Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The US Environmental Protection Agency report released in January 1993, Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders, has stirred considerable discussion and interest in the issues surrounding tobacco and health. The report addresses major health effects of environmental tobacco smoke (ETS), concluding (1) that ETS is causally associated with lung cancer in nonsmoking adults and should be classified as a group A, or known human carcinogen, with approximately 3000 excess deaths yearly; (2) that ETS produces an increased risk of development of acute lower respiratory tract irritation, asthma, and acute lower respiratory tract infections in children exposed in the home; and (3) that ETS is associated with an increase risk of sudden infant death syndrome. Other studies implicate ETS in between 35,000 and 40,000 premature deaths each year from cardiovascular disease. The Council on Scientific Affairs (CSA) agrees that ETS should be classified as a human carcinogen, and strongly supports the findings of other groups concerning both lung cancer and ETS-induced respiratory tract illnesses in children. The CSA concludes that exposure to passive smoke, whether in utero or during infancy, is associated with an increased risk of sudden infant death syndrome. The CSA agrees that the available evidence suggests that ETS exposure leads to increased risk for cardiovascular disease. It is clear that these morbidity and mortality estimates represent a significant public health threat that demands attention from the health community as well as government regulatory agencies involved with health protection.
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PMID:Environmental tobacco smoke. Health effects and prevention policies. Council on Scientific Affairs, American Medical Association. 800 May 57

Most information on results with radiotherapy (RT) for stage I non-small cell lung cancer (NSCLC) is based on retrospective studies on RT-treated inoperable NSCLC cases. Thus, the role of RT for stage I NSCLC, as a curative modality, has not yet been established. A literature search for studies on stage I non-small cell lung carcinoma (NSCLC) treated by RT alone resulted in 18 papers published between 1988 and 2000. The majority of stage I patients received RT treatment because they were medically inoperable. The main contraindications for surgery were grave impairment of pulmonary function and serious cardiovascular disease. Local recurrence was the most common reason for treatment failure (median value 40%) but varied highly between the studies, ranging from 6.4 to 70%. In contrast with local recurrence, regional failure was not a major problem (0-3.2%). Generally, smaller tumour size, low T-stage and increased dose had a favourable impact on local control and increased local control was followed by increased survival. No serious treatment complications were recorded in the majority of these studies. Overall treatment results were, however, disappointing. The median survival in these studies ranged from 18 to 33 months. The 3- and 5-year overall survival was 34+/-9 and 21+/-8% (mean value+/-1 S.E.), respectively. The cause-specific survival at 3 and 5 years was 39+/-10 and 25+/-9% (mean value+/-1 S.E.), respectively. Dose escalation, in a setting with conformal RT using involved field or stereotactic RT, should be the focus of developmental therapeutic strategies with inoperable stage I NSCLC to improve local control and survival.
Lung Cancer 2003 Jul
PMID:The role of radiotherapy in treatment of stage I non-small cell lung cancer. 1282 6

Surgical resection is the treatment of choice for non-advanced lung cancer, but is encumbered with an overall relative poor long time prognosis. The purpose of this study was to examine if long time survival for patients operated for non-small cell lung cancer have changed over a 15 years period. We retrospectively studied hospital records of the 351 patients operated, with the intention to cure, for a primary non-small cell carcinoma (NSCLC) in our department between 1 January 1988 and 31 December 2002. Preoperative clinical variables were noted together with variables allowing staging based on pathological examination. Absolute survival and survival relative to expected was studied for the whole group using uni- and multivariate Cox analyses. Early 30 days mortality was 2.0%. The 5-year absolute and relative survivals for all patients were 46.3% and 52.6%, respectively. After 10 years corresponding values were 32.9% and 44.6%. At the end of the study, the 15-year absolute survival was 27.8% with a relative survival of 46.2%. Univariate analysis revealed that age, gender, nodular stage, tumour size, p-stage, type of resection, time of operation and additional cardiovascular disease at the time of operation significantly influenced survival. Multivariate analysis for all patients revealed that low age, female gender, low nodular stage, and operation late in the study period were significant prognostic factors predicting improved survival. When including a population based age- and gender-adjusted median expected life time for every patient as a predictor for survival, only female gender and low nodular stage were additional significant and independent positive prognostic factors.
Lung Cancer 2005 Feb
PMID:The female gender has a positive effect on survival independent of background life expectancy following surgical resection of primary non-small cell lung cancer: a study of absolute and relative survival over 15 years. 1594 3

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is the rate-limiting enzyme in the mevalonate pathway that provides essential intermediates for the membrane anchorage and biologic functions of growth-related proteins. Contrary to preclinical studies showing the growth-suppressive activity of statins, competitive inhibitors of HMG CoA reductase, clinical application of statins in cancer is precluded by their lack of activity at levels prescribed for the prevention of cardiovascular disease and by their dose-limiting toxicities at high doses. The dysregulated and elevated HMG CoA reductase activity in tumors retains sensitivity to the isoprenoid-mediated posttranscriptional down-regulation, an action that complements the statin-mediated inhibition and may lead to synergistic impact of blends of isoprenoids and lovastatin on tumor HMG CoA reductase activity and consequently tumor growth. d-gamma- and d-delta-tocotrienols, vitamin E isomers containing an isoprenoid moiety, and lovastatin-induced concentration-dependent inhibition of the 48-hr proliferation of murine B16 melanoma cells with IC50 values of 20 +/- 3, 14 +/- 3, and 1.5 +/- 0.4 microM respectively. A blend of lovastatin (1 microM) and d-gamma-tocotrienol (5 microM) totally blocked cell growth, an impact far exceeding the sum of inhibitions induced by lovastatin (12%) and d-gamma-tocotrienol (8%) individually. Synergistic impact of these two agents was also shown in human DU145 prostate carcinoma and human A549 lung carcinoma cells. C57BL6 mice were fed diets supplemented with 12.5 mg lovastatin/kg body weight, 62.5 mg d-delta-tocotrienol/kg body weight, or a blend of both agents for 22 days following B16 cell implantation; only the latter had significantly lower tumor weight than those with no supplementation. Co-administration of isoprenoids that posttranscriptionally down-regulate tumor reductase may lower the effective dose of statins and offer a novel approach to cancer chemo-prevention and/or therapy.
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PMID:Tocotrienols potentiate lovastatin-mediated growth suppression in vitro and in vivo. 1739 88

Surgical resection is the standard treatment for stage I non-small cell lung cancer (NSCLC). However, elderly patients with NSCLC often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD) or cardiovascular disease, and are not suitable candidates for surgery. Different modalities to treat stage I NSCLC have been developed, such as stereotactic radiotherapy (SRT), proton beam radiotherapy and carbon ion radiotherapy (CIRT). Between April 1999 and November 2003, we treated 129 patients with stage I NSCLC using CIRT. In this study, we focused on 28 patients aged 80 years and older who underwent CIRT, and analyzed the effectiveness of CIRT in treating their lung cancer and the impact on their activity of daily life (ADL). The 5-year local control rate for these patients was 95.8%, and the 5-year overall survival rate was 30.7%, but there were no patients who started home oxygen therapy or had decreased ADL. Our data demonstrate that CIRT was effective in treating elderly patients with stage I NSCLC.
Lung Cancer 2009 Apr
PMID:Carbon ion radiotherapy for elderly patients 80 years and older with stage I non-small cell lung cancer. 1876 51

The integral membrane protein p22(phox) forms a heterodimeric enzyme complex with NADPH oxidases (Noxs) and is required for their catalytic activity. Nox4, a Nox linked to cardiovascular disease, angiogenesis, and insulin signaling, is unique in its ability to produce hydrogen peroxide constitutively. To date, p22(phox) constitutes the only identified regulatory component for Nox4 function. To delineate structural elements in p22(phox) essential for formation and localization of the Nox4-p22(phox) complex and its enzymatic function, truncation and point mutagenesis was used. Human lung carcinoma cells served as a heterologous expression system, since this cell type is p22(phox)-deficient and promotes cell surface expression of the Nox4-p22(phox) heterodimer. Expression of p22(phox) truncation mutants indicates that the dual tryptophan motif contained in the N-terminal amino acids 6-11 is essential, whereas the C terminus (amino acids 130-195) is dispensable for Nox4 activity. Introduction of charged residues in domains predicted to be extracellular by topology modeling was mostly tolerated, whereas the exchange of amino acids in predicted membrane-spanning domains caused loss of function or showed distinct differences in p22(phox) interaction with various Noxs. For example, the substitution of tyrosine 121 with histidine in p22(phox), which abolished Nox2 and Nox3 function in vivo, preserved Nox4 activity when expressed in lung cancer cells. Many of the examined p22(phox) mutations inhibiting Nox1 to -3 maturation did not alter Nox4-p22(phox) association, further accenting the differences between Noxs. These studies highlight the distinct interaction of the key regulatory p22(phox) subunit with Nox4, a feature which could provide the basis for selective inhibitor development.
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PMID:Mutational analysis reveals distinct features of the Nox4-p22 phox complex. 1884 43

This paper summarizes the phase II and III clinical trial experience with cetuximab in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Single-arm and randomized phase II studies show that adding cetuximab to platinum-based doublets has favorable efficacy compared to chemotherapy alone or historical control groups that did not receive cetuximab. Two phase III studies have been conducted with different primary endpoints: overall survival in the pivotal FLEX trial, and progression-free survival (PFS) as assessed by an independent radiologic review committee in the supportive BMS 099 trial. FLEX shows that adding cetuximab significantly prolongs survival compared to chemotherapy alone. BMS 099 did not meet its primary objective, but did show that adding cetuximab significantly prolongs PFS as assessed by investigators. Across all studies, the safety and tolerability of adding cetuximab was predictable and manageable, and did not exacerbate the toxicity associated with chemotherapy. These trials enrolled a broad population of NSCLC patients regardless of histological subtype or comorbid cardiovascular disease, populations that have been underrepresented in clinical trials of other biologics. Cetuximab does not carry restrictions in use due to safety, and therefore it may be a particularly valuable option for patients who are not eligible for other biologics.
Lung Cancer 2010 Jun
PMID:Emerging profile of cetuximab in non-small cell lung cancer. 1978 64

Orthotopic heart transplantation (OHT) may represent the only treatment option for patients with end-stage cardiovascular disease due to mediastinal radiation therapy (MRT). The primary aim of this study was to evaluate the safety and efficacy of OHT in this patient population. We conducted a retrospective, single-center cohort study of patients with MRT-associated cardiovascular disease who underwent OHT between January 1987 and September 2008. Nine patients (3 men), aged 46 +/- 11 years at the time of their OHT, were identified. Time from MRT to OHT was 26 +/- 11 years. Lymphoma was the indication for MRT in all patients. Five patients had non-ischemic dilated cardiomyopathy, 2 had ischemic cardiomyopathy and 2 had constrictive pericarditis. Three patients expired in the peri-operative period, whereas another patient died 3 years post-transplant from lung carcinoma. Two additional patients developed a secondary malignancy post-transplant. Five patients are still alive at a mean follow-up of 10 +/- 8 years. Early survival rate is poor in patients who undergo OHT for MRT-associated end-stage cardiovascular disease. In addition, long-term follow-up shows an elevated incidence of malignancies. Our results raise concern about the safety and efficacy of performing OHT in patients with MRT-associated cardiovascular disease.
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PMID:Mediastinal radiation and adverse outcomes after heart transplantation. 1980 88

The primary aim of lung cancer screening is to improve survival from lung cancer by identifying early stage non-small cell lung cancers and prolong survival through their surgical removal. In a post-hoc analysis of 10,054 screening participants from the National Lung Screening Trial (NLST) we show that the risk of lung cancer, according to the PLCOm2012 model, is closely related to the likelihood of having chronic obstructive pulmonary disease (COPD). Those at greatest risk for lung cancer have the highest prevalence of COPD and greater likelihood of dying of a non-lung cancer cause. This "competing cause of death" effect occurs because smokers eligible for lung cancer screening have a high prevalence of comorbid disease and greater likelihood of dying from cardiovascular disease, respiratory disease or other cancers. This means high risk smokers at greatest risk of lung cancer may not necessarily benefit from screening due to greater inoperability and premature death. In this analysis we show that the benefit of annual computed tomography (CT) screening is greatest in those with normal lung function or only mild-to-moderate COPD. We found no mortality benefit in those with severe or very severe COPD (GOLD 3-4). We also show that the efficiency of screening, based on optimizing the number of lung cancer deaths averted per 1,000 persons screened, is best achieved by screening those at intermediate risk. By combining clinical risk variables with a gene-based risk score, even greater reductions in lung cancer mortality can be achieved with CT. We suggest a biomarker-led outcomes-based approach may help to better define which eligible smokers might defer screening (low risk of lung cancer), discontinue screening (high risk of overtreatment with little benefit) or continue screening to achieve the greatest reduction in lung cancer mortality.
Transl Lung Cancer Res 2018 Jun
PMID:Chronic obstructive pulmonary disease (COPD) and lung cancer screening. 3005 Jul 72

A significant reduction in lung cancer specific mortality rate was demonstrated by the National Lung Screening Trial (NLST) in participants who had annual low-dose computed tomography (LDCT) screening. In addition to early detection of lung cancer, lung cancer screening (LCS) provides an opportunity to detect cardiovascular disease, pulmonary disease (such as chronic obstructive pulmonary disease and interstitial lung disease), and extrapulmonary neoplasms, such as thyroid, breast, kidney, liver, esophageal, pancreatic and mediastinal tumors. Considering the fact that 22.3% of the certified deaths in the computed tomography (CT) arm of the NLST trial were due to extrapulmonary malignancies, compared to 22.9% of deaths from lung cancer, it is possible that early diagnosis and treatment of clinically significant incidental findings may further decrease morbidity and mortality in screening participants. In this article we review prevalence, clinical relevance and management of incidentally detected extrapulmonary malignancies.
Transl Lung Cancer Res 2018 Jun
PMID:Extrapulmonary neoplasms in lung cancer screening. 3005 Jul 74


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