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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.
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PMID:Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape. 1111 36

Involvement of arachidonic acid cyclooxygenase (COX) and lipoxygenase (LOX) metabolites in platelet aggregation and coagulation induced by two varieties of cancer cells of murine transplantable tumors was studied. A lung alveolar carcinoma (LAC) and a fibrosarcoma (FS), induced platelet aggregation and plasma coagulation (P<0.05). Pretreatment of both tumor lines with a COX inhibitor did not block the tumor cell induced platelet aggregation (TCIPA). COX [12(S)-HTT] and LOX [12(S)-HETE], metabolites of washed platelets (WP), alone or co-incubated with LAC or FS cells, were analyzed. We observed higher 12(S)-HETE release with respect to 12(S)HHT when WP were co-incubated with LAC cells. With both neoplastic cell (NC) lines prothrombin time (PT) was shortened. Pretreatment of NC with iodoacetic acid, soybean trypsin inhibitor or Factor X-deficient plasma increased the PT. These results indicate that AA metabolites play a role on the procoagulation and platelet aggregation induced by mesenchymal and epithelial murine cancers.
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PMID:COX and LOX eicosanoids modulate platelet activation and procoagulation induced by two murine cancer cells. 1113 75

Genistein is a plant isoflavonoid bearing potent tumor growth-regulating characteristics. This effect of genistein has been attributed partially to its tyrosine kinase-regulating properties, resulting in cell-cycle arrest and limited angiogenesis. Genistein has been used in chemotherapy-resistant cases of advanced leukemia with promising results. Here we demonstrate that genistein primarily affects nucleic acid synthesis and glucose oxidation in tumor cells using the [1,2-(13)C2]glucose isotope as the single tracer and gas chromatography/mass spectrometry to follow various intracellular glucose metabolites. The ribose fraction of RNA demonstrated a rapid 4.6%, 16.4%, and 46.3% decrease in isotope uptake through the nonoxidative branch of the pentose cycle and a sharp 4.8%. 24.6%, and 48% decrease in 13CO2 release from glucose after 2, 20, and 200 micromol/L genistein treatment, respectively. Fatty acid synthesis and the 13C enrichment of acetyl units were not significantly affected by genistein treatment. De novo glycogen synthesis from media glucose was not detected in cultured MIA cells. It can be concluded from these studies that genistein controls tumor growth primarily through the regulation of glucose metabolism, specifically targeting glucose carbon incorporation into nucleic acid ribose through the nonoxidative steps of the pentose cycle, which represents a new paradigm for the antiproliferative action of a plant phytochemical.
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PMID:Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. 1113 60

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy.
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PMID:Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. 1120 97

The p8 gene is a recently identified gene with mitogenic activity. p8 expression is induced in acute pancreatitis, pancreatic development, and regeneration. However, the expression of p8 in pancreatic cancer is not reported. We investigated p8 expression in 72 human pancreatic tissues, including 38 pancreatic cancers (PCs), by immunohistochemistry. p8 was overexpressed (positive cells >25% in 1,000 cells) in 71% (27 of 38) of PCs, but in only 17% (3 of 18) of chronic pancreatitis cases. There was no overexpression in mucinous cystadenoma or in normal pancreas. The p8 overexpression rate in PC was significantly higher than that in other conditions (P < 0.05). Reverse transcription-PCR analysis confirmed p8 mRNA overexpression (tumor/nontumor ratio >2) in 75% (3 of 4) of PCs. p8 was overexpressed also in human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). These results suggest that p8 is involved in the development of pancreatic cancer, reflecting its mitogenic activity.
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PMID:Expression of p8 in human pancreatic cancer. 1123 85

On radiograms, glial tumors are usually seen to invade in a finger-like fashion, while non-central nervous system (CNS) tumors expand in a mass-like fashion. We prepared organotypic brain slice cultures from newborn rats to investigate the invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U-373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080 (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area that was centered at a junction between deep cortical layers and the striatum, punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different rhodamine-labeled tumor cells at that site, and observed their invasive behavior under an inverted fluorescent microscope. Over the course of several days, all glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest. Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice cultures, we also investigated the regulatory effect on tumor invasion of forced expression of glial fibrillary acidic protein (GFAP) after gene transfection. The forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our results show that organotypic brain slice cultures are an excellent medium for studying the invasive features of glial and non-CNS tumors.
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PMID:The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats. 1125 Nov 66

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In this study, we characterized VEGF-C expression in cultured human pancreatic cancer cell lines and determined whether the presence of VEGF-C in human pancreatic cancers is associated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was associated with increased lymphatic vessels invasion and lymph node metastasis, but not with decreased patient survival. These findings indicate that VEGF-C and its receptor are commonly overexpressed in human pancreatic cancers and that this factor may contribute to the lymphangiogenic process and metastasis in this disorder.
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PMID:Overexpression of lymphangiogenic growth factor VEGF-C in human pancreatic cancer. 1129 31

Pancreatic cancer is a highly metastatic disease that responds poorly to currently-available treatment. In order to better visualize and understand the chronology and specificity of metastatic targeting of pancreatic cancer, two human pancreatic cancer cell lines, expressing green fluorescent protein (GFP), were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tumor fragments were transplanted by surgical orthotopic implantation (SOI) to the nude mouse pancreas for fluorescence visualization of the chronology of pancreatic tumor growth and metastatic targeting. BxPC-3-GFP tumors developed rapidly in the pancreas and spread regionally to the spleen and retroperitoneum as early as six weeks. Distant metastases in BxPC-3-GFP were rare. In contrast, MIA-PaCa-2-GFP grew more slowly in the pancreas but rapidly metastasized to distant sites including liver and portal lymph nodes. Regional metastases in MIA-PaCa-2-GFP were rare. These studies demonstrate that pancreatic cancers have highly specific and individual 'seed-soil' interactions governing the chronology and sites of metastatic targeting.
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PMID:Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models. 1131 94

The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the clinical significance of that overexpression is uncertain. In the present study we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor growth in certain patients with those diseases. We quantified HER2 expression in various human pancreatic cancer cell lines and studied the bioactivity of this antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed in vitro in cell lines with high levels of HER2/neu expression. Cell lines with low levels of this protein did not respond significantly to the antibody. In vivo we studied two different pancreatic cancer cell lines in an orthotopic mouse model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa-2 tumor cell line, which expressed high levels of HER2/neu. These data suggest that Herceptin treatment of patients with pancreatic cancer who express high levels of the HER2/neu oncogene may be reasonable.
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PMID:Therapy for pancreatic cancer with a recombinant humanized anti-HER2 antibody (herceptin). 1133 75

Migratory cells including invasive tumor cells frequently express CD44, a major receptor for hyaluronan and membrane-type 1 matrix metalloproteinase (MT1-MMP) that degrades extracellular matrix at the pericellular region. In this study, we demonstrate that MT1-MMP acts as a processing enzyme for CD44H, releasing it into the medium as a soluble 70-kD fragment. Furthermore, this processing event stimulates cell motility; however, expression of either CD44H or MT1-MMP alone did not stimulate cell motility. Coexpression of MT1-MMP and mutant CD44H lacking the MT1-MMP-processing site did not result in shedding and did not promote cell migration, suggesting that the processing of CD44H by MT1-MMP is critical in the migratory stimulation. Moreover, expression of the mutant CD44H inhibited the cell migration promoted by CD44H and MT1-MMP in a dominant-negative manner. The pancreatic tumor cell line, MIA PaCa-2, was found to shed the 70-kD CD44H fragment in a MT1-MMP-dependent manner. Expression of the mutant CD44H in the cells as well as MMP inhibitor treatment effectively inhibited the migration, suggesting that MIA PaCa-2 cells indeed use the CD44H and MT1-MMP as migratory devices. These findings revealed a novel interaction of the two molecules that have each been implicated in tumor cell migration and invasion.
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PMID:Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. 1138 Oct 77


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