ABSTRACT
The potential application of dendritic cells (DC) sensitized with cytosine-phosphoric acid-guanine (CpG) oligodeoxynucleotide (ODN) and tumor antigen as a vaccine against murine melanoma was investigated with freshly isolated mouse bone marrow-derived dendritic cells. For the DC vaccine preparation, DC were sensitized with the B16 tumor antigen and CpG ODN was used to promote further maturation of the DC. The immunogenic activity of the vaccine was evaluated in vitro by determining the proliferation of T lymphocytes and the killing effect of cytotoxic T lymphocytes (CTL) on B16 tumor cells. The DC vaccine was injected intraperitoneally and tumor inhibition in mice bearing B16 xenografts was examined. All mice were cared for under an approved SIMM Institutional Animal Care and Use Committee (IACUC) protocol. In vitro, this DC vaccine promoted the proliferation of T lymphocytes and showed a potent killing effect on the target B16 cells. In vivo experiments showed that after treatment or pre-immunization both the tumor volume and weight were significantly decreased. The DC vaccine with CpG ODN and tumor antigen exhibited an inhibitory effect against melanoma, providing a potential method for melanoma cancer treatment.
ABSTRACT
<p><b>BACKGROUND</b>Tissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor alpha (TNFalpha) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect.</p><p><b>METHODS</b>Various doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFalpha for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor kappaB was tested by electromobility shift assay.</p><p><b>RESULTS</b>As the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor kappaB.</p><p><b>CONCLUSIONS</b>Celecoxib can downregulate the expression of tissue factor induced by TNFalpha in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor kappaB.</p>
Subject(s)
Humans , Celecoxib , Cell Line, Tumor , Cyclooxygenase 2 Inhibitors , Pharmacology , Gene Expression Regulation , NF-kappa B , Metabolism , Pancreatic Neoplasms , Metabolism , Pathology , Pyrazoles , Pharmacology , Sulfonamides , Pharmacology , Thromboplastin , Genetics , Tumor Necrosis Factor-alphaABSTRACT
<p><b>OBJECTIVE</b>To study the characters of chronic pancreatitis complicated by non-calculous obstructive jaundice, and discuss the methods for differentiation and treatment.</p><p><b>METHOD</b>Twenty cases selected from January 1985 to December 2004 were analysed in the fields of differentiation and treatment.</p><p><b>RESULTS</b>All cases didn't present with typical clinical presentations and radiological features. Jaundice was presented as the main complaint. Stricture of the intra-pancreatic common bile duct was the symbolic radiological feature. Pancreatic disseminated inflammation was verified pathologically in these cases. CT, ultrasound, EUS, ERCP, MRCP and antigen-marker of neoplasm failed to offer the data for differentiation. The diagnosis could only be determined by pathological exam. The obstructive jaundice could be solved by biliary-enteric anastomoses successfully.</p><p><b>CONCLUSIONS</b>The patients with sole complaint of obstructive jaundice account for 15% of all inpatients with chronic pancreatitis. There exists a direct relationship between the jaundice and the pancreatic inflammation. This disorder should be differentiated from total pancreatic carcinoma, but few differentiated material could be offered by preoperative studies. Pathological result derived from the tissue sample obtained within the exploration would be reliable for diagnosis. The bypass between biliary tract and intestine would be a safe and economical treatment method.</p>