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)

SOX2 and POU5F1 (OCT3 or OCT4) transcription factors are implicated in FGF4 expression in embryonic stem (ES) cells. SOX2, POU5F1, and FGF4 are key molecules for the integrome network in oncology and stem cell biology. SOX2 gene at human chromosome 3q26.33, SOX1 gene at 13q34, and SOX3 gene at Xq27.1 constitute a subfamily among the SOX gene family. Here, rat Sox2 and Xenopus sox2 genes were identified and characterized by using bioinformatics for comparative genomics and comparative proteomics analyses. Rat Sox2 gene, encoding a 319-aa protein, was located around the nucleotide position 73213-75621 of rat genome sequence AC123231.4. Xenopus tropicalis sox2 complete coding sequence, encoding a 311-aa protein, was derived from CR760314.1 cDNA. Rat Sox2 showed 98.4%, 97.8%, 92.2%, 88.1% and 86.8% total amino-acid identity with mouse Sox2, human SOX2, chicken sox2, Xenopus sox2 and zebrafish sox2, respectively. SOX123C domain was identified as the novel domain corresponding to the C-terminal region conserved among SOX1, SOX2 and SOX3 orthologs. Vertebrate SOX1, SOX2 and SOX3 orthologs were found consisting of HMG box and SOX123C domain. SOX9, TCF/LEF, POU2F1 and COMP1 binding sites were conserved among human SOX2 promoter, rat Sox2 promoter, and mouse Sox2 promoter. SOX2 mRNA was expressed in ES cells, fetal brain, anaplastic oligodendroglioma, rhabdomyosarcoma, and small cell lung carcinoma. Due to the pivotal role of SOX2 in the early embryogenesis, SOX2 promoter and SOX2 protein were well conserved during vertebrate evolution. This is the first report on comparative integromics analyses on the SOX2 orthologs.
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PMID:Comparative genomics on SOX2 orthologs. 1607 94

Anti-Hu syndrome is a paraneoplastic neurological syndrome, most frequently associated with small cell carcinoma of the lung. Subacute sensory neuronopathy is thought to be the most frequent presentation of the anti-Hu syndrome, but it seems that sensory-motor neuropathy is the most common form in the anti-Hu neuropathy. Neurological symptoms often appear before the associated cancer has been identified. Sometimes the tumor is discovered months or even a few years after the appearance of the neurological syndrome. FDG-PET scan seems a better method for finding the tumor in patients with paraneoplastic neurological syndrome and anti-Hu antibodies who had negative test results after an initial workup using radiological methods. In this case report we present a patient with the anti-Hu syndrome associated with an unclassified rhabdomyosarcoma with epitheloid cellular morphology and neuroendocrine differentiation.
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PMID:Unclassified rhabdomyosarcoma in a patient with anti-Hu syndrome. 1639 22

Anticancer activity studies of 2-(4-fluorophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FABT), as one of the most promising derivatives from the N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole set, have been continued. The tested compound inhibited proliferation of tumor cells derived from cancers of nervous system (medulloblastoma/rhabdosarcoma, neuroblastoma, and glioma) and peripheral cancers including colon adenocarcinoma and lung carcinoma. The anticancer effect of FABT was attributed to decreased cell division and inhibited cell migration. Furthermore, in anticancer concentrations it exerted a trophic effect in neuronal cell culture and had no influence on viability of normal cells including astrocytes, hepatocytes, and skin fibroblasts. Moreover, a prominent neuroprotective activity of FABT was observed in the neuronal cultures exposed to neurotoxic agents like serum deprivation and glutamate. To determine probability of tautomeric transition and indicate potential sites of interactions of FABT molecule with the receptor, quantum-chemical calculations with the ab initio Hartree-Fock model were made.
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PMID:Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole based compound. 1735 Aug 46

A 38-year-old man, a chronic smoker, presented to us with a large left upper lobe mass lesion and left-sided pleural effusion. After resection, a residual mass remained. On histopathologic examination, a diagnosis of pleiomorphic rhabdomyosarcoma stage III of the lung was made. Chemotherapy using IRS (Intergroup Rhabdomyosarcoma Study) IV protocol with radiation therapy (RT) at week 9 was planned. The tumor progressed within 6 weeks of chemotherapy to involve the diaphragm and the pericardium (inoperable disease). Chemotherapy was abandoned, and we referred the patient to receive RT, which the patient refused; and he died of progressive disease 1 month later. The poor response to chemotherapy suggests that alternative treatment modalities including RT/second-look surgery or novel chemotherapeutic strategies should be tried in such a case.
Clin Lung Cancer 2007 May
PMID:Primary pulmonary rhabdomyosarcoma in adults: case report and review of literature. 1756 41

Although advances have been made in understanding the role of hypoxia in the stem cell niche, almost nothing is known about a potentially similar role of hypoxia in maintaining the tumor stem cell (TSC) niche. Here we show that a highly tumorigenic fraction of side population (SP) cells is localized in the hypoxic zones of solid tumors in vivo. We first identified a highly migratory, invasive, and tumorigenic fraction of post-hypoxic side population cells (SPm([hox]) fraction) in a diverse group of solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, and small-cell lung carcinoma. To identify the SPm((hox)) fraction, we used an "injured conditioned medium" derived from bone marrow stromal cells treated with hypoxia and oxidative stress. We found that a highly tumorigenic SP fraction migrates to the injured conditioned medium in a Boyden chamber. We show that as few as 100 SPm((hox)) cells form rapidly growing tumors in vivo. In vitro exposure to hypoxia increases the SPm((hox)) fraction significantly. Quantitative real-time polymerase chain reaction and immunofluorescence studies showed that SPm((hox)) cells expressed Oct-4, a "stemness" gene having a potential role in TSC maintenance. In nude mice xenografts, SPm((hox)) cells were localized to the hypoxic zones, as demonstrated after quantum dot labeling. These results suggest that a highly tumorigenic SP fraction migrates to the area of hypoxia; this migration is similar to the migration of normal bone marrow SP fraction to the area of injury/hypoxia. Furthermore, the hypoxic microenvironment may serve as a niche for the highly tumorigenic fraction of SP cells.
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PMID:Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction. 1846 64

Two 2-(monohalogenophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles were synthesized by reaction of sulfinyl bis(2,4-dihydroxythiobenzoyl) with 4-substituted 3-thiosemicarbazides and evaluated for their antiproliferative activity in tumor cells and for cytotoxicity in normal cells. Both derivatives in micromolar concentrations elicited a prominent antiproliferative effect in tumor cells derived from cancers of the nervous system (rhabdomyosarcoma/medulloblastoma, glioma) and peripheral cancers, including breast adenocarcinoma and lung carcinoma. The anticancer effect was attributed to decreased DNA synthesis and was not connected with apoptosis induction. Both compounds were not toxic to normal human skin fibroblasts.
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PMID:Evaluation of the antiproliferative activity of 2-(monohalogenophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. 1875 2

Coxsackievirus A9 (CAV9), a member of the genus Enterovirus in the family Picornaviridae, possesses an integrin-binding arginine-glycine-aspartic acid (RGD) motif in the C terminus of VP1 capsid protein. CAV9 has been shown to utilize integrins alphaVbeta3 and alphaVbeta6 as primary receptors for cell attachment. While CAV9 RGD-mutants (RGE and RGDdel) are capable of infecting rhabdomyosarcoma (RD) cell line, they grow very poorly in an epithelial lung carcinoma cell line (A549). In this study, the relationships between CAV9 infectivity in A549 and RD cells, receptor expression and integrin binding were analysed. A549 cells were shown to express both integrins alphaVbeta3 and alphaVbeta6, whereas alphaVbeta6 expression was not detected on the RD cells. Native CAV9 but not RGE and RGDdel mutants bound efficiently to immobilized alphaVbeta3 and alphaVbeta6. Adhesion of CAV9 but not RGE/RGDdel to A549 cells was also significantly higher than to RD cells. In contrast, no affinity or adhesion of bacterially produced VP1 proteins to the integrins or to the cells was detected. Function-blocking antibodies against alphaV-integrins blocked CAV9 but not CAV9-RGDdel infectivity, indicating that the viruses use different internalization routes; this may explain the differential infection kinetics of CAV9 and RGDdel. In an affinity assay, soluble alphaVbeta6, but not alphaVbeta3, bound to immobilized CAV9. Similarly, only soluble alphaVbeta6 blocked virus infectivity. These data suggest that CAV9 binding to alphaVbeta6 is a high-affinity interaction, which may indicate its importance in clinical infections; this remains to be determined.
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PMID:Integrin alphaVbeta6 is a high-affinity receptor for coxsackievirus A9. 1908 89

Emerging evidence suggests a role for glutamate and its receptors in the biology of cancer. This study was designed to systematically analyze the expression of ionotropic and metabotropic glutamate receptor subunits in various human cancer cell lines, compare expression levels to those in human brain tissue and, using electrophysiological techniques, explore whether cancer cells respond to glutamate receptor agonists and antagonists. Expression analysis of glutamate receptor subunits NR1-NR3B, GluR1-GluR7, KA1, KA2 and mGluR1-mGluR8 was performed by means of RT-PCR in human rhabdomyosarcoma/medulloblastoma (TE671), neuroblastoma (SK-NA-S), thyroid carcinoma (FTC 238), lung carcinoma (SK-LU-1), astrocytoma (MOGGCCM), multiple myeloma (RPMI 8226), glioma (U87-MG and U343), lung carcinoma (A549), colon adenocarcinoma (HT 29), T cell leukemia cells (Jurkat E6.1), breast carcinoma (T47D) and colon adenocarcinoma (LS180). Analysis revealed that all glutamate receptor subunits were differentially expressed in the tumor cell lines. For the majority of tumors, expression levels of NR2B, GluR4, GluR6 and KA2 were lower compared to human brain tissue. Confocal imaging revealed that selected glutamate receptor subunit proteins were expressed in tumor cells. By means of patch-clamp analysis, it was shown that A549 and TE671 cells depolarized in response to application of glutamate agonists and that this effect was reversed by glutamate receptor antagonists. This study reveals that glutamate receptor subunits are differentially expressed in human tumor cell lines at the mRNA and the protein level, and that their expression is associated with the formation of functional channels. The potential role of glutamate receptor antagonists in cancer therapy is a feasible goal to be explored in clinical trials.
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PMID:Expression of glutamate receptor subunits in human cancers. 1952 64

Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity and affinity. Though these properties are also highly desirable for therapeutic applications, rabbit antibodies have remained untapped for human disease therapy. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAbs), we generated a panel of neutralizing RabMAbs against human vascular endothelial growth factor-A (VEGF). These neutralizing RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF protein family. Guided by sequence and lineage analysis of a panel of neutralizing RabMAbs, we humanized the lead candidate by substituting non-critical residues with human residues within both the frameworks and the CDR regions. We showed that the humanized RabMAb retained its parental biological properties and showed potent inhibition of the growth of H460 lung carcinoma and A673 rhabdomyosarcoma xenografts in mice. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics.
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PMID:A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. 2014 Feb 8

The study was performed to determine the frequency and origin for metastatic disease to the pancreas as found in an endoscopic ultrasound directed fine-needle aspiration series. The records of the Departments of Pathology at the University of Utah School of Medicine and the David Geffen School of Medicine were electronically searched for all fine-needle aspirates obtained from pancreatic masses between January 1, 2002 and March 31, 2010. All cases with a diagnosis of metastatic disease were reviewed and whenever possible correlated with subsequent resection specimens. A total of 17 metastatic malignancies to the pancreas were detected in pancreatic FNAs representing 0.73% of all cases. Primaries included eight renal cell carcinomas, one medullary carcinoma of the thyroid, four lymphomas, one alveolar rhabdomyosarcoma, one squamous cell carcinoma derived from the esophagus, and a second squamous cell carcinoma originating from a lung primary and a small cell carcinoma of the lung. Metastatic renal cell carcinoma was the most frequent metastasis to the pancreas representing 47% of metastatic lesions detected by FNA. The metastatic deposits could be detected in the pancreas as many as 10 years following the original diagnosis and resection of the renal cell carcinoma.
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PMID:Metastatic disease to the pancreas documented by endoscopic ultrasound guided fine-needle aspiration: a seven-year experience. 2233 24


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