Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF). The growth of 17 of the 22 cell lines was not significantly and reproducibly affected by NGF. There was minor (1.2-fold) but reproducible stimulation of clonal growth in one glioblastoma cell line (86-HG-39) by NGF, but in this cell line NGF induced no growth modulation in a tritiated thymidine uptake assay. However, clonal growth of another glioblastoma cell line (87-HG-31) and all three lung cancer cell lines tested (HTB 119, HTB 120, CCL 185) could be stimulated up to 3-fold by NGF with a dose-response relationship for the growth factor. Growth stimulation by NGF could be completely reversed by neutralizing anti-NGF antibody and by the tyrosine kinase inhibitor genistein. Evaluation of secondary plating efficiency revealed the stimulation of colony formation as representing self-renewal and not terminal differentiation. Reverse transcriptase-PCR experiments in the five responding cell lines showed expression of both low-affinity NGF receptor (glycoprotein 75) and c-trk transcripts on the mRNA level. Of the five responding cell lines, only 86-HG-39, the cell line with the lowest responsiveness, revealed low-affinity NGF receptor on the protein level; the other four cell lines with high responsiveness, including the three lung cancer cell lines, expressed no low-affinity NGF receptor as shown by fluorescence-activated cell sorter analysis and immunoprecipitation using the ME 20.4 antibody. Immunoprecipitation using anti-trk antibodies was negative in all five responding cell lines. However, binding studies with iodinated NGF showed only low-affinity binding on the 86-HG-39 cell line and only high-affinity binding on the high-responder cell lines CCL 185 and 87-HG-31. In summary, our data suggest that NGF can be operative in stimulation of clonal growth of malignant tumor cells. High-affinity but not low-affinity binding sites mediate signal transduction for clonal growth and signaling involves tyrosine kinase activity.
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PMID:Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. 753 48

A human Hanganutziu-Deicher (HD) antibody and a chicken anti-N-glycolyneuroaminyllactosylceramide (HD3) antibody were compared in their reaction against HD antigen-active ganglioside (HD3) and a glycoprotein (GP) by radioimmunoassay (RIA). The human antibody had a 50 times higher reactivity with the glycoprotein, while the chicken antibody reacted equally with both antigens. Both antibodies had a higher reactivities with HD antigen(s) in sera of five of eight lung cancer patients than 54 normal human sera. Since four of the above five sera had no abnormal titers to GP, it was concluded that their immunological status was antigen excess. The chicken antibody may be useful in follow-up studies of cancer patients to correlate the expression of HD antigen in tissues and sera with the elevation of HD antibodies, offering alternative methods of clinical prognosis of tumor growth and/or metastases. The human HD antibody may also be useful for the detection of HD antigens of glycoprotein nature.
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PMID:Potential use of specific human and chicken antibodies for detection of Hanganutziu-Deicher antigen(s) in sera of cancer patients. 773 48

Enzyme immunoassay performed in patients with malignant and benign affections of the lungs determined antibodies (Abs) to glycoprotein isolated from saprophyte microorganism Bacilus megaterium H. In pulmonary tuberculosis and nonspecific pulmonary inflammation the above Abs occurred in patients with fibrous-proliferative changes and associated neoplastic conditions. In lung cancer the Abs were detected in well and moderately differentiated tumors. Nondifferentiated and poorly differentiated variants did not exhibit any rise in Abs to glycoprotein.
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PMID:[Antibodies to Bacillus megaterium H glycoprotein in patients with lung diseases]. 777 57

An ELISA to detect a glycoprotein TAA-specific immune complexe (IC) has been developed utilizing a murine monoclonal antibody, AD1-40F4, that recognizes a 90kD subunit of the antigen. In this study we determined the applicability of the assay to assess the presence of the glycoprotein TAA-IC in lung cancer patients. The incidence of glycoprotein TAA-IC was 63% (33/89), significantly higher (p < 0.05) than normal controls (3.2%; 8/250). Comparative analyses of pre- and post-operative sera of non-small cell lung cancer patients revealed that in 30% (20/66) of patients, the ELISA value for the marker did not become negative, i.e., decrease below the cut-off level (0.410 ODnm) after surgical resection of the tumor. It is postulated that these patients either had extensive disease or microscopic metastases that were not resectable. Evaluation of post-operative glycoprotein TAA-IC results in relation to disease recurrence revealed a significant association between the presence of the antigen in serum and disease recurrence. There did not appear to be any association between the glycoprotein TAA-IC and the other conventional marker, CEA; however, using more than one marker increases the incidence of detection of the disease.
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PMID:Prognostic value of a 90kD subunit containing glycoprotein tumor-associated antigen specific immune complexes in lung cancer patients. 784 31

Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimens given prior to bone marrow and peripheral stem-cell rescue. Despite its high degree of efficacy in a number of malignancies, the optimal dose, schedule, and dosing form remain to be defined. It is possible that continuous or prolonged inhibition of the substrate, i. e., topoisomerase II, may be the key factor for the cytotoxic effects of etoposide. Clinical studies have shown the activity of etoposide to be schedule-dependent, with prolonged dosing, best accomplished by the oral dosing form, offering a therapeutic advantage. This benefit awaits validation by prospective randomized studies, some of which are in progress. Recent clinical investigations have focused on the use of etoposide in combination with (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity of etoposide; (b) agents such as cyclosporin A and verapamil to alter the p-glycoprotein (mdr1) function; and (c) topoisomerase I inhibitors to modulate the substrate upon which it acts. There is continued interest in the development of etoposide to its maximal clinical dimensions and in the examination of alternative biochemical and mechanistic approaches to further our understanding of this highly active agent.
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PMID:Etoposide: current status and future perspectives in the management of malignant neoplasms. 807 20

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.
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PMID:Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer. 811 11

KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma-associated antigen and is also regarded as an indicator of disease activity of interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants and consists of multiple heterogeneous antigen molecules. We have searched for circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6 as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6-associated molecule detected by a bimonoclonal bideterminant sandwich assay using the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the positive rate increased with the progression of clinical stage. Elevated levels were not detected in normal individuals or in patients with benign lung diseases, other histologic types of lung cancer, gastric cancer, colon cancer or breast cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as a serum tumor marker for pulmonary adenocarcinoma.
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PMID:A new serum tumor marker, CAM 123-6, highly specific to pulmonary adenocarcinoma. 814 2

The term multidrug resistance is defined in this article as cellular resistance to anticancer agents due to a decreased concentration of active drug at the target sites that is caused by increased metabolism or altered transport or routing of the active drug species. Resistance related to alterations in the drug targets or apoptotic pathways is not discussed. Until recently multidrug resistance was associated almost exclusively with p-glycoprotein (Pgp)-overexpression. However, other non-Pgp-related mechanisms have been tracked down. It has been shown that transfection of the gene that encodes a novel drug transport protein, the multidrug resistance protein, induces cross-resistance for many multidrug resistance drugs as well as active transport of daunorubicin from tumor cells. Surprisingly, it has also been found that multidrug resistance protein mediates transport of negatively charged species that are not classic multidrug resistance drugs, such as leukotriene C4 and other glutathione conjugates as well as negatively charged dyes. It was therefore suggested that multidrug resistance protein is identical with the multispecific organic anion transporter. The transport rate of several positively charged drugs (vincristine, rhodamine-123, daunorubicin) by multidrug resistance protein appeared to be dependent on the cellular glutathione levels. Multidrug resistance protein seems to be constitutively expressed in normal tissues at a low level with few tissues having higher expression. Multidrug resistance protein overexpression in in vitro-selected MDR cell lines occurs relatively frequently in lung cancer and leukemia cell lines and often precedes Pgp overexpression. Differential expression has been demonstrated in tumor samples, which suggests a role in resistance to chemotherapy in at least certain tumor types. Modulation studies of multidrug resistance protein activity are still scarce. Other non-Pgp, non-multidrug resistance protein multidrug resistance mechanisms probably exist but have not been identified at the molecular level as yet.
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PMID:Multidrug resistance proteins and other drug transport-related resistance to natural product agents. 854 2

Prostate-specific antigen (PSA) is a glycoprotein produced by the epithelial cells of the prostate. PSA is currently used clinically to diagnose and monitor prostate carcinoma. In previous work we have demonstrated that 30% of breast tumors and, more rarely other tumors, contain significant amounts of PSA. PSA appears to be a favorable prognostic indicator in breast cancer. Here, using a sensitive assay, we demonstrated for the first time that lung adenocarcinomas and squamous cell carcinomas also contain PSA. PSA in lung tumor extracts was present mainly in its 33 KDa form (free PSA), at levels measurable by commercial methods. The presence of PSA was associated more closely with male patients and adenocarcinomas. The physiological role of PSA in lung tissue and the prognostic significance of PSA in lung cancer remain to be determined. These and our previous data as well as reports by other groups support the view that PSA is a ubiquitous biochemical marker of steroid hormone action.
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PMID:Immunoreactive prostate-specific antigen in lung tumors. 858 5

Changes in the concentration of haptoglobin-glycoprotein-globulin fraction of blood serum were studied in patients with lung cancer. It was found, that haptoglobin concentration increased in accordance to a disease stage. Formation of haptoglobin hemoglobin (Hp-Hb) complex in the sera of patients may be of great importance for neutralization of superoxidative products.
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PMID:[Serum haptoglobin in lung cancer patients]. 859 75


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