Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) has been identified as an important growth regulator of lung cancer cells. Elevation of serum levels of IL-6 has been found in a subpopulation of lung cancer patients, but rarely in patients with benign lung diseases. Approximately 15% of non-small cell lung cancer (NSCLC) tumors exhibit neuroendocrine (NE) properties (NSCLC-NE) and have been suggested to have the biological characteristics similar to small cell lung cancer (SCLC) with early metastasis and initial responsiveness to chemotherapy. We recently showed that IL-6 promotes cell proliferation and downregulates the expression of neuron-specific enolase (NSE, one of the major NE markers) in NSCLC-NE cells. In this study, we show that IL-6 stimulates a transient increase of tyrosine phosphorylation of STAT3 in a dose-dependent fashion. Inhibition of STAT3 signaling pathway by either AG-490 (JAK2-specific inhibitor) or overexpression of STAT3Y705F (a dominant-negative STAT3) reverses NSE expression in IL-6- treated NSCLC-NE cells. In addition, IL-6 induces phosphorylation and activation of p38 MAPK. SB-203580, a p38 MAPK-specific inhibitor, inhibits IL-6-induced p38 MAPK phosphorylating activity and suppresses IL-6-stimulated cell proliferation. Together, our results indicate that STAT3 signaling pathway is involved in IL-6-induced NE differentiation and that p38 MAPK is associated with IL-6-stimulated growth regulation in NSCLC-NE cells. These data suggest that both kinase pathways play critical roles in the pathogenesis of NSCLC-NE malignancies, providing new molecular targets for future therapeutic approaches.
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PMID:IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells. 1589 58

Tumor metastasis to the pancreas is a rare but recognized cause of acute pancreatitis. Autopsy series have reported a 24-40% of pancreatic involvement in small cell lung cancer. However, only a very few cases of tumor-induced acute pancreatitis have been described. Budd-Chiari syndrome complicating lung cancer is a rarely reported condition. We report a 68-year-old woman with extensive small cell lung cancer with the unusual initial presentation of both acute pancreatitis and acute Budd-Chiari syndrome. This patient suffered from progressive epigastralgia for 3 weeks. Severe epigastralgia with radiation to back and progressive jaundice developed 2 days prior to admission. After admission, the liver enlarged rapidly and the ascites increased markedly. Chest roentgenogram showed a mass lesion over the left lower lung field. Poorly differentiated carcinoma cells were found in ascites and bone marrow. The patient died on the ninth day of hospitalization before chemotherapy was initiated. Prompt diagnosis of extensive-stage small cell lung cancer may allow early chemotherapy treatment which favorably influences recovery when the pancreatitis is mild. Although prolonged survival might have been expected had this patient recovered from pancreatitis and received chemotherapy, diagnosis was delayed due to difficulty in immunohistochemical diagnosis of the tumor and the unusual clinical presentation. The use of stains employing antibodies against neurofilament and neuron-specific enolase cell antigens is important for early diagnosis of poorly differentiated metastatic tumor cells.
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PMID:Acute pancreatitis combined with acute Budd-Chiari syndrome as the initial manifestation of small cell lung cancer. 1603 34

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin lymphoma of exclusively B-cell phenotype developing in the pleural cavity of patients after more than 20-year history of pyothorax resulting from an artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. The most common symptoms on admission are chest pain and fever. Serum neuron-specific enolase level suggesting a diagnosis of small cell lung cancer is occasionally elevated. Histologically PAL usually shows a diffuse proliferation of large cells of B-cell type (diffuse large B-cell lymphoma [DLBL]). In PAL cells, representative B-cell markers other than CD20 are frequently negative with aberrant expression of T-cell markers such as CD2. A gene expression profile of PAL is distinct from nodal DLBL in its higher expression level of interferon-inducible genes. PAL is strongly associated with Epstein-Barr virus (EBV) infection with expression of EBV latent genes such as EBNA-2, LMP-1, together with EBNA-1. Taken together, PAL is a distinct entity both in its clinicopathologic presentation as well as its gene expression profile. Use of an artificial pneumothorax, EBV infection, and cytokines and reactive oxygen species produced in longstanding pyothorax might be important factors for PAL development.
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PMID:Pyothorax-associated lymphoma: a lymphoma developing in chronic inflammation. 1633 Sep 29

Large cell neuroendocrine carcinoma (LCNEC) is a newly recognized clinicopathologic entity. The clinical features of advanced LCNEC are still unclear, because most of the previous reports have described resected cases. The aim of this study was to clarify the clinical characteristics and response to chemotherapy in patients with advanced LCNEC. From June 2002 to July 2004, nine patients (seven men and two women, median age 61) with advanced LCNEC were admitted to our hospital. We reviewed the clinical manifestations, tumor markers, and treatment of these patients. Seven of nine patients (78%) were current or ex-smokers. As for tumor markers, the levels of progastrin-releasing peptide (proGRP) and neuron-specific enolase (NSE) were elevated in six patients (67%) and five patients (56%), respectively. The diagnosis of LCNEC was made based on the resected specimens in 8 patients including resection of brain metastasis in 1 and CT-guided needle biopsy in 1. One patient was stage IIIA, 1 was stage IIIB, 3 were stage IV, and 4 had postoperative recurrence. Treatment included chemotherapy alone in 7 patients, chemotherapy plus whole brain radiation in 1, and postoperative radiotherapy in 1. Of 7 patients treated by chemotherapy alone who had received carboplatin-based chemotherapy. 5 showed partial response, yielding response rate of 71.4%. The proGRP level was frequently elevated in patients with advanced LCNEC and the response rate of LCNEC to carboplatin-based chemotherapy was comparable to that of small cell lung cancer.
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PMID:[A clinical study of advanced large cell neuroendocrine carcinoma]. 1697 12

Neuroendocrine tumours of lungs represent a subgroup of pulmonary tumours with typical morphofunctional traits. In light microscopy, the four principal types of the tumours (typical and atypical carcinoids, small cell lung cancer, large cell neuroendocrine carcinoma) demonstrate typical arrangement of cells (organoid nesting, palisading, a trabecular pattern, and rosette-like structures), variable number of mitoses, presence or absence of necrosis. In ultrastructure, neuroendocrine tumours manifest groups of cells with cytoplasmic granules (and the so called dense-core neurosecretory granules in particular). Neuroendocrine cells release hormones to circulation or in a paracrine manner. Some pulmonary tumours exhibit no neuroendocrine morphology at the level of light microscopy but demonstrate ultrastructural and/or immunohistochemical traits of neuroendocrine differentiation. Proteins the presence of which confirms neuroendocrine origin of the tumours have been found relatively early to include neuron-specific enolase (NSE), the group of chromogranins and synaptophysin. Present study aimed at summing up results of investigations conducted in, approximately, recent 30 years pertaining expression and/or serum concentrations of four neuroendocrine markers (chromogranin A, neuron-specific enolase, synaptophysin, protein gene product 9.5) and at an attempt to evaluate the role of such studies in extension of diagnostic and prognostic potential as related to neuroendocrine pulmonary tumours. Until now, the most sensitive and specific marker or marker combination for early detection of neuroendocrine subtypes of lung tumours has not been identified. All of the markers examined in present study were detected both in the typical neuroendocrine pulmonary tumours and in a certain proportion of non-endocrine tumours. In the case of chromogranin A improved sensitivity and specificity of immunocytochemical studies was obtained using a panel of antibodies directed to various epitopes of the protein. Both in endocrine and non-endocrine tumours, neuron-specific enolase (NSE) is thought to represent mainly a prognostic index, and only quantitation of serum concentrations of the protein or of the fraction of immunopositive cells may permit to differentiate between subtypes of the tumours. Synaptophysin is regarded to represent one of the most specific markers of neuroendocrine differentiation, manifesting a much higher sensitivity than chromogranin A and NSE. With increasing frequency, PGP 9.5 is regarded to provide a prognostic marker in diagnosis of non-small cell lung carcinomas rather than of typical neuroendocrine tumours.
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PMID:Selected markers (chromogranin A, neuron-specific enolase, synaptophysin, protein gene product 9.5) in diagnosis and prognosis of neuroendocrine pulmonary tumours. 1758 39

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 usefulness of serum pro-gastrin-releasing peptide (ProGRP) as a tumor marker in patients with small cell lung cancer has recently drawn the attention of many research centers. The aim of the study was the evaluation of ProGRP, neuron-specific enolase (NSE), soluble fragment of cytokeratin 19 (CYFRA 21-1) and lactate dehydrogenase (LDH) levels at the time of diagnosis and during chemo- and radiotherapy of small cell lung cancer patients with limited disease (SCLC-LD). The studies were performed on a group of 64 patients with SCLC-LD who had received no prior therapy. All the patients were given the same treatment regimen. ProGRP, NSE, CYFRA 21-1 and LDH were measured before each course of chemotherapy and then at 3 and 6 months after the end of treatment. Prior to therapy, elevated levels of ProGRP, NSE, CYFRA 21-1 and LDH were found in 79.7%, 57.8%, 23.4%, and 12.5% of the patients respectively. Before the second chemotherapy course, all the tumor marker levels except LDH decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during consecutive courses of therapy, while NSE and CYFRA 21-1 fluctuated within reference ranges. When the study group was divided with respect to the effect of treatment evaluated six months from its termination, significant differences in ProGRP levels were found between both subgroups throughout all therapy and follow-up, except for the fifth course of chemotherapy. Differences in NSE levels were only significant for the first two courses and follow-up. Univariate analysis showed significant relationships between disease-free survival and the initial levels of NSE and CYFRA 21-1 as well as between overall survival and prophylactic cranial irradiation (PCI) and the initial ProGRP, NSE and CYFRA 21-1 levels. Changes of ProGRP level seem to be more precise than NSE as a tool for monitoring therapy in SCLC patients with limited disease, but for prediction of relapse, in addition to NSE determinations of ProGRP seem to be optimal.
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PMID:ProGRP and NSE in therapy monitoring in patients with small cell lung cancer. 1903 51

We examined the association between chemotherapy-induced myelosuppression and prognosis in extensive-stage small cell lung cancer (ED SCLC). We retrospectively analysed 91 patients with ED SCLC who received a combination of cisplatin or carboplatin, etoposide or irinotecan between November 1995 and December 2007. Patients were categorized into two groups (grade 0 to 2 or grade 3 to 4) according to the worst neutropenia, thrombocytopenia, or anemia during first-line chemotherapy and were analysed for overall survival (OS) and time to progression (TTP). By univariate analysis, OS and TTP were significantly better in patients who developed grade 3 to 4 neutropenia than those who developed grade 0 to 2. Additionally, performance status (PS), LDH (lactate dehydrogenase), and neuron-specific enolase were prognostic factors for OS. By multivariate analysis, PS was an independent prognostic factor for OS. There were no independent prognostic factors for TTP. Myelosuppression during chemotherapy is not a prognostic factor in ED SCLC.
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PMID:[Chemotherapy-induced myelosuppression and treatment efficacy in extensive-stage small cell lung cancer]. 1992 Mar 85

We examined the association between chemotherapy-induced myelosuppression and prognosis in limited-stage disease small cell lung cancer (LD SCLC). We retrospectively analyzed 76 patients with LD SCLC who received combination cisplatin or carboplatin of etoposide or irinotecan. Patients were categorized into two groups (grade 0 to 2 or grade 3 to 4) according to the worst neutropenia, anemia, or thrombocytopenia during first-line chemotherapy and were analyzed for overall survival (OS) and time to progression (TTP). From univariate analysis, OS was significantly better in patients who developed grade 0 to 2 anemia or thrombocytopenia than those who developed grade 3 to 4. In addition, performance status, neuron-specific enolase (NSE), and pro-gastrin-releasing protein were identified as prognostic factors. By multi-variate analysis, NSE was an independent prognostic factor for OS. There were no independent prognostic factors for TTP. Myelosuppression during chemotherapy is not a prognostic factor in LD SCLC. Our results show doses of platinum doublet chemotherapy were adequate in patients with LD SCLC.
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PMID:[Chemotherapy-induced myelosuppression and treatment efficacy in limited-stage disease small cell lung cancer]. 2015 78

The aim of this work is to establish a pre-analytical approach suitable for the neuron-specific enolase (NSE) measurement. This enzyme which is synthesized by neurons and neuroendocrine cells, is a marker useful for the diagnosis and the monitoring of patients with neuroendocrine tumors (neuroblastoma, small cell lung cancer) and during stroke to assess neuronal damage. This NSE measurement is very sensitive to hemolysis due to the abundance of the enzyme in red blood cells. Two methods of evaluation of hemolysis have been compared: the determination of free haemoglobin (Hb) by spectrophotometry and the indirect measurement of an hemolytic index with a multiparameter analyzer, the Modular (Roche Diagnostics). The correlation between these 2 methods on 42 samples is very satisfactory: Y (free Hb) = 12.337 X (index) + 31.743 r = 0.997. The NSE assay is based on TRACE (Time Resolved Amplified Cryptate Emission) technology, on a Kryptor (BRAHMS). The influence of hemolysis on the determination of NSE was confirmed by overloading with hemoglobin (hemolysate) 3 pools of serum with NSE concentrations close to the threeshold decision. The determination of NSE shows an increase in concentration parallely to the hemolytic index (about 150% for an hemolytic index of 10). Consequently, in our laboratory the NSE determination is realized only for samples presenting an hemolytic index < or = 10, this allowing a good monitoring of kinetics of this marker.
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PMID:[Importance of hemolysis on neuron-specific enolase measurement]. 2034 52


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