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)

Monoclonal antibodies (MAbs) 126 (immunoglobulin M) and 14.18 (immunoglobulin G3) react strongly with the cell surface of small cell carcinoma of the lungs (SCCL) and are unreactive with most normal tissues and other neoplasms with the notable exception of tumors derived from cells of neural crest origin. These MAbs react specifically with the oligosaccharide portion of the disialoganglioside GD2. Analysis of total gangliosides from cultured cell lines derived from SCCL indicates that GD2 is a predominant ganglioside. A comparison of the reactivities of MAbs against GD2 with those directed against gangliosides GM2 and GD3, each differing from GD2 by a single sugar residue, clearly indicates that GD2 is preferentially expressed by cultured cells derived from SCCL. Membranes isolated from these cells exhibit GD2 synthetase activity which specifically converts the precursor GD3 to GD2 in the presence of uridine diphosphate-N-acetyl galactosamine as the glycosyl donor. We present evidence that in SCCL, GD2 serves as a relevant target antigen for monoclonal antibody-mediated cytolysis. Specifically, we demonstrate that MAb 14.18 (immunoglobulin G3), can lyse small cell carcinoma of the lung targets by either complement- or antibody-dependent cellular cytotoxicity.
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PMID:Biosynthesis and expression of the disialoganglioside GD2, a relevant target antigen on small cell lung carcinoma for monoclonal antibody-mediated cytolysis. 301 21

The lipid-bound sialic acid (LSA) levels increased in the metastasizing Lewis lung carcinoma (3LL) and significantly decreased in blood plasma of the tumour-bearing mice after cyclophosphamide treatment correlating with the drug therapeutic effect. 5-fluorouracil that was less active in the used therapeutic doses did not cause similar changes in the LSA levels. No correlation was found between the LSA levels in adenocarcinoma 755 and the drug antitumour activity. It was observed that the content of hematoside, GM1 and GD1b sharply increases and GD3 and GD1a levels significantly decrease under the cyclophosphamide treatment of the Lewis tumour.
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PMID:[Changes in the content and composition of gangliosides of tumors as affected by chemotherapeutic agents]. 651 Mar 46

The fate of anti-tumor monoclonal antibodies (mAbs) after binding to the cell surface is one of the important factors for application of mAbs in therapy. For mAbs to remain on the cell surface for a long time is preferable character for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). On the other hand, quick internalization of mAbs into cytoplasm is advantageous for cytotoxic effects of toxins or cytotoxic drugs conjugated with mAbs. In this study we investigated the localization of anti-carbohydrate mAbs in vitro by immunocytochemical methods at the electron microscopic level. Anti-ganglioside GM3 mAb (mouse IgM) was localized both in cytoplasmic vesicles and on the cell surface membrane of mouse melanoma cells after incubation for 30 min at 37 degrees C. Anti-ganglioside GM2 mAb (mouse IgM), anti-ganglioside GD2 mAb (mouse IgG3) anti-ganglioside GD3 mAb (mouse IgG3) mainly existed on the cell surface of human small cell lung carcinoma cells, human neuroblastoma cells and human melanoma cells, respectively, after incubation for 30 min at 37 degrees C. On the other hand, anti-sialyl Lea mAb (mouse IgG1) was intensively incorporated into the cytoplasm of human colon tumor cells under the same conditions. Anti-ganglioside GD3 mAb and anti-sialyl Lea mAb were radiolabelled with 125Iodine and traced in in vitro culture. When the cells were incubated in the presence of the 125I-mAb for 90 min on ice, the ratio of intracellular counts to surface counts was 8/92 for anti-ganglioside GD3 mAb and 31/69 for anti-sialyl Lea mAb respectively. After the subsequent incubation for 60 min at 37 degrees C, the ratio altered to 13/87 for anti-ganglioside GD3 mAb and 54/46 for anti-sialyl Lea antigen mAb. This study suggested that internalization of anti-carbohydrate mAbs after the binding to the cell surface was different among the mAbs depending on the character of antigens. In conclusion, anti-ganglioside mAbs have beneficial characters for CDC or ADCC while anti-sialyl Lea mAb is suitable for immunoconjugates.
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PMID:Immunocytochemical study on internalization of anti-carbohydrate monoclonal antibodies. 829 35

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.
Lung Cancer 1997 Aug
PMID:Ganglioside expression in lung cancer cell lines. 926 45

Gangliosides on tumor cells have been suggested as potential target antigens for specific immunotherapy in various types of cancer including small cell lung cancer (SCLC). In this study we have compared the expression of three gangliosides that have been described as tumor-associated antigens, FucGM1, GM2 and GD3 in SCLC tissue specimens collected at autopsy, using a double-layer immunofluorescence staining method and specific monoclonal antibodies (Mabs) directed against these ganliosides. We found expression of FucGM1, GD3 and GM2 in (70% (n=20), 60% (n=15) and 40% (n75% of the tumor cells in all lesions from the same patient (five of eight cases). Our results indicate that FucGM1 is a relevant ganglioside antigen in SCLC, and suggest that specific immunotherapy involving more than one ganglioside antigen in SCLC should at least include FucGM1 and GD3.
Lung Cancer 2000 Apr
PMID:Reactivity of monoclonal antibodies with ganglioside antigens in human small cell lung cancer tissues. 1070 6

The characteristic feature of small cell lung cancer carcinoma (SCLC) is the aberrant expression and abundant presentation of fucosyl-GM1 ganglioside (FucGM1). In the present study we searched for the presence of anti-FucGM1 ganglioside, as well as anti-GM1, GM2 and GD3 ganglioside autoantibodies in the sera of patients with SCLC and as a control, in sera of patients with renal cell cancer (RC) and healthy blood donors. The autoantibodies against FucGM1 were present at low titer in only three of 36 SCLC patients, and with similar titer in two of 36 RC patients and four of 36 healthy controls. Likewise, the autoantibodies against GM2 and GM3 gangliosides were found only sporadically and with the same titer and frequency in cancer patients as in healthy persons. Anti-GD3 autoantibodies could not be detected in any of the screened sera.
Lung Cancer 2001 Dec
PMID:Small cell lung cancer is not associated with the presence of anti-fucosyl-GM1 ganglioside autoantibodies reactive in immunoenzymatic test. 1171 35

A number of cancer vaccine and gene therapy approaches are being evaluated in patients with lung cancer. Cancer vaccine strategies include GM-CSF gene-modified cancer cells, liposomal MUC1 peptide, anti-idiotype antibody targeting GD3, Mage-3 peptide, and mutant p53 pulsed dendritic cells among others. Preliminary human trials have demonstrated immune responses as well as tumor regression in late stage disease. The largest human gene therapy experience in lung cancer is with intratumoral gene replacement therapy, predominantly with p53, but such approaches are limited to locoregional disease control. Earlier stage gene therapy programs targeting the immune system or tumor vasculature hold promise as systemic therapies for treatment of advanced, disseminated disease.
Lung Cancer 2003 Aug
PMID:Lung cancer vaccines and gene therapy. 1286 69

GD3, a ganglioside expressed on tumors of neuroectodermal origin such as melanoma and small-cell lung carcinoma (SCLC), is an attractive vaccine target but is poorly immunogenic. Our group has pursued several strategies designed to immunize patients against GD3 including using BEC2, an anti-idiotypic monoclonal antibody that mimics GD3. Pilot trials in melanoma and SCLC indicate that BEC2 can induce an anti-GD3 antibody response in a subset of patients and also suggests that immunization with BEC2 is associated with improved survival. A phase III trial is underway in SCLC patients to determine the effects of BEC2 on overall survival.
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PMID:Vaccinating against GD3 ganglioside using BEC2 anti-idiotypic monoclonal antibody. 1290 Dec 30

Tumors expressing a high level of certain types of tumor-associated carbohydrate antigens (TACAs) exhibit greater metastasis and progression than those expressing low level of TACAs, as reflected in decreased patient survival rate. Well-documented examples of such TACAs are: (i) H/Le(y)/Le(a) in primary non-small cell lung carcinoma; (ii) sialyl-Le(x) (SLe(x)) and sialyl-Le(a) (SLe(a)) in various types of cancer; (iii) Tn and sialyl-Tn in colorectal, lung, breast, and many other cancers; (iv) GM2, GD2, and GD3 gangliosides in neuroectodermal tumors (melanoma and neuroblastoma); (v) globo-H in breast, ovarian, and prostate cancer; (vi) disialylgalactosylgloboside in renal cell carcinoma. Some glycosylations and TACAs suppress invasiveness and metastatic potential. Well-documented examples are: (i) blood group A antigen in primary lung carcinoma; (ii) bisecting beta1 --> 4GlcNAc of N-linked structure in melanoma and other cancers; (iii) galactosylgloboside (GalGb4) in seminoma. The biochemical mechanisms by which the above glycosylation changes promote or suppress tumor metastasis and invasion are mostly unknown. A few exceptional cases in which we have some knowledge are: (i) SLe(x) and SLe(a) function as E-selectin epitopes promoting tumor cell interaction with endothelial cells; (ii) some tumor cells interact through binding of TACA to specific proteins other than selectin, or to specific carbohydrate expressed on endothelial cells or other target cells (carbohydrate-carbohydrate interaction); (iii) functional modification of adhesive receptor (integrin, cadherin, CD44) by glycosylation. So far, a few successful cases of anti-cancer vaccine in clinical trials have been reported, employing TACAs whose expression enhances malignancy. Examples are STn for suppression of breast cancer, GM2 and GD3 for melanoma, and globo-H for prostate cancer. Vaccine development canbe extended using other TACAs, with the following criteria for success: (i) the antigen is expressed highly on tumor cells; (ii) high antibody production depending on two factors: (a) clustering of antigen used in vaccine; (b) choice of appropriate carrier protein or lipid; (iii) high T cell response depending on choice of appropriate carrier protein or lipid; (iv) expression of the same antigen in normal epithelial tissues (e.g., renal, intestinal, colorectal) may not pose a major obstacle, i.e., these tissues are not damaged during immune response. Idiotypic anti-carbohydrate antibodies that mimic the surface profile of carbohydrate antigens, when administered to patients, elicit anti-carbohydrate antibody response, thus providing an effect similar to that of TACAs for suppression of tumor progression. An extension of this idea is the use of peptide mimetics of TACAs, based on phage display random peptide library. Although examples are so far highly limited, use of such "mimotopes" as immunogens may overcome the weak immunogenicity of TACAs in general.
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PMID:Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. 1453 9

The composition of biologically active sphingolipids in hepatoma 22, breast adenocarcinoma, Lewis lung carcinoma, large intestine adenocarcinoma, cervical carcinoma, and melanomas M3 and B16 was compared to elucidate the similarity and differences in sphingolipids of subcutaneously transplantable murine tumors. The sphingolipid composition of the tumors was found to widely vary. The sphingomyelin, ceramide, glucosyl- and lactosylceramide, and ganglioside GD3 contents in hepatoma 22 are higher than those in normal tissue. No common regularities for tumors of different origin were observed in the ratios of bioeffectors inhibiting proliferation and stimulating apoptosis and bioeffectors stimulating cell growth and survival. However, the Cer/(GlcCer + LacCer) ratios were very low and practically equal in two melanoma strains, which probably indicates the degree of tumor malignancy. The results suggest that the content and composition of sphingolipids in tumors depend on their histogenesis.
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PMID:[Biologically active sphingolipids in transplantable tumors of different histogenesis]. 1652 27


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