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)

From January 1987 to December 1990, 26/105 previously untreated patients affected by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since 19 of them were older than 70 years and 7 suffered from severe chronic diseases, received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5, every 3 weeks until disease progression. After a minimum of two courses, 24 patients were evaluable for response: 13 with limited disease (LD) and 11 with extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol violation). Response rate, by disease stage, was: in the 13 LD, 1 complete response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the 11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95% confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of response was 7 months (range 2-32). Median overall duration of survival was 9 months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of courses delivered, whereas no further important side-effects were recorded, excluding alopecia, which was common. Teniposide used alone appeared a safe and effective palliative treatment for poor-risk patients; the major limitation was the low CR rate.
Eur J Cancer 1992
PMID:Teniposide as single drug therapy for elderly patients affected by small cell lung cancer. 137 89

The proliferation of small cell lung cancer (SCLC) cells appears sustained by multiple autocrine and paracrine circuits involving Ca2+ mobilizing neuropeptides. Consequently, broad spectrum neuropeptide antagonists which inhibit SCLC growth in vitro have been suggested as potential anticancer agents. Here we evaluated this hypothesis using xenografts of WX322 cells, a SCLC cell line that responds to multiple Ca2+ mobilizing neuropeptides. The broad spectrum neuropeptide antagonists [Arg6,D-Trp7,9,MePhe8]substance P(6-11) and [D-Arg1,D-Phe5,Trp7,9Leu11[substance P were shown to inhibit the growth of WX322 xenografts in nude mice. Similar results were obtained with xenografts of the SCLC cell line H69. The results indicate that broad spectrum neuropeptide antagonists can inhibit the growth of SCLC in vivo and suggest that these antagonists could be useful in the treatment of SCLC.
Cancer Res 1992 Aug 15
PMID:Broad spectrum neuropeptide antagonists inhibit the growth of small cell lung cancer in vivo. 137 15

The interaction between LFA-1 and its natural ligand, ICAM-1, plays an important role in leukocyte adhesion and signal transduction. LFA-1-mediated T-cell adhesion is generally activated by CD3-mediated signal in association with T-cell receptor-mediated recognition of the antigen/major histocompatibility complex on antigen-presenting cells. In the present study, we compared spontaneous or bispecific antibody (BsAb)-directed LAK cell cytotoxicity against ICAM-1+ or ICAM-1- small cell lung cancer (SCLC) cell lines. gamma-Interferon (IFN-gamma)-induced ICAM-1 expression on ICAM-1- SCLC cell lines, and susceptibility to LAK cells was increased simultaneously. Increased cytolysis of the IFN-gamma-treated SCLC was inhibited by an anti-ICAM-1 monoclonal antibody (mAb). Furthermore, LAK cell cytotoxicity directed by BsAb, which was composed of OKT3 and anti-SCLC mAb, was also increased by the IFN-gamma treatment of SCLC, and this increase was inhibited by an anti-ICAM-1 mAb but not by anti-Class I or anti-CD2 mAb. These results suggest that a prior administration of IFN-gamma would enhance the efficacy of the following specific targeting therapy utilizing BsAb and LAK cells by up-regulating the ICAM-1 expression on tumor target cells. The combinational use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients.
Cancer Res 1992 Sep 15
PMID:Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x antitumor antibody-directed lymphokine activated killer cell cytotoxicity. 138 Dec 73

Homozygous deletions are instrumental in the detection and cloning of tumor suppressor genes. We report the isolation and characterization of 39 new single-copy probes saturating a submicroscopic homozygous deletion detected in the DNA of the small cell lung cancer (SCLC) cell line U2020. The probes were selected from a large collection, covering the entire length of chromosome 3 with an estimated average spacing of 100-150 kb. Based on the number of probes in the deletion and the probe density, the size of the U2020 submicroscopic deletion was estimated to be in the range of 4-7 megabases. Among the deleted loci, 17 showed conservation across species, probably representing potential coding gene sequences. By genetic and physical mapping of a large randomly chosen fraction of the deleted probes, we defined the location of the U2020 deletion within chromosome band 3p12. Our cloning strategy is based on narrowing the region of interest by eliminating probes that retain heterozygosity in SCLC samples, thus selecting for probes in the region of common loss.
Genes Chromosomes Cancer 1992 Sep
PMID:Molecular characterization of a large homozygous deletion in the small cell lung cancer cell line U2020: a strategy for cloning the putative tumor suppressor gene. 138 47

Studies of mutant genotypes of the retinoblastoma susceptibility gene (RB1) in different solid tumors have mainly been concentrated on the demonstration of loss of heterozygosity (LOH) at both internal and external polymorphic sites. One reason for this is the complex organization of the gene. The p105RB protein has been shown to interact with both DNA and regulatory cellular proteins and oncoproteins. The amino acids encoded by exon 21 are implicated in several of these interactions. Both point mutations and intragenic deletions involving exon 21 have previously been reported in human tumors. We have examined RB1 exon 21 from a number of human tumor types where significant LOH in or around the RB1 gene has been reported. DNA from 78 primary tumors was amplified using the polymerase chain reaction (PCR) with primers covering exon 21, followed by constant denaturant gel electrophoresis (CDGE). The 78 tumors included 11 breast carcinomas, 30 nonsmall cell lung carcinomas, 6 colon carcinomas, and 31 sarcomas. The small cell lung cancer cell line NCI-H209, previously shown to harbour a point mutation in codon 706: TGT- greater than TTT (Cys- greater than Phe), was detected using CDGE. Apart from this control mutant cell line, we did not detect any mutations in the examined region in any of the tumors.
Genes Chromosomes Cancer 1992 Sep
PMID:No alterations in exon 21 of the RB1 gene in sarcomas and carcinomas of the breast, colon, and lung. 138 57

Using fluorescence in situ hybridisation (FISH) the chromosomal location and relative order of six human chromosome 3 probes has been determined. The sensitivity of the technique has enabled the relative mapping of probes carrying inserts as small as 500 basepairs (bp), thus allowing the following proximal-distal probe order to be proposed: D3S30 (3p13-14), D3S4 (3p13-14), D3S2 (distal 3p14), D3S32 (3p21), D3S48E (3p21-23), and D3S11 (3p22-23). These data combined with the deletion mapping data of other researchers raise the possibility that the loss of more than one region of the short arm of chromosome 3 may be important in the development of small cell lung cancer.
Genes Chromosomes Cancer 1992 Apr
PMID:Ordering of six polymorphic DNA markers important in the delineation of 3p deletions in neoplasia. 138 64

It is now well accepted that differences exist in the intrinsic radiosensitivity of human tumour cells although the molecular basis of this is still unclear. Current evidence suggests that of the lesions induced in DNA by ionising radiation, double-strand breaks (DSB) are the most closely linked to cell death. In this study, levels of DSB were measured by neutral filter elution under conditions of both repair inhibition and maximum recovery and compared with clonogenic survival curves for high (HDR) and low dose-rate (LDR) irradiation in human carcinoma lines of differing radiosensitivity. Four human lung carcinoma lines were used, two small-cell (SCLC; HC12 and HX149) and two non-small cell lines (NSCLC; HX147A7 and HX148G7). Cell survival was measured by soft agar and monolayer colony-forming assays as appropriate and a large variation in sensitivity of the cell lines was seen (alpha values of 0.06 to 0.56 Gy-1). We have previously reported that the damage induced at high dose rate does vary in these cell lines but not in a way which correlates with their cell survival response [5]. Following irradiation to 15 Gy at low dose rate essentially no DSBs were detected in any of the four lines but at 70 Gy the more sensitive SCLC showed more residual damage than in the more radioresistant NSCLC lines. The prime determinant of the difference between the LDR and HDR damage curves is likely to be repair occurring during irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Cancer 1992
PMID:Differences in the level of DNA double-strand breaks in human tumour cell lines following low dose-rate irradiation. 138 73

A 15-year experience with paraneoplastic sensory neuronopathy at the Mayo Clinic is reviewed. Of 26 patients with paraneoplastic sensory neuropathy, 19 had small cell lung cancer, 4 had breast cancer, and 3 had other neoplasms. There was a striking predominance of females (20:6). Neuropathic symptoms (pain, paresthesia, sensory loss) were asymmetric at onset, with a predilection for the upper limbs; in three patients, symptoms were confined to the arms. Electrophysiologic testing revealed absent sensory responses and normal or minimally altered motor responses. Slightly more than half the patients had associated autonomic, cerebellar, or cerebral abnormalities. In some patients, treatment of the neoplasm seemed to halt progression of the neuronopathy, but none had neurologic improvement and most continued to worsen, even when the oncologic response was good. Distinguishing between paraneoplastic and nonparaneoplastic sensory neuronopathies can be difficult, but prominent neuropathic pain, neurologic dysfunction involving more than the peripheral sensory system, or an increased cerebrospinal fluid protein value should prompt a careful search for a cancer.
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PMID:The distinctive clinical features of paraneoplastic sensory neuronopathy. 139 44

In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.
Cancer Res 1992 Nov 01
PMID:Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study. 139 20

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.
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PMID:Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome. 140 77


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