0000000000182266
AUTHOR
Nektaria Simiantonaki
Local staging of rectal carcinoma and assessment of the circumferential resection margin with high-resolution MRI using an integrated parallel acquisition technique
Purpose To assess the diagnostic accuracy of integrated parallel acquisition technique (iPAT) in local staging of rectal carcinoma in comparison to conventional high-resolution MRI. Materials and Methods A total of 28 patients with a neoplasm of the rectum and 15 control patients underwent MRI of the pelvis. High-resolution images were acquired conventionally and with iPAT using a modified sensitivity encoding (mSENSE). Image quality, signal-to-noise and contrast-to-noise ratios (SNR, CNR), tumor extent, nodal status, and delineation of the circumferential resection margin (CRM) were compared. In 19 patients with a carcinoma, MR findings were correlated with the histopathological diagnosis.…
Endothelial VEGFR-3 expression in colorectal carcinomas is associated with hematogenous metastasis
Vascular endothelial growth factor receptor 3 (VEGFR-3) is a major inducer of lymphangiogenic signalling and seems to be involved also in angiogenesis. Since both processes are closely linked with tumor metastasis this study investigated the expression of VEGFR-3 in tumor-associated vessels in colorectal carcinomas and evaluated its relevance for lymphogenous and hematogenous metastasis. In a comparative study between microvascular endothelial cells isolated from the tumor (HCTEC) and the corresponding non-neoplastic tissue (HCMEC) from five patients with colorectal cancer VEGFR-3 expression was measured using a specific ELISA. The expression pattern was individually different, with cases s…
Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression
Abstract Background Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Methods Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in n…
Comparative study of human colonic tumor-derived endothelial cells (HCTEC) and normal colonic microvascular endothelial cells (HCMEC): Hypoxia-induced sVEGFR-1 and sVEGFR-2 levels
Colorectal carcinoma growth and progression is dependent on the vasculature of the tumor microenvironment. Tumor-derived endothelial cells differ functionally from their normal counterpart. For this reason we isolated microvascular endothelial cells from human colon cancer tissue (HCTEC) and compared them with endothelial cells from normal colonic tissue (HCMEC) of the same donor. Since hypoxia is a universal hallmark of carcinomas, we examined its effects on HCTEC of five patients in comparison with the corresponding HCMEC, with respect to the secretion of the soluble form of the two important vascular endothelial growth factor (VEGF) receptors, VEGFR-1 and -2. After dissociation by dispas…
Effect of Pro-inflammatory Stimuli on Tumor Cell-Mediated Induction of Endothelial Cell Adhesion Molecules in Vitro
The object of our study was the question about the relevance of the tumor surrounding inflammatory cells with respect to the metastatic potential of the tumor cells. To imitate the role of inflammatory cells, three colon carcinoma (HT-29, HRT-18, and SW-620), one breast carcinoma (MCF-7), and one melanoma (ST-ML-12) cell lines were treated with pro-inflammatory stimuli, LPS, TNF-alpha, or IL-1beta. HUVEC monolayers were then stimulated by the collected supernatants (SN) of the tumor cells, following washing out of the applied stimuli. Analysis of CAM expression on HUVEC was performed using cell enzyme immunoassay. E-selectin, VCAM-1, and, in part, ICAM-1 were significantly up-regulated on H…
Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression
The transcription factor NFkappaB regulates the expression of several tumor-related molecules associated with tumor progression and metastasis. However, the precise mechanisms by which its activation mediates these processes in diverse tumors are unknown. In this study we determined the expression of NFkappaB in various colorectal carcinoma cell lines, in a series of 90 non-metastatic and metastatic colorectal tumors and in an in vitro 3D-spheroid model of HT-29 cells simulating morphological hallmark of these adenocarcinomas, namely neoplastic glandular nests around a necrotic center. We show that the inactive cytoplasmic NFkappaB form is evidently up-regulated in the tumor epithelium, esp…
Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4
In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 …
Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer.
Signaling mediating colorectal cancer (CRC) progression is incompletely understood. Previously, we identified lipopolysaccharide (LPS), an endotoxin of ubiquitously existing colonic bacteria, as a pivotal stimulus increasing the metastatic potential of human CRC. Since the ubiquitous colonic bacteria release large amounts of LPS this observation could be of enormous relevance for the progression of CRC. In this study we present data contributing to the elucidation of its mode of action. Since both receptors CD14 and TLR4 act as LPS mediators, we determined their expression in various CRC cell lines and in 115 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CRC specimens…
Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor.
Recently, we identified htid-1, the human counterpart of the Drosophila tumor suppressor gene lethal(2)tumorous imaginal discs [l(2)tid], as a direct molecular ligand of the adenomatous polyposis coli (APC) tumor suppressor. The gene encodes three cytosolic (Tid50, Tid48 and Tid46) and three mitochondrial (Tid43, Tid40 and Tid38) proteins. In the colorectal epithelium the cytosolic forms hTid50/hTid48 interact under physiological conditions with the N-terminal region of APC. This complex which associates with additional proteins such as Hsp70, Hsc70, Actin, Dvl and Axin defines a novel physiological state of APC unrelated to beta-catenin degradation. Here we show that the expression of the …
Effect of Chemokine Receptors CXCR4 and CCR7 on the Metastatic Behavior of Human Colorectal Cancer
AbstractPurpose: The expression of chemokine receptors CXCR4 and CCR7 has been associated with tumor dissemination and poor prognosis in a limited number of tumor entities. However, no data are currently available on the impact of chemokine receptor expression on disease progression and prognosis in human colorectal cancer.Experimental Design: The expression of CXCR4 and CCR7 was evaluated in 96 patients with histologically confirmed colorectal cancers and in four colorectal cancer cell lines by immunohistochemical staining. Furthermore, cell migration assays were done with SW480, SW620, and LS174T cancer cells to confirm the effect of the CXCR4 ligand stromal cell–derived factor 1α on migr…
Chemokine receptor CCR7 enhances intrahepatic and lymphatic dissemination of human hepatocellular cancer.
Despite many pathophysiological analyses, the process of tumor dissemination of hepatocellular carcinoma (HCC) remains vague. In diverse tumor entities, expression of the chemokine receptor, CCR7, has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, whether CCR7 exerts similar effects in human HCC. CCR7 expression analysis was performed in vitro on human hepatoma cell lines (Huh7, Hep3B, wt HepG2, p53 dominant negative transfected HepG2). In addition, CCR7 expression was evaluated in 39 patients with hepatocellular cancer and correlated with both, tumor and patients characteristics. Human hepatocellular carcinoma samples and hepatoma cell lines displayed varia…
Hypoxia-induced reduction of sVEGFR-2 levels in human colonic microvascular endothelial cells in vitro: Comparative study with HUVEC.
The functionality of large-vessel endothelial cells, such as human umbilical vein endothelial cells (HUVEC), may differ significantly from that in the microvasculature. We established a method for the isolation of human colonic microvascular endothelial cells (HCMEC). Since colonic diseases are often accompanied by hypoxia we examined its effects on HCMEC of five individuals in comparison with HUVEC, with respect to the secretion of the soluble form of the two important vascular endothelial growth factor (VEGF) receptors, VEGFR-1 and 2. After dissociation by dispase/collagenase of mucosal and submucosal tissue obtained from normal adult colon, HCMEC were isolated using CD31-coated magnetic …
Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines
Adaptation to hypoxia, a universal hallmark of carcinomas, is a critical step for tumor cell survival and growth. One of the principal regulators of hypoxia-responsive pathways is the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha). Currently, it is known that tumoral production of members of the vascular endothelial growth factor (VEGF)-family (VEGFs) may promote tumor growth and progression by acting on carcinoma cells that express the cognate receptors (VEGFRs). However, the influence of hypoxia in the formation of such a tumoral VEGF/VEGFR loop is not completely understood. In the present study we examined the potential existence of a HIF-1 alpha/VEGF/VEGFR autocrine…