ABSTRACT
The high occurrence of neural invasion in pancreatic carcinoma, which can be as much as 90%-l00%,leads to the poor survival rate in patients. The classical pathology includes invasion of both the extrapancreatic and intrapancreatic neurons. Metastasis into the extrapancreatic plexus promotes invasion into the intrapancreatic neurons and therefore results in pain. An increased in the diagnosis of new-onset diabetes mellitus, on the other hand, correlates with an increase in pancreatic cancer. This implies that hyperglycemia may promote neural invasion of pancreatic carcinoma. Novel auxiliary therapy of pancreatic carcinoma with neural invasion includes controlling of blood sugar and optogenetics, a new genetic technology which can further be utilized for surveillance.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer.</p><p><b>METHODS</b>A human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays.</p><p><b>RESULTS</b>After transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G(1) phase. The proportion of cells in the G(1) phase was significantly increased from 58.51% to 75.92%, and in the S and G(2)/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48%, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G(2)/M phase accumulation, from 11.48% to 53.47%. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01 - 10 mg/L) than those devoid of p14ARF expression (P < 0.01). Western blotting showed p14ARF upregulates p53 expression.</p><p><b>CONCLUSION</b>Combined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.</p>
Subject(s)
Humans , Fluorouracil , Pharmacology , Pancreatic Neoplasms , Genetics , Therapeutics , Transfection , Tumor Cells, Cultured , Tumor Suppressor Protein p14ARF , Genetics , Tumor Suppressor Protein p53 , Genetics , Up-Regulation , PhysiologyABSTRACT
Objectives To investigate the r el ationship between pancreatic ischemia and cytokines released in rats with acute pancreatitis(AP). Methods 20 acute edematous pancreatitis(AEP) and 20 acute necrotizing pancreatits(ANP) rat models wer e induced by injection of sodium taurocholate into the pancreatic duct, another 10 normal rats were used as control. At 12 hours after the induction of AP, 10 r ats in each group were sacrificed, blood and pacreatic tissue samples were taken for measurement of TNF-? and IL-10 levels. The pathological study of pancre as was performed, and pancreatic blood flow(PBF) was measured by Doppler ultraso und instrument.Results The TNF -? and IL-10 levels in serum and pancreatic tissue increased after the induction of AP, IL-10 levels elevated more significantly in AEP rats, TNF-? levels e levated more significantly in ANP rats. PBF reduced in AP rats, and the amplitud e of PBF measured by Doppler ultrasound was closely correlated with serum and ti ssue TNF-?, IL-10 levels, inflammation, hemorrhage and necrosis scores.Conclusion The reduction of PBF and the i ncreasement of cytokines developed simultaneously in rats with AP, hence both of them are important pathogenic factors of AP.
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Objective: To investigate the effective methods of nutritional support, to improve the endurance for the operation and to promote postoperative recovery in patients undergoing liver transplantation. Methods: The perioperative nutritional condition and nutritional-support methods were reviewed in 33 patients with liver transplantation. In the first 3 postoperative days, parenteral nutrition (PN) was used in combination with infusion of human albumin and plasma. From the 4th to 5th day, enteral nutrition (EN) was used in combination with PN. Finally, the complete oral intake of food was applied. Results: Of 33 patients, there were 30 patients whose serum levels of total protein (TP) and albumin (ALB) were elevated, and glutamic-pyruvic transminase (GPT), total-bilirubin (T-BIL) and combined-bilirubin (D-BIL) were descended after nutrition support. Conclusion: The operative endurance and postoperative recovery were improved effectively by proper nutritional support in liver transplantation patients.
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Objective To study the effect of intra-tumor injection of slow-release 5-FU on pancreatic carcinoma cells in nude mice,and on changes in serum tumor markers and cellular immunity of patients with pancreatic carcinoma.Methods (1) In vitro experiments, the releasing action and anti-tumor effect of slow-release 5-FU were studied. Measurement of the concentration of effused fluid,calculation of amount of drug released,and observation of the inhibitory effects of effused fluid on PC3 strains of pancreatic cancer cellswere perfomed.(2) Human pancreatic carcinoma strain PC-3 cells were cultured and inoculated into 60 nude mice,and were randomly divided into 5 groups according to various treatments received: NS injection as control group(A group), 5-FU (10 mg/kg)IV injection group(B group), stroma implant group(C group), intra-tumor injection of high dose slow-release 5-FU (4mg/kg) group(D group) and intra-tumor injection of low dose slow-release 5-FU (1mg/kg) group(E group). Tumor size were measured before and 14 days after treatment. On week 2, histological changes of the tumors were examined. The apoptotic index (AI) of the tumor cells was detected by terminal-deoxynucleotide transferase mediated d-UTP nick end labeling(TUNEL) and expression of bcl-2 and Bax by immunohistochemistry.(3) 69 cases of unresectable pancreatic carcinoma were divided into 3 groups randomly:intra-tumor injection of slow-release 5-FU treated group(treatment group), intra-venous injection of 5-FU group( chemotherapy group), and control group. The serum values of CD3+, CD4+, CD8+, CD4+/ CD8+, NK cells, CEA, CA50, CA19-9, CA125 and CA242 were measured in all patients 1 day before and 14 days after operation. Results (1) There was 0.85 mg 5-FU released in the 1st day and 0.45 mg 5-FU released in the 3rd day. The release remained constant at 0.25 mg and continued for about 14 days. (2) The tumor growth suppression rate on the 1st day by effusion fluid of slow-release 5-FU was 60.27% and on the 3rd day was 34.25%. Later, it remained at about 25.00%. The tumor growth rate was slower in D and E group than in other groups (P