[Effect of CIK on long-term survival in the treatment of HCC after RFA combined TACE].

OBJECTIVE: To evaluate the clinical effects of autologous cytokine-induced killer cell(CIK) on the cumulative survival and reactivation rate of hepatitics B virus(HBV) after radiofrequency ablation(RFA) combined with transcatheter arterial chemoembolization(TACE). METHODS: A total of 156 patients with hepatocellular carcinoma treated from June 2006 to September 2012 in Shengli Oilfield Central Hosptial were divided into control group(RFA, TACE) and research group(RFA, TACE, CIK). According to the tumors number, diameter and vascular invasion condition, the patients were divided into another 4 groups: the high and low risk group with tumor ≤5 cm, the high and low risk group with tumor>5 cm.The prognosis of these groups was analyzed. The effects on HBV reactivation rate between antiviral and unantiviral patients were respectively analyzed . RESULTS: The ratios of the research and control group over 1-, 3-, 5-year were 75.3%(70/93), 58.9%(53/90), 21.5%(20/93)vs 71.4%(45/63), 55.6%(35/63), 22.2%(14/63)(P>0.05), the ratios of the research and control group in the high risk group with tumor≤5 cm were 75.0%(18/24), 58.3%(14/24), 37.5%(9/24)vs 58.8%(10/17), 41.2%(7/17), 23.5%(4/17)(P<0.05). The incidences of HBV reactivation for the research and control group were 6.0% and 24.3%(P<0.05). CONCLUSION: Postoperative adjuvant CIK therapy with tumor≤5 cm after RFA combined with TACE is beneficial to the high risk group and decreases the risk of HBV reactivation.

Action of cholera toxin on dispersed acini from rat pancreas. Post-receptor modulation involving cyclic AMP and calcium.

In dispersed acini from rat pancreas, cholera toxin caused a significant increase in cellular cyclic AMP but little or no change in amylase secretion. The presence of a secretagogue that causes mobilization of cellular calcium (e.g., cholecystokinin, carbamylcholine, bombesin or ionophore A23187) caused a substantial increase in the effect of cholera toxin on enzyme secretion. Cholera toxin did not alter calcium transport or the changes in calcium transport caused by other secretagogues, and secretagogues that mobilize cellular calcium did not alter cellular cyclic AMP or the increase in cyclic AMP caused by cholera toxin. These results indicate that in dispersed acini from rat pancreas there is post-receptor modulation of the action of cholera toxin by secretagogues that mobilize cellular calcium and that this modulation is a major determinant of the effect of the toxin on enzyme secretion.

The importance of the amino acid in position 32 of cholecystokinin in determining its interaction with cholecystokinin receptors on pancreatic acini.

In the C-terminal heptapeptide of cholecystokinin, replacement of the penultimate residue, aspartic acid, by beta-alanine caused a 300-fold decrease in the potency with which the peptide stimulated enzyme secretions, whereas replacement by glutamic acid caused a 1000-fold decrease in potency. The beta-alanine-substituted peptide was approximately ten times more potent when the n terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl, and the glutamic acid-substituted peptide was approximately twice as potent when the N terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl. Changes in the ability of the peptide to stimulate amylase secretion were accompanied by corresponding changes in the ability of the peptide to inhibit binding of 125I-labeled cholecystokinin. The magnitude of stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same with each analogue as it was with the unaltered peptide. Replacing the aspartyl residue by beta-alanine or glutamic acid or replacing the N-terminal t-butyloxycarbonyl moiety by benzyloxycarbonyl caused an equivalent decrease in the ability of the peptide to stimulate enzyme secretion and its ability to cause residual stimulation of enzyme secretion. In contrast, the N-terminal desamino analogue of cholecystokinin heptapeptide was ten times less potent than the unaltered peptide in stimulating amylase secretion, but 100 times less potent than the unaltered peptide in causing residual stimulation of enzyme secretion.

Secretagogue-induced membrane alterations in dispersed acini from rat pancreas.

Dispersed acini from rat pancreas were used to examine the effects of various pancreatic secretagogues on the fine structure of the acinar cell plasma membrane. With the C-terminal octapeptide of cholecystokinin, the C-terminal tetrapeptide of cholecystokinin, carbamylcholine, bombesin, A23187, vasoactive intestinal peptide or 8-bromo cyclic adenosine monophosphate, concentrations of the secretagogues that caused maximal stimulation of enzyme secretion did not produce alterations of the acinar cell plasma membrane. Supramaximal concentrations of the C-terminal octapeptide of cholecystokinin, the C-terminal tetrapeptide of cholecystokinin or carbamylcholine induced the formation of cytoplasmic protrusions at the basolateral plasma membrane of the pancreatic acinar cell, whereas supramaximal concentration of bombesin, A23187, vasoactive intestinal peptide or 8-bromo cyclic AMP did not alter the morphology of the acinar cell. Effects of the C-terminal octapeptide of cholecystokinin could be detected as early as after two minutes of incubation and these effects progressed for up to 30 minutes of incubation.

Epidermal growth factor and its receptors in human pancreatic carcinoma.

The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells.

Watery diarrhea syndrome caused by multihormonal malignant pancreatic islet cell tumor secreting somatostatin, vasoactive intestinal peptide, serotonin, and prostaglandin E--a clinicopathological, biochemical, immunohistochemical, and ultrastructural study.

The pathophysiological, biochemical, histological, ultrastructural, and immunohistochemical characters of a case of malignant pancreatic islet cell tumor with watery diarrhea syndrome were carefully investigated. Four hormones or mediators--somatostatin (SST), vasoactive intestinal peptide (VIP), serotonin, and prostaglandin E--were markedly elevated in the circulation. The diagnosis was further confirmed by exploratory laparotomy and autopsy. The contents of SST and VIP in tumor tissues were very high. Gel chromatography of tumor extract revealed single peaks for both SST and VIP. Immunohistochemical studies of tumor tissues showed numerous immunoreactive cells to anti-SST, moderate amount of VIP-positive cells, and a few hCG-, insulin-, and glucagon-positive cells. In conclusion, this is an unusual case of Verner-Morrison syndrome in which three kinds of bioactive hormones or mediators were simultaneously secreted; peptides, amine, and prostaglandin.

Effects of gastrointestinal peptides on formation of gallstone in guinea pigs.

In light of the effects of gastrointestinal (GI) peptides on bile secretion and biliary tract mobility, we studied the effects of GI peptides on gallstone formation in guinea pigs fed on low protein lithogenic diet. The peptides under study included cholecystokinin octapeptide (CCK-8), vasoactive intestinal peptide (VIP), somatostatin (SRIF), secretin (SEC), and neurotensin (NT). Hepatic bile flow, electrolytes, and other bile components were also measured. It was found that CCK-8 and VIP suppressed the formation of gallstones and increased hepatic bile flow and Na+, K+, Cl- output significantly. On the other hand, SRIF significantly promoted gallstone formation. The rates of gallstone formation in CCK-8, VIP, and SRIF treated guinea pigs were 15.4%, 23.5%, and 88.0%, respectively, in contrast to 56.8% in the control group. The inhibitory effect of CCK-8 and promoting effect of SRIF on gallstone formation were dose-dependent.

Survey on use of antimicrobial agents and bacterial resistance in Huashan Hospital.

A cross-section study was carried out to assess the general patterns in use of antimicrobial agents and the trends of bacterial resistance in Huashan Hospital. Of 2,400 patients whose charts were reviewed, 61% were given such drugs. 3,596 antibiotic courses were prescribed. Gentamicin was most frequently used. Results of the susceptibility test of 320 bacterial strains showed a high percentage of resistance against gentamicin, ampicillin, and chloramphenicol. Our findings suggest that antibiotic policies in the hospital need reappraising.

The diagnostic significance of carbohydrate antigen CA 19-9 in serum and pancreatic juice in pancreatic carcinoma.

CA 19-9 is a carbohydrate antigen isolated from human colon carcinoma cell line, and is reportedly a tumor marker for pancreatic carcinoma. In this study we determined serum CA 19-9 in 71 normal subjects, 103 patients with benign digestive diseases, 85 patients with periampullary cancers, and 160 patients with other digestive cancers. Serum CA 19-9 was elevated only in 2.3% of normals and benign digestive disease patients, whereas it was increased in 72.7%, 86.4%, and 89.5% of pancreatic, ampullary, and choledochal carcinoma patients, respectively. Of other digestive cancer patients, it was elevated in 23.8%. In addition, very high serum CA 19-9 (greater than 120 u/m) was more often observed in patients with pancreatic, ampullary, and biliary cancer patients than in GL cancer patients (54.1% vs 9.4%, p less than 0.001). In 18 normal subjects and 68 patients with benign and malignant diseases, it was found that CA 19-9 content in the pancreatic juice was significantly increased in pancreatic, ampullary, and choledochal cancer patients, whereas in chronic pancreatitis patients it was normal, indicating that it is a specific and valuable tumor marker in differential diagnosis of pancreatic cancer.

[Effect of CCK receptor antagonists on plasma CCK bioassay].

Fasting and postprandial plasma CCK levels of 102 normal subjects were measured by bioassay with dispersed rat pancreatic acini. The reference values ranged from 0 to 4.2 pmol/L (CCK-8 equivalents) for fasting and from 1.1 to 13.5 pmol/L for postprandial state. There was no significant difference between male and female, or in different age groups. The effects of CCK receptor antagonists of 3 different categories on CCK bioactivity in plasma measured by the bioassay were investigated. L 364,718 (5 nmol/L), proglumide (1.0 mmol/L), or Bt2-cGMP (0.1 mmol/L) was either extracted by SEP-PAK C18 cartridges together with human plasma containing 8 pmol/L of CCK-8, or added into the plasma extracts before the assay. The CCK bioactivity was inhibited by all of the 3 CCK antagonists. The action of L364,718 could be eliminated by the procedure of plasma extraction, but not of proglumide or Bt2-cGMP. It was suggested that CCK bioassay can be used even if L364,718 was administered. However, CCK cannot be measured accurately if there are proglumide or Bt2-cGMP in the plasma.

[A multiclinic double-blind, comparative clinical trial on misoprostol in the treatment of duodenal ulcer].

A clinical trial of misoprostol, an analog of PGE1 produced by G.D. Searle & Co., on treatment of duodenal ulcer was carried out in five hospitals in Beijing, Shanghai, and Guangzhou. Totally 94 cases were treated with misoprostol 200 micrograms q.i.d. for 4 weeks. A parallel comparison was made, using cimetidine 200 mg q.i.d. A double-blind, double-dummy study was conducted. The result showed that the therapeutic efficacy of misoprostol in duodenal ulcer is similar to that of cimetidine. The ulcer healing rate in four weeks being 60.7% and 67.9% respectively, while the overall effectiveness rate being 77.7% and 80.2%. There was no statistically significant difference between the two medication groups. The side effect of misoprostol is mainly mild diarrhea (6.4%), but it disappears despite the continued use of medication. To our impression, misoprostol represents a new therapeutic approach for treatment of peptic ulcer in addition to acid controlling H2 blockers.

[The effect of proglumide on gallstone formation in guinea pigs].

In this study, the chronic effects of proglumide (PGM, a cholecystokinin/gastrin receptor antagonist) on gallstone formation and hepatic bile secretion were investigated as follows: Group 1: Fed with low protein (14%) lithogenic diet. Group 2: Fed with the same lithogenic diet and was given PGM (250 mg/kg, bid, p. o.). Group 3: Fed with commercial guinea pig chow (protein content 22%). Eight weeks later the animals were operated under urethane anesthesia, the gallbladders were removed and examined for gallstones. Meanwhile, by bile duct cannulation, the hepatic bile flow and bile contents were measured. It was found that: (1) the animal model was valid for the purpose specified; (2) the rate of gallstone formation was significantly lower in PGM group than in the controls (17.5% vs 56.8%, P less than 0.01); and (3) PGM significantly enhanced the flow rates and electrolyte contents and decreased the unconjugated bilirubin content of the hepatic bile. It is concluded that PGM may suppress gallstone formation in guinea pigs on lithogenic diet, and this may be related to its stimulatory effect on hepatic bile secretion and to its ability to induce a decrease in unconjugated bilirubin in the hepatic bile.

[Gastrointestinal transit time (GITT) in normal Chinese and patients].

Two kinds of radiopaque pellets were ingested as markers to determine GITT in 60 normal subjects, 7 patients with ulcerative colitis (UC), 10 patients with idiopathic constipation (IC) and 8 patients with other diseases. The food contained 10-20g dietary fiber per day. Besides, GITT was determined in 14 normal subjects whose dietary content was 40-50g or 10g MO YU and 10-20g dietary fiber per day. Results are expressed in hours as 50% transit time (mean +/- s) and the values or normal subjects are as the follows: total GITT 25.0 +/- 7.3h, mouth iteum TT 9.0 +/- 3.3h, colonic TT 15.9 +/- 7.5h. There was no difference in age or sex groups. However, in high dietary fiber or MO YU group, GITT shortened significantly. Abnormal GITT was shown in patients with UC, IC, other gut and systemic diseases. In conclusion, the method employed in the present study is simple, safe and useful in the clinical study of gastrointestinal motility; and may provide important information to elucidate the pathophysiology of the diseases related to disorders in motility of the digestive tract.