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)

Human folate receptor (hFR, folate-binding protein) is a single-chain glycoprotein with high specific affinity for folic acid and methotrexate. We have created 4 monoclonal antibodies (MAbs) to hFR, all of which react specifically with purified hFR in Western blots. Flow cytometry indicated that the antibodies all had patterns of reactivity against epithelial cell lines similar to that of antibody MW207 (workshop antibody 12), labeling 2 breast-tumor cell lines and 2 of 5 SCLC without labeling the one non-small-cell carcinoma tested. We used the antibodies to trace the in situ distribution of hFR in histologically normal tissues and in lung tumors by a sensitive alkaline-phosphatase-anti-alkaline-phosphatase immunohistochemical technique. In frozen sections of normal lung, hFR was diffusely distributed on cell membranes of type-1 and type-2 pneumocytes and mucociliary and basilar respiratory epithelial cells of distal bronchi. The receptor was focally expressed by mucociliary cells of proximal respiratory mucosa and by macrophages, but was not detected in stromal smooth muscle, fibroblasts or lymphoid cells. In tumors, hFR was heavily and diffusely expressed on cell membranes of 9 of 10 pulmonary adenocarcinomas, 5 of 5 bronchioloalveolar carcinomas and 2 of 2 carcinoid tumors. It was focally expressed in 3 of 5 large-cell lung carcinomas and was absent from 4 of 5 small-cell carcinomas, 18 of 22 invasive squamous carcinomas, 2 of 2 in situ squamous carcinomas, and 13 of 13 squamous dysplasias of bronchial mucosa. We conclude that hFR is heavily expressed in situ by normal alveolar and bronchial epithelium and by adenocarcinoma of lung. It is usually absent from small-cell carcinoma and squamous tumors at levels detectable by immunohistochemistry.
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PMID:New anti-lung-cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma. 819 1

We developed an IgG1 mouse monoclonal antibody (ONS-M21) directed against a cell surface antigen of medulloblastomas and gliomas in immunisation of mice with the ONS-76 medulloblastoma cell line. The antibody specifically reacted with medulloblastomas, supratentorial primitive neuroectodermal tumours (SPNETs) and gliomas, but not with other neuroectodermally derived tumours (neuroblastoma and melanoma) or with other kinds of tumours (meningioma, neurinoma, leukaemia, and small cell lung cancer). No reactivity was identified with normal body tissues, including peripheral blood cells. Characterisation of the ONS-M21 antigen showed that it was a trypsin-sensitive glycoprotein with a molecular weight of 80 kDa on SDS-PAGE. The pattern of reactivity and the biochemical properties of this antigen were different from those of other markers of medulloblastoma. These results indicate that ONS-M21 detects a new tumour-associated cell surface antigen specifically expressed by medulloblastomas, SPNETs, and gliomas. This is the first report that medulloblastomas may share common cell surface antigens with gliomas, although most studies have concluded that medulloblastoma has a predominantly neuronal phenotype. The lack of reactivity with normal tissue implies that ONS-M21 has potential applications as both a diagnostic tool and a therapeutic agent.
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PMID:Characterisation of a new mouse monoclonal antibody (ONS-M21) reactive with both medulloblastomas and gliomas. 821 97

TSC-36 (TGF-beta1-stimulated clone 36) is a TGF-beta1 inducible gene whose product is an extracellular glycoprotein that contains a single follistatin module. TSC-36 is highly expressed in the lung, but its physiological function is unknown. In an attempt to elucidate it, we investigated the effect of TSC-36 on proliferation of human lung cancer cell lines. We found a correlation between expression of TSC-36 and cell growth: TSC-36 mRNA was not detected in cells derived from small cell lung cancer (SCLC) cells, a highly aggressive neoplasm, but was detected in some non-small cell lung cancer (NSCLC) cells, a moderately aggressive neoplasm. This suggested an antiproliferative function for TSC-36. To address this question, NSCLC PC-14 cells, which express very low level of TSC-36 protein, were transfected with TSC-36 cDNA and the proliferative capacity of stable transfectants was determined by measuring the doubling time, colony forming activity in soft agar and the level of incorporation of (3)H-thymidine into DNA. Under normal culture conditions, the transfected cells showed a longer doubling time, lower plating efficiency and lower rate of DNA synthesis than the parental cells and the control neo transfectant cells. These findings suggested that expression of TSC-36 caused growth inhibition in human lung cancer cells.
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PMID:Expression of a TGF-beta1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines. 1081 77

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.
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PMID:Differential osteopontin expression in lung cancer. 1152 Jun 6

P-selectin (CD62P) is a cell adhesion molecule expressed on stimulated endothelial cells and on activated platelets. It interacts with PSGL-1 (P-selectin glycoprotein ligand-1; CD162) on leukocytes and mediates recruitment of leukocytes during inflammation. P-selectin also binds to several types of cancer cells in vitro and facilitates growth and metastasis of colon carcinoma in vivo. Here we show that P-selectin, but not E-selectin, binds to NCI-H345 cells, a cell line derived from a human small cell lung cancer. EDTA or P7 (a leukocyte adhesion blocking mAb to P-selectin), but not PL5 (a leukocyte adhesion blocking mAb to PSGL-1), can inhibit this binding. P-selectin affinity chromatography can precipitate a approximately 110-kDa major band and a approximately 220-kDa minor band from [3H]-glucosamine-labeled NCI-H345 cells. No expression of PSGL-1 protein and mRNA can be detected in NCI-H345 cells. Taken together, these results suggest that NCI-H345 cells express glycoprotein ligands for P-selectin that are distinct from leukocyte PSGL-1.
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PMID:Characterization of glycoprotein ligands for P-selectin on a human small cell lung cancer cell line NCI-H345. 1167 90

Small cell lung cancer (SCLC) is an aggressive form of lung cancer associated with cigarette smoking and presently accounts for approximately 20% of all lung cancer cases. SCLC cells derive from a neuroendocrine origin and therefore their antigenic profile coincides, to a great extent, with that of neuroendocrine cells. Multiple attempts to generate SCLC-specific MoAbs during the past decade have failed because all SCLC-specific MoAbs isolated also react against neuroendocrine tissues or normal immune cells. Cross-reactivity with normal antigens raises safety concerns due to the inevitable toxicity of such interactions and the dreaded effects. The concept of DIAAD trade mark ( Differential Immunization for Antigen and Antibody Discovery) provides for an immune response that can be effectively focused on cancer antigens. The object is to overcome obstacles resulting from an antigenic hierarchical pattern biased towards a response to dominant antigens in order to induce a robust immune response to cancer antigens. Cancer antigens are weak or nonimmunogenic molecules. Due to the fact that the immune system responds more strongly to immunodominant antigens than to weak immunogenic antigens, cancer cell proliferation is unencumbered. DIAAD employs protocols of induction of tolerance and immunity, conducted in sequential order to "biologically subtract" the immune response of dominant antigens expressed by normal cells. This biological subtraction is achieved in a laboratory animal by first eliminating the immune response to the normal cells or closely related cancer cells, followed by immunization of the same laboratory animal with diseased cells. This procedure directs the immune response exclusively towards antigens expressed by the diseased and not the normal cells. Our objective was to use DIAAD to generate monoclonal antibodies specific to SCLC antigens that are not shared by neuroendocrine cells by contrasting a pool of human SCLC cell lines with a pool of human neuroendocrine cancer cell lines. Four monoclonal antibodies reacted strongly and exclusively with SCLC cells and identified a membrane molecule comprising a single chain glycoprotein. Two of four antibodies were selected for a detailed analysis that revealed a narrow tissue specificity of antigen expressed by colon, lung, and pancreatic cancers (less than 20% staining was found on breast, ovarian and prostate cancer). These antibodies did not bind to various other cancers such as kidney, carcinoid, lymphoma, sarcoma, adrenal, liver, melanoma, seminoma, leiomyoma, basal cell cancer, or undifferentiated cancer. The epitope recognized by the selected MoAbs was destroyed with the removal of carbohydrates from SCLC cells. This result does not exclude the possibility of protein-carbohydrate cooperation in epitope recognition. However, it strongly suggests the pivotal role of carbohydrates in antibody binding to this molecule. Upon binding to the extracellular molecule on SCLC cells, the antibodies were shown to internalize. A low or insignificant level of internalization was recorded following incubation of the antibodies with neuroendocrine-derived tumors. The capacity of these antibodies to internalize upon binding the extracellular receptors renders them potential candidates for prodrug or immunotoxin-targeted therapeutics. In a qualitative experiment involving immunoaffinity purification, the SCLC antigen was shown to be differentially detected in sera of SCLC patients. Plans are being generated to explore the possible utility of this novel SCLC-specific antigen recognized by the above MoAbs as a new biomarker for early diagnosis of the disease, as well as for therapeutic intervention for SCLC.
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PMID:A new small cell lung cancer (SCLC)-specific marker discovered through antigenic subtraction of neuroblastoma cells. 1266 43

FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC.
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PMID:Aberrant methylation of FBN2 in human non-small cell lung cancer. 1595 Oct 52

Sialyl Lewis(a) (sLe(a)), also termed CA19-9 antigen, is recognized by murine mAb19-9 and is expressed on the cancer cell surface as a glycolipid and as an O-linked glycoprotein. It is highly expressed in a variety of gastrointestinal epithelial malignancies including colon cancer and pancreatic cancer, and in breast cancer and small cell lung cancer, but has a limited expression on normal tissues. sLe(a) is known to be the ligand for endothelial cell selectins suggesting a role for sLe(a) in cancer metastases and adhesion. For these reasons, sLe(a) may be a good target for antibody mediated immunotherapy including monoclonal antibodies and tumor vaccines. However, sLe(a) is structurally similar to sLe(x) and other blood group related carbohydrates which are widely expressed on polymorphonucleocytes and other circulating cells, raising concern that immunization against sLe(a) will induce antibodies reactive with these more widely expressed autoantigens. We have shown previously both in mice and in patients that conjugation of a variety of carbohydrate cancer antigen to keyhole limpet hemocyanin (KLH) and administration of this conjugate mixed with saponin adjuvants QS-21 or GPI-0100 are the most effective methods for induction of antibodies against these cancer antigens. We describe here for the first time the total synthesis of pentenyl glycoside of sLe(a) hexasaccharide and its conjugation to KLH to construct a sLe(a)-KLH conjugate. Groups of five mice were vaccinated subcutaneously four times over 6 weeks. Sera were tested against sLe(a)-HSA by ELISA and against sLe(a) positive human cell lines adenocarcinoma SW626 and small cell lung cancer (SCLC) DMS79 by FACS. As expected, mice immunized with unconjugated sLe(a) plus GPI-0100 or unconjugated sLe(a) mixed with KLH plus GPI-0100 failed to produce antibodies against sLe(a). However, mice immunized with sLe(a)-KLH conjugate without GPI-0100 produced low levels of antibodies and mice immunized with sLe(a)-KLH plus GPI-0100 produced significantly higher titer IgG and IgM antibodies against sLe(a) by ELISA. These antibodies were highly reactive by FACS and mediated potent complement mediated cytotoxicity against sLe(a) positive SW626 and DMS79 cells. They showed no detectable cross reactivity against a series of other blood group-related antigens, including Le(y), Le(x), and sLe(x) by dot blot immune staining. This vaccine is ready for testing as an active immunotherapy for treating sLe(a) positive cancer in clinical settings.
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PMID:Synthesis of sialyl Lewis(a) (sLe (a), CA19-9) and construction of an immunogenic sLe(a) vaccine. 1919 Sep 7

Among all cancers, lung cancer is the major cause of deaths. Lung cancer can be categorized into two classes for prognostic and treatment purposes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Both categories of cancer are resistant to certain drugs. Various mechanisms behind drug resistance are over-expression of superficial membrane proteins [glycoprotein (P-gp)], lung resistance-associated proteins, aberration of the intracellular enzyme system, enhancement of the cell repair system and deregulation of cell apoptosis. Structure-performance relationships and chemical compatibility are consequently major fundamentals in surfactant-based formulations, with the intention that a great deal investigation is committed to this region. With the purpose to understand the potential of P-gp in transportation of anti-tumor drugs to cancer cells with much effectiveness and specificity, several surfactant-based delivery systems have been developed which may include microspheres, nanosized drug carriers (nanoparticles, nanoemulsions, stealth liposomes, nanogels, polymer-drug conjugates), novel powders, hydrogels and mixed micellar systems intended for systemic and/or localized delivery.
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PMID:Surfactant-based drug delivery systems for treating drug-resistant lung cancer. 2501 59

Immunotherapy has emerged in recent years as a promising therapeutic approach in lung cancer. Two approaches are of particular interest: immune checkpoint inhibition, which aims to counteract the physiologic mechanisms of immune tolerance co-opted by some tumors, and vaccine therapy, which enables enhanced exposure to tumor antigen. Immune checkpoint therapies include the monoclonal antibody blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) with ipilimumab, as well as antibody blockade of the programmed cell death-1 (PD-1) receptor and the PD-1 ligand. These immune checkpoint therapies have been evaluated in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with early evidence of activity. Vaccines include antigen specific therapies which induce specific antitumor immunity against relevant tumor-associated antigens. In lung cancer, these include the melanoma-associated antigen-A3 (MAGE-A3), membrane-associated glycoprotein (MUC-1), and the epidermal growth factor receptor (EGFR). Whole tumor vaccines have also been evaluated in lung cancer and influence the patient's immune system to allow recognition of the tumor as foreign creating de novo immunity. This review summarizes the evidence to date for the efficacy and safety of immunotherapies in lung cancer.
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PMID:Immunotherapy in lung cancer. 2580 76


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