Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered structure and regulation of the c-myc proto-oncogene have been associated with a variety of human tumours and derivative cell lines, including Burkitt's lymphoma, promyelocytic leukaemia and small cell lung cancer (SCLC). The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or expressed in tumours or cell lines derived from neuroblastoma, retinoblastoma and SCLC. Here we describe a third myc-related gene (L-myc) cloned from SCLC DNA with homology to a small region of both the c-myc and N-myc genes. Human genomic DNA shows an EcoRI restriction fragment length polymorphism (RFLP) of L-myc defined by two alleles (10.0- and 6.6-kilobase (kb) EcoRI fragments), neither associated disproportionately with SCLC. Mouse and hamster DNAs exhibit a 12-kb EcoRI L-myc homologue, which indicates conservation of the gene in mammals. Gene mapping studies assign L-myc to human chromosome region 1p32, a location distinct from that of either c-myc or N-myc but associated with cytogenetic abnormalities in certain human tumours. This L-myc sequence is amplified 10-20-fold in four SCLC cell line DNAs and in one SCLC tumour specimen taken directly from a patient. Either the 10.0- or 6.6-kb allele can be amplified and in heterozygotes only one of the two alleles was amplified in any SCLC genome. SCLC cell lines with amplified L-myc sequences express L-myc-derived transcripts not seen in SCLC with amplified c-myc or N-myc genes. In addition, some SCLCs without amplification also express L-myc-related transcripts. Together, these findings suggest an enlarging role for myc-related genes in human lung cancer and provide evidence for the concept of a myc family of proto-oncogenes.
 ...
PMID:L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. 299 22

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.
 ...
PMID:Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids. 301 23

A new method for the determination of serum neuron-specific enolase is presented. It consists of two steps: first, an immunocapture of gamma-subunit containing isoenzymes by absorption on immobilized anti-gamma antibodies; second, bioluminescence assay of enolase activities in untreated control samples and in the supernates of antibody treated samples. Total and alpha alpha activities are obtained, from which the neuron-specific enolase activity (alpha gamma + gamma gamma) can then be calculated by difference. As compared to the procedures currently in use, the immunocapture method is very rapid (30 min) and is more suitable for small series of determinations as needed in clinical chemistry applications. Reference interval values for serum found by this method agree with published data. When tested with samples from patients suffering from neuroblastoma or small cell lung cancer, it confirms the specific elevations in neuron-specific enolase activity previously described for these cancers, using other analytical approaches.
 ...
PMID:Determination of serum neuron-specific enolase by differential immunocapture. 302 76

Neuron-specific enolase (NSE) is an enzyme detectable in nervous and neuroendocrine tissue. Increased serum levels of NSE are found in small cell lung cancer and in patients with neuroblastoma, in whom NSE is used as a serum tumor marker. We have investigated 32 patients with histologically proven medullary thyroid carcinoma, a tumor of neuroendocrine origin, in which the classical tumor marker calcitonin (CT) was pathologically elevated. Positive immunocytochemistry for NSE and CT in C-cells was obtained in all cases. Increased serum NSE levels were found in only 5 of 32 patients, there was no correlation between NSE and CT concentrations. We also compared NSE and CT serum levels during long-term follow-up and again found no correlation between NSE and CT. After i.v. stimulation tests with pentagastrin and calcium, no correlation was found between NSE and CT serum levels. We conclude, therefore, that in medullary thyroid carcinoma NSE is useful for immunocytochemistry but not a reliable serum tumor marker.
 ...
PMID:Neuron-specific enolase in medullary thyroid carcinoma: immunohistochemical demonstration, but no significance as serum tumor marker. 331 43

Cell lines established from small cell lung cancer (SCLC), a neuroendocrine tumor, have low or absent expression of class I major histocompatibility complex antigens. To determine whether this phenomenon occurs also in vivo, 244 routine paraffin-embedded tumors including 32 SCLC and 79 non-SCLC (NSCLC) lung cancers were studied for expression of beta 2-microglobulin (beta 2m) by an avidin-biotin coupled immunoperoxidase technique. The majority of SCLC tumors lacked beta 2m expression, while some had weak, focal expression. In contrast, most NSCLC expressed beta 2m, often strongly. The difference between SCLC and NSCLC was highly significant statistically, suggesting that beta 2m can be used as a clinical immunodiagnostic marker for distinguishing NSCLC from SCLC. In addition, certain other neuroendocrine tumors (neuroblastoma, bronchial and midgut carcinoid tumors) lacked beta 2m expression, whereas some (pheochromocytoma, medullary thyroid carcinoma, and peripheral neuroectodermal tumors) usually stained positively. Such non-neuroendocrine tumors as colon, breast, and prostate carcinomas showed moderate to high expression of beta 2m. Selective absence of beta 2m expression by certain neuroendocrine tumors appears to be a phenomenon of biological and diagnostic importance.
 ...
PMID:Paucity of beta 2-microglobulin expression on small cell lung cancer, bronchial carcinoids and certain other neuroendocrine tumors. 352 83

Marrow transplantation is effective treatment for a number of hematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is successful in the treatment of aplastic anemia with 70-85% long-term survival. It offers 10-30% apparent cures for patients with acute leukemia who have relapsed at least once, and for those with chronic myelocytic leukemia in blast crisis. Although still somewhat controversial, it appears to be the treatment of choice for patients with acute nonlymphoblastic leukemia in first chemotherapy induced remission, and for those with chronic myelogenous leukemia in the chronic phase since approximately 50-60% of these patients experience long-term, disease-free survival. Patients with acute lymphoblastic leukemia grafted in second or subsequent remission may expect a 30% "cure" of their disease. Marrow grafting is the only effective treatment for many patients with inherited immunologic deficiencies and certain genetic storage diseases. Cures of congenital Fanconi's anemia, Blackfan-Diamond anemia, osteopetrosis, paroxysmal nocturnal hemoglobinuria and thalassemia major have been achieved. Marrow transplantation is being explored for the therapy of patients with lymphoma, Hodgkin's disease, preleukemia, multiple myeloma, hairy cell leukemia, small cell lung cancer, testicular cancer, ovarian cancer and neuroblastoma. Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. More recently, marrow transplants from HLA-nonidentical family members and even from unrelated donors have been successfully explored.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Marrow transplantation: the Seattle experience. 391 47

Monoclonal antibodies with selectivity for human lung cancer were produced by immunizing BALB/c mice with an established line of human small cell lung cancer (NCI-H69) and fusing the mouse spleen cells to mouse myeloma line X63-Ag8.653. The resulting hybrid cells were initially screened by immunoautoradiography for production of antibodies that would react with NCI-H69 and another small cell lung cancer line (NCI-H128) but not its autologous B-lymphoblastoid line (NCI-H128BL). Stable monoclonal antibody-producing lines were isolated by repeated cloning. Three independently derived monoclonal antibodies, designated 525A5, 534F8, and 538F12, were found to react with three of the major types of human lung cancer (small cell, adenocarcinoma, and squamous carcinoma). They did not react with bronchioloalveolar and large cell lung cancers, myeloma, lymphomas, leukemias, osteogeneic sarcoma, mesothelioma, hypernephroma, malignant melanoma, simian virus 40-transformed human fetal lung cells, skin fibroblast lines, human B-lymphoblastoid lines, human erythrocytes, and rodent cells. Interestingly, these antibodies also bound to three out of three human neuroblastomas and two out of three breast cancers but failed to react with mouse neuroblastoma and rat pheochromocytoma. The monoclonal antibodies reacted with human small cell lung cancer tumors obtained at autopsy, but had insignificant reactions with normal human lung, liver, spleen, and skeletal muscle. We conclude that monoclonal antibodies have been generated that react with common antigenic determinants expressed on several human lung cancer types, neuroblastoma, and some breast cancers, but are not detectable by our current assays on a variety of other human tumors or normal adult human tissues. Such antibodies are of potential clinical and biological importance.
 ...
PMID:Monoclonal antibodies that demonstrate specificity for several types of human lung cancer. 627 Jun 85

Two murine IgG2Ak monoclonal antibodies (703D4, 704A 1) were produced and characterized after immunization with a human large cell lung cancer line (NCI-H 157). These antibodies detect different epitopes on 31 kilodalton [35S]methionine incorporating protein(s). Radiobinding and immunohistochemical studies show these antibodies bind to most (11/13) human non-small cell lung cancer (adenocarcinoma, epidermoid, and large cell), but not to small cell lung cancer (0/11) tumors tested. The epitopes these antibodies recognized are also expressed on human melanomas (7/8), two other tumors (osteogenic sarcoma, renal cell carcinoma), but not on many other human tumors (breast, colon, neuroblastoma, lymphoid), and not on a panel of normal adult human tissues. Because the antigen(s) are preserved after fixation and because of their ability to distinguish lung cancer types from each other and normal tissues, they should be of clinical, as well as of biologic interest.
 ...
PMID:Monoclonal antibodies that distinguish non-small cell from small cell lung cancer. 630 2

The antigen expression of human small cell lung cancer (SCLC) was studied using a panel of 21 independent rat monoclonal antibodies. The panel was selected by isolating hybridomas producing antibodies reactive with two SCLC lines but not with autologous B-lymphoblastoid lines. The antibodies were then tested in radiobinding assays against a panel of 17 SCLC lines, 13 non-small cell lung cancer lines, 6 SCLC necropsy specimens, 13 neuroectodermal lines (melanomas, neuroblastomas, glioblastomas), 15 other human lines, the glycolipid extracts of SCLC, human meconium, and human red blood cells. Using immunohistochemical assays, 14 of the antibodies were tested against normal lung, liver, and kidney, and lung cancer biopsies and xenografts. These analyses revealed the following: (a) SCLC elicited predominantly immunoglobulin M antibodies despite hyperimmunization; (b) the 21 antibodies displayed distinct binding and immunohistochemical phenotypes, indicating that they recognized many different epitopes; (c) 14 of the 21 antibodies reacted with glycolipid determinants; (d) the 21 determinants were expressed on over 80% of SCLC cell lines, necropsy samples, and xenografts; (e) the determinants were also expressed on normal adult bronchial epithelium, proximal tubules of adult kidney, and in a few instances on other normal cell types; (f) the antigens were expressed less frequently on nonsmall cell lung cancer samples but did not clearly distinguish SCLC from non-small cell lung cancer; (g) biochemical and morphological variants of SCLC exhibiting more malignant and undifferentiated behavior and containing greatly amplified c-myconcogenes failed to express several determinants or expressed them at lower levels; (h) and finally, while many human cell lines failed to express the antigens including human melanoma and glioblastoma lines, human neuroblastoma lines frequently did express the SCLC antigens. These detailed studies utilizing a panel of distinct monoclonal antibodies define a series of antigens on the surface of the majority of SCLC undescribed previously.
 ...
PMID:Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies. 671 99

Paraneoplastic syndromes such as the subacute sensory neuronopathy (SSN) and paraneoplastic cerebellar degeneration (PCD) are associated with autoantibodies directed against various neural antigenic structures. SSN is characterised by autoantibodies against a neuronal intranuclear component called Hu (M. W. 35 to 40 kD), whereas in PCD these antibodies are directed against a Purkinje cell cytoplasmic component called (M. W. 34 and 65 kD). Neuroblastoma cell lines maintained in culture have been shown to contain neuronal antigens. We have demonstrated the presence of the Hu antigen in neuroblastoma cell lines such as SKN-SH, LAN-1 and IMR-32 by both immunocytochemistry and immunoblots of nuclear extracts. The Yo paraneoplastic antigen has been found to be expressed in HeLa cells. These methods may be used for screening of patients with suspected paraneoplastic disease and/or malignancy. Western blot analysis appears to be superior to immunohistochemistry alone. In our experience only 11 out of 122 SCLC patients were positive for the anti-Hu antibody, whereas 5 out of 5 patients with SSN/SCLC were positive, and all of the neurological controls were negative. The availability of cell lines expressing paraneoplastic antigens offers an easy diagnostic assay which may complement or replace conventional immunohistochemistry.
 ...
PMID:Autoantibodies in neurological paraneoplastic diseases. 753 34


<< Previous 1 2 3 4 5 6 7 8 Next >>