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Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC.An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels.PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power.The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.

Background: Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine (Kyn) and induces immune tolerance in tumour cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. Methods: An immunohistochemical microarray analysis of IDO1 expression was performed for 77 surgically resected cases of EHBDC, and the results were compared with various clinicopathologic variables including survival data. CD8+ tumour infiltrating lymphocytes (TILs) were also investigated to elucidate their relationship with IDO1 expression and prognosis through a combination analysis with IDO1 expression. Results: IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001), and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high /CD8low subgroup showed the worst prognosis in terms of overall survival (P = 0.025, Cox risk ratio = 2.168) and disease-free survival (P = 0.015, Cox risk ratio = 2.460) in a multivariate analysis. Conclusions: Our study confirmed that high IDO1 expression was correlated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic prediction tool in the patients with EHBDC.

Glioblastoma multiforme is one of the most aggressive human malignant brain tumors. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as the death ligand, which induces preferential apoptosis of transformed cancer cells. In this study, we demonstrated that the newly synthesized diethylamino-curcumin mimic with trizolyl benzene (YM-4) enhances cytotoxicity in combination with TRAIL in human glioblastoma cells. We synthesized diethylamino-curcumin mimic with trizolyl benzene (YM-4) and investigated possible apoptotic cell signaling by co-treatment with YM-4 and TRAIL on human glioblastoma cells. Caspase-8, 9, and 3 and poly (ADP-ribose) polymerase were more efficiently cleaved with cotreatment of YM-4 and TRAIL than treatment with each alone in human glioblastoma cells. Co-treatment with YM-4 and TRAIL significantly increased the expression of Bax and Smac/Diablo and also inhibited the expression of the X-linked inhibitor of apoptosis protein and Survivin in human glioblastoma cells. These results demonstrated that YM-4 can be an anticancer candidate that can be effective on human glioblastoma cells in combination with TRAIL.

PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after H2O2 treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, IL-1β, TNF-α, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, IL-1β, p-Erk1/2, NF-κB, TNF-α, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating IL-1β, TNF-α, and subsequent signals, such as p-Erk1/2, NF-κB, COX-2, PGE2, and MMPs.

Introduction Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and anti-inflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice. Methods Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 45 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI. Results Treatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histological changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein 70 and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IkB-α) was significantly decreased in the eupatilin pretreatment group. Conclusions Eupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.

Background To overcome a shortage of donors, cadaveric pediatric en bloc kidneys can be used to expand the donor pool. Recent evidence shows that en bloc kidney transplantation (EBKT) has better outcomes than standard-criteria deceased adult donor kidney transplantation. We reviewed our experiences of EBKT and their outcomes. Methods From September 1996 to January 2016, 15 EBKTs were performed in Asan Medical Center. The characteristics of donors and recipients were analyzed. Graft survival was analyzed by means of serum creatinine levels. Results Nine male and 6 female donors were used. The mean age and body weight of donors was 2.79 years (range, 0.25–14) and 13.14 kg (range, 5.5–35). The mean weight of en bloc kidneys was 117.43 g (range, 36–146). Recipient median age was 39.13 years and body weight was 49.47 kg. Ureteral anastomosis was performed by means of side-to-side anastomosis and then bladder anastomosis in 9 patients and by bladder patch anastomosis in 4 patients. Serum creatinine levels at discharge and latest follow-up were 0.97 mg/dL (range, 0.7–1.54) and 0.89 mg/dL (range, 0.44–2.58). Delayed graft function developed in 3 patients and clinical rejection developed in 2 patients. We performed graftectomy on post-operative day 1 because of graft thrombosis. The rest maintained their graft function well. Graft survival was comparable with that of kidney transplantation from standard donors. Conclusions EBKT showed excellent graft function and outcomes at our center. As an approach to expand the donor pool and improve graft utilization, EBKT is acceptable and should be more widely used.

Previous reports have shown that PPARβ/δ agonists ameliorate insulin resistance associated with type 2 diabetes mellitus (T2DM). To determine the role of PPARβ/δ in tumor necrosis factor α (TNFα)-mediated insulin resistance, we investigated expression levels of adiponectin and insulin receptor (IR) in response to treatment with the PPARβ/δ agonist GW501516 with or without TNFα, a proinflammatory cytokine, in differentiated 3T3-L1 adipocytes. GW501516 induced adipocyte differentiation and the expression of adiponectin in a dose-dependent manner in differentiated adipocytes. TNFα treatment reduced adiponectin expression at the end of differentiation. This effect was reversed by GW501516 co-treatment with TNFα. TNFα treatment decreased adipogenic marker genes such as PPARγ, aP2, resistin, and GLUT4, and GW501516 reversed the effects of TNFα. GW501516 treatment increased the expression of insulin receptor and inhibited TNFα-mediated repression of insulin receptor. Our results showed that GW501516 abrogated TNFα-induced insulin resistance. In summary, our study demonstrated that the PPARβ/δ agonist, GW501516 reversed TNFα-induced decreases in adipocyte differentiation and adiponectin expression, and improved insulin sensitivity by increasing the expression of insulin receptor. Therefore, PPARδ may be a promising therapeutic target for treatment of insulin resistance in patients with T2DM.

Background Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng . Methods The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK–p53–caspase-3 signaling cascade.

A 47-year-old man developed chronic alcoholic liver cirrhosis and end-stage renal disease. He underwent blood-type-compatible liver transplantation with a graft from his daughter. After 8 months, sequential ABO-incompatible (ABOi) kidney transplantation was performed, with his brother as the donor (A to O). The patient had anti-A antibody titers (1:256). We performed pretransplant desensitization, including administration of rituximab, mycophenolate mofetil, tacrolimus, and prednisolone 2 weeks before the scheduled transplantation, and plasmaphresis (PP) and administered an intravenous immunoglobulin injection. The patient un- derwent PP before kidney transplantation until the anti-A antibody titer was

The adverse effects of anticancer drugs can prompt patients to end their treatment despite the efficacy. Cisplatin is a platinum-based molecule widely used to treat various forms of cancer, but frequent and long-term use of cisplatin is limited due to severe nephrotoxicity. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin on cisplatin-induced kidney damage, oxidative stress, and inflammation to evaluate its possible use in renal damage. Cisplatin-induced LLC-PK1 renal cell damage was significantly reduced by tetrahydrocurcumin treatment. Additionally, the protective effect of tetrahydrocurcumin on cisplatin-induced oxidative renal damage was investigated in rats. Tetrahydrocurcumin was orally administered every day at a dose of 80 mg/kg body weight for ten days, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) in 0.9 % saline on day four. The creatinine clearance levels, which were markers of renal dysfunction, in cisplatin-treated rats were recovered nearly back to normal levels after administration of tetrahydrocurcumin. Moreover, tetrahydrocurcumin exhibited protective effects against cisplatin-induced oxidative renal damage in rats by inhibiting cyclooxygenase-2 and caspase-3 activation. These results collectively provide therapeutic evidence that tetrahydrocurcumin ameliorates renal damage by regulating inflammation and apoptosis.

The present study investigated the renoprotective effect of anArtemisia asiaticaextract and eupatilin in kidney epithelial (LLC-PK1) cells. Although cisplatin is effective against several cancers, its use is limited due to severe nephrotoxicity. Eupatilin is a flavonoid compound isolated from theArtemisiaplant and possesses antioxidant as well as potent anticancer properties. In the LLC-PK1 cellular model, the decline in cell viability induced by oxidative stress, such as that induced by cisplatin, was significantly and dose-dependently inhibited by theA. asiaticaextract and eupatilin. The increased protein expressions of phosphorylated JNK and p38 by cisplatin in cells were markedly reduced afterA. asiaticaextract or eupatilin cotreatment. The elevated expression of cleaved caspase-3 was significantly reduced byA. asiaticaextract and eupatilin, and the elevated percentage of apoptotic cells after cisplatin treatment in LLC-PK1 cells was markedly decreased by cotreatment withA. asiaticaextract or eupatilin. Taken together, these results suggest thatA. asiaticaextract and eupatilin could cure or prevent cisplatin-induced renal toxicity without any adverse effect; thus, it can be used in combination with cisplatin to prevent nephrotoxicity.

The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are important to the increase in the biological activities of Panax ginseng. This study was carried out to identify the renoprotective active component of P. ginseng using the Maillard reaction model experiment with ginsenoside Re and leucine. Ginsenoside Re was gradually converted into less-polar ginsenosides Rg2, Rg6 and F4 by heat-processing, followed by separation of the glucosyl moiety at carbon-20. The free radical-scavenging activity of the ginsenoside Re-leucine mixture was increased by heat-processing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of MRPs from the reaction of glucose and leucine. The cisplatin-induced LLC-PK1 renal cell damage was also significantly reduced by treatment with MRPs. Moreover, the heat-processed glucose-leucine mixture (major MRPs from the ginsenoside Re-leucine mixture) showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of caspase-3 activation.

Heme oxygenase-1 (HO-1) is an important catalytic enzyme in heme degradation, which increases during stressful conditions. It plays a major role in antioxidative and antiapoptotic processes and is associated with tumor growth and metastasis. This study aimed to evaluate the degree of HO-1 expressions in hepatocellular carcinoma (HCC) surgical specimens and the correlation between HO-1 expression and patient prognosis. Formalin-fixed, paraffin-embedded HCC tissue samples (n = 96) were included in the analysis, and the expression of HO-1 was evaluated by immunohistochemical staining. We reviewed clinical features of patients and evaluated the prognostic role of HO-1 in patient survival and recurrence. Positive HO-1 expression was identified in 43 cases (44.8%) and was frequently found in patients with advanced histology (Edmondson–Steiner [E-S] grade 2, 3, 4), α-fetoprotein (AFP) level of more than 200 IU/mL, and the presence of microvascular and capsular invasion (P

The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection.In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III gastric cancer patients who underwent curative surgery.Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P 0.001) and intestinal type (P = 0.002).HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.

Background Recently improved patient and graft survivals, as well as decreased of postoperative morbidity have ushered in pancreas transplantation (PT) due to technical refinements as well as better immunosuppression and postoperative management. Herein we analyzed the outcomes of PT over a 19-year experiences at a single center. Methods All recipients who underwent deceased donor or living donor PT from July 1992 to July 2011 were enrolled in this study. We reviewed their medical records, including operative records, as well as clinical and laboratory findings. We analyzed graft and patient survival rates using the Kaplan-Meier method. Results One hundred fifty-three cases were performed between July 1992 and July 2011. The indication for PT was type I diabetes in 125 (81.7%), and type II diabetes in 28 (18.3%) patients. The pancreas donor was deceased in 139 (90.8%) and living in 14 cases (9.2%). The type of PT was simultaneous pancreas-kidney transplantation ( n = 91, 59.5%), pancreas alone ( n = 49; 32.0%), or pancreas after kidney ( n = 13, 8.5%). Median follow-up was 43.0 months (range 0–228). At 1, 5, and 10 years overall patient survivals were 93.8%, 88.1%, and 85.1%, and graft survivals, 82.3%, 70.6%, and 64.6%, respectively. When we divided the deceased donor PT recipients into two groups according to when they underwent PT (up to 2005 [ n = 54]) vs 2006 and later [ n = 85]), the recent group showed significantly improved patient and graft survival rates ( P n = 65) and type II ( n = 20) patients ( P = .159). Conclusion Considering the improved quality of life and long-term patient survival, PT can be an effective treatment strategy in diabetic patients requiring insulin regardless of type of disorder.

The anti-hyperlipidemic effects of dietary supplementation with sea tangle Laminaria japonica were investigated using an animal model in which normal rats were fed either sea tangle, sea tangle ethanol extract (EE-ST) and sea tangle extracted residue (ER-ST). Total lipid and triglyceride levels in the serum were significantly ( P < 0.05) reduced in rats fed ER-ST at a dose of 200 mg/kg body weight when compared to hyperlipidemic control rats. Significant decreases in serum total cholesterol and low density lipoproteincholesterol levels also occurred in rats fed ER-ST at 200 mg/kg body weight. In addition, the atherosclerosis index and superoxide dismutase in blood lipids were significantly ( P < 0.05) lowered in rats fed ER-ST at 200 mg/kg body weight as compared to control rats. In conclusion, sea tangle and ER-ST exhibited beneficial anti-hyperlipidemic and anti-arteriosclerosis effects.

Preventive effects and corresponding molecular mechanisms of mugwort (Artemisia argyi) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that A. argyi extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases. The flavonoid compounds isolated from A. argyi improved the viability of iodixanol-treated cells against contrast-induced nephrotoxicity. Seven compounds (1, 2, 3, 15, 16, 18, and 19) from 19 flavonoids exerted a significant protective effect. Based on the in silico oral-bioavailability and drug-likeness assessment, which evaluate the drug potential of these compounds, compound 2 (artemetin) showed the highest oral bioavailability (49.55%) and drug-likeness (0.48) values. We further investigated the compound–target–disease network of compound 2, and proliferator-activated receptor gamma (PPAR-γ) emerged as a predicted key marker for the treatment of contrast-induced nephrotoxicity. Consequently, compound 2 was the preferred candidate, and its protective effect was mediated by inhibiting the contrast-induced inflammatory response through activation of PPAR-γ and inhibition of MAPK phosphorylation and activation of caspases.

Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway.

An extract of Artemisia asiatica was reported to possess antioxidative and cytoprotective actions in various experiments. Ischemia-reperfusion injury remains a major problem in kidney transplant, and the inflammatory response to ischemia-reperfusion injury exacerbates the resultant renal injury. In the present study, we investigated whether an extract of Artemisia asiatica exhibits renoprotective effects against ischemia-reperfusion-induced acute kidney injury in mice.Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. An extract of Artemisia asiatica (100 mg/kg oral) was administered 4 days before ischemia-reperfusion injury. Sham operation and phosphate-buffered saline were used as controls. Blood and renal tissues were evaluated at 48 hours after ischemiareperfusion injury.Treatment with an extract of Artemisia asiatica significantly decreased blood urea nitrogen, serum creatinine levels, and kidney tubular injury (P ≤ .05). Western blot showed that an extract of Artemisia asiatica significantly increased the level of heme oxygenase-1 and B-cell lymphoma 2 at 48 hours after ischemia-reperfusion injury and attenuated the level of inducible nitric oxide synthase.An extract of Artemisia asiatica improves acute renal ischemia-reperfusion injury by reducing inflammation and apoptosis. These findings suggest that an extract of Artemisia asiatica is a potential therapeutic agent against acute ischemia-induced renal damage.

A new curcumin mimic library (III) is synthesized using the Huisgen cycloaddition of alkynes with azide (I).

Epigallocatechin gallate (EGCG) and curcumin are well known to naturally-occurring anticancer agents. The aim of this study was to verify the combined beneficial anticancer effects of curcumin and EGCG on PC3 prostate cancer cells, which are resistant to chemotherapy drugs and apoptosis inducers. EGCG showed weaker inhibitory effect on PC3 cell proliferation than two other prostate cancer cell lines, LNCaP and DU145. Co-treatment of curcumin improved antiproliferative effect of EGCG on PC3 cells. The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound. Moreover, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells. These results suggest that the enhanced inhibitory effect of EGCG on PC3 cell proliferation by curcumin was mediated by the synergic up-regulation of p21-induced growth arrest and followed cell growth arrest. [BMB Reports 2015; 48(8): 461-466]

Because of poor prognosis, clinical treatment of triple-negative (TN) breast cancer remains the most challenging factor in cancer treatment. Extensive research into alternative cancer therapies includes studying the naturopathic effects of the medicinal herb ginseng. This study investigates the anti-neoplastic properties of ginseng sapogenins and the derivatives: (1) (20(S)-protopanaxadiol (PPD), (2) 20(S)-protopanaxatriol), (3) (20(S)-dihydroprotopanaxadiol, and (4) 20(S)-dihydroprotopanaxatriol). These compounds were found to prevent the proliferation of MDA-MB-231 human breast cancer cells. PPD was the most potent inhibitor, exhibiting an IC₅₀ (5.87 μM) comparable to that of the chemotherapeutic drug taxol. Furthermore, PPD induced dose-dependent cleavage of caspase-8, caspase-3, and PARP in MDA-MB-231 cells. Thus, we propose that PPD acts as anti-cancer agent by stimulating caspase-dependent apoptosis in breast cancer cells.

Laparoscopic cholecystectomy (LC) is the treatment of choice for gallbladder stones. One of the major complications associated with LC is bile duct injury; ligation or cutting of a bile duct can result in significant segmental biliary obstruction with cholangitis or bile leak, which can progress to bile peritonitis or biliary fistula. Most postoperative bilomas and bile leaks can be treated by percutaneous drainage and decompression of the biliary system by endoscopic stent placement or nasobiliary drainage. When conservative methods fail despite prolonged drainage, selective intrahepatic biliary ethanol and micro-coil embolization may be an alternative treatment. We report three successful cases where postoperative bilomas associated with laparoscopic cholecystectomy have been managed with intrabiliary ethanol ablation and micro-coil embolization.

A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors.

Ginsenoside Re is a triol type triterpene glycoside and is abundantly present in ginseng berry. In the present study, we verified that ginsenoside Re can be transformed into less-polar ginsenosides, namely, Rg2, Rg6, and F4, by heat-processing. The products of heat-processed ginsenoside Re inhibited phosphorylation of CDK2 at Thr160 by upregulation of p21 level, resulting in S phase arrest. The products of heat-processed ginsenoside Re also activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Concurrently, alteration of mitochondrial factors such as Bcl-2 and Bax was also observed. Moreover, pretreatment with Z-VAD-fmk abrogated caspase-8, -9, and -3 activations by the products of heat-processed ginsenoside Re. We further confirmed that the anticancer effects of the products of heat-processed ginsenoside Re in AGS cells are mainly mediated via generation of less-polar ginsenosides Rg6 and F4.

The epithelial-mesenchymal transition (EMT) is a pivotal cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which, in turn, promotes the metastatic potential of cancer. Ginseng is a perennial plant belonging to the genus Panax that exhibits a wide range of pharmacological and physiological activities. Ginsenosides 20-Rg3, which is the active component of ginseng, has various medical effects, such as anti-tumorigenic, anti-angiogenesis, and anti-fatiguing activities. In addition, ginsenosides 20(S)-Rg3 and 20(R)-Rg3 are epimers, and this epimerization is produced by steaming. However, the possible role of 20(S)-Rg3 and 20(R)-Rg3 in the EMT is unclear. We investigated the effect of 20(S)-Rg3 and 20(R)-Rg3 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the repressive role of 20(S)-Rg3 and 20(R)-Rg3 in lung cancer migration, invasion, and anoikis resistance, we investigated the potential use of 20(S)-Rg3 and 20(R)-Rg3 as inhibitors of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here, we show that 20(R)-Rg3, but not 20(S)-Rg3, markedly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker vimentin during initiation of the TGF-β1-induced EMT. 20(R)-Rg3 also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, 20(R)-Rg3 markedly inhibited TGF-β1-regulated matrix metalloproteinase-2 and activation of Smad2 and p38 mitogen activated protein kinase. Taken together, our findings provide new evidence that 20(R)-Rg3 suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.

Buerger's disease is almost always a disease of the blood vessels in the extremities. Conversely, mesenteric involvement of Buerger's disease is rare, and no true series have been reported. We report the case of a 37-year-old man with clinical symptoms of upper extremity Buerger's disease, who underwent surgery for extensive small bowel infarction. Histopathologic findings revealed that the mesenteric arteries were swollen and infiltrated with neutrophils, but not associated with fibrinoid necrosis. The lumen was occluded by a highly cellular thrombus with the appearance of a microabscess. These findings were compatible with acute-stage mesenteric Buerger's disease and postoperative studies revealed multiple occluded segments in the small and medium-sized arteries of both legs and the left arm, suggestive of Buerger's disease in the extremities.

Superior mesenteric artery (SMA) syndrome is a rare condition in which the third part of the duodenum is trapped between the abdominal aorta and the SMA. Any disease process decreasing the angle between the aorta and the SMA can result in external compression of the duodenum and subsequent intestinal obstruction. Aneurysms of the pancreaticoduodenal artery (PDA) and its branches are also rare and account for only 2% of all splanchnic artery aneurysms. We report a case of SMA syndrome that developed after successful coil embolization of a ruptured PDA aneurysm.

Purpose: In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. Methods: Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. Results: The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients’ survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). Conclusion: Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts.

Micropapillary carcinoma (MPC) is an aggressive variant of adenocarcinoma, with a high incidence of lymph node (LN) metastasis in several organs, although not yet well described in the stomach. Thus, we compared the clinicopathologic characteristics, including survival data and immunohistochemical profiles of cell adhesion molecules (E-cadherin, β-catenin, IQGAP-1, and CD44v6), of MPCs with those of adenocarcinomas lacking MPC components (non-MPC) in the stomach. We compared 72 MPC cases with 160 non-MPC cases. Most gastric MPCs arose from tubular or papillary adenocarcinomas, and the proportion of MPC components ranged from 5% to 80%. MPCs were characterized by more frequent lymphovascular invasion and LN metastasis (P0.0001), higher tumor node metastasis (TNM) stage (P=0.019), advanced age (65 y; P0.0001), and more frequent CD44v6 and aberrant β-catenin expression (P0.0001). The overall 5-year survival rates for patients with MPC were significantly worse than those with non-MPC (30% vs. 67%; P=0.002). Furthermore, when it was stratified by TNM stages, the survival rates were distinguished between MPC and non-MPC groups in TNM stages I to II (P=0.0003), but not in TNM stages III to IV. The presence of the MPC component was associated with a significantly worse patient survival by univariate (P=0.0003) and multivariate (P=0.04) analyses in patients with stages I to II gastric carcinoma. In conclusion, recognition of the MPC component in gastric carcinoma is critical, because the MPC component is associated with more frequent LN metastasis and a worse prognosis, especially in stages I to II gastric cancer.