Search results for: liver tumor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1465

Search results for: liver tumor

1225 No Histological and Biochemical Changes Following Administration of Tenofovir Nanoparticles: Animal Model Study

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

Abstract:

Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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1224 Development and Characterization of Soya Phosphatidylcholine Complex of Coumestans from Eclipta alba for the Management of Hepatotoxicity

Authors: Abhishek Kumar Jain, Anki Jain, Yuvraj Singh Dangi, Brajesh Kumar Tiwari

Abstract:

The plant Eclipta alba Hassk. (Family: Compositae) contains coumestans (wedelolactone and demethyl wedelolactone) used in liver disorders. The objective of the present investigation was to develop a formulation of these coumestans in combination with the soya phosphatidylcholine (PC), in order to overcome the limitation of absorption and to investigate the protective effect of coumestans–phosphatidylcholine complex (C-PC) on carbon tetrachloride induced acute liver damage in rats. Methanolic extract (ME) of the whole plant of Eclipta alba was fractionated with water and then with ehylacetate. Coumestans were characterized in the ethylacetate fraction of methanolic extract (EFME). The C-PC was prepared by dissolving EFME and PC in 1:1 ratio in dichloromethane and heating at 60°C for 2 h. The C-PC was characterized by DSC and FTIR spectroscopy. In vitro drug release from EFME and C-PC through egg membrane was measured using UV-Visible spectrophotometer. The hepatoprotective activity of C-PC (equivalent to 5.35 and 10.7 mg/kg body weight of EFME), ME 250 mg/kg and EFME 5.35 mg/kg was evaluated by measuring various enzymes level. C-PC significantly provided better protection to the liver by restoring the enzyme levels of SGPT, SGOT, ALP and total billirubin with respect to carbon tetrachloride (CCl4) treated group (P < 0.001). Histopathological studies were also performed. The C-PC provided better protection to rat liver than ME and EFME at similar doses as well as shown significant regeneration of hepatocytes, central vein, intact cytoplasm, and nucleus.

Keywords: hepatotoxicity, wedelolactone, soya phosphatidylcholine, eclipta alba

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1223 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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1222 Effects of α-IFN –SingleWalled Carbon NanoTube and α-IFN-PLGA Encapsulated on Breast Cancer in Rats Induced by DMBA by Using CA15-3 Tumor Marker

Authors: Anoosh Eghdami

Abstract:

Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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1221 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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1220 Expression of Fibrogenesis Markers after Mesenchymal Stem Cells Therapy for Experimental Liver Cirrhosis

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

Abstract:

Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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1219 Management of Renal Malignancies with IVC Thrombus: Our Experience

Authors: Sujeet Poudyal

Abstract:

Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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1218 Differential Infection of Primary Human B-Cells and EBV Positive B-Lymphoma Cell Lines by Recombinant AAV Serotypes

Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

Abstract:

B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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1217 Functionalized SPIO Conjugated with Doxorubicin for Tumor Diagnosis and Chemotherapy Enhanced by Applying Magnetic Fields

Authors: Po-Chin Liang, Yung-Chu Chen, Chi-Feng Chiang, Yun-Ping Lin, Wen-Yuan Hsieh, Win-Li Lin

Abstract:

The aim of this study was to develop super paramagnetic iron oxide (SPIO) nano-particles comprised of a magnetic Fe3O4 core and a shell of aqueous stable self-doped polyethylene glycol (PEG) with a high loading of doxorubicin (SPIO-PEG-D) for tumor theranostics. The in-vivo MRI study showed that there was a stronger T2-weighted signal enhancement for the group under a magnetic field, and hence it indicated that this group had a better accumulation of SPIO-PEG than the group without a magnetic field. In the anticancer evaluation of SPIO-PEG-D, the group with a magnetic field displayed a significantly smaller tumor size than the group without. The overall results show that SPIO-PEG-D nanoparticles have the potential for the application of MRI/monitoring chemotherapy and the therapy can be locally enhanced by applying an external magnetic field.

Keywords: super paramagnetic iron oxide nano particles, doxorubicin, chemotherapy, MRI, magnetic fields

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1216 PD-L1 Expression in Papillary Thyroid Carcinoma Arising Denovo or on Top of Autoimmune Thyroiditis

Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana

Abstract:

Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.

Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis

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1215 The Role of Il-6-Mediated NS5ATP9 Expression in Autophagy of Liver Cancer Cells

Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

Abstract:

Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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1214 An Abbattoir-Based Study on Relative Prevalence of Histopathologic Patterns of Hepatic Lesions in One-Humped Camels (Camelus deromedarius), Semnan, Iran

Authors: Keivan Jamshidi, Afshin Zahedi

Abstract:

An abattoir based study was carried out during spring 2011 to investigate pathological conditions of the liver in camels (Camelus deromedarius) slaughtered in the Semnan slaughter house, Northern East of Iran. In this study, 40 carcasses out of 150 randomly selected carcasses inspected at postmortem, found with liver lesions. Proper tissue samples obtained from the livers with macroscopic lesions, fixed in 10% neutral buffer formaldehyde, processed for routine histopathological techniques, and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by H&E staining techniques. In histopathological examination of hepatic tissues, following changes were observed: Hydatid cysts; 65%, Cirrhosis; 10%, Hepatic lipidosis (Mild to Severe fatty changes); 12.5%, Glycogen deposition; 2.5%, Cholangitis; 2.8%, Cholangiohepatitis; 5%, Calcified hydatid cyst; 2.5%, Hepatic abscess; 2.5%, lipofuscin pigments; 17.5%. It is concluded that the highest and lowest prevalent patterns of hepatic lesions were hydatid cysts and Hepatic abscess respectively.

Keywords: camel, liver, lesion, pathology, slaughterhouse

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1213 Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-on in Toxic Liver Damage Test

Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

Abstract:

The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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1212 Involvement of Multi-Drug Resistance Protein (Mrp) 3 in Resveratrol Protection against Methotrexate-Induced Testicular Damage

Authors: Mohamed A. Morsy, Azza A. K. El-Sheikh, Abdulla Y. Al-Taher

Abstract:

The aim of the present study is to investigate the effect of resveratrol (RES) on methotrexate (MTX)-induced testicular damage. RES (10 mg/kg/day) was given for 8 days orally and MTX (20 mg/kg i.p.) was given at day 4 of experiment, with or without RES in rats. MTX decreased serum testosterone, induced histopathological testicular damage, increased testicular tumor necrosis factor-α level and expression of nuclear factor-κB and cyclooxygenase-2. In MTX/RES group, significant reversal of these parameters was noticed, compared to MTX group. Testicular expression of multidrug resistance protein (Mrp) 3 was three- and five-folds higher in RES- and MTX/RES-treated groups, respectively. In vitro, using prostate cancer cells, each of MTX and RES alone induced cytotoxicity with IC50 0.18 ± 0.08 and 20.5 ± 3.6 µM, respectively. RES also significantly enhanced cytotoxicity of MTX. In conclusion, RES appears to have dual beneficial effect, as it promotes MTX tumor cytotoxicity, while protecting the testes, probably via up-regulation of testicular Mrp3 as a novel mechanism.

Keywords: resveratrol, methotrexate, multidrug resistance protein 3, tumor necrosis factor-α, nuclear factor-κB, cyclooxygenase-2

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1211 Ancelim: Health System Restoration Protocol for Cancer Patients

Authors: Mark Berry

Abstract:

A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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1210 Sider Bee Honey: Antitumor Effect in Some Experimental Tumor Cell Lines

Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

Abstract:

Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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1209 Chemical Speciation and Bioavailability of Some Essential Metal Ions In Different Fish Organs at Lake Chamo, Ethiopia

Authors: Adane Gebresilassie Hailemariam, Belete Yilma Hirpaye

Abstract:

The enhanced concentrations of heavy metals, especially in sediments, may indicate human-induced perturbations rather than natural enrichment through geological weathering. Heavy metals are non-biodegradable, persist in the environment, and are concentrated up to the food chain, leading to enhanced levels in the liver and muscle tissues of fishes, aquatic bryophytes, and aquatic biota. Marine organisms, in general fish in particular, accumulate metals to concentrations many times higher than present in water or sediment as they can take up metals in their organs and concentrate at different levels. Thus, metals acquired through the food chain due to pollution are potential chemical hazards, threatening consumers. The Nile tilapia (oreochromic niloticus), catfish (clarius garpinus), and water samples were collected from five sampling sites, namely, inlet-1, inlet-2, center, outlet-1 and outlet-2 of Lake Chamo. The concentration of major and trace metals Na, K, Mg, Ca, Cr, Co, Ni, Mn and Cu in the two fish muscles, gill and liver, was determined using an atomic absorption spectrometer (AAS) and flame photometer (FP). Metal concentrations in the water have also been evaluated within the two consecutive seasons, winter (dry) and spring (wet). The results revealed that the concentration of those metals in Tilapia’s (O. niloticus) muscle, gill, and liver were Na 44.5, 35.1, 28, Mg 2.8, 8.41, 4.61, K 43, 32, 30, Ca 1.5, 6.0, 5.5, Cr 0.91, 1.2, 3.5, Co 3.0, 2.89, 2.62, Ni 0.94, 1.99, 2.2, Mn 1.23, 1.51, 1.6 and Cu 1.1, 1.99, 3.5 mg kg-1 respectively and in catfish’s muscle, gill and liver Na 25, 39, 41.5, Mg 4.8, 2.87, 6, K 29, 38, 40, Ca 2.5, 8.10, 3.0, Cr 0.65, 3.5, 5.0, Co 2.62, 1.86, 1.73, Ni 1.10, 2.3, 3.1, Mn 1.54, 1.57, 1.59 and Cu 1.01, 1.10, 3.70 mg kg-1 respectively. The highest accumulation of Na and K were observed for tilapia muscle and catfish gill, Mg and Ca got higher in tilapia gill and catfish liver, while Co is higher in muscle of the two fish. The Cr, Ni, Mn and Cu levels were higher in the livers of the two fish species. In conculusion, metal toxicity through food chain is the current dangerous issue for human and othe animals. This needs deep focus to promot the health of living animals. The Details of the work are going to be discussed at the conference.

Keywords: bioaccumulation, catfish, essential metals, nile tilapia

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1208 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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1207 Brain Tumor Segmentation Based on Minimum Spanning Tree

Authors: Simeon Mayala, Ida Herdlevær, Jonas Bull Haugsøen, Shamundeeswari Anandan, Sonia Gavasso, Morten Brun

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In this paper, we propose a minimum spanning tree-based method for segmenting brain tumors. The proposed method performs interactive segmentation based on the minimum spanning tree without tuning parameters. The steps involve preprocessing, making a graph, constructing a minimum spanning tree, and a newly implemented way of interactively segmenting the region of interest. In the preprocessing step, a Gaussian filter is applied to 2D images to remove the noise. Then, the pixel neighbor graph is weighted by intensity differences and the corresponding minimum spanning tree is constructed. The image is loaded in an interactive window for segmenting the tumor. The region of interest and the background are selected by clicking to split the minimum spanning tree into two trees. One of these trees represents the region of interest and the other represents the background. Finally, the segmentation given by the two trees is visualized. The proposed method was tested by segmenting two different 2D brain T1-weighted magnetic resonance image data sets. The comparison between our results and the standard gold segmentation confirmed the validity of the minimum spanning tree approach. The proposed method is simple to implement and the results indicate that it is accurate and efficient.

Keywords: brain tumor, brain tumor segmentation, minimum spanning tree, segmentation, image processing

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1206 Targeted Photodynamic Therapy for Intraperitoneal Ovarian Cancer, A Way to Stimulate Anti-Tumoral Immune Response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

Abstract:

Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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1205 Dynamic Modelling of Hepatitis B Patient Using Sihar Model

Authors: Alakija Temitope Olufunmilayo, Akinyemi, Yagba Joy

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Hepatitis is the inflammation of the liver tissue that can cause whiteness of the eyes (Jaundice), lack of appetite, vomiting, tiredness, abdominal pain, diarrhea. Hepatitis is acute if it resolves within 6 months and chronic if it last longer than 6 months. Acute hepatitis can resolve on its own, lead to chronic hepatitis or rarely result in acute liver failure. Chronic hepatitis may lead to scarring of the liver (Cirrhosis), liver failure and liver cancer. Modelling Hepatitis B may become necessary in order to reduce its spread. So, dynamic SIR model can be used. This model consists of a system of three coupled non-linear ordinary differential equation which does not have an explicit formula solution. It is an epidemiological model used to predict the dynamics of infectious disease by categorizing the population into three possible compartments. In this study, a five-compartment dynamic model of Hepatitis B disease was proposed and developed by adding control measure of sensitizing the public called awareness. All the mathematical and statistical formulation of the model, especially the general equilibrium of the model, was derived, including the nonlinear least square estimators. The initial parameters of the model were derived using nonlinear least square embedded in R code. The result study shows that the proportion of Hepatitis B patient in the study population is 1.4 per 1,000,000 populations. The estimated Hepatitis B induced death rate is 0.0108, meaning that 1.08% of the infected individuals die of the disease. The reproduction number of Hepatitis B diseases in Nigeria is 6.0, meaning that one individual can infect more than 6.0 people. The effect of sensitizing the public on the basic reproduction number is significant as the reproduction number is reduced. The study therefore recommends that programme should be designed by government and non-governmental organization to sensitize the entire Nigeria population in order to reduce cases of Hepatitis B disease among the citizens.

Keywords: hepatitis B, modelling, non-linear ordinary differential equation, sihar model, sensitization

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1204 Cratoxy Formosum (Jack) Dyer Leaf Extract-Induced Human Breast and Liver Cancer Cells Death

Authors: Benjaporn Buranrat, Nootchanat Mairuae

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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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1203 Hepatoprotective Activity of Ethanolic Extract of Terminalia paniculata against Anti-Tubercular Drugs (ATT) Induced Hepatotoxicity in Wistar Albino Rats

Authors: Mohana Babu Amberkar, Meena Kumari K, Ravi, Arjun, Christopher Rockson

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The aim of this research is to evaluate the hepatoprotective activity of Terminalia paniculata (Tp) against ATT induced hepatic damage in rats.Three hepatotoxic ATT drugs Isoniazid + Rifampicin + Pyrazinamide, silymarin as standard hepatoprotective drug and 0.5% carboxymethylcellulose (CMC) as a control were used. Tp extract and silymarin were administered orally with ATT drugs for 90 days. Two doses 250 and 500 mg/kg of Tp extract, ATT drugs and silymarin were administered as suspensions with 0.5% CMC. ATT treated rats showed a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxides in the serum vs. control. Treatment of silymarin and Tp (250mg/kg) extract showed hepatoprotective activity against the hepatic damage by ATT. This was evident from significant reduction in serum liver enzymes levels, and also there was a significant increase in serum proteins, albumin and total liver tissue thiols as compared to the ATT treated groups. Tp was found to possess hepatoprotective property.

Keywords: antitubercular drugs, hepatoprotective, liver enzymes, Terminalia paniculata

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1202 The Effect of Size and Tumor Depth on Histological Clearance Margins of Basal Cell Carcinomas

Authors: Martin Van, Mohammed Javed, Sarah Hemington-Gorse

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Aim: Our aim was to determine the effect of size and tumor depth of basal cell carcinomas (BCCs) on surgical margin clearance. Methods: A retrospective study was conducted at the Welsh Centre for Burns and Plastic Surgery (WCBPS), Morriston Hospital between 1 Jan 2016 – 31 July 2016. Only patients with confirmed BCC on histopathological analysis were included. Patient data including anatomical region treated, lesion size, histopathological clearance margins and histological sub-types were recorded. An independent T-test was performed determine statistical significance. Results: A total of 228 BCCs were excised in 160 patients. Eleven lesions (4.8%) were incompletely excised. The nose area had the highest rate of incomplete excision. The mean diameter of incompletely excised lesions was 11.4mm vs 11.5mm in completely excised lesions (p=0.959) and the mean histological depth of incompletely excised lesions was 4.1mm vs. 2.5mm for completely excised BCCs (p < 0.05). Conclusions: BCC tumor depth of > 4.1 mm was associated with high rate of incomplete margin clearance. Hence, in prospective patients, a BCC tumor depth (>4 mm) on tissue biopsy should alert the surgeon of potentially higher risk of incomplete excision of lesion.

Keywords: basal cell carcinoma, excision margins, plastic surgery, treatment

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1201 Borderline Ovarian Tumor: Management of Recurrence After Conservative Surgical Treatment

Authors: Ghorbeli Eya, Naija Lamia, Khessairi Nayssem, Saadallah Fatma, Slimane Maher, Tarek Ben Dhiab

Abstract:

INTRODUCTION: Borderline ovarian tumors account for 15 to 20% of ovarian tumors. Prognostic factors of recurrence include the stage of the disease, presence of peritoneal implants, micropapillary pattern, microinvasion and intra-epithelial carcinoma. Fertility sparing constitutes a major therapeutic issue in young patients that leads to conservative surgical treatment in specific cases. METHODS: We conducted a retrospective descriptive study including patients treated at the Salah Azaiez Institute for Borderline Ovarian Tumor who underwent conservative surgical treatment from 2003 to 2018. RESULTS: Nine patients were included in our study. The median age was 33 years. Three patients were nulliparous. Given the age, conservative treatment was indicated in all these patients. Cystectomy without ovariectomy was indicated in 5 of the 9 women, which was within the margin of tumor resection on definitive anatomopathic examination in 3 of the 5 women. In contrast, given the impossibility of ovarian conservation, total annexectomy was carried out in 4 of all these women. All of the patients were followed regularly postoperatively; three had a carcinomatous transformation as an ovarian adenocarcinoma at an average interval of 18 months. Among these three patients, a single one presented intra-peritoneal metastases, requiring radical surgical treatment and adjuvant chemotherapy with 6 cures of Carbo-Taxol, with a good tolerance and a complete response. Moreover, one patient had a recurrence on the contralateral ovary as a Borderline mucinous ovarian tumor. For the remaining four women, after a median follow-up of 35 months, one patient fell spontaneously pregnant during follow-up, and three patients were in complete remission at 16 months. CONCLUSION: Borderline tumors of the ovary usually occur in young patients, which makes conservative treatment advisable if possible, but this always comes with a risk of recurrence and/or carcinomatous transformation, especially if the conservative surgical procedure was a cystectomy instead of a total annexectomy, and even more so if the resection margins were tumoral.

Keywords: ovarian tumor, conservative treatment, surgical management, borderline ovarian tumor, recurrence management

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1200 Connecting MRI Physics to Glioma Microenvironment: Comparing Simulated T2-Weighted MRI Models of Fixed and Expanding Extracellular Space

Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

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Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

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1199 Laparoscopic Management of Cysts Mimicking Hepatic Cystic Echinococcosis in Children (A Case Series)

Authors: Assia Haif, Djelloul Achouri, Zineddine Soualili

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Introduction: Laparoscopic treatment of liver echinococcosis cyst has become popular. In parallel, the diagnostic approach of cystic liver lesions is based on the number of lesions and their distribution. The etiologies of cystic masses in children are different, and the role of imaging in their characterization and pre-therapeutic evaluation is essential. The main differential diagnoses of hepatic hydatid cysts can be discovered intraoperatively by minimally invasive surgery. Methods: The clinical data contained seven patients with hepatic cystic who underwent laparoscopic surgery in the Department of Pediatric Surgery, SETIF, Algeria, from 2015 to 2022. Results: Of reported seven patients, five are male, and the remaining two are female. Abdominal pain was the most frequent clinical signs. Biological parameters were within normal limits, Abdominal ultrasound, practiced in all cases, completed by abdominal computed tomography (CT), showed a hydatid cystic. For all patients, surgical procedures were performed under laparoscopy. Total cystectomy in four patients, fenestration or subtotal cystectomy in three patients, respectively. A histopathological feature confirmed the nature of the cysts. During the follow-up period, there was no recurrence. Conclusions: Laparoscopic liver surgery is a safe and effective approach, it is an alternative to conventional surgery and a reproducible method. Laparoscopic surgery approach should follow the same principals with those of open surgery. This surgical technique can rectify the diagnosis of hydatid cyst, the histopathological examination confirms the nature of the cystic lesion.

Keywords: children, cyst, echinococcosis, laparoscopic, liver

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1198 Computer-Aided Diagnosis System Based on Multiple Quantitative Magnetic Resonance Imaging Features in the Classification of Brain Tumor

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

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Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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1197 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images

Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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1196 In vivo Inhibition and Restoration of Acetyl Cholinesterase Activities in Induced Clarias Gariepinus

Authors: T. O. Ikpesu, I. Tongo, A. Ariyo

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This study was conducted to assess the effects of an organophosphate pesticide glyphosate formulation on neurological enzymes in the brain, liver and serum of juvenile Clarias gariepinus, and also to examine the antidotal prospect of Garcinia kola seeds extract. The fish divided into five groups were exposed to different treatments of glyphosate formulation and Garcinia kola seeds extract. Acetyl cholinesterase activities in the brain, liver and serum of the fish were estimated in the experimental and control fishes on day -7, 14, 21 and of 28 by spectrophotometrical methods. The enzyme was significantly (p < 0.05) inhibited in glyphosate formulation test. The inhibition percentages of AChE ranged for the brain, liver and serum between 40.7–59.4%, 50-57% and 27.5–51.3%, respectively. The aberrated parameters were recovered in G. kola seeds extract treated aquaria, and was dose and time dependent. The present study demonstrated that in vivo glyphosate formulation exposure caused AChE inhibition in the brain, liver and the serum. The brain tissue, however, might be suggested as a good indicator tissue for aquatic pollutants exposure in the fish and G. kola seeds extract has shown to be a good remedy for neurology restoration in a noxious circumstance. The findings has shown that xenobiotics could be eliminated from aquatic organisms, especially fish, and could be put into practice in areas at risk of pollutants. This approach can reduce the risks of biomagnification of poison in sea food. Hence, formulation of this plant extracts into capsule should be encouraged and supported.

Keywords: glyphosate, Clarias gariepinus, brain, Garcinia kola, acetyl cholinesterase, enzymes

Procedia PDF Downloads 387