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)

Autofluorescence bronchoscopy is an important tool for the early detection of preinvasive bronchial lesions. However, autofluorescence bronchoscopy has difficulty distinguishing between preinvasive lesions and other benign epithelial changes. A new autofluorescence imaging bronchovideoscope system (AFI) comprises three signals, including an autofluorescence (460-690 nm) on excitation blue light (395-445 nm) and two different bands of reflected light: G' (550 nm) and R' (610 nm). We hypothesized that color analyses of these three wave lengths would improve our ability to differentiate between inflammation and preinvasive lesions. In order to prove this hypothesis and to evaluate the efficacy of AFI for detecting preinvasive lesions, we conducted a prospective study. A total of 32 patients with suspected or known lung cancer were entered into this study. Conventional white light bronchovideoscopy (WLB) and light induced fluorescence endoscopy (LIFE) were performed prior to using AFI. WLB and LIFE detected 62 lesions, including lung cancers (n=2), squamous dysplasias (n=30), and bronchitis (n=30). By utilizing AFI, 24 dysplasias and 2 cancer lesions were magenta in color, while 25 bronchitis lesions were blue. The sensitivities of detecting dysplasia by LIFE and AFI were 96.7% and 80%, respectively. The specificity of AFI (83.3%) was significantly higher than that of LIFE (36.6%) (p=0.0005). We conclude that AFI appears to represent a significant advance in distinguishing preinvasive and malignant lesions from bronchitis or hyperplasia under circumstances where LIFE would identify these all as abnormal lesions.
Lung Cancer 2005 Jun
PMID:Effective detection of bronchial preinvasive lesions by a new autofluorescence imaging bronchovideoscope system. 1589 98

Inactivation of the cadherin-mediated cell-cell adhesion system is believed to play a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracytoplasmic binding molecules (alpha-catenin, beta-catenin, and plakoglobin) was examined immunohistochemically in 84 cases of intrabronchial precancerous lesions (bronchial squamous metaplasia (BSM) without atypia, BSM with atypia, dysplasia), and 21 cases of carcinoma in situ, and 4 cases of microinvasion to the bronchial wall, and 32 cases of stage I well differentiated squamous cell carcinoma (squamous cell carcinoma) to investigate the association between expression of E-cadherin and/or catenins and cancer progression. Reduced expression of E-cadherin and/or catenins was closely correlated with an atypical grade of dysplasia in the basal layer (p<0.05). In particular, downregulation of E-cadherin and/or catenins was associated with an atypical grade of BSM with atypia in intrabronchial lesions (p<0.01). We conclude that downregulation of alpha-catenin and/or beta-catenin, which may reflect dysfunction of the cadherin-mediated cell-cell adhesion system, is an important marker for atypical grade during carcinogenesis of the bronchial epithelium.
Lung Cancer 2005 Jun
PMID:Frequent loss of E-cadherin and/or catenins in intrabronchial lesions during carcinogenesis of the bronchial epithelium. 1589

The Research Institute for Diagnosis and Treatment of Early Lung Cancer (RIDTELC) Lung Study was initiated to determine whether lung cancer screening by automated sputum cytometry combined with conventional sputum cytology and auto-fluorescence in addition to white light bronchoscopy could enhance the detection rate of early lung cancer. The present study analyses the initial findings to evaluate the efficiency of automated sputum cytology in predicting the diagnosis of lung cancer. In this study, malignancy grade was used as a predictive parameter for lung cancer. In total, 2,480 heavy smokers (>30 pack-yrs), aged 50-74 yrs, with no previous cancer in the last 5 yrs, received chest radiology, conventional sputum cytology and sputum cytometry screening. In total, twenty-seven lung cancers were diagnosed, representing a prevalence of 1.1%, 25 of which provided sputum samples. Positive automated sputum cytology results were seen in 176 smokers (7.2%), 10 (0.4%) of whom had severe dysplasia or higher lesions (positive results) by conventional sputum cytology examination. Out of 25 tumour cases, 20 had suspicious results using automated sputum cytology, representing 80% sensitivity. One patient out of 24 with tumours had positive results on conventional sputum cytology, representing a sensitivity of 4.2%. For all stages of squamous cell lung cancer and later stage adenocarcinoma the sensitivity of automated sputum cytology was 100%. For adenocarcinoma stage I sensitivity was 25%. In conclusion, DNA analysis of sputum slides by automated sputum cytology may be a suitable tool for the detection of early lung cancer and the characterisation of a high-risk group with pre-invasive lesions for follow-up.
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PMID:Predictive value of image cytometry for diagnosis of lung cancer in heavy smokers. 1592 48

Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects.
Lung Cancer 2005 Aug
PMID:High prevalence of occult endobronchial malignancy in high risk patients with moderate sputum atypia. 1602 12

Pulmonary epithelium is known to undergo a preneoplastic process prior to the development of lung carcinoma. Squamous dysplasia and atypical adenomatous hyperplasia have been identified and classified as preinvasive lesions of squamous cell carcinoma and peripheral pulmonary adenocarcinoma, respectively. However, these commonly recognized preinvasive lesions do not completely explain the development of all histological types of lung carcinoma. By examining 114 resection lung specimens, we concluded that there are four histological patterns of bronchial epithelial dysplasia based on morphological features (basal cell dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with transitional differentiation, and squamous dysplasia). The histological patterns were further characterized by immunohistochemistry. Basal cell dysplasia was focally positive for cytokeratin (CK) 17 and 10/13; columnar cell dysplasia was generally positive for CK7, 8, and 18; bronchial epithelial dysplasia with transitional differentiation had a heterogeneous immunoprofile, while squamous dysplasia was positive for CK10/13 and focally positive for CK17. Various degrees of abnormal expression of p53 and Ki-67 were found in the different types of bronchial epithelial dysplasia. The cases were divided into three groups based on degree and extent of bronchial epithelial dysplasia. By Crosstabs McNemar test, the Mann-Whitney U-test (for two independent groups), the Kruskal-Wallis one-way nonparametric ANOVA (for >2 independent groups) and Spearman correlation analysis, the degree and extent of bronchial epithelial dysplasia was shown to be positively correlated with the incidence of bronchogenic carcinoma and multifocal primary lung carcinoma (P<0.05). These findings indicated the following: (1) bronchial epithelium can develop various patterns of dysplasia with abnormal/ambiguous cell differentiation and abnormal expressions of p53 and Ki-67. Thus, these bronchial epithelial dysplastic lesions may represent a preneoplastic process. (2) The degree of bronchial epithelial dysplasia may significantly predispose individuals to bronchogenic carcinoma and multifocal primary lung carcinoma.
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PMID:Histological types and significance of bronchial epithelial dysplasia. 1641 91

Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are highly associated with the pathogenesis of cigarette smoke related lung diseases but their role in the malignant conversion of bronchial epithelium is unclear. The immunohistochemical expression of inducible, endothelial and neuronal nitric oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers, 20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and 24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of non-smokers was mainly negative for nitrotyrosine, while it was higher in the alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025, p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal looking bronchial epithelium of smokers and COPD, whereas metaplasia and dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of cases. Strong immunoreactivity for iNOS and nNOS was also found more often in dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of NOSs in lung carcinogenesis.
Lung Cancer 2006 Mar
PMID:Nitric oxide synthases are associated with bronchial dysplasia. 1642 Sep 64

The combination of white light and autofluorescence bronchoscopy has been reported to show better sensitivity in detecting dysplasia and cancer of the bronchus than white light alone. However, fiberoptic bronchoscopy has been replaced by videoendoscopy at most leading facilities for over a decade. To avoid interruption of the videoendoscopy examination to perform fiberscopy-based autofluorescence examination as well as enhancing the sensitivity of intraepithelial lesions, autofluorescence diagnosis system integrated into a videoendoscope (SAFE 3000, Pentax, Tokyo) was created. A total of 154 consecutive patients were studied using this system, containing 83 known or suspected lung cancer cases, 46 of the cases with abnormal sputum cytology findings, 10 follow up cases following lung cancer operations, and 15 heavy smokers with respiratory symptoms. Abnormal findings were recognized by white light and/or SAFE 3000 at 166 sites and biopsies were taken to evaluate the relationship between endoscopic findings and pathology results. The sensitivity of the system for CIS+dysplasia was 65% in white light and 90% in SAFE. This videoendoscopy-based autofluorescence system had significantly higher sensitivity for intraepithelial lesions than white light videoendoscopy alone.
Lung Cancer 2006 Apr
PMID:Early detection of bronchial lesions using newly developed videoendoscopy-based autofluorescence bronchoscopy. 1649 11

Survivin is an inhibitor of apoptosis protein, which is overexpressed in many carcinomas, including lung carcinoma. The aim of this immunohistochemical study was to investigate the role of survivin in the early steps of lung carcinogenesis and non-small cell lung carcinomas (NSCLC), and its relationship with expression of p53 protein, a tumor suppressor gene involved in cell cycle control. In the normal bronchial epithelium, low-grade atypical adenomatous hyperplasia (AAH) and non-neoplastic lung parenchyma adjacent to tumor, survivin was found completely negative. Expression of survivin was detected in the areas of squamous metaplasia and dysplasia as well as high-grade AAH lesions adjacent to tumor. Survivin was expressed in 50 (64%) and p53 in 41 (53%) NSCLC. Survivin expression was significantly correlated with lymph node metastasis (p=0.02). There was no correlation between survivin and p53 expression. The patients with expression of survivin had significantly worse prognosis (Log-rank test, p=0.003). Multivariate Cox regression analysis showed TNM stage (p<0.001) and survivin expression (p=0.003) as independent prognostic indicators. In conclusion, survivin expression might be an early step in lung carcinogenesis. Survivin expression might also be used as a prognostic indicator predicting the worse outcome in NSCLC, and might be a novel target for the treatment of patients with preinvasive lesions of lung and NSCLC.
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PMID:Survivin expression in pre-invasive lesions and non-small cell lung carcinoma. 1681 May 43

The aim of the present study was to evaluate the expression of blood group antigens in squamous bronchial metaplasia in order to determine whether this factor could identify patients at risk of lung cancer. In total, 100 bronchial biopsies were included in the present study. The cases were classified according to the World Health Organization grading system. Immunohistochemical stains for histo-blood groups A and B, and reactivity tests to p53 and the cellular proliferation index were performed. A total of 56 (56%) patients belonged to blood group A. Among them, six (10.7%) patients who did not express antigen in squamous metaplasia, showed carcinoma at the moment of the biopsy (n = 3) or developed synchronous lung carcinoma (n = 3). A total of nine (9%) patients belonged to blood group B. Loss of antigenic expression was observed in five cases. All of them developed synchronous lung carcinoma. The patients with low- and high-grade dysplasia developed lung cancer in 71 and 100% of the cases, respectively. In conclusion, the findings of the present study suggest that the loss of histo-blood antigens expression is an event in the carcinogenesis of bronchial mucosa and it is usually associated with high-grade lesions and hyperproliferative activity.
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PMID:Expression of histo-blood group antigens in bronchial squamous metaplasia. 1700 87

The tumor suppressor function of the retinoblastoma protein pRB is largely dependent upon its capacity to inhibit the E2F transcription factors and thereby cell proliferation. Attempts to study the interplay between pRB and the E2Fs have been hampered by the prenatal death of Rb; E2f nullizygous mice. In this study, we isolated Rb; E2f3 mutant embryonic stem cells and generated Rb(-/-); E2f3(-/-) chimeric mice, thus bypassing the lethality of the Rb(-/-); E2f3(-/-) germ line mutant mice. We show that loss of E2F3 has opposing effects on two of the known developmental defects arising in Rb(-/-) chimeras; it suppresses the formation of cataracts while aggravating the retinal dysplasia. This model system also allows us to assess how E2f3 status influences tumor formation in Rb(-/-) tissues. We find that E2f3 is dispensable for the development of pRB-deficient pituitary and thyroid tumors. In contrast, E2f3 inactivation completely suppresses the pulmonary neuroendocrine hyperplasia arising in Rb(-/-) chimeric mice. This hyperproliferative state is thought to represent the preneoplastic lesion of small-cell lung carcinoma. Therefore, our observation highlights a potential role for E2F3 in the early stages of this tumor type.
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PMID:Selective requirements for E2f3 in the development and tumorigenicity of Rb-deficient chimeric tissues. 1721 Jun 34


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