• 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.15 no.10
• /
• pp.4367-4372
• /
• 2014

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.1
• /
• pp.381-385
• /
• 2015

Background:Hepatocellular carcinoma (HCC) is the second most common malignancy in Egypt. Data mining is a method of predictive analysis which can explore tremendous volumes of information to discover hidden patterns and relationships. Our aim here was to develop a non-invasive algorithm for prediction of HCC. Such an algorithm should be economical, reliable, easy to apply and acceptable by domain experts. Methods: This cross-sectional study enrolled 315 patients with hepatitis C virus (HCV) related chronic liver disease (CLD); 135 HCC, 116 cirrhotic patients without HCC and 64 patients with chronic hepatitis C. Using data mining analysis, we constructed a decision tree learning algorithm to predict HCC. Results: The decision tree algorithm was able to predict HCC with recall (sensitivity) of 83.5% and precession (specificity) of 83.3% using only routine data. The correctly classified instances were 259 (82.2%), and the incorrectly classified instances were 56 (17.8%). Out of 29 attributes, serum alpha fetoprotein (AFP), with an optimal cutoff value of ${\geq}50.3ng/ml$ was selected as the best predictor of HCC. To a lesser extent, male sex, presence of cirrhosis, AST>64U/L, and ascites were variables associated with HCC. Conclusion: Data mining analysis allows discovery of hidden patterns and enables the development of models to predict HCC, utilizing routine data as an alternative to CT and liver biopsy. This study has highlighted a new cutoff for AFP (${\geq}50.3ng/ml$). Presence of a score of >2 risk variables (out of 5) can successfully predict HCC with a sensitivity of 96% and specificity of 82%.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.2115-2121
• /
• 2014

The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), ${\gamma}$-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN-induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.10
• /
• pp.4303-4310
• /
• 2015

Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9 % normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and ${\gamma}$-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.2 no.2
• /
• pp.204-210
• /
• 1999

Purpose: We assessed the nutritional status and the alterations of oral diets during anti-cancer chemotherapy in pediatric oncology patients. Methods: Twenty children with malignancy were evaluated from day 0 until day 21 of post-chemotherapy. Nutritional status was assessed by body weight and biochemical parameters. The amount and calories of oral diets were assessed and food preference before and during chemotherapy were analysed by questionnelle. Results: 1) The underlying diseases of 20 patients were 11 acute lymphoblastic lekemia, 2 non-Hodgkin's lymphoma, 2 Langerhans cell histiocytosis, 2 Wilm's tumor, 2 brain tumor, 1 rhabdomyosarcoma. 2) There were weight loss during chemotherapy in 8 patients (40.0%), weigt gain in 5 patients (25.0%), and no significant changes in 7 patients (35.0%). 3) Biochemical parameters showed no significant interval changes during chemotherapy except elevation of serum ALT level. 4) The daily caloric intakes of oral diets during chemotherapy were 310~600 Kcal which was much lower than average of daily recommended calory for Korean children. 5) The most favorate food was altered by chemotherapy, from meats to carbonated beverages and unfavorate food was not altered as vegetables. Conclusion: The periodic assessment of nutritional status and dietary supplements according to preferred foods of patients will be required for the optimal nutrition care in cancer patients.

• The Journal of Internal Korean Medicine
• /
• v.22 no.4
• /
• pp.669-674
• /
• 2001

Objectives: The purpose of this study was to examine the efficacy of Hangamdan(Kangaidan) on 60 patients who have suffered from breast cancer. Methods: Hangamdan(Kangaidan) was administered to patients for over 1 months continuously. We checked improvement of clinical symptoms, changes of chemistry hematological test. Results: The results obtained are summarized as follows. Hangamdan(Kangaidan) has significant effect on the improvement of clinical symptoms. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(92.1%) were observed. The effects of the symptoms were diarrhea(37.3%), abdominal pain (25.3%), general body weakness(22.9%), nausea(20.5%) and etc. in orders. And analysis of hematology attached by breast cancer, maintenance and increasing of WBC(89.9%), RBC(74.7%), Hgb(81.1%), Platelet(92.4%) were observed. After taken Hangamdan(Kangaidan), maintenance and decreasing of AST(85.9%), ALT(94.8%), ${\gamma}$-GTP(87.5%), BUN(88.3%), Creatinine(90.9%) were observed. And increasing of IL-12(25%), IFN-${\gamma}$(83%) were observed. Conclusions: From the above results, it is suggested that Hangamdan(Kangaidan) have significant effects on recovery of immune modulation.

• Radiation Oncology Journal
• /
• v.11 no.1
• /
• pp.109-117
• /
• 1993

To analyze biochemical changes of liver function following combined radiotherapy and hyperthermia, we reviewed retrospectively 37 patients with hepatocellular carcinoma treated with radiotherapy and hyperthermia between July 1988 and December 1990 at Department of Radiation Oncology, Yonsei University College of Medicine. Mean age was 52.7 years and male to female ratio was 11:1. The patients were classified as follows; to A and B group by Child's classification, to M and L group by irradiated volume, and subclassified into BM, BL, AM and AL group according to the combination of Child's classification and irradiated volume. Radiation dose to the primary tumor was 3060 cGy with daily 180 cGy, 5 fraction per week using 10 MV or 4 MV linear accelerator. Hyperthermia (Thermotron RF-8) was performed more than 4 times in all patients. Biochemical parameters including albumin (Alb), total bilirubin (T. Bil), aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), and alkaline phosphatase (ALP) were regularly followed from 1 week before the treatment to 3 months after the treatment. The results are summerized as follows; 1) In all the patient, mean ALP level peaked at 1 month, decreased at 2 months, slightly increased at 3 months after the treatment. Mean SGOT and SGPT levels peaked at 1 month after the treatment. Mean T. Bil level increased continuously and highest at 3 months after the treatment. Mean Alb level did not show significant changes.; 2) Mean ALP level retured to normal level at 3 month after the treatment in A but increased in B group and the differences were statistically significant (p<0.01). Mean SGOT and SGPT levels peaked 1 month in A and 2 months after the treatment in B group. All the biochemical parameters did not show significant difference between M and L group. Mean ALP level increased at 3 months after the treatment in BM and BL groups and decreased in AM and AL groups. Mean SGOT level increased at 3 months after the treatment in BL groups.; 3) Hepatic failure occurred within 3 months after the treatment in 4 patients, all of whom were in BL group. It is suggested that pre-treatment liver function and irradiated volume influence biochemical changes of liver in patients with hepatocellular carcinoma following combined radiotherapy and hyperthermia, and this treatment modality appears generally to be safe but might cause hepatic failure particularly in patient with poor liver function and large treatment volume.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.22 no.6
• /
• pp.1525-1531
• /
• 2008

Acer tegmentosum Max which is one of the specialized wildness medicinal herbs in gangwon province, has been widely used for hepatitis, liver cirrhosis, hepatic cancer, leukemia, diabetes mellitus, renal necrosis and edema, etc. In this study, the antioxidative and hepatoprotective effects of in vitro and in vivo were investigated in order to evaluate the possibility as hepatoprotective agents. Oral administration of methanol and butanol extact of Acer tegmentosum Max to d-galactosamine (D-GaIN) induced experimental liver injured rats was significantly reduced activities of marker enzymes(AST, ALT) and LDH activity in serum. Salidroside(Sal) isolated from the BuOH extract of Acer termentosum Max potenty showed the scavenzing effect on DPPH and inhibitory effect on lipid peroxidation. And significantly decrcease of MDA level in liver and activities of SOD GSH-Px and catalase were significantly improved by the treatment of Sal. Results of this study revealed that Sal could afford a significant protection in the alleviation of D-GaIN-induced hepatocellular injury.

• The Journal of Internal Korean Medicine
• /
• v.22 no.4
• /
• pp.547-555
• /
• 2001

Objectives: Obesity is regarded as the aggregation of needless risk factors, for instance, cardiovascular disease, joint disease, induce cancer. We studied on interrelation between abnormal liver function and obesity. Methods: We analyzed liver function, T.Cholesterol, Triglyceride before and after lose weight treatment. The collateral condition is over 6 weeks period on obesity treatment, no liver injury and no complicated another disease on personal past history and found out abnormal impression on biochemical liver function blood test. Results: The improvement rate of LFT, compare with before treatment is 10.6% in T.Bilirubin, 11.1% in ALP, 21% in AST, 38% in ALT, 37.3% in r-GTP, 9.2% in LDH and decreased 2.7% in T.Protein, increased 2.3% in Albumin. Hyperlipidemia is 19.4% in T.Cholesterol, 42.5% in Triglyceride. Conclusions: LFT and Hyperlipidemia of abnormal liver function patients, caused by obesity, is improved to normal limit in proportion to reduce patient's weight.