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)

We describe the case of a 52-year-old Japanese woman with advanced adenocarcinoma of the lung, in whom once-daily treatment with 250 mg ZD1839 ('Iressa') demonstrated a marked antitumour effect. She had initially achieved a partial response with cisplatin-based combination chemotherapy, but had subsequently progressed and had failed to respond to salvage chemotherapy. She had also received whole-brain irradiation for brain metastases. On admission, the patient was confined to bed due to dyspnoea and had rapidly progressing hypoxia secondary to lymphangitis carcinomatosa and a massive right pleural effusion. She was treated with oxygen supplementation and oral ZD1839, which, within a week, led to marked tumour regression and gradually improving dyspnoea. The main adverse event observed was a grade 2 rash. A month after starting ZD1839 treatment, the patient was discharged without the need for oxygen supplementation and had since returned to full-time work. This is a demonstration of ZD1839 producing a dramatic clinical response when administered to a patient with poor performance status who had received extensive prior treatment with cytotoxic agents.'Iressa' is a trademark of the AstraZeneca group of companies.
Lung Cancer 2003 Apr
PMID:Dramatic effect of ZD1839 ('Iressa') in a patient with advanced non-small-cell lung cancer and poor performance status. 1516

The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size. We examined p53 mutations in exons 5-8 in 202 cases of AC and 82 cases of SCC from smoking lung cancer patients in the Western Pennsylvania region. The percent of cases with p53 mutation was significantly lower in ACs (40/202, 20%) compared to SCCs (29/82, 35%, P=0.006). The proportion of mutations present that were G to T transversions was not significantly different between the two tumor types (52% of p53 mutations in AC compared to 32% in SCC). G to A transitions either did not differ in frequency in the two types of lung cancer (20% of mutations in AC and 24% of mutations in SCC). A distinct spectrum was observed, however, in the p53 mutation pattern in the two types of lung cancer. ACs showed a strong preference for a mutational hotspot at codons 248 and 249, while squamous cell tumors showed mutational events spread throughout exons 5-8, with a preference for codon 267. Mutations at codon 267 in SCC were all C to T transitions that occurred at CpG sites. Both tumor types demonstrated preferential mutation of the non-transcribed strand (100% of all G to T transversions and 55% of the G to A transitions). These results suggest that p53 mutations in both types of lung tumors may arise from adduction by both PAHs and nitrosamines. Mutations arising in ACs appear selectively in regions of p53 that produce more rigid proteins, suggesting a drastic change in p53 function is needed to result in ACs, while less constrained changes in p53 function can result in SCCs. Mutation in p53 was not found to be related to patient survival in this group of patients, while tumor size and degree of differentiation were poor survival predictors.
Lung Cancer 2003 May
PMID:Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types. 1271 Nov 14

To investigate the role of tobacco and some other known or suspected factors responsible for the risk of developing adenocarcinoma of the lung, and to compare with other cell types (squamous-, small- and large-cell cancers) in Czech women, we conducted a case-control study. Data collected by personal interviews from 145 cases of adenocarcinoma of the lung, 221 lung cancer cases of other cell types, and 1624 controls were analyzed using unconditional logistic regression. Cigarette smoking was the main determinant of all major cell types of lung cancer among Czech women, its effect was weaker on adenocarcinoma than on squamous-, small- and large-cell cancers. Among never smokers, passive smoking in childhood (before age 16) did not significantly increase the risk of adenocarcinoma (OR=1.35, 95%CI 0.75-2.45), contrasting with an elevation in the risk of squamous-, small- and large-cell cancers combined (OR=2.10, 95%CI 1.02-4.33). Excess risk associated with consumption of red meat daily or several times per week (OR=1.81, 95%CI 1.04-3.18) was restricted to squamous-, small- and large-cell cancers combined. Wine drinking, at higher frequency than once per month, was inversely associated with the risk of adenocarcinoma (OR=0.46, 95%CI 0.23-0.92), however, not with squamous-, small- and large-cell cancers combined (OR=0.77, 95%CI 0.47-1.28). Inverse associations with the risk of squamous-, small- and large-cell cancers combined emerged for the quantity of menstrual flow (OR=0.63, 95%CI 0.40-0.99), and pains or mental tension related to menses (OR=0.61, 95%CI 0.42-0.89).
Lung Cancer 2003 Sep
PMID:Adenocarcinoma of the lung among women: risk associated with smoking, prior lung disease, diet and menstrual and pregnancy history. 1292 19

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.
Lung Cancer 2003 Nov
PMID:MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment? 1456 86

Bronchioloalveolar carcinoma of the lung (BAC) is a subtype of adenocarcinoma of the lung. Although traditionally grouped with other non-small cell lung carcinomas (NSCLC), BAC has unique morphological features and clinical behavior such as bilateral lung involvement, indolent course and lack of association with smoking. Some epidemiologic studies report a significant increase in the incidence of BAC. We used the SEER database to compare the incidence, demographics, and overall survival of BAC patients as compared to other NSCLC types over the past two decades (1979-1998). Although the incidence of BAC has increased over the past two decades, BAC represents less than 4% of all NSCLC in every time period evaluated. The 1 year survival rate is significantly better for BAC patients relative to other histological subtypes of NSCLC. There has not been a marked increase in the incidence of BAC reported to SEER over the past 20 years.
Lung Cancer 2004 Aug
PMID:The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database. 1524 83

We herein report a case of metastasis to the thyroid from lung adenocarcinoma mimicking thyroid carcinoma. The thyroid tumor was palpated in the left lobe of the thyroid and diagnosed as primary thyroid carcinoma by fine-needle aspiration cytology. The patient also had a large pulmonary tumor and tiny pulmonary nodules, which were respectively diagnosed as moderately differentiated adenocarcinoma of the lung and intrapulmonary metastases from the main large lung carcinoma by the pathological examination of the biopsy specimens obtained by video-assisted thoracic surgery. Hemithyroidectomy with radical neck dissection was performed. The thyroid tumor was diagnosed as metastasis to the thyroid from lung adenocarcinoma, because it showed mucin production, positive immunoreactivity for carcinoembryonic antigen and negative immunoreactivities for thyroglobulin and calcitonin. The patient received systemic chemotherapy and died of the disease 1 year and 7 months after the diagnosis was made.
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PMID:Metastasis to the thyroid from lung adenocarcinoma mimicking thyroid carcinoma. 1529 34

DNA methylation markers provide a powerful tool to make diagnoses based on genetic material obtained directly from tumors or from "remote" locations such as sputum, pleural fluid, or serum. In particular when limited cell numbers are available, amplifyable DNA markers can provide a very sensitive tool for cancer detection and classification. Malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, can be difficult to distinguish from adenocarcinoma of the lung when limited material is available. In an attempt to identify molecular markers for MM and adenocarcinoma, we examined the DNA methylation status of 14 loci. Analysis of methylation levels in 10 MM and 8 adenocarcinoma cell lines showed that methylation of APC was significantly elevated in adenocarcinoma compared to MM cell lines (P=0.0003), while methylation of CDH1 was higher in MM (P<0.02). Subsequent examination of the methylation status of the 14 loci in 6 MM and 7 adenocarcinoma primary tumors, which yielded similar methylation profiles, supported these observations. Comparison of methylation in MM cell lines and tumors versus non-tumor lung tissue indicated that APC exhibits less methylation in MM (P=0.003) while RASSF1, PGR1, ESR1, and CDH1 show more methylation in MM, the latter two showing the most significant difference between the two tissue types (P< or = 0.0001). Comparison of methylation in adenocarcinoma cell lines and tumors versus non-tumor lung tissue showed methylation of ESR1, PGR1 and RASSF1 to be significantly elevated in adenocarcinoma, with RASSF1 being most significant (P=0.0002). Thus, with the examination of 14 loci, we have identified 5 candidates that show potential for distinguishing between MM, adenocarcinoma and/or non-cancer lung. Our observations support the strong potential of methylation markers as tools for accurate diagnosis of neoplasms in and around the lung.
Lung Cancer 2005 Feb
PMID:Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung. 1563 18

Although the most frequently altered oncogenes and tumor suppressor genes in non-small cell lung carcinoma (NSCLC) have been recognized, the exact mechanisms responsible for the progression and phenotypic expression of carcinoma, particularly adenocarcinoma of the lung are uncertain. Fifty-six cases of adenocarcinoma of the lung (11 bronchioloalveolar carcinoma [BAC], 25 stage 1, 20 stage 2) and paired 19 lymph node metastases (LNM) of stage 2 adenocarcinomas were analyzed for loss of heterozygosity (LOH). Analysis included a panel of 14 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 10q, and 17p. LOH on chromosomes 1p (P = 0.0209) and 17p (P = 0.0274) was more frequently present in stage 1 adenocarcinomas than in BAC. There was no significant difference between BAC, stage 1 and stage 2 adenocarcinoma in the frequency of LOH at individual chromosomal arms. The pattern of LOH in LNM of stage 2 adenocarcinoma was similar to the primary tumor. Overall fractional allelic loss (FAL) was significantly different between BAC and stage 1 invasive adenocarcinoma (P = 0.0013), and it was significantly higher in stage 1 adenocarcinoma than in stage 2 adenocarcinoma (P = 0.0062) and their LNM (P = 0.0001). Stage 2 adenocarcinomas showed significantly higher overall FAL than their LNM (P = 0.022). Our study failed to identify a single target gene responsible for progression of lung adenocarcinoma. A trend towards lower overall FAL in advanced stage tumors and in their metastases suggests that clonal selection may play a role in lung adenocarcinoma progression.
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PMID:Clonal selection of adenocarcinoma of the lung as determined by loss of heterozygosity. 1571 39

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.
Lung Cancer 2005 Jun
PMID:Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis. 1589 2

The protein-kinase family is the most frequently mutated gene family found in human cancer. Gefitinib, an ATP-competitive inhibitor of epidermal growth factor receptor (EGFR), also appears to be particularly effective in adenocarcinoma of the lung and in patients without smoking history. To determine whether lung tumors sensitive to gefitinib contained mutations within the tyrosine kinase (TK) domain of EGFR, we screened exons 18-23 of EGFR of tumors in 20 patients with non-small cell lung cancer (NSCLC) who had been treated with gefitinib. Nine (45%) tumors had TK domain mutations. All mutations were observed in adenocarcinoma. Seven (77.8%) of 9 cases with mutated types showed sensitivity to gefitinib, while no cases of 11 with wild type showed gefitinib sensitivity. Such mutations were more frequently observed in patients who had never smoked (5/8 or 62.5%) than in smokers (4/12 or 33.3%). The patients with mutations of EGFR to have a more favorable prognosis than those with wild type (p=0.033). These data show that adenocarcinomas from patients who had never smoked comprise a specific subset of patients with NSCLC sensitive to gefitinib treatment.
Lung Cancer 2006 Jan
PMID:Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese. 1619 42


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