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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the diagnostic usefulness of measurement of the soluble cytokeratin 19 fragment, a new tumor marker, in 391 patients with lung cancer and in 424 patients with benign lung diseases. Serum concentrations of cytokeratin 19 fragment were measured by a sandwich ELISA (CYFRA). The cut-off value was defined as 3.5 ng/ml, which is associated with a specificity of 85% for benign lung diseases. CYFRA had a high sensitivity (57.5%) in all subjects with lung carcinoma, and had a higher sensitivity for squamous cell carcinoma (73.1%, n = 141) than squamous cell carcinoma-related antigen (61.0%). CYFRA was associated with a relatively high sensitivity (42.1%) in early-stage squamous cell carcinoma (stage I, based on the classification of the Japan Lung Cancer Society), but the CYFRA titer was higher in advanced squamous cell carcinoma than in early-stage squamous cell carcinoma. Our findings suggest that CYFRA is potentially useful for diagnosis and monitoring of lung carcinoma, especially for squamous cell carcinoma.
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PMID:Clinical usefulness of CYFRA assay in diagnosing lung cancer: measurement of serum cytokeratin fragment. 753 Feb 41

We developed a new and automated assay for the detection of lung cancer associated cytokeratin 19 fragments in patients' sera/plasma. This new tumour marker assay CYFRA 21-1 was evaluated in technical and clinical studies using the multibatch analysers ES 300 and ES 600 from Boehringer Mannheim GmbH. The analytical performance was shown to be excellent. The clinical data from 2,037 patients demonstrate that for non-small-cell lung carcinoma CYFRA 21-1 has a higher diagnostic sensitivity compared to the established markers. Mainly for squamous cell carcinoma CYFRA 21-1 was superior (60%) to CEA (18%) or SCC (31%).
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PMID:Cytokeratin 19 fragments: a new marker for non-small-cell lung cancer. 769 15

A new human cancer cell line was established from a metastatic lesion of a small cell lung carcinoma (SCLC-R1) and maintained in continuous culture with a doubling time of 62 h. The SCLC-R1 line, whose ultrastructural features are presented, showed a diploid DNA content, a translocation involving chromosome 16 [t(16;?)(q24;?)] and noticeable deletions in the FHIT (fragile histidine triad) region in the short arm of chromosome 3 [del(3)(p14)] and in the telomeric region of the short arm of chromosome 12 [del(12)(p13)]. The involvement of 12p in metastatic small cell lung cancer is reported here for the first time. No amplification or rearrangements were evident in the c-myc, L-myc, N-myc, int-2, c-erbB-2, H-ras, K-ras, c-mos, and hst-1 genes by Southern blot analysis. Wild-type p53, RB, K-ras and H-ras genes were evident by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. The neuron specific enolase (NSE) level was much higher in the cell line's cytosol than in the patient's serum and the cell line also had high expression of chromogranin A and cytokeratin 19. SCLC-R1 cells were sensitive to cisplatin, carboplatin and doxorubicin. The clinical history of the patient from whom the cell line was derived is reported. The characteristics of this new cell line indicate it to be a useful experimental model to investigate lung cancer biology and anticancer drug response.
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PMID:Chromosomal alterations, biological features and in vitro chemosensitivity of SCLC-R1, a new cell line from human metastatic small cell lung carcinoma. 971 81

Cytokeratin 19 is particularly abundant in carcinoma of the lung. The CYFRA 21-1 assay has recently been developed for detection of a cytokeratin 19 fragment in serum. In the current study, the prognostic information provided by the CYFRA 21-1 assay in operable nonsmall cell lung cancer (NSCLC) was analysed. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (DiaSorin) in 94 patients with operable NSCLC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. Elevated preoperative CYFRA 21-1 levels were identified in 42% of patients with NSCLC. The number of patients with elevated levels of this marker increased with tumour node metastasis (TNM) stage (p=0.02). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (p<0.001) and with disease-free survival (p<0.001). The results remained significant when the comparisons were adjusted, using the stratified log-rank test, for patient's TNM stage (p<0.001 for both overall and disease-free survival). Elevated preoperative levels of CYFRA 21-1 decreased the probability of survival or surviving without recurrence 15 months or more after the operation. This was confirmed by the results of the multivariate analysis. In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in nonsmall cell lung cancer and may be useful in identifying resected cancer patients at high risk for treatment failure.
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PMID:Preoperative CYFRA 21-1 level as a prognostic indicator in resected nonsmall cell lung cancer. 987 3

The CYFRA 21-1 assay which detects cytokeratin 19 (CK19) fragment is widely used as a tumor marker for lung cancer. However, the reason why some lung cancer cell lines release CK19 fragment in culture supernatants and others do not, remains unclear. It was hypothesized that the release of CK19 fragment may be elucidated by the expression of mRNA for CK19. In order to prove this, the mRNA for CK19 was quantitatively evaluated by the competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR). The level of CYFRA 21-1 in the culture supernatant was measured by an immunoradiometric assay. CK19 protein synthesis was evaluated by a Western blotting and immunohistochemistry. Fourteen lung cancer cell lines were evaluated, and the amount of mRNA correlated well with the level of CYFRA 21-1 in culture supernatants. Analysis of genomic DNA for CK19 demonstrated that three cell lines which could not produce CYFRA 21-1, conjectured that some abnormalities in exon 1 or the 5'-region upstream from exon 1. In conclusion, it was demonstrated that the release of CK19 fragment was closely related to the expression of mRNA for CK19, and the possibility that genomic change of CK19 DNA down-regulated the expression of mRNA for CK19 was suggested.
Lung Cancer 2000 Oct
PMID:Mechanisms of the release of CYFRA21-1 in human lung cancer cell lines. 1100 10

Cyfra 21-1 is a tumor marker based on the determination of water-soluble cytokeratin 19 which is secreted by normal or malignantly transformed epithelial cells. It is suggested to be a valuable marker in patients with non-small cell lung carcinoma (NSCLC). A prospective clinical study was conducted to investigate the value of Cyfra 21-1 for diagnosis, determination of subtypes, staging, and evaluation of therapy response in patients with lung carcinoma (Ca). Sixty-nine patients (mean age: 60.9 +/- 9.2 years, M/F:12.8) treated between 1994 and 1998 inclusive, and 13 healthy smokers (mean age:50.9 +/- 4.8 years, M/F:1.6) constituted the study group and control group, respectively. Venous blood samples (10 ml) were obtained from all subjects. Posttreatment blood samples were also obtained from 14 NSCLC patients. Cyfra 21-1 levels (cutoff value 3.3 ng/ml) were determined by ELSA-Cyfra 21-1 kit (CIS bio international, France) through immunoradiometric assay (IRMA). Cyfra 21-1 levels did not differ between smoking and non-smoking subjects within each group (p > 0.05). Cyfra 21-1 was significantly elevated in lung Ca cases irrespective of the cell type (p < 0.05). It was significantly elevated in squamous cell and adenocarcinoma varieties with the most prominent elevation in squamous cell type (p < 0.05). In lung Ca, the specificity and sensitivity of Cyfra 21-1 was 92.3% and 52.2%, respectively. Sensitivity was 65.5% for NSCLC, 70.5% for squamous cell, and 45.5% for adenocarcinoma varieties, with highest sensitivity rates in Stage IIIA + IIIB (87.5%) and Stage IV (75%) of squamous cell lung Ca. Cyfra 21-1 level was significantly decreased after treatment in NSCLC patients (n 14) (p < 0.01). Cyfra 21-1 is a tumor marker that helps to establish the diagnosis and differentiation of cell type and evaluation of response to therapy in patients with NSCLC.
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PMID:Evaluation of Cyfra 21-1: a potential tumor marker for non-small cell lung carcinomas. 1147 94

The CYFRA 21-1 assay which detects the cytokeratin 19 (CK19) fragment is widely used as a tumor marker for lung cancer. We previously suggested that the failure of PCR amplification of exon 1 is closely related to the inability of the expression of mRNA for CK19, and hypothesized that point mutations might exist within exon 1. In order to prove this, sequence analysis of the promoter region and exon 1 was performed in 14 human lung cancer cell lines. Among the 14 lung cancer cell lines evaluated, point mutations within the promoter region (at -99, G-->C) of the CK19 gene were demonstrated in two cell lines (Lu135 and HI1017). In addition, point mutations within exon 1 (at 90, T-->C, Ala-->Ala and at 179, G-->C, Gly-->Ala) were also demonstrated in three cell lines (LU135, HI1017, and LC2/AD). Point mutations within the promoter region of CK19 (at -99) and within exon 1 (at 179) were confirmed by analysis of digestion by specific restriction enzymes. Since the same point mutation within exon 1 (at 179) was observed in genomes of normal volunteers, this mutation was considered as a single nucleotide polymorphism. In contrast, there were no mutations within the promoter region of exon 1 in genomes of normal volunteers. After a computer search, it was demonstrated that several transcription factors bind to the sense primer sequence which was designed for amplification of exon 1. In addition, after point mutations within the promoter region occurred (at -99), new sequences appeared to which known transcription factors (AP2) bind. In conclusion, analysis of genomic DNA for CK19 suggested that expression of mRNA for CK19 was regulated by several transcription factors which bound to the specific sequence with the promoter region of the CK19 gene. It was also suggested that the mutation in the promoter region of the CK19 gene down-regulated the expression of mRNA for CK19.
Lung Cancer 2001 Dec
PMID:The point mutation in the promoter region and the single nucleotide polymorphism in exon 1 of the cytokeratin 19 gene in human lung cancer cell lines. 1171 36

Lung tumor markers fall into several categories including oncofetal proteins, structural proteins and their fragments, enzymes, membrane antigens, peptide and non-peptide hormones. Cytokeratins (CK) are well known structural proteins whose degradation gives rise to soluble fragments, measurable in the blood of patients and capable of cancer marking. Among them, Tissue Polypeptide Antigen (TPA), Tissue Polypeptide-Specific Antigen (TPS) and Cytokeratin-19-Fragments (Cyfra 21-1) are the most studied CK fragments' complexes. This article will review biological characteristics and clinical properties of these substances, emphasizing as their concentration in the peripheral blood might reflect the mass of tumor, the rate of cancer cell lysis, and other potentially unfavorable tumor characteristics. Assaying the concentration of CK fragments in the blood is an easy and effective way to assess lung cancer and monitor its clinical evolution.
Lung Cancer 2001 Dec
PMID:Lung tumor markers of cytokeratin origin: an overview. 1172 Jul 44

In small-cell lung carcinoma (SCLC) tumour cell contamination of leukaphereses is unknown. The present study was performed to define appropriate markers for reverse transcriptase polymerase chain reaction (RT-PCR), then to assess the contamination rate of leukaphereses and corresponding bone marrow samples. Immunocytochemistry (ICC) and RT-PCR methods were also compared. Among the 33 patients included, analyses were performed in 16 who had multiple leukaphereses and 17 who had only bone marrow. Leukapheresis products and bone marrow were analysed by ICC using several specific monoclonal antibodies against neural-cell adhesion molecule (N-CAM), epithelial glycoprotein (EGP-40) and cytokeratins (CK). Samples were also analyzed by RT-PCR for expression for N-CAM, synaptophysin, neuron-specific enolase, chromogranin, cytokeratin-18/-19, CEA, EGP-40, apomucin type 1 (MUC-1) and human endothelial cell-specific molecule (ESM-1). Using ICC staining, contaminating tumour cells were detected in 34% of leukaphereses (27% in patients with limited disease and 43% in those with extensive disease). N-CAM was the most reliable marker for detection of contamination. For RT-PCR, CK-19 and CEA were the only appropriate markers. Positive signal rate in leukaphereses increased to 78% (89% for patients with limited disease and 67% for extensive disease). In bone marrow, both techniques were in agreement whereas in leukaphereses, RT-PCR was better than ICC. A high rate of tumour cell contamination was demonstrated not only in bone marrow but also in leukaphereses from SCLC patients. The most appropriate technique was RT-PCR mainly in patients with limited disease.
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PMID:High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR. 1174 93

This retrospective study aimed at determining the prognostic significance of neuroendocrine markers chromogranin A (CgA), pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE), together with the cytokeratin 19 marker CYFRA 21-1 in small cell lung cancer (SCLC). A total of 148 histologically proven and previously untreated SCLC patients were included. Among them 118 patients received a cisplatin-etoposide combination or cisplatin-etoposide-cyclophosphamide-4'-epidoxorubicin combination. All tumour markers were tested using immunoradiometric assays except for ProGRP which was tested using an enzyme-linked immunosorbent assay. The thresholds for marker serum titrations were 53 pg/ml, 65, 17, and 3.6 ng/ml for ProGRP, CgA, NSE and CYFRA 21-1 respectively. Univariate analysis showed that patients affected by one of the following characteristics proved to have a significant shorter survival in comparison with the opposite status of each variable: age over 63 years, extensive-stage, serum LDH level higher than 600 U/l, serum NSE level higher than 17 ng/ml, serum CgA level higher than 65 ng/ml and serum CYFRA 21-1 level higher than 3.6 ng/ml. In addition, there was a trend towards a statistical significance for a high serum alkaline phosphatase level and a performance status equal to or worse than two. The following variables were independent determinants of a poor outcome: a poor performance status (hazard ratio [95% confidence interval]: 1.51 [1.02-2.22]), a high CgA level (HR: 1.61 [1.06-2.45]), a high CYFRA 21-1 level (HR: 2.10 [1.40-3.14]) and an age older than 63 years (HR: 1.68 [1.14-2.48]). When the multivariate analysis was restricted to patients receiving a cisplatin-etoposide-based chemotherapy, the same variables were prognostic determinants with nearly similar hazard ratios. In conclusion, aside classical variables such as age and performance status, high serum CYFRA 21-1 and high serum CgA level in SCLC are both prognostic determinants of prognosis, in particular in patients receiving conventional chemotherapy consisting of cisplatin and etoposide-based combinations.
Lung Cancer 2003 Feb
PMID:Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer. 1258 64


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