Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We identified an antigen recognized on a human non-small-cell lung carcinoma by a cytotoxic T lymphocyte clone derived from autologous tumor-infiltrating lymphocytes. The antigenic peptide is presented by HLA-A2 and is encoded by the CALCA gene, which codes for calcitonin and for the alpha-calcitonin gene-related peptide. The peptide is derived from the carboxy-terminal region of the preprocalcitonin signal peptide and is processed independently of proteasomes and the transporter associated with antigen processing. Processing occurs within the endoplasmic reticulum of all tumoral and normal cells tested, including dendritic cells, and it involves signal peptidase and the aspartic protease, signal peptide peptidase. The CALCA gene is overexpressed in medullary thyroid carcinomas and in several lung carcinomas compared with normal tissues, leading to recognition by the T cell clone. This new epitope is, therefore, a promising candidate for cancer immunotherapy.
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PMID:Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway. 1862 12

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.
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PMID:Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice. 1869 9

Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis, and its expression is up-regulated in many carcinomas. In the present study, we found that a microRNA miR-126 has a binding site in 3'-untranslated region of the VEGF-A mRNA. In eight lung cancer cell lines, expression of miR-126 was down-regulated. Reporter gene assay showed that the co-transfection of mir-126 expression vector with pLuc-VEGF/mir126BS could reduce the activity of luciferase. Transfection experiments showed that miR-126 could decrease the expression of VEGF-A. Three human lung carcinoma cell lines A549, Y-90 and SPC-A1 were investigated as cancer models in vitro, and A549 infected by lentivirus-miR-126 (LV-miR-126) was studied in tumor xenograft model. Infection of LV-miR-126 can down-regulate the expression of VEGF-A in A549, Y-90 and SPC-A1 cell lines and can inhibit the growth of these cells. In addition, flow cytometry analysis revealed that LV-miR-126 infection can induce cell cycle G1 arrest in A549, Y-90 and SPC-A1 cells. Furthermore, in nude mice, the average weight of A549 tumor nodules in experimental group was reduced from 0.8035+/-0.1521 to 0.6235+/-0.0757g, with the inhibitive rate being 22.4%. All these results revealed that miR-126 may have a tumor suppressor function in lung cancer cells and could be a promising treatment in anticancer therapy.
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PMID:MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. 1922 90

Lung cancer is the most common cancer worldwide. Early detection might reduce morbidity. In this study we evaluate a microCT imaging algorithm to assess in-vivo tumour load and quantification of tumour growth in a transgenic disease model of lung adenocarcinomas. MicroCT was carried out with n=10 SPC-raf transgenic mice without gating in spontaneously breathing and isoflurane anaesthetised animals. Segmentation of the air-filled spaces was obtained using a region growing algorithm by 3 independent observers. Inter- and intra-observer variability of the algorithm was determined and compared against an alternative region growing algorithm. Due to the multiple very small tumor nodules that occur and the low signal-to-noise ratio direct volumetric measurement of solitary tumor nodules is not feasible. However, tumor growth can be assessed by measuring the decrease in the segmented volume of the aerated lung areas. The presented algorithm can thus be used to evaluate therapeutic efficacies of novel treatment strategies. The imaging algorithm allows in vivo quantification of lung tumor load and tumor growth in transgenic mice with an acceptable intra- and interobserver variability.
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PMID:In vivo microCT quantification of lung tumor growth in SPC-raf transgenic mice. 1927 75

Amplification and over-expression of HER2/neu oncogene is found in diverse types of human cancers, and is closely related to tumor occurrence, metastasis, angiogenesis and chemotherapy resistance. Therapeutic agents targeting HER2/neu have been intensively addressed over the past decades. In non-small cell lung cancers (NSCLCs), the prevalence of HER2/neu activation, its role in prognosis, and its possible implications as a therapeutic target, are still to be elucidated. Here we show that the abundant or moderate over-expression of HER2/neu could be detected in both pulmonary adenocarcinoma and pulmonary large cell carcinoma cell lines. Stable knockdown of HER2/neu expression in the NSCLC cell line SPC-A-1 was achieved by vector-based small interfering RNAs (siRNAs), which consequently caused significant decrease in cell proliferation and clone forming efficiency, as well as cell cycle arrest at G(1) phase. Compared with the parental NSCLC cells, HER2/neu knockdown cells exhibited attenuated capacities in developing tumors in nude mice, and the growth tumors xenografts derived from these cells were dramatically regressed. These data provided direct evidence that HER2/neu signaling is essential for tumorigenicity of NSCLC cells, and suggested that siRNAs targeted to HER2/neu may provide a novel therapeutic strategy in the treatment of NSCLC, especially when combined with traditional therapeutics or via development of vector-based siRNAs of multiple targets that synergistically contribute to carcinogenesis, e.g. EGFR and HER2/neu.
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PMID:Inhibition of non-small cell lung cancer cell proliferation and tumor growth by vector-based small interfering RNAs targeting HER2/neu. 1933 4

Clear cell renal cell carcinoma (ccRCC) is the most common malignancy of the adult kidney and displays heterogeneity in clinical outcomes. Through comprehensive gene expression profiling, we have identified previously a set of transcripts that predict survival following nephrectomy independent of tumor stage, grade, and performance status. These transcripts, designated as the SPC (supervised principal components) gene set, show no apparent biological or genetic features that provide insight into renal carcinogenesis or tumor progression. We explored the relationship of this gene list to a set of genes expressed in different anatomical segments of the normal kidney including the cortex (cortex gene set) and the glomerulus (glomerulus gene set), and a gene set expressed after serum stimulation of quiescent fibroblasts (the core serum response or CSR gene set). Interestingly, the normal cortex, glomerulus (part of the normal renal cortex), and CSR gene sets captured more than 1/5 of the genes in the highly prognostic SPC gene set. Based on gene expression patterns alone, the SPC gene set could be used to sort samples from normal adult kidneys by the anatomical regions from which they were dissected. Tumors whose gene expression profiles most resembled the normal renal cortex or glomerulus showed better survival than those that did not, and those with expression features more similar to CSR showed poorer survival. While the cortex, glomerulus, and CSR signatures predicted survival independent of traditional clinical parameters, they were not independent of the SPC gene list. Our findings suggest that critical biological features of lethal ccRCC include loss of normal cortical differentiation and activation of programs associated with wound healing.
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PMID:Alteration of gene expression signatures of cortical differentiation and wound response in lethal clear cell renal cell carcinomas. 1955 79

Despite the type I insulin-like growth factor receptor (IGF-IR) being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung type II alveolar cells (surfactant protein C [SPC]-IGFIR) or Clara cells (CCSP-IGFIR) in a doxycycline-inducible manner. Overexpression of IGF-IR in either cell type caused multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas. These tumors expressed thyroid transcription factor 1 and Kruppel-like factor 5 in most tumor cells. Similar to our previous work with lung tumors that developed in the mouse mammary tumor virus-IGF-II transgenic mice, the lung tumors that develop in the SPC-IGFIR and CCSP-IGFIR transgenic mice expressed high levels of the cyclic adenosine monophosphate response element binding protein that was localized primarily to the nucleus. Although elevated IGF-IR expression can initiate lung tumor development, tumors can become independent of IGF-IR signaling as IGF-IR down-regulation in established tumors produced tumor regression in some, but not all, of the tumors. These findings implicate IGF-IR as an important initiator of lung tumorigenesis and suggest that the SPC-IGFIR and CCSP-IGFIR transgenic mice can be used to further our understanding of human lung cancer and the role IGF-IR plays in this disease.
Neoplasia 2009 Jul
PMID:Type I insulin-like growth factor receptor induces pulmonary tumorigenesis. 1956 12

A series of honokiol analogues were synthesized by modifying the 5- and/or 3'-position(s) of honokiol to assess their anti-tumor effects. Some compounds exerted more potent anti-proliferative activities than those of honokiol on K562 leukemia cells, A549 alveolar basal epithelial cells, SPC-A1 adenocarcinoma cells and A2780 human ovarian carcinoma cells in vitro. Compounds 2b, 3a, and 3c displayed most potent anti-proliferative activities against these tested cell strains and their anti-drug resistance effects were evaluated in vitro on cisplatin-resistant A2780 human ovarian carcinoma cells. The structure-activity relationship was also proposed.
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PMID:Semi-synthesis and anti-proliferative activity evaluation of novel analogues of Honokiol. 1958 78

Livin, a novel member of inhibitors of apoptosis protein, is highly expressed in tumor tissues. It is a potential target in tumor therapy. Silencing its gene expression has been found to promote tumor cell apoptosis or increase tumor sensitivity to therapies. This paper studied the effect of livin anti-apoptotic activity and examined its molecular mechanisms. In the study, higher levels of cell apoptosis were measured by FACS in the experiment group with livin expression silenced than that in controls (P < 0.05). After livin gene expression was knocked down, cleaved caspase-3 protein was up-regulated but caspase-3 mRNA expression was almost the same, the phosphorylated JNK1 protein was down-regulated but JNK1 mRNA and total JNK1 protein expression was approximately the same too. The results suggest that livin may exert anti-apoptotic action on SPC-A1 by activating JNK1 signaling pathway and inhibiting caspase-3 activation.
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PMID:Livin abrogates apoptosis of SPC-A1 cell by regulating JNKI signaling pathway. 1969 Sep 82

Gambogic acid (GA) is one of the important active ingredients of gamboge. Our study examined the expression of transferrin receptors (TFR) on the cell surface of human lung SPC-A1 and SK-MES-1 cells and measured their GA-induced apoptosis rate. The results showed that SPC-A1 cells with a higher TFR expression were more sensitive at the same GA concentrations. To examine its distribution in cultured cells and study the mechanisms of apoptosis, we labeled GA with a (125)I tracer and examined the expression of apoptosis-related proteins. we found that GA uptake into SPC-A1 cells was higher than into SK-MES-1 cells; apoptosis-related proteins Caspase 2, Caspase 9, Caspase 10, Bax and p53 were involved in GA-induced apoptosis. We conclude that GA has an apoptosis-promoting effect on non small cell lung cancer cells. In clinical practice, the histopathological quantitation of TFR expression levels in tumor tissues may become a predictor of the sensitivity of patients' tumors to GA treatment.
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PMID:Mechanisms of gambogic acid-induced apoptosis in non-small cell lung cancer cells in relation to transferrin receptors. 2007 Dec 91


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