Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The solitary pulmonary nodule (SPN) is a relatively common imaging finding, often representing a diagnostic challenge. Radiological appearance, growth rate calculation during follow up and probability of malignancy assessment by the Bayes' theorem are widely used for identifying the nature of a SPN. Molecular imaging by fluoro-18 deoxy glucose positron emission tomography has revolutionised non-invasive diagnosis of lung cancer, but the low-cost, widely available conventional nuclear imaging modalities still remain valid in the field. We present a case of a growing SPN in a middle-aged male smoker. Growth rate assessment by sequential computed tomography scans, over a follow up period of five years, was suggestive of benign histology, while Bayesian analysis warranted histological confirmation of the nodule's nature. Imaging by both labelled somatostatin analogue technetium 99m-depreotide ((99m)Tc-depreotide) and thallium 201-chloride was almost exclusive of malignancy. The nodule was excised and histology showed a pulmonary hamartoma. We briefly discuss the relative role of invasive and non-invasive methods, with emphasis in conventional radionuclide molecular imaging, for the identification of the nature of SPN.
Hell J Nucl Med
PMID:The contribution of conventional nuclear molecular imaging in characterising the nature of a growing solitary pulmonary nodule. Report of a case. 1745 Feb 48

Lung cancer is the most common cancer worldwide with 900,000 new cases each year in men and 330,000 in women, being also the major cause of death from cancer. In Greece about 4,000 persons die every year due to lung carcinoma. One of the major problems in the follow up of these patients is the difficulty of early detection of recurrent disease. Tumor markers are of particular interest in this respect. Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins that show increased levels in patients with carcinomas. CYFRA 21-1 assays determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients with various types of lung cancer after surgery or chemotherapy. Ninety-six consecutive patients were studied during a two years period. Forty-five of them had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC). Moreover, 52 healthy individuals were studied to estimate the cut off value of CYFRA 21-1. Increased serum levels of the marker were found in patients with lung cancer compared to controls (P<0.001). The cut off value was estimated as 3.3 ng/ml with 96% specificity. Before the treatment there was no difference in the sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels, 52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC and especially in SCC among other histotypes of NSCLC when different stages of the disease were compared. Patients with extended disease, metastatic or recurrent disease had also more increased levels of the marker (P<0.001). One month after surgical ablation of the primary lung lesion, 28/58 patients showed a drop in the levels of the marker as an indication of the tumor ablation. From the 58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1 levels with a sensitivity of 92% and specificity of 95%. From the 38 patients that underwent chemotherapy treatment, 24 had a depravation of the disease and 21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer.
Hell J Nucl Med
PMID:[The importance of the tumor marker CYFRA 21-1 in patients with lung cancer after surgery or chemotherapy]. 1745 Feb 57

The aim of our study was to analyze how many oncology patients might benefit from a) integrated positron emission tomography - multidetector computed tomography (PET/MDCT) and additionally b) clinically relevant information provided by either the CT scan or PET scan. A total of 285 consecutive patients 164 male and 121 female, age range 17-84 years, 153 lung cancer, 112 lymphoma, 20 miscellaneous, referred for PET and separate CT scan, were included. The CT scan was performed after the intravenous injection of a soluble contrast media. Patients were retrospectively classified into six Groups: Group I: No pathological uptake on the PET scan, Group II: Suspected lesions were correctly identified by the PET scan alone, Group III: Side-by-side evaluation of PET and CT appeared sufficient to assess the localization of lesions, Group IV: Side-by-side reading was not sufficient and integrated PET/CT was considered beneficial. Additionally all patients with a CT scan with additional clinical relevant information (not visualized by the PET scan) were classified in Group V. Group VI was set for lesions detected by PET alone (not visualized by the CT scan). The CT scan was used as the gold standard to confirm or disprove PET lesion localization. Our results showed: A number of 77 patients, (Group I: 77/285, 27%) had no pathologic fluorine-18-fluorodeoxyglucose (18F-FDG)-uptake. Lesions were correctly localized by either conventional PET alone (Group II: 76/285, 27%) or side-by-side evaluation of PET and CT scans (Group III: 44/285, 15%). Integrated PET/CT or software fusion, was considered beneficial in 31% (88/285) of the patients with pathological 18F-FDG-uptake (Group IV). Additionally to the above, in 15% of all patients clinically relevant information, referring to disseminated small pulmonary lesions, abdominal aortic aneurysms >5 cm, thrombi or pulmonary emboli, was also provided by the CT scan (Group V). Also, in 7% of all patients, unsuspected pathological lesions, mainly bone metastases, were correctly detected by PET alone (Group VI). In conclusion, in 54% of all oncologic patients, PET alone was diagnostic. In 46% of all patients side-by-side reading (15%) or integrated PET/CT images (31%) were considered beneficial for more accurate anatomical localization of the lesions. Additionally, the CT scan added clinically relevant information in 15% of all patients and the PET scan showed unsuspected metastases in 7% of all studied patients. Therefore, integrated reading of PET and MDCT images by nuclear physicians and radiologists may gain quality in the staging of oncology patients.
Hell J Nucl Med
PMID:Diagnostic evaluation of separately acquired PET and CT images by nuclear medicine physicians and radiologists in cancer patients. 1768 86

Early metastasis and a poor five-year survival make lung cancer the leading cause of cancer related deaths worldwide. The clinical profile of lung cancer patients in India differs from the West as they present earlier, with squamous cell carcinoma being the commonest histological type. We compared gene expression profiles in primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA libraries containing differentially expressed genes in the tumors were constructed. Differential expression was confirmed by reverse Northern blot analysis. DNA of confirmed clones was sequenced and subjected to GenBank Blast searches. RNA expression levels were then analyzed by Northern blotting and validated by semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed gene cDNA fragments of LSCC were analyzed. The differentially expressed genes included those associated with cellular metabolism, cell-cycle, -structure, -adhesion, transcription, proliferation, apoptosis and signal transduction. The study provided first evidence that KIAA0767, a Death Inducing Protein, a novel p53 independent target of E2F1, and Geminin, an inhibitor of DNA replication are differentially expressed in LSCC. Identification of the differentially expressed genes in lung cancer in this study may serve as better molecular markers for early diagnosis and identifying novel intervention sites for anticancer therapy.
 ...
PMID:Molecular profiling of genes in squamous cell lung carcinoma in Asian Indians. 1830 64

The flexible heteroarotinoids (Flex-Het) represent a novel type of atypical retinoids lacking activity in binding to and transactivating retinoid receptors. Preclinical studies have shown that Flex-Hets induce apoptosis of cancer cells while sparing normal cells and exhibit anticancer activity in vivo with improved therapeutic ratios over conventional retinoid receptor agonists. Flex-Hets have been shown to induce apoptosis through activation of the intrinsic apoptotic pathway. The present study has revealed a novel mechanism underlying Flex-Het-induced apoptosis involving induction of death receptor 5 (DR5). The representative Flex-Het SHetA2 effectively inhibited the growth of human lung cancer cells in cell culture and in mice. SHetA2 induced apoptosis, which could be abrogated by silencing caspase-8 expression, indicating that ShetA2 triggers a caspase-8-dependent apoptosis. Accordingly, SHetA2 up-regulated DR5 expression, including cell surface levels of DR5, and augmented tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Importantly, small interfering RNA (siRNA)-mediated blockade of DR5 induction conferred cell resistance to SHetA2-induced apoptosis, as well as SHetA2/TRAIL-induced apoptosis. These results show that DR5 induction is a key component of apoptosis induced by SHetA2 or by SHetA2 combined with TRAIL. SHetA2 exerted CAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter. Consistently, SHetA2 induced CHOP expression, which paralleled DR5 up-regulation, whereas siRNA-mediated blockage of CHOP induction prevented DR5 up-regulation, indicating CHOP-dependent DR5 up-regulation by SHetA2. Collectively, we conclude that CHOP-dependent DR5 up-regulation is a key event mediating SHetA2-induced apoptosis.
 ...
PMID:CAAT/enhancer binding protein homologous protein-dependent death receptor 5 induction is a major component of SHetA2-induced apoptosis in lung cancer cells. 1859 35

DNA repair is an essential mechanism for cells to maintain their genomic integrity under endogenous or exogenous assault. Reduced DNA repair capacity (DRC) is associated with increased risk for several environmentally related cancers. The micronucleus in peripheral lymphocytes has been validated as a biomarker of chromosomal damage, increasing cancer risk in human populations. We hypothesized that suboptimal DRC is associated with the increase in chromosomal damage among 94 coke-oven workers and 64 noncoke-oven controls. DRC was evaluated in isolated lymphocytes by comet assay. Chromosomal damage in peripheral lymphocytes was detected by cytokinesis-block micronucleus assay. Four common coding single nucleotide polymorphisms in the XRCC1 gene were genotyped. Coke-oven workers have significantly increased urinary 1-hydroxypyrene (9.0; 6.8-11.7 microg/L versus 1.5, 1.3-1.7 microg/L; P<0.01) and micronucleus frequency (7.4 per thousand+/-4.3 per thousand versus 3.0 per thousand+/-3.0 per thousand; P<0.01), and decreased DRC (55.9%+/-16.4% versus 63.6%+/-18.5%; P<0.01) compared with controls. Significant correlations between DRC and micronucleus frequency were found in coke-oven workers (r=-0.32; P<0.01; n = 94) and all study subjects (r=-0.32; P<0.001; n=158) but not in controls (r=-0.21; P=0.11; n=64). Variants of the Arg399Gln polymorphism were associated with a decreased DRC in both coke-oven workers (51.6%+/-16.1% versus 60.6%+/-15.7%; P<0.01) and controls (59.1%+/-18.5% versus 68.4%+/-17.5%; P=0.04). The complicated interrelationship of these multiple biomarkers was also identified by path analysis. These findings should facilitate developing a biomarker-based risk assessment model for lung cancer in this occupational population.
 ...
PMID:Suboptimal DNA repair capacity predisposes coke-oven workers to accumulate more chromosomal damages in peripheral lymphocytes. 1924 Feb 42

Lung cancer (LC) has an unfavorable prognosis especially when the disease is extensive at presentation. Accurate staging is therefore needed for treatment planning of these patients. In the present study the role of positron emission tomography/computerized tomography (PET/CT) in the detection of extra thoracic metastases in LC is being evaluated. In all 52 of our patients with stage IIIA or lower of LC disease, a whole body (18)F-FDG PET/CT was performed. All patients were also subjected to general clinical evaluation, chest X-rays and chest contrast enhanced CT (CECT) and were confirmed by histopathology or magnetic resonance imaging or radiology. Incidental extra thoracic malignant lesions were found by (18)F-FDG PET/CT in 9 out of the 52 patients (17.3%). No false positive lesions were found. As for the primary LC diagnosed by fine needle aspiration cytology (FNAC): (18)F-FDG PET/CT diagnosed all 52 cases, CECT detected 46 cases and chest X-rays detected 28 cases. The diagnostic accuracy was 100%, 92% and 53.8% respectively. As for the 9 cases with extrathoracic metastases diagnosed by (18)F-FDG PET/CT they were confirmed: by biopsy 6, by MRI 2 and by X-rays with or without biopsy 2. In conclusion, (18)F-FDG PET/CT had better diagnostic accuracy in diagnosing LC stage IIIA or lower, than CECT or chest X-rays. Extrathoracic metastases were high: 9/52 as diagnosed by (18)F-FDG PET/CT and standardized up take value.
Hell J Nucl Med
PMID:The importance of 18F-FDG PET/CT, CT and X-rays in detecting primary stage III A lung cancer and the incidence of extra thoracic metastases. 2368 45

Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs) and have a high risk for lung cancer. Limited evidence has demonstrated a direct link between exposure to PAHs and early genetic damage in exposed workers. The cytokinesis-block micronucleus (CBMN) cytome assay is a comprehensive system for measuring DNA damage and cytotoxicity. In the current study, we investigated different chromosomal damage endpoints including micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs), in 141 PAH-exposed subjects and 66 unexposed controls. The frequencies of MN, NPBs and NBUDs were all significantly higher in PAH-exposed workers than in controls (2.4-, 5-, and 3-fold, respectively). We further classified the PAH-exposed workers into different PAHs exposure groups based on their work positions on the oven and their urinary 1-hydroxypyrene and found that the frequencies of NPBs and NBUDs increased with the increasing level of both external and internal PAHs exposure levels. Similar trend was not found for MN due to the reduced MN frequency in the highest PAHs exposure group compared with the second highest PAHs exposure group. Using principal component analysis, we confirmed that the frequencies of NPBs and NBUDs are more sensitive to reflect the external or internal levels of PAHs exposure. In PAH-exposed subjects, NPB and NBUD frequencies were influenced by gender and females have lower frequencies of NPB and NBUD. Taken together, our observations indicate that NPBs and NBUDs are more sensitive and reliable biomarkers for genetic damages induced by PAHs and could potentially be used for the biomonitoring of genotoxin-exposed populations.
 ...
PMID:Biomarkers measured by cytokinesis-block micronucleus cytome assay for evaluating genetic damages induced by polycyclic aromatic hydrocarbons. 1954 Mar 55

We conducted an extended follow-up and spatial analysis of the American Cancer Society (ACS) Cancer Prevention Study II (CPS-II) cohort in order to further examine associations between long-term exposure to particulate air pollution and mortality in large U.S. cities. The current study sought to clarify outstanding scientific issues that arose from our earlier HEI-sponsored Reanalysis of the original ACS study data (the Particle Epidemiology Reanalysis Project). Specifically, we examined (1) how ecologic covariates at the community and neighborhood levels might confound and modify the air pollution-mortality association; (2) how spatial autocorrelation and multiple levels of data (e.g., individual and neighborhood) can be taken into account within the random effects Cox model; (3) how using land-use regression to refine measurements of air pollution exposure to the within-city (or intra-urban) scale might affect the size and significance of health effects in the Los Angeles and New York City regions; and (4) what exposure time windows may be most critical to the air pollution-mortality association. The 18 years of follow-up (extended from 7 years in the original study [Pope et al. 1995]) included vital status data for the CPS-II cohort (approximately 1.2 million participants) with multiple cause-of-death codes through December 31, 2000 and more recent exposure data from air pollution monitoring sites for the metropolitan areas. In the Nationwide Analysis, the influence of ecologic covariate data (such as education attainment, housing characteristics, and level of income; data obtained from the 1980 U.S. Census; see Ecologic Covariates sidebar on page 14) on the air pollution-mortality association were examined at the Zip Code area (ZCA) scale, the metropolitan statistical area (MSA) scale, and by the difference between each ZCA value and the MSA value (DIFF). In contrast to previous analyses that did not directly include ecologic covariates at the ZCA scale, risk estimates increased when ecologic covariates were included at all scales. The ecologic covariates exerted their greatest effect on mortality from ischemic heart disease (IHD), which was also the health outcome most strongly related with exposure to PM2.5 (particles 2.5 microm or smaller in aerodynamic diameter), sulfate (SO4(2-)), and sulfur dioxide (SO2), and the only outcome significantly associated with exposure to nitrogen dioxide (NO2). When ecologic covariates were simultaneously included at both the MSA and DIFF levels, the hazard ratio (HR) for mortality from IHD associated with PM2.5 exposure (average concentration for 1999-2000) increased by 7.5% and that associated with SO4(2-) exposure (average concentration for 1990) increased by 12.8%. The two covariates found to exert the greatest confounding influence on the PM2.5-mortality association were the percentage of the population with a grade 12 education and the median household income. Also in the Nationwide Analysis, complex spatial patterns in the CPS-II data were explored with an extended random effects Cox model (see Glossary of Statistical Terms at end of report) that is capable of clustering up to two geographic levels of data. Using this model tended to increase the HR estimate for exposure to air pollution and also to inflate the uncertainty in the estimates. Including ecologic covariates decreased the variance of the results at both the MSA and ZCA scales; the largest decrease was in residual variation based on models in which the MSA and DIFF levels of data were included together, which suggests that partitioning the ecologic covariates into between-MSA and within-MSA values more completely captures the sources of variation in the relationship between air pollution, ecologic covariates, and mortality. Intra-Urban Analyses were conducted for the New York City and Los Angeles regions. The results of the Los Angeles spatial analysis, where we found high exposure contrasts within the Los Angeles region, showed that air pollution-mortality risks were nearly 3 times greater than those reported from earlier analyses. This suggests that chronic health effects associated with intra-urban gradients in exposure to PM2.5 may be even larger between ZCAs within an MSA than the associations between MSAs that have been previously reported. However, in the New York City spatial analysis, where we found very little exposure contrast between ZCAs within the New York region, mortality from all causes, cardiopulmonary disease (CPD), and lung cancer was not elevated. A positive association was seen for PM2.5 exposure and IHD, which provides evidence of a specific association with a cause of death that has high biologic plausibility. These results were robust when analyses controlled (1) the 44 individual-level covariates (from the ACS enrollment questionnaire in 1982; see 44 Individual-Level Covariates sidebar on page 22) and (2) spatial clustering using the random effects Cox model. Effects were mildly lower when unemployment at the ZCA scale was included. To examine whether there is a critical exposure time window that is primarily responsible for the increased mortality associated with ambient air pollution, we constructed individual time-dependent exposure profiles for particulate and gaseous air pollutants (PM2.5 and SO2) for a subset of the ACS CPS-II participants for whom residence histories were available. The relevance of the three exposure time windows we considered was gauged using the magnitude of the relative risk (HR) of mortality as well as the Akaike information criterion (AIC), which measures the goodness of fit of the model to the data. For PM2.5, no one exposure time window stood out as demonstrating the greatest HR; nor was there any clear pattern of a trend in HR going from recent to more distant windows or vice versa. Differences in AIC values among the three exposure time windows were also small. The HRs for mortality associated with exposure to SO2 were highest in the most recent time window (1 to 5 years), although none of these HRs were significantly elevated. Identifying critical exposure time windows remains a challenge that warrants further work with other relevant data sets. This study provides additional support toward developing cost-effective air quality management policies and strategies. The epidemiologic results reported here are consistent with those from other population-based studies, which collectively have strongly supported the hypothesis that long-term exposure to PM2.5 increases mortality in the general population. Future research using the extended Cox-Poisson random effects methods, advanced geostatistical modeling techniques, and newer exposure assessment techniques will provide additional insight.
 ...
PMID:Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality. 1962 30

The causes of prostate cancer (PC) and its progression are not yet known. Mortality and incidence from PC has increased throughout European countries until early 1990s. In Greece, PC is the second commonest cancer in men after lung cancer. The traditional Greek diet old in its origin may protect against common chronic diseases, including PC. Hormonal causes have been postulated in the aetiology of PC, mainly because androgen ablation causes regression of PC. Total and free prostate specific antigen (PSA and fPSA) screening were introduced to detect PC at an early stage, to reduce PC specific mortality, differentiate PC from hypertrophy and monitor response after hormonal treatment in advanced PC.
Hell J Nucl Med
PMID:Prostate cancer incidence, mortality, total and free prostate specific antigen. 1967 60


<< Previous 1 2 3 4 5 Next >>