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)

To screen for glycoproteins showing aberrant sialylation patterns in sera of cancer patients and apply such information for biomarker identification, we performed SELDI-TOF MS analysis coupled with lectin-coupled ProteinChip arrays (Jacalin or SNA) using sera obtained from lung cancer patients and control individuals. Our approach consisted of three processes (i) removal of 14 abundant proteins in serum, (ii) enrichment of glycoproteins with lectin-coupled ProteinChip arrays, and (iii) SELDI-TOF MS analysis with acidic glycoprotein-compatible matrix. We identified 41 protein peaks showing significant differences (p<0.05) in the peak levels between the cancer and control groups using the Jacalin- and SNA-ProteinChips. Among them, we identified loss of Neu5Ac (alpha2,6) Gal/GalNAc structure in apolipoprotein C-III (apoC-III) in cancer patients through subsequent MALDI-QIT-TOF MS/MS. Furthermore, subsequent validation experiments using an additional set of 60 lung adenocarcinoma patients and 30 normal controls demonstrated that there is a higher frequency of serum apoC-III with loss of alpha2,6-linkage Neu5Ac residues in lung cancer patients compared to controls. Our results have demonstrated that lectin-coupled ProteinChip technology allows the high-throughput and specific recognition of cancer-associated aberrant glycosylations, and implied a possibility of its applicability to studies on other diseases.
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PMID:Targeted serum glycoproteomics for the discovery of lung cancer-associated glycosylation disorders using lectin-coupled ProteinChip arrays. 1932 76

The cell surface is covered by a dense layer of protein- and lipid-linked glycans. Although it has been known that distinct glycan structures are associated with cancer, the whole spectrum of cancer-associated glycans has remained undiscovered. In the present study, we analyzed the protein-linked cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric glycan profiling of cancer patient tissue samples. In lung cancer, we detected accumulation of a novel group of tumor-associated glycans. These protein-linked glycans carried abnormal nonreducing terminal beta-N-acetyl-D-glucosamine (GlcNAc) residues. A similar phenomenon was also detected in structural analyses of tumor-derived glycosphingolipids. This showed that glycan biosynthesis may dramatically change in cancer and that direct glycome analysis can detect the resulting marker glycans. Based on the structural knowledge, we further devised a covalent labeling technique for the detection of GlcNAc-expressing tumors with a specific transferase enzyme. In normal tissues, terminal GlcNAc antigens are capped by galactosylation. Similarly to common cancer-associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc antigens result from incomplete glycosylation. In conclusion, the identified terminal GlcNAc glycans should be recognized as a novel class of tumor markers.
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PMID:Analysis of the human cancer glycome identifies a novel group of tumor-associated N-acetylglucosamine glycan antigens. 1958 98

Membrane-bound proteases have recently emerged as critical mediators of tumorigenesis, angiogenesis, and metastasis. However, the mechanisms by which they regulate these processes remain unknown. As the cell surface serine protease fibroblast activation protein (FAP) is selectively expressed on tumor-associated fibroblasts and pericytes in epithelial tumors, we set out to investigate the role of FAP in mouse models of epithelial-derived solid tumors. In this study, we demonstrate that genetic deletion and pharmacologic inhibition of FAP inhibited tumor growth in both an endogenous mouse model of lung cancer driven by the K-rasG12D mutant and a mouse model of colon cancer, in which CT26 mouse colon cancer cells were transplanted into immune competent syngeneic mice. Interestingly, growth of only the K-rasG12D-driven lung tumors was also attenuated by inhibition of the closely related protease dipeptidyl peptidase IV (DPPIV). Our results indicate that FAP depletion inhibits tumor cell proliferation indirectly, increases accumulation of collagen, decreases myofibroblast content, and decreases blood vessel density in tumors. These data provide proof of principle that targeting stromal cell-mediated modifications of the tumor microenvironment may be an effective approach to treating epithelial-derived solid tumors.
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PMID:Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. 2022 91

Lung cancer accounts for the most cancer-related deaths. The identification of cancer-associated genes and the related pathways are essential to prevent many types of cancer. In this paper, a more systematic approach is considered. First, we did pathway analysis using Hyper Geometric Distribution (HGD) and significantly overrepresented sets of reactions were identified. Second, feature-selection-based Particle Swarm Optimisation (PSO), Information Gain (IG) and the Biomarker Identifier (BMI) for the identification of different types of lung cancer were used. We also evaluated PSO and developed a new method to determine the BMI thresholds to prioritize genes. We were able to identify sets of key genes that can be found in several pathways. Experimental results show that our method simplifies features effectively and obtains higher classification accuracy than the other methods from the literature.
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PMID:Oncogenes and pathway identification using filter-based approaches between various carcinoma types in lung. 2224 31

Tumorigenesis requires the concerted action of multiple pathways, including pathways that stimulate proliferation and increase metabolism. Progesterone receptor membrane component 1 (Pgrmc1) is related to cytochrome b5, binds to heme, and is associated with DNA damage resistance and apoptotic suppression. Pgrmc1 is induced by carcinogens, including dioxin, and is up-regulated in multiple types of cancer. In the present study, we found that Pgrmc1 increased in vivo tumor growth, anchorage-independent growth, and migration. Pgrmc1 also promoted proliferation in the absence of serum in A549 non-small cell lung cancer cells but enhanced proliferation regardless of serum concentration in MDA-MB-468 breast cancer cells. Pgrmc1 promotes cholesterol synthesis and binds to Insig (insulin-induced gene), Scap (sterol regulatory element binding protein cleavage activating protein), and P450 proteins, but Pgrmc1 did not affect cholesterol synthesis in lung cancer cells. Pgrmc1 is also associated with progesterone signaling and plasminogen activator inhibitor (PAI1) RNA binding protein, but neither progesterone activity nor PAI1 transcript levels were altered in Pgrmc1-knockdown lung cancer cells. Pgrmc1 homologues bind to aryl ligands identified in an in silico screen, and we have found that a Pgrmc1 ligand induced cell death in a Pgrmc1-specific manner in multiple breast and lung tumor cell lines. Our data support a role for Pgrmc1 in promoting cancer-associated phenotypes and provide a therapeutic approach for targeting Pgrmc1 with a small molecule in lung and breast cancer.
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PMID:Progesterone receptor membrane component 1 (Pgrmc1): a heme-1 domain protein that promotes tumorigenesis and is inhibited by a small molecule. 2016 97

CD147 is a novel cancer-associated biomarker that plays an important role in the invasion and metastasis of human lung cancer. In spite of its many known functions, little is known about CD147 transcriptional regulation. In this study, we explored the regulation of CD147 in human lung cancer tissues. Over 60% of the human lung cancer tissues expressed differential high levels of CD147. We then cloned the 5'-flanking region of the human CD147 gene and identified a critical promoter region at -108 to -42 which contained one binding site for Sp1, which was essential in up-regulating CD147 promoter activity. These results were proven by blocking Sp1 using RNAi or mithramycin A treatment and up-regulating Sp1 using transfection with eukaryotic expression vector. Consistent with the CD147 transcription activation, a high level of Sp1 expression was detected in lung cancer cell lines overexpressing CD147. Chromatin immunoprecipitation assay showed that much more Sp1 could bind to the CD147 promoter in 95-D with CD147 high expression than in SK-MES-1 with CD147 low expression. There was a significant positive correlation between CD147 expression and Sp1 expression level detected by immunohistochemistry (r = 0.831). Collectively, our results suggest that Sp1 is essential for regulating the CD147 gene expression in human lung cancer.
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PMID:Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. 2038 26

AIDS-associated lung cancer has an increasing incidence, unaccounted for by smoking, and occurs consistently at a younger age than matched controls. We investigated whether known and new cancer-associated polyomaviruses, including the newly identified Merkel cell virus, may play a role in its etiopathogenesis. Although viruses target conserved pathways in cellular evolution, we are unable to suggest that the viruses studied here induce novel mechanisms of oncogenic dysregulation in AIDS-associated lung cancer.
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PMID:No evidence for a polyomavirus association or aetiology in AIDS-associated nonsmall cell lung cancer. 2040 Aug 84

Paraneoplastic retinopathy including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), and paraneoplastic optic neuropathy (PON) are visual disorders associated with systemic cancer. Patients with CAR typically present with progressive loss of vision and photopsia, which are related to dysfunction of both cones and rods in photoreceptors. The triad of photosensitivity, ring scotoma, and a reduced caliber of the retinal arteriole along with undetectable signals in electroretinogram (ERG) are specific manifestations of CAR. CAR is associated most commonly with small-cell lung cancer (SCLC) and occasionally with gynecologic tumors, and it is usually caused by autoantibodies against recovering, which is a calcium-binding photoreceptor protein that participates in the transduction of light. MAR is characterized by shimmering, flickering, or pulsating photopsias, and usually occurs in the patients with a cutaneous melanoma. MAR differs from CAR in terms of visual acuity and color vision and is associated with a characteristic pattern detected in ERG. Autoantibodies against the bipolar cells of the retina have been identified in patients with MAR. Patients with PON frequently present with progressive visual loss and optic disc edema, or with other paneoplastic neurologic syndromes related to SCLC, such as paraneoplastic encephalomyelitis or retinitis, ophthalmoplegia, and subacute cerebellar syndrome. Autoantibodies against collapsin-responsive mediator protein-5 (CRMP-5, also called anti-CV2) are considered to be as the causative factor. Treatments with corticosteroids, plasma exchange, and intravenous immune globulin as well as treatment of the tumor itself, occasionally improves these paraneoplastic visual syndromes. However, the prognosis depends on their underlying malignancy.
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PMID:[Paraneoplastic retinopathy and optic neuropathy]. 2042 Jan 77

Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor-the G protein-coupled receptor 5A (Gprc5a). Microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice defined a loss-of-Gprc5a gene signature, which revealed many aberrations in cancer-associated pathways. To assess the relevance of this mouse tumor suppressor to human lung cancer, the loss-of-Gprc5a signature was cross species compared with and integrated with publicly available gene expression data of human normal lung tissue and non-small cell lung cancers. The loss-of-Gprc5a signature was prevalent in human lung adenocarcinomas compared with squamous cell carcinomas or normal lung. Furthermore, it identified subsets of lung adenocarcinomas with poor outcome. These results demonstrate that gene expression patterns of Gprc5a loss in nontumorigenic mouse lung epithelial cells are evolutionarily conserved and important in human lung adenocarcinomas.
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PMID:A Gprc5a tumor suppressor loss of expression signature is conserved, prevalent, and associated with survival in human lung adenocarcinomas. 2056 52

It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs). Moreover, KM104GFP (GFP-labeled human fibroblast cell line) co-cultured with human cancer cell line Capan-1 showed significantly higher migration activity than KM104GFP alone. No such phenomenon occurred when KM104GFP and Capan-1 were cultured separately. Even after KM104GFP were sorted from co-cultured Capan-1, KM104GFP retained their enhanced migration activity until passage-5 of culture in the absence of cancer cells. Despite a similar level of phosphorylation of ERK1/2 after exposure to PDGF-BB, the inhibitory effect of MEK inhibitor was significantly higher on migration of KM104GFP that had been sorted from co-cultured Capan-1 than of KM104GFP alone. This higher dependence on ERK1/2 signaling for cell migration was also seen in CAFs obtained from cancer tissue. The results of this study indicate that by association with cancer cells, CAFs can acquire enhanced migration activity which could be kept after separation from cancer cells and suggest the possibility that higher dependence on ERK1/2 signaling for enhanced migration activity would be one of the biological properties of CAFs.
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PMID:Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts. 2059 59


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