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      Enzyme‐linked Immunosorbent Assay of Pro‐gastrin‐releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron‐specific Enolase Measurement

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          Abstract

          Our previous study demonstrated that pro‐gastrin‐releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme‐linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non‐SCLC patients and patients with non‐tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron‐specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.

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          Most cited references9

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer.

            Serum neuron-specific enolase (NSE) levels in 94 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with those in 30 adult controls. 38 of the SCLC patients had limited disease and 56 had extensive disease. Serum NSE was raised (greater than 12.0 ng/ml) in 69% of all patients (mean 52.35 +/- 11.56, range 4.1-850 ng/ml); it was raised in 15/38 (39%) of patients with limited stage disease and in 49/56 (87%) of those with extensive stage disease. Extensive stage patients had significantly higher mean NSE level (59 ng/ml) than did limited stage patients (13.8 ng/ml). Serum NSE was raised in 34/41 (84%) of patients with metastases at 1 or 2 sites and in all patients with metastases at 3 or more sites. Serial measurements in 23 patients receiving combination chemotherapy showed an excellent correlation between serum NSE and clinical response. Continuous cell-lines of SCLC, established from 10 of the patients in this study, all expressed high levels of NSE. These studies indicate that serum NSE may be a useful marker for staging and for monitoring response to therapy in patients with SCLC.
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              Pro-gastrin-releasing peptide(31-98) is a specific tumor marker in patients with small cell lung carcinoma.

              Gastrin-releasing peptide (GRP) is a specific and an actively secreted product of small cell lung carcinoma (SCLC) cells. Based on this observation, we attempted to develop a new approach for early detection of SCLC and for monitoring therapeutic response in SCLC patients. Recombinant human ProGRP(31-98), a region common to three types of human ProGRP molecules, was synthesized, and a convenient radioimmunoassay system was developed; in this assay, the minimum detectable amount in serum was 10 pM when 0.1 ml of unextracted serum was used. Serum levels of immunoreactive ProGRP(31-98) were measured in 247 normal subjects, 180 patients with nonmalignant pulmonary diseases, 231 patients with non-SCLC, and 140 patients with SCLC. The percentages of subjects with the level greater than 10 pM in normal subjects and patients with nonmalignant pulmonary diseases and with non-SCLC were 1.2, 2.2, and 3.0%, respectively. In contrast, 76% of patients with SCLC had elevated levels; the positive rates in SCLC patients with limited and extensive diseases were 73 and 79%, respectively, indicating that the serum Pro-GRP(31-98) level could serve as a reliable tumor marker in SCLC patients, even at a relatively early stage of this disease. Moreover, changes in the serum ProGRP(31-98) showed excellent correlation with the therapeutic responses in SCLC patients. These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.
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                Author and article information

                Journal
                Jpn J Cancer Res
                Jpn. J. Cancer Res
                10.1111/(ISSN)1349-7006a
                CAS
                Japanese Journal of Cancer Research : Gann
                Blackwell Publishing Ltd (Oxford, UK )
                0910-5050
                1876-4673
                July 1995
                : 86
                : 7 ( doiID: 10.1111/cas.1995.86.issue-7 )
                : 698-705
                Affiliations
                [ 1 ]Growth Factor Division, National Cancer Center Research Institute, 5‐1‐1 Tsukiji, Chuo‐ku, Tokyo 104
                [ 2 ]Research & Development Laboratory, Tonen Corporation, 1‐3‐1 Nishitsurugaoka, Ohi‐machi, Irumagun, Saitama 356
                [ 3 ]Research and Development Center, Terumo Corporation, 1500, Inokuchi, Nakaimachi, Ashigarakami‐gun, Kanagawa 259‐01
                [ 4 ]Department of Internal Medicine, National Cancer Center Hospital East, 6‐5‐1 Kashiwanoha, Kashiwa‐shi, Chiba 277
                Author notes
                [*] [* ]To whom all correspondence should be addressed.
                Article
                CAE698
                10.1111/j.1349-7006.1995.tb02455.x
                5920889
                7559089
                d36809ac-2d8a-48db-b7c7-ef6aba0aee24
                History
                Page count
                References: 13, Pages: 8
                Categories
                Article
                Custom metadata
                2.0
                July 1995
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.6.9 mode:remove_FC converted:04.11.2015

                gastrin‐releasing peptide,pro‐gastrin‐releasing peptide(31‐98),small cell lung carcinoma,elisa,tumor marker

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