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Transformed Cell Lines (transformed + cell_line)
Selected AbstractsDevelopment of a swine model of secondary liver tumor from a genetically induced swine fibroblast cell lineHPB, Issue 3 2008R. Abbas Abstract Aim. Metastatic disease is the most common liver tumor. Although alternative therapies have been developed for non-surgical candidates, those therapies lacked ideal testing prior to clinical application because of a paucity of large animal models. The purpose of the present study was to develop a model for secondary liver tumor in a large animal. Material and methods. Fibroblasts were isolated from swine ear lobules and then transfected with amphotrophic retroviruses encoding human or murine genetic material (hTERT, p53DD, cyclinD-1, CDK4R24C, Myc T58A, RasG12V). Transformed cell lines were finally inoculated subcutaneously (s.c.) into: 1) immunodeficient mice (nude), 2) immunocompetent mice (wild type), 3) immunosuppressed swine (under tacrolimus or corticosteroids), 4) immunocompetent swine, and 5) into the liver and portal circulation of swine under steroid-based immunosuppression. Results. In the murine model, tumor growth was evident in 100% of the nude mice (n=5), with a peak size of 20 mm (15.22±4.5 mm; mean±SD) at the time of sacrifice (3 weeks). Tumor growth was evident in 71% of the wild mice (n=21), with a peak size of 7.8 mm (4.19±1.1 mm) by the third week of growth. In the swine model, tumor growth was evident in 75% (3/4 ears; n=2) of swine under tacrolimus-based immunosuppression versus 50% of swine under steroids-based immunosuppression (n=2). Tumor growth was slow in two animals, while in one animal the tumor was larger with a peak growth of 42 mm at 3 weeks. The tumor pattern in the ear lobules was characterized by slow growth, with a peak size of 6,8 mm in the immunocompetent swine at 3 weeks. All tumors were shown to be malignant by histology. In contrast, inoculums of the transformed fibroblast cell line in swine livers showed no evidence of tumor growth at 3 weeks. Conclusions. Development of a transformed swine fibroblast cell line was successful, resulting in an in vivo malignant tumor. Cell line inoculums had tumorigenic properties in nude mice, wild-type mice, and immunosuppressed swine, as judged by uncontrolled cell growth, invasion of surrounding tissue, neoangiogenesis, and invasion of normal vasculature, resulting in the formation of tumor nodules. Such properties were not observed in swine upon inoculation into the liver/portal circulation. [source] Cigarette smoke condensate induces nuclear factor kappa-b activity and proangiogenic growth factors in aerodigestive cells,THE LARYNGOSCOPE, Issue 8 2010Joseph Rohrer MD Abstract Objectives/Hypothesis: Aerodigestive cancer risk of both lung and head and neck cancers has been linked to the genotoxic effects of tobacco use. These effects include upregulation of nuclear factor kappa-B (NF,B) and its downstream products associated with both lung and head and neck cancer malignant progression. Study Design: Bench Research. Methods: In the present study we examined the effects of cigarette smoke condensate on functional activation of NF,B in human papillomavirus (HPV)-transformed oral cavity cells (HOK 16B cells) and transformed bronchial epithelium (Beas2B cells) using the head and neck squamous cancer cell line, UMSCC 38, as a comparison. Luciferase reporter gene assays with two types of transiently transfected NF,B reporter genes were employed and downstream NF,B-dependent products, interleukin-6, interleukin-8, and vascular endothelial growth factor, were assayed by enzyme-linked immunosorbent assay. Results: All cell lines were able to dose dependently activate NF,B reporter genes after exposure to cigarette smoke condensate (P < .05). However, the HPV premalignant, transformed cell line had a much more robust NF,B response (3.45-fold) versus the squamous cancer cell line (1.62-fold) and SV40 transformed Beas2B (1.83). Both NF,B reporter genes had similar response curves. Conclusions: This study demonstrates cigarette smoke products might be more potent promoters of an NF,B-dependent progression from HPV+ premalignancy to cancer rather than after tumors are established. Future studies should focus on abrogating NF,B increases during malignant progression and premalignancy. This might be even more relevant in the HPV+ patient with premalignancy. Laryngoscope, 2010 [source] Upregulation of plakophilin-2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell,cell-attachment characteristic for transformed mesenchymal cellsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Steffen Rickelt Abstract In contrast to the desmosome-containing epithelial and carcinoma cells, normal and malignantly transformed cells derived from mesenchymal tissues and tumors are connected only by adherens junctions (AJs) containing N-cadherins and/or cadherin-11, anchored in a cytoplasmic plaque assembled by ,- and ,-catenin, plakoglobin, proteins p120 and p0071. Here, we report that the AJs of many malignantly transformed cell lines are characterized by the additional presence of plakophilin-2 (Pkp2), a protein hitherto known only as a major component of desmosomal plaques, i.e., AJs of epithelia and carcinomatous cells. This massive acquisition of Pkp2 and its integration into AJ plaques of a large number of transformed cell lines is demonstrated with biochemical and immunolocalization techniques. Upregulation of Pkp2 and its integration into AJs has also been noted in some soft tissue tumors insitu and some highly proliferative colonies of cultured mesenchymal stem cells. As Pkp2 has recently been identified as a functionally important major regulatory organizer in AJs and related junctions in epithelial cells and cardiomyocytes, we hypothesize that the integration of Pkp2 into AJs of "soft tissue tumor" cells also can serve functions in the upregulation of proliferation, the promotion of malignant growth in general as well as the close-packing of diverse kinds of cells and the metastatic behavior of such tumors. We propose to examine its presence in transformed mesenchymal cells and related tumors and to use it as an additional diagnostic criterion. © 2009 UICC [source] Biomolecular characterization of human glioblastoma cells in primary cultures: Differentiating and antiangiogenic effects of natural and synthetic PPAR, agonistsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008E. Benedetti Gliomas are the most commonly diagnosed malignant brain primary tumors. Prognosis of patients with high-grade gliomas is poor and scarcely affected by radiotherapy and chemotherapy. Several studies have reported antiproliferative and/or differentiating activities of some lipophylic molecules on glioblastoma cells. Some of these activities in cell signaling are mediated by a class of transcriptional factors referred to as peroxisome proliferator-activated receptors (PPARs). PPAR, has been identified in transformed neural cells of human origin and it has been demonstrated that PPAR, agonists decrease cell proliferation, stimulate apoptosis and induce morphological changes and expression of markers typical of a more differentiated phenotype in glioblastoma and astrocytoma cell lines. These findings arise from studies mainly performed on long-term cultured transformed cell lines. Such experimental models do not exactly reproduce the in vivo environment since long-term culture often results in the accumulation of further molecular alterations in the cells. To be as close as possible to the in vivo condition, in the present work we investigated the effects of PPAR, natural and synthetic ligands on the biomolecular features of primary cultures of human glioblastoma cells derived from surgical specimens. We provide evidence that PPAR, agonists may interfere with glioblastoma growth and malignancy and might be taken in account as novel antitumoral drugs. J. Cell. Physiol. 217: 93,102, 2008. © 2008 Wiley-Liss, Inc. [source] UV-enhanced Expression of a Reporter Gene is Induced at Lower UV Fluences in Transcription-coupled Repair Deficient Compared to Normal Human Fibroblasts, and is Absent in SV40-transformed Counterparts,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2000Murray A. Francis ABSTRACT UV irradiation enhances transcription of a number of cellular and viral genes. We have compared dose responses for alterations in expression from reporter constructs driven by the human and murine cytomegalovirus (CMV) immediate early (IE) promoters in cells from patients with deficiencies in nucleotide excision repair (complementation groups of xeroderma pigmentosum and Cockayne syndrome) following UV exposure, or infection with UV-damaged recombinant vectors. Results suggest that unrepaired damage in active genes triggers increased reporter activity from constructs driven by the CMV promoters in human fibroblasts. Similar to human fibroblasts, HeLa cells and cells from Li,Fraumeni syndrome patients (characterized by an inherited mutation in the p53 gene) also displayed an increase in reporter activity following UV exposure; however, this response was absent in all simian virus 40 (SV40)-transformed cell lines examined. This suggests that a pathway affected by SV40-transformation (other than p53) plays an essential role in UV-enhanced expression from the CMV IE promoter. [source] | |||||||||||||