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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jaagsiekte retrovirus (JSRV) causes ovine pulmonary adenomatosis (OPA) that resembles bronchioloalveolar carcinoma (BAC) in humans. To test the possible role of JSRV in human diseases, DNA specimens from 103 individuals either healthy or suffering from lung carcinomas were analyzed for JSRV sequences. orf-x sequences were detected in 19 of 64 samples and gag-prt sequences in 4 of 38 samples, predominantly in individuals from Africa. Sequences obtained from orf-x amplimers varied in-between each other and differed from control endogenous ovine JSRV sequence. No association with lung cancer was found. This is the first report of JSRV-like sequences detected in humans.
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PMID:Detection and characterization of betaretroviral sequences, related to sheep Jaagsiekte virus, in Africans from Nigeria and Cameroon. 1535 Dec 3

Using the "one-bead one-peptide" combinatorial technology, a library of random cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino acids, was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment and proliferation of bronchioloalveolar carcinoma cells (H1650), employing a "cell growth on bead" assay. Consensus peptide sequences of cNleDXXXXc and cXNleDXXXXc (where Nle is norleucine) were identified. With alanine scanning and site-directed deletion, a typical ligand consisted of a motif of -NleDI/V/Nle- with two flanking cysteines. These peptide ligands were specific for promoting cell attachment of the H1650 cells and the cells of lymphoid cancers (Jurkat and Raji) but not other selected human cell lines of lung cancer and fibroblast. In an antibody blocking assay, integrin alpha(4)beta(1), which was overexpressed in H1650, Jurkat, and Raji, was identified as a putative receptor for these peptide ligands. Using Chinese hamster ovary cells transfected with either wild-type or mutant integrin alpha(4), a critical binding site for these peptides was localized to the glycine residue at position 190 of integrin alpha(4).
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PMID:Novel peptide ligands for integrin alpha 4 beta 1 overexpressed in cancer cells. 1548

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) have recently been described in patients with non-small-cell lung cancer (NSCLC) who achieve radiographic regressions to the EGFR inhibitor gefitinib. One of these mutations, L858R (Leu-->Arg), is also found in NSCLC cell line H3255, which is very sensitive to gefitinib treatment. We characterized nine NSCLC cell lines (three isolated from patients with bronchioloalveolar carcinoma and six isolated from patients with adenocarcinoma) for their in vitro sensitivity to gefitinib. Of these, only H3255 (EGFR(L858R)) and H1666 (EGFR(WT)) are sensitive to gefitinib with IC(50) values of 40 nmol/L and 2 micromol/L, respectively. We examined the effects of gefitinib on H3255 and cell lines containing wild-type EGFR that are either sensitive (H1666) or resistant (A549 and H441) to gefitinib exposure in vitro. Gefitinib treatment (1 micromol/L) leads to significant apoptosis accompanied by increased poly(ADP-ribose) polymerase cleavage only in the H3255 cell line, leads to G(1)-S arrest in H1666, and has no effects in the A549 and H441 cell lines. Although EGFR and AKT are constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is completely inhibited by gefitinib treatment only in the H3255 cell line. These findings further characterize a mechanism by which gefitinib treatment of NSCLC harboring EGFR(L858R) leads to a dramatic response to gefitinib.
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PMID:Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. 1549 41

Lung cancer, a highly lethal malignancy, is the leading cause of cancer-related mortality in the US, accounting for 28% of all deaths related to cancer. Non-small cell lung cancer comprises 80-85% of lung cancer diagnoses and includes the histologies of adenocarcinoma and its subtype bronchoalveolar carcinoma, squamous cell carcinoma and large cell carcinoma. This article reviews the use of cytotoxic chemotherapies and other systemic treatments for patients with advanced (metastatic and/or recurrent) non-small cell lung cancer. Despite great efforts, only minor gains have been made over the past decade in the treatment of advanced non-small cell lung cancer for patients with a good performance status in terms of prolonging survival and improving quality of life. Currently, the standard of treatment is a platinum-based doublet, with the second agent being selected contingent upon the comorbidities of the patient and the toxicity profile of the drug. The focus of clinical research is centered on the application of the use of targeted, molecularly directed therapies, likely used in combination with either cytotoxics and/or other novel targeted agents, in an attempt to improve the therapeutic ratio of systemic treatments for this large population.
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PMID:Systemic treatment of advanced non-small cell lung cancer. 1551 Feb 41

Cadherins are Ca(2+-)dependent cell-cell adhesion molecules which interact with intracellular proteins called catenins. Cadherins are the most interesting adhesion molecules and among them most important is epithelial E-cadherin. Loss of the function or/and the expression of any of the elements of E-cadherin/catenins complex make the cell incapable to adhere resulting to a loss of the normal architecture of tissues. Reduced, absent or disorganised expression of E-cadherin has been found in several carcinomas, including lung cancer. Soluble E-cadherin found in serum from patients with lung cancer could be a tumor marker, while alterations observed in non-small cell lung cancer probably play a role in manifestation of a malignant phenotype. Reduced expression of E-cadherin is a key event in tumorgenicity and metastasis and possible therapeutic strategies are based on that conclusion. In addition, E-cadherin has a role as a marker of differential diagnosis between bronchioloalveolar carcinoma and conventional pulmonary carcinoma as well as between mesothelioma and metastatic pulmonary adenocarcinoma. Small cell lung cancer cells express several types of cadherins too. In conclusion, many studies are in process and it is very possible that soon some cadherins will be used as useful biomarkers and theraupeutic targets in cases of primary lung cancer.
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PMID:Cadherin superfamily of adhesion molecules in primary lung cancer. 1562 55

Erlotinib (OSI-774; Tarceva) is an orally available, highly specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The results of 3 phase II studies with erlotinib in non-small-cell lung cancer (NSCLC) are reviewed herein: (1) in patients with chemotherapy-resistant, HER1/EGFR-expressing NSCLC of all histologies, (2) in patients with bronchoalveolar carcinoma previously untreated or treated with chemotherapy, and (3) as first-line therapy in elderly patients with NSCLC of all histologies. These studies have evaluated tumor response, survival, and symptom improvement. Erlotinib was given as an oral, continuous daily dose of 150 mg. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in approximately two thirds of patients. Withdrawals caused by toxicity were rare. The response rates were 12.3%, 25%, and 13.3%, respectively. Mature survival data are available for the first trial. The median survival was 8.4 months, and the 1-year survival rate was 40%. All responding patients in the first and second trials presented skin rash. In addition, survival correlated with the occurrence and severity of rash in the first trial. No data on the correlation between rash and survival are available for the second and third trials. Erlotinib is active and well tolerated in patients with NSCLC as first- and second-line therapy. Cutaneous rash appears to be a surrogate marker of clinical benefit, but this finding needs to be confirmed in ongoing and future studies.
Clin Lung Cancer 2004 Dec
PMID:Phase II clinical trial data with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) in non-small-cell lung cancer. 1563 53

Besides gastrointestinal hamartomatous polyposis and melanin spots in the skin and mucosa, patients with the Peutz-Jeghers syndrome (PJS) have repeatedly been observed with a variety of tumours, including lung cancer. Available data indicate an increased cancer risk among PJS patients, which suggests that the gene involved in PJS, STK11 on chromosome 19p13.3, may be a tumour suppressor gene. Herein, bronchioloalveolar carcinoma (BAC) of mucinous type is reported in a 22-year old male PJS patient with a novel germline frameshift insertion in exon 2 at codon 118 of the STK11 gene. Molecular studies of his BAC indicated loss of heterozygosity (LOH) in the region of STK11 on chromosome 19p13.3. This observation supports the hypothesis that STK11 is a tumour suppressor gene which is involved in the development of lung adenocarcinoma.
Lung Cancer 2005 Feb
PMID:Bronchioloalveolar carcinoma: a new cancer in Peutz-Jeghers syndrome. 1563 28

Using 32 small adenocarcinomas of the lung including bronchioloalveolar carcinoma (BAC), the reproducibility of diagnosis by the modified diagnostic criteria for small adenocarcinoma (Cancer 75; 2844, 1995) and the effectiveness of an educational program for 27 volunteer general pathologists were examined. The average coincidence rate of the diagnosis before and after the program was 42.4% and 56.6%, respectively. The coincidence rate after the program was significantly higher than that before the program (P < 0.05). In contrast, the average coincidence rate of six lung cancer specialists was 71.4%, and this was significantly higher than that for general pathologists after the program (P < 0.05). When the cases were divided into two groups (in situ adenocarcinoma (BAC and BAC with alveolar collapse) and early invasive adenocarcinoma), the average coincidence rate for the general pathologists after the program increased to 85.3%, which was significantly higher than that before the program (80.3%; P < 0.05). The rate for the specialists was 89%, which was higher than that for the general pathologists after the program but not significantly so. This trial was thought to provide a theoretical background for the histological diagnosis of peripheral type adenocarcinoma of the lung and to justify the existing diagnostic criteria.
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PMID:Reproducibility of the diagnosis of small adenocarcinoma of the lung and usefulness of an educational program for the diagnostic criteria. 1566 Jun 97

In clinical trials, response rate is an important endpoint for assessing the efficacy of an anticancer drug. The Response Evaluation Criteria for Solid Tumors (RECIST) has been widely used as a standard method to assess response. The RECIST requires only 1-dimensional measurement of tumor size. However, bronchioloalveolar carcinoma (BAC), which commonly presents as infiltrative or micronodular lesions, is not always readily assessable by RECIST. During the past 2 years, we have been developing computer-based programs to more accurately measure tumor size on chest computed tomography (CT) scans. In a first-generation computer-assisted image analysis (CAIA) system, we were able to capture and quantify lesions on CT scans by linking the software programs of eFilm, HyperSnap, and Scion. We have applied this CAIA approach to measuring BAC response to gefitinib in the Southwest Oncology Group (S0126) trial. However, this first-generation CAIA system involves multiple manual steps and is therefore labor intensive. We are now developing a fully automated CAIA program based on a versatile software platform, ImageJ, created at the National Institutes of Health. Taking theoretical and physical considerations into account, Java plug-in programs for ImageJ are created to automatically analyze CT scans in the Digital Imaging and Communications in Medicine format. We have demonstrated the feasibility of an ImageJ-based automated CAIA program for measuring BAC bidimensionally on CT scans. This automated CAIA system will be applied in a prospective clinical trial of the GVAX vaccine in patients with BAC.
Clin Lung Cancer 2005 Mar
PMID:Computer-assisted image analysis of bronchioloalveolar carcinoma. 1584 78

We retrospectively analysed the results of patients with advanced non-small-cell lung cancer treated with gefitinib to derive clinical factors predictive of response and a favourable survival outcome. Patients were treated with gefitinib 250 mg per day and re-evaluated 4-8 weeks later with repeat CT scan and every 8 weeks thereafter to assess response and the duration of response. Pathology review by a histopathologist was conducted, in particular to confirm a recently published result of bronchioloalveolar carcinoma histology or its components as predictive of response to gefitinib. Logistic regression and Cox regression analytical methods were applied to determine factors that could predict for response and improved overall survival. A total of 110 patients were treated. The overall response rate was 32% partial responses (PRs). Only never-smoking status was predictive of response in the logistic regression analysis, adjusted OR=6.1, 95% CI=1.7, 21.5. The presence of a PR and good performance status were predictive of a favourable survival outcome from the Cox regression modelling. Responders had an adjusted HR of 3.0, 95% CI=1.5-5.8 compared to nonresponders, while patients with ECOG status 0-1 had an adjusted HR of 0.42, 95% CI=0.25-0.72, compared with patients with ECOG status 2-4. Bronchioloalveolar carcinoma or its components were distinctly absent on pathology review. In conclusions, Never-smoking status is an important clinical predictor of a favourable response to gefitinib.
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PMID:Gefitinib is more effective in never-smokers with non-small-cell lung cancer: experience among Asian patients. 1594 27


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