Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half-life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs.
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PMID:Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. 257 97

Merkel cell carcinoma is a rapidly proliferating neoplasm of neuroectodermal origin presenting in skin. Karyotypes obtained in direct preparations of three Merkel cell carcinomas were analyzed and compared with six other tumors which were reported in the literature. Of the nine tumors studied so far, eight (89 per cent) showed structural abnormalities of chromosome 1. These abnormalities were in the form of trisomy for chromosome 1q22----ter. Furthermore, it was also observed that the breaks of these rearrangements on chromosome 1 occurred at the bands to which c-oncogenes N-ras (p31), L-myc (p32), c-src (p36), c-ski (q22-22), and the beta-subunit of the nerve growth factor (NGF) (p22) were localized. In addition to structural changes, five out of the nine tumors (55.5 per cent) were trisomic for chromosome 1. Merkel cell tumors are often confused with small cell carcinoma of lung or peripheral neuroepithelioma. The cytogenetic abnormalities such as rearrangement of chromosome 3p and t(11;22)(q23;q12) which characterize lung carcinoma and peripheral neuroepithelioma, respectively, were not seen in any of the nine Merkel cell tumors studied. Thus it appears that rearrangement of chromosome 1 was non-randomly associated with Merkel cell carcinoma. It is of interest to note that genes involved in neuronal development and or differentiation have been mapped to the bands at which breaks occurred in these tumors. The significance of these changes is briefly discussed.
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PMID:Non random cytogenetic changes characterize Merkel cell carcinoma. 276 51

Lonidamine, a substituted indazole carboxylic acid that inhibits cellular respiration, was given in an escalating oral schedule to 20 evaluable patients with measurable extensive small cell carcinoma of the lung. Two partial responses occurred. Reversible acceptable toxicity included myalgia, nausea, hyperesthesia, photophobia, somnolence, and testicular pain. The drug was not myelosuppressive. Lonidamine has modest activity in small cell lung cancer and further studies are warranted.
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PMID:Phase II study of lonidamine in patients with small cell carcinoma of the lung. 282 92

A murine monoclonal antibody (mAb A23-16) was produced that recognizes a glycoprotein antigen preferentially expressed on the surface of human small cell lung carcinoma cells. This antibody is of IgG 1 isotype, has an association constant of 5 x 10(7) M-1, and reacts preferentially with human small cell lung carcinoma cell lines and fresh frozen sections in enzyme-linked immunosorbent assays and immunoperoxidase assays, respectively. The antigen recognized by A23-16 is a sulfated glycoprotein with phosphorylated threonine residues. The mature 90-kDa molecule has intrachain disulfide bonds and appears to be derived from a 76-kDa precursor, that is neither sulfated nor phosphorylated, but contains N-linked oligosaccharides. Conversion of the 76-kDa precursor to the mature form is accompanied by processing of these oligosaccharides from the high mannose to the complex type, although the increase in molecular mass from 76 to 90 kDa cannot be accounted for by this modification alone. MAb A23-16 reacts with its target antigen independent of the N-linked oligosaccharides, but requires intact intrachain disulfide bond(s) for reactivity. These studies on the molecular characterization of a monoclonal antibody-defined glycoprotein, preferentially expressed by small cell lung cancer, provide a basis for further structural and functional studies that may eventually lead to a delineation of its biological relevance for neoplastic transformation.
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PMID:Biochemical characterization of a sulfated phosphoglycoprotein antigen expressed on human small cell lung carcinoma. 282 63

Bombesin-like peptides are found in many different human tumors and are thought to function as an autocrine growth factor for small cell lung cancer in humans. In this study, a human small cell lung carcinoma (NCI-H69) was s.c. implanted bilaterally into the flanks of 12 nude mice. The mice were randomized and divided into two groups and given either bombesin (20 micrograms/kg) or saline i.p. 3 times a day. Tumor areas were measured twice weekly for 6 wk. At sacrifice, the tumors and normal pancreas were excised, weighed, and assayed for DNA, RNA, and protein content. Significant stimulation of tumor growth was observed at weeks 4, 5, and 6. Tumor weight at sacrifice was significantly elevated (77%) above the control, as was DNA content (78%). Bombesin significantly increased the weight (42%), DNA (48%), and protein (61%) contents of the normal mouse pancreas. We conclude that bombesin may act as an autocrine growth factor, or indirectly through the release of other growth factors, on human small cell lung carcinoma.
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PMID:Effects of bombesin on growth of human small cell lung carcinoma in vivo. 283 Sep 65

A series of 104 patients with limited small cell lung carcinoma was treated by combination of chemotherapy and radiotherapy from August 1975 to July 1981. 104 patients were divided into three groups: prophylactic irradiation to supraclavicular areas (14 patients), non-prophylactic group (72 patients), non-prophylactic irradiation with positive supraclavicular lymph node metastasis after the treatment (18 patients). The 5 year survival rates of the three groups were 14%, 6% and 0%. Distant metastasis rates after the treatment were 36%, 52% and 61%, respectively. The supraclavicular lymph node metastasis rate after the treatment was higher in patients with intra-thoracic lymph node metastasis before the treatment (25%) than in those without this metastasis (0%). It is suggested that, for small cell lung cancer patients, especially with intra-thoracic lymph node metastasis before the treatment, prophylactic irradiation to the supraclavicular areas be valuable.
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PMID:[Value of prophylactic irradiation to supraclavicular areas in small cell lung carcinoma--analysis of 104 patients]. 283 43

A series of 1019 patients with small cell carcinoma of the lung, treated at the Department of Radiotherapy and Oncology at the Helsinki University Central Hospital during the period 1963-1982, included 19 patients who survived for 5 years or more after the diagnosis. The clinical data of these patients were retrospectively studied in order to elucidate factors which may have contributed to the more favourable outcome. All of the 5-year survivors were previously untreated, and all had a good performance status at the time of diagnosis. In 95%, the disease was limited to one hemithorax, and 74% had a stage I or II tumour. All treatment modalities, except immunotherapy, were used during the two decades. Surgery alone, or with adjuvant radiotherapy, and/or chemotherapy, was the primary treatment in eight of the long-term survivors (42%). Chemotherapy, either alone or in combination with radiotherapy, was the primary treatment in 10/19 (53%) patients and radiotherapy alone was given to one of the 5-year survivors. The objective response rate to the primary treatment was 100% and complete response was achieved in 95%. There were seven carcinoma related deaths after 5-year disease-free survival. The first site of relapse was the central nervous system in three cases and the liver in three cases. Acute myocardial infarction was the cause of death in five patients. One patient died of the other carcinoma and six are still alive with no evidence of SCCL. In conclusion, a good performance status at diagnosis, no pretreatment weight loss, the extent of disease and good response to the primary treatment appeared to be prognostically important in the present study. Some patients with very limited disease may benefit from primary treatment comprising surgery and adjuvant chemotherapy.
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PMID:Long-term survival in small cell carcinoma of the lung. 283 96

Among 14 patients with carcinoma of the lung and scleroderma, 9 had no history of smoking. The 14 cases of primary lung carcinoma occurred in a population of 3550 patients with a diagnosis of scleroderma. Scleroderma preceded the diagnosis of lung cancer by at least 6 years in 8 cases. Scleroderma and lung carcinoma were diagnosed within 3 years of each other in 4 cases. The most frequent type of carcinoma in our series was small cell carcinoma, which accounted for 5 of the 14 cases. Our data indicate an increased risk of carcinoma of the lung in patients with scleroderma, even among nonsmokers. Small cell carcinoma of the lung is probably much more common in patients with scleroderma in whom lung carcinoma develops than is indicated by previous reports.
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PMID:Lung cancer and scleroderma. 284 7

Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed "classic" SCLC lines, have properties similar to SCLC tumors in patients, including high expression of neuroendocrine markers and low c-myc oncogene expression. A significant number of SCLC lines characterized as "biochemical or morphologic variant" SCLC lines have decreased levels of endocrine differentiation markers associated with increased proliferative indices, amplification of the c-myc oncogene, and growth patterns and biochemical markers more typical of non-SCLCs. To delineate further the relationships between these phenotypes and the molecular events involved, we have inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma, including adherent monolayer growth patterns, increased cloning efficiency, increased levels of non-SCLC cell markers, ultrastructural characteristics and an acquired resistance to polyamine depletion typical of large cell carcinoma, but not SCLC, in vitro. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The findings provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types.
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PMID:v-Ha-ras oncogene insertion: a model for tumor progression of human small cell lung cancer. 284 76

In Swiss 3T3 fibroblasts, antibodies which recognize a phosphotyrosine residue (P-Tyr antibodies) identify a 115-kDa cell surface protein (p115) that becomes phosphorylated on tyrosine as a response to bombesin stimulation of quiescent cells. The extent of phosphorylation is dose-dependent and correlates with the mitogenic effect induced by bombesin, measured by [3H]thymidine incorporation. Tyrosine phosphorylation of p115 is detectable minutes after addition of bombesin and precedes the activation of c-fos and c-myc gene transcription. Immunocomplexes of phosphorylated p115 with P-Tyr antibodies bind 125I-labeled [Tyr4]bombesin in a specific and saturable manner and display an associated tyrosine protein kinase activity enhanced by bombesin. P-Tyr antibodies also recognize a protein of 115 kDa, phosphorylated at tyrosine, in four human SCLC lines producing bombesin but not in a non-producer "variant" line. Phosphorylation of SCLC p115 does not require the addition of exogenous bombesin. As in the case of the p115 immunoprecipitated from mouse fibroblasts, the SCLC p115 is phosphorylated in an immunocomplex kinase assay. These observations are in agreement with the hypothesis of autocrine activation of bombesin receptors in human small cell lung carcinoma cells.
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PMID:A tyrosine protein kinase activated by bombesin in normal fibroblasts and small cell carcinomas. 285 93


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