gastrins and Carcinoma--Non-Small-Cell-Lung

As we expand our knowledge of the initiators and promoters of lung cancer, early detection and intervention strategies show great potential in individuals at high risk, especially smokers and exsmokers. Documented mutations of dominant oncogenes and tumor suppressor genes in human lung cancer cells may represent important steps in the pathogenesis of invasive cancer. The precise molecular events and their sequence that lead to tumor promotion in lung cancer, however, are less well understood. Chemointervention with agents like the retinoids may halt proliferation of cancer cells prior to the development of metastatic competence. Use of anti-growth-factor therapy and peptide hormone antagonists may also have a role in intervention approaches. This paper reviews present understanding of the initiation and promotion of lung cancer, as well as preventive strategies currently proposed for patients at risk.

Topics: Carcinogens; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Gastrin-Releasing Peptide; Gastrins; Genes, ras; Genes, Tumor Suppressor; Humans; Lung Neoplasms; Oncogenes; Peptides; Protein Processing, Post-Translational; Retinoids; Smoking; Tumor Cells, Cultured

Lung cancer is one of the most common cancer, there is a significant difference between the treatment and prognosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC tumor cells usually express neuroendocrine tumor (NET) markers, among which there are many studies on chromogranin A (CgA), synaptophysin (Syn), neuronspecific enolase (NSE) and pro-gastrin-releasing peptide (Pro-GRP) with SCLC. The levels of CgA, NSE and pro-GRP were related to the stage of SCLC, which were significantly higher in patients with extensive stage than in patients with limited stage, and their expression was significantly correlated with lower survival rate. Syn as an auxiliary diagnostic index of SCLC is more sensitive than CgA, and has high practical value in the differential diagnosis of SCLC and poorly differentiated squamous cell carcinoma; NSE is the most commonly used tumor marker in SCLC; Pro-GRP has stronger diagnostic advantages than CEA and NSE in distinguishing SCLC from NSCLC. Although these net markers are not specific markers of SCLC, their combined use with each others or combined with CT as an auxiliary diagnostic index may improve the level of differential diagnosis of SCLC, and they have a certain value in the staging of the disease, which is very important for the formulation of SCLC treatment strategy, their detection is conducive to the prevention and control of the disease.. 肺癌是常见的癌症之一，小细胞肺癌（SCLC）与非小细胞肺癌（NSCLC）在治疗和预后上有显著差异。SCLC的肿瘤细胞可表达一些神经内分泌肿瘤（NET）标志物，其中关于嗜铬粒蛋白A（CgA）与突触素（Syn）和神经元特异性烯醇化酶（NSE）及胃泌素释放肽前体（Pro-GRP）与SCLC的相关研究较多。CgA、NSE及Pro-GRP水平均与SCLC的分期有关，广泛期患者其水平显著高于局限期患者，且其表达与较低的生存率显著相关。Syn作为SCLC的辅助诊断指标时敏感度高于CgA，且在SCLC与低分化鳞癌的鉴别诊断中有较高的实用价值；NSE是目前临床上SCLC中使用最多的肿瘤标志物；Pro-GRP在SCLC与NSCLC的区分上具有强于CEA和NSE的诊断优势。尽管这些NET标志物均不是SCLC的特异性标志物，但它们联合运用或作为辅助诊断指标与CT联合使用或许能提高对SCLC的鉴别诊断水平，且它们在疾病的分期上有一定的价值，而疾病分期对SCLC治疗策略的制定十分重要，它们的检测有利于疾病的预防和控制。.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Chromogranin A; Gastrins; Humans; Lung Neoplasms; Peptide Fragments; Phosphopyruvate Hydratase; Protein Precursors; Small Cell Lung Carcinoma; Synaptophysin

To distinguish lung cancer by detecting 6 tumor markers in serum and establishing three classifying models of artificial neural networks (ANN), decision tree (CART), Fisher discrimination analysis, and to compare the differences among three models.. The levels of serum CEA, gastrin, NSE, sialic acid (SA), Cu/ Zn, Ca in 50 healthy individuals, 40 patients with lung benign disease and 50 patients with lung cancers were detected by means of radioimmunology, spectrophotometry, atomic absorption spectrophotometry, respectively, and then developed ANN, CART and Fisher discrimination analysis models.. The sensitivity of ANN, CART and Fisher discrimination analysis models were 100%, 93.33%, 84.00%, the specificity were 100%, 100%, 98.89%, the accuracy were 91.67%, 86.11%, 85.00%. The areas under receiver operating curve (AUROC) of ANN, CART and Fisher discrimination analysis models were 0.964, 0.953, 0.812, respectively. There was no significantly statistical difference between ANN and CART (P > 0.05), while there were significantly statistical differences not only between Fisher discrimination analysis and ANN, but also Fisher discrimination analysis and CART (P < 0.05).. The effects of ANN, CART models established by 6 tumor markers were better than that of Fisher discrimination analysis in discrimination of lung cancer.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Decision Trees; Diagnosis, Differential; Discriminant Analysis; Gastrins; Humans; Lung Neoplasms; N-Acetylneuraminic Acid; Neural Networks, Computer; ROC Curve; Sensitivity and Specificity; Small Cell Lung Carcinoma

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.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Division; Gastrins; Glycine; Humans; Lung Neoplasms; Mice; Mice, Transgenic; Middle Aged; Prognosis; Survival Analysis; Time Factors

Numerous epidemiologic studies suggest a relationship between lung cancer and peptic ulcer disease. Furthermore, various lung cancers synthesize and release a number of peptides such as gastrin and gastrin-releasing peptide that could cause acid hypersecretion; however, Zollinger-Ellison syndrome (ZES), because of a lung tumor, has never been described. We report such a patient for the first time. A 60-year-old man with a non-small cell lung carcinoma (large cell type) presented with diarrhea, heartburn, abdominal pain, and duodenal ulcers. Evaluation showed ZES was present (fasting hypergastrinemia, hyperchlorhydria) and control of all symptoms by omeprazole. No abdominal or cardiac tumor, the other known locations of gastrinomas causing ZES, was found on detailed tumor imaging studies. Resection of the lung tumor resulted in a decrease in gastrin levels to normal values. Plasma radioimmunoassays showed elevated gastrin, chromogranin A and normal levels of gastrin-releasing peptide, and 9 other hormones. The tumor showed similar immunocytochemical results. The characteristics of this case are compared with 100 cases of sporadic abdominal gastrinomas, and the evidence reviewed suggests why ZES should be considered in patients with lung cancer with peptic symptoms.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Chromogranin A; Chromogranins; Gastric Acid; Gastrins; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Synaptophysin; Zollinger-Ellison Syndrome

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.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Gastrins; Humans; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase

Progastrin-releasing peptide (proGRP) is a specific tumor marker in patients with small cell lung carcinoma (SCLC). It has been reported that serum proGRP levels rarely are elevated in patients with nonsmall cell lung carcinoma (NSCLC); the reported frequency is <3%. The purpose of this study was to examine the clinicopathologic features of NSCLC patients with high serum proGRP levels.. The authors measured serum proGRP levels with a TND-4 kit, a newly developed enzyme-linked immunoadsorbent assay, in 544 NSCLC and 206 SCLC patients. Pathologic features were examined using conventional hematoxylin and eosin staining and histochemical and immunohistochemical staining using polyclonal antibodies to proGRP, chromogranin A, calcitonin, and monoclonal antibody to the neural cell adhesion molecule (NCC-Lu-243).. The serum proGRP levels were elevated in 140 SCLC patients (68.0%) and in 23 NSCLC patients (4.2%). Seven of these 23 NSCLC patients had serum proGRP levels > or = 100 pg/mL. They included two patients with renal dysfunction, one patient diagnosed cytologically with adenocarcinoma without undergoing precise pathologic examination, two patients diagnosed histologically with squamous cell carcinoma with foci of small cell elements, and two patients diagnosed with large cell neuroendocrine carcinoma and poorly differentiated adenocarcinoma, respectively, which showed neuroendocrine differentiation on immunohistologic analysis. The remaining 16 NSCLC patients had serum proGRP levels < 70 pg/mL.. Nearly all NSCLC patients had serum proGRP levels < 100 pg/mL. However, if an NSCLC patient presents with a proGRP level > or = 100 pg/mL, the clinicopathologic features must be examined with regard to the small cell component, neuroendocrine differentiation, and renal dysfunction.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Gastrins; Humans; Lung Neoplasms; Male; Middle Aged; Protein Precursors; Renal Insufficiency

The gastrin gene is known to be expressed in all classes of bronchogenic carcinomas. Furthermore, high levels of gastrin have been reported in both the bronchoalveolar lavage (BAL) fluid and serum of patients with lung cancer. Based on these preliminary data a study was conducted to evaluate the usefulness of gastrin measurements in the diagnosis and staging of lung cancer.. Thirty-five patients with lung cancer (26 non-small cell (NSCLC) and nine small cell (SCLC)) and 25 patients with chronic obstructive pulmonary disease underwent fibreoptic bronchoscopy and BAL. Gastrin levels were determined in both BAL fluid and the serum and compared with each other and with staging.. No difference was found between the gastrin levels in the BAL fluid or serum of the study groups. There was no correlation with the stage in NSCLC and no correlation was found between the gastrin levels in the serum and the BAL fluid. A significant difference was seen in gastrin levels in BAL fluid between extensive and limited SCLC (p < 0.05).. There is no evidence of clinical usefulness for gastrin measurements in lung cancer.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Gastrins; Humans; L-Lactate Dehydrogenase; Lung Diseases, Obstructive; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

We investigated the effects of our synthetic bombesin/gastrin-releasing peptide (GRP) antagonists and somatostatin analogue RC-160 on the growth of human small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (non-SCLC) lines in nude mice. Athymic nude mice bearing xenografts of the SCLC NCl-H69 line or non-SCLC NCl-H157 line were treated for 5 and 4 weeks, respectively, with somatostatin analogue RC-160 or various bombesin/GRP antagonists. RC-160, administered s.c. peritumorally at a dose of 100 micrograms per animal per day, inhibited the growth of H69 SCLC xenografts as shown by more than 70% reduction in tumour volumes and weights, as compared with the control group. Bombesin/GRP antagonists, RC-3440, RC-3095 and RC-3950-II, given s.c. peritumorally at a dose of 20 micrograms per animal per day, also inhibited the growth of H69 SCLC tumours. RC-3950-II had the greatest inhibitory effect and decreased tumour volume and weights by more than 80%. The growth of H-157 non-SCLC xenografts was significantly reduced by treatment with RC-160, but not with bombesin/GRP antagonist RC-3095. In mice bearing either tumour model, administration of RC-160 significantly decreased serum growth hormone and gastrin levels. Specific high-affinity receptors for bombesin and somatostatin were found on membranes of SCLC H69 tumours, but not on non-SCLC H157 tumours. Receptor analyses demonstrated high-affinity binding sites for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the membranes of H69 and H157 tumours. EGF receptors were down-regulated on H69 tumours after treatment with RC-160 and bombesin/GRP antagonists. The concentration of binding sites for EGF and IGF-I on the H157 tumours was decreased after treatment with RC-160, but bombesin/GRP antagonist RC-3095 had no effect. These results demonstrate that bombesin/GRP antagonists inhibit the growth of H-69 SCLC, but not of H-157 non-SCLC xenografts in nude mice, whereas somatostatin analogue RC-160 is effective in both tumour models. This raises the possibility that these peptide analogues could be used selectively in the treatment of various subclasses of lung cancer.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Binding Sites; Body Weight; Bombesin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Division; Gastrin-Releasing Peptide; Gastrins; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Transplantation; Peptide Fragments; Peptides; Receptors, Somatotropin; Somatostatin; Substrate Specificity; Transplantation, Heterologous