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)

Twenty-seven small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous and small cell and/or anaplastic carcinoid-type histologic features were studied by light and electron microscopy. It was shown that the small cells have morphologic characteristics of APUD cells. Also presented are the histologic features of a carcinoma of the lung with large cell undifferentiated carcinoma, adenocarcinoma, squamous cell carcinoma, and giant cell carcinoma areas in the primary site and in several metastatic foci. Two of the renal metastases showed small cell carcinoma. The combined tumors and the numerous other similar neoplasms described in the literature and reviewed here suggest an endodermal origin for digestive and respiratory tract APUD cells based on the hypothesis that cancer is a clonal proliferation, and mucous and squamous cell differentiation is an endodermal rather than neural crest characteristic. The ultrastructural features of tumors of cells of known neural crest origin, including a medullary carcinoma of the thyroid, three carotid body tumors, a pheochromocytoma, and two cutaneous melanomas were compared with those of other APUD cell tumors including small cell carcinomas of the lung, two bronchial carcinoids, a carcinoid of the appendix, and a carcinoid of the kidney. Cells of the latter group sometimes possessed cytoplasmic tonofibrils, round compact masses of cytoplasmic microfilaments, and ductal lumina. These features were lacking in the former group and may signify a different embryologic origin. The histologic, histopathologic, and embryologic evidence regarding the origin of digestive and respiratory tract APUD cells is reviewed, showing that the former are, and the latter probably are, of endodermal and not neuroectodermal origin.
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PMID:The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature. 3 40

We have used transient expression assays to identify a cis-acting region in the 5' flanking sequence of murine c-mos which, when deleted, allows expression from the c-mos promoter in NIH 3T3 cells. This negative regulatory sequence, located 400 to 500 nucleotides upstream of the c-mos ATG, also inhibited expression from a heterologous promoter. In addition to NIH 3T3 cells, the c-mos negative regulatory sequence was active in BALB/3T3 cells, PC12 rat pheochromocytoma cells, and A549 human lung carcinoma cells. Site-specific mutagenesis identified three possibly interacting regions that were involved in negative regulatory activity, located around -460, -425, and -405 with respect to the ATG. RNase protection analysis indicated that once the negative regulatory sequences were deleted, transcription in NIH 3T3 cells initiated from the same transcription initiation sites normally utilized in spermatocytes, approximately 280 nucleotides upstream of the ATG. Deletions beyond the spermatocyte promoter, however, allowed transcription initiation from progressively downstream c-mos sequences. Deletion or mutation of sequences surrounding the oocyte promoter at -53 also had little effect on expression of c-mos constructs in NIH 3T3 cells. Therefore, the major determinant of c-mos expression in NIH 3T3 cells was removal of the negative regulatory sequence rather than the utilization of a unique promoter. The c-mos negative regulatory sequences thus appear to play a significant role in tissue-specific c-mos expression by inhibiting transcription in somatic cells.
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PMID:Identification of a negative regulatory element that inhibits c-mos transcription in somatic cells. 153 71

A subtraction library was constructed from human insulinoma (beta cell tumor) and glucagonoma (alpha cell tumor) cDNA phagemid libraries. Differential screening of 153 clones with end-labeled mRNAs from insulinoma, glucagonoma, and HeLa cells resulted in the isolation of a novel cDNA clone designated IA-1. This cDNA clone has a 2838-base pair sequence consisting of an open reading frame of 1530 nucleotides, which translates into a protein of 510 amino acids with a pI value of 9.1 and a molecular mass of 52,923 daltons. At the 3'-untranslated region there are seven ATTTA sequences between two polyadenylation signals (AATAAA). The IA-1 protein can be divided into two domains based upon the features of its amino acid sequence. The NH2-terminal domain of the deduced protein sequence (amino acids 1-250) has four classical pro-hormone dibasic conversion sites and an amidation signal sequence, Pro-Gly-Lys-Arg. The COOH-terminal domain (amino acids 251-510) contains five putative "zinc-finger" DNA-binding motifs of the form X3-Cys-X2-4-Cys-X12-His-X3-4-His-X4 which has been described as a consensus sequence for members of the Cys2-His2 DNA-binding protein class. Northern blot analysis revealed IA-1 mRNA in five of five human insulinoma and three of three murine insulinoma cell lines. Expression of this gene was undetectable in normal tissues. Additional tissue studies revealed that the message is expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, pituitary tumor, and small cell lung carcinoma. The restricted tissue distribution and unique sequence motifs suggest that this novel cDNA clone may encode a protein associated with the transformation of neuroendocrine cells.
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PMID:A novel human insulinoma-associated cDNA, IA-1, encodes a protein with "zinc-finger" DNA-binding motifs. 163 55

Restriction-fragment-length polymorphism analysis was performed on several different types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, stomach cancer, and small-cell lung carcinoma (SCLC), to determine the chromosomal loci of putative tumor-suppressor genes in each type of tumor because less of heterozygosity (LOH) is supposed to unmask the recessive mutation of tumor-suppressor gene in the remaining allele. Chromosomal loci showing frequent LOH differed among these tumors, suggesting that there are several tumor-suppressor genes in the human genome and that critical genes for the development of each type of tumor are different. In some cases LOH was observed in the early stage of tumor such as chromosome 3p loss in carcinoma of the uterine cervix, and in other cases it was observed only in the advanced stage of tumor such as chromosomes 4 and 16q loss in hepatocellular carcinoma. These results suggest that there are two different types of tumor-suppressor genes: one is the gene whose inactivation is responsible for malignant transformation of a normal cell and the other is the gene whose inactivation is responsible for the progression of a tumor cell. In SCLC, LOH at three different chromosomal loci, 3p, 13q, and 17p, was simultaneously observed in nearly 100% of tumors. It was observed even in stage I tumors and an untreated tumor, and it occurred prior to N-myc amplification. These results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC.
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PMID:Chromosomal localization of putative tumor-suppressor genes in several human cancers. 168 40

We report our experience with the management of 7 primary nonrenal parenchymal malignancies with vena caval tumor thrombus. Included are 3 cases of adrenal cortical carcinoma and 1 each of transitional cell carcinoma, embryonal cell testicular carcinoma, pheochromocytoma and primary small cell carcinoma of the lung with metastases to the kidney. Surgical treatment and followup are presented, as well as a review of the literature. An aggressive surgical approach is warranted because prolonged survivals free of disease are possible.
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PMID:Management of primary nonrenal parenchymal malignancies with vena caval thrombus. 198 10

A monoclonal antibody, 6H7, was produced by the immunization of small cell carcinoma of the lung (SCCL). Immunohistochemical examination indicated that 6H7 reacted not only with SCCL but also various neuronal and/or endocrine tumors such as neuroblastoma, pheochromocytoma, carcinoid and adrenal cortical tumors. 6H7 was also reactive with normal neuroendocrine tissues including brain, spinal cord, thyroid follicular cells, pancreatic islet cells and adrenal cells. 6H7 did not react with squamous cell carcinomas, one large cell carcinoma or most adenocarcinomas of the lung, or carcinomas of the stomach, colon, pancreas, breast and esophagus. The antigen recognized by 6H7 was analyzed on gel filtration after purification of the antigen by liquid chromatography which indicated the molecular weight of the antigen to be 270,000-300,000. From SDS-PAGE analysis the antigen reactive with 6H7 appeared to consist of polypeptide dimers of 128,000.
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PMID:Monoclonal antibody directed against neuroendocrine properties of both normal and malignant cells. 246 61

We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (SCLC) on voltage-gated (K+-stimulated) 45Ca2+ flux in cell lines derived from a human SCLC (MAR10) and from a rat pheochromocytoma (PC12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2+ flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/10(6) cells; p less than 0.001) or non-SCLC-LEMS IgG (0.35 nmol/10(6) cells; p less than 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/10(6) cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC-associated LEMS.
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PMID:Lambert-Eaton myasthenic syndrome: immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity. 254 62

Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.
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PMID:Expression of a multidrug resistance gene in human cancers. 256 56

Clinically significant adrenal hemorrhage due to adrenal metastases has rarely been reported. We describe three cases of this unusual entity, two from lung carcinoma and one from sarcoma. Adrenal hemorrhage was bilateral in two patients, and was the presenting manifestation of malignancy in two. A computed tomography diagnosis of hemorrhage within bilateral adrenal metastases was made when adrenal masses rapidly enlarged in one case, and when previously resolving hematomas showed enlargement in a second case. The third case was believed to represent a pheochromocytoma preoperatively. We conclude that significant adrenal hemorrhage can result from adrenal metastases and can be the presenting manifestation of metastatic tumor. In the patient without discernible risk factors for adrenal hemorrhage, underlying malignancy should be considered as a possible cause, even if the hemorrhage is bilateral.
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PMID:Clinically significant adrenal hemorrhage secondary to metastases. Computed tomography observations. 281 83

We have found that neuroendocrine tumors (including neuroblastoma, ganglioneuroma, gut carcinoid, pheochromocytoma, medullary thyroid carcinoma, insulinoma, glucagonoma, prolactinoma, carotid body tumor, and small cell lung carcinoma) produce considerable amounts (about 1000-80,000 ng/g tissue) of the alpha subunit of guanine nucleotide-binding protein, GO (GO alpha), whereas nonneuroendocrine tumors contain less than 300 ng of GO alpha/g tissue. GO alpha in the neuroendocrine tumors was present both in the soluble fraction, and cholate-extractable membrane-bound fraction of tissues. Immunoblots of membrane fractions of neuroblastoma and carcinoid tissues confirmed that the immunoreactive substance in the tumor tissues was GO alpha. Immunohistochemically, GO alpha was localized consistently in the cell membrane and occasionally in the cytoplasm of neuroendocrine tumors. GO alpha was also detected in sera of 73% patients with neuroblastoma at diagnosis, whereas serum GO alpha concentrations in control children, or patients with nonneuroendocrine tumors were lower than the detection limit of the immunoassay method employed. Serum GO alpha concentrations in patients with neuroblastoma changed with the clinical course; they fell in patients responding to treatment and increased in patients who relapsed. Since GO alpha, a specific protein in the neural and neuroendocrine cells, was found to be produced in considerable amounts by all types of neuroendocrine tumors but not in nonneuroendocrine tumors, GO alpha might be a useful biomarker for neuroendocrine tumors.
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PMID:Production of the alpha subunit of guanine nucleotide-binding protein GO by neuroendocrine tumors. 282 34


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