• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8271-8279
• /
• 2016

Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6455-6461
• /
• 2012

Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031). ${\chi}^2$ tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P=0.012), rather than later stage recurrence. Conclusion: The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3045-3050
• /
• 2013

Purpose: Hepatic resection is arguably the preferred treatment for huge hepatocellular carcinoma (H-HCC). Estimating the remnant liver volume is therefore essential. This study aimed to evaluate the feasibility of using computer-assisted volumetric analysis for this purpose. Methods: The study involved 40 patients with H-HCC. Laboratory examinations were conducted, and a contrast CT-scan revealed that 30 cases out of the participating 40 had single-lesion tumors. The remaining 10 had less than three satellite tumors. With the consensus of the team, two physicians conducted computer-assisted 3D segmentation of the liver, tumor, and vessels in each case. Volume was automatically computed from each segmented/labeled anatomical field. To estimate the resection volume, virtual lobectomy was applied to the main tumor. A margin greater than 1 cm was applied to the satellite tumors. Resectability was predicted by computing a ratio of functional liver resection (R) as (Vresected-Vtumor)/(Vtotal-Vtumor) x 100%, applying a threshold of 50% and 60% for cirrhotic and non-cirrhotic cases, respectively. This estimation was then compared with surgical findings. Results: Out of the 22 patients who had undergone hepatectomies, only one had an R that exceeded the threshold. Among the remaining 18 patients with non-resectable H-HCC, 12 had Rs that exceeded the specified ratio and the remaining 6 had Rs that were < 50%. Four of the patients who had Rs less than 50% underwent incomplete surgery due to operative findings of more extensive satellite tumors, vascular invasion, or metastasis. The other two cases did not undergo surgery because of the high risk involved in removing the tumor. Overall, the ratio of functional liver resection for estimating resectability correlated well with the other surgical findings. Conclusion: Efficient pre-operative resectability assessment of H-HCC using computer-assisted volumetric analysis is feasible.

• Nutritional Sciences
• /
• v.5 no.2
• /
• pp.53-59
• /
• 2002

This study was conducted to examine the effects of dietary sources of fatty acids and protein on serum protein profiles, hepatic functional enzyme activities, mammary tumor incidence and tumor weight in 7, 12-dimethylbenz($\alpha$)anthracene (DMBA)-treated rats. The sources of dietary fatty acids were 18n6 (rich in linoleic acid), 18n3 (rich in linolenic acid) and 22n3 (rich in DHA) : sources of dietary protein were casein (C) and soy protein isolate (S). mammary tumors (MTs) were chemically induced by DMBA (9 mg/100 g body weight) which was gastrically intubated at 7 weeks of age. Each experimental diet was given for the following 25 weeks. Casein-fed rats (group C) exhibited significantly higher levels of weight gain and FER (food efficiency ratio) than did group S. Group C showed higher levels of serum protein and globulin, and higher albumin/globulin (A/G) ratios than group S. Liver functional enzyme activities (GOT, GPT, ALP, LDH, $\gamma$-GT) and LDH/GOT ratios were not influenced by dietary protein. GPT activity was lower in the group given 18n3, and ALP activity was lower in the group given 18n6. The incidence and total number of MTs appeared to be lower in the group given 22n3 than in the group given 18n3 or 18n6, even though the average weight of MTs was highest in the group given 22n3, The average weight of MTs was higher in the C group than in the S group. MT incidence had a positive correlation with LDH activity and LDH/GOT ratio. The average weight of MTs had a negative correlation with serum albumin levels and A/G ratios, and a positive correlation with ALP activity. This research suggests that the measurement of serum protein profiles and liver functional enzyme activities may be utilized to monitor the development of mammary tumors.

• Journal of Gastric Cancer
• /
• v.22 no.4
• /
• pp.339-347
• /
• 2022

Purpose: Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology. Materials and Methods: A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47). Results: The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349). Conclusions: Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1297-1303
• /
• 2012

Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

• Advances in pediatric surgery
• /
• v.14 no.2
• /
• pp.153-163
• /
• 2008

Inflammatory myofibroblastic tumor (IMT) is a rare reactive lesion characterized by the feature of myofibroblasts and a mixed inflammatory infiltrate that rarely undergoes malignant transformation. Extrapulmonary IMTs in children have been described involving the mesentery, omentum, retroperitoneum, abdominal soft tissues, liver, bladder, mediastinum, head and neck, extremity, appendix, and kidney. Medical records of children treated with abdominal IMT between 1985 and 2005 were reviewed retrospectively. Seven children were treated for IMT with the mean age of 3 y 2 m (range, 1 y 1 m to 14 y). Tumors were located in transverse mesocolon (n=2), omentum (n=1), porta hepatis (n=2), complex site (antrum, duodenum, common bile duct, porta hepatis) (n=2). The symptoms included abdominal mass, fever, jaundice, abdominal pain and anemia. The masses were excised totally in transverse mesocolon, omentum IMT and there is no evidence of recurrence (follow-up periods: 6 y 8 m, 8 y 9 m, 4 y 10 m). In porta hepatis IMT, liver transplantations were performed and there is no evidence of recurrence (follow period: 6 y 8 m, 8 y 7 m). In one case of complex site IMT, partial excision of mass was performed and he still survived with no change of the residual tumor during follow-up period. The other one of complex site IMT denied further treatment after the biopsy. In conclusion, complete surgical excision including liver transplantation and close follow-up are mandatory for the abdominal IMT in child.

• Proceedings of the Ginseng society Conference
• /
• 2002.10a
• /
• pp.317-334
• /
• 2002

Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

• Journal of The Korean Radiological Technologist Association
• /
• v.29 no.1
• /
• pp.139-139
• /
• 2003

• The Korean Journal of Nuclear Medicine
• /
• v.12 no.2
• /
• pp.17-22
• /
• 1978

Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particullary in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients in liver cirrhosis, 5(27.8%) of 18 patients in hepatoma, 5(71. %) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2(66.7%) of 3 patients in liver ablscesses, 2(66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryodic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver cirrhosis patients.