Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the value of detection of 4 tumor markers(CEA, CA125, gastrin, and NSE) for histological types in patients with lung cancer and to improve the predicted efficiency of tumor markers for distinguishing between small cell lung cancer(SCLC) and non-small cell lung cancer (NSCLC), these 4 tumor markers in serum were determined in 51 patients (21 cases with SCLC, 30 cases with NSCLC) with confirmed primary diagnosis of lung cancer of different histology by radioimmunoassay. Linear learning machine method, PRIMA method and KNN method were used to classify SCLC and NSCLC. The levels of gastrin and NSE in SCLC were apparently higher than those of gastrin and NSE in NSCLC, but the levels of CEA and CA125 in SCLC were significantly lower than those in NSCLC. Smoking had an effect on the levels of CEA and CA125, but had little effect on those of gastrin and NSE. The total accuracy of the three methods was over 85% in distinguishing SCLC from NSCLC. So combined detection of the four tumor markers in serum might be useful in the prediction of histological types in patients with lung cancer.
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PMID:[Value of combined detection of tumor markers for the prediction of small cell and non-small cell lung cancer]. 1252 Sep 21

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

The ability of nonpeptide antagonists to interact with gastrin releasing peptide receptors on lung cancer cells was investigated. PD176252 (3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide) and PD168368 (3-(1H-Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide) inhibited specific 125I-gastrin releasing peptide binding to NCI-H1299 cells with IC50 values of 20 and 1500 nM, respectively. Similar binding results were obtained using NCI-H157, H345 and N592 human lung cancer cells. PD176252 inhibited the ability of 1 nM bombesin to cause elevation of cytosolic calcium in Fura-2 loaded NCI-H345 or H1299 cells, whereas it had no effect on basal cytosolic calcium. PD176252 antagonized the ability of 10 nM bombesin to cause elevation of c-fos mRNA in NCI-H1299 cells. Also, PD176252 inhibited the ability of 100 nM bombesin to cause tyrosine phosphorylation of focal adhesion kinase in NCI-H1299 cells. Using a [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, PD176252 was more potent than PD168368 at inhibiting NCI-H1299 proliferation. Also, 1 microM PD176252 significantly inhibited lung cancer colony number in vitro. PD176252 in a dose-dependent manner inhibited NCI-H1299 xenograft growth in nude mice in vivo. These results indicate that PD176252 is a gastrin releasing peptide receptor antagonist, which inhibits the proliferation of lung cancer cells.
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PMID:Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of lung cancer cells. 1290 92

The somatostatin analogue octreotide was the first radiopeptide to be used for the scintigraphic diagnosis of tumors. Somatostatin receptor scintigraphy (SRS) has proven its value, especially in the detection of gut neuroendocrine tumors. In some tumor types, it is considered the diagnostic gold standard. In carcinoid tumors of the lung, SRS is of major importance in diagnostic workup. Furthermore, the combination of computed tomography scanning and SRS is a reliable and cost-effective approach for the evaluation of single pulmonary nodules. Despite these favorable properties, SRS fails in the detection of metastases of lung cancer. The problem of false-positive results in SRS resulting from inflammatory disease might be overcome by the use of new radiopeptides such as cholecystokinin-B receptor-binding gastrin analogues. This article focuses on the current status of peptide-receptor scintigraphy in the diagnosis of lung tumors and on future developments in this field.
Clin Lung Cancer 2003 Sep
PMID:Imaging lung tumors with peptide-based radioligands. 1459 95

The less processed forms of gastrin have recently been shown to act as trophic factors for both normal and malignant colonic cells. Although incompletely processed forms of gastrin such as glycine-extended gastrin and progastrin are also expressed in human lung cancers, the clinical significance of this expression has not been addressed. Consequently, we investigated the effects of overexpression of glycine-extended gastrin in a mouse strain that is prone to developing lung cancer and also examined the expression of incompletely processed gastrins in primary human lung cancers. We found that transgenic overexpression of glycine-extended gastrin in FVB/N mice resulted in a significant increase in the prevalence and growth of bronchoalveolar carcinoma. In addition, a substantial subset of human lung cancers was found to express progastrin and/or glycine-extended gastrin. Overexpression of glycine-extended gastrin by human lung cancers was associated with a significantly decreased survival. Taken together, these results suggest that glycine-extended gastrin may play a role in the growth and progression of some human lung cancers.
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PMID:Glycine-extended gastrin promotes the growth of lung cancer. 1472 24

The insulinoma-associated 1 (INSM1) gene is expressed exclusively during early embryonal development, but has been found re-expressed at high levels in neuroendocrine tumors. The regulatory region of the INSM1 gene is therefore a potential candidate for regulating expression of a therapeutic gene in transcriptionally targeted cancer gene therapy against neuroendocrine tumors. We analyzed expression of a reporter gene from a 1.7 kb region of the INSM1 promoter in a large number of small-cell lung cancer (SCLC) cell lines. This INSM1 promoter region showed very high levels of expression in most of the SCLC cell lines and expression was absent in cell lines of non-neuroendocrine origin. Inclusion of the general transcriptional enhancer from SV40 compromised the specificity of the promoter and did not enhance transcription in most of the SCLC cell lines. For comparison, the region of the gastrin releasing peptide (GRP) previously suggested for SCLC gene therapy was analyzed in a similar manner. High expression was observed for a number of cell lines, but unlike for the INSM1 promoter, reporter gene expression from the GRP promoter did not correlate to the relative GRP mRNA levels, demonstrating that this region may not contain all necessary regulatory elements. Expression of the suicide gene herpes simplex virus thymidine kinase (HSV-TK) from the INSM1 promoter in combination with treatment with the prodrug ganciclovir (GCV) caused a significant increase in GCV sensitivity specifically in INSM1-expressing cell lines. The INSM1 promoter is therefore a potential novel tool for transcriptionally targeted gene therapy for neuroendocrine tumors.
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PMID:The insulinoma-associated 1: a novel promoter for targeted cancer gene therapy for small-cell lung cancer. 1605 25

Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.
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PMID:Peptide hormones and lung cancer. 1663 28

The effects of a bombesin/gastrin releasing peptide (BB/GRP) receptor antagonist, PD176252, and histone deacetylase (HDAC) inhibitor, MS-275, were investigated on human lung cancer cell lines. Using the MTT assay, PD176252 and MS-275 inhibited the proliferation of NCI-H1299 cells with IC50 values of 7 and 5 microg/mL, respectively. Using MS-275 and PD176252 together, the ability to inhibit lung cancer cellular growth increased significantly. The combination index for MS-275 and PD176252 was <0.2, indicating that the compounds are highly synergistic in inhibiting lung cancer cellular growth. Also, MS-275 and PD176252 together strongly inhibited the clonal growth of NCI-H345 or NCI-H1299 cells. MS-275 had little effect on the expression of lung cancer cellular GRP or GRP receptors, but increased expression of transforming growth factor-beta receptor II (TGF-beta RII). These results indicate that GRP receptor antagonists may potentiate the action of histone deacetylase inhibitors on lung cancer cellular proliferation by increasing expression of tumor suppressor genes.
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PMID:Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation. 1669 Oct 10

The aim of this study was to evaluate the individual diagnostic utility of tumour and inflammatory markers in patients with different pulmonary diseases. The usefulness of neuron-specific enolase (NSE), carcino-embryonic antigen (CEA), serum pro-gastrin releasing peptide (ProGRP) and CYFRA 21-1, as tumour markers, and C-reactive protein (CRP) and tumour necrosis factor-alpha (TNFalpha) as inflammatory markers for diagnosis, treatment and monitoring of patients with different pulmonary afflictions was investigated. Eighty healthy individuals were also included. Serum samples were also obtained from 20 patients suffering from bronchitis, 20 with lung fibrosis and 30 with sarcoidosis. Moreover, serum marker levels were analyzed in 139 patients with different pulmonary malignancies: 29 patients with adenocarcinoma, 30 patients with squamous cell carcinoma, 80 patients with small cell lung cancer (SCLC). All tumour markers showed significantly elevated values in malignant diseases. The levels of ProGRP in patients with benign diseases were significantly higher than those in the healthy group (35.4 +/- 6.6 compared with 21.3 +/- 9.2 pg/ml respectively). The serum ProGRP levels were elevated in SCLC patients (1673.9 +/- 706 pg/ml). The elevation was significantly higher than that of the benign reference group. The acute phase response had a wide range in patients with malignant tumours. Serum CRP levels were significantly higher in patients with SCLC (38.5 +/- 7.6 mg/dl) than in the benign reference group. In conclusion, when serum tumour markers are abnormally elevated in patients with lung cancer, CEA, CYFRA 21-1, NSE and ProGRP are useful clinical markers, good indicators of disease extent and may have important prognostic value. In particular, NSE and ProGRP have a very high sensitivity for SCLC detection.
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PMID:Value of tumour and inflammatory markers in lung cancer. 1764 94

The purposes of this study were to assess the relationship of serum levels of pro-gastrin-releasing protein (ProGRP) and neuron-specific enolase (NSE) at relapse with survival after relapse and the response to salvage therapy and to assess whether serum levels of ProGRP and NSE at relapse are useful markers for detecting relapse earlier than are symptoms or radiographic findings in patients with small-cell lung cancer (SCLC). The subjects of this study were 103 patients with SCLC who had achieved a complete response (CR) or partial response (PR) to first-line chemotherapy. We retrospectively evaluated whether ProGRP or NSE increased earlier than symptoms or radiographic findings appeared, and the association between response to salvage therapy and levels of ProGRP or NSE at relapse. In addition, we evaluated the association between survival after relapse and clinical and demographic factors at relapse, including age, sex, response to first-line treatment, sensitivity to first-line treatment, stage, performance status (PS), and serum levels of ProGRP, NSE, and lactate dehydrogenase. At relapse, 69.3% of patients had elevated serum levels of ProGRP, 60.2% had elevated serum levels of NSE, and 81.3% had elevated serum levels of either ProGRP or NSE. However, almost all asymptomatic relapses were detected with radiographic studies. The rate of CR to salvage chemotherapy was significantly lower in patients with elevated levels of NSE (2.2%) than in patients without (26.7%; p=0.001). Univariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, stage, and PS at relapse were prognostic factors for survival after relapse. Multivariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, and PS at relapse were independent prognostic factors after relapse. In conclusion, serum levels of ProGRP and NSE at relapse are not useful markers for detecting relapse earlier than are symptoms or radiographic findings. On the other hand, the serum level of NSE at relapse is a useful predictive marker for CR to salvage chemotherapy and a useful prognostic factor after relapse in patients with SCLC who have achieved a CR or PR to first-line chemotherapy.
Lung Cancer 2011 Feb
PMID:Are levels of pro-gastrin-releasing peptide or neuron-specific enolase at relapse prognostic factors after relapse in patients with small-cell lung cancer? 2053 24


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