Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2167

Search results for: liver cancer

2167 Evaluating the Diagnostic Accuracy of the ctDNA Methylation for Liver Cancer

Authors: Maomao Cao

Abstract:

Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

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2166 Higher Freshwater Fish and Sea Fish Intake Is Inversely Associated with Liver Cancer in Patients with Hepatitis B

Authors: Maomao Cao

Abstract:

Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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2165 Classifier for Liver Ultrasound Images

Authors: Soumya Sajjan

Abstract:

Liver cancer is the most common cancer disease worldwide in men and women, and is one of the few cancers still on the rise. Liver disease is the 4th leading cause of death. According to new NHS (National Health Service) figures, deaths from liver diseases have reached record levels, rising by 25% in less than a decade; heavy drinking, obesity, and hepatitis are believed to be behind the rise. In this study, we focus on Development of Diagnostic Classifier for Ultrasound liver lesion. Ultrasound (US) Sonography is an easy-to-use and widely popular imaging modality because of its ability to visualize many human soft tissues/organs without any harmful effect. This paper will provide an overview of underlying concepts, along with algorithms for processing of liver ultrasound images Naturaly, Ultrasound liver lesion images are having more spackle noise. Developing classifier for ultrasound liver lesion image is a challenging task. We approach fully automatic machine learning system for developing this classifier. First, we segment the liver image by calculating the textural features from co-occurrence matrix and run length method. For classification, Support Vector Machine is used based on the risk bounds of statistical learning theory. The textural features for different features methods are given as input to the SVM individually. Performance analysis train and test datasets carried out separately using SVM Model. Whenever an ultrasonic liver lesion image is given to the SVM classifier system, the features are calculated, classified, as normal and diseased liver lesion. We hope the result will be helpful to the physician to identify the liver cancer in non-invasive method.

Keywords: segmentation, Support Vector Machine, ultrasound liver lesion, co-occurance Matrix

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2164 The Effect of Endurance Training and Taxol Consumption on Cyclooxygenase-2 and Prostaglandin E2 Levels in the Liver Tissue of Mice with Cervical Cancer

Authors: Alireza Barari, Maryam Firozi-Niyaki, Maryam Kamarlouei

Abstract:

Background: Herbs have a strong anti-cancer effect. Also, exercise is one of several lifestyle factors known to lower the risk of developing cancer. The aim of this study was to investigate the effect of endurance training and taxol on cyclooxygenase-2 and prostaglandin E2 in the liver tissue of mice with cervical cancer. Materials and Methods: In this experimental study, 35 female C57 mice were randomly divided into 5 groups (n=7 in each group): control (healthy), control (cancer), complement (cancer), training-supplementary (cancer) and training (cancer). The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/kg/day of pure taxol was injected intra peritoneally. The dependent variables of this study were measured 24 hours after the last training session by ELISA. Results: The results showed that the use of taxol and endurance training reduced the levels of cyclooxygenase-2 and prostaglandin E2 in the liver tissues of C57 mice with cervical cancer. Conclusion: Induction of the cancerous tissue in mice with cervical cancer increases the levels of cyclooxygenase-2 and prostaglandin E2 and endurance training along with taxol may reduce these levels.

Keywords: cervical cancer, taxol, endurance training, cyclooxygenase-2, prostaglandin E2

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2163 Transplant Oncology: An Evolution Field of Treating Cancer by Transplantation

Authors: Maen Abdelrahim, Abdullah Esmail

Abstract:

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients’ survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting will be discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.

Keywords: transplant oncology, liver transplantation, cholangiocarcinoma, neuroendocrine tumor, liver metastases, hepatocellular carcinoma, circulating tumor DNA, colorectal cancers, immunotherapy

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2162 Computer-Aided Classification of Liver Lesions Using Contrasting Features Difference

Authors: Hussein Alahmer, Amr Ahmed

Abstract:

Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

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2161 In vitro Comparison Study of Biologically Synthesized Cupper-Disulfiram Nanoparticles with Its Free Corresponding Complex as Therapeutic Approach for Breast and Liver Cancer

Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

Abstract:

The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

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2160 Hypoxia Tolerance, Longevity and Cancer-Resistance in the Mole Rat Spalax – a Liver Transcriptomics Approach

Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln

Abstract:

The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.

Keywords: cancer, hypoxia, longevity, transcriptomics

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2159 Cratoxy Formosum (Jack) Dyer Leaf Extract-Induced Human Breast and Liver Cancer Cells Death

Authors: Benjaporn Buranrat, Nootchanat Mairuae

Abstract:

Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.

Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death

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2158 Nanotechnology-Based Treatment of Liver Cancer

Authors: Lucian Mocan

Abstract:

We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

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2157 Numerical Simulation of Heating Characteristics in a Microwave T-Prong Antenna for Cancer Therapy

Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This research is presented with microwave (MW) ablation by using the T-Prong monopole antennas. In the study, three-dimensional (3D) finite-element methods (FEM) were utilized to analyse: the tissue heat flux, temperature distributions (heating pattern) and volume destruction during MW ablation in liver cancer tissue. The configurations of T-Prong monopole antennas were considered: Three T-prong antenna, Expand T-Prong antenna and Arrow T-Prong antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The microwave power deliveries were 10 W; the duration of ablation in all cases was 300s. Our numerical result, heat flux and the hotspot occurred at the tip of the T-prong antenna for all cases. The temperature distribution pattern of all antennas was teardrop. The Arrow T-Prong antenna can induce the highest temperature within cancer tissue. The microwave ablation was successful when the region where the temperatures exceed 50°C (i.e. complete destruction). The Expand T-Prong antenna could complete destruction the liver cancer tissue was maximized (6.05 cm³). The ablation pattern or axial ratio (Widest/length) of Expand T-Prong antenna and Arrow T-Prong antenna was 1, but the axial ratio of Three T-prong antenna of about 1.15.

Keywords: liver cancer, T-Prong antenna, finite element, microwave ablation

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2156 Role of Molecular Changes and Immunohistochemical in Early Detection of Liver Cancer

Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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2155 NS5ABP37 Inhibits Liver Cancer by Impeding Lipogenesis and Cholesterogenesis

Authors: Shenghu Feng, Jun Cheng

Abstract:

The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.

Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress

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2154 The Predictive Value of Serum Bilirubin in the Post-Transplant De Novo Malignancy: A Data Mining Approach

Authors: Nasim Nosoudi, Amir Zadeh, Hunter White, Joshua Conrad, Joon W. Shim

Abstract:

De novo Malignancy has become one of the major causes of death after transplantation, so early cancer diagnosis and detection can drastically improve survival rates post-transplantation. Most previous work focuses on using artificial intelligence (AI) to predict transplant success or failure outcomes. In this work, we focused on predicting de novo malignancy after liver transplantation using AI. We chose the patients that had malignancy after liver transplantation with no history of malignancy pre-transplant. Their donors were cancer-free as well. We analyzed 254,200 patient profiles with post-transplant malignancy from the US Organ Procurement and Transplantation Network (OPTN). Several popular data mining methods were applied to the resultant dataset to build predictive models to characterize de novo malignancy after liver transplantation. Recipient's bilirubin, creatinine, weight, gender, number of days recipient was on the transplant waiting list, Epstein Barr Virus (EBV), International normalized ratio (INR), and ascites are among the most important factors affecting de novo malignancy after liver transplantation

Keywords: De novo malignancy, bilirubin, data mining, transplantation

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2153 The Physiological Effect of Cold Atmospheric Pressure Plasma on Cancer Cells, Cancer Stem Cells, and Adult Stem Cells

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

Abstract:

Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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2152 Diallyl Trisulfide Protects the Rat Liver from CCl4-Induced Injury and Fibrogenesis by Attenuating Oxidative Stress

Authors: Xiao-Jing Zhu, Liang Zhou, Shi-Zhong Zheng

Abstract:

Various studies have shown that diallyl trisulfide (DATS) can protect the liver injury, and DATS has a strong antioxidant property. The aim of this study is to evaluate the in vivo role of DATS in protecting the liver against injury and fibrogenesis and further explores the underlying mechanisms. Our results demonstrated that DATS protected the liver from CCl4-caused injury by suppressing the elevation of ALT and AST activities, and by improving the histological architecture of the liver. Treatment with DATS or colchicine improved the liver fibrosis by sirius red staining and immunofluorescence. In addition, immunohistochemistry, western blot, and RT-PCR analyses indicated that DATS inhibited HSC activation. Furthermore, DATS attenuated oxidative stress by increasing glutathione and reducing lipid peroxides and malondialdehyde. These findings suggest that the protective effect of DATS on CCl4-caused liver injury and liver fibrogenesis was, at least partially, attributed to its antioxidant activity.

Keywords: liver fibrogenesis, liver injury, oxidative stress, DATS

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2151 Diagnosis and Analysis of Automated Liver and Tumor Segmentation on CT

Authors: R. R. Ramsheeja, R. Sreeraj

Abstract:

For view the internal structures of the human body such as liver, brain, kidney etc have a wide range of different modalities for medical images are provided nowadays. Computer Tomography is one of the most significant medical image modalities. In this paper use CT liver images for study the use of automatic computer aided techniques to calculate the volume of the liver tumor. Segmentation method is used for the detection of tumor from the CT scan is proposed. Gaussian filter is used for denoising the liver image and Adaptive Thresholding algorithm is used for segmentation. Multiple Region Of Interest(ROI) based method that may help to characteristic the feature different. It provides a significant impact on classification performance. Due to the characteristic of liver tumor lesion, inherent difficulties appear selective. For a better performance, a novel proposed system is introduced. Multiple ROI based feature selection and classification are performed. In order to obtain of relevant features for Support Vector Machine(SVM) classifier is important for better generalization performance. The proposed system helps to improve the better classification performance, reason in which we can see a significant reduction of features is used. The diagnosis of liver cancer from the computer tomography images is very difficult in nature. Early detection of liver tumor is very helpful to save the human life.

Keywords: computed tomography (CT), multiple region of interest(ROI), feature values, segmentation, SVM classification

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2150 Transcriptomic Analysis of Non-Alcoholic Fatty Liver Disease in Cafeteria Diet Induced Obese Rats

Authors: Mohammad Jamal

Abstract:

Non-alcoholic fatty liver disease (NAFLD) has become one of the most chronic liver diseases, prevalent among people with morbid obesity. NAFLD does not develop clinically significant liver disease, however cirrhosis and liver cancer develop in subset and currently there are no approved therapies for the treatment of NAFLD. The study is aimed to understand the various key genes involved in the mechanism of NAFLD which can be valuable for developing diagnostic and predictive biomarkers based on their histologic stage of liver. The study was conducted on 16 male Sprague Dawley rats. The animals were divided in two groups: control group (n=8) fed on ad libitum normal chow and regular water and the cafeteria group (CAF)) (n=8) fed on high fatty/ carbohydrate diet. The animals received their respective diet from 4 weeks onwards from D.O.B until 25 weeks. Liver was extracted and RT² Profiler PCR Array was used to assess the NAFLD related genes. Histological evaluation was performed using H&E stain in liver tissue sections. Our PCR array results showed that genes involved in anti-inflammatory activity (Ifng, IL10), fatty acid uptake/oxidation (Fabp5), apoptosis (Fas), lipogenesis (Gck and Srebf1), Insulin signalling (Igfbp1) and metabolic pathway (pdk4) were upregulated in the liver of cafeteria fed obese rats. Bloated hepatocytes, displaced nucleus and higher lipid content were seen in the liver of cafeteria fed obese rats. Although Liver biopsies remain the gold standard in evaluating NAFLD, however an approach towards non-invasive markers could be used in understanding the physiology, therapeutic potential, and the targets to combat NAFLD.

Keywords: biomarkers, cafeteria diet, obesity, NAFLD

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2149 Thermodynamic and Immunochemical Studies of Antibody Biofunctionalized Gold Nanoparticles Mediated Photothermal Ablation in Human Liver Cancer Cells

Authors: Lucian Mocan, Flaviu Tabaran, Teodora Mocan, Cristian Matea, Cornel Iancu

Abstract:

We present method of Gold Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinoma cell line), based on a simple gold nanoparticle carrier system, such as serum albumin (BSA), and demonstrate its selective therapeutic efficacy. Hyperspectral, contrast phase, and confocal microscopy combined immunochemical staining were used to demonstrate the selective internalization of HSA-GNPs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. We examined the ability of laser-activated carbon nanotubes to induce Hsp70 expression using confocal microscopy. Hep G2 cells heat-shocked (laser activated BSA-GNPs) to 42°C demonstrated an up-regulation of Hsp70 compared with control cells (BSA-GNPs treated cells without laser), which showed no detectable constitutive expression of Hsp70. We observed a time-dependent induction in Hsp70 expression in Hep G2 treated with BSA-GNPs and LASER irradiated. The post-irradiation apoptotic rate of HepG2 cells treated with HSA-GNPs ranged from 88.24% (for 50 mg/L) at 60 seconds, while at 30 minute the rate increased to 92.34% (50 mg/L). These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, liver cancer, albumin, laser irradiation

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2148 Grape Seed Extract in Prevention and Treatment of Liver Toxic Cirrhosis in Rats

Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

Abstract:

The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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2147 Coaxial Helix Antenna for Microwave Coagulation Therapy in Liver Tissue Simulations

Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

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2146 Physiochemical and Histological Study on the Effect of the Hibernation on the Liver of Uromastyx acanthinura (Bell, 1825)

Authors: Youssef. K. A. Abdalhafid, Ezaldin A. M. Mohammed, Masoud M. M. Zatout

Abstract:

This study described the changes in the liver of Uromastyx acanthinura (Bell, 1825) males and females during hibernation and activity seasons. The results revealed that, hibernation causes increase fatty liver and pigment cells with abundant damage, comparing with nearly normal structure and less fatty liver after the hibernation with almost normal pattern. Genomic DNA showed apparent separation during hibernation. Also, caspase 3 and caspase 7 activity reached a high level in the liver tissue during hibernation comparing with activity season.

Keywords: histological liver, DNA fragmentation, hibernation, caspase 3 and caspase 7

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2145 Hexane Extract of Thymus serpyllum L.: GC-MS Profile, Antioxidant Potential and Anticancer Impact on HepG2 (Liver Carcinoma) Cell Line

Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

Abstract:

Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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2144 Liver and Liver Lesion Segmentation From Abdominal CT Scans

Authors: Belgherbi Aicha, Hadjidj Ismahen, Bessaid Abdelhafid

Abstract:

The interpretation of medical images benefits from anatomical and physiological priors to optimize computer- aided diagnosis applications. Segmentation of liver and liver lesion is regarded as a major primary step in computer aided diagnosis of liver diseases. Precise liver segmentation in abdominal CT images is one of the most important steps for the computer-aided diagnosis of liver pathology. In this papers, a semi- automated method for medical image data is presented for the liver and liver lesion segmentation data using mathematical morphology. Our algorithm is currency in two parts. In the first, we seek to determine the region of interest by applying the morphological filters to extract the liver. The second step consists to detect the liver lesion. In this task; we proposed a new method developed for the semi-automatic segmentation of the liver and hepatic lesions. Our proposed method is based on the anatomical information and mathematical morphology tools used in the image processing field. At first, we try to improve the quality of the original image and image gradient by applying the spatial filter followed by the morphological filters. The second step consists to calculate the internal and external markers of the liver and hepatic lesions. Thereafter we proceed to the liver and hepatic lesions segmentation by the watershed transform controlled by markers. The validation of the developed algorithm is done using several images. Obtained results show the good performances of our proposed algorithm

Keywords: anisotropic diffusion filter, CT images, hepatic lesion segmentation, Liver segmentation, morphological filter, the watershed algorithm

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2143 Comparative Stem Cells Therapy for Regeneration of Liver Fibrosis

Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

Abstract:

Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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2142 Comparison between Transient Elastography (FibroScan) and Liver Biopsy for Diagnosis of Hepatic Fibrosis in Chronic Hepatitis C Genotype 4

Authors: Gamal Shiha, Seham Seif, Shahera Etreby, Khaled Zalata, Waleed Samir

Abstract:

Background: Transient Elastography (TE; FibroScan®) is a non-invasive technique to assess liver fibrosis. Aim: To compare TE and liver biopsy in hepatitis C virus (HCV) patients, genotype IV and evaluate the effect of steatosis and schistosomiasis on FibroScan. Methods: The fibrosis stage (METAVIR Score) TE, was assessed in 519 patients. The diagnostic performance of FibroScan is assessed by calculating the area under the receiver operating characteristic curves (AUROCs). Results: The cut-off value of ≥ F2 was 8.55 kPa, ≥ F3 was 10.2 kPa and cirrhosis = F4 was 16.3 kPa. The positive predictive value and negative predictive value were 70.1% and 81.7% for the diagnosis of ≥ F2, 62.6% and 96.22% for F ≥ 3, and 27.7% and 100% for F4. No significant difference between schistosomiasis, steatosis degree and FibroScan measurements. Conclusion: Fibroscan could accurately predict liver fibrosis.

Keywords: chronic hepatitis C, FibroScan, liver biopsy, liver fibrosis

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2141 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line

Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

Abstract:

Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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2140 Liver Histopathological Findings after Treatment with Anastrazole and Letrozole in Ovariectomized Rats

Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea

Abstract:

Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studies

Keywords: anastrazole, letrozole, liver, rats

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2139 Latest Advances in the Management of Liver Diseases

Authors: Rabab Makki, Deputy Chief Dietitian

Abstract:

Malnutrition is commonly seen in Liver Disease patients. Prevalence of malnutrition in cirrhosis, is as high as 65-90%. Protein depletion and reduced muscle function are common. There are many mechanisms of malnutrition in liver cirrhosis e.g. insulin resistance, low respiratory quotient, increased glucogenesis etc. Nutrition support improves outcome in patients unable to maintain an intake of 35-40 Kcal/kg and 1.2-1.5 gm/kg/day. Simple methods of assessment such as subjective global assessment, calorie counting, MMC are useful. The value of BCAAs remains uncertain despite a considerable number of studies. Normal protein diets have been given safely to patients with hepatic encephalopathy. Restriction of protein not more than 48 hours pre- and pro-biotic, glutamine, fish oil etc are all part of the latest advanced techniques used.

Keywords: liver cirrhosis, omega 3 for liver disease, nutrition management, malnutrition

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2138 Role of Tyrosine-Phosphorylated STAT3 in Liver Regeneration: Survival, DNA Synthesis, Inflammatory Reaction and Liver Mass Recovery

Authors: JiYoung Park, SueGoo Rhee, HyunAe Woo

Abstract:

In liver regeneration, quiescent hepatocytes need to be primed to fully respond to growth factors such as hepatocyte growth factor. To understand the priming process, it is necessary to analyze patterns of gene expression that occur during liver regeneration after partial hepatectomy (PHx). Recently, tyrosine phosphorylation of signal transducer and activator of transcription 3 (pYSTAT3) has been shown to play an important role in initiating liver regeneration. In order to evaluate the role of pYSTAT3 on liver regeneration after PHx, we used an intrabody which can selectively inhibit pYSTAT3. In our previous studies, an intrabody had been shown that it bound specifically to the pYSTAT3. Adenovirus-mediated expression of the intrabody in HepG2 cells, as well as mouse liver, blocked both accumulation of pYSTAT3 in the nucleus and downstream target of pYSTAT3. In this study, PHx was performed on intrabody-expressing mice and the expression levels of liver regeneration-related genes were analyzed. We also measured liver/body weight ratios and the related cellular signaling pathways were analyzed. Acute phase response genes were reduced in an intrabody-expressing mice during liver regeneration than in control virus-injected mice. However, the time course of liver mass restoration in intrabody-expressing mice was similar to that observed in control virus-injected mice. We also observed that the expression levels of anti-apoptotic genes, such as Bcl2 and Bcl-xL were decreased in intrabody-expressing mice whereas the expression of cell cycle-related genes such as cyclin D1, and c-myc was increased. Liver regeneration after PHx was partially impaired by the selective inhibition of pYSTAT3 with a phosphorylation site-specific intrabody and these results indicated that pYSTAT3 might have limited role in liver mass recovery.

Keywords: STAT3, pYSTAT3, liver regeneration, intrabody

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