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Tumor Lines (tumor + line)
Selected AbstractsAnti-tumor MHC class,Ia-unrestricted CD8 T,cell cytotoxicity elicited by the heat shock protein gp96EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2004Ana Goyos Abstract In Xenopus as in mammals, gp96 stimulates MHC-restricted cellular immunity against chaperoned minor histocompatibility (H) antigens (Ag). In adult Xenopus, gp96 also elicits peptide-specific effectors against MHC class,Ia-negative 15/0 tumors. To determine whether gp96 can generate functionally heterogeneous CD8+ effectors (CTL that kill MHC class,Ia+ minor,H-Ag-disparate lymphoblasts and MHC class,Ia, tumor targets), LG-6 isogenetic frogs were immunized with gp96 purified either from MHC-identical but minor,H-Ag-disparate LG-15 normal tissues or from the MHC class,Ia-negative 15/0 tumor line (derived from LG-15 frogs). LG-15 normal liver-derived gp96 did not induce detectable CD8+in vitro killing against 15/0 tumor cells. However, 15/0-derived gp96 did induce killing against both MHC class,Ia+ LG-15 lymphoblasts and the MHC class,Ia, 15/0 tumor, but not against another MHC class,Ia, tumor (B3B7) or against LG-6 lymphoblasts. Tumor killing was better when 15/0 rather than normal LG-15 irradiated stimulators were used, but in vitro stimulation without prior in vivo immunization was ineffective. These data suggest that (1),15/0-derived gp96 chaperones minor,H-Ag shared with normal LG-15 lymphocytes and elicits MHC-restricted CTL, and (2),15/0-derived gp96, but not normal liver-derived gp96, generates CD8+ effectors that kill 15/0 tumor cells in the absence of MHC class,Ia expression. [source] Small cell neuroendocrine carcinoma of the maxillary sinus,A case report and nude mouse transplantable model,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2002Kazuma Noguchi DDS Abstract Background A rare case of small cell neuroendocrine carcinoma (SNEC) arising in the maxillary sinus is presented, and a SNEC tumor line serially transplantable in nude mice was established. Tumor marker for SNEC is also discussed. Methods The tumor tissues obtained from operated material were heterotransplanted subcutaneously into nude mice. Histopathologic studies and immunoradiometric assays for NSE and pro-GRP in serum were performed. Results The primary lesion was composed of tumor nests of small cells with hyperchromatic nuclei and was positive for NSE and chromogranin A immunohistochemically. Serum levels of NSE and pro-GRP changed dynamically, reflecting the clinical status. Nude mouse tumor showed similar histologic features to those of original tumor and expressed NSE. Neuroendocrine granules were detected in tumor cells in electron microscopy. Serum NSE level in nude mice was elevated in proportion to the relative tumor weight. Conclusions Serum NSE and pro-GRP were useful tumor markers for extrapulmonary SNEC. A SNEC tumor transplantable in nude mice would provide a valuable model for characterization of this lesion. © 2002 Wiley Periodicals, Inc. [source] Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin-3 and supports cell migrationINTERNATIONAL JOURNAL OF CANCER, Issue 5 2005Claudia Paret Abstract C4.4A is a member of the Ly6 family, with low homology to uPAR. It has been detected mainly on metastasizing carcinoma cells and proposed to be involved in wound healing. So far, C4.4A has been observed as an orphan receptor, and its functional activity has not been explored. Using recombinant rat C4.4A (rrC4.4A) made in a eukaryotic expression system, we demonstrate by immunohistology that C4.4A ligands are strongly expressed in tissues adjacent to squamous epithelia of, e.g., tongue and esophagus, the expression pattern partly overlapping with laminin (LN) and complementing the C4.4A expression that is found predominantly on the basal layers of squamous epithelium. ELISA screening of several components of the extracellular matrix revealed selective binding of rrC4.4A to LN1 and LN5 and that transfection of the BSp73AS tumor line with C4.4A cDNA (BSp73AS-1B1) promoted LN1 and LN5 binding. Binding of BSp73AS-1B1 to LN5 and, less markedly, LN1 induced spreading, lamellipodia formation and migration. C4.4A also associates with galectin-3 in nontransformed tissues and tumor lines. There is evidence that the association of C4.4A with galectin-3 influences LN adhesion. C4.4A was described originally as a metastasis-associated molecule. Our findings that LN1 and LN5 are C4.4A ligands, that galectin-3 associates with C4.4A and that C4.4A ligand binding confers a migratory phenotype are well in line with the supposed metastasis association. © 2005 Wiley-Liss, Inc. [source] Characterization of p21Ras -mediated apoptosis induced by protein kinase C inhibition and application to human tumor cell linesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004James S. Liou Suppression of PKC activity can selectively induce apoptosis in cells expressing a constitutively activated p21Ras protein. We demonstrate that continued expression of p21Ras activity is required in PKC-mediated apoptosis because farnesyltransferase inhibitors abrogated the loss of viability in p21Ras -transformed cells occurring following PKC inhibition. Studies utilizing gene transfer or viral vectors demonstrate that transient expression of oncogenic p21Ras activity is sufficient for induction of apoptosis by PKC inhibition, whereas physiologic activation of p21Ras by growth factor is not sufficient to induce apoptosis. Mechanistically, the p21Ras -mediated apoptosis induced by PKC inhibition is dependent upon mitochondrial dysregulation, with a concurrent loss of mitochondrial membrane potential (,m). Cyclosporine A, which prevented the loss of ,m, also inhibited HMG-induced DNA fragmentation in cells expressing an activated p21Ras. Induction of apoptosis by PKC inhibition in human tumors with oncogenic p21Ras mutations was demonstrated. Inhibition of PKC caused increased apoptosis in MIA-PaCa-2, a human pancreatic tumor line containing a mutated Ki,ras allele, when compared to HS766T, a human pancreatic tumor line with normal Ki,ras alleles. Furthermore, PKC inhibition induced apoptosis in HCT116, a human colorectal tumor line containing an oncogenic Ki,ras allele but not in a subline (Hke3) in which the mutated Ki,ras allele had been disrupted. The PKC inhibitor 1- O -hexadecyl-2- O -methyl-rac-glycerol (HMG), significantly reduced p21Ras -mediated tumor growth in vivo in a nude mouse MIA-PaCa-2 xenograft model. Collectively these studies suggest the therapeutic feasibility of targeting PKC activity in tumors expressing an activated p21Ras oncoprotein. J. Cell. Physiol. 198: 277,294, 2004. © 2003 Wiley-Liss, Inc. [source] Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin-3 and supports cell migrationINTERNATIONAL JOURNAL OF CANCER, Issue 5 2005Claudia Paret Abstract C4.4A is a member of the Ly6 family, with low homology to uPAR. It has been detected mainly on metastasizing carcinoma cells and proposed to be involved in wound healing. So far, C4.4A has been observed as an orphan receptor, and its functional activity has not been explored. Using recombinant rat C4.4A (rrC4.4A) made in a eukaryotic expression system, we demonstrate by immunohistology that C4.4A ligands are strongly expressed in tissues adjacent to squamous epithelia of, e.g., tongue and esophagus, the expression pattern partly overlapping with laminin (LN) and complementing the C4.4A expression that is found predominantly on the basal layers of squamous epithelium. ELISA screening of several components of the extracellular matrix revealed selective binding of rrC4.4A to LN1 and LN5 and that transfection of the BSp73AS tumor line with C4.4A cDNA (BSp73AS-1B1) promoted LN1 and LN5 binding. Binding of BSp73AS-1B1 to LN5 and, less markedly, LN1 induced spreading, lamellipodia formation and migration. C4.4A also associates with galectin-3 in nontransformed tissues and tumor lines. There is evidence that the association of C4.4A with galectin-3 influences LN adhesion. C4.4A was described originally as a metastasis-associated molecule. Our findings that LN1 and LN5 are C4.4A ligands, that galectin-3 associates with C4.4A and that C4.4A ligand binding confers a migratory phenotype are well in line with the supposed metastasis association. © 2005 Wiley-Liss, Inc. [source] Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Aniruddha Choudhury Abstract Silencing of a specific mRNA using double stranded RNA oligonucleotides represents one of the newest technologies for suppressing a specific gene product. Small interfering RNA (siRNA) are 21 nucleotides long, double stranded RNA fragments that are identical in sequence to the target mRNA. We designed 3 such siRNA against the Her2/neu (HER2) gene. The HER2 gene is known to play an important role in the oncogenesis of several types of cancers, such as breast, ovarian, colon and gastric cancers. Introduction of the siRNA into HER2 positive tumor lines in vitro greatly reduced the cell surface expression of the HER2 protein. Concurrently, a range of effects on cell physiology, such as growth inhibition or apoptosis, was observed. The expression of HLA class I was observed to be upregulated when HER2 was silenced with siRNA. Treatment of SKBr3 and MCF7/HER2 tumor cell lines with the HER2 siRNA resulted in growth arrest of cells in the late G1/S-phase. Our results suggest that siRNA may be an effective method of abrogating the effect of HER2 in tumorigenesis. © 2003 Wiley-Liss, Inc. [source] Combined Use of PCA and QSAR/QSPR to Predict the Drugs Mechanism of Action.MOLECULAR INFORMATICS, Issue 4 2009An Application to the NCI ACAM Database Abstract During the years the National Cancer Institute (NCI) accumulated an enormous amount of information through the application of a complex protocol of drugs screening involving several tumor cell lines, grouped into panels according to the disease class. The Anti-cancer Agent Mechanism (ACAM) database is a set of 122 compounds with anti-cancer activity and a reasonably well known mechanism of action, for which are available drug screening data that measure their ability to inhibit growth of a panel of 60 human tumor lines, explicitly designed as a training set for neural network and multivariate analysis. The aim of this work is to adapt a methodology (previously developed for the analysis of DNA minor groove binders) for the analysis of NCI ACAM database, using Principal Component Analysis (PCA) and QSAR/QSPR for the prediction of the mechanism of action of anti-cancer drugs. The entire database was splitted in a training set of 60 structures and a test set of 48 ones, and each set was expressed in form of a matrix on which further procedures were performed. Three statistical parameters were calculated: First Attempt of Prediction (FAP) expresses the percentage of correct predictions at first attempt, Total Attempt of Prediction (TAP) expresses the total percentage of correct predictions across all the three attempts, Non-Classified (NC) expresses the percentage of compounds whose mechanism of action has failed to be predicted. The predictive ability of this approach is variable, but the results obtained are generally good; using 50% Growth Inhibiting concentration (GI50) values as training data, we were able to assign a correct mechanism of action with a good degree of reliability (more than 79%). [source] Correlation of thrombospondin-1 and transforming growth factor-, expression with malignancy of gliomaNEUROPATHOLOGY, Issue 3 2000Tomoyuki Kawataki The expression of thrombospondin-1 (TSP-1) and its role in gliomas have not been well examined. In the present study TSP-1 expression in a panel of malignant glioma cell lines and the expression of TSP-1 and transforming growth factor (TGF-,) proteins in low-grade and malignant glioma tissues were investigated. Reverse transcription-polymerase chain reaction analysis showed that nine of nine malignant glioma cell lines expressed TSP-1 mRNA, and seven of nine glioma lines expressed TSP-2 mRNA. Production and secretion of TSP-1 were examined in the T98G glioblastoma cell line by western blot analysis. Total TSP-1 protein content in the supernatant was 10 times higher than that in the cell lysate. Secretion of TSP-1 was examined in these glioma cell lines by western blot analysis. All glioma lines secreted significant levels of TSP-1. Bioassay showed that all tumor lines had the capacity to activate latent TGF-,. Localization of TSP-1, TGF-,1, -,2, and -,3 was examined immunohistochemically in surgically resected glioma tissues, including 11 glioblastomas, six anaplastic astrocytomas, and eight astrocytomas. Most glioblastomas expressed high levels of both TSP-1 and TGF-,. Anaplastic astrocytomas expressed moderate levels of TSP-1 and TGF-,. Most malignant gliomas expressed various levels of TGF-,1, -,2, and -,3. The expression of both proteins, however, was weak in low-grade gliomas. Normal brain tissues around the tumors were negatively or very weakly positively stained for TSP-1 and TGF-,. These results indicate that most malignant glioma cells express TSP-1 in vitro and in vivo, and the expression of TSP-1 and TGF-,in vivo correlates with the histologic malignancy of glioma. Overexpression of both TSP-1 and TGF-, may increase the biologic malignancy of malignant gliomas, through generating the active form of TGF-, in tumor tissues. [source] Fiber-knob modifications enhance adenoviral tropism and gene transfer in malignant gliomaTHE JOURNAL OF GENE MEDICINE, Issue 3 2007Sophy Zheng Abstract Background Malignant gliomas remain refractory to Ad5-mediated gene therapy due to deficiency of the coxsackie adenovirus receptor on tumor cells. The purpose of this study was to evaluate whether changes in adenoviral tropism can enhance gene transfer in the context of malignant glioma. Methods We have identified several receptors that are over-expressed on tumor cells and created a series of pseudotyped Ad5 vectors that recognize these receptors: Ad5-RGD which binds ,v,3/,v,5 integrins; Ad5/3 which contains adenovirus serotype 3 knob and binds to CD46; Ad5-Sigma which incorporates the reovirus sigma knob and binds to junctional adhesion molecule-1; and Ad5-pk7 which contains the polylysine motif and binds heparan sulfate proteoglycans. We also investigated the Ad5-CAV1 vector, which contains the knob of canine adenovirus type 1, a virus previously shown to infect glioma via an unknown mechanism. In this study, we compared these modified vectors for their ability to promote the expression of luciferase transgene both in vitro and in vivo. Results Our results indicate that all five modified vectors attained higher mean luciferase activity vs. control. Among them, Ad5-CAV1 and Ad5-pk7 attained the highest transduction efficiency independent of different tumor lines or infection time. Ad5-Sigma and Ad5-pk7 also demonstrated the least nonspecific infection in normal human astrocytes. Most importantly, Ad5-pk7 achieved 1000-fold increased transgene expression in human glioma xenografts in vivo. Conclusions These results indicate that modifications of adenoviral tropism can enhance gene transfer in tumors that are poorly susceptible to adenoviral vectors and warrant further development of Ad5-pk7 for glioma gene therapy. Copyright © 2007 John Wiley & Sons, Ltd. [source] | |||||||||||||