population-based controls matched on race and age participated. Multivariable unconditional logistic regression models were used to estimate risk associated with a history of COPD, chronic bronchitis or emphysema. Results Lung cancer risk increased significantly for white women with a history of COPD (OR=1.85; 95% CI 1.21–2.81), but this was not seen in African American women. Risk associated with a history of chronic bronchitis was strongest when diagnosed at age 25 or earlier (OR=2.35, 95% CI 1.17–4.72); emphysema diagnosed within nine years of lung cancer was also associated with substantial risk (OR=6.36, 95% CI 2.36–17.13). Race, pack-years of smoking, exposure to environmental tobacco smoke as an adult, childhood asthma and exposure to asbestos were associated with a history of COPD among lung cancer cases. Conclusions In women, COPD is associated with risk of lung cancer differentially by race. Untangling whether COPD is in the causal pathway or simply shares risk factors will require future studies to focus on specific COPD features while exploring underlying genetic susceptibility to these diseases. PMID:19190518

  18. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jr; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2010-02-01

    In this work, we utilized multiphoton microscopy for the label-free diagnosis of non-cancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from human. Our results show that the combination of second harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from non-cancerous lung tissues. Specifically, non-cancerous lung tissues are largely fibrotic in structure while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI or SAAID) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55 +/-0.23 and 0.87+/-0.15 respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13 respectively. Intrinsic fluorescence ratio (FAD/NADH) of SCC and non-cancerous tissues are 0.40+/-0.05 and 0.53+/-0.05 respectively, the redox ratio of SCC diminishes significantly, indicating that increased cellular metabolic activity. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from non-cancerous tissues. With additional development, multiphoton microscopy may be used for the clinical diagnosis of lung cancers.

  19. Molecular biology of lung cancer: clinical implications.

    PubMed

    Larsen, Jill E; Minna, John D

    2011-12-01

    Lung cancer is a heterogeneous disease clinically, biologically, histologically, and molecularly. Understanding the molecular causes of this heterogeneity, which might reflect changes occurring in different classes of epithelial cells or different molecular changes occurring in the same target lung epithelial cells, is the focus of current research. Identifying the genes and pathways involved, determining how they relate to the biological behavior of lung cancer, and their utility as diagnostic and therapeutic targets are important basic and translational research issues. This article reviews current information on the key molecular steps in lung cancer pathogenesis, their timing, and clinical implications. Published by Elsevier Inc.

  20. Cancer Stem Cells in Lung Tumorigenesis

    PubMed Central

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2011-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets. PMID:20493987

  1. Trends in lung cancer incidence rates, Oklahoma 2005-2010.

    PubMed

    Mowls, Dana S; McCaffree, D Robert; Beebe, Laura A

    2015-01-01

    Lung cancer is the second most frequently diagnosed cancer among men and women in the United States. With cigarette smoking causing the majority of cases, patterns in lung cancer are often monitored to understand the impact of anti-tobacco efforts. The purpose of this research was to investigate trends in lung cancer incidence rates for the period 2005-2010 in Oklahoma. Data on Oklahoma's incident cases of lung cancer (2005-2010) were obtained from the Centers for Disease Control and Prevention WONDER system. Annual percent change (APC) was calculated by linear regression to characterize trends in lung cancer incidence rates over time for the overall population, by gender, by age group, and by age group within gender. Rates were considered to increase or decrease if the p-value for trend was <0.05. From 2005 through 2010, lung cancer incidence rates declined from 81.96 to 68.19 per 100,000 population, with an APC of -3.58% (p-value: 0.0220). When subgroups were examined, declines were observed among all males (APC: -4.25%; p-value: 0.0270), males <65 years (APC: -5.32%; p-value: 0.0008), females <65 years (APC: -4.85%; p-value: 0.0044), and persons aged 55-64 years (APC: -6.38%; p-value: 0.0017). Declines in lung cancer incidence rates occurred during 2005-2010 among the overall population and within select demographic groups in Oklahoma. Although trends were stable for several demographic groups, rates of lung cancer incidence were lower in 2010 compared to 2005. Continued evidence-based tobacco control efforts are needed to ensure further reductions in lung cancer incidence rates in the state of Oklahoma.

  2. Incidence and risk factors for skin cancer following lung transplantation.

    PubMed

    Rashtak, Shadi; Dierkhising, Ross A; Kremers, Walter K; Peters, Steve G; Cassivi, Stephen D; Otley, Clark C

    2015-01-01

    Relative to other solid-organ transplantations, limited studies characterize skin cancer among lung-transplant recipients. We sought to assess the cumulative incidence, tumor burden, and risk factors for skin cancer among patients with lung transplantation. Medical records of patients at Mayo Clinic who had undergone lung transplantation between 1990 and 2011 were reviewed (N = 166). At 5 and 10 years posttransplantation the cumulative incidence was 31% and 47% for any skin cancer, 28% and 42% for squamous cell carcinoma, 12% and 21% for basal cell carcinoma, and 53% and 86% for death, respectively. Four patients died of metastatic squamous cell carcinoma. The cumulative incidence for a subsequent skin cancer of the same type 4 years after an initial skin cancer was 85% and 43% for squamous and basal cell carcinoma, respectively. Increasing age, male gender, skin cancer history, and more recent year of transplantation were associated with increased risk of skin cancer posttransplantation. Sirolimus was not associated with decreased risk, nor did voriconazole show an increased risk for skin cancer. Retrospective and tertiary single-center design of the study is a limitation. Skin cancers frequently occur in lung-transplant recipients. The risk of subsequent skin cancer is increased substantially in patients who develop a skin cancer after their transplantation. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Mortality from lung cancer in Ontario uranium miners.

    PubMed Central

    Kusiak, R A; Ritchie, A C; Muller, J; Springer, J

    1993-01-01

    Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Ontario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increases as the intensity of exposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especially great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages. PMID:8217852

  4. 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 - ...

  5. Lung cancer screening: the way forward

    PubMed Central

    Field, J K; Duffy, S W

    2008-01-01

    To take lung cancer screening into national programmes, we first have to answer the question whether low-dose computed tomography (LDCT) screening and treatment of early lesions will decrease lung cancer mortality compared with a control group, to accurately estimate the balance of benefits and harms, and to determine the cost-effectiveness of the intervention. PMID:18665179

  6. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Cancer.gov

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  7. 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.

  8. A consensus statement on the gender perspective in lung cancer.

    PubMed

    Isla, D; Majem, M; Viñolas, N; Artal, A; Blasco, A; Felip, E; Garrido, P; Remón, J; Baquedano, M; Borrás, J M; Die Trill, M; García-Campelo, R; Juan, O; León, C; Lianes, P; López-Ríos, F; Molins, L; Planchuelo, M Á; Cobo, M; Paz-Ares, L; Trigo, J M; de Castro, J

    2016-11-24

    Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

  9. Pathogenesis sequences in Gejiu miners with lung cancer: an introduction.

    PubMed

    Li, Bian; Ruan, Yonghua; Ma, Liju; Hua, Hairong; Li, Zhou; Tuo, Xiaoyu; Zhou, Zheyan; Li, Ting; Liu, Shiyue; Jin, Kewei

    2015-09-01

    Tin miners in Gejiu, Yunnan Province, China are at high risk of developing lung cancer with significant occupational characteristics. Tissue samples from these miners presented pathological characteristics, such as fibroplasia in carcinomas, peri-cancerous tissue in lung cancers, and hyperplasia and dysplasia of epithelial cells in peri-cancerous tissue. Carcinomas induced by Yunnan tin mine dust in the animal experiment underwent inflammation, fibroplasia, hyperplasia, dysplasia, and carcinogenesis of epithelial cells. A correlated and synergistic relationship was observed between bronchial epithelial cell transformation and fibroblast activation in vitro induced by mine dust. Fibroblast hyperplasia and activation are important factors that promote the transformation and carcinogenesis of epithelial cells. Our findings suggested that pulmonary fibrosis may increase the risk and promote the occurrence of lung cancer, which can lead to lung fiber hyperplasia.

  10. Tobacco and lung cancer: risks, trends, and outcomes in patients with cancer.

    PubMed

    Warren, Graham W; Cummings, K Michael

    2013-01-01

    Tobacco use, primarily associated with cigarette smoking, is the largest preventable cause of cancer mortality, responsible for approximately one-third of all cancer deaths. Approximately 85% of lung cancers result from smoking, with an additional fraction caused by secondhand smoke exposure in nonsmokers. The risk of lung cancer is dose dependent, but can be dramatically reduced with tobacco cessation, especially if the person discontinues smoking early in life. The increase in lung cancer incidence in different countries around in the world parallels changes in cigarette consumption. Lung cancer risks are not reduced by switching to filters or low-tar/low-nicotine cigarettes. In patients with cancer, continued tobacco use after diagnosis is associated with poor therapeutic outcomes including increased treatment-related toxicity, increased risk of second primary cancer, decreased quality of life, and decreased survival. Tobacco cessation in patients with cancer may improve cancer treatment outcomes, but cessation support is often not provided by oncologists. Reducing the health related effects of tobacco requires coordinated efforts to reduce exposure to tobacco, accurately assess tobacco use in clinical settings, and increase access to tobacco cessation support. Lung cancer screening and coordinated international tobacco control efforts offer the promise to dramatically reduce lung cancer mortality in the coming decades.

  11. Microsatellite alteration in multiple primary lung cancer

    PubMed Central

    Shen, Cheng; Wang, Xin; Tian, Long

    2014-01-01

    Patients with pulmonary neoplasms have an increased risk for developing a second tumor of the lung, either at the same time or different times. It is important to determine if the second tumor represents an independent primary tumor or recurrence/metastasis, because it will significantly change the management and prognosis. Microsatellite instability (MSI) and loss of heterozygosity (LOH) represents molecular disorders acquired by the cell during neoplastic transformation. Both are associated with genetic instability. Functional silencing of tumour suppressor genes may be the consequence of genomic instability, particularly of the globally occurring LOH phenomenon. Numerous studies have confirmed the role of MSI/LOH at both the early and the late stages of multiple primary lung cancer. This paper reviews the published literatures focused on the role of MSI/LOH significance in multiple primary lung cancer. Additionally, a new method based on the allelic variations at polymorphic microsatellite markers was offered that it does not rely on collection of normal tissue, performed with minimal tumor sample, and will complement clinical criteria for diagnostic discrimination between multiple primary cancers versus solitary metastatic diseases. PMID:25364529

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

    ClinicalTrials.gov

    2017-04-12

    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

  13. Increased insulin-like growth factor 1 receptor (IGF1R) expression in small cell lung cancer and the effect of inhibition of IGF1R expression by RNAi on growth of human small cell lung cancer NCI-H446 cell.

    PubMed

    Wang, Zhigang; Lu, Pingfang; Liang, Zhu; Zhang, Zhanfei; Shi, Weicheng; Cai, Xiaobi; Chen, Chunyuan

    2015-01-01

    Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in tumourigenesis that may be an attractive target for anti-cancer treatment. In this study, the expression and clinical significance of IGF1R were investigated in serum and lung cancer tissues from small cell lung cancinoma (SCLC). We also compared the effect of IGF1R up-regulation and IGF1R inhibition on viability and apoptosis of NCI-H446 cells. We found the concentration of IGF1R in blood serum was significantly increased and positive IGF1R protein in cancer tissue was more prevalent in SCLC. A statistically significant correlation among IGF1R-positve tumors, lymph node metastasis and local invasion was discussed. Furthermore, IGF1R overexpression lead to an increase of cell survival and suppressed cell apoptosis, IGF1R silencing mediated by RNAi abrogate this response of NCI-H446 cells. Our results further demonstrated that the effects of these treatments may be assigned to the effective inhibition of lung cancer cells from Akt/P27(Kip1) pathway in IGF-1R signaling. These features may have important implications for future anti-IGF1R therapeutic approaches.

  14. Lung cancer epidemiology: contemporary and future challenges worldwide

    PubMed Central

    Wojciechowska, Urszula; Mańczuk, Marta; Łobaszewski, Jakub

    2016-01-01

    Over the last century, lung cancer from the rarest of diseases became the biggest cancer killer of men worldwide and in some parts of the world also of women (North America, East Asia, Northern Europe, Australia and New Zealand). In 2012 over 1.6 million of people died due to lung cancer. The cause-effect relationship between tobacco smoking and lung cancer occurrence has been proven in many studies, both ecological and clinical. In global perspective one can see the increasing tobacco consumption trend followed by ascending trends of lung cancer mortality, especially in developing countries. In some more developed countries, where the tobacco epidemics was on the rise since the beginning of the 20th century and peaked in its mid, in male population lung cancer incidence trend reversed or leveled off. Despite predicted further decline of incidence rates, the absolute number of deaths will continue to grow in these countries. In the remaining parts of the world the tobacco epidemics is still evolving what brings rapid increase of the number of new lung cancer cases and deaths. Number of lung cancer deaths worldwide is expected to grow up to 3 million until 2035. The figures will double both in men (from 1.1 million in 2012 to 2.1 million in 2035) and women (from 0.5 million in 2012 to 0.9 million in 2035) and the two-fold difference between sexes will persist. The most rapid increase is expected in Africa region (AFRO) and East Mediterranean region (EMRO). The increase of the absolute number of lung cancer deaths in more developed countries is caused mostly by population aging and in less developed countries predominantly by the evolving tobacco epidemic. PMID:27195268

  15. Lung cancer epidemiology: contemporary and future challenges worldwide.

    PubMed

    Didkowska, Joanna; Wojciechowska, Urszula; Mańczuk, Marta; Łobaszewski, Jakub

    2016-04-01

    Over the last century, lung cancer from the rarest of diseases became the biggest cancer killer of men worldwide and in some parts of the world also of women (North America, East Asia, Northern Europe, Australia and New Zealand). In 2012 over 1.6 million of people died due to lung cancer. The cause-effect relationship between tobacco smoking and lung cancer occurrence has been proven in many studies, both ecological and clinical. In global perspective one can see the increasing tobacco consumption trend followed by ascending trends of lung cancer mortality, especially in developing countries. In some more developed countries, where the tobacco epidemics was on the rise since the beginning of the 20th century and peaked in its mid, in male population lung cancer incidence trend reversed or leveled off. Despite predicted further decline of incidence rates, the absolute number of deaths will continue to grow in these countries. In the remaining parts of the world the tobacco epidemics is still evolving what brings rapid increase of the number of new lung cancer cases and deaths. Number of lung cancer deaths worldwide is expected to grow up to 3 million until 2035. The figures will double both in men (from 1.1 million in 2012 to 2.1 million in 2035) and women (from 0.5 million in 2012 to 0.9 million in 2035) and the two-fold difference between sexes will persist. The most rapid increase is expected in Africa region (AFRO) and East Mediterranean region (EMRO). The increase of the absolute number of lung cancer deaths in more developed countries is caused mostly by population aging and in less developed countries predominantly by the evolving tobacco epidemic.

  16. Lung cancer stem cells and implications for future therapeutics.

    PubMed

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

    2014-07-01

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

  17. Lung cancer tissue diagnosis in poor lung function: addressing the ongoing percutaneous lung biopsy FEV1 paradox using Heimlich valve.

    PubMed

    Abdullah, R; Tavare, A N; Creamer, A; Creer, D; Vancheeswaran, R; Hare, S S

    2016-08-01

    Many centres continue to decline percutaneous lung biopsy (PLB) in patients with poor lung function (particularly FEV1 <1 L) due to the theoretically increased risk of pneumothorax. This practice limits access to novel lung cancer therapies and minimally invasive surgical techniques. Our retrospective single-centre analysis of 212 patients undergoing PLB, all performed prospectively and blinded to lung function, demonstrates that using ambulatory Heimlich valve chest drain (HVCD) to treat significant postbiopsy pneumothorax facilitates safe, diagnostic, early discharge lung biopsy irrespective of lung function with neither FEV1 <1 L nor transfer coefficient for carbon monoxide (TLCO) <40% predicted shown to be independent predictors of HVCD insertion or pneumothorax outcomes. Incorporating ambulatory HVCD into standard PLB practice thereby elegantly bridges the gap that currently exists between tissue diagnosis in patients with poor lung function and the advanced therapeutic options available for this cohort.

  18. Increasing radiation therapy dose is associated with improved survival in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer.

    PubMed

    Koshy, Matthew; Malik, Renuka; Weichselbaum, Ralph R; Sher, David J

    2015-02-01

    To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non-small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log-rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). This comparative effectiveness analysis of SBRT dose for patients with stage I non-small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The Impact of the Cancer Genome Atlas on Lung Cancer

    PubMed Central

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2016-11-07

    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

  1. Functions and mechanisms of long noncoding RNAs in lung cancer

    PubMed Central

    Peng, Zhenzi; Zhang, Chunfang; Duan, Chaojun

    2016-01-01

    Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs) are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field. PMID:27499635

  2. New Immunotherapy and Lung Cancer.

    PubMed

    Sánchez de Cos Escuín, Julio

    2017-08-17

    Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response. These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%-25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results. This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. 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

  4. Lung cancer trends: smoking, obesity, and sex assessed in the Staten Island University's lung cancer patients.

    PubMed

    Gupta, Shilpi; Hassan, Samer; Bhatt, Vijaya R; Abdul Sater, Houssein; Dilawari, Asma

    2014-01-01

    The incidence of lung cancer in the United States decreased by 1.8% from 1991 to 2005 while it increased by 0.5% in females. We assessed whether nonsmokers afflicted with lung cancer at Staten Island University Hospital are disproportionately female in comparison to national averages. We also evaluated different factors including race, histology, and body mass index (BMI) in correlation with smoking history. A retrospective chart review was conducted from 2005 to 2011 on 857 patients. Patients were divided into two groups according to their smoking status: current or ever-smokers, and former or never-smokers. A chi-square test for categorical data and multivariate logistic regression analyses was used to study the relation between BMI and the other clinical and demographic data. Forty-nine percent of patients were men and 51% were women with a mean age at diagnosis of 67.8 years. Current smokers were most common (50.2%) followed by ever-smokers (18.2%), former smokers (15.8%) and never-smokers (15.6%). Forty eight percent had stage IV lung cancer upon presentation. Never-smokers with lung cancer were 24 times more likely to be females. However, the proportion of female former smokers (31.6%) was lower than the proportion of male former smokers (68.4%) (P=0.001). There was no significant association between American Joint Committee on Cancer (AJCC) stage, sex, race, and histological type in the two smoking groups. Current/ever-smokers tended to be younger at age of diagnosis (P=0.0003). BMI was lower in the current/ever-smokers (26.8 kg/m(2)) versus former/never-smokers (28.8) in males (P=0.0005). BMI was significantly higher in males (30.26) versus females (25.25) in the never-smoker category (P=0.004). Current smokers, compared to others, had a lower BMI in males (26.4 versus 28.3; P=0.0001) and females (25.5 versus 26.9; P=0.013) but the mean BMI for all groups was in the overweight/obese range. Our population of lung cancer patients although demographically

  5. Smoking correlates with increased cytoskeletal protein-related coding region mutations in the lung and head and neck datasets of the cancer genome atlas.

    PubMed

    Yavorski, John M; Blanck, George

    2016-12-01

    Cancer from smoking tobacco is considered dependent on mutagens, but significant molecular aspects of smoking-specific, cancer development remain unknown. We defined sets of coding regions for oncoproteins, tumor suppressor proteins, and cytoskeletal-related proteins that were compared between nonsmokers and smokers, for mutation occurrences, in the lung adenocarcinoma (LUAD), head and neck squamous carcinoma (HNSC), bladder carcinoma (BLCA), and pancreatic adenocarcinoma ( PAAD) datasets from the cancer genome atlas (TCGA). We uncovered significant differences in overall mutation rates, and in mutation rates in cytoskeletal protein-related coding regions (CPCRs, including extracellular matrix protein coding regions), between nonsmokers and smokers in LUAD and HNSC (P < 0.001), raising the question of whether the CPCR mutation differences lead to different clinical courses for nonsmoker and smoker cancers. Another important question inspired by these results is, whether high smoker cancer mutation rates would facilitate genotoxicity or neoantigen-based therapies. No significant, mutation-based differences were found in the BLCA or PAAD datasets, between nonsmokers and smokers. However, a significant difference was uncovered for the average number of overall cancer mutations, in LUAD, for persons who stopped smoking more than 15 years ago, compared with more recent smokers (P < 0.032).

  6. Smoking increases carcinogenic polycyclic aromatic hydrocarbons in human lung tissue.

    PubMed

    Goldman, R; Enewold, L; Pellizzari, E; Beach, J B; Bowman, E D; Krishnan, S S; Shields, P G

    2001-09-01

    Tobacco smoke is a major source of human exposure to polycyclic aromatic hydrocarbons (PAHs). The concentration of PAHs in lung tissue would reflect an individual's dose, and its variation could perhaps reflect cancer risk. Eleven PAHs were measured in 70 lung tissue samples from cancer-free autopsy donors by gas chromatography-mass spectrometry. There were 37 smokers and 33 nonsmokers as estimated by serum cotinine concentration. The sum of PAH concentrations was higher in smokers (P = 0.01), and there was a dose-response relationship for greater smoking (P < 0.01). Smoking increased the concentration of five PAHs including benzo(a)pyrene, which increased approximately 2-fold. The risk for increasing carcinogenic PAHs (odds ratio, 8.20; 95% confidence interval, 2.39-28.09) was 3-fold compared with noncarcinogenic PAHs (odds ratio, 2.61; 95% confidence interval, 0.75-9.12). A higher concentration of PAHs was detected in the lung tissue of males, although the estimated smoking was similar in males and females. Race was not associated with PAH concentrations overall, but PAH concentrations appeared to be higher in African-American males than in any other group. Age was weakly correlated with an increase in fluoranthene and pyrene. The measurement of PAHs in human lung tissue can be used to estimate the actual dose to the target organ.

  7. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China

    SciTech Connect

    Engels, E.A.; Shen, M.; Chapman, R.S.; Pfeiffer, R.M.; Yu, Y.Y.; He, X.Z.; Lan, Q.

    2009-03-15

    Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios (HRs) ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.

  8. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China

    PubMed Central

    Engels, Eric A.; Shen, Min; Chapman, Robert S.; Pfeiffer, Ruth M.; Yu, Ying-Ying; He, Xingzhou; Lan, Qing

    2008-01-01

    Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1000 person-years). The association was especially pronounced in the first five years after tuberculosis diagnosis (hazard ratios [HRs] ranging 6.7–13) but remained strong 5–9.9 years (HR 3.4, 95%CI 1.3–9.1) and 10+ years (HR 3.0, 95%CI 1.3–7.3) after tuberculosis. These associations were similar among men and women, and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease, and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis. PMID:19058197

  9. Growth Inhibitory Effect of (E)-2,4-bis(p-hydroxyphenyl)-2-Butenal Diacetate through Induction of Apoptotic Cell Death by Increasing DR3 Expression in Human Lung Cancer Cells.

    PubMed

    Lee, Ung-Soo; Ban, Jung Ok; Yeon, Eung Tae; Lee, Hee Pom; Udumula, Venkatareddy; Ham, Young Wan; Hong, Jin Tae

    2012-11-01

    The Maillard Reaction Products (MRPs) are chemical compounds which have been known to be effective in chemoprevention. Death receptors (DR) play a central role in directing apoptosis in several cancer cells. In our previous study, we demonstrated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal, a MRP product, inhibited human colon cancer cell growth by inducing apoptosis via nuclear factor-κB (NF-κB) inactivation and G2/M phase cell cycle arrest. In this study, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate, a new (E)-2,4-bis(p-hydroxyphenyl)-2-butenal derivative, was synthesized to improve their solubility and stability in water and then evaluated against NCI-H460 and A549 human lung cancer cells. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate reduced the viability in both cell lines in a time and dose-dependent manner. We also found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate increased apoptotic cell death through the upregulation of the expression of death receptor (DR)-3 and DR6 in both lung cancer cell lines. In addition to this, the transfection of DR3 siRNA diminished the growth inhibitory and apoptosis inducing effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate on lung cancer cells, however these effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate was not changed by DR6 siRNA. These results indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate inhibits human lung cancer cell growth via increasing apoptotic cell death by upregulation of the expression of DR3.

  10. Can microRNAs improve the management of lung cancer patients? A clinician's perspective.

    PubMed

    Tufman, Amanda; Tian, Fei; Huber, Rudolf Maria

    2013-12-05

    The treatment of patients with lung cancer is increasingly individualised. Rather than treating lung cancer as a single disease, clinicians are often called upon to consider the precise histology and molecular biology of each tumour in addition to the individual characteristics of each patient. Paralleling advances in lung cancer management, advances in the detection of lung cancer are changing practice. Lung cancer screening promises to find disease at a curable stage; however, the high false positive rate in screening trials has clinical and fiscal ramifications which demand attention. Biomarkers able to stratify for the risk of cancer, prognosticate the course of disease, or predict the response to treatment are in increasing demand. This paper summarizes some of the clinical problems faced by those treating lung cancer patients, and examines how knowledge about the role of microRNAs in lung cancer biology may change patient management.

  11. Can MicroRNAs Improve the Management of Lung Cancer Patients? A Clinician's Perspective

    PubMed Central

    Tufman, Amanda; Tian, Fei; Huber, Rudolf Maria

    2013-01-01

    The treatment of patients with lung cancer is increasingly individualised. Rather than treating lung cancer as a single disease, clinicians are often called upon to consider the precise histology and molecular biology of each tumour in addition to the individual characteristics of each patient. Paralleling advances in lung cancer management, advances in the detection of lung cancer are changing practice. Lung cancer screening promises to find disease at a curable stage; however, the high false positive rate in screening trials has clinical and fiscal ramifications which demand attention. Biomarkers able to stratify for the risk of cancer, prognosticate the course of disease, or predict the response to treatment are in increasing demand. This paper summarizes some of the clinical problems faced by those treating lung cancer patients, and examines how knowledge about the role of microRNAs in lung cancer biology may change patient management. PMID:24396506

  12. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification.

    PubMed

    Inamura, Kentaro

    2017-01-01

    Lung cancer is the leading cause of cancer-related death worldwide due to late diagnoses and limited treatment interventions. Recently, comprehensive molecular profiles of lung cancer have been identified. These novel characteristics have enhanced the understanding of the molecular pathology of lung cancer. The identification of driver genetic alterations and potential molecular targets has resulted in molecular-targeted therapies for an increasing number of lung cancer patients. Thus, the histopathological classification of lung cancer was modified in accordance with the increased understanding of molecular profiles. This review focuses on recent developments in the molecular profiling of lung cancer and provides perspectives on updated diagnostic concepts in the new 2015 WHO classification. The WHO classification will require additional revisions to allow for reliable, clinically meaningful tumor diagnoses as we gain a better understanding of the molecular characteristics of lung cancer.

  13. Nasal Swab Shows Promise in Confirming Lung Cancers

    MedlinePlus

    ... 163805.html Nasal Swab Shows Promise in Confirming Lung Cancers Simple technique is based on cancer DNA ... 27, 2017 MONDAY, Feb. 27, 2017 (HealthDay News) -- Lung cancer remains by far the leading cancer killer ...

  14. Genomic heterogeneity of multiple synchronous lung cancer

    PubMed Central

    Liu, Yu; Zhang, Jianjun; Li, Lin; Yin, Guangliang; Zhang, Jianhua; Zheng, Shan; Cheung, Hannah; Wu, Ning; Lu, Ning; Mao, Xizeng; Yang, Longhai; Zhang, Jiexin; Zhang, Li; Seth, Sahil; Chen, Huang; Song, Xingzhi; Liu, Kan; Xie, Yongqiang; Zhou, Lina; Zhao, Chuanduo; Han, Naijun; Chen, Wenting; Zhang, Susu; Chen, Longyun; Cai, Wenjun; Li, Lin; Shen, Miaozhong; Xu, Ningzhi; Cheng, Shujun; Yang, Huanming; Lee, J. Jack; Correa, Arlene; Fujimoto, Junya; Behrens, Carmen; Chow, Chi-Wan; William, William N.; Heymach, John V.; Hong, Waun Ki; Swisher, Stephen; Wistuba, Ignacio I.; Wang, Jun; Lin, Dongmei; Liu, Xiangyang; Futreal, P. Andrew; Gao, Yanning

    2016-01-01

    Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events. PMID:27767028

  15. Association between environmental dust exposure and lung cancer in dogs.

    PubMed

    Bettini, Giuliano; Morini, Maria; Marconato, Laura; Marcato, Paolo Stefano; Zini, Eric

    2010-12-01

    The objective of this study was to investigate the relationship between the accumulation of black dust matter in lungs (anthracosis) and primary lung cancer in dogs. A retrospective study was carried out on material from 35 dogs with primary lung cancer and 160 controls. The amount, histological appearance and birefringence of anthracosis were assessed in pulmonary specimens by light microscopy, and the odds ratio (OR) calculated for dogs with primary lung cancer. The same factors were analysed to identify an association between tumour histotype, histological grade, and clinical stage. Papillary adenocarcinoma was most commonly diagnosed (45.7%). The majority of tumours were of histological grade II, and the lung cancer was more often localised (clinical stage I). An increased risk of lung cancer was observed in dogs with higher amounts of anthracosis (OR: 2.11, CI 95%: 1.20-3.70; P < 0.01), which suggests an association between anthracosis due to inhalation of polluted air and lung cancer in dogs.

  16. Imaging Primary Lung Cancers in Mice to Study Radiation Biology

    SciTech Connect

    Kirsch, David G.; Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.; Perez, Bradford A.; Santiago, Philip M.; Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen

    2010-03-15

    Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

  17. Detection of Lung Cancer with Volatile Organic Biomarkers in Exhaled Breath and Lung Cancer Cells

    NASA Astrophysics Data System (ADS)

    Yu, Jin; Wang, Di; Wang, Le; Wang, Ping; Hu, Yanjie; Ying, Kejing

    2009-05-01

    In patients with lung cancer, volatile organic compounds (VOCs) are excreted in exhaled breath. In this article, exhaled breath of 30 lung cancer paitients and 30 healthy people were collected, preconcentrated by solid-microextraction(SPME) and analyzed with gas chrom-atography and mass spectrometry (GC/MS). A predictive model composed of 5 VOCs out of 16 candidate VOCs detected in the lung cancer patients is constructed by discriminant analysis, with a sensitivity of 76.7% and specificity of 96.7%. We detected exhaled VOCs of 3 different lung cancer cell lines and human bronchial epithelial cell lines. 2-Tridicanone is considered the distinctive marker of lung cancer cells, which is found in lung cancer patients' exhaled breath as well. Compared to healthy people, patients with lung cancer had distinctive VOCs in their exhaled breath. The predictive model can work as diagnosis reference for lung cancer. VOCs found in lung cancer cell line help the cognition of the mechasim VOCs generating in lung cancer patients.

  18. Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells

    PubMed Central

    Moody, Terry W.; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A.; Berna, Marc; Thill, Michelle; Jensen, Robert T.; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D.; Giaccone, Giuseppe; Wink, David A.

    2009-01-01

    The effects of dithiolethione-modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 μg/ml concentrations significantly reduced prostaglandin (PG)E2 levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 μg/ml, respectively. Using the MTT assay, 10 μg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18 mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE2 levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC, PMID:19628293

  19. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage

    PubMed Central

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  20. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC.

  1. Epigenetic regulation of ANKRD18B in lung cancer.

    PubMed

    Liu, Wen-Bin; Han, Fei; Jiang, Xiao; Yin, Li; Chen, Hong-Qiang; Li, Yong-Hong; Liu, Yong; Cao, Jia; Liu, Jin-Yi

    2015-04-01

    The identification of the key genetic and epigenetic changes underlying lung carcinogenesis would aid effective early diagnosis and targeted therapies for lung cancer. In this study, we screened a novel hypermethylated gene ankyrin repeat domain 18B (ANKRD18B), to determine whether it is regulated by DNA methylation and clarify its biological and clinical implications in lung cancer. Methylation status and expression level were analyzed by methylation-specific PCR, bisulfite genomic sequencing, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We detected ANKRD18B hypermethylation in 52 of 98 (53.1%) primary lung cancer tissues and in nine of 10 (90%) cell lines, whereas no methylation was seen in 10 normal lung tissue samples. ANKRD18B methylation was more frequently observed in patients with poor differentiation (P < 0.05). Notably, 62 pairs of samples from patients whose tumor tissue showed hypermethylation of ANKRD18B exhibited the same aberrant methylation in 72.7% and 69.7% of their corresponding plasma and sputum samples, respectively; whereas no hypermethylation of ANKRD18B was detected in the sputum and plasma from patients whose tumor sample lacked this alteration. In addition, ANKRD18B mRNA expression was significantly decreased or silenced in lung cancer tissues and cell lines associated with hypermethylation of the ANKRD18B region. Demethylation agent 5-aza-2'-deoxycytidine significantly increased ANKRD18B mRNA expression in lung cancer cell lines. Furthermore, overexpression of ANKRD18B suppressed lung cancer cell growth. These results suggest that the expression of ANKRD18B is regulated by CpG island hypermethylation in lung cancer. Our findings confirm the importance of the identification of new markers of epigenetic dysregulation in cancer.

  2. Retrospective Analysis of Lung Transplant Recipients Found to Have Unexpected Lung Cancer in Explanted Lungs.

    PubMed

    Nakajima, Takahiro; Cypel, Marcelo; de Perrot, Marc; Pierre, Andrew; Waddell, Tom; Singer, Lianne; Roberts, Heidi; Keshavjee, Shaf; Yasufuku, Kazuhiro

    2015-01-01

    Unexpected lung cancer is sometimes found in explanted lungs. The objective of this study was to review these patients and their outcomes to better understand and optimize management protocols for lung transplant candidates with pulmonary nodules. Retrospective analysis of pretransplant imaging and clinicopathologic characteristics of patients who were found to have lung cancer in their explanted lungs was performed. From January 2003 to December 2012, 13 of 853 lung transplant recipients were found to have unexpected lung cancer in their explanted lung (1.52%). Of them, 9 cases were for interstitial lung disease (2.8%; 9/321 recipients) and 4 cases were for chronic obstructive pulmonary disease (1.57%; 4/255 recipients). The median period between computed tomographic scan and lung transplantation was 2.40 months (range: 0.5-19.2). On computed tomographic scan, only 3 cases were shown to possibly have a neoplasm by the radiologist. The staging of these lung cancers was as follows: 3 cases of IA, 1 case of IB, 5 cases of IIA, 1 case of IIIA, and 3 cases of IV. Of 13 cases, 9 died owing to cancer progression. On the contrary, only 1 stage I case with small cell lung cancer showed cancer recurrence. The median survival time was 339 days, and the 3-year survival rate was 11.0%. In conclusion, most of the patients with unexpected lung cancer showed poor prognosis except for the early-stage disease. The establishment of proper protocol for management of such nodules is important to improve the management of candidates who are found to have pulmonary nodules on imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Development of lung cancer CT screening operating support system

    NASA Astrophysics Data System (ADS)

    Ishigaki, Rikuta; Hanai, Kozou; Suzuki, Masahiro; Kawata, Yoshiki; Niki, Noboru; Eguchi, Kenji; Kakinuma, Ryutaro; Moriyama, Noriyuki

    2009-02-01

    In Japan, lung cancer death ranks first among men and third among women. Lung cancer death is increasing yearly, thus early detection and treatment are needed. For this reason, CT screening for lung cancer has been introduced. The CT screening services are roughly divided into three sections: office, radiology and diagnosis sections. These operations have been performed through paper-based or a combination of paper-based and an existing electronic health recording system. This paper describes an operating support system for lung cancer CT screening in order to make the screening services efficient. This operating support system is developed on the basis of 1) analysis of operating processes, 2) digitalization of operating information, and 3) visualization of operating information. The utilization of the system is evaluated through an actual application and users' survey questionnaire obtained from CT screening centers.

  4. Lung Cancer Risk Following Detection of Pulmonary Scarring by Chest Radiography in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Yu, Ying-Ying; Pinsky, Paul F.; Caporaso, Neil E.; Chatterjee, Nilanjan; Baumgarten, Mona; Langenberg, Patricia; Furuno, Jon P.; Lan, Qing; Engels, Eric A.

    2010-01-01

    Background Fibrotic scars are frequently found in proximity to lung cancer at the time of cancer diagnosis. However, the nature of the relationship between pulmonary scarring and lung cancer remains uncertain. Our objective was to test whether localized pulmonary scarring is associated with increased lung cancer risk. Methods Cohort analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We included 66 863 cancer-free trial participants aged 55 to 74 years, who received a baseline chest radiographic examination and were followed up subsequently for up to 12 years. We used proportional hazards models to estimate hazard ratios (HRs) for lung cancer associated with scarring, adjusting for age, sex, race, and cigarette smoking, and in relation to laterality of scarring. The main outcome measure was incident lung cancer. Results Scarring was present on the baseline chest radiograph for 5041 subjects (7.5%). Scarring was associated with elevated lung cancer risk (809 lung cancer cases [HR, 1.5; 95% confidence interval {CI}, 1.2-1.8]). This association was specific for cancer in the lung ipsilateral to the scar (HR, 1.8; 95% CI, 1.4-2.4) and absent for contralateral cancer (HR, 0.9; 95% CI, 0.7-1.2). Ipsilateral lung cancer risk was elevated throughout the follow-up period (interval-specific HRs, 1.6, 2.0, 2.1, and 1.7 during 0.01-2.00, 2.01-4.00, 4.01-6.00, and 6.01-12.00 years after baseline chest radiography, respectively). Conclusions The relationship between pulmonary scarring and lung cancer was specific to the same lung and extended over time. These findings are consistent with the hypothesis that localized inflammatory processes associated with scarring promote the subsequent development of lung cancer. PMID:19029496

  5. [Identification of occupational exposures among patients with lung cancer].

    PubMed

    Cellier, Camille; Charbotel, Barbara; Carretier, Julien; Rebattu, Paul; Fayette, Jérôme; Pérol, Maurice; Claude, Line; Philip, Thierry; Fervers, Béatrice

    2013-01-01

    Despite the rising number of lung cancers recognized as occupational disease, occupational lung cancers are still under-reported. To improve the recognition of occupational lung cancer, we implemented at the Léon-Bérard Cancer Centre, a questionnaire-based process to identify occupational exposures in these patients and improve compensation. Between January 2010 and December 2011, 91 lung cancer patients responded to a questionnaire. An "occupational cancer" consultation was proposed to patients reporting exposure to carcinogens or jobs with risk of exposure. Fifty-one patients were seen in consultation (34 following the questionnaire and 17 directly addressed by the oncologist). A suspicion of high or average imputability was identified in 31 (60.8%) patients and a compensation process seemed possible for 27 (61.4%). Asbestos was the most common carcinogen identified. Among 17 compensation processes engaged, 12 succeeded and one is ongoing. The complexity of the administrative process seems to be an obstacle for patients and perpetuates inequality. The implementation of our approach increased the identification and the compensation of occupational lung cancer. Our approach responds to the objectives of the National Cancer Plan and helps to improve the overall care of patients with cancer. This approach has been awarded by the national label in 2011 "Year of the patients and their rights".

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

    SciTech Connect

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

    1995-03-01

    Data are presented on the risks of cancers other than lung cancer in a cohort of iron miners from northern Sweden occupationally exposed to elevated levels of the radioactive gas radon. Compared with rates for the four northernmost counties of Sweden, mortality was increased for all cancers other than lung cancer (ratio of observed to expected deaths 1.21, 95% confidence interval 1.03-1.41), stomach cancer (ratio of observed to expect- ed deaths 1.45, 95% confidence interval 1.04-1.98), and rectal cancer (ratio of observed to expected deaths 1.94, 95% confidence interval 1.03-3.31). Despite these overall increases, mortality was not significantly associated with cumulative exposure to radon, either for all cancers other than lung cancer or for any site of cancer other than lung cancer individually. However, the data from this cohort on its own have limited power; and for several sites of cancer the data in this study would be consistent with a radon-related increase. Further study of cancers other than lung cancer in populations exposed to radon is required. 8 refs., 2 tabs.

  7. Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

    PubMed Central

    He, Bei Ping; Wang, Jian Jun; Zhang, Xian; Wu, Yan; Wang, Miao; Bay, Boon-Huat; Chang, Alex Yuang-Chi

    2006-01-01

    The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidated. In this study, we have investigated microglial reactions in brain tissues with metastatic lung cancer cells and evaluated the cytotoxic effects of lipopolysaccharide (LPS)-activated microglia on metastatic lung cancer cells in vitro. In the vicinity of metastatic lung cancer mass in the brain, microglia showed signs of significant activation. There was an obvious increase in the number of microglia labeled with ionized calcium binding adaptor molecule 1 (Iba-1) antibody, a specific marker of microglia. The microglia were observed to form a clear boundary between the tumor mass and normal brain tissue. In the region where the tumor mass was situated, only a few microglia expressed inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), indicating differential activation in those microglia. The supernatant from LPS-activated microglia induced apoptosis of metastatic lung cancer cells in vitro in a dose- and time-dependent manner. However, at lower concentrations of activated microglial supernatant, trophic effects on cancer cells were observed, some lung cancer cells being insensitive to microglial cytotoxicity. Together with the observation that TNF-α alone induced proliferation of the tumor cells, the findings provide possible clues to the mechanism involved in metastasis of lung cancer cells to the brain. PMID:17088948

  8. Anthropometry and the Risk of Lung Cancer in EPIC

    PubMed Central

    Dewi, Nikmah Utami; Boshuizen, Hendriek C.; Johansson, Mattias; Vineis, Paolo; Kampman, Ellen; Steffen, Annika; Tjønneland, Anne; Halkjær, Jytte; Overvad, Kim; Severi, Gianluca; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Li, Kuanrong; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Klinaki, Eleni; Tumino, Rosario; Palli, Domenico; Mattiello, Amalia; Tagliabue, Giovanna; Peeters, Petra H.; Vermeulen, Roel; Weiderpass, Elisabete; Torhild Gram, Inger; Huerta, José María; Agudo, Antonio; Sánchez, María-José; Ardanaz, Eva; Dorronsoro, Miren; Quirós, José Ramón; Sonestedt, Emily; Johansson, Mikael; Grankvist, Kjell; Key, Tim; Khaw, Kay-Tee; Wareham, Nick; Cross, Amanda J.; Norat, Teresa; Riboli, Elio; Fanidi, Anouar; Muller, David; Bueno-de-Mesquita, H. Bas

    2016-01-01

    The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)2) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0–34.9 versus 18.5–25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings. PMID:27370791

  9. Anthropometry and the Risk of Lung Cancer in EPIC.

    PubMed

    Dewi, Nikmah Utami; Boshuizen, Hendriek C; Johansson, Mattias; Vineis, Paolo; Kampman, Ellen; Steffen, Annika; Tjønneland, Anne; Halkjær, Jytte; Overvad, Kim; Severi, Gianluca; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Li, Kuanrong; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Klinaki, Eleni; Tumino, Rosario; Palli, Domenico; Mattiello, Amalia; Tagliabue, Giovanna; Peeters, Petra H; Vermeulen, Roel; Weiderpass, Elisabete; Torhild Gram, Inger; Huerta, José María; Agudo, Antonio; Sánchez, María-José; Ardanaz, Eva; Dorronsoro, Miren; Quirós, José Ramón; Sonestedt, Emily; Johansson, Mikael; Grankvist, Kjell; Key, Tim; Khaw, Kay-Tee; Wareham, Nick; Cross, Amanda J; Norat, Teresa; Riboli, Elio; Fanidi, Anouar; Muller, David; Bueno-de-Mesquita, H Bas

    2016-07-15

    The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.

  10. PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes xenograft tumor growth in A549 human lung cancer cells

    SciTech Connect

    Yu, Zhenhai; Huang, Liangqian; Qiao, Pengyun; Jiang, Aifang; Wang, Li; Yang, Tingting; Tang, Shengjian; Zhang, Wei; Ren, Chune

    2016-05-13

    Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed in many tumor cells, and plays an important role in the Warburg effect. In previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl 2013). However, the functions of PKM2 Thr454 modification in cancer cells still remain unclear. Here we find PKM2 translocates into the nucleus after Thr454 phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances mitochondrial respiration, decreases pentose phosphate pathway, and enhances chemosensitivity in A549 cells. In addition, the mutant (T454A) PKM2 reduces xenograft tumor growth in nude mice. These findings demonstrate that PKM2 T454 phosphorylation is a potential therapeutic target in lung cancer.

  11. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects

    PubMed Central

    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-01-01

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118). PMID:27566586

  12. Frequency of breast cancer, lung cancer, and tobacco use articles in women's magazines from 1987 to 2003.

    PubMed

    Tobler, Kyle J; Wilson, Philip K; Napolitano, Peter G

    2009-01-01

    The objective of this study was to compare the frequency of articles in women's magazines that address breast cancer, lung cancer, and tobacco use from 1987-2003 and to ascertain whether the annual number of articles reflected corresponding cancer mortality rates from breast cancer and lung cancer and the number of female smokers throughout this time period. We reviewed 13 women's magazines published in the United States from 1987-2003 using the search terms breast cancer, lung cancer, smoking, and tobacco. We reviewed the abstracts or entire articles to determine relevance. A total of 1044 articles addressed breast cancer, lung cancer, or tobacco use: 681 articles related to breast cancer, 47 related to lung cancer, and 316 related to tobacco use. The greater number of breast cancer articles compared to lung cancer articles was statistically significant (P value < .0001). The greater number of breast cancer articles compared to lung cancer articles combined with tobacco use articles was also statistically significant (P = .0012). The annual number breast cancer articles compared to the breast cancer mortality rate demonstrated a negative relationship. The annual number of lung cancer articles compared to the lung cancer mortality rate demonstrated no relationship. The annual number of tobacco use articles compared to the annual number of female smokers demonstrated no relationship. Breast cancer was more frequently represented than lung cancer or tobacco use in women's magazines from 1987-2003 despite the increase in lung cancer mortality, a decrease in breast cancer mortality, and an insignificant change in the number of female smokers.

  13. 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 ... lung cancer are given intravenously or by mouth. Lung Cancer Research The large-scale National Lung Screening ...

  14. HIV infection in the etiology of lung cancer: confounding, causality, and consequences.

    PubMed

    Kirk, Gregory D; Merlo, Christian A

    2011-06-01

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

  15. Risk of lung cancer among former chromium smelter workers.

    PubMed

    Rosenman, K D; Stanbury, M

    1996-05-01

    Hexavalent chromium is a known carcinogen. Previous epidemiologic studies in the 1950s of United States workers from seven facilities producing chromium compounds from chromite ore have reported a markedly increased risk for dying from lung cancer. As part of a high risk notification project of workers from four of these facilities, a mortality study was performed. The cohort was assembled in 1990-1991 from the Social Security records of four former chromate producing facilities in northern New Jersey. The study subjects were known to have worked at these facilities some time between 1937 and 1971. Proportionate mortality and proportionate cancer mortality ratios (PCMR) were calculated. The overall risk for lung cancer was a PCMR of 1.51 (confidence limits [CL] 1.29-1.74) for white men and 1.34 (CL 1.00-1.75) for black men. These risks increased with increasing duration of employment and latency since time of first employment. The PCMR for greater than 20 years duration of work and more than 20 years since first exposure was 1.94 (CL 1.15-3.06) for white men and 3.08 (CL 1.13-6.71) for black men. The risk for lung cancer for white men remains elevated more than 20 years after exposure has ceased (PCMR, 1.29; CL 1.03-1.60). The PCMR for nasal cavity/sinus cancer was also found to be a significantly increased, 5.18 (CL 2.37-11.30). A cluster of bladder cancer was seen among black workers from one facility, (PCMR, 3.30; CL 1.42-6.51). Despite the cessation of exposure, former chromium workers remain at significantly increased risk of lung cancer. Although there have been case reports of nasal cavity/ sinus cancer in association with chromium exposure, this is the first epidemiologic study to report a significant increase in these cancers. Limitations in this study include lack of exposure data and lack of information on smoking habits. The lack of increase in other smoking-related diseases besides lung cancer indicates that the increase in lung cancer cannot be

  16. 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.

  17. Lung cancer surgery: an up to date

    PubMed Central

    Baltayiannis, Nikolaos; Chandrinos, Michail; Anagnostopoulos, Dimitrios; Tsakiridis, Kosmas; Mpakas, Andreas; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Courcoutsakis, Nikolaos; Zarogoulidis, Konstantinos

    2013-01-01

    According to the International Agency for Research on Cancer (IARC) GLOBOCAN World Cancer Report, lung cancer affects more than 1 million people a year worldwide. In Greece according to the 2008 GLOBOCAN report, there were 6,667 cases recorded, 18% of the total incidence of all cancers in the population. Furthermore, there were 6,402 deaths due to lung cancer, 23.5% of all deaths due to cancer. Therefore, in our country, lung cancer is the most common and deadly form of cancer for the male population. The most important prognostic indicator in lung cancer is the extent of disease. The Union Internationale Contre le Cancer (UICC) and the American Joint Committee for Cancer Staging (AJCC) developed the tumour, node, and metastases (TNM) staging system which attempts to define those patients who might be suitable for radical surgery or radical radiotherapy, from the majority, who will only be suitable for palliative measures. Surgery has an important part for the therapy of patients with lung cancer. “Lobectomy is the gold standard treatment”. This statement may be challenged in cases of stage Ia cancer or in patients with limited pulmonary function. In these cases an anatomical segmentectomy with lymph node dissection is an acceptable alternative. Chest wall invasion is not a contraindication to resection. En-bloc rib resection and reconstruction is the treatment of choice. N2 disease represents both a spectrum of disease and the interface between surgical and non-surgical treatment of lung cancer Evidence from trials suggests that multizone or unresectable N2 disease should be treated primarily by chemoradiotherapy. There may be a role for surgery if N2 is downstaged to N0 and lobectomy is possible, but pneumonectomy is avoidable. Small cell lung cancer (SCLC) is considered a systemic disease at diagnosis, because the potential for hematogenous and lymphogenic metastases is very high. The efficacy of surgical intervention for SCLC is not clear. Lung cancer

  18. Radiation-induced esophagitis in lung cancer

    PubMed Central

    Baker, Sarah; Fairchild, Alysa

    2016-01-01

    Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. PMID:28210168

  19. Missed lung cancer: when, where, and why?

    PubMed Central

    del Ciello, Annemilia; Franchi, Paola; Contegiacomo, Andrea; Cicchetti, Giuseppe; Bonomo, Lorenzo; Larici, Anna Rita

    2017-01-01

    Missed lung cancer is a source of concern among radiologists and an important medicolegal challenge. In 90% of the cases, errors in diagnosis of lung cancer occur on chest radiographs. It may be challenging for radiologists to distinguish a lung lesion from bones, pulmonary vessels, mediastinal structures, and other complex anatomical structures on chest radiographs. Nevertheless, lung cancer can also be overlooked on computed tomography (CT) scans, regardless of the context, either if a clinical or radiologic suspect exists or for other reasons. Awareness of the possible causes of overlooking a pulmonary lesion can give radiologists a chance to reduce the occurrence of this eventuality. Various factors contribute to a misdiagnosis of lung cancer on chest radiographs and on CT, often very similar in nature to each other. Observer error is the most significant one and comprises scanning error, recognition error, decision-making error, and satisfaction of search. Tumor characteristics such as lesion size, conspicuity, and location are also crucial in this context. Even technical aspects can contribute to the probability of skipping lung cancer, including image quality and patient positioning and movement. Albeit it is hard to remove missed lung cancer completely, strategies to reduce observer error and methods to improve technique and automated detection may be valuable in reducing its likelihood. PMID:28206951

  20. Perceptions of lung cancer and potential impacts on funding and patient care: a qualitative study.

    PubMed

    Tran, Kim; Delicaet, Kendra; Tang, Theresa; Ashley, Leslie Beard; Morra, Dante; Abrams, Howard

    2015-03-01

    The objective of this study was to explore health-care professionals', health administrators', and not-for-profit cancer organization representatives' perceptions of lung cancer-related stigma and nihilism and the perceived impacts on funding and patient care. This is a qualitative descriptive study using semi-structured interviews, which was conducted in Ontario, Canada. Seventy-four individuals from medical oncology, radiation oncology, thoracic surgery, respirology, pathology, radiology, primary care, palliative care, nursing, pharmacy, social work, genetics, health administration, and not-for-profit cancer organizations participated in this study. Participants described lung cancer-related stigma and nihilism and its negative impact on patients' psychological health, lung cancer funding, and patient care. The feeling of guilt and shame experienced by lung cancer patients as a result of the stigma associated with the disease was described. In terms of lung cancer funding, stigma was described as a reason lung cancer receives significantly less research funding compared to other cancers. In terms of patient care, lung cancer-related nihilism was credited with negatively impacting physician referral patterns with the belief that lung cancer patients were less likely to receive referrals for medical treatment. Health-care professionals, health administrators, and not-for-profit cancer organization representatives described lung cancer-related stigma and nihilism with far-reaching consequences. Further work is needed to increase education and awareness about lung cancer to reduce the stigma and nihilism associated with the disease.

  1. Increasing Radiation Therapy Dose Is Associated With Improved Survival in Patients Undergoing Stereotactic Body Radiation Therapy for Stage I Non–Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Malik, Renuka; Weichselbaum, Ralph R.; Sher, David J.

    2015-02-01

    Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non–small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log–rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I non–small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.

  2. Occupation and lung cancer risk in Leningrad Province, Russia.

    PubMed

    Baccarelli, A; Tretiakova, Maria; Gorbanev, S; Lomtev, A; Klimkina, Irina; Tchibissov, V; Averkina, Olga; Dosemeci, M

    2005-01-01

    To investigate the association between occupation and lung cancer risk in Leningrad Province, Russia, we identified 540 pathologically diagnosed lung cancer cases (474 males and 66 females) and 582 controls (453 males and 129 females) from the 1993-1998 autopsy records of the 88 state hospitals of the Province. Lifetime occupational histories were obtained from personal records coded according to the standard Russian occupational classification system. Lung cancer risk was increased in workers in the manufacturing industry, particularly in the food industry and wholesale/retail trade and in the miscellaneous manufacturing industry. An increased risk was also found in subjects employed in chemical and metal production for 10 years or more. When we considered the association between specific occupations and lung cancer, waste incineration operators and loaders exhibited an excess risk that increased with employment duration. The present study, which is the first to evaluate the risk of lung cancer by occupation in Russia, suggests the presence in Leningrad Province of exposure in the workplace to lung carcinogens that require further characterization to develop targeted and effective preventive measures.

  3. Altered glutamine metabolism and therapeutic opportunities for lung cancer

    PubMed Central

    Mohammed, Mohammed A.; Deng, Xingming; Khuri, Fadlo R.; Owonikoko, Taofeek K.

    2014-01-01

    Disordered cancer metabolism was described almost a century ago as an abnormal adaptation of cancer cells to glucose utilization especially under hypoxic conditions; the so-called Warburg effect. Greater research interest in this area in the last several decades has led to the recognition of the critical coupling of specific malignant phenotypes such as increased proliferation and resistance to programmed cell death (apoptosis) with altered metabolic handling of key molecules that are essential for normal cellular metabolism. The altered glucose metabolism frequently encountered in cancer cells has been exploited for cancer diagnosis and treatment. More recently, the role of other glycolytic pathway intermediates as well as alternative pathways for energy generation and macromolecular synthesis in cancer cells has become recognized. Especially, the important role of altered glutamine metabolism in the malignant behavior of cancer cells and the potential exploitation of this cellular adaptation for therapeutic targeting has emerged as an important area of cancer research in the last decade. Expectedly, attempts to exploit this understanding for diagnostic and therapeutic ends are running apace with the elucidation of the complex metabolic alterations that accompany neoplastic transformation. Because lung cancer is a leading cause of cancer death with limited curative therapy options, careful elucidation of the mechanism and consequences of disordered cancer metabolism in lung cancer is warranted. This review provides a concise, systematic overview of the current understanding of the role of altered glutamine metabolism in cancer and how these findings intersect with current and future approaches to lung cancer management. PMID:24377741

  4. Geographic distribution and epidemiology of lung cancer during 2011 in Zhejiang province of China.

    PubMed

    Lin, Xia-Lu; Chen, Yan; Gong, Wei-Wei; Wu, Zhao-Fan; Zou, Bao-Bo; Zhao, Jin-Shun; Gu, Hua; Jiang, Jian-Min

    2014-01-01

    To explore etiology for providing scientific clues for the prevention of lung cancer. Data for lung cancer incidence and meteorological geographic factors from 25 counties in Zhejiang province of China during 2011 were studied. Stepwise multiple regression and correlation analysis were performed to analyze the geographic distribution and epidemiology of lung cancer. 8,291 new cases (5,998 in males and 2,293 females) of lung cancer during 2011 in Zhejiang province were reported in the 25 studied counties. Reported and standardized incidence rates for lung cancer were 58.0 and 47.0 per 100,000 population, respectively. The incidence of lung cancer increased with age. Geographic distribution analysis shows that the standardized incidence rates of lung cancer in northeastern Zhejiang province were higher than in the southwestern part, such as in Nanhu, Fuyang, Wuxing and Yuyao counties, where the rates were more than 50 per 100,000 population. In the southwestern Zhejiang province, for instance, in Yueqing, Xianju and Jiande counties, the standardized incidence rates of lung cancer were lower than 37 per 100,000 population. Spearman correlation tests showed that forest coverage rate, air quality index (AQI), and annual precipitation level are associated with the incidence of lung cancer. Lung cancer in Zhejiang province shows obvious regional differences. High incidence appears associated with low forest coverage rate, poor air quality and low annual precipitation. Therefore, increasing the forest coverage rate and controlling air pollution may play an important role in lung cancer prevention.

  5. Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review

    PubMed Central

    Xu, Xiao; Wang, Bing; Wu, Kan; Deng, Qinghua; Xia, Bing; Ma, Shenglin

    2016-01-01

    Objective Thoracic radiotherapy (TRT) is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC). However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy. Materials and Methods A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED) and median overall survival (mOS), median progression-free survival (mPFS), 1-, 3-, and 5-year overall survival (OS) as well as local relapse (LR) were evaluated. Results In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001) and the mPFS (R2 = 0.045, p<0.001). The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001). A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001) and the mPFS (p<0.001), improved the 1-, 3-, and 5-year OS (p<0.001) and decreased the rate of LR (p<0.001). Conclusion This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial. PMID:27227819

  6. Cancer risk among lung transplant recipients with cystic fibrosis.

    PubMed

    Fink, Aliza K; Yanik, Elizabeth L; Marshall, Bruce C; Wilschanski, Michael; Lynch, Charles F; Austin, April A; Copeland, Glenn; Safaeian, Mahboobeh; Engels, Eric A

    2017-01-01

    Previous studies demonstrated increased digestive tract cancers among individuals with cystic fibrosis (CF), particularly among lung transplant recipients. We describe cancer incidence among CF and non-CF lung recipients. We used data from the US transplant registry and 16 cancer registries. Standardized incidence ratios (SIRs) compared cancer incidence to the general population, and competing risk methods were used for the cumulative incidence of colorectal cancer. We evaluated 10,179 lung recipients (1681 with CF). Risk was more strongly increased in CF recipients than non-CF recipients for overall cancer (SIR 9.9 vs. 2.7) and multiple cancers including colorectal cancer (24.2 vs. 1.7), esophageal cancer (56.3 vs. 1.3), and non-Hodgkin lymphoma (61.8 vs. 9.4). At five years post-transplant, colorectal cancer was diagnosed in 0.3% of CF recipients aged <50 at transplant and 6.4% aged ≥50. CF recipients have increased risk for colorectal cancer, suggesting a need for enhanced screening. Copyright © 2016 European Cystic Fibrosis Society. All rights reserved.

  7. Lung Cancer Mutations and Use of Targeted Agents in Hispanics

    PubMed Central

    Cress, W. Douglas; Chiappori, Alberto; Santiago, Pedro; Muñoz-Antonia, Teresita

    2015-01-01

    Hispanic/Latinos (H/L) are expected to grow to over 24% of the USA population by 2050 and lung cancer is the number one cause of cancer death among H/L men. Due to the information that is becoming available via genetic testing, lung cancer molecular profiling is allowing for increasing application of personalized lung cancer therapies. However, to benefit the most people, development of these therapies and genetic tests must include research on as many racial and ethnic groups as possible. The purpose of this review is to bring attention to the fact that the mutations driving lung cancer in H/Ls differ in frequency and nature relative to the non-Hispanic White (WNH) majority that dominate current databases and participate in clinical trials that test new therapies. Clinical trials using new agents targeting genetic alterations (driver mutations) in lung cancer have demonstrated significant improvements in patient outcomes (for example, gefitinib, erlotinib or crizotinib for lung adenocarcinomas harboring EGFR mutations or EML4-ALK fusions, respectively). The nature and frequencies of some lung cancer driver mutations have been shown to be considerably different among racial and ethnic groups. This is particularly true for H/Ls. For example, several reports suggest a dramatic shift in the mutation pattern from predominantly KRAS in a WNH population to predominantly EGFR in multiple H/L populations. However, these studies are limited, and the effects of racial and ethnic differences on the incidence of mutations in lung cancer remain incompletely understood. This review serves as a call to address this problem. PMID:25626064

  8. Pharmacoeconomics of systemic therapies for lung cancer.

    PubMed

    Bordeleau, Louise

    2006-01-01

    The purpose of this article is to review the economics of systemic therapies for the treatment of lung cancer. Lung cancer treatment is moderately expensive. The overall cost to society is significant given its high incidence. Most analyses in patients with small cell lung cancer focus on supportive care measures. The economics of chemotherapy in patients with advanced small cell lung cancer, as assessed in one study, shows alternating chemotherapy to be cost effective. Numerous economic analyses of chemotherapy in patients with non-small cell lung cancer (NSCLC) have been completed using varying methodologies in a number of countries. In patients with advanced NSCLC, third generation chemotherapy in the first-line setting can be administered within reasonable incremental cost effectiveness. Single-agent docetaxel chemotherapy in the second-line setting has also been shown to fall within a reasonable cost-effective range. Based on this review, systemic therapies for lung cancer are, for the most part, cost effective. Information on the cost-utility of systemic therapies is more limited. In a population of cancer patients with poor prognosis, the inclusion of quality indicators in the calculation of costs (i.e. cost-utility analyses) will be of great importance to refine our understanding of costs and benefits using a more global approach. Future economic analyses of adjuvant chemotherapy and novel targeted therapies will be of great interest.

  9. Physical activity and lung cancer prevention.

    PubMed

    Emaus, Aina; Thune, Inger

    2011-01-01

    Since lung cancer is among the cancers with the highest incidence and has the highest mortality rate of cancer worldwide, the means of reducing its impact are urgently needed. Emerging evidence shows that physical activity plays an etiological role in lung cancer risk reduction. The majority of studies support the fact that total and recreational physical activity reduces lung cancer risk by 20-30% for women and 20-50% for men, and there is evidence of a dose-response effect. The biological mechanisms operating between physical activity and lung cancer are likely complex and influenced by many factors including inherited or acquired susceptibility genes, gender, smoking, and other environmental factors. Several plausible biological factors and mechanisms have been hypothesized linking physical activity to reduced lung cancer risk including: improved pulmonary function, reduced concentrations of carcinogenic agents in the lungs, enhanced immune function, reduced inflammation, enhanced DNA repair capacity, changes in growth factor levels and possible gene-physical activity interactions. Future research should target the possible subgroup effects and the biologic mechanisms that may be involved.

  10. Plasma immunoreactive calcitonin in lung cancer.

    PubMed

    Roos, B A; Lindall, A W; Baylin, S B; O'Neil, J; Frelinger, A L; Birnbaum, R S; Lambert, P W

    1979-01-01

    We have measured plasma calcitonin in 135 untreated eucalemic men with lung cancer and a control/smoker population. Calcitonin levels were determined by radioimmunoassay and validated by immunoextraction. Plasma immunoreactive calcitonin moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human calcitonin radioimmunoassays of cancer-patient plasmas were detected by parallel plasma incubations in a salmon calcitonin radioimmunoassay system which does not detect human calcitonin and by immunoprecipitation of tracer at the end of radioimmunoassay incubations. Heating fresh plasmas to 65 degrees C for 1.5 hours reduced radioimmunoassay artifacts without loss of calcitonin moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma calcitonin radioimmunoassay measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma calcitonin seemed to be elevated in 18% (14/80) of basal plasma samples obtained from patients with epidermoid or with anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causing no inhibition of antibody-tracer binding in the salmon calcitonin radioimmunoassays, and immunoextractable with human calcitonin antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15/55) of plasmas from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive calcitonin recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated calcitonin is much larger than calcitonin monomer.

  11. Lung Cancer Risk Associated With New Solid Nodules in the National Lung Screening Trial.

    PubMed

    Pinsky, Paul F; Gierada, David S; Nath, P Hrudaya; Munden, Reginald

    2017-09-12

    As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial (NLST). Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations. Subjects were tracked for lung cancer incidence and mortality. We examined the incidence of new nodules and their associated lung cancer risk by nodule size (i.e., mean diameter). A total of 25,002 subjects underwent the baseline LDCT screening examination and either a T1 or T2 LDCT screen. At both T1 and T2, 2.6% of subjects had new solid nodules. Of the new solid nodules, 53.0% were < 6 mm, 29.5% were 6 to < 10 mm, and 17.1% were ≥ 10 mm. Lung cancer risk (defined as diagnosis within 2 years of baseline) increased from 1.1% for nodules < 4 mm to 24.0% for those ≥ 20 mm. Compared with solid nodules detected at baseline, the cancer risk was higher for new solid nodules that were 4 to < 6 mm (p < 0.001) and 6 to < 8 mm (p < 0.001) but lower for new nodules ≥ 20 mm (p = 0.03). Cancers associated with new nodules had significantly poorer survival than did those associated with baseline nodules and were significantly less likely to be adenocarcinoma. The incidence of new nodules was 2-3% annually, with the cancer risk increasing by nodule size. New nodules may convey differential lung cancer risks by size, compared with baseline nodules.

  12. Cigarette smoke radioactivity and lung cancer risk.

    PubMed

    Karagueuzian, Hrayr S; White, Celia; Sayre, James; Norman, Amos

    2012-01-01

    To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

  13. 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

  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.

  15. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    DTIC Science & Technology

    2011-09-01

    such as that which occurs in chronic obstructive pulmonary disease (COPD) and emphysema , is associated with increased risk of lung cancer. These...the mechanical properties of lung tissue are seen in a number of disease states including cancer, COPD, asthma and emphysema , where changes in the

  16. Lung cancer in patients diagnosed with silicosis should be investigated.

    PubMed

    Güngen, Adil Can; Aydemir, Yusuf; Çoban, Hikmet; Düzenli, Hasan; Tasdemir, Canantan

    2016-01-01

    Silicosis is an interstitial lung disease developing as a result of inhalation of inorganic silica particles. In silicosis cases developing as a result of environmental and occupational exposure, an increase is observed in Turkey especially depending upon denim sandblasting. We present a 35-year-old female case who was applied to our hospital due to complaint of progressive dyspnea, had a history of working in denim sandblasting for 18 months, were diagnosed with silicosis as a result of high resolution computed tomography (HRCT) and diagnosed with lung adenocarcinoma as a result of transbronchial lung biopsy made due to clinical deterioration and radiological progression within three months. The purpose of this report was to point out that lung cancer can develop in patients followed up with diagnosis of silicosis or radiologic findings in silicosis can be confused with lung cancer.

  17. Passive smoking and lung cancer in nonsmoking women.

    PubMed Central

    Brownson, R C; Alavanja, M C; Hock, E T; Loy, T S

    1992-01-01

    OBJECTIVES. The causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case-control study. METHODS. Case patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 lifetime nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from driver's license and Medicare files. RESULTS. No increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all household members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers. CONCLUSIONS. Ours and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoking. Comprehensive actions to limit smoking in public places and worksites are well-advised. PMID:1443304

  18. Multitarget FISH analysis in the diagnosis of lung cancer.

    PubMed

    Bubendorf, Lukas; Müller, Phaedra; Joos, Ladina; Grilli, Bruno; Vogel, Sandrine; Herzog, Michelle; Barascud, Audrey; Feichter, Georg; Dalquen, Peter; Tamm, Michael

    2005-04-01

    The aim of the present study was to explore the diagnostic usefulness of the multitarget fluorescence in situ hybridization (FISH) test, LAVysion (Vysis, Downers Grove, IL), for the detection of lung cancer cells in cytologic specimens. Specimens from bronchial washings, bronchial brushings, and transbronchial fine-needle aspirates (TBNAs) from 100 patients with suspected lung cancer and from a control group of 71 patients with nonneoplastic lung disorders were analyzed. FISH positivity was defined as more than 5 cells with gains of at least 2 chromosomes or gene loci. FISH significantly improved the sensitivity of bronchial brushings from 49% to 73%. The specificities of FISH and cytologic examination were 87% and 100%, respectively. In contrast, FISH provided no additional diagnostic information in TBNAs and bronchial washings. There was no increased prevalence of genetic changes in contralateral bronchial washings from patients with lung cancer compared with the control group. The quantity of previous smoking had no effect on the prevalence of chromosomal changes.

  19. Exhaled breath analysis for lung cancer.

    PubMed

    Dent, Annette G; Sutedja, Tom G; Zimmerman, Paul V

    2013-10-01

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

  20. Exhaled breath analysis for lung cancer

    PubMed Central

    Sutedja, Tom G.; Zimmerman, Paul V.

    2013-01-01

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

  1. 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

  2. DIXDC1 increases the invasion and migration ability of non-small-cell lung cancer cells via the PI3K-AKT/AP-1 pathway.

    PubMed

    Xu, Zhonghai; Liu, Di; Fan, Chuifeng; Luan, Lan; Zhang, Xiupeng; Wang, Enhua

    2014-11-01

    DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated with a high cell proliferation index. We demonstrated DIXDC1 overexpression in 55% (92/167) of non-small cell lung cancer (NSCLC) cases, compared to adjacent noncancerous lung tissues (P < 0.01). Overexpression of DIXDC1 was associated with lymph node metastasis and more advanced TNM stage (P < 0.001 and P = 0.001, respectively). Kaplan-Meier survival curves and log-rank testing indicated that overexpression of DIXDC1 correlated with worse overall survival in NSCLC (P = 0.031). DIXDC1 was more abundant in seven NSCLC lines than the bronchial cell line HBE, and modulation of its expression regulated AP-1 activity; MMP2, MMP7, and MMP9 protein and mRNA; and invasion ability. Metalloproteinase induction was reversed by PI3K/AKT and AP-1 inhibition. These results suggest DIXDC1 is associated with stage and prognosis in NSCLC, and may promote invasion and migration through PI3K-AKT/AP-1-dependent activation of metalloproteinases.

  3. Predictors of lung cancer among former asbestos-exposed workers.

    PubMed

    Świątkowska, Beata; Szubert, Zuzanna; Sobala, Wojciech; Szeszenia-Dąbrowska, Neonila

    2015-09-01

    Despite extensive literature concerning the risk of lung cancer incidence among asbestos workers there is still lack of data specifying the association between the level of exposure and the frequency of cancer occurrence. The aim of the analysis was to assess the influence of smoking and selected factors related to occupational exposure on the risk of the incidence of lung cancer among the workers who were exposed to asbestos dust in the past. The assessment was performed based on the case-control studies carried out within a cohort including 7,374 former workers of asbestos processing plants, examined over the years 2000-2013. Analysis of the material was based on the calculation of the odds ratio (OR) using conditional logistic regression modeling, adjusted for cigarette smoking, cumulative exposure, branch and time since last exposure. During the survey period there were 165 cases of lung cancer. Among the individuals who smoked, the relative risk of lung cancer incidence was twice as high in the persons smoking more than 20 pack-years (OR=2.23; 95% CI: 1.45-3.46) than it was in the case of the non-smokers. Analysis revealed that the risk of lung cancer in the group with the highest exposure was two times higher in comparison with the low cumulative asbestos exposure (OR=1.99; 95% CI: 1.22-3.25). The risk continued to increase until 30 years after cessation of asbestos exposure and started to decline many years after the last exposure. Influence of the mentioned above characteristics is particularly visible for tumors located in the lower parts of the lungs. Our findings confirm the strong evidence that the lung cancer risk is associated with asbestos exposure and it increases along with the increasing exposure. A strategy of smoking cessation among the individuals exposed to asbestos dust would potentially have health promoting effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Cryptogenic fibrosing alveolitis and lung cancer: the BTS study.

    PubMed

    Harris, J M; Johnston, I D A; Rudd, R; Taylor, A J Newman; Cullinan, P

    2010-01-01

    The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02). These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

  5. Genetic polymorphisms of XPD and CDA and lung cancer risk.

    PubMed

    Zhou, Min; Wan, Huan-Ying; Gao, Bei-Li; Ding, Yong-Jie; Jun, Rong-Xia

    2012-08-01

    To determine the susceptibility genes of lung cancer, we investigated the frequency distributions of the xeroderma pigmentosum complementary group D (XPD) and cytidine deaminase (CDA) genes in patients. A case-control study was conducted involving lung cancer patients and healthy controls. The genotypic distributions of XPD exon 10 G→A (Asp312Asn) and 23 T→G (Lys751Gln), and CDA 79 A→C (Lys27Gln) and 208 G→A (Ala70Thr), were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated that the XPD Asp312Asn genotype distribution was G/G (82.52%) and A/G (17.48%) in the lung cancer patients, and G/G (82.52%), A/G (16.50%) and A/A (10.98%) in the controls. The genotypes of Lys751Gln were T/T (83.49%) and T/G (16.50%) in the lung cancer patients, and T/T (84.47%) and T/G (15.53%) in the controls. Mutations in the XPD single nucleotide polymorphism loci did not demonstrate a significant difference between the two groups (P>0.05). The risk of lung cancer in individuals with mutations at positions 312 and 751 increased 6.13-fold (P=0.047). The CDA Lys27Gln genotype distribution was A/A (78.65%), A/C (20.39%) and C/C (0.98%) in the lung cancer patients, and A/A (79.61%), A/C (19.42%) and C/C (0.98%) in the controls (P=0.985). The CDA Ala70Thr genotype distribution was G/G (98.06%) and A/G (1.94%) in the controls, while all the genotypes were wild-type in the lung cancer patients. The difference between the lung cancer patients and the controls was not statistically significant (P=0.155). There was also no significant difference in the frequency distribution of XPD or CDA between the different pathological types (P>0.05). Our findings demonstrate that the mutation of XPD codons 312 and 751 increases the risk of lung cancer. By contrast, polymorphisms of CDA appear to have little association with lung cancer.

  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. CLPTM1L polymorphism and lung cancer risk

    PubMed Central

    Tang, Min; Bian, Xiaonian; Zhao, Qiuliang

    2015-01-01

    The association of Cleft Lip and Palate Transmembrane Protein 1 (CLPTM1L) rs31489 polymorphism with risk of lung cancer has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between CLPTM1L rs31489 polymorphism and risk of lung cancer is needed among a larger study population. A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases was carried out to identify studies investigating the association between lung cancer risk and CLPTM1L rs31489 polymorphism. The strength of the association between CLPTM1L rs31489 polymorphism and lung cancer risk was estimated by calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In the overall analysis, there was significant association between CLPTM1L rs31489 polymorphism and lung cancer risk under an allele model (OR = 1.12; 95% CI, 1.06-1.18; P < 0.00001; I2 = 57%). Subgroup analysis by ethnicity was performed. Stratified analysis by ethnicity showed that a statistically increased cancer risk was found in the Caucasian population (OR = 1.15; 95% CI, 1.10-1.21; P < 0.00001; I2 = 22%), but there was no significant association between lung cancer risk and CLPTM1L rs31489 polymorphism in the Asian population (OR = 1.03; 95% CI, 0.97-1.08; P = 0.37; I2 = 15%). In conclusion, this meta-analysis demonstrates that CLPTM1L rs31489 polymorphism significantly modified the risk of lung cancer. PMID:26064290

  8. CLPTM1L polymorphism and lung cancer risk.

    PubMed

    Tang, Min; Bian, Xiaonian; Zhao, Qiuliang

    2015-01-01

    The association of Cleft Lip and Palate Transmembrane Protein 1 (CLPTM1L) rs31489 polymorphism with risk of lung cancer has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between CLPTM1L rs31489 polymorphism and risk of lung cancer is needed among a larger study population. A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases was carried out to identify studies investigating the association between lung cancer risk and CLPTM1L rs31489 polymorphism. The strength of the association between CLPTM1L rs31489 polymorphism and lung cancer risk was estimated by calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In the overall analysis, there was significant association between CLPTM1L rs31489 polymorphism and lung cancer risk under an allele model (OR = 1.12; 95% CI, 1.06-1.18; P < 0.00001; I(2) = 57%). Subgroup analysis by ethnicity was performed. Stratified analysis by ethnicity showed that a statistically increased cancer risk was found in the Caucasian population (OR = 1.15; 95% CI, 1.10-1.21; P < 0.00001; I(2) = 22%), but there was no significant association between lung cancer risk and CLPTM1L rs31489 polymorphism in the Asian population (OR = 1.03; 95% CI, 0.97-1.08; P = 0.37; I(2) = 15%). In conclusion, this meta-analysis demonstrates that CLPTM1L rs31489 polymorphism significantly modified the risk of lung cancer.

  9. Lower lung cancer mortality in obesity.

    PubMed

    Leung, Chi C; Lam, Tai H; Yew, Wing W; Chan, Wai M; Law, Wing S; Tam, Cheuk M

    2011-02-01

    Malignancy is the leading cause of death in Hong Kong, and lung cancer tops the list of all cancer deaths. A cohort of clients aged ≥65 years, enrolled at 18 elderly health centres in Hong Kong from 2000 to 2003, was followed up prospectively through linkage with the territory-wide death registry for causes of death until 31 December 2008, using the identity card number as unique identifier. All subjects with suspected cancer, significant weight loss of >5% within past 6 months or obstructive lung disease at the baseline were excluded. After a total of 423 061 person-years of follow-up, 932, 690 and 1433 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies, respectively. Body mass index (BMI) was independently (and negatively) associated with death from lung cancer after adjustment for other baseline variables, whereas there was only a minor or no effect for other smoking-related malignancies and non-tobacco-related malignancies. Obesity with BMI ≥30 [adjusted hazard ratio (HR), 0.55, 95% confidence interval (CI) 0.38-0.80] was associated with reduced lung cancer mortality, which was more prominent than the opposing effect of underweight (adjusted HR, 1.38, 95% CI 1.05-1.79). Consistent effects of BMI were observed after stratification into never-smokers and ever-smokers and in sensitivity analysis after excluding deaths within the first 3 years. Obesity was associated with lower lung cancer mortality in this prospective cohort analysis. As the effect was rather specific for lung cancer, further studies are indicated to explore the underlying mechanism.

  10. [The new TNM classification in lung cancer].

    PubMed

    Wrona, Anna; Jassem, Jacek

    2010-01-01

    This paper presents the new TNM classification in lung cancer and its history. Seventh edition of tumor, node, metastasis (TNM) classification in lung cancer has been published by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) at the beginning of 2009. The changes were based upon the results of the international project of the International Association for the Study of Lung Cancer (IASLC). The database included 81.495 patients from the entire world (68.463 with non-small cell lung cancer and 13.032 with small cell lung cancer) treated with various modalities between 1990 and 2000. The collected data were validated internally and externally. The tumor size was considered of prognostic relevance: T1 tumors were subdivided into T1a (≤ 2 cm) and T1b (〉 2 cm - ≤ 3 cm), T2 tumors into T2a (〉 3 cm - ≤ 5 cm) and T2b (〉 5 cm - ≤ 7 cm), and T2 tumors 〉 7 cm were reclassified as T3. Tumors with the additional nodules in the same lobe as the primary tumor were classified as T3, those with additional nodules in another ipsilateral lobe - as T4. There were no changes in N category. In the M category, M1 was subclassified into M1a (contralateral lung nodules and pleural dissemination) and M1b (distant metastasis). Large T2 tumors (T2bN0M0) were upstaged from IB to IIA, small T2 tumors (T2aN1M0) were downstaged from the IIB to IIA and T4N0-N1M0 - from IIIB to IIIA. The TNM classification was also recommended for small cell lung cancer instead of previously used categories of limited and extensive disease.

  11. Silicosis and risk of lung cancer or lung tuberculosis: a cohort study

    SciTech Connect

    Westerholm, P.; Ahlmark, A.; Maasing, R.; Segelberg, I.

    1986-10-01

    This is a study of cancer mortality, cancer incidence, and incidence of lung tuberculosis among cases of silicosis reported to the National Swedish Pneumoconiosis Register during 1959-1977. Two occupational categories were extracted - mining, tunneling, and quarrying (n = 284) and iron and steel foundries (n = 428), respectively. Control groups were drawn from a national register of persons undergoing periodic health examinations with regard to silicosis risk. The controls were matched for occupation, age, and time of first exposure. In cases drawn from mining, quarrying, and tunneling workers seven deaths in lung cancer were observed and two among the controls. Among iron and steel foundry workers the corresponding numbers were 10 and 6. The values for expected numbers, based on general population statistics, were 1.3 and 2.6, respectively, for these two occupational groups. When cancer incidence statistics were used, the case/control ratio for lung cancer was 2.1 for mining, quarrying, and tunneling and 0.6 for iron and steel foundries. There were 29 cases of lung tuberculosis registered among the silicosis cases during the follow-up period. Only one tuberculosis case was observed among the controls. The results demonstrate that persons with silicosis contracted in the mining, quarrying, and tunneling occupations are subject to an increased risk of lung cancer.

  12. Differential roles of STAT3 in the initiation and growth of lung cancer.

    PubMed

    Zhou, J; Qu, Z; Yan, S; Sun, F; Whitsett, J A; Shapiro, S D; Xiao, G

    2015-07-01

    Signal transducer and activator of transcription 3 (STAT3) is linked to multiple cancers, including pulmonary adenocarcinoma. However, the role of STAT3 in lung cancer pathogenesis has not been determined. Using lung epithelial-specific inducible knockout strategies, we demonstrate that STAT3 has contrasting roles in the initiation and growth of both chemically and genetically induced lung cancers. Selective deletion of lung epithelial STAT3 in mice before cancer induction by the smoke carcinogen, urethane, resulted in increased lung tissue damage and inflammation, K-Ras oncogenic mutations and tumorigenesis. Deletion of lung epithelial STAT3 after establishment of lung cancer inhibited cancer cell proliferation. Simultaneous deletion of STAT3 and expression of oncogenic K-Ras in mouse lung elevated pulmonary injury, inflammation and tumorigenesis, but reduced tumor growth. These studies indicate that STAT3 prevents lung cancer initiation by maintaining pulmonary homeostasis under oncogenic stress, whereas it facilitates lung cancer progression by promoting cancer cell growth. These studies also provide a mechanistic basis for targeting STAT3 to lung cancer therapy.

  13. Racial and Ethnic Differences in the Epidemiology of Lung Cancer and the Lung Cancer Genome

    PubMed Central

    Schabath, Matthew B.; Cress, W. Douglas; Muñoz-Antonia, Teresita

    2017-01-01

    Background Globally and in the United States, lung cancer has been the most common cancer for the past several decades. In addition to the well-established geographical- and sex-specific differences in lung cancer incidence, mortality and survival, there is also growing evidence for racial and ethnic differences. Methods Based on available published data, we present a summary of the current knowledge and substantive findings related to racial and ethnic differences in lung cancer. Results Although this report is not a systematic review, we summarized the current knowledge and substantive findings related to racial and ethnic differences in lung cancer with a particular focus on lung cancer statistics(incidence, mortality, and survival), cigarette smoking, prevention and early detection, and the lung cancer genome. Finally, we summarize some the systems-level and provider-related issues that likely contribute to racial and ethnic-specific health disparities and provide some suggestions for future strategies that may reduce the disproportionate burden of lung cancer. Conclusions Although lung carcinogenesis is a multifactorial process driven by exogenous exposures (e.g., cigarette smoking), inherited genetic variations, and an accumulation of somatic genetic events, this multifactorial process appears to have racial and ethnic differences which in turn impacts the observed epidemiologic differences in incidence, mortality, and survival. PMID:27842323

  14. Diesel engine exhaust and lung cancer: an unproven association.

    PubMed Central

    Muscat, J E; Wynder, E L

    1995-01-01

    The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient evidence to implicate diesel exhaust as a human lung carcinogen. Four studies found increased risks associated with long-term exposure, although two of the four studies were based on the same cohort of railroad workers. Six studies were inconclusive due to missing information on smoking habits, internal inconsistencies, or inadequate characterization of diesel exposure. Four studies found no statistically significant associations. It can be concluded that short-term exposure to diesel engine exhaust (< 20 years) does not have a causative role in human lung cancer. There is statistical but not causal evidence that long-term exposure to diesel exhaust (> 20 years) increases the risk of lung cancer for locomotive engineers, brakemen, and diesel engine mechanics. There is inconsistent evidence on the effects of long-term exposure to diesel exhaust in the trucking industry. There is no evidence for a joint effect of diesel exhaust and cigarette smoking on lung cancer risk. Using common criteria for determining causal associations, the epidemiologic evidence is insufficient to establish diesel engine exhaust as a human lung carcinogen. Images p812-a PMID:7498093

  15. A simple model for predicting lung cancer occurrence in a lung cancer screening program: The Pittsburgh Predictor.

    PubMed

    Wilson, David O; Weissfeld, Joel

    2015-07-01

    A user-friendly method for assessing lung cancer risk may help standardize selection of current and former smokers for screening. We evaluated a simple 4-factor model, the Pittsburgh Predictor, against two well-known, but more complicated models for predicting lung cancer risk. Trained against outcomes observed in the National Lung Screening Trial (NLST), the Pittsburgh Predictor used four risk factors, duration of smoking, smoking status, smoking intensity, and age, to predict 6-year lung cancer incidence. After calibrating the Bach and PLCOM2012 models to outcomes observed in the low-dose computed tomography arm of the NLST, we compared model calibration, discrimination, and clinical usefulness (net benefit) in the NLST and Pittsburgh Lung Screening Study (PLuSS) populations. The Pittsburgh Predictor, Bach, and PLCOM2012 represented risk equally well, except for the tendency of PLCOM2012 to overestimate risk in subjects at highest risk. Relative to the Pittsburgh Predictor, Bach and PLCOM2012 increased the area under the receiver operator characteristic curve by 0.007-0.009 and 0.012-0.021 units, respectively, depending on study population. Across a clinically relevant span of 6-year lung cancer risk thresholds (0.01-0.05), Bach and PLCOM2012 increased net benefit by less than 0.1% in NLST and 0.3% in PLuSS. In exchange for a small reduction in prediction accuracy, a simpler lung cancer risk prediction model may facilitate standardized procedures for advising and selecting patients with respect to lung cancer screening. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Lung cancer treatment rates and the role of the lung cancer nurse specialist: a qualitative study.

    PubMed

    Tod, Angela Mary; Redman, Judy; McDonnell, Ann; Borthwick, Diana; White, John

    2015-12-18

    This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. 4 Hospital NHS Foundation Trusts in England. A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. Four LCNSs, comprised the 'cases'. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took part in a group interview and 60 lung cancer multidisciplinary team (MDT) members and coordinators were observed in the MDT meeting. The LCNS is crucial within the MDT and can act as a catalyst to patient access to treatment. The study identified the clinical activity (assessment, managing symptoms, psychological support and information provision) and role characteristics that can facilitate treatment access. These characteristics are the LCNS's presence across the patient pathway, acting as the 'hub' of the MDT, maintaining a holistic patient focus and working to an advanced level of practice. The findings indicate how factors may have a cumulative impact on treatment access. If UK patient with lung cancer survival rates are to improve in line with comparable countries, we need to employ every advantage. This study demonstrates how the LCNS role may open doors to positive patient outcomes, including treatment. Further research is required to explore patients' experiences, decision-making and attitudes to treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Lung cancer treatment rates and the role of the lung cancer nurse specialist: a qualitative study

    PubMed Central

    Redman, Judy; McDonnell, Ann; Borthwick, Diana; White, John

    2015-01-01

    Objectives This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. Setting 4 Hospital NHS Foundation Trusts in England. Design A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. Participants Four LCNSs, comprised the ‘cases’. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took part in a group interview and 60 lung cancer multidisciplinary team (MDT) members and co-ordinators were observed in the MDT meeting. Results The LCNS is crucial within the MDT and can act as a catalyst to patient access to treatment. The study identified the clinical activity (assessment, managing symptoms, psychological support and information provision) and role characteristics that can facilitate treatment access. These characteristics are the LCNS's presence across the patient pathway, acting as the ‘hub’ of the MDT, maintaining a holistic patient focus and working to an advanced level of practice. The findings indicate how factors may have a cumulative impact on treatment access. Conclusions If UK patient with lung cancer survival rates are to improve in line with comparable countries, we need to employ every advantage. This study demonstrates how the LCNS role may open doors to positive patient outcomes, including treatment. Further research is required to explore patients’ experiences, decision-making and attitudes to treatment. PMID:26685023

  18. Mortality due to lung cancer in Mexico.

    PubMed

    Ruíz-Godoy, L; Rizo Rios, P; Sánchez Cervantes, F; Osornio-Vargas, A; García-Cuellar, C; Meneses García, A

    2007-11-01

    The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a

  19. Risk of lung cancer in Parkinson's disease

    PubMed Central

    Xie, Xin; Luo, Xiaoguang; Xie, Mingliang; Liu, Yang; Wu, Ting

    2016-01-01

    Recently, growing evidence has revealed the significant association between Parkinson's disease (PD) and cancer. However, controversy still exists concerning the association between PD and lung cancer. A comprehensive article search for relevant studies published was performed using the following online databases: PubMed, Web of Science and Embase up to August 31, 2016. The pooled risk ratio (RR) and their 95 % confidence intervals (CI) were calculated using the method of inverse variance with the random-effects model. Fifteen studies comprising 348,780 PD patients were included in this study. The pooled result indicated that patients with PD were significantly associated with a decreased risk of lung cancer (RR: 0.53, 95% CI: 0.41−0.70, P < 0.001). In addition, subgroup analyses performed in Western population also confirmed the significant inverse relationship between PD and risk of lung cancer (RR: 0.48, 95% CI: 0.39−0.60, P < 0.001). In the subgroup analysis, a reduced risk of lung cancer in PD patients from Western population was consistent regardless of study design, gender, or study quality. In conclusion, PD patients were significantly associated with a reduced risk of lung cancer in Western population. The relationship between them in Asian population needs to be confirmed by future studies. PMID:27801674

  20. Treatment options for small cell lung cancer.

    PubMed

    Wolf, Todd; Gillenwater, Heidi H

    2004-07-01

    Lung cancer remains the leading cause of cancer-related death in the United States. Small cell lung cancer (SCLC) comprises 15% to 25% of all lung cancers. The leading cause of lung cancer remains smoking, and rates of smoking continue to rise in women, whereas rates in other subgroups have slowed. In this article we review recent advances in the treatment of limited-stage as well as extensive-stage small cell lung cancer. In limited-stage disease, the best survival results are observed when patients are treated with twice-daily thoracic radiotherapy given concurrently with chemotherapy. Patients who have been successful in smoking cessation during therapy for limited-stage disease may have a survival benefit over those who are unable to quit smoking during treatment. In extensive-stage disease, the most significant trial is one comparing irinotecan plus cisplatin and etoposide plus cisplatin, showing a survival advantage for the irinotecan arm. This trial may change the standard of care for patients with extensive-stage disease. A similar ongoing trial in the United States is attempting to confirm these results.

  1. 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

  2. Retinoids in lung cancer chemoprevention and treatment.

    PubMed

    Toma, S; Raffo, P; Isnardi, L; Palumbo, R

    1999-01-01

    In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as

  3. Hormones of adipose tissue and their biologic role in lung cancer.

    PubMed

    Ntikoudi, E; Kiagia, M; Boura, P; Syrigos, K N

    2014-02-01

    Adipose tissue secretes numerous bioactive peptides, collectively termed "adipocytokines" or "adipokines". Adipokines act in a paracrine, autocrine, or endocrine manner and regulate several physiological and pathological processes. Increasing evidence indicates that adipokines are implicated also in several malignancies, including lung cancer as well. The aim of this study is to summarize data concerning adipokines in lung cancer pathogenesis, prognosis and survival; the role of adipokines in lung cancer cachexia is also examined. A systematic literature search was performed in the electronic database of Medline. Several studies and review articles met the inclusion criteria. Leptin and adiponectin are the best studied adipokines. The majority of the relevant studies has investigated the potential correlations mainly between leptin, adiponectin, and sometimes also resistin, and nutritional status, systemic inflammation of lung cancer or lung cancer cachexia and have also assessed their prognostic significance. Few other studies have studied genetic variations in leptin, leptin receptor and adiponectin genes and their association with lung cancer susceptibility and prognosis. The ongoing list of adipokines associated with lung cancer also includes resistin, chemerin, and visfatin. Increasing evidence points to the involvement of certain adipocytokines in lung cancer development, progression and prognosis. No conclusive evidence exists so far with regards to the role of adipocytokines in lung cancer cachexia. Future, longitudinal studies are warranted in order to clarify the role of adipocytokines in lung cancer and also uncover adipocytokines as novel therapeutic targets. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. 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

    2016-11-01

    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. New molecularly targeted therapies for lung cancer.

    PubMed

    Sun, Sophie; Schiller, Joan H; Spinola, Monica; Minna, John D

    2007-10-01

    Lung cancer is the leading cause of cancer death worldwide. The disease is particularly difficult to detect, and patients often present at an advanced stage. Current treatments have limited effectiveness, and unfortunately, the prognosis remains poor. Recent insights into the molecular pathogenesis and biologic behavior of lung cancer have led to the development of rationally designed methods of early detection, prevention, and treatment of this disease. This article will review the important clinical implications of these advances, with a focus on new molecularly targeted therapies currently in development.

  6. New molecularly targeted therapies for lung cancer

    PubMed Central

    Sun, Sophie; Schiller, Joan H.; Spinola, Monica; Minna, John D.

    2007-01-01

    Lung cancer is the leading cause of cancer death worldwide. The disease is particularly difficult to detect, and patients often present at an advanced stage. Current treatments have limited effectiveness, and unfortunately, the prognosis remains poor. Recent insights into the molecular pathogenesis and biologic behavior of lung cancer have led to the development of rationally designed methods of early detection, prevention, and treatment of this disease. This article will review the important clinical implications of these advances, with a focus on new molecularly targeted therapies currently in development. PMID:17909619

  7. 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 prove...

  8. 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 prove...

  9. 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 medical...

  10. 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 prove...

  11. 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 medical...

  12. 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 prove...

  13. 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

  14. Asbestosis and lobar site of lung cancer

    PubMed Central

    Weiss, W.

    2000-01-01

    OBJECTIVE—To assess the evidence for the hypothesis that lung cancer has a predilection for the lower lobes in workers with asbestosis.
METHOD—A review of the available literature with relevant information.
RESULTS—Six published reports were analysed. In four studies limited to series of cases with diagnoses of asbestosis, three showed lower lobe predominance of lung cancer whereas the fourth study included cases in which the radiographic readings did not meet the usual criterion of profusion for asbestosis. One cohort study showed lower lobe predominance; the other reported only 33% lower lobe cancers compared with 20% in unexposed controls.
CONCLUSION—There is some support for the hypothesis but more studies are needed.


Keywords: asbestos; asbestosis; lung cancer PMID:10769303

  15. Recent advances in personalized lung cancer medicine

    PubMed Central

    Okimoto, Ross A; Bivona, Trever G

    2014-01-01

    The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine. PMID:25506379

  16. Economic Burden for Lung Cancer Survivors in Urban China.

    PubMed

    Zhang, Xin; Liu, Shuai; Liu, Yang; Du, Jian; Fu, Wenqi; Zhao, Xiaowen; Huang, Weidong; Zhao, Xianming; Liu, Guoxiang; Mao, Zhengzhong; Hu, Teh-Wei

    2017-03-15

    With the rapid increase in the incidence and mortality of lung cancer, a growing number of lung cancer patients and their families are faced with a tremendous economic burden because of the high cost of treatment in China. This study was conducted to estimate the economic burden and patient responsibility of lung cancer patients and the impact of this burden on family income. This study uses data from a retrospective questionnaire survey conducted in 10 communities in urban China and includes 195 surviving lung cancer patients diagnosed over the previous five years. The calculation of direct economic burden included both direct medical and direct nonmedical costs. Indirect costs were calculated using the human capital approach, which measures the productivity lost for both patients and family caregivers. The price index was applied for the cost calculation. The average economic burden from lung cancer was $43,336 per patient, of which the direct cost per capita was $42,540 (98.16%) and the indirect cost per capita was $795 (1.84%). Of the total direct medical costs, 35.66% was paid by the insurer and 9.84% was not covered by insurance. The economic burden for diagnosed lung cancer patients in the first year following diagnosis was $30,277 per capita, which accounted for 171% of the household annual income, a percentage that fell to 107% after subtracting the compensation from medical insurance. The economic burden for lung cancer patients is substantial in the urban areas of China, and an effective control strategy to lower the cost is urgently needed.

  17. Economic Burden for Lung Cancer Survivors in Urban China

    PubMed Central

    Zhang, Xin; Liu, Shuai; Liu, Yang; Du, Jian; Fu, Wenqi; Zhao, Xiaowen; Huang, Weidong; Zhao, Xianming; Liu, Guoxiang; Mao, Zhengzhong; Hu, Teh-wei

    2017-01-01

    Background: With the rapid increase in the incidence and mortality of lung cancer, a growing number of lung cancer patients and their families are faced with a tremendous economic burden because of the high cost of treatment in China. This study was conducted to estimate the economic burden and patient responsibility of lung cancer patients and the impact of this burden on family income. Methods: This study uses data from a retrospective questionnaire survey conducted in 10 communities in urban China and includes 195 surviving lung cancer patients diagnosed over the previous five years. The calculation of direct economic burden included both direct medical and direct nonmedical costs. Indirect costs were calculated using the human capital approach, which measures the productivity lost for both patients and family caregivers. The price index was applied for the cost calculation. Results: The average economic burden from lung cancer was $43,336 per patient, of which the direct cost per capita was $42,540 (98.16%) and the indirect cost per capita was $795 (1.84%). Of the total direct medical costs, 35.66% was paid by the insurer and 9.84% was not covered by insurance. The economic burden for diagnosed lung cancer patients in the first year following diagnosis was $30,277 per capita, which accounted for 171% of the household annual income, a percentage that fell to 107% after subtracting the compensation from medical insurance. Conclusions: The economic burden for lung cancer patients is substantial in the urban areas of China, and an effective control strategy to lower the cost is urgently needed. PMID:28294998

  18. Explorations of lung cancer stigma for female long term survivors

    PubMed Central

    Brown, Cati; Cataldo, Janine

    2013-01-01

    Lung cancer is the leading cause of cancer death in women, accompanied by greater psychological distress than other cancers. There is minimal but increasing awareness of the impact of lung cancer stigma (LCS) on patient outcomes. LCS is associated with increased symptom burden and decreased quality of life. The purpose of this study was to explore the experience of female long term lung cancer survivors in the context of LCS and examine how participants discursively adhere to or reject stigmatizing beliefs. Findings situated within Cataldo et al.’s theoretical model include: 1) addiction and tobacco marketing as possible precursors for LCS, 2) the possible role of expert providers as LCS enhancers, 3) response of overlapping complicated identity shifts, 4) simultaneous rejection and assumption of LCS, and 5) information control via advocacy activities as a LCS mitigation response. These findings expand the current understanding of LCS, and call for future conceptual exploration and theoretical revision, particularly with respect to the possibility of interaction between relevant related stigma(s) and LCS. As the number of women living with lung cancer increases, with longer survival times, the effect of LCS and other experiences of discrimination on patient outcomes could be substantial. PMID:23414179

  19. Mortality from lung cancer among Sardinian patients with silicosis.

    PubMed Central

    Carta, P; Cocco, P L; Casula, D

    1991-01-01

    The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the

  20. Chinese consensus on early diagnosis of primary lung cancer (2014 version).

    PubMed

    Hu, Jie; Qian, Gui-Sheng; Bai, Chun-Xue

    2015-09-01

    The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.

  1. Does lung cancer attract greater stigma than other cancer types?

    PubMed

    Marlow, Laura A V; Waller, Jo; Wardle, Jane

    2015-04-01

    Cancer stigma can have widespread effects, influencing the behaviour and wellbeing of patients as well as the community and even research funding. Patients with lung cancer report feeling particularly stigmatised because of the association with a behaviour (smoking) that is perceived to be personally controllable. However, there are other dimensions of cancer stigma, that might be more severe for other cancers. The present study therefore examined differences in attitudes towards lung cancer and four other cancer types, using a multidimensional measure of cancer stigma, to extend findings beyond personal responsibility attributions. Participants were a non-patient sample (n=1205) who were randomised to complete a survey online relating to one of five cancer types (lung, colorectal, skin, breast and cervical). Stigma was assessed using the Cancer Stigma Scale (CASS). There were significant differences across the five cancer types on all CASS subscales: awkwardness (F(4, 1009)=5.16, p<0.001), severity (F(4, 984)=26.24, p<0.001), avoidance (F(4, 1008)=5.38, p<0.001), policy opposition (F(4, 1009)=8.38, p<0.001), personal responsibility (F(4, 995)=31.67, p<0.001) and financial discrimination (F(4, 957)=9.45, p<0.001). Lung cancer attracted higher stigma scores than breast and cervical cancer on all subscales. Lung cancer was similar to skin cancer on personal responsibility, avoidance, and policy opposition, but attracted higher stigma in the domains of awkwardness, severity and financial discrimination. Lung cancer was similar to colorectal cancer for awkwardness, but significantly higher on all other subscales. Lung cancer stigma extends beyond personal responsibility attributions to other dimensions, particularly perceived severity of the disease and tolerance of financial discrimination against patients with the disease. Future work is needed to develop and evaluate interventions designed to limit cancer stigma for patients, health professionals and the community

  2. Air pollution and lung cancer: diesel exhaust, coal combustion

    SciTech Connect

    Higgins, I.T.

    1984-03-01

    It is known, that cigarette smoking is by far the most important cause of lung cancer and that about a dozen occupational exposures are also established as causes of this disease. There has been continuing uncertainty about the role of general air pollution. During the past few years, this uncertainty has been compounded with anxiety that the increasing use of diesel-powered vehicles might lead to a deterioration in air quality and, with it, an increase in the incidence of lung cancer. The purpose of this paper is to assess the current role of air pollution as a factor in lung cancer and specifically the contribution of diesel exhaust emissions to the incidence of that disease.

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

    ClinicalTrials.gov

    2016-12-12

    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

  4. 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.

  5. Wood Dust Exposure and Risk of Lung Cancer

    PubMed Central

    Bhatti, Parveen; Newcomer, Laura; Onstad, Lynn; Teschke, Kay; Camp, Janice; Morgan, Michael; Vaughan, Thomas L.

    2011-01-01

    Objectives Despite the compelling association between wood dust and sinonasal cancer, there has been little systematic and rigorous study of the relationship between wood dust and lung cancer. We investigated whether a history of exposure to wood dust through occupational and hobby-related activities was associated with increased lung cancer risk. Methods We conducted a population-based case-control study, with 440 cases, identified from 1993 to 1996 through the Fred Hutchinson Cancer Research Center Cancer Surveillance System for western Washington State, and 845 age-matched controls, identified by random-digit dialing. Using detailed work and personal histories, quantitative estimates of cumulative exposure to wood dust (thought to be primarily from softwood) were calculated for each participant. Using unconditional logistic regression adjusted for age and smoking status, risk of lung cancer was examined in relation to employment in wood-related occupations, working with wood as a hobby, as well as cumulative wood dust exposure that took into account both occupational and hobby-related sources. Results While we observed an increased risk of lung cancer associated with working in a sawmill (OR=1.5; 95% CI: 1.1, 2.1), we found n