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)

Interleukin-3 (IL-3) is a glycoprotein produced primarily by activated T-lymphocytes. As a hematopoietic growth factor it affects the proliferation, maturation, and survival of progenitor cells of the myeloid, erythroid, and megakaryocyte lineages. Initial studies in cancer patients with normal bone marrow using IL-3 doses of > 5 micrograms/kg daily produced a doubling of the neutrophil count within 2-3 days and that of platelet counts by days 10-12. Phase I-II clinical trials have examined the response to IL-3 in various clinical states, and ongoing phase III studies are currently assessing the clinical relevance. In the treatment of relapsed lymphoma, small-cell lung cancer, and breast and ovarian cancer, IL-3 at doses of 5-10 micrograms/kg daily given mainly subcutaneously for 5-10 days has been shown to maintain chemotherapy schedules while preserving adequate granulocyte and platelet numbers in the peripheral blood. At these doses, side effects were uncommon. The translation of these observations into clinical phase III studies has been disappointing, with no clear-cut clinical advantage being observed in the treated group. This reflects the relative lack of myelosuppression seen with most current regimens for solid tumors. The role of combined treatment with IL-3 in association with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor after cytotoxic treatment has yet to be established. However, it has been shown that they may act synergistically, resulting in significantly higher numbers of progenitor cells in the peripheral blood than when either is used alone. Combinations with IL-6 are also under study, as is the use of "cocktails" for ex vivo expansion of progenitors. This latter approach would allow single, small collections to be used for multiple infusions of progenitors and could support significant dose-intensification regimens by relieving myelosuppression. It is clear that the place of these newer cytokines in current treatment remains to be clarified.
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PMID:Is interleukin 3 active in anticancer drug-induced thrombocytopenia? 876 24

Since the discovery of KDN glycoprotein in 1986, the occurrence of KDN (= 2-keto-3-deoxy-D-glycero-D-galactonononic acid) glycan chains has been reported for different organisms ranging from bacteria to lower vertebrates, including amphibians and fish. Recently, the presence of alpha2-->8-linked oligo/polyKDN groups in mammalian tissues was shown by immunohistochemical and immunoblotting methods. In this communication we report the detection and quantitation of the KDN residues in glycoprotein and glycolipid fractions of rat tissues and human lung cancer cell lines by a highly sensitive fluorometric high-performance liquid chromatography (HPLC) method. We now provide unequivocal chemical proof of the occurrence of KDN in mammals by isolation of KDN from pig submaxillary gland and by structural assignment using chemical methods including fast atom bombardment-mass spectrometry, fluorescence-assisted HPLC analysis, gas-liquid chromatography, and 1H NMR spectroscopy.
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PMID:Identification of 2-keto-3-deoxy-D-glycero--galactonononic acid (KDN, deaminoneuraminic acid) residues in mammalian tissues and human lung carcinoma cells. Chemical evidence of the occurrence of KDN glycoconjugates in mammals. 879 86

Mucin glycoprotein can promote tumor-cell invasion metastasis and modulate the immune recognition of cancer. This study aimed to elucidate the clinical significance of mucin gene overexpression in lung cancer. We collected 60 lung cancer samples and paired non-tumorous lung portions of varying types and stages. Slot-blot analysis with specific anti-sense oligonucleotide probes derived from tandem repeat sequence of MUC1, -2, -3, -4, 5B and 5AC were utilized to compare the amount of mucin gene mRNA in tumor samples with that of the non-tumorous counterparts. A ratio higher than 1.5 for each specific mucin mRNA amount was considered to indicate mucin gene overexpression in tumors. Immunohistochemical staining of monoclonal antibodies against mature airway mucin (17Q2) and MUC1 mucin protein (HMFG2) were also used to analyze mucin protein. The study showed that overexpression of mucin genes frequently occurred in lung cancer (25 out of 60, 41.7%), but that there was no preferential expression of a particular mucin gene or a combination of mucin genes in these tumors. The overexpression of mucin genes and mucin protein had no correlation with tumor stage, nodal stage, histology or pathological differentiation grade. Tumors of smokers had higher MUC5B and MUC5AC mRNA expression ratios than those of non-smokers. Tumors with increased expression of mucin genes tended to be associated with post-operative relapse, especially when MUC5B and MUC5AC genes were overexpressed (p = 0.015 and 0.025, respectively). The study suggests that overexpression of novel tracheobronchial mucin genes may result in an increased likelihood of post-operative lung-cancer recurrence or metastases.
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PMID:Overexpression of MUC5 genes is associated with early post-operative metastasis in non-small-cell lung cancer. 898 Feb 47

Resistance to chemotherapy is a major cause for failure in the treatment of lung cancer. Compared to conventional cytotoxic drugs, immunotoxins act by different mechanisms and thus might be promising for the treatment of chemoresistant cancer. The monoclonal antibody MOC31 recognises the epithelial glycoprotein-2 (EGP-2), a cell-surface antigen associated with small-cell lung cancer (SCLC) and a major fraction of lung adenocarcinomas. An immunotoxin composed of MOC31 and a recombinant from of Pseudomonas exotoxin A lacking the cell-binding domain (ETA252-613) was prepared and its effect on lung cancer cell lines examined. MOC31 ETA252-613 was selectively cytotoxic to EGP-2-positive SCLC and adenocarcinoma cell lines inhibiting proliferation by 50% at concentrations ranging from 0.01 nM to 0.3 nM. Moreover, the immunotoxin reduced the number of clonogenic tumour cells from cultures by factors of 10(4) and 10(5) during a 24-h and a 3-week exposure respectively. In athymic mice, the immunotoxin, which revealed a serum half-life of approximately 4 h, caused substantial regression of small (40 mm3) chemoresistant tumour xenografts and significantly delayed the growth of larger tumours (120 mm3). This finding indicates that MOC31-ETA252-613 may be useful for the treatment of lung cancer in the setting of chemoresistant minimal residual disease.
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PMID:A novel immunotoxin recognising the epithelial glycoprotein-2 has potent antitumoural activity on chemotherapy-resistant lung cancer. 911 78

The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short-term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from short-term cultures. Twenty-four patients with MDR(-) and seven with MDR +(++) were available for survival analysis. Median survival for MDR (-) patients was 10 months, whereas for MDR +(++) patients it was 2 months. This was statistically significance (p < 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.
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PMID:Multidrug-resistant gene expression in small-cell lung cancer. 925 98

Lung Cancer Associated Protein (LCAP) is a high molecular weight glycoprotein defined by the monoclonal antibody (MAb) DF-L1 prepared against a primary adenocarcinoma of the lung. Previous studies have demonstrated that LCAP circulates at elevated levels in patients with lung cancer. However, a suitable assay for monitoring LCAP levels has not been available. The present work describes the development of a double-determinant LCAP assay using MAb TRD-L1 as the capture antibody and MAb DF-L1 as the tracer. In 60 normal subjects, the mean LCAP level was 4.8 U/ml with 2 (3.3%) subjects having values > 12 U/ml (mean + 2SDS). By contrast, 37 of 67 (55.2%) patients with lung cancer had LCAP levels > 12 U/ml. Moreover, only 14 of 203 (6.9%) patients with benign lung disease had elevated levels. LCAP levels were most commonly elevated (62.7%) in patients with adenocarcinoma of the lung and with advanced disease. These results indicate that LCAP as detected by MAb TRD-L1 is a potentially useful marker for the evaluation of patients with lung cancer.
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PMID:Detection of the circulating lung cancer marker LCAP with a new monoclonal antibody TRD-L1. 934 32

Tenascin-C is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions during organogenesis and tissue remodelling. It has therefore been proposed as a stromal marker for epithelial malignancy. To test this hypothesis, 30 human lung cancers, presenting a variety of clinicopathological features, and six specimens of normal tissue were examined by Western and Northern blotting of tenascin-C protein and mRNA. The results obtained were: (1) elevated tenascin-C expression was detected in all 30 cases by Western blotting, with mRNA increase in 22 of them; (2) mRNA for a large isoform of tenascin-C, including an alternatively spliced sequence, was expressed in lung cancer tissues but not in normal lungs; and (3) metastasis to lymph nodes was frequently found in cases whose tenascin-C was degraded into small fragments. These results suggest that tenascin-C degradation can be used as a marker for metastatic potential of a tumour.
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PMID:Expression and degeneration of tenascin-C in human lung cancers. 945 52

The study of tumour markers in lung cancer has focused mainly on serum-based analysis. The controversy about carcinoembryonic antigen (CEA), pregnancy specific glycoprotein 1 (SP1) and beta human chorionic gonadotropin (betahCG) production in lung carcinoma has been reported in several studies. The aims of this study were: to explore an expression of CEA, SP1 and betahCG in various histological types of lung carcinoma with respect to the grade of differentiation; and to define the relationship between tumour marker expression and serum marker concentration. Ninety two lung tumours (75 non-small cell carcinomas (NSCLC) and 17 small cell lung carcinomas (SCLC)) entered the study. Tumour marker expression was compared with the serum levels of CEA, SP1 and betahCG in 57 patients (pts) with NSCLC and four pts with SCLC. Positive immunostaining of CEA and SP1 was observed in 87% NSCLC, and betahCG was found in 24% NSCLC. In the SCLC group positive staining showed in 29% of tumours, SP1 in 51% and betahCG in 18%. Positive CEA expression ranged from 50-100% within the carcinomatous cell population (pcp) and was more characteristic for well and moderately differentiated adenocarcinomas. This finding was in contrast to squamous cell carcinomas, where the majority of tumours expressed CEA in 1-50% pcp. A significant negative correlation was noticed for adenocarcinoma between tumour expression and grade of histological differentiation for CEA (P < 0.001) and SP1 (P = 0.023). Results were not significant for squamous carcinoma. Significant differences of serum CEA concentration were noticed between adenocarcinoma and squamous carcinoma (P = 0.003). In addition, a statistically significant relation was found between serum CEA concentration and an early (I + II) and advanced (IIIa + IIIb + IV) stage of NSCLC (P = 0.031). A significant correlation was noticed when serum CEA and tumour CEA expression was compared for NSCLC (P < 0.001), and for serum betahCG and tumour betahCG (P = 0.019).
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PMID:Expression of CEA and trophoblastic cell markers by lung carcinoma in association with histological characteristics and serum marker levels. 951 51

Tc-99m MIBI is used as a tumor imaging agent and has been proposed to measure p-glycoprotein function, which plays an important role in tumor multidrug resistance to chemotherapy. It has been reported that lung cancer and breast cancer with a high retention of Tc-99m MIBI have been more responsive to chemotherapy than tumors with low retention. Thus Tc-99m MIBI SPECT could be used as a measure of p glycoprotein function and consequently may serve as a predictor of the tumor's responsiveness to chemotherapeutic agents. Described here are two patients with lymphomas, one with non-Hodgkin's lymphoma and the other with Hodgkin's disease, who underwent Tc-99m MIBI thoracic SPECT before and after chemotherapy. The sequential studies demonstrated a reduction in tumor size and diminished tumor uptake in one patient and disappearance of tumor uptake after a course of chemotherapy in the other patient. The data suggest that elevated Tc-99m MIBI uptake in a tumor as a result of retention by p glycoprotein not only demonstrates mediastinal involvement of lymphomas but also may be used to forecast responsiveness to chemotherapy.
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PMID:Functional retention of Tc-99m MIBI in mediastinal lymphomas as a predictor of chemotherapeutic response demonstrated by consecutive thoracic SPECT imaging. 971 81

The tumour-associated antigen epithelial glycoprotein-2 (EGP-2) is a promising target for detection and treatment of a variety of human carcinomas. Antibodies to this antigen have been successfully used in patients for imaging of small-cell lung cancer and for adjuvant treatment of minimal residual disease of colon cancer. We describe here the isolation and complete characterization of high-affinity single-chain variable fragments (scFv) to the EGP-2 antigen. First, the binding kinetics of four murine whole antibodies directed to EGP-2 (17-1A, 323/A3, MOC-31 and MOC-161) were determined using surface plasmon resonance (SPR). The MOC-31 antibody has the lowest apparent off-rate, followed by MOC-161 and 323/A3. The V-genes of the two MOC hybridomas were cloned as scFv in a phage display vector and antigen-binding phage were selected by panning on recombinant antigen. The scFvs compete with the original hybridoma antibodies for binding to antigen and specifically bind to human carcinomas in immunohistochemistry. MOC-31 scFv has an off-rate which is better than those of the bivalent 17-1A and 323/A3 whole antibodies, providing it with an essential characteristic for tumour retention in vivo. The availability of these high-affinity anti-EGP-2 antibody fragments and of their encoding V-genes creates a variety of possibilities for their future use as tumour-targeting vehicles.
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PMID:High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting. 983 71


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