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)

Gastrin has been postulated to be a physiological growth factor, but compelling in vitro evidence of this has been difficult to obtain. In the present study we investigated whether small cell lung carcinoma cell lines could provide a useful model system to study the effects of gastrin on signal transduction and cell proliferation in vitro. We found that the addition of gastrin to small cell lung cancer cells loaded with the fluorescent Ca2+ indicator fura 2-tetraacetoxymethylester causes a rapid and transient increase in the intracellular concentration of Ca2+ ([Ca2+]i) followed by homologous desensitization. The [Ca2+]i response was especially prominent in the small cell lung carcinoma cell line H510. In this cell line, gastrin I, gastrin II, cholecystokinin residues 26-33 (CCK-8), and unsulfated CCK-8 increased [Ca2+]i in a concentration-dependent fashion with half-maximum effects at 7, 2.5, 3, and 5 nM, respectively. The Ca(2+)-mobilizing effects of gastrin and CCK-8 were prevented by proglumide, benzotript, and the specific gastrin/CCKB receptor antagonist L365260. Gastrin stimulated the clonal growth of H510 cells in semisolid (agarose-containing) medium, increasing both the number and the size of the colonies. Gastrin and CCK agonists were equally effective in promoting clonal growth. The broad-spectrum neuropeptide antagonists [D-Arg1,D-Phe5,D-Trp7,9,Leu11] substance P and [Arg6,D-Trp7,9,MePhe8] substance P (6-11) markedly inhibited gastrin-stimulated Ca2+ mobilization and clonal growth. These results show that gastrin acts as a direct growth factor through gastrin/CCKB receptors and demonstrate, for the first time, that these peptides can stimulate the proliferation of cells outside the gastrointestinal tract.
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PMID:Gastrin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer cells. 132 22

Small cell lung cancer (SCLC) cells express several characteristics of neuronal cells, including synthesis of neuropeptides and expression of the respective receptors. Establishment and maintenance of the neuronal phenotype of SCLC may depend on expression of gene transcription factors inherent to the central nervous system. The present study shows the nervous system-specific transcription factor N-Oct 3 (brain-2) to be expressed in all 13 SCLC cell lines investigated. Furthermore, N-Oct 3 (brain-2) was also found in SCLC-derived skin metastasis. In contrast, in extracts and RNA of non-SCLC cell lines and non-SCLC tumor tissues, such as lung squamous, large cell, and adenocarcinoma, expression of N-Oct 3 (brain-2) was not detectable. These data support the concept that SCLC cells derive from the neuroectodermal cell lineage since expression of N-Oct 3 (brain-2) protein is highly abundant at the neural tube stage and in the adult restricted to the neuroectodermal cell lineage.
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PMID:Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2). 132 24

In order to clarify the pathogenesis of paraneoplastic syndrome, immunohistochemical studies were performed in a patient with subacute sensory neuropathy secondary to a small cell lung cancer. The case was a 73-year-old ex-farmer, whose chief complaints were pins and needles sensation of distal limbs and gait difficulty. After 6 weeks prodromata of pain in the upper limbs and numbness in all the limbs, he became unable to stand up without assistance. Neurological examinations on admission revealed marked sensory disturbances with glove and stocking type hypalgesia to pin prick and the loss of position and vibration senses in the distal extremities. His deep tendon reflexes also decreased in all the limbs. A chest X-ray showed a mass in the left upper lung field. A transbronchial lung biopsy of the mass revealed a small cell carcinoma. He was treated with anti-cancer drugs and radiation but he died of pneumonia after 8 months illness. Autopsy revealed a marked demyelination of the entire posterior column of the spinal cord. Dorsal root ganglia were infiltrated by lymphocytes with significant neuronal loss. Immunohistochemically, most of the infiltrated cells around the neurons were classified as CD8+ with fewer CD4+ lymphocytes. No B-lymphocytes were detected in the ganglia. The HLA-ABC and HLA-DR positive cells were found only among the satellite cells, not in the neurons. The serum and CSF from the patient were immunohistologically reacted with the nuclei and cytoplasm of all neurons of human as well as of rats, indicating the presence of anti-Hu type antineuronal antibody in the patient's CSF as well as serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical studies of paraneoplastic subacute sensory neuropathy--an analysis of antineuronal antibody and infiltrated lymphocytes]. 132 6

Human cDNA clones for NSCL-1 and NSCL-2, two basic domain helix-loop-helix (bHLH) genes expressed predominantly in the developing nervous system, were obtained from a fetal brain cDNA library. The full-length transcripts and the genomic structures were determined. The cDNAs for the two genes encode predicted proteins of similar size (133 and 135 amino acids for NSCL-1 and NSCL-2, respectively) and structure. The carboxyl-terminal 75 amino acids of the two proteins contain the bHLH motif and differ from each other by only three conservative amino acid changes, while the amino-terminal portions are markedly divergent from each other. In addition to the similar protein structure, the genes have a similar genomic organization, suggesting a close evolutionary relationship. The 5'-regulatory regions of the two genes share some features (i.e. potential TATA, CCAAT, and GATA binding sites) but also differ significantly in their G+C content. NSCL-1 is relatively G+C-rich (63%) in the sequences upstream of transcription initiation and has multiple potential binding sites for transcription factors that bind to G+C-rich sequences (e.g. AP-2). NSCL-2 is relatively A+T-rich (63%) in this region and has a potential binding site for AP1. Studies of expression in normal tissues demonstrated expression of NSCL-1 and NSCL-2 in the developing central and peripheral nervous system, most likely in developing neurons. Additional Northern analysis studies in cell lines revealed expression of these genes in some cell lines derived from tumors with neural or neuroendocrine features such as neuroblastoma, PNET, and small cell lung cancer. NSCL-1 is expressed in a larger number of these cell lines. The differences in expression may parallel differences in developmental regulation.
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PMID:A comparative structural characterization of the human NSCL-1 and NSCL-2 genes. Two basic helix-loop-helix genes expressed in the developing nervous system. 132 19

In serum and cerebrospinal fluid of 6 out of 15 patients with small cell lung cancer circulating antineuronal antibodies could be detected by indirect immunofluorescence. None of the patients showed signs of a neurological paraneoplastic syndrome, usually associated with the presence of these antibodies. On sections of frontal brain, cerebellum, dorsal root ganglia and peripheral nerve, obtained at autopsy, a direct immunofluorescence test was performed. Only in antibody-positive individuals were membrane-bound immunoglobulin deposits detected on neurons of dorsal root ganglia and Purkinje cells. The present study showed that circulating antineuronal antibodies reach the central and peripheral nervous system in vivo. These findings support the theory that these antibodies might be directly involved in the pathogenesis of neurological paraneoplastic syndromes.
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PMID:Circulating antineuronal antibodies reach neurons in vivo: an autopsy study. 132 44

Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth characteristics, but a different radiosensitivity. The 54A tumors are twice as radiosensitive as the 54B's. In the present study the tumors were treated with 2.5, 10, and 40 Gy. For comparison, nude mice were given cranial irradiation at the same three doses, and the effect was evaluated by in vivo 31P-MRS. No effect was observed in brain at any dose level. In contrast, 40 Gy induced a statistically significant reduction in ATP/Pi ratio during the 12-h post-irradiation period. This effect was more pronounced in 54A than in 54B. Some reduction was observed following 10 Gy, whereas 2.5 Gy induced no changes in ATP/Pi. The differential effect on tumors and brain might be relevant for monitoring irradiation effects by in vivo 31P-MRS in patients with brain metastases.
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PMID:Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy. 132 55

At Indiana University, we began clinical trials with ifosfamide in 1981. Although our initial efforts were in a variety of tumor types, including pancreatic cancer, we have most recently focused our attention on two tumors that have historically exhibited a higher degree of chemosensitivity--testicular cancer and small cell lung cancer (SCLC). In phase II trials, ifosfamide has proven to have single-agent activity in both diseases. Coupling this data with preclinical observations of synergy with cisplatin and etoposide, we began trials of ifosfamide plus cisplatin with either vinblastine (VeIP) or etoposide (VIP) in patients with recurrent germ cell tumors; we also investigated the use of VIP in SCLC. In third-line or greater therapy for recurrent germ cell tumors, a 36% disease-free status was attained, with 16% of patients continuously free of disease for 5 or more years. Currently, ifosfamide is being evaluated as part of initial therapy in patients with advanced disease. In SCLC, VIP has also been investigated as part of initial therapy in patients with extensive disease. The complete response rate of 38% achieved in 37 evaluable patients has spurred the Hoosier Oncology Group to compare the VIP regimen to cisplatin/etoposide in patients with extensive-disease SCLC. Ifosfamide has the broad range of clinical activity, but its ultimate role as part of initial therapy remains to be discerned.
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PMID:Clinical trials with ifosfamide: the Indiana University experience. 132 10

Ifosfamide, an analogue of the alkylating agent cyclophosphamide, is one of the most active agents in the treatment of small cell lung cancer (SCLC). As a single agent, the drug produces a greater than 50% objective response rate. Recent studies using ifosfamide in combination with other active agents, ie, cisplatin, carboplatin, and etoposide, In the treatment of limited-stage and extensive-stage SCLC have achieved high overall response rates and complete responses (CRs). However, the CR rate is higher in limited-disease patients. Additional studies are needed with the various ifosfamide-containing regimens to precisely define their role in the treatment of SCLC in both limited-disease and extensive-disease patients.
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PMID:Overview of ifosfamide in small cell lung cancer. 132 14

During the past 5 years, ifosfamide has been used increasingly in combination chemotherapy for small cell lung cancer (SCLC). The high activity and favorable toxicity spectrum (with the uroprotector mesna) will encourage further use. A policy of no dosage reduction is feasible in patients receiving combination chemotherapy with ifosfamide given as a 24-hour intravenous (IV) infusion, which is much more convenient than the more commonly used 4- to 5-day fractionated regimen. This policy has resulted in actual 2-year survivals of 22% to 33% among SCLC patients not intensively staged. The stability of ifosfamide and its high bioavailability have allowed its use in chronic, 7-day ambulatory IV infusions, with decreased toxicity and hospitalization. Recently, oral and subcutaneous administration also have been tried, again allowing outpatient treatment. The first studies with hemopoietic growth factor support, eg, granulocyte colony-stimulating factor, conducted with combination chemotherapy with ifosfamide-containing regimens in SCLC, demonstrated significant reduction in neutropenia, infections, and antibiotic use. It is clear that the dosage of ifosfamide can be intensified in the future. The broad versatility of the drug will allow interesting new studies, including those to be conducted with outpatients.
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PMID:Novel approaches with ifosfamide in small cell lung cancer. 132 15

Lung cancer is the most lethal cancer in the United States, with 143,000 deaths predicted for 1991. The cure rate is extremely low (approximately 13%), in part because the propensity for early spread precludes surgical cure in most patients. Thus, chemotherapy or other systemic therapies are the only way to improve the dismal results. Cisplatin is an active agent in small cell lung cancer (SCLC) and perhaps the most active agent in nonsmall cell lung cancer (NSCLC). The toxicities and inconvenience of cisplatin make it less than ideal for lung cancer therapy. Carboplatin was developed to provide a less toxic, more convenient alternative to cisplatin. The data presented in this review suggest that carboplatin may be substituted for cisplatin in the treatment of extensive-stage SCLC. In limited-stage SCLC, there are insufficient data to determine whether it should replace cisplatin when used simultaneously with chest irradiation and etoposide. It may be substituted for cisplatin in cycles not using irradiation. In NSCLC, carboplatin may be used alone or with etoposide for the palliative management of metastatic disease. Its role in earlier stages of NSCLC needs investigation.
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PMID:Clinical experiences with carboplatin (paraplatin) in lung cancer. 132 16


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