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

Lung carcinomas represent a heterogeneous group of tumours with large variations in the biochemical, clinical, morphological and pathological manifestations. Despite the neuroendocrine features of small cell lung cancer (SCLC), it is today generally accepted that all types of lung cancer emanate from a common endodermally derived multipotent stem cell of the bronchial epithelium. NCAM (neutral cell adhesion molecule) has been shown to be a sensitive marker of SCLC. The presence of NCAM, with the alpha (2,8) polysialic acid units characteristic of embryonal NCAM, in SCLC and in a portion of NSCLC, seems to correlate with the malignant behaviour and prognosis of the tumours, suggesting that NCAM may have a functional role in the clinicopathological manifestations of lung cancer. Fuc-GM1 with 2-hydroxy fatty acids as a characteristic component of the ceramide has been found to be a unique ganglioside of SCLC, detected in the tissues as well as in serum from SCLC patients using specific monoclonal antibodies. Accumulation of sialylated and fucosylated polylactosamine type 2 carbohydrate glycolipid and glycoprotein antigens was found in serum and tissues of lung tumours in accordance with what is described in gastrointestinal carcinomas, and these antigens may be regarded as general carcinoma antigens irrespective of organ. Sialylated and fucosylated type 1 antigens, and gangliosides with NeuAc alpha (2,6)Gal linkage were also accumulated in lung cancer. The human immune system has been found to recognize lung cancer carbohydrate antigens, which might be human lung cancer autoantigens.
 ...
PMID:Carbohydrate antigens in human lung carcinomas. 152 May 24

We have studied MAbs* for their ability to detect SCLC and differentiate this tumor type from the other lung tumor histotypes in cryostat sections of biopsy specimens taken at bronchoscopy from patients with suspected primary lung tumor disease. MAb F12, specific for the ganglioside fucosyl-GM1, reacted with 58% of the cases with SCLC (n = 19) and with less than 3% of those with non-SCLC (n = 38). MAb 123C3, specifically reactive with NCAM, reacted with 78% of the SCLC cases (n = 23). With this MAb no positive staining was seen in the non-SCLC cases (n = 41). None of the two MAbs reacted with tissue sections without tumor. In combined analysis with MAbs F12 and 123C3, all SCLC cases (n = 15) were positive with either and 47% with both of the MAbs. Our results show that both MAbs F12 and 123C3 are highly specific for SCLC in bronchoscopic biopsy tissue specimens, whereas the sensitivity for this histotype tends to be higher with MAb 123C3 than with F12 (P = 0.14). When used in combination, all SCLC cases could be identified. These MAbs may therefore be valuable as complements to current histopathologic characterization and differentiation of lung cancer.
 ...
PMID:Immunohistochemical detection of two small cell lung carcinoma-associated antigens defined by MAbs F12 and 123C3 in bronchoscopy biopsy tissues. 165 59

With the aid of a highly specific murine monoclonal antibody, F12, an immunofluorescence method was elaborated that allowed sensitive and specific detection of the ganglioside antigen fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) in different types of human lung cancer and normal tissues. Nineteen of 21 cases of small cell lung cancer were positive with the F12 immunofluorescence method as compared to 2 of 10 squamous epithelial cell lung cancers and 1 of 5 large cell lung cancer specimens. Specimens of lung adenocarcinoma (8 cases) and bronchial carcinoid (3 cases) were all negative, as were 2 examined cases of neuroblastoma. No fucosyl-GM1 could be detected in normal lung and bronchus. However, in thymus, spleen, and lamina propria of the small intestine sparsely distributed clusters of small round cells were stained as well as intramural ganglionic cells of the small intestine and islet cells of the pancreas. All other normal tissues tested were negative. Results obtained with immunofluorescence closely agreed with immunochemical determination of fucosyl-GM1 in lipid extracts of tissues. Our findings suggest that fucosyl-GM1 is strongly associated with small cell cancer of the lung and demonstrate that this tumor-associated antigen can be detected with high sensitivity and specificity with an immunofluorescence method based on the use of the F12 monoclonal antibody.
 ...
PMID:Immunohistological detection of fucosyl-GM1 ganglioside in human lung cancer and normal tissues with monoclonal antibodies. 264 49

Although not quite as well protected as in the CNS, nerve fibres in peripheral nerves are relatively protected from systemic immune responses and inflammatory reactions by the specialized endoneurial endothelial and perineurial barriers. Expression of MHC class II molecules is restricted to a few macrophage-like cells. Compared with peripheral nerve trunks, there are more of these cells and more permeable blood vessels in the dorsal root ganglia and spinal roots. These are sites of predilection for the inflammatory response in experimental allergic neuritis. This experimental disease can be induced by immunization with either of two myelin proteins, P0 and P2, and a similar but less inflammatory, more chronic demyelinating neuropathy can be induced in rabbits with the glycolipid galactocerebroside. In myelin protein induced EAN CD4+ T helper cell responses are sufficient to transfer full-blown disease but antibodies, of undefined specificity, may also play a part. In rabbit galactocerebroside neuritis, antibodies are probably more important and are directed predominantly against a haptenic group including galactose. Experimental allergic neuritis provides an accurate histological model of GBS and CIDP. A small proportion of patients with GBS and CIDP show T-cell responses to P0 and/or P2 which may mark important pathogenetic reactions. Also some patients with GBS and CIDP have antibodies to gangliosides, including for instance the most abundant peripheral nerve ganglioside LM1, which may also be important. In particular, patients with acute severe GBS and marked axonal degeneration often have IgG antibodies to GM1 and GD1b, while patients with Miller Fisher syndrome are characterized by antibodies to GQ1b. IgM antibodies to ganglioside GM1 are often found in multifocal motor neuropathy with conduction block, but are not a sensitive or specific test for that condition. Antibodies to sulphatide have recently been found in some patients with distal predominantly sensory axonal neuropathy. High titres of antibody to MAG which also react with SGPG are specific for IgM paraproteinaemic demyelinating neuropathy. Antibodies to an approximately 37kDa protein present in neuronal nuclei (Hu) are specific for paraneoplastic sensory neuronopathy usually associated with SCLC. Autoimmune responses to neural antigens have become useful diagnostically in some diseases and probably indicate important pathogenetic mechanisms. In inflammatory demyelinating neuropathy, macrophage-mediated demyelination is probably targetted by both antibody and T-cell mediated autoimmune responses. The nature of the autoantigen and the relative importance of T- versus B-cell responses are likely to vary depending on the nature of any initiating immunization and the host immunogenetic background.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Inflammatory neuropathies. 792 91

Cholera toxin (CT) inhibited the growth of three out of 10 small cell lung cancer (SCLC) cell lines and two out of seven non-small cell lung cancer (NSCLC) cell lines when tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. These CT-sensitive as well as CT-resistant cell lines bound well to the non-toxic CT-B subunit-fluorescein isothiocyanate conjugate (FITC-CTB) when assayed by flow cytometry. Using the reaction of horseradish peroxidase-conjugated CT-B (HRP-CTB) on thin-layer chromatography (TLC), we analyzed gangliosides extracted from SCLC cell lines, CT-resistant SBC-1, minimally CT-sensitive SBC-3 and CT-sensitive SBC-5. HRP-CTB was found to react not only with GM1, but also with Fuc-GM1, GD1b and other gangliosides on TLC. Although CT-resistant SBC-1 cells bound well to FITC-CTB, the binding of gangliosides extracted from SBC-1 cells to HRP-CTB was markedly decreased when compared to those from CT-sensitive SBC-5 cells. The CT resistance of the minimally CT-sensitive SBC-3 cell lines, which binds weakly FITC-CTB and HRP-CTB, was partially reversed by exogenous GM1 pretreatment. These observations suggest that the amount of gangliosides, such as GM1, Fuc-GM1 and GD1b, on the cells, rather than the CT-binding ability to the cells, plays a major role in cytotoxicity by CT.
 ...
PMID:Inhibitory effects of cholera toxin on in vitro growth of human lung cancer cell lines. 828 10

Lung carcinomas represent a highly heterogenous group of tumors, which includes small cell lung cancer (SCLC). The ganglioside fucosyl-GM1 (FucGM1) was originally identified as a highly selective marker for SCLC. A number of monoclonal antibodies against FucGM1 have been produced against the purified ganglioside, and their specificity validated. With monoclonal antibodies, FucGM1 has been detected in tissues as well as in serum samples from SCLC patients. A sensitive, quantitative assay method for FucGM1 was developed based on scintillation proximity immunoassay (SPA): A specific monoclonal antibody against FucGM1 is bound to immunosorbent particles that contain a fluor. When radiolabelled FucGM1 binds to these particles, the fluor is excited, and the photons emitted can be measured directly in a beta-counter. This sensitive assay for FucGM1 has several potential diagnostic applications: differential diagnosis of SCLC, development of serum assays for diagnosis and monitoring of disease progression, and monitoring of patient response to therapy. The expression of FucGM1 in SCLC cells is heterogeneous, and may depend on the differentiated state of tumor cells. However, monoclonal antibodies specific for FucGM1 may have important future applications for radioimmunoimaging as well as in immunotherapy for SCLC.
 ...
PMID:Monoclonal antibodies for diagnosis and potential therapy of small cell lung cancer--the ganglioside antigen fucosyl-GM1. 830 35

Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.
 ...
PMID:Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. 876 May 90

Gangliosides are complex glycolipid constituents of cell membranes. They are involved in many biological functions including cell-cell recognition, cell-matrix attachment, cell growth and cell differentiation. Analysis of tumor associated gangliosides may aid in the characterisation of tumour cells and their degree of malignant transformation. We have characterised a total of eight lung cancer cell lines (four small cell and four non-small cell lung cancer) with respect to ganglioside and alpha v integrin receptor expression. Ganglioside GD3 was detected using the monoclonal antibody R24. Ganglioside GM1 was detected using the beta-subunit of cholera toxin. Ganglioside 9-O-acetyl GD3 and the alpha v integrin receptor were measured using commercially available monoclonal antibodies. Our results indicate that small cell lung cancer cell lines express significant levels of GD3 and 9-O-acetyl GD3. Ganglioside GM1 and alpha v integrin receptor were not specific to any histological subtype. The expression of ganglioside GM1 and GD3 was independent of cell-cycle phase. We conclude that GD3 and 9-O-acetyl GD3 expression may be additional markers of the Small Cell Lung Cancer phenotype, but their significance is unknown. Therefore a characteristic ganglioside pattern cannot be defined according to histological subtype. alpha v integrin receptor expression is not unique to cells expressing GD3.
 ...
PMID:Ganglioside expression in lung cancer cell lines. 926 45

Expression of a number of antigens associated with small cell lung cancer (SCLC) have been proposed as a marker of malignancy and the diagnostic tool for the staging procedures and important prognostic factor. Since the bone marrow (BM) was described as a frequent site for SCLC metastases, we have decided to assess clinical importance of cancer cells detection in BM, using immunofluorescence with MAC-1, MAC-31, NSE and anti-Fucosyl-GM1 (PF3) antibodies. The group of 32 patients with SCLC was assessed using our panel of antibodies. Control group consisted of 5 patients with other malignancies (3 patients with malignant lymphoma, 1 with chronic lymphocytic leukaemia and 1 with non-SCLC). The study revealed no correlation between the expression of SCLC markers in patients BM and the cancer treatment outcome measured as a response for treatment, time to progression, and survival time, and no significant difference was found between the patients and control group.
 ...
PMID:[The use of monoclonal antibodies in the detection of small cell lung cancer metastases in bone marrow]. 1048 25

Although small cell lung cancer (SCLC) is highly responsive to chemotherapy, relapses are common, and most patients die within 2 years of diagnosis. After initial therapy, standard treatment is observation alone. We have been investigating immunization against selected gangliosides as adjuvant therapy directed against residual and presumably resistant disease persisting after chemotherapy and irradiation. Previously, we reported that the presence of anti-GM2 ganglioside antibodies is associated with a prolonged disease-free survival in patients with melanoma, and that SCLC patients immunized with BEC2, an anti-idiotypic monoclonal antibody that mimics the ganglioside GD3, had a prolonged survival compared with historical controls. In the present trial, fucosyl-alpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3) Galbeta1-4Glcbeta1-1Cer (Fuc-GM1), a ganglioside expressed on the SCLC cell surface, was selected as a target for active immunotherapy. Fuc-GM1 is present on most SCLCs but on few normal tissues. SCLC patients achieving a major response to initial therapy were vaccinated s.c. on weeks 1, 2, 3, 4, 8, and 16 with Fuc-GM1 (30 microg) conjugated to the carrier protein keyhole limpet hemocyanin and mixed with the adjuvant QS-21. Ten patients received at least five vaccinations and are evaluable for response. All patients demonstrated a serological response, with induction of both IgM and IgG antibodies against Fuc-GM1, despite prior treatment with chemotherapy with or without radiation. Posttreatment flow cytometry demonstrated binding of antibodies from patients' sera to tumor cells expressing Fuc-GM1. In the majority of cases, sera were also capable of complement-mediated cytotoxicity. Mild transient erythema and induration at injection sites were the only consistent toxicities. The Fuc-GM1-KLH + QS-21 vaccine is safe and immunogenic in patients with SCLC. Continued study of this and other ganglioside vaccines is ongoing.
 ...
PMID:Immunogenicity of a fucosyl-GM1-keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer. 1053 41


1 2 Next >>