• Journal of Gastric Cancer
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• v.3 no.3
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• pp.139-144
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• 2003

Purpose: Because of an improving gastric cancer detection program and treatment methods, we can expect improved survival of patients with gastric cancer. Given the longer survival times, the chance of an occurrence of multiple primary malignant tumors other than stomach is increased in the same patients. The purpose of this study is to analyze the clinical characteristrics and the survival of patients with gastric cancer and other malignancies. Materials and Methods: A retrospective study of 3669 patients with gastric cancer observed at our department between January 1994 to December 2002 was conducted. Associated tumors were diagnosed using the Warren and Gates criteria, and included tumors that were not considered to be a metastasis, invasion, or recurrence of the gastric cancer. Results: Of all 3669 patients, $2.07\%$ (n=76) had primary tumors other than gastric cancer, $63\%$ of which were synchronous (n=48) and $37\%$ metachronous (n=28). The mean age of the study group was 64.9 (65.5 in males, 61.8 in females), and the male-to-female ratio was 4.8 : 1. The most common cancer associated with gastric cancer was a hepatocellular carcinoma ($23.7\%$), followed by colorectal cancer ($17.1\%$), esophageal cancer ($10.5\%$), breast cancer ($6.6\%$). Of the 45 patients who had undergone a resection, 14 were in stage I, 12 in stage II, 13 in stage III, and 6 in stage IV. No statistically significant differences were found between the synchronous and the metachronous groups with regard to age, sex ratio, differentiation, and stage. The 5-year survival rates of the metachronous and the resected patients were significantly higher than those of the synchronous and the non resected patients, respectively. Conclusion: Due to increasing length of the follow-up period for patients with gastric cancer, another malignancy may develop in other organs. Therefore, physicians should pay attention to detect other cancers early in these patients, and a surgical resection is recommended as the treatment of choice in the management of multiple primary cancer associated with gastric cancer.

• Journal of Gastric Cancer
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• v.4 no.1
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• pp.1-6
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• 2004

Purpose: Despite numorous reports on the relationship between the level of carcinoembryonic antigen (CEA) in gall bladder bile and liver metastasis in colorectal cancer, no similar studies have been carried out for gastric carcinomas. We, therefore, undertook the present study to establish the relationship between the gall bladder bile CEA and liver metastasis as well as the post-operative survival rate in gastric carcinoma patients with curative resections. Materials and Methods: In 373 gastric cancer patients (252 males, 121 females, age $21\∼76$ years) operated on at Kosin University Hospital between 1989 1996, the CEA concentration in the gall bladder bile was determined during the operation and the value was related to the rates of post-operative survival and liver metastasis during follow-up period. Results: The overall rate of patient survival decreased gradually with increase in TNM stage. The 13-year postoperative survival rates for stages Ia, Ib, II, IIIa, and IIIb were $95.7\%,\;92.5\%,\;79.9\%,\;50.9\%,\;and\;43.3\$, respectively, and the 10-year survival rate for stage IV was $22.6\%$. The patients with a high ($\geq$10 ng/ml) biliary CEA showed a significantly lower rate of survival than those with a low (<10 ng/ml) biliary CEA. The 13-year cumulative survival rate was $55.4\%$ for the high CEA group and $76.5\%$ for the low CEA group (P<0.01). Also, the patients with a high biliary CEA showed a significantly higher rate ($11.5\%$) of liver metastasis than those with a low biliary CEA ($1.9\%$) (P<0.000). In patients with TNM stages (I and II), the CEA level did not affect the post-operative survival rates ($95.4\%\;and87.7\%$ in the high and low CEA groups, P>0.10), but in those with high TNM stages (III and IV), the survival rate was significantly lower in the high CEA group ($25.9\%$) than in the low CEA group ($57.8\%$) (P<0.05). Conclusion: These result suggest that the gall bladder bile CEA level obtained in an advanced-staged gastric cancer operation may be used in predicting the post-operational survival rate and in sorting out patients with a high risk for cancer recurrence, especially in the liver area.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.595-603
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• 2016

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.623-629
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• 2016

(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1), a marine cembrenolide diterpene, has anticancer activity against colon cancer cells such as HT-29, SNU-C5/5-FU (fluorouracil-resistant SNU-C5) and SNU-C5. However, the action mechanism of LS-1 on SNU-C5 human colon cancer cells has not been fully elucidated. In this study, we investigated whether the anticancer effect of LS-1could result from apoptosis via the modulation of $Wnt/{\beta}$-catenin and the TGF-${\beta}$ pathways. When treated with the LS-1, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3 and cleavage of poly (ADP-ribose) polymerase in SNU-C5 cells. Furthermore, the apoptosis induction of SNU-C5 cells upon LS-1 treatment was also accompanied by the down-regulation of $Wnt/{\beta}$-catenin signaling pathway via the decrease of GSK-$3{\beta}$ phosphorylation followed by the decrease of ${\beta}$-catenin level. In addition, the LS-1 induced the activation of TGF-${\beta}$ signaling pathway with the decrease of carcinoembryonic antigen which leads to decrease of c-Myc, an oncoprotein. These data suggest that the LS-1 could induce the apoptosis via the down-regulation of $Wnt/{\beta}$-catenin pathway and the activation of TGF-${\beta}$ pathway in SNU-C5 human colon cancer cells. The results support that the LS-1 might have potential for the treatment of human colon cancer.

• Journal of Life Science
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• v.28 no.4
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• pp.415-420
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• 2018

Schisandra chinensis (Turcz.) Baill. (omija) is often used in Chinese medicine to treat various human diseases, and is known to possess various bioactive components such as schizandrin and gomisin A. In the present study, we prepared ethanol extracts of pomace of Schisandra chinensis (PSC) and investigated their effects on cell viability and expression changes of pro-apoptotic genes such as ATF3, NAG-1 and p21 in human colorectal cancer HCT116 cells. PSC significantly reduced cell viability in a dose-dependent manner, and also dramatically induced the expression of ATF3, NAG-1 and p21 genes, with resveratrol used as a positive control. We also assessed the effects of pure compound schizandrin (SZ) derived from Schisandra chinensis on cell viability and expression of pro-apoptotic genes such as ATF3, NAG-1 and p21. The results showed that SZ also decreased cell viabilities in a dose-dependent manner and increased the expression of ATF3, NAG-1 and p21 genes. In addition, apoptosis was detected in SZ-treated HCT116 cells, which was confirmed with PARP cleavage. PARP cleavage was recovered in part by the transfection of NAG-1 siRNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by SZ. Overall, our findings may contribute to understanding the molecular mechanisms of anti-proliferative and pro-apoptotic activities mediated by PSC and SZ.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6997-7005
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• 2013

Aim: To present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan. Materials and Methods: All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. Results: A total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens. Conclusions: Squamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4435-4440
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• 2013

Aloe vera gel supercritical $CO_2$ extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (${\geq}0.5$ mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ${\geq}2.5$ mm, the incidence and multiplicity of large polyps (${\geq}2.5$ mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.

• Journal of Hospice and Palliative Care
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• v.8 no.2
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• pp.200-208
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• 2005

Purpose: Palliative procedures or surgical interventions not only manage various symptoms of malignant gastrointestinal obstruction, but also improve the quality of life. We investigated the clinical characteristics and prognostic factors of terminal cancer patients with palliative procedures for malignant gastrointestinal obstruction. Methods: We retrospectively reviewed the medical records of 48 terminal cancer patients with palliative procedures for malignant gastrointestinal obstruction at Sam Anyang hospital from May in 2002 to May in 2005. We excluded patients with palliative tumor resection. We analyzed prognostic factors in symtom-free survival and overall survival using Kaplan-Meier method, univariate and multivariate analysis. Results: There were 25 males (52%) and 23 females (48%), and median age of 48 patients was 65 years. The most common cause of malignant gastrointestinal obstruction was colorectal (26 patients, 55%), followed by stomach (10, 21%). Twenty patients (42%) received previous treatment (chemotherapy, surgery, and radiotherapy) and 28 (58%) never received any. Eighteen of 20 had received chemotherapy. The most common symptom was pain (15 patients, 31%). Twenty three patients (48%) had Eastern Cooperative Oncology Group(ECOG) performance status of 1 or 2 score and 25 patients (52%) 3 or 4 score. The most common palliative procedure was colostomy and there was no mortality concerning the palliative procedures. By univariate and multivariate analysis, performance status was the only independent prognostic factor in overall survival and symptom-free survival. Overall survival was 150 days and symptom-free survival was 90 days. Conclusion:. We confirmed that perftatdormance status is significant independent prognostic factor in terminal cancer patients with palliative procedures for malignant gastrointestinal obstruction.

• Preventive Nutrition and Food Science
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• v.15 no.2
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• pp.137-142
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• 2010

Previous studies report that organo-sulfur compounds derived from garlic inhibited smooth muscle cell (SMC) proliferation and induced apoptosis of cancer cells. Recently, lipid-soluble compounds such as diallyl sulfides (DAS) and diallyl disulfides (DADS) have been reported to more effectively suppress tumor cell proliferation. However, there were few studies on the suppressive effects of lipid-soluble garlic sulfur compounds on the proliferation and migration of vascular smooth muscle cells (VSMC). Therefore, this study investigated the effect of DAS and DADS on VSMC proliferation/migration induced by oleic acid (OA), a principal fatty acid in circulating triglyceride of blood stream. Assays performed include a tetrazole (MTT) assay, a wound healing assay and a Western blots. VSMC proliferations were enhanced by OA in a dose-dependent manner at concentrations of $10{\sim}50\;{\mu}M$ and inhibited by DAS and DADS compared to non-treated control. OA-induced proliferations were also attenuated by DAS and DADS. OA-induced cell migrations were 2.5 times higher than non-treated control, and they were significantly attenuated by DAS (32% at $150\;{\mu}M$ and 50% at $200\;{\mu}M$) and DADS (40% at $150\;{\mu}M$ and 46% at $200\;{\mu}M$). OA-induced cell migration was also attenuated by PD98059 (ERK inhibitor), SB203580 (P38 inhibitor) and particularly by LY204002 (PI3K inhibitor) and SP600125 (JNK2 inhibitor). Additionally, Western blot assays showed that OA-induced JNK1/2-phosphorylation was down-regulated after treatment with DAS and DADS. In conclusion, the findings of our study support the idea that DAS and DADS may have a suppressive effect on the proliferation and migration of OA-induced VSMC and that this effect may be partly associated with PI3K and JNK2 pathways.