• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4671-4675
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• 2016

Background and aim: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide, with an overall 5-year survival of <5% mainly due to presence of advanced disease at time of diagnosis. Therefore development of valid biomarkers to diagnose pancreatic cancer in early stages is an urgent need. This study concerned the sensitivity and specificity of serum ICAM 1 versus CA 19-9 in differentiation between pancreatic cancer and healthy subjects and acohort of patients with chronic pancreatitis with a focus on assessing validity in diagnosis of early stages of pancreatic cancer. Methods: A cohort of 50 patients with histologically diagnosed pancreatic tumors, 27 patients with chronic pancreatitis, and 35 healthy controls were enrolled. Serum samples for measurement of CA19-9 and I-CAM 1 were obtained from all groups and analyzed for significance regarding diagnosis and disease stage. Results: At a cut off value of (878.5 u/ml) I-CAM 1 had 82% and 82.26% sensitivity and specificity for differentiation between cancer and non-cancer cases, with higher sensitivity and specificity than CA19-9 at different cut offs (CA19-9 sensitivity and specificity ranged from 64-80% and 56.4 - 61.2% respectively). The AUC was 0.851 for I-CAM and 0.754 for CA19-9. Neither of the markers demonstrated significance for distinguishing between early and late cancer stages. Conclusion: ICAM 1 is a useful marker in differentiation between malignant and benign pancreatic conditions, and superior to CA19-9 in this regard. However, neither of the markers can be recommended for use in differentiation between early and late stage pancreatic cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.27-31
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• 2002

${\gamma}-Aminobutyric$ Acid (GABA) is contained in pancreatic islet ${\beta}-cells$ although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h),$ given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA $(30\;{\mu}mol/kg/h)$ also further increased the amylase secretion stimulated by CCK (30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h)$ also dose-dependently elevated pancreatic amylase secretion evoked by CCK alone. Bicuculline $(100\;{\mu}mol/kg/h),$ a $GABA_A-receptor$ antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK plus secretin or CCK alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via $GABA_A-receptor$ in anesthetized rats, which may account for elevating the action of CCK released by sodium oleate.

• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.745-754
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• 1997

This study was designed to investigate the effects of cholate and deoxycholate on pancreatic exocrine secretion in conscious sheep with external bile and pancreatic fistulae. Bile and pancreatic juices were collected for a basal period of 2 hours. The pancreatic juice was returned to the intestine. Bile salts were infused into the jugular vein or duodenum for 90 minutes at the rate of 0.7mg/kg/min. Cholate and deoxycholate significantly increased the flow rate, pH and bicarbonate concentration of bile juice, but decreased the flow rate of pancreatic juice. The effects induced by intraduodenal infusion of both bile salts were significantly greater than those by intravenous infusion. Protein concentration and amylase activity in pancreatic juice were also significantly decreased by both bile salts; the effects were greater when the bile salts were infused into the duodenum than into the vein. The inhibitory effects induced by deoxycholate infusion were significantly greater than those by cholate infusion. The plasma concentration of secretin was significantly increased by intravenous infusion of deoxycholate, but it was not effected by intraduodenal infusion of both bile salts. The results indicated that cholate and deoxycholate markedly increased the secretion of bile juice and decreased the pancreatic exocrine secretion, although these effects were variable depending on the chemical composition or infusion routes.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.31-36
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• 1981

Heavy metals which are present as trace elements in human body have been known to modify various enzymatic reaction. These metals can be essential or non-essential. Zinc, copper and calcium are essential in maintaining some biological processes, whereas non-essential metals such as cadmium, lead and mercury produce accumulatve toxic effect. Cadmium accumulated in pancreas can cause toxicity and damage of pancreatic cells, thereby influencing CHO metabolism. Lead compounds are known to produce toxic effects on the kidney, digestive system and brain fellowed by inhibition of activity of ${\rho}-aminolevulinic$ acid and biosynthesis of hemoproteins and cytochrome. Evidence has been accumulated that zinc not only acts as a cofactor in enzyme reaction but also prevents toxic effect induced by heavy metal such as copper and cadmium. To demonstrate the effect of heavy metals on pancreatic secretion, part of uncinate pancreas was taken and incubated in Krebs-Ringer bicarbonate buffer with heavy metals used. Additional treatment with CCK-OP was performed when needed. After incubation during different period of time, medium was analyzed for amylase activity using Bernfeld's method. The present study was attempted in order to elucidate the effect of several kinds of heavy metal on exocrine pancreatic secretion in vitro. The results obtained are as follows: 1) CCK-OP stimulated significantly amylase release from pancreatic fragments in vitro. 2) CCK-OP response of amylase release from pancreatic fragments was inhibited by treatmant with cadmium, especially high doses of cadmium. 3) CCK-OP response of amylase release from pancreatic fragments was inhibited when pretreated with $10^{-4}M$ copper chloride. 4) Lead chloride at the concentration of $10^{-3}M\;and\;10^{4}M$ stimulated the basal amylase release in vitro but CCK-OP response did not augment by lead chloride. 5) Zine chloride did not affect amylase release from pancreatic fragment in vitro. From the results mentioned above, it is suggested that CCK-OP response was inhibited it the amylase release from pancreatic fragments pretreated with cadmium and copper chloride.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.30-38
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• 2008

Objectives: The main goals of cancer treatment are improvement of quality of life and survival prolongation. There is a limitation to prolonging the survival time in hepatobiliary and pancreatic cancer. The purpose of this study was to evaluate the quality of life of hepatobiliary and pancreatic cancer patients who visited for traditional Korean cancer treatment. Methods: We evaluated the quality of life of 23 hepatobiliary and pancreatic cancer patients who visited for oriental medicine treatment at East-West Neo Medical Center from June to October of 2007. FACT-G (Functional Assessment Cancer Therapy-General), used in this study, is a scale for evaluation of QOL confirmed validity and reliability, popularly used in many countries to evaluate QOL of cancer patients. Results: The average age of enrolled patients was 57. There were 10 hepatocellular carcinoma patients, 7 pancreatic cancer patients, 6 biliary tract cancer patients. Twenty one patients were in stage IV and 20 patients had distant metastases. By Sasang constitution, Taeumin were 7, Soyangin were 8, and Soeumuin were 8. The baselines of FACT-G score in the first visit were from 34.33 to 85, and the mean score was 67.3. The mean score of FACT-G in hepatocellular carcinoma patients was 67.5, that of pancreatic cancer patients was 62.5, and that of biliary tract cancer patients was 71. Conclusions: This study is valuable as an initial QOL study of hepatobiliary and pancreatic cancer patients who visited an oriental medical clinic. We believe that consistent studies will be necessary to demonstrate oriental treatment-related quality of life with hepatobiliary and pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5133-5139
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• 2013

Background: Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes. Methods: Publications were identified which assessed prognostic significance of PNI status in resected pancreatic cancer up to February 2013. A meta-analysis was performed to clarify the association between PNI status and clinical outcomes. Results: A total of 21 studies met the inclusion criteria, covering 4,459 cases. Analysis of these data showed that intrapancreatic PNI was correlated with reduced overall survival only in resected pancreatic ductal adenocarcinoma (PDAC) patients (HR=1.982, 95%CI: 1.526-2.574, p=0.000). Extrapancreatic PNI was correlated with reduced overall survival in all resected pancreatic cancer patients (HR=1.748, 95%CI: 1.372-2.228, p=0.000). Moreover, intrapancreatic PNI status may be associated with tumor recurrence in all resected pancreatic cancer patients (HR=2.714, 95%CI: 1.885-3.906, p=0.000). Conclusion: PNI was an independent and poor prognostic factor in resected PDAC patients. Moreover, intrapancreatic PNI status may be associated with tumor recurrence.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.129-135
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• 2000

Previously, we have reported that ${\rho}-chlorophenylalanine$ (PCPA), a serotonin depletor, profoundly increased pancreatic fluid and bicarbonate secretion but remarkably inhibited pancreatic amylase secretion in anesthetized rats. The present study was performed to verify the detailed effects of PCPA on pancreatic amylase synthesis that is directly related to amylase exocrine secretion. PCPA significantly decreased pancreatic RNA and protein contents as well as the amylase activity. However, pancreatic DNA content, trypsin and chymotrypsin activities were not influenced by the treatment of PCPA. The rate of pancreatic amylase synthesis, which was assessed by the amount of incorporated $[^{35}S]-methionine$ into amylase for 1 h, was also significantly decreased by 44% in PCPA-treated rats. In order to determine whether the PCPA-induced decrease of amylase synthesis resulted from change in the level of amylase mRNA, Northern blot analysis was performed. The mRNA expression level of amylase was also decreased by 48% in the PCPA-treated rats, indicating that the inhibitory effect of PCPA on the synthesis of pancreatic amylase was mainly regulated at a step prior to translation. It was also revealed in SDS-polyacrylamide gel electrophoresis that the qualitative change of amylase was induced by PCPA. The 54 KDa amylase band seems to be degraded into small molecular weight protein bands in PCPA-treated rats, suggesting that the PCPA- induced decrease of amylase may be partly attributed to the degradation of synthesized amylase.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.609-617
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• 2017

Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

• Animal cells and systems
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• v.4 no.2
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• pp.187-193
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• 2000

Regional distribution and relative frequency of endocrine cells in the pancreas of the red-eared slider, Trachemys scripta elegans, were investigated by immunohistochemical methods. Chromogranin (Cg) A-, serotonin-, insulin-, glucagon-, somatostatin-, bovine pancreatic polypeptide (BPP)- and human pancreatic polypeptede (HPP)-immunoreactive cells were identified in this study. Most of immunoreactive cells in the exocrine and endocrine pancreas (Langerhans islet) were generally spherical or spindle-shaped (open-typed cell), while occasionally cells round in shape (close-typed cell) were found in the basal portion or interepithelial regions of the pancreatic duct. These immunoreactive cells were located in the exocrine, endocrine pancreas and/or basal or interepithelial portion of the pancreatic duct. Serotonin-immunoreactive cells were found in the basal portion of epithelia of the pancreatic duct at a low frequency and interacinar region of the exocrine at a moderate frequency. Insulin-immunoreactive cells were found in the central portion of the endocrine pancreas, interacinar regions of the exocrine pancreas and basal portion of the epithelia of the pancreatic duct at high, moderate and low frequencies, respectively. Glucagon-immunoreactive cells were detected in the periphery of the endocrine pancreas, interacinar region of the exocrine pancreas and basal portion of the epithelia or interepithelia of the pancreatic duct at high, moderate and moderate frequencies, respectively. Somatostatin-immunoreactive cells were dispersed in the whole area of the endocrine pancreas, interacinar regions of exocrine pancreas and basal portion of the epithelia or interepithelia of the pancreatic duct at a moderate frequency. BPP- and HPP-immunoreactive cells were detected in the iinteracinar region of the exocrine pancreas at moderate and hige frequencies, respectively. However, no Cg A- and motilin-immunoreactive cells were detected in this study.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.249-256
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• 1986

The present study was performed to investigate a possible influence of the adrenergic nervous system on pancreatic exocrine secretion stimulated by intraduodenal acid perfusion. Pancreatic secretion was collected in rats anesthetized with urethane after 24 hours fasting. The duodenal lumen was perfused (0.2 ml/min) with HCI solution in a concentration of 0.005, 0.01, 0.02, 0.05 or 0.1 N When the volume of panceratic juice secreted for IS min became constant phentolamine (1 mg/kg), $noradrenaline\;(10\;{\mu}g/kg),\;Propranolol\;(1\;mg/kg),\;and \;isoproterenol\;(1\;{\mu}g/kg)$ were administered through the jugular vein in bolus. The secretory volume and protein output were measured in the pancreatic juice collected for 15 min. 1) HCI, perfused intraduodenally in graded concentrations from 0.005 N to 0.1 N, increased the pancreatic secretory volume and protein output dose-dependently. 2) In the basal state as well as in the stimulated state by the duodenal acid perfusion, phentolamine increased the pancreatic secretory volume and protein output while propranolol inhibited the volume and protein output. 3) In the basal state, noradrenaline did not change the pancreatic secretory volume but increased the protein output while isoproterenol increased both of the secretory volume and the protein output. These results strongly suggest that ${\alpha}-adrenoceptors$ in the rat pancreas exert an inhibitory influence on the pancreatic exocrine secretion including volume and protein output in the basal state as well as in the stimulated state by the intraduodenal acid perfusion while ${\beta}-adrenoceptors$ play a stimulatory role in the pancreatic exocrine secretion. However, in the physiological situation, adrenergic excitation may stimulate the protein output through ${\beta}-adrenoceptors$ without change in the secretory volume in the rat pancreas.