Search results for: critical cancer
5858 Investigation of The Effects of Hydroxytyrosol on Cytotoxicity, Apoptosis, PI3K/Akt, and ERK 1/2 Pathways in Ovarian Cancer Cell Cultures
Authors: Latife Merve Oktay, Berrin Tugrul
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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer
Procedia PDF Downloads 3505857 1D PIC Simulation of Cold Plasma Electrostatic Waves beyond Wave-Breaking Limit
Authors: Prabal Singh Verma
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Electrostatic Waves in plasma have emerged as a new source for the acceleration of charged particles. The accelerated particles have a wide range of applications, for example in cancer therapy to cutting and melting of hard materials. The maximum acceleration can only be achieved when the amplitude of the plasma wave stays below a critical limit known as wave-breaking amplitude. Beyond this limit amplitude of the wave diminishes dramatically as the coherent energy of the wave starts to convert into random kinetic energy. In this work, spatiotemporal evolution of non-relativistic electrostatic waves in a cold plasma has been studied in the wave-breaking regime using a 1D particle-in-cell simulation (PIC). It is found that plasma gets heated after the wave-breaking but a fraction of initial energy always remains with the remnant wave in the form of Bernstein-Greene-Kruskal (BGK) mode in warm plasma. Another interesting finding of this work is that the frequency of the resultant BGK wave is found be below electron plasma frequency which decreases with increasing initial amplitude and the acceleration mechanism after the wave-breaking is also found to be different from the previous work. In order to explain the results observed in the numerical experiments, a simplified theoretical model is constructed which exhibits a good agreement with the simulation. In conclusion, it is shown in this work that electrostatic waves get shower after the wave-breaking and a fraction of initial coherent energy always remains with remnant wave. These investigations have direct relevance in wakefield acceleration experiments.Keywords: nonlinear plasma waves, longitudinal, wave-breaking, wake-field acceleration
Procedia PDF Downloads 3725856 Comprehensive Care and the Right to Autonomy of Children and Adolescents with Cancer
Authors: Sandra Soca Lozano, Teresa Isabel Lozano Pérez, Germain Weber
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Cancer is a chronic disease of high prevalence in children and adolescents. Medical care in Cuba is carried out by a multidisciplinary team and family is the mediator between this team and the patient. Around this disease, there are interwoven many stereotypes and taboos by its relation to death. In this research report, we describe the work paradigm of psychological care to patients suffering from these diseases in the University Pediatric Hospital Juan Manuel Márquez of Havana, Cuba. We present the psychosocial factors that must be taken into account to provide comprehensive care and ensuring the quality of life of patients and their families. We also present the factors related to the health team and the management of information done with the patient. This is a descriptive proposal from the working experience accumulated in the named institution and in the review of the literature. As a result of this report we make a proposal of teamwork and the aspects in which psychological intervention should be continue performing in terms of increasing the quality of the care made by the health team. We conclude that it is necessary to continue improving the information management of children and adolescents with theses health problems and took into account their right to autonomy.Keywords: comprehensive care, management of information, psychosocial factors, right to autonomy
Procedia PDF Downloads 3275855 Critical Success Factors for Sustainable Smart City Project in India
Authors: Debasis Sarkar
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Development of a Smart City would depend upon the development of its infrastructure in a smart way. Primarily based on the ideology of the fourth industrial revolution a Smart City project should have Smart governance, smart health care, smart building, smart transportation, smart mobility, smart energy, smart technology and smart citizen. Considering the Indian scenario of current state of cities in India, it has become very essential to decide the specific parameters which would govern the development of a Smart City project. It has been observed that there are significant parameters beyond Information and Communication Technology (ICT), which govern the development of a Smart City project. This paper is an attempt to identify the Critical Success Factors (CSF) which are significantly responsible for the development of a Smart City project in Western India. Responses to questionnaire survey were analyzed on basis of Likert scale. They were further critically evaluated with help of Factor Comparison Method (FCM) and Analytical Hierarchy Process (AHP). The project authorities need to incorporate Building Information Modeling (BIM) to make the smart city project more collaborative. To make the project more sustainable, use of flyash in the concrete used, reduced usage of cement and steel, use of alternate fuels like biodiesel is recommended.Keywords: analytical hierarchical process, building information modeling, critical success factors, factor comparison method
Procedia PDF Downloads 2465854 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.
Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani
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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.
Procedia PDF Downloads 3435853 Lipid-Coated Magnetic Nanoparticles for Frequency Triggered Drug Delivery
Authors: Yogita Patil-Sen
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Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)
Procedia PDF Downloads 2275852 Cytotoxic Effect of Biologically Transformed Propolis on HCT-116 Human Colon Cancer Cells
Authors: N. Selvi Gunel, L. M. Oktay, H. Memmedov, B. Durmaz, H. Kalkan Yildirim, E. Yildirim Sozmen
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Object: Propolis which consists of compounds that are accepted as antioxidant, antimicrobial, antiseptic, antibacterial, anti-inflammatory, anti-mutagenic, immune-modulator and cytotoxic, is frequently used in current therapeutic applications. However, some of them result in allergic side effects, causing consumption to be restricted. Previously our group has succeeded in producing a new biotechnological product which was less allergenic. In this study, we purpose to optimize production conditions of this biologically-transformed propolis and determine the cytotoxic effects of obtained new products on colon cancer cell line (HCT-116). Method: Firstly, solid propolis samples were dissolved in water after weighing, grinding and sizing (sieve-35mesh) and applied 40 kHz/10 min ultrasonication. Samples were prepared according to inoculation with Lactobacillus plantarum in two different proportions (2.5% and 3.5%). Chromatographic analyzes of propolis were performed by UPLC-MS/MS (Waters, Milford, MA) system. Results were analysed by UPLC-MS/MS system MassLynx™ 4.1 software. HCT-116 cells were treated with propolis examples at 25-1000 µg/ml concentrations and cytotoxicity were measured by using WST-8 assay at 24, 48, and 72 hours. Samples with biological transformation were compared with the non-transformed control group samples. Our experiment groups were formed as follows: untreated (group 1), propolis dissolved in water ultrasonicated at 40 kHz/10 min (group 2), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 2.5% L. plantarum L1 strain (group 3), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 3.5% L. plantarum L3 strain (group 4). Obtained data were calculated with Graphpad Software V5 and analyzed by two-way ANOVA test followed by Bonferroni test. Result: As a result of our study, the cytotoxic effect of propolis samples on HCT-116 cells was evaluated. There was a 7.21 fold increase in group 3 compared to group 2 in the concentration of 1000 µg/ml, and it was a 6.66 fold increase in group 3 compared to group 1 at the end of 24 hours. At the end of 48 hours, in the concentration of 500 µg/ml, it was determined 4.7 fold increase in group 4 compared to group 3. At the same time, in the concentration of 750 µg/ml it was determined 2.01 fold increase in group 4 compared to group 3 and in the same concentration, it was determined 3.1 fold increase in group 4 compared to group 2. Also, at the 72 hours, in the concentration of 750 µg/ml, it was determined 2.42 fold increase in group 3 according to group 2 and in the same time, in the concentration of 1000 µg/ml, it was determined 2.13 fold increase in group 4 according to group 2. According to cytotoxicity results, the group which were ultrasonicated at 40 kHz/10min and inoculated 3.5% L. plantarum L3-strain had a higher cytotoxic effect. Conclusion: It is known that bioavailability of propolis is halved in six months. The data obtained from our results indicated that biologically-transformed propolis had more cytotoxic effect than non-transformed group on colon cancer cells. Consequently, we suggested that L. plantarum-transformation provides both reduction of allergenicity and extension of bioavailability period by enhancing healthful polyphenols.Keywords: bio-transformation, propolis, colon cancer, cytotoxicity
Procedia PDF Downloads 1295851 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis
Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini
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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry
Procedia PDF Downloads 1455850 Women-Hating Masculinities: How the Demand for Prostitution Fuels Sex Trafficking
Authors: Rosa M. Senent
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Over the centuries, prostitution has been problematized from many sides, with women always at the center of the debate. However, prostitution is a gendered, demand-driven phenomenon. Thus, a focus must be put on the men who demand it, as an increasing number of studies have been done in the last few decades. The purpose of this paper is to expose how men's discourse online reveals the link between their demand for paid sex in prostitution and sex trafficking. The methodological tool employed was Critical Discourse Analysis (CDA). A critical analysis of sex buyers' discourse online showed that online communities of sex buyers are a useful tool in researching their behavior towards women, that their knowledge of sex trafficking and exploitation do not work as a deterrent for them to buy sex, and that the type of masculinity that sex buyers endorse is characterized by attitudes linked to the perpetuation of violence against women.Keywords: masculinities, prostitution, sex trafficking, violence
Procedia PDF Downloads 1355849 Employees Retention through Effective HR Practices
Authors: Choi Sang Long
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It is vital for Human Resource (HR) managers to address and overcome employees’ turnover intention in their organization. Ability to keep good employees is critical for ensuring success of the organization in future. People are seeking many ways of live that is meaningful and less complicated and this new lifestyle actually has an impact on how an employee must be motivated and managed. Therefore, this paper discusses extensively on the impact of human resource practices that can alter the negative effect on the organization due to high employees’ turnover. These critical practices are employees’ career development, performance management, training and a fair compensation scheme.Keywords: turnover intention, career development, performance management, compensation, human resource management, organization
Procedia PDF Downloads 4845848 An Advanced Match-Up Scheduling Under Single Machine Breakdown
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When a machine breakdown forces a Modified Flow Shop (MFS) out of the prescribed state, the proposed strategy reschedules part of the initial schedule to match up with the preschedule at some point. The objective is to create a new schedule that is consistent with the other production planning decisions like material flow, tooling and purchasing by utilizing the time critical decision making concept. We propose a new rescheduling strategy and a match-up point determination procedure through a feedback mechanism to increase both the schedule quality and stability. The proposed approach is compared with alternative reactive scheduling methods under different experimental settings.Keywords: advanced critical task methods modified flow shop (MFS), Manufacturing, experiment, determination
Procedia PDF Downloads 4035847 Simulation Tools for Training in the Case of Energy Sector Crisis
Authors: H. Malachova, A. Oulehlova, D. Rezac
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Crisis preparedness training is the best possible strategy for identifying weak points, understanding vulnerability, and finding possible strategies for mitigation of blackout consequences. Training represents an effective tool for developing abilities and skills to cope with crisis situations. This article builds on the results of the research carried out in the field of preparation, realization, process, and impacts of training on subjects of energy sector critical infrastructure as a part of crisis preparedness. The research has revealed that the subjects of energy sector critical infrastructure have not realized training and therefore are not prepared for the restoration of the energy supply and black start after blackout regardless of the fact that most subjects state blackout and subsequent black start as key dangers. Training, together with mutual communication and processed crisis documentation, represent a basis for successful solutions for dealing with emergency situations. This text presents the suggested model of SIMEX simulator as a tool which supports managing crisis situations, containing training environment. Training models, possibilities of constructive simulation making use of non-aggregated as well as aggregated entities and tools of communication channels of individual simulator nodes have been introduced by the article.Keywords: communication, energetic critical infrastructure, training, simulation
Procedia PDF Downloads 3785846 Electronic Resources and Information Literacy in Higher Education Library
Authors: Nirmal Singh, Rajesh Kumar
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Abstract- Information literacy aims to develop both critical understanding and active participation in scholars. It enables scholars to interpret and make informed judgments as users of information sources, and it also enables them to become producers of information in their own right, and thereby to become more powerful participants in society. Information literacy is about developing people‘s critical and creative abilities. Digital media – and particularly the Internet – significantly increase the potential for such active participation of the individual, provided scholars have the means and training to effectively access and use them. This paper provides definition, standards and importance of information literacy (IL). Keywords: Information literacy, Digital Media, Training, Communications Technologies.Keywords: Information literacy, Digital Media, Training, , Communications Technologies
Procedia PDF Downloads 1485845 Isolation and Characterization of Anti-melanoma (Skin Cancer) Compounds from Corchorus olitorius .L
Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh
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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.Keywords: corchorus olitorius, melanoma, drug development, strophanthidin
Procedia PDF Downloads 1265844 Effects of Cell Phone Electromagnetic Radiation on the Brain System
Authors: A. Alao Olumuyiwa
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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)
Procedia PDF Downloads 3405843 Antioxidant and Anticancer Activities of Ethanolic Extract from Monascus purpureus
Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi
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Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract
Procedia PDF Downloads 4075842 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line
Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan
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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA
Procedia PDF Downloads 1315841 VISSIM Modeling of Driver Behavior at Connecticut Roundabouts
Authors: F. Clara Fang, Hernan Castaneda
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The Connecticut Department of Transportation (ConnDOT) has constructed four roundabouts in the State of Connecticut within the past ten years. VISSIM traffic simulation software was utilized to analyze these roundabouts during their design phase. The queue length and level of service observed in the field appear to be better than predicted by the VISSIM model. The objectives of this project are to: identify VISSIM input variables most critical to accurate modeling; recommend VISSIM calibration factors; and, provide other recommendations for roundabout traffic operations modeling. Traffic data were collected at these roundabouts using Miovision Technologies. Cameras were set up to capture vehicle circulating activity and entry behavior for two weekdays. A large sample size of filed data was analyzed to achieve accurate and statistically significant results. The data extracted from the videos include: vehicle circulating speed; critical gap estimated by Maximum Likelihood Method; peak hour volume; follow-up headway; travel time; and, vehicle queue length. A VISSIM simulation of existing roundabouts was built to compare both queue length and travel time predicted from simulation with measured in the field. The research investigated a variety of simulation parameters as calibration factors for describing driver behaviors at roundabouts. Among them, critical gap is the most effective calibration variable in roundabout simulation. It has a significant impact to queue length, particularly when the volume is higher. The results will improve the design of future roundabouts in Connecticut and provide decision makers with insights on the relationship between various choices and future performance.Keywords: driver critical gap, roundabout analysis, simulation, VISSIM modeling
Procedia PDF Downloads 2835840 SIPTOX: Spider Toxin Database Information Repository System of Protein Toxins from Spiders by Using MySQL Method
Authors: Iftikhar Tayubi, Tabrej Khan, Rayan Alsulmi, Abdulrahman Labban
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Spider produces a special kind of substance. This special kind of substance is called a toxin. The toxin is composed of many types of protein, which differs from species to species. Spider toxin consists of several proteins and non-proteins that include various categories of toxins like myotoxin, neurotoxin, cardiotoxin, dendrotoxin, haemorrhagins, and fibrinolytic enzyme. Protein Sequence information with references of toxins was derived from literature and public databases. From the previous findings, the Spider toxin would be the best choice to treat different types of tumors and cancer. There are many therapeutic regimes, which causes more side effects than treatment hence a different approach must be adopted for the treatment of cancer. The combinations of drugs are being encouraged, and dramatic outcomes are reported. Spider toxin is one of the natural cytotoxic compounds. Hence, it is being used to treat different types of tumors; especially its positive effect on breast cancer is being reported during the last few decades. The efficacy of this database is that it can provide a user-friendly interface for users to retrieve the information about Spiders, toxin and toxin protein of different Spiders species. SPIDTOXD provides a single source information about spider toxins, which will be useful for pharmacologists, neuroscientists, toxicologists, medicinal chemists. The well-ordered and accessible web interface allows users to explore the detail information of Spider and toxin proteins. It includes common name, scientific name, entry id, entry name, protein name and length of the protein sequence. The utility of this database is that it can provide a user-friendly interface for users to retrieve the information about Spider, toxin and toxin protein of different Spider species. The database interfaces will satisfy the demands of the scientific community by providing in-depth knowledge about Spider and its toxin. We have adopted the methodology by using A MySQL and PHP and for designing, we used the Smart Draw. The users can thus navigate from one section to another, depending on the field of interest of the user. This database contains a wealth of information on species, toxins, and clinical data, etc. This database will be useful for the scientific community, basic researchers and those interested in potential pharmaceutical Industry.Keywords: siptoxd, php, mysql, toxin
Procedia PDF Downloads 1705839 Nature of a Supercritical Mesophase
Authors: Hamza Javar Magnier, Leslie V. Woodcock
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It has been reported that at temperatures above the critical there is no “continuity of liquid and gas”, as originally hypothesized by van der Waals. Rather, both gas and liquid phases, with characteristic properties as such, extend to supercritical temperatures. Each phase is bounded by the locus of a percolation transition, i.e. a higher-order thermodynamic phase change associated with percolation of gas clusters in a large void, or liquid interstitial vacancies in a large cluster. Between these two-phase bounds, it is reported there exists a mesophase that resembles an otherwise homogeneous dispersion of gas micro-bubbles in liquid (foam) and a dispersion of liquid micro-droplets in gas (mist). Such a colloidal-like state of a pure one-component fluid represents a hitherto unchartered equilibrium state of matter besides pure solid, liquid or gas. Here we provide compelling evidence, from molecular dynamics (MD) simulations, for the existence of this supercritical mesophase and its colloidal nature. We report preliminary results of computer simulations for a model fluid using a simplistic representation of atoms or molecules, i.e. a hard-core repulsion with an attraction so short that the atoms are referred to as “adhesive spheres”. Molecular clusters, and hence percolation transitions, are unambiguously defined. Graphics of color-coded clusters show colloidal characteristics of the supercritical mesophase.Keywords: critical phenomena, mesophase, supercritical, square-well, critical parameters
Procedia PDF Downloads 4205838 Identifying, Reporting and Preventing Medical Errors Among Nurses Working in Critical Care Units At Kenyatta National Hospital, Kenya: Closing the Gap Between Attitude and Practice
Authors: Jared Abuga, Wesley Too
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Medical error is the third leading cause of death in US, with approximately 98,000 deaths occurring every year as a result of medical errors. The world financial burden of medication errors is roughly USD 42 billion. Medication errors may lead to at least one death daily and injure roughly 1.3 million people every year. Medical error reporting is essential in creating a culture of accountability in our healthcare system. Studies have shown that attitudes and practice of healthcare workers in reporting medical errors showed that the major factors in under-reporting of errors included work stress and fear of medico-legal consequences due to the disclosure of error. Further, the majority believed that increase in reporting medical errors would contribute to a better system. Most hospitals depend on nurses to discover medication errors because they are considered to be the sources of these errors, as contributors or mere observers, consequently, the nurse’s perception of medication errors and what needs to be done is a vital feature to reducing incidences of medication errors. We sought to explore knowledge among nurses on medical errors and factors affecting or hindering reporting of medical errors among nurses working at the emergency unit, KNH. Critical care nurses are faced with many barriers to completing incident reports on medication errors. One of these barriers which contribute to underreporting is a lack of education and/or knowledge regarding medication errors and the reporting process. This study, therefore, sought to determine the availability and the use of reporting systems for medical errors in critical care unity. It also sought to establish nurses’ perception regarding medical errors and reporting and document factors facilitating timely identification and reporting of medical errors in critical care settings. Methods: The study used cross-section study design to collect data from 76 critical care nurses from Kenyatta Teaching & Research National Referral Hospital, Kenya. Data analysis and results is ongoing. By October 2022, we will have analysis, results, discussions, and recommendations of the study for purposes of the conference in 2023Keywords: errors, medical, kenya, nurses, safety
Procedia PDF Downloads 2345837 Towards Developing A Rural South African Child Into An Engineering Graduates With Conceptual And Critical Thinking Skills
Authors: Betty Kibirige
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Students entering the University of Zululand (UNIZULU) Science Faculty mostly come with skills that allow them to prepare for exams and pass them in order to satisfy requirements for entry into a tertiary Institution. Some students hail from deep rural schools with limited facilities, while others come from well-resourced schools. Personal experience has shown that it may take a student the whole time at a tertiary institution following the same skills as those acquired in high school as a sure means of entering the next level in their development, namely a postgraduate program. While it is apparent that at this point in human history, it is totally impossible to teach all the possible content in any one subject, many academics approach teaching and learning from the traditional point of view. It therefore became apparent to explore ways of developing a graduate that will be able to approach life with skills that allows them to navigate knowledge by applying conceptual and critical thinking skills. Recently, the Science Faculty at the University of Zululand introduced two Engineering programs. In an endeavour to approach the development of the Engineering graduate in this institution to be able to tackle problem-solving in the present-day excessive information availability, it became necessary to study and review approaches used by various academics in order to settle for a possible best approach to the challenge at hand. This paper focuses on the development of a deep rural child in a graduate with conceptual and critical thinking skills as major attributes possessed upon graduation. For this purpose, various approaches were studied. A combination of these approaches was repackaged to form an approach that may appear novel to UNIZULU and the rural child, especially for the Engineering discipline. The approach was checked by offering quiz questions to students participating in an engineering module, observing test scores in the targeted module and make comparative studies. Test results are discussed in the article. It was concluded that students’ graduate attributes could be tailored subconsciously to indeed include conceptual and critical thinking skills, but through more than one approach depending mainly on the student's high school background.Keywords: graduate attributes, conceptual skills, critical thinking skills, traditional approach
Procedia PDF Downloads 2335836 PEG-b-poly(4-vinylbenzyl phosphonate) Coated Magnetic Iron Oxide Nanoparticles as Drug Carrier System: Biological and Physicochemical Characterization
Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki
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Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution
Procedia PDF Downloads 4585835 Informational Support, Anxiety and Satisfaction with Care among Family Caregivers of Patients Admitted in Critical Care Units of B.P. Koirala Institute of Health Sciences, Nepal
Authors: Rosy Chaudhary, Pushpa Parajuli
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Background and Objectives: Informational support to family members has a significant potential for reducing this distress related to hospitalization of their patient into the critical care unit, enabling them to cope better and support the patient. The objective of the study is to assess family members’ perception of informational support, anxiety, satisfaction with care and to reveal the association with selected socio-demographic variables and to investigate the correlation between informational support, anxiety and satisfaction with care. Materials and Methods: A descriptive cross-sectional study was conducted in 39 family caregivers of patients admitted in critical care unit of BPKIHS(B.P. Koirala Institute of Health Sciences). Consecutive sampling technique was used wherein data was collected over duration of one month using interview schedule. Descriptive and inferential statistics were used. Results: The mean age of the respondents was 34.97 ± 10.64 and two third (66.70%) were male. Mean score for informational support was 25.72(SD = 5.66; theoretical range of 10 - 40). Mean anxiety was 10.41 (SD = 5.02; theoretical range of 7 - 21). Mean score for satisfaction with care was 40.77 (SD = 6.77; theoretical range of 14 - 64). A moderate positive correlation was found between informational support and satisfaction with care (r = 0.551, p < .001) and a moderate negative correlation was found between anxiety and satisfaction with care (r = -0.590; p = 0.000). No relationship was noted between informational support and anxiety. Conclusion: The informational support and satisfaction of the family caregivers with the care provided to their patients was satisfactory. More than three fourth of the family caregivers had anxiety; the factors associated being educational status of the caregivers, the family income and duration of visiting hours. There was positive correlation between informational support and satisfaction with care provided justifying the need for comprehensive information to the family caregivers by the health personnel. There was negative correlation between anxiety and satisfaction with care.Keywords: anxiety, caregivers, critical care unit, informational support, family
Procedia PDF Downloads 3445834 Etiological Factors for Renal Cell Carcinoma: Five-Year Study at Mayo Hospital Lahore
Authors: Muhammad Umar Hassan
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Renal cell carcinoma is a subset of kidney cancer that arises in the lining of DCT and is present in parenchymal tissue. Diagnosis is based on lab reports, including urinalysis, renal function tests (RFTs), and electrolyte balance, along with imaging techniques. Organ failure and other complications have been commonly observed in these cases. Over the years, the presentation of patients has varied, so carcinoma was classified on the basis of site, shape, and consistency for detailed analysis. Lifestyle patterns and occupational history were inquired about and recorded. Methods: Data from 100 patients presenting to the oncology and nephrology department of Mayo Hospital in the year 2015-2020 were included in this retrospective study on a random basis. The study was specifically focused on three risk factors. Smoking, occupational exposures, and Hakim medicine are taken by the patient for any cause. After procurement of data, follow-up contacts of these patients were established, resulting in a detailed analysis of lifestyle. Conclusion: The inference drawn is a direct causal link between smoking, industrial workplace exposure, and Hakim medicine with the development of Renal Cell Carcinoma. It was shown in the majority of the patients and hence confirmed our hypothesis.Keywords: renal cell carcinoma, kidney cancer, clear cell carcinoma
Procedia PDF Downloads 945833 Chemopreventive Potency of Medicinal and Eatable Plant, Gromwell Seed on in Vitro and in Vivo Carcinogenesis Systems
Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki
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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems
Procedia PDF Downloads 4765832 Reformulation of Theory of Critical Distances to Predict the Strength of Notched Plain Concrete Beams under Quasi Static Loading
Authors: Radhika V., J. M. Chandra Kishen
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The theory of critical distances (TCD), due to its appealing characteristics, has been successfully used in the past to predict the strength of brittle as well as ductile materials, weakened by the presence of stress risers under both static and fatigue loading. By utilising most of the TCD's unique features, this paper summarises an attempt for a reformulation of the point method of the TCD to predict the strength of notched plain concrete beams under mode I quasi-static loading. A zone of micro cracks, which is responsible for the non-linearity of concrete, is taken into account considering the concept of an effective elastic crack. An attempt is also made to correlate the value of the material characteristic length required for the application of TCD with the maximum aggregate size in the concrete mix, eliminating the need for any extensive experimentation prior to the application of TCD. The devised reformulation and the proposed power law based relationship is found to yield satisfactory predictions for static strength of notched plain concrete beams, with geometric dimensions of the beam, tensile strength, and maximum aggregate size of the concrete mix being the only needed input parameters.Keywords: characteristic length, effective elastic crack, inherent material strength, modeI loading, theory of critical distances
Procedia PDF Downloads 945831 Breast Cancer Metastasis Detection and Localization through Transfer-Learning Convolutional Neural Network Classification Based on Convolutional Denoising Autoencoder Stack
Authors: Varun Agarwal
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Introduction: With the advent of personalized medicine, histopathological review of whole slide images (WSIs) for cancer diagnosis presents an exceedingly time-consuming, complex task. Specifically, detecting metastatic regions in WSIs of sentinel lymph node biopsies necessitates a full-scanned, holistic evaluation of the image. Thus, digital pathology, low-level image manipulation algorithms, and machine learning provide significant advancements in improving the efficiency and accuracy of WSI analysis. Using Camelyon16 data, this paper proposes a deep learning pipeline to automate and ameliorate breast cancer metastasis localization and WSI classification. Methodology: The model broadly follows five stages -region of interest detection, WSI partitioning into image tiles, convolutional neural network (CNN) image-segment classifications, probabilistic mapping of tumor localizations, and further processing for whole WSI classification. Transfer learning is applied to the task, with the implementation of Inception-ResNetV2 - an effective CNN classifier that uses residual connections to enhance feature representation, adding convolved outputs in the inception unit to the proceeding input data. Moreover, in order to augment the performance of the transfer learning CNN, a stack of convolutional denoising autoencoders (CDAE) is applied to produce embeddings that enrich image representation. Through a saliency-detection algorithm, visual training segments are generated, which are then processed through a denoising autoencoder -primarily consisting of convolutional, leaky rectified linear unit, and batch normalization layers- and subsequently a contrast-normalization function. A spatial pyramid pooling algorithm extracts the key features from the processed image, creating a viable feature map for the CNN that minimizes spatial resolution and noise. Results and Conclusion: The simplified and effective architecture of the fine-tuned transfer learning Inception-ResNetV2 network enhanced with the CDAE stack yields state of the art performance in WSI classification and tumor localization, achieving AUC scores of 0.947 and 0.753, respectively. The convolutional feature retention and compilation with the residual connections to inception units synergized with the input denoising algorithm enable the pipeline to serve as an effective, efficient tool in the histopathological review of WSIs.Keywords: breast cancer, convolutional neural networks, metastasis mapping, whole slide images
Procedia PDF Downloads 1245830 One-Step Synthesis and Characterization of Biodegradable ‘Click-Able’ Polyester Polymer for Biomedical Applications
Authors: Wadha Alqahtani
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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer
Procedia PDF Downloads 1095829 Impact of Helicobacter pylori Infection on Colorectal Adenoma-Colorectal Carcinoma Sequence
Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis
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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis
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