Search results for: tumor necrosis factor α

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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Authors: Othmane Zarhali, Cécilia Aubrun, Emmanuel Bacry, Jean-Philippe Bouchaud, Jean-François Muzy

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The Nested factor model was introduced by Bouchaud and al., where the asset return fluctuations are explained by common factors representing the market economic sectors and residuals (noises) sharing with the factors a common dominant volatility mode in addition to the idiosyncratic mode proper to each residual. This construction infers that the factors-residuals log volatilities are correlated. Here, we consider the case of a single factor where the only dominant common mode is a S-fbm process (introduced by Peng, Bacry and Muzy) with Hurst exponent H around 0.11 and the residuals having in addition to the previous common mode idiosyncratic components with Hurst exponents H around 0. The reason for considering this configuration is twofold: preserve the Nested factor model’s characteristics introduced by Bouchaud and al. and propose a framework through which the stylized fact reported by Peng and al. is reproduced, where it has been observed that the Hurst exponents of stock indices are large as compared to those of individual stocks. In this work, we show that the Log S-fbm Nested factor model’s construction leads to a Hurst exponent of single stocks being the ones of the idiosyncratic volatility modes and the Hurst exponent of the index being the one of the common volatility modes. Furthermore, we propose a statistical procedure to estimate the Hurst factor exponent from the stock returns dynamics together with theoretical guarantees, with good results in the limit where the number of stocks N goes to infinity. Last but not least, we show that the factor can be seen as an index constructed from the single stocks weighted by specific coefficients.

Keywords: hurst exponent, log S-fbm model, nested factor model, small intermittency approximation

Procedia PDF Downloads 50

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

Procedia PDF Downloads 141

Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

Procedia PDF Downloads 244

Authors: Taleb L., Benarbia M., Boutira F. M., Allam H., Boukerche A.

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Introduction and purpose of the study: Meningiomas are the most common non-glial intracranial tumors in adults, accounting for approximately 30% of all central nervous system tumors. The aim of our study is to determine the epidemiological, clinical, therapeutic, and evolutionary characteristics of a cohort of patients with intracranial meningioma treated with radiotherapy at the Emir Abdelkader Cancer Center in Oran. Material and methods: This is a retrospective study of 44 patients during the period from 2014 to 2020. The overall survival and relapse-free survival curves were calculated using the Kaplan-Meier method. Results and statistical analysis: The median age of the patients was 49 years [21-76 years] with a clear female predominance (sex ratio=2.4). The average diagnostic delay was seven months [2 to 24 months], the circumstances of the discovery of which were dominated by headaches in 54.5% of cases (n=24), visual disturbances in 40.9% (n=18), and motor disorders in 15.9% (n=7). The seat of the tumor was essentially at the level of the base of the skull in 52.3% of patients (n=23), including 29.5% (n=13) at the level of the cavernous sinus, 27.3% (n=12) at the parasagittal level and 20.5% (n=9) at the convexity. The diagnosis was confirmed surgically in 36 patients (81.8%) whose anatomopathological study returned in favor of grades I, II, and III in respectively 40.9%, 29.5%, and 11.4% of the cases. Radiotherapy was indicated postoperatively in 45.5% of patients (n=20), exclusive in 27.3% (n=12) and after tumor recurrence in 27.3% of cases (n=18). The irradiation doses delivered were as follows: 50 Gy (20.5%), 54 Gy (65.9%), and 60 Gy (13.6%). With a median follow-up of 69 months, the probabilities of relapse-free survival and overall survival at three years are 93.2% and 95.4%, respectively, whereas they are 71.2% and 80.7% at five years. Conclusion: Meningiomas are common primary brain tumors. Most often benign but can also progress aggressively. Their treatment is essentially surgical, but radiotherapy retains its place in specific situations, allowing good tumor control and overall survival.

Keywords: diagnosis, meningioma, surgery, radiotherapy, survival

Procedia PDF Downloads 100

Authors: Farzad Yavari, Hamid Chegini, Saeed Lotfi

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This paper reviews the comparison of Resin Rich (RR) and Vacuum Pressure Impregnation (VPI) insulation system qualities for stator bar of rotating electrical machines. Voltage endurance and tangent delta are two diagnostic tests to determine the quality of insulation systems. The paper describes the trend of dissipation factor while performing voltage endurance test for different stator bar samples made with RR and VPI insulation system methods. Some samples were made with the same strands and insulation thickness but with different main wall material to prove the influence of insulation system methods on stator bar quality. Also, some of the samples were subjected to voltage at the temperature of their insulation class, and their dissipation factor changes were measured and studied.

Keywords: VPI, resin rich, insulation, stator bar, dissipation factor, voltage endurance

Procedia PDF Downloads 198

Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

Procedia PDF Downloads 151

Authors: Maryam Sayadi, Rana Sedighpour, Hossein Rezaie

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In this study, in order to evaluate water quality of Gamasiab and Gharehsoo rivers located in Kermanshah province, the information of a 5-year statistical period during the years 2014-2018 was used. To evaluate the hydrochemistry of water, first the type and hydrogeochemical facies of river water were determined using Stiff and Piper diagrams. Then, based on Gibbs diagram and combination diagrams, the factors controlling the chemical parameters of the two rivers were identified. Saturation indices were used to predict the possibility of dissolution and deposition of some minerals. Then, in order to classify water in different sections, fourteen water quality indicators for different uses along with WHO standard were used. Finally, factor analysis was used to determine the processes affecting the hydrochemistry of the two rivers. The results of this study showed that in both rivers, the predominant type and facies are bicarbonate of calcite. Also, the main factor in changing the chemical quality of water in both Gamasiab and Gharehsoo rivers is the water-rock reaction. According to the results of factor analysis in both rivers, two factors have the greatest impact on water quality in the region. Among the parameters of Gamasiab river in the first factor, HCO3-, Na+ and Cl-, respectively, had the highest factor loads, and in the second factor, SO42- and Mg2+ were selected as the main parameters. The parameters Ca2+, Cl- and Na have the highest factor loads in the first factor and in the second factor Mg2+ and SO42- have the highest factor loads in Gharehsoo river. The dissolution of carbonate formations due to their abundance and expansion in the two basins has a more significant effect on changing water chemistry. It has saturated the water of rivers with aragonite, calcite and dolomite. Due to the low contribution of the second factor in changing the chemical parameters, the water of both rivers is saturated with respect to evaporative minerals such as gypsum, halite and anhydrite in all stations. Based on Schoeller diagrams, Wilcox and other quality indicators in these two sections, the amount of main physicochemical parameters are in the desired range for drinking and agriculture. The results of Langelier, Ryznar, Larson-Skold and Puckorius indices showed that water is corrosive in industry.

Keywords: factor analysis, hydrochemical, saturation index, surface water quality

Procedia PDF Downloads 126

Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

Procedia PDF Downloads 347

Authors: Luz del Carmen Rubí Félix Peña, Jose Adan Felix-Ortiz, Ely Sara Lopez-Alvarez, Wenceslao Valenzuela-Quiñonez

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On a global scale, Mexico is the sixth largest producer of farmed white shrimp (Penaeus vannamei). The activity suffered significant economic losses due to acute hepatopancreatic necrosis (AHPND) caused by a strain of Vibrio parahaemolyticus. For control, the first option is the application of antibiotics in food, causing changes in the environment and bacterial communities, which has produced greater virulence and resistance of pathogenic bacteria. An alternative treatment is silver nanoparticles (AgNPs) generated by green synthesis, which have shown an antibacterial capacity by destroying the cell membrane or denaturing the cell. However, the doses at which these are effective are still unknown. The aim is to calculate the minimum inhibitory concentration (MIC) using the Gompertz, Richard, and Logistic model of biosynthesized AgNPs against a strain of V. parahaemolyticus. Through the testing of different formulations of AgNPs synthesized from Euphorbia prostrate (Ep) extracts against V. parahaemolyticus causing AHPND in white shrimp. Aqueous and ethanol extracts were obtained, and the concentration of phenols and flavonoids was quantified. In the antibiograms, AgNPs were formulated in ethanol extracts of Ep (20 and 30%). The inhibition halo at well dilution test were 18±1.7 and 17.67±2.1 mm against V. parahaemolyticus. A broth microdilution was performed with the inhibitory agents (aqueous and ethanolic extracts and AgNPs) and 20 μL of the inoculum of V. parahaemolyticus. The MIC for AgNPs was 6.2-9.3 μg/mL and for ethanol extract of 49-73 mg/mL. The Akaike index (AIC) was used to choose the Gompertz model for ethanol extracts of Ep as the best data descriptor (AIC=204.8, 10%; 45.5, 20%, and 204.8, 30%). The Richards model was at AgNPs ethanol extract with AIC=-9.3 (10%), -17.5 (20 and 30%). The MIC calculated for EP extracts with the modified Gompertz model were 20 mg/mL (10% and 20% extract) and 40 mg/mL at 30%, while Richard was winner for AgNPs-synthesized it was 5 μg/mL (10% and 20%) and 8 μg/mL (30%). The solver tool Excel was used for the calculations of the models and inhibition curves against V.parahaemolyticus.

Keywords: green synthesis, euphorbia prostata, phenols, flavonoids, bactericide

Procedia PDF Downloads 106

Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

Procedia PDF Downloads 222

Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

Procedia PDF Downloads 453

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

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Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 114

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

Procedia PDF Downloads 226

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

Procedia PDF Downloads 399

Authors: S. Lecheb, A. Nour, A. Chellil, H. Mechakra, N. Hamad, H. Kebir

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The work involves develops attended by a numerical execution of the eXtend Finite Element Method premises a measurement by the fracture process cracked so many cracked plates an application will be processed for the calculation of the stress intensity factor SIF. In the first we give in statically part the distribution of stress, displacement field and strain of composite plate in two cases uncrack/edge crack, also in dynamical part the first six modes shape. Secondly, we calculate Stress Intensity Factor SIF for different orientation angle θ of central crack with length (2a=0.4mm) in plan strain condition, KI and KII are obtained for mode I and mode II respectively using X-FEM method. Finally from crack inclined involving mixed modes results, the comparison we chose dangerous inclination and the best crack angle when K is minimal.

Keywords: stress intensity factor (SIF), crack orientation, glass/epoxy, natural frequencies, X-FEM

Procedia PDF Downloads 516

Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

Abstract:

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Boxiang Zhuang

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This study analyzes the clinical manifestations, hearing rehabilitation methods and outcomes of a complex case of neurofibromatosis type II (NF2). Methods: The clinical manifestations, medical history, clinical data, surgical methods and postoperative hearing rehabilitation outcomes of an NF2 patient were analyzed to determine the hearing reconstruction method and postoperative effect for a special type of NF2 acoustic neuroma. Results: The patient had bilateral acoustic neuromas with profound sensorineural hearing loss in both ears. Peripheral blood genetic testing did not reveal pathogenic gene mutations, suggesting mosaicism. The patient had an intracochlear schwannoma in the right ear and severely impaired vision in both eyes. Cochlear implantation with tumor retention was performed in the right ear. After 2 months of family-based auditory and speech rehabilitation, the Categories of Auditory Performance (CAP) score improved from 0 to 5. Conclusion: NF2 has complex clinical manifestations and poor prognosis. For NF2 patients with intracochlear tumors, cochlear implantation with tumor retention can be used to reconstruct hearing.

Keywords: NF2, intracochlear schwannoma, hearing reconstruction, cochlear implantation

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Authors: A. Rifa’i, Y. Takeshita, M. Komatsu

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After Yogyakarta earthquake in 2006, the main problem that occurred in the first yard of Prambanan Temple is ponding area that occurred after rainfall. Soil characterization needs to be determined by conducting several processes, especially permeability coefficient (k) in both saturated and unsaturated conditions to solve this problem. More accurate and efficient field testing procedure is required to obtain permeability data that present the field condition. One of the field permeability test equipment is Constant Discharge procedure to determine the permeability coefficient. Necessary adjustments of the Constant Discharge procedure are needed to be determined especially the value of geometric factor (F) to improve the corresponding value of permeability coefficient. The value of k will be correlated with the value of volumetric water content (θ) of an unsaturated condition until saturated condition. The principle procedure of Constant Discharge model provides a constant flow in permeameter tube that flows into the ground until the water level in the tube becomes constant. Constant water level in the tube is highly dependent on the tube dimension. Every tube dimension has a shape factor called the geometric factor that affects the result of the test. Geometric factor value is defined as the characteristic of shape and radius of the tube. This research has modified the geometric factor parameters by using empty material tube method so that the geometric factor will change. Saturation level is monitored by using soil moisture sensor. The field test results were compared with the results of laboratory tests to validate the results of the test. Field and laboratory test results of empty tube material method have an average difference of 3.33 x 10^-4 cm/sec. The test results showed that modified geometric factor provides more accurate data. The improved methods of constant discharge procedure provide more relevant results.

Keywords: constant discharge, geometric factor, permeability coefficient, unsaturated soils

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Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: Koo-Yeon Kim, Eun-Hye Kim, Tae-Il Son

Abstract:

Epidermal Growth Factor (EGF, Mw=6,045) has been reported to have high efficiency of wound repair and anti-wrinkle effect. However, the half-life of EGF in the body is too short to exert the biological activity effectively when applied in free form. Growth Factors can be stabilized by immobilization with carbohydrates from thermal and proteolytic degradation. Low molecular weight chitosan (LMCS) and its derivate prepared by hydrogen peroxide has high solubility. LM6A6DC was successfully prepared as a reactive carbohydrate for the stabilization of EGF by the reactions of LMCS with alkalization, tosylation, azidation and reduction. The structure of LM6A6DC was confirmed by FT-IR, 1H NMR and elementary analysis. For enhancing the stability of free EGF, EGF was attached with LM6A6DC by using water-soluble carbodiimide. EGF-LM6A6DC conjugates did not show any cytotoxicity on the Normal Human Dermal Fibroblast(NHDF) 3T3 proliferation at least under 100 ㎍/㎖. In the result, it was considered that LM6A6DC is suitable to immobilize of growth factor.

Keywords: epidermal growth factor (EGF), low-molecular-weight chitosan, immobilization

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Authors: Abder-Rahman Ali, Antoine Vacavant, Manuel Grand-Brochier, Adélaïde Albouy-Kissi, Jean-Yves Boire

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In this paper, we present a new segmentation approach for liver lesions in regions of interest within MRI (Magnetic Resonance Imaging). This approach, based on a two-cluster Fuzzy C-Means methodology, considers the parameter variable compactness to handle uncertainty. Fine boundaries are detected by a local recursive merging of ambiguous pixels with a sequential forward floating selection with Zernike moments. The method has been tested on both synthetic and real images. When applied on synthetic images, the proposed approach provides good performance, segmentations obtained are accurate, their shape is consistent with the ground truth, and the extracted information is reliable. The results obtained on MR images confirm such observations. Our approach allows, even for difficult cases of MR images, to extract a segmentation with good performance in terms of accuracy and shape, which implies that the geometry of the tumor is preserved for further clinical activities (such as automatic extraction of pharmaco-kinetics properties, lesion characterization, etc).

Keywords: defuzzification, floating search, fuzzy clustering, Zernike moments

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Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto

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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.

Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation

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