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)

Small cell lung carcinoma-associated paraneoplastic encephalomyeloneuronopathy involves the nervous system at various levels resulting in cerebellar degeneration, limbic encephalitis, myelopathy, sensory neuronopathy or brainstem encephalitis. Anti-neuronal nuclear antibody, which has been termed ANNA-1/anti-Hu/Type II a antibody, is observed in the serum or cerebrospinal fluid of the patients and is highly specific for the disorder. This antibody reacts with the nucleoproteins of most neurons in the nervous system and recognizes a group of nucleoproteins in neurons with a molecular weight of 34-42 kd, suggesting that the pathogenesis of this disorder may be autoimmune. Several cDNA clones encoding the antigens have been cloned; that is, HuD, PLE21/HuC and He1-N1. These antigens contain three highly similar RRMs as well as Drosophila ELAV and RBP9 proteins do. Several autoantigens 70K, A, B", and Ro contain RRM, and Ro antigen shares B cell epitopes with these antigens. Thus, RRMs may represent or encompass an autoimmune crossreactive determinant.
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PMID:[Recent advances in paraneoplastic encephalomyeloneuronopathy]. 799 2

The PLE21/HuC neural protein is an autoantigen for anti-neuronal nuclear autoantibodies (ANNA-1/anti-Hu/Type IIa antibodies) from a patient with paraneoplastic limbic encephalomyelitis and small cell lung carcinoma. This antigen belongs to the Hu/ELAV-like protein family, contains three RNA recognition motifs (RRMs) and has RNA binding capacity. In many autoimmune diseases mediated by autoantibodies, antibodies often interfere with the biological functions of their target antigens. To investigate the influences of the autoantibodies on the biological function of the antigen, we mapped the regions which were required for the antibody recognition and for the RNA binding. Deletion analysis of the antigen revealed that the epitopes for the antibodies were localized in the regions of 12 residues, amino acids 161-172, and eight residues, amino acids 29-38, of the first and second RRMs. It was also shown that the eight residues, amino acids 29-38, and the 10 residues, amino acids 187-194, were required for the RNA binding. Although amino acids 29-38 were necessary for both the antibody recognition and the RNA bindings, pre-incubation of the PLE21 antigen with the antibodies did not inhibit the formation of the complex of PLE21, the antibodies and RNA. Thus, the regions required for the antibody recognition are not identical with those for the RNA binding, and it seems unlikely that the autoantibodies interfere with RNA binding of the antigen.
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PMID:Antibody recognition and RNA binding of a neuronal nuclear autoantigen associated with paraneoplastic neurological syndromes and small cell lung carcinoma. 1037 67

n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision)-like genes belong to a family codifying for onconeural RNA-binding proteins, also called Hu antigens. Anti-Hu-antibodies (anti-Hu-Ab) are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN), and low titres of anti-Hu-Ab were found in neural/neuroendocrine neoplasms, especially small cell lung cancer (SCLC). To date, few studies have been published focused on the genetic causes of their involvement in the pathogenesis of neuroendocrine tumors (NE). Here we analyzed 20 primary human neuroendocrine lung tumor tissues for somatic mutations in the HuD gene. Two inactivating mutations (a frameshift and a stop codon mutation) and 11 nucleotide changes were detected in the coding sequence of HuD gene in 7 different lung tumors. Our results on SCLC and carcinoid tissues support the hypothesis that alterations of nELAV genes could be involved in the onset and/or progression of a subset of neuroendocrine lung tumors.
Lung Cancer 2010 Jan
PMID:Molecular analysis of the HuD gene in neuroendocrine lung cancers. 1941 Mar 29