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Human Pancreatic (human + pancreatic)

Distribution by Scientific Domains
Chemistry40%

Terms modified by Human Pancreatic

  • human pancreatic cancer cell
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  • human pancreatic cancer cell line
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  • human pancreatic carcinoma cell
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    Selected Abstracts

    Ribonucleases expressed by human pancreatic adenocarcinoma cell lines

    FEBS JOURNAL, Issue 5 2000
    Ester Fernández-Salas
    Human ribonucleases have been considered as a possible tumor marker for pancreatic cancer, and elevated serum levels of ribonuclease activity in patients with pancreatic cancer have been reported by many authors. The reason for this elevation is unknown. In this study, we demonstrate that human pancreatic adenocarcinoma cell lines synthesize and secrete different ribonucleases. We isolated and characterized human pancreatic, or secretory, ribonuclease (RNase 1) from the conditioned media of the human pancreatic adenocarcinoma cell lines Capan-1, MDAPanc-3, IBF-CP3 and Panc-1, and the ampullary adenocarcinoma cell line MDAAmp-7, which represent a wide range of differentiation stages. Only one of these cell lines, Panc-1, produces significant amounts of nonsecretory ribonuclease. We then established a purification procedure for both secretory and nonsecretory ribonucleases, consisting of concentration of the supernatant by tangential filtration, anion-exchange and cation-exchange liquid chromatography and C4 RP-HPLC. Ribonuclease activity fractions were monitored using both the spectrophotometric and negative-staining zymogram techniques. The results of N-terminal sequence analysis, kinetic analysis and endoglycosidase digestion studies indicate that the main ribonuclease secreted by all the cell lines is the secretory-type ribonuclease and that it is composed of several differently N -glycosylated forms. Northern blot analyses confirm that some of the cell lines express secretory ribonuclease mRNA. The mRNA levels produced by Panc-1 and MDAPanc-28 are too low to be detected. Similar levels of expression of nonsecretory ribonuclease are found by Northern blot analysis in all the cell lines except Panc-1, which expresses higher levels. Here, we describe, for the first time, that several human pancreatic cancer cell lines with different degrees of differentiation express and secrete ribonucleases. This fact indicates that one origin of the elevated serum RNase levels in patients with pancreatic cancer are tumor cells. Analysis of the oligosaccharide moiety of the RNase 1 secreted by Capan-1 shows that it is highly glycosylated and its N -glycan chains are significantly different from that of the RNase 1 produced by normal pancreas. These results renew the possibility of using human serum RNase 1 determination as a tumor marker. [source]

    Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing ability

    INTERNATIONAL JOURNAL OF CANCER, Issue 2 2010
    Ying-Yi Li
    Abstract We previously demonstrated that Pim-3, a protooncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not in normal tissues of endoderm-derived organs, including pancreas, liver, colon and stomach. Moreover, aberrantly expressed Pim-3 can prevent tumor cell apoptosis by inactivating a proapoptotic molecule, Bad, and enhancing the expression of an antiapoptotic molecule, Bcl-XL. These observations prompted us to speculate that a chemical targeting Pim-3 kinase may be a good candidate for a novel type of anticancer drug. Hence, we screened various low-molecule compounds by examining their capacity to inhibit Pim-3 kinase activity in vitro. We observed that some synthetic intermediates of stemonamide can inhibit in vitro activities of Pim-3 kinase and its related kinases, such as Pim-1 and Pim-2. Moreover, these compounds inhibit in vitro cell proliferation of various human pancreatic, hepatocellular and colon cancer cell lines. Furthermore, the compounds can induce apoptosis of human pancreatic cancer cell lines in vitro by reducing the amount of phospho-Ser112 -Bad, but not total amounts of Bad and Pim-3. Finally, when the compound was administered to nude mice injected with a human pancreatic cancer cell line, it retarded tumor growth by increasing apoptotic cell numbers and decreasing proliferating cell numbers without causing serious adverse effects on blood counts. These observations indicate that the chemicals and its related compounds may be effective for the treatment of tumors of endoderm-derived organs, particularly the pancreas. [source]

    Anti-tumor efficacy of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-,-D-arabinofuranosyl) cytosine (4,-thio-FAC) in human pancreatic and ovarian tumor xenograft models

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005
    Deborah A. Zajchowski
    Abstract 1-(2-Deoxy-2-fluoro-4-thio-,- D -arabinofuranosyl) cytosine (4,-thio-FAC) is a deoxycytidine analog that has been shown previously to have impressive anti-proliferative and cytotoxic effects in vitro and in vivo toward colorectal and gastric tumors. In our present studies, the pharmacokinetic behavior in nude mice and the effectiveness of 4,-thio-FAC against human pancreatic and ovarian tumor growth were assessed in comparison with standard chemotherapeutic agents. Potent in vitro anti-proliferative effects were observed against pancreatic (Capan-1, MIA-PaCa-2, BxPC-3) and ovarian (SK-OV-3, OVCAR-3, ES-2) cancer cell lines with IC50 of 0.01,0.2 ,M. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously (s.c.) implanted human pancreatic tumor xenografts or intraperitoneally (i.p.) disseminated human ovarian xenografted tumors. Oral daily administration of 4,-thio-FAC for 8,10 days significantly inhibited the growth of gemcitabine-resistant BxPC-3 pancreatic tumors and induced regression of gemcitabine-refractory Capan-1 tumors. 4,-Thio-FAC was also a highly effective inhibitor of ovarian peritoneal carcinomatosis. In the SK-OV-3 and ES-2 ovarian cancer models, 4,-thio-FAC prolonged survival to a greater extent than that observed with gemcitabine. Furthermore, the superiority of 4,-thio-FAC to carboplatin and paclitaxel was demonstrated in the ES-2 clear cell ovarian carcinoma model. Studies provide evidence that 4,-thio-FAC is a promising new alternative to gemcitabine and other chemotherapeutic drugs in the treatment of a variety of tumor indications, including pancreatic and ovarian carcinoma. © 2004 Wiley-Liss, Inc. [source]

    Use of 111In,L,LDL radiotracers to detect human pancreatic and mice melanoma tumors

    APPLIED ORGANOMETALLIC CHEMISTRY, Issue 4 2003
    Pascale Urizzi
    Abstract The present study was designed to evaluate the potential of labeled low-density lipoprotein with 111In using a lipid chelating agent (bis(stearylamide) of diethylenetriaminepentaacetic acid: L) to detect pancreatic tumors and melanoma in mice by gamma-scintigraphy. We compare the biodistribution of radioactivity and scintigraphic images in nude mice heterotransplanted with human cancerous pancreatic duct cells (Capan-1) and in mice transplanted with murine tumor cells (B16 melanoma). Biodistribution studies showed that radioactivity was twice as high in the Capan-1 xenograft after injection of the radiolabel than after injection of radiometal alone, and 34-fold higher in the B16 tumor. On gamma-scintigraphic imaging, the Capan-1 tumor was just visible, whereas the B16 melanoma was clearly imaged. The lack of contrast of the Capan-1 tumor compared with the B16 melanoma could be due to a poor vascularization. Copyright © 2003 John Wiley & Sons, Ltd. [source]