Search results for "Transform"
showing 10 items of 3975 documents
Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.
1997
We have shown that the oval cell line OCICDE 22 can be transformed by the highly carcinogenic fiord-region diol epoxides of benzo[c]phenanthrene. Mutational activation of the ras proto-oncogene family has been proposed to be a critical event in the formation of tumors induced by polycyclic aromatic hydrocarbons. Therefore, we investigated whether in the earlier transformed OCICDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OCICDE 22 cells by the 4 stereoisomeric benzo[c]phenan-threne diol epoxides in vitro is independent of activation of the Ha-ras proto-oncogene. In addition, Northern and Western blot analy…
Genomic Abnormalities Acquired in the Blastic Transformation of Splenic Marginal Zone B-cell Lymphoma
2003
Among 20 cases of typical splenic marginal zone lymphoma (SMZL), two cases had blastic transformation. The genetic mechanisms underlying the morphologic transformation were investigated by comparing genetic changes in initial and blastic phases. A complex karyotype including trisomy of 3q and genomic gain of 17q22-q24 was seen in both cases at diagnosis. However, the extra copy of 3q was lost during the transformation process in both tumors. Additionally, the Karpas 1718 cell line, which was derived from a patient with transformed SMZL and carried a trisomy of 3q, also evidenced the spontaneous loss of the extra 3q during the culturing process. Other acquired abnormalities observed exclusiv…
Carcinosarcoma of monoclonal origin arising in a dermoid cyst of ovary: a case report.
2005
Abstract Background Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated. Case presentation A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC). The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio. Positive staining for vimentin, alpha smooth muscle actin and CD1…
Vascularity, perfusion rate and local tissue oxygenation of tumors derived from ras-transformed fibroblasts.
2007
Tumors derived from ras-transformed rat fibroblasts were investigated in order to gain insight into possible interrelationships between oncogenic transformations and therapeutically relevant parameters of the metabolic micromilieu of solid tumors in vivo. Tumors grew in nude mice after injection of in vitro-passaged cells. Growth rates, early stages of angiogenesis, perfusion and tissue oxygenation were assessed. Compared with the parental cell line, both ras transformants grew very rapidly and exhibited an early onset of angiogenesis. Perfusion rates of one ras-transformed tumor line were similar to those of the parental tumors whereas reduced flow values were detected in tumors of the oth…
Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development
2008
Abstract Purpose: Antibody-based cancer therapies have emerged as the most promising therapeutics in oncology. The purpose of this study was to discover novel targets for therapeutic antibodies in solid cancer. Experimental Design: We combined data mining and wet-bench experiments to identify strictly gastrocyte lineage–specific cell surface molecules and to validate them as therapeutic antibody targets. Results: We identified isoform 2 of the tight junction molecule claudin-18 (CLDN18.2) as a highly selective cell lineage marker. Its expression in normal tissues is strictly confined to differentiated epithelial cells of the gastric mucosa, but it is absent from the gastric stem cell zone. …
Transforming Growth Factor-β–Mediated Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression and Apoptosis in Hepatoma Cells Requires Fun…
2008
Abstract Transforming growth factor-β (TGF-β) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. We recently identified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as an important mediator of TGF-β–induced apoptosis in hepatoma cells. In this study, we have further explored the mechanism by which TGF-β up-regulates TRAIL expression. The 5′-flanking region of the TRAIL gene was isolated and characterized. Deletion mutants of the 5′-untranslated region of the TRAIL gene revealed a region comprising nucleotides −1950 to −1100 responsible for TRAIL induction following treatment with TGF-β. Within this region, we have identified an activator …
Apoptosis and the liver
2000
Regulation of the homeostatic balance between cell proliferation and programmed cell death, apoptosis, is essential for development and maintenance of multicellular organisms. Apoptosis is a genetically and evolutionarily highly conserved process. Analysis of the molecular mechanisms of apoptosis has led to a better understanding of many human diseases. Notably in cancer, but also in infectious or autoimmune disease, a deficiency in apoptosis is one of the key events in pathophysiology. On the other hand, overefficient apoptosis, as observed in fulminant liver failure, may be equally harmful for the organism indicating that a tight regulation of the apoptotic machinery is essential for surv…
Chronic inflammatory IFN-γ signaling suppresses hepatocarcinogenesis in mice by sensitizing hepatocytes for apoptosis.
2011
Abstract Chronic liver inflammation is a critical component of hepatocarcinogenesis. Indeed, inflammatory mediators are believed to promote liver cancer by upholding compensatory proliferation of hepatocytes in response to tissue damage. However, inflammation can also mediate the depletion of malignant cells, but the difference between tumor-suppressive and tumor-promoting inflammation is not defined at the molecular level. Here, we analyzed the role of the major inflammatory mediator IFN-γ in chemical hepatocarcinogenesis of transgenic mice that overexpress IFN-γ in the liver; these mice manifest severe chronic inflammatory liver damage and lasting compensatory regeneration. We found that …
Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis.
2005
V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2; synonyms HER2, NEU) encodes a transmembrane glycoprotein with tyrosine kinase-specific activity that acts as a major switch in different signal-transduction processes. ERBB2 amplification and overexpression have been found in a number of human cancers, including breast, ovary and kidney carcinoma. Our aim was to detect ERBB2-regulated target genes that contribute to its tumorigenic effect on a genomewide scale. The differential gene expression profile of ERBB2-transfected and wild-type mouse fibroblasts was monitored employing DNA microarrays. Regulated expression of selected genes was verified by RT-PCR and validated by West…
Molecular principles of cancer invasion and metastasis (Review)
2009
The main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. Drastic phenotypic and biochemical changes occur during the metamorphosis of a normal tissue cell into an invasive cancer cell. These alterations concern various areas such as growth factor signaling, cell-cell adhesion, gene expression, motility or cell shape. Cancer cells of epithelial origin can even shed their typical qualities and characteristics and adopt a mesenchymal-like phenotype. This is often referred to as an epithelial-mesenchymal transition. Various oncogenes, tumor suppressor genes and metastasis suppressor genes are known to affect the invasiveness and…